Japanese iodine intake from edible seaweeds is amongst the highest in the world. Predicting the t... more Japanese iodine intake from edible seaweeds is amongst the highest in the world. Predicting the type and amount of seaweed the Japanese consume is difficult due to day-today meal variation and dietary differences between generations and regions. In addition, iodine content varies considerably between seaweed species, with cooking and/or processing having an influence on iodine content. Due to all these factors, researchers frequently overestimate, or underestimate, Japanese iodine intake from seaweeds, which results in misleading and potentially dangerous diet and supplementation recommendations for people aiming to achieve the same health benefits seen by the Japanese. By combining information from dietary records, food surveys, urine iodine analysis (both spot and 24-hour samples) and seaweed iodine content, we estimate that the Japanese iodine intake-largely from seaweeds-averages 1,000-3,000 μg/day (1-3 mg/day).
h i g h l i g h t s Dried urine iodine and creatinine extract quantitatively correlates well with... more h i g h l i g h t s Dried urine iodine and creatinine extract quantitatively correlates well with liquid urine. Filter paper strips can be easily shipped and stored. Urine iodine and creatinine are stable at ambient temperature when dried on filter paper. Dried urine iodine and creatinine are run using a 96-well format.
Daily injections of estradiol or the antiestrogen tamoxifen initially stimulate uterine weight in... more Daily injections of estradiol or the antiestrogen tamoxifen initially stimulate uterine weight increase and progesterone receptor synthesis, though continued tamoxifen fails to maintain the increased weight. The stimulatory actions of both estradiol and tamoxifen are inhibited or reversed by a single injection of progesterone. It has been hypothesized that progesterone antagonizes estrogen action by reducing estrogen receptor levels, but in the present experiments neither cytoplasmic nor nuclear estrogen receptor was affected. We conclude that progesterone acts at a point beyond estrogen receptor availability or translocation to antagonize estrogen action.
Six patients with inoperable, nonoperative, or recurrent meningiomas were treated with the anties... more Six patients with inoperable, nonoperative, or recurrent meningiomas were treated with the antiestrogenic agent tamoxifen (Nolvadex) during an 8-12-month period. Computer tomographic, scintigraphic, and clinical evidence of an unspecific tumor response was only encountered in one patient after 4 months of therapy with tamoxifen. The 2-year results did not indicate a favorable response to antiestrogenic treatment. The significance of sex-steroid receptors and their possible prognostic value in endocrine therapy of meningiomas is discussed.
In this study we report on the content and bioactivity of plant (phyto) estrogens and progestins ... more In this study we report on the content and bioactivity of plant (phyto) estrogens and progestins in various foods, herbs, and spices, before and after human consumption. Over 150 herbs traditionally used by herbalists for treating a variety of health problems were extracted and tested for their relative capacity to compete with estradiol and progesterone binding to intracellular receptors for progesterone (PR) and estradiol (ER) in intact human breast cancer cells. The six highest ERbinding herbs that are commonly consumed were soy, licorice, red clover, thyme, tumeric, hops, and verbena. The six highest PR-binding herbs and spices commonly consumed were oregano, verbena, tumeric, thyme, red clover and damiana. Some of the herbs and spices found to contain high phytoestrogens and phytoprogestins were further tested for bioactivity based on their ability to regulate cell growth rate in ER (+) and ER (-) breast cancer cell lines and to induce or inhibit the synthesis of alkaline phosphatase, an end product of progesterone action, in PR (+) cells. In general, we found that ER-binding herbal extracts were agonists, much like estradiol, whereas PR-binding extracts, were neutral or antagonists. The bioavailability of phytoestrogens and phytoprogestins in vivo were studied by quantitating the ER-binding and PR-binding capacity of saliva following consumption of soy milk, exogenous progesterone, medroxyprogesterone acetate, or wild mexican yam products containing diosgenin. Soy milk caused a dramatic increase in saliva ER-binding components without a concomitant rise in estradiol. Consumption of PR-binding herbs increased the progestin activity of saliva, but there were marked differences in bioactivity. In summary, we have demonstrated that many of the commonly consumed foods, herbs, and spices contain phytoestrogens and phytoprogestins that act as agonists and antagonists in vivo.
A study protocol is presented for the investigation of meditative movement (MM) as a treatment fo... more A study protocol is presented for the investigation of meditative movement (MM) as a treatment for pulmonary dysfunction in flight attendants (FA) who were exposed to secondhand cigarette smoke while flying before the smoking ban. The study will have three parts, some of which will run concurrently. The first is a data gathering and screening phase, which will gather data on pulmonary and other aspects of the health of FA, and will also serve to screen participants for the other phases. Second is an exercise selection phase, in which a variety of MM exercises will be taught, over a 16-week period, to a cohort of 20 FA. A subset of these exercises will be selected on the basis of participant feedback on effectiveness and compliance. Third is a 52-week randomized controlled trial to evaluate the effectiveness of a digitally delivered form of the previously selected exercises on a group of 20 FA, as compared with an attention control group. Outcome measures to be used in all three parts of the study include the 6-min walk test as a primary measure, as well as a range of biomarkers, tests, and questionnaires documenting hormonal, cardio-respiratory, autonomic, and affective state. This study is registered at ClinicalTrials.gov. Identifier: NCT02612389.
Sex hormone metabolism is altered during mammary gland tumorigenesis, and different metabolites m... more Sex hormone metabolism is altered during mammary gland tumorigenesis, and different metabolites may have different effects on mammary epithelial cells. This study aimed to evaluate associations between urinary sexual metabolite levels and breast cancer risk among premenopausal women of Mainland China. The molecular metabolism of the cancer-related metabolites was also explored based on the clinical data. The sex hormone metabolites in the urine samples of patients with breast cancer versus normal healthy women were analyzed comprehensively. Among many alterations of sex hormone metabolisms, 4-hydroxy estrogen (4-OH-E) metabolite was found to be significantly increased in the urine samples of patients with breast cancer compared with the normal healthy controls. This was the most important risk factor for breast cancer. Several experiments were conducted in vitro and in vivo to probe this mechanism. 4-Hydroxyestradiol (4-OH-E2) was found to induce malignant transformation of breast cells and tumorigenesis in nude mice. At the molecular level, 4-OH-E2 compromised the function of spindle-assembly checkpoint and rendered resistance to the anti-microtubule drug. Further, transgenic mice with high expression of CYP1B1, a key enzyme of 4-hydroxy metabolites, were established and stimulated with estrogen. Cancerous tissue was found to appear in the mammary gland of transgenic mice.
Summay.-This study investigated in 40 young university women the possible relationships between l... more Summay.-This study investigated in 40 young university women the possible relationships between levels of testosterone and specific measures of overall self-confidence and self-confidence in approaching mathematics. Correlations of-.43 and-.49 with each measure of self-confidence, respecrively, and level of testosterone were found in the portion of the sample displaying normal ovulatory function. There was no correlation (r=.02) benveen the measures of mathematics and overall self-confidence. 19 women did nor display normal ovulatory function. The only significant result for the full sample was a significant correlation of-.73 benveen scores on the Bem Sex Role hventory Mascuhiry and overall self-confidence. The reasons for the high anovulatory percentage are not clear, nor are the associations which anovulation might have with either hormonal levels or the personality characteristics in question.
Iodine is crucial for thyroid hormone production. However, recent epidemiologic studies have show... more Iodine is crucial for thyroid hormone production. However, recent epidemiologic studies have shown that breast cancer patients have an elevated risk of developing thyroid cancer and vice versa. A notable finding in this study is that iodine stimulated the transcriptional activity of estrogen receptor-α (ER-α) in breast cancer cells. Iodine stimulated expression of several ER-α regulated gene including PS2, Cathepsin D, CyclinD1, and PR both in vitro and in nude mice, which is consistent with its stimulation of both anchorage-dependent and-independent growth of ER-α positive breast cancer cells and the effect to dampen tumor shrinkage of MCF-7 xenograft in ovariectomized nude mice. Analyses of clinical urine samples from breast cancer patients undergoing surgery demonstrated that urinary iodine levels were significantly higher than that in controls; and this increased level is due to the antiseptic use of iodine during breast surgery. The present study indicates that excess iodine intake may be an unfavorable factor in breast cancer by stimulation of ER-α transcriptional activity.
Specific uptake of tritiated 17b-oestradiol and R5020, a synthetic progestin, in breast cancer ce... more Specific uptake of tritiated 17b-oestradiol and R5020, a synthetic progestin, in breast cancer cell lines (MCF7 and T47D) growing in monolayer culture in multiwelt plates has been shown. Binding characteristics, calculated by Scatchard analysis, indicate the presence of steroid receptors of similar affinities and capacities to those already obtained with broken cell preparations. Lysis of the cells by treatment with a hypotonic buffer reveals the subcellular localization of the receptors so the method can be used to study receptor dynamics such as nuclear translocation and processing. Cell growth can be measured by DNA determination directly in the multiwell plates. Thus, the method provides a convenient way of studying the effects of steroid hormones (or any antihormone or chemotherapeutic agent) on growth and receptor content of breast cancer cells in monolayer culture.
Monoclonal antibodies (MAbs), recently produced against human progesterone receptors (PR), were u... more Monoclonal antibodies (MAbs), recently produced against human progesterone receptors (PR), were used for immunocytochemical localization of PR. The specificity of the immunocytochemical assay for PR was demonstrated by incubation with control MAbs, preabsorption of MAbs with highly purified human PR, and by the cell and tissue distribution of the immunostaining reaction. With human breast cancer cell lines, immunoreactivity was confined to cells that contain PR by steroid-binding assay. Moreover, immunostaining was induced by estradiol in estrogen-responsive cells, MCF-7 and ZR-75-1. In a preliminary study with 33 breast carcinomas, a good correspondence was obtained between immunocytochemical staining and PR content assessed by conventional steroid-binding assay. Immunoperoxidase localization was also obtained with other human target tissues. In normal breast and benign breast disease, immunoreactivity was observed with nuclei of ductal epithelial cells and hyperplastic epithelium. In uterus, immunostaining of endometrium was localized to nuclei of stromal and glandular epithelial cells and in myometrium to nuclei of smooth muscle cells. The effect of the progestin agonist, R5020, and antagonist, RU 486, on PR localization was investigated with the PR-rich T47D human breast cancer cell line. In the absence of hormone, immunostaining was exclusively nuclear. This was true under a number of cell culture conditions designed to eliminate endogenous progestins from the culture medium. Exclusive nuclear localization of PR was not due to a failure of the MAbs to recognize unoccupied PR, since each MAb bound equally well in vitro with different receptor forms. These included liganded and unliganded cytosol PR, molybdate stabilized PR, and nuclear-transformed receptors. Nor was failure to detect cytoplasmic staining due to a selective destruction or loss of unoccupied PR from the cytoplasmic compartment as a result of cell fixation. This was assessed by dot blot immunoassay of PR antigen distribution in subcellular fractions of fixed and unfixed cells. Continuous exposure of cells to R5020 resulted in a transient (30-60 min) increase in nuclear staining intensity (without change in cytoplasmic reactivity), followed by a progressive decline in immunoreactivity. By 24 h of R5020 treatment, the vast majority of cells displayed no immunostaining reaction. These immunocytochemical data are consistent with progestins down regulating their own receptors due to a loss in cellular PR content and not to inactivation of receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
Human maternal placentophagy is a rare but growing practice in several industrialized countries a... more Human maternal placentophagy is a rare but growing practice in several industrialized countries among postpartum mothers seeking a variety of purported health benefits attributed to the practice. These postpartum mothers typically consume their placenta as a processed, encapsulated supplement. To determine whether free (unconjugated) steroid hormones and melatonin in placenta can survive the encapsulation process (namely steaming and dehydration), we analyzed 28 placenta samples processed for encapsulation using liquid chromatography tandem-mass spectrometry (LC-MS/MS) to evaluate the concentration of 17 hormones. The results revealed detectable concentrations for 16 of the hormones analyzed, some in concentrations that could conceivably yield physiological effects.
European Journal of Cancer and Clinical Oncology, Aug 1, 1983
A model system is presented to explain how tyrosinase, an enzyme unique to pigmented cells such a... more A model system is presented to explain how tyrosinase, an enzyme unique to pigmented cells such as normal and malignant melanocytes can oxidize ['HI-estradiol to radiolabeled products which closely resemble the tight binding of ['HI-estradiol to estrogen receptor. In the modelsystem studied, tyrosinaseoxidized [2,4,6,7-3H]-estradiol to ['HI-water and ['HI-estradiol metabolites, the latter of which formed ring-substituted conjugates with nucleophiles like monothioglycerol and BSA. Radiolabeled estradiol without tritium in the C-2 position (i.e. [6,7-3H]-estrudiol) failed to liberate [3H]-water when exposed to tyrosinase but, nevertheless, did form ring-substituted ['HI-estrudiol adducts with nucleophiles. The ['HI-water and the ring-substituted radiolabeled products possessed several characteristics of a genuine estrogen receptor protein in that they were resistant to dextran-coated charcoal (DCC) adsorption and their enzymatic formation was inhibited with non-steroidal estrogens like diethylstilbestrol. Other natural (estradiol) and synthetic (hydroxytamoxijen) estrogens which contain the phenol grouping aLso inhibited the enzymatic oxidation of ['HI-estradiol. Although it was difficult to differentiate estrogen receptor from tyrosinase using the conventional DCC assay system, several differences in these two proteins permitted a distinction to be made between them. First, tyrosinase oxidation of['H]-estrudiol wasmarkedly inhibited by sulfhydyl reducing agents (monothioglycerol) that stabilize ['HIestradiol binding to estrogen receptor. Second, estrogen receptor adsorbed by hydroxylapatite whereas tyrosinase did not, thus permitting the separation of these two proteins prior to incubation with ['HI-estrudiol. We conclude that the ['HIestradiol binding components in melanoma previously reported to be estrogen receptor probably represent instead the radiolabeled products of the tyrosinasecatalyzed oxidation of ['HI-estradiol.
Introduction: High dose testosterone (T) has been used for treating hormone-sensitive breast canc... more Introduction: High dose testosterone (T) has been used for treating hormone-sensitive breast cancers for many years. However, a drawback to T therapy is its propensity to convert to estradiol (E2) via aromatase, which can override the growth inhibitory effects of T and stimulate estrogen sensitive tumors. Aromatase is higher in some women than others, particularly those with active tumors, truncal obesity, and inflammatory conditions contributing to and caused by cancer. Oral aromatase inhibitors (AI) have been used to prevent conversion of T to E2. While this effectively reduces E2 burden, systemic oral AI require higher dosing, which often leads to severe side effects. As an alternative to oral AI therapy, researchers have found that T combined with a much lower dose of AI in a solitary pellet implant placed in the subcutaneous (SC) tissue, or alternatively, into the breast adjacent to a primary tumor, is effective in reducing tumor burden and maintaining a low systemic level of E...
Introduction: PCOS is one of the most common endocrine issues affecting women today, with almost ... more Introduction: PCOS is one of the most common endocrine issues affecting women today, with almost 10% of women suffering from this condition. CAH is a rarer disease that affects both men and women at a rate of around 1:1000 people. The problem with these two disorders arises in the fact that variants of these conditions may have very similar clinical presentations. This makes a proper diagnosis and treatment protocol difficult. Both PCOS and CAH present with high androgens but differ in that the former usually presents with high cortisol/insulin resistance, and the latter with low cortisol and aldosterone. Another difficulty in diagnosis is due to CAH presenting itself in 4 variants; 21-hydroxylase deficiency, the most common with over 95% prevalence, 11-hydroxylase deficiency, 3β-hydroxysteroid dehydrogenase type 2 deficiency, and 17α-hydroxylase deficiency. We have developed and validated an LC-MS/MS assay using a first morning saliva that measures a full panel of steroids necessar...
Aim: Coronavirus disease 2019 antibody testing often relies on venous blood collection, which is ... more Aim: Coronavirus disease 2019 antibody testing often relies on venous blood collection, which is labor-intensive, inconvenient and expensive compared with finger-stick capillary dried blood spot (DBS) collection. The purpose of our work was to determine if two commercially available anti-severe acute respiratory syndrome coronavirus 2 enzyme-linked immunosorbent assays for IgG antibodies against spike S1 subunit and nucleocapsid proteins could be validated for use with DBS. Materials & methods: Kit supplied reagents were used to extract DBS, and in-house DBS calibrators were included on every run. Results: Positive/negative concordance between DBS and serum was 100/99.3% for the spike S1 subunit assay and 100/98% for the nucleocapsid assay. Conclusion: Validation of the DBS Coronavirus disease 2019 IgG antibody assays demonstrated that serum and DBS can produce equivalent results with minimal kit modifications.
Many FA who flew prior to the ban on smoking in commercial aircraft exhibit an unusual pattern of... more Many FA who flew prior to the ban on smoking in commercial aircraft exhibit an unusual pattern of long-term pulmonary dysfunction. This randomized controlled study tested the hypothesis that digitally delivered meditative movement (MM) training improves chronic obstructive pulmonary disease (COPD)-related symptoms in flight attendants (FA) who were exposed to secondhand cigarette smoke (SHCS) while flying. Phase I of this two-phase clinical trial was a single-arm non-randomized pilot study that developed and tested methods for MM intervention; we now report on Phase II, a randomized controlled trial comparing MM to a control group of similar FA receiving health education (HE) videos. Primary outcomes were the 6-min walk test and blood levels of high sensitivity C-reactive protein (hs-CRP). Pulmonary, cardiovascular, autonomic and affective measures were also taken. There were significant improvements in the 6-min walk test, the Multidimensional Assessment of Interoceptive Awareness (MAIA) score, and the COPD Assessment Test. Non-significant trends were observed for increased dehydroepiandrosterone sulfate (DHEAS) levels, decreased anxiety scores and reduced blood hs-CRP levels, and increased peak expiratory flow (PEF). In a Survey Monkey questionnaire, 81% of participants who completed pre and post-testing expressed mild to strong positive opinions of the study contents, delivery, or impact, while 16% expressed mild negative opinions. Over the course of the year including the study, participant adoption of the MM practices showed a significant and moderately large correlation with overall health improvement; Pearson's R = 0.62, p < 0.005. These results support the hypothesized benefits of video-based MM training for this population. No adverse effects were reported.
Objectives Little psychoneuroendocrine research has focused on steroid hormone responses to non-p... more Objectives Little psychoneuroendocrine research has focused on steroid hormone responses to non-physical competition in middle childhood. This study sought to observe testosterone, estradiol, dehydroepiandrosterone (DHEA), androstenedione, and cortisol responses in children during a mixed-sex, team, academic competition. Methods Salivary steroid hormones were collected, along with measures of performance, Body Mass Index, and pubertal development in ethnically Chinese boys (n = 18) and girls (n = 27), aged 9-10 years, during a math competition (N = 45). Results Testosterone and estradiol levels were generally low and unmeasurable. Nearly every competitor experienced decreases in cortisol and cortisol/DHEA molar ratio. Preand post-match DHEA and androstenedione did not significantly change. Exploratory analyses revealed a positive correlation between DHEA change and team performance among non-active participants (i.e. did not attempt to answer a question). ANCOVAs revealed differences in percentage change in androstenedione between active (n = 20) and non-active participants (n = 25) and among winners (n = 7) and losers (n = 38), and positive associations with age. Percentage change in cortisol was significantly lower among losers compared to winners. Performance measures were positively correlated with DHEA change and percentage change in androstenedione.
Japanese iodine intake from edible seaweeds is amongst the highest in the world. Predicting the t... more Japanese iodine intake from edible seaweeds is amongst the highest in the world. Predicting the type and amount of seaweed the Japanese consume is difficult due to day-today meal variation and dietary differences between generations and regions. In addition, iodine content varies considerably between seaweed species, with cooking and/or processing having an influence on iodine content. Due to all these factors, researchers frequently overestimate, or underestimate, Japanese iodine intake from seaweeds, which results in misleading and potentially dangerous diet and supplementation recommendations for people aiming to achieve the same health benefits seen by the Japanese. By combining information from dietary records, food surveys, urine iodine analysis (both spot and 24-hour samples) and seaweed iodine content, we estimate that the Japanese iodine intake-largely from seaweeds-averages 1,000-3,000 μg/day (1-3 mg/day).
h i g h l i g h t s Dried urine iodine and creatinine extract quantitatively correlates well with... more h i g h l i g h t s Dried urine iodine and creatinine extract quantitatively correlates well with liquid urine. Filter paper strips can be easily shipped and stored. Urine iodine and creatinine are stable at ambient temperature when dried on filter paper. Dried urine iodine and creatinine are run using a 96-well format.
Daily injections of estradiol or the antiestrogen tamoxifen initially stimulate uterine weight in... more Daily injections of estradiol or the antiestrogen tamoxifen initially stimulate uterine weight increase and progesterone receptor synthesis, though continued tamoxifen fails to maintain the increased weight. The stimulatory actions of both estradiol and tamoxifen are inhibited or reversed by a single injection of progesterone. It has been hypothesized that progesterone antagonizes estrogen action by reducing estrogen receptor levels, but in the present experiments neither cytoplasmic nor nuclear estrogen receptor was affected. We conclude that progesterone acts at a point beyond estrogen receptor availability or translocation to antagonize estrogen action.
Six patients with inoperable, nonoperative, or recurrent meningiomas were treated with the anties... more Six patients with inoperable, nonoperative, or recurrent meningiomas were treated with the antiestrogenic agent tamoxifen (Nolvadex) during an 8-12-month period. Computer tomographic, scintigraphic, and clinical evidence of an unspecific tumor response was only encountered in one patient after 4 months of therapy with tamoxifen. The 2-year results did not indicate a favorable response to antiestrogenic treatment. The significance of sex-steroid receptors and their possible prognostic value in endocrine therapy of meningiomas is discussed.
In this study we report on the content and bioactivity of plant (phyto) estrogens and progestins ... more In this study we report on the content and bioactivity of plant (phyto) estrogens and progestins in various foods, herbs, and spices, before and after human consumption. Over 150 herbs traditionally used by herbalists for treating a variety of health problems were extracted and tested for their relative capacity to compete with estradiol and progesterone binding to intracellular receptors for progesterone (PR) and estradiol (ER) in intact human breast cancer cells. The six highest ERbinding herbs that are commonly consumed were soy, licorice, red clover, thyme, tumeric, hops, and verbena. The six highest PR-binding herbs and spices commonly consumed were oregano, verbena, tumeric, thyme, red clover and damiana. Some of the herbs and spices found to contain high phytoestrogens and phytoprogestins were further tested for bioactivity based on their ability to regulate cell growth rate in ER (+) and ER (-) breast cancer cell lines and to induce or inhibit the synthesis of alkaline phosphatase, an end product of progesterone action, in PR (+) cells. In general, we found that ER-binding herbal extracts were agonists, much like estradiol, whereas PR-binding extracts, were neutral or antagonists. The bioavailability of phytoestrogens and phytoprogestins in vivo were studied by quantitating the ER-binding and PR-binding capacity of saliva following consumption of soy milk, exogenous progesterone, medroxyprogesterone acetate, or wild mexican yam products containing diosgenin. Soy milk caused a dramatic increase in saliva ER-binding components without a concomitant rise in estradiol. Consumption of PR-binding herbs increased the progestin activity of saliva, but there were marked differences in bioactivity. In summary, we have demonstrated that many of the commonly consumed foods, herbs, and spices contain phytoestrogens and phytoprogestins that act as agonists and antagonists in vivo.
A study protocol is presented for the investigation of meditative movement (MM) as a treatment fo... more A study protocol is presented for the investigation of meditative movement (MM) as a treatment for pulmonary dysfunction in flight attendants (FA) who were exposed to secondhand cigarette smoke while flying before the smoking ban. The study will have three parts, some of which will run concurrently. The first is a data gathering and screening phase, which will gather data on pulmonary and other aspects of the health of FA, and will also serve to screen participants for the other phases. Second is an exercise selection phase, in which a variety of MM exercises will be taught, over a 16-week period, to a cohort of 20 FA. A subset of these exercises will be selected on the basis of participant feedback on effectiveness and compliance. Third is a 52-week randomized controlled trial to evaluate the effectiveness of a digitally delivered form of the previously selected exercises on a group of 20 FA, as compared with an attention control group. Outcome measures to be used in all three parts of the study include the 6-min walk test as a primary measure, as well as a range of biomarkers, tests, and questionnaires documenting hormonal, cardio-respiratory, autonomic, and affective state. This study is registered at ClinicalTrials.gov. Identifier: NCT02612389.
Sex hormone metabolism is altered during mammary gland tumorigenesis, and different metabolites m... more Sex hormone metabolism is altered during mammary gland tumorigenesis, and different metabolites may have different effects on mammary epithelial cells. This study aimed to evaluate associations between urinary sexual metabolite levels and breast cancer risk among premenopausal women of Mainland China. The molecular metabolism of the cancer-related metabolites was also explored based on the clinical data. The sex hormone metabolites in the urine samples of patients with breast cancer versus normal healthy women were analyzed comprehensively. Among many alterations of sex hormone metabolisms, 4-hydroxy estrogen (4-OH-E) metabolite was found to be significantly increased in the urine samples of patients with breast cancer compared with the normal healthy controls. This was the most important risk factor for breast cancer. Several experiments were conducted in vitro and in vivo to probe this mechanism. 4-Hydroxyestradiol (4-OH-E2) was found to induce malignant transformation of breast cells and tumorigenesis in nude mice. At the molecular level, 4-OH-E2 compromised the function of spindle-assembly checkpoint and rendered resistance to the anti-microtubule drug. Further, transgenic mice with high expression of CYP1B1, a key enzyme of 4-hydroxy metabolites, were established and stimulated with estrogen. Cancerous tissue was found to appear in the mammary gland of transgenic mice.
Summay.-This study investigated in 40 young university women the possible relationships between l... more Summay.-This study investigated in 40 young university women the possible relationships between levels of testosterone and specific measures of overall self-confidence and self-confidence in approaching mathematics. Correlations of-.43 and-.49 with each measure of self-confidence, respecrively, and level of testosterone were found in the portion of the sample displaying normal ovulatory function. There was no correlation (r=.02) benveen the measures of mathematics and overall self-confidence. 19 women did nor display normal ovulatory function. The only significant result for the full sample was a significant correlation of-.73 benveen scores on the Bem Sex Role hventory Mascuhiry and overall self-confidence. The reasons for the high anovulatory percentage are not clear, nor are the associations which anovulation might have with either hormonal levels or the personality characteristics in question.
Iodine is crucial for thyroid hormone production. However, recent epidemiologic studies have show... more Iodine is crucial for thyroid hormone production. However, recent epidemiologic studies have shown that breast cancer patients have an elevated risk of developing thyroid cancer and vice versa. A notable finding in this study is that iodine stimulated the transcriptional activity of estrogen receptor-α (ER-α) in breast cancer cells. Iodine stimulated expression of several ER-α regulated gene including PS2, Cathepsin D, CyclinD1, and PR both in vitro and in nude mice, which is consistent with its stimulation of both anchorage-dependent and-independent growth of ER-α positive breast cancer cells and the effect to dampen tumor shrinkage of MCF-7 xenograft in ovariectomized nude mice. Analyses of clinical urine samples from breast cancer patients undergoing surgery demonstrated that urinary iodine levels were significantly higher than that in controls; and this increased level is due to the antiseptic use of iodine during breast surgery. The present study indicates that excess iodine intake may be an unfavorable factor in breast cancer by stimulation of ER-α transcriptional activity.
Specific uptake of tritiated 17b-oestradiol and R5020, a synthetic progestin, in breast cancer ce... more Specific uptake of tritiated 17b-oestradiol and R5020, a synthetic progestin, in breast cancer cell lines (MCF7 and T47D) growing in monolayer culture in multiwelt plates has been shown. Binding characteristics, calculated by Scatchard analysis, indicate the presence of steroid receptors of similar affinities and capacities to those already obtained with broken cell preparations. Lysis of the cells by treatment with a hypotonic buffer reveals the subcellular localization of the receptors so the method can be used to study receptor dynamics such as nuclear translocation and processing. Cell growth can be measured by DNA determination directly in the multiwell plates. Thus, the method provides a convenient way of studying the effects of steroid hormones (or any antihormone or chemotherapeutic agent) on growth and receptor content of breast cancer cells in monolayer culture.
Monoclonal antibodies (MAbs), recently produced against human progesterone receptors (PR), were u... more Monoclonal antibodies (MAbs), recently produced against human progesterone receptors (PR), were used for immunocytochemical localization of PR. The specificity of the immunocytochemical assay for PR was demonstrated by incubation with control MAbs, preabsorption of MAbs with highly purified human PR, and by the cell and tissue distribution of the immunostaining reaction. With human breast cancer cell lines, immunoreactivity was confined to cells that contain PR by steroid-binding assay. Moreover, immunostaining was induced by estradiol in estrogen-responsive cells, MCF-7 and ZR-75-1. In a preliminary study with 33 breast carcinomas, a good correspondence was obtained between immunocytochemical staining and PR content assessed by conventional steroid-binding assay. Immunoperoxidase localization was also obtained with other human target tissues. In normal breast and benign breast disease, immunoreactivity was observed with nuclei of ductal epithelial cells and hyperplastic epithelium. In uterus, immunostaining of endometrium was localized to nuclei of stromal and glandular epithelial cells and in myometrium to nuclei of smooth muscle cells. The effect of the progestin agonist, R5020, and antagonist, RU 486, on PR localization was investigated with the PR-rich T47D human breast cancer cell line. In the absence of hormone, immunostaining was exclusively nuclear. This was true under a number of cell culture conditions designed to eliminate endogenous progestins from the culture medium. Exclusive nuclear localization of PR was not due to a failure of the MAbs to recognize unoccupied PR, since each MAb bound equally well in vitro with different receptor forms. These included liganded and unliganded cytosol PR, molybdate stabilized PR, and nuclear-transformed receptors. Nor was failure to detect cytoplasmic staining due to a selective destruction or loss of unoccupied PR from the cytoplasmic compartment as a result of cell fixation. This was assessed by dot blot immunoassay of PR antigen distribution in subcellular fractions of fixed and unfixed cells. Continuous exposure of cells to R5020 resulted in a transient (30-60 min) increase in nuclear staining intensity (without change in cytoplasmic reactivity), followed by a progressive decline in immunoreactivity. By 24 h of R5020 treatment, the vast majority of cells displayed no immunostaining reaction. These immunocytochemical data are consistent with progestins down regulating their own receptors due to a loss in cellular PR content and not to inactivation of receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
Human maternal placentophagy is a rare but growing practice in several industrialized countries a... more Human maternal placentophagy is a rare but growing practice in several industrialized countries among postpartum mothers seeking a variety of purported health benefits attributed to the practice. These postpartum mothers typically consume their placenta as a processed, encapsulated supplement. To determine whether free (unconjugated) steroid hormones and melatonin in placenta can survive the encapsulation process (namely steaming and dehydration), we analyzed 28 placenta samples processed for encapsulation using liquid chromatography tandem-mass spectrometry (LC-MS/MS) to evaluate the concentration of 17 hormones. The results revealed detectable concentrations for 16 of the hormones analyzed, some in concentrations that could conceivably yield physiological effects.
European Journal of Cancer and Clinical Oncology, Aug 1, 1983
A model system is presented to explain how tyrosinase, an enzyme unique to pigmented cells such a... more A model system is presented to explain how tyrosinase, an enzyme unique to pigmented cells such as normal and malignant melanocytes can oxidize ['HI-estradiol to radiolabeled products which closely resemble the tight binding of ['HI-estradiol to estrogen receptor. In the modelsystem studied, tyrosinaseoxidized [2,4,6,7-3H]-estradiol to ['HI-water and ['HI-estradiol metabolites, the latter of which formed ring-substituted conjugates with nucleophiles like monothioglycerol and BSA. Radiolabeled estradiol without tritium in the C-2 position (i.e. [6,7-3H]-estrudiol) failed to liberate [3H]-water when exposed to tyrosinase but, nevertheless, did form ring-substituted ['HI-estrudiol adducts with nucleophiles. The ['HI-water and the ring-substituted radiolabeled products possessed several characteristics of a genuine estrogen receptor protein in that they were resistant to dextran-coated charcoal (DCC) adsorption and their enzymatic formation was inhibited with non-steroidal estrogens like diethylstilbestrol. Other natural (estradiol) and synthetic (hydroxytamoxijen) estrogens which contain the phenol grouping aLso inhibited the enzymatic oxidation of ['HI-estradiol. Although it was difficult to differentiate estrogen receptor from tyrosinase using the conventional DCC assay system, several differences in these two proteins permitted a distinction to be made between them. First, tyrosinase oxidation of['H]-estrudiol wasmarkedly inhibited by sulfhydyl reducing agents (monothioglycerol) that stabilize ['HIestradiol binding to estrogen receptor. Second, estrogen receptor adsorbed by hydroxylapatite whereas tyrosinase did not, thus permitting the separation of these two proteins prior to incubation with ['HI-estrudiol. We conclude that the ['HIestradiol binding components in melanoma previously reported to be estrogen receptor probably represent instead the radiolabeled products of the tyrosinasecatalyzed oxidation of ['HI-estradiol.
Introduction: High dose testosterone (T) has been used for treating hormone-sensitive breast canc... more Introduction: High dose testosterone (T) has been used for treating hormone-sensitive breast cancers for many years. However, a drawback to T therapy is its propensity to convert to estradiol (E2) via aromatase, which can override the growth inhibitory effects of T and stimulate estrogen sensitive tumors. Aromatase is higher in some women than others, particularly those with active tumors, truncal obesity, and inflammatory conditions contributing to and caused by cancer. Oral aromatase inhibitors (AI) have been used to prevent conversion of T to E2. While this effectively reduces E2 burden, systemic oral AI require higher dosing, which often leads to severe side effects. As an alternative to oral AI therapy, researchers have found that T combined with a much lower dose of AI in a solitary pellet implant placed in the subcutaneous (SC) tissue, or alternatively, into the breast adjacent to a primary tumor, is effective in reducing tumor burden and maintaining a low systemic level of E...
Introduction: PCOS is one of the most common endocrine issues affecting women today, with almost ... more Introduction: PCOS is one of the most common endocrine issues affecting women today, with almost 10% of women suffering from this condition. CAH is a rarer disease that affects both men and women at a rate of around 1:1000 people. The problem with these two disorders arises in the fact that variants of these conditions may have very similar clinical presentations. This makes a proper diagnosis and treatment protocol difficult. Both PCOS and CAH present with high androgens but differ in that the former usually presents with high cortisol/insulin resistance, and the latter with low cortisol and aldosterone. Another difficulty in diagnosis is due to CAH presenting itself in 4 variants; 21-hydroxylase deficiency, the most common with over 95% prevalence, 11-hydroxylase deficiency, 3β-hydroxysteroid dehydrogenase type 2 deficiency, and 17α-hydroxylase deficiency. We have developed and validated an LC-MS/MS assay using a first morning saliva that measures a full panel of steroids necessar...
Aim: Coronavirus disease 2019 antibody testing often relies on venous blood collection, which is ... more Aim: Coronavirus disease 2019 antibody testing often relies on venous blood collection, which is labor-intensive, inconvenient and expensive compared with finger-stick capillary dried blood spot (DBS) collection. The purpose of our work was to determine if two commercially available anti-severe acute respiratory syndrome coronavirus 2 enzyme-linked immunosorbent assays for IgG antibodies against spike S1 subunit and nucleocapsid proteins could be validated for use with DBS. Materials & methods: Kit supplied reagents were used to extract DBS, and in-house DBS calibrators were included on every run. Results: Positive/negative concordance between DBS and serum was 100/99.3% for the spike S1 subunit assay and 100/98% for the nucleocapsid assay. Conclusion: Validation of the DBS Coronavirus disease 2019 IgG antibody assays demonstrated that serum and DBS can produce equivalent results with minimal kit modifications.
Many FA who flew prior to the ban on smoking in commercial aircraft exhibit an unusual pattern of... more Many FA who flew prior to the ban on smoking in commercial aircraft exhibit an unusual pattern of long-term pulmonary dysfunction. This randomized controlled study tested the hypothesis that digitally delivered meditative movement (MM) training improves chronic obstructive pulmonary disease (COPD)-related symptoms in flight attendants (FA) who were exposed to secondhand cigarette smoke (SHCS) while flying. Phase I of this two-phase clinical trial was a single-arm non-randomized pilot study that developed and tested methods for MM intervention; we now report on Phase II, a randomized controlled trial comparing MM to a control group of similar FA receiving health education (HE) videos. Primary outcomes were the 6-min walk test and blood levels of high sensitivity C-reactive protein (hs-CRP). Pulmonary, cardiovascular, autonomic and affective measures were also taken. There were significant improvements in the 6-min walk test, the Multidimensional Assessment of Interoceptive Awareness (MAIA) score, and the COPD Assessment Test. Non-significant trends were observed for increased dehydroepiandrosterone sulfate (DHEAS) levels, decreased anxiety scores and reduced blood hs-CRP levels, and increased peak expiratory flow (PEF). In a Survey Monkey questionnaire, 81% of participants who completed pre and post-testing expressed mild to strong positive opinions of the study contents, delivery, or impact, while 16% expressed mild negative opinions. Over the course of the year including the study, participant adoption of the MM practices showed a significant and moderately large correlation with overall health improvement; Pearson's R = 0.62, p < 0.005. These results support the hypothesized benefits of video-based MM training for this population. No adverse effects were reported.
Objectives Little psychoneuroendocrine research has focused on steroid hormone responses to non-p... more Objectives Little psychoneuroendocrine research has focused on steroid hormone responses to non-physical competition in middle childhood. This study sought to observe testosterone, estradiol, dehydroepiandrosterone (DHEA), androstenedione, and cortisol responses in children during a mixed-sex, team, academic competition. Methods Salivary steroid hormones were collected, along with measures of performance, Body Mass Index, and pubertal development in ethnically Chinese boys (n = 18) and girls (n = 27), aged 9-10 years, during a math competition (N = 45). Results Testosterone and estradiol levels were generally low and unmeasurable. Nearly every competitor experienced decreases in cortisol and cortisol/DHEA molar ratio. Preand post-match DHEA and androstenedione did not significantly change. Exploratory analyses revealed a positive correlation between DHEA change and team performance among non-active participants (i.e. did not attempt to answer a question). ANCOVAs revealed differences in percentage change in androstenedione between active (n = 20) and non-active participants (n = 25) and among winners (n = 7) and losers (n = 38), and positive associations with age. Percentage change in cortisol was significantly lower among losers compared to winners. Performance measures were positively correlated with DHEA change and percentage change in androstenedione.
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