Papers by gordon strewler
BoneKEy osteovision, Apr 1, 2007
BoneKEy osteovision, Dec 1, 2006
BoneKEy osteovision, Mar 1, 2007
Osteocyte apoptosis is an important early step in the activation and targeting of osteoclastic re... more Osteocyte apoptosis is an important early step in the activation and targeting of osteoclastic resorption after fatigue damage. Osteocytes surrounding microcracks undergo apoptosis and co-localize with areas resorbed by osteoclasts. A pan-caspase inhibitor blocked fatigue-induced apoptosis and the activation of osteoclastic resorption.-ES Chen Y, Alman BA. Wnt pathway, an essential role in bone regeneration.
BoneKEy osteovision, Dec 1, 2007
BoneKEy osteovision, May 1, 2006
The hematopoietic stem cell niche has been defined as a microenvironment in bone that supports th... more The hematopoietic stem cell niche has been defined as a microenvironment in bone that supports the stem cell, controls decisions between quiescence and proliferation of stem cells, and provides a mechanism for the self-renewal of stem cells. It is likely that at least two hematopoietic stem cell niches exist in bone: an endosteal niche, in which hematopoietic stem cells are adherent to osteoblasts, and an endothelial niche. Like self-renewing adult tissues, tumors may also be maintained by stem cells. It is likely that a tumor stem cell niche also exists in bone and shares many of the characteristics of the hematopoietic stem cell niche. The principal determinants of bone metastasis may be factors in this microenvironment that control the entry of tumor cells into the niche, permit long-term quiescence of tumor stem cells within the niche and induce their eventual awakening.
Cell Metabolism, Aug 1, 2007
Surgical Clinics of North America, Jun 1, 1995
Journal of Biological Chemistry, 1978
Incubation of homogenates of rat renal cortex at 4 degrees resulted in increased cAMP phosphodies... more Incubation of homogenates of rat renal cortex at 4 degrees resulted in increased cAMP phosphodiesterase activity; the increase was much more rapid in hypotonic medium than in one of physiological tonicity. cAMP phosphodiesterase activity did not increase with incubation of supernatant fractions (48,000 x g, 20 min) prepared from isotonic homogenates. Extraction of the isotonic particulate fraction with hypotonic buffer released an activator which increased cAMP phosphodiesterase activity of the supernatant fraction. The kidney phosphodiesterase activator differed from a heat-stable, calcium-dependent protein activator of phosphodiesterase in that it was destroyed by heating (90 degrees for 10 min) and was not inhibited by EGTA. The phosphodiesterases of rat renal cortex were partially resolved by chromatography on DEAE-Bio-Gel, and a cAMP phosphodiesterase that is sensitive to the kidney activator was identified. This phosphodiesterase was separable from that affected by a calcium-dependent phosphodiesterase activator from bovine brain and from cGMP-stimulated cAMP phosphodiesterase. As determined by sucrose density gradient centrifugation, after incubation with the kidney activator, the activated form of phosphodiesterase had a lower sedimentation velocity than did the unactivated form.
Neurology, Aug 1, 1972
The spread of heroin use from urban ghettoes t o suburbs and towns and from hardcore addicts to a... more The spread of heroin use from urban ghettoes t o suburbs and towns and from hardcore addicts to a larger youthful population has been a matter of current attention and concern. The cardiac, pulmonary, hepatic, and infectious complications have been described in detail;’ less has been written about the neurological complications. In the most extensive report of such complications so far published, Richter and Baden have described transverse myelitis, middle cerebral artery occlusion, septic embolism with abscess formation, bland embolism with infarction, and bilateral necrosis of the basal ganglia in the addict population a t Harlem HospitaL2 We recently cared for a young woman who developed a left hemiparesis following heroin injection. The circumstances surrounding this and the results of subsequent laboratory and angiographic studies suggested that her stroke was the result of a hypersensitivity reaction to either the drug or to a substance that had been used to cut it. Since a hypersensitivity reaction has also been suggested as the cause of the transverse myelitis seen in heroin addicts, we felt that this case should be put o n record.
American Journal of Physiology-renal Physiology, Feb 1, 1986
The renal effects of parathyroid hormone (PTH) include a decreased rate of acidification by the p... more The renal effects of parathyroid hormone (PTH) include a decreased rate of acidification by the proximal tubule. To determine whether this effect represented a PTH action on the Na+-H+ antiporter, we investigated the effect of PTH on the established opossum kidney (OK) cell line. This cell line retains several features characteristic of proximal tubule cells, including an amiloride-sensitive Na+-H+ antiporter and high-affinity PTH receptors with a coupled cAMP response. We measured steady-state intracellular pH and amiloride-sensitive 22Na+ uptake as a reflection of the activity of the Na+-H+ antiporter. Under bicarbonate and CO2-free conditions, the steady-state intracellular pH of OK cell cultures was modified by altering the rate of Na+-H+ exchange. When Na+-H+ exchange was inhibited by amiloride, intracellular pH fell. Conversely, augmenting antiporter activity by addition of monensin, a Na+-H+ exchange ionophore, raised intracellular pH. PTH (2.5 X 10(-8) M) lowered intracellular pH by up to 0.17 pH units, and half of the maximum PTH effect was present at a concentration of 10(-12) M. This effect was not seen in the presence of amiloride or in the absence of sodium, suggesting that a functional Na+-H+ antiporter is necessary for its expression. The decrease in intracellular pH was reproduced by forskolin and 8-bromo-cAMP, suggesting that this is a cAMP-mediated effect. PTH, forskolin, and 8-bromo-cAMP also decreased the amiloride-sensitive component of 22Na+ uptake in OK cells by up to 64%, whereas the amiloride-insensitive component was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
Molecular Endocrinology, Apr 1, 1990
Differentiation of mouse embryonal carcinoma cells to the parietal endoderm phenotype is associat... more Differentiation of mouse embryonal carcinoma cells to the parietal endoderm phenotype is associated with expression of PTH-responsive adenylate cyclase. A PTH-like protein (PLP), which binds to PTH receptors and activates adenylate cyclase in classical PTH target cells was recently isolated and cloned. We assessed whether the parietal endoderm phenotype is associated with the expression of PLP or its receptor. A 1.4-kilobase PLP transcript was detected in the mouse parietal endoderm cell line PYS-2. No hybridizing transcripts were evident in undifferentiated mouse embryonal carcinoma cells PSA-1 or F9. However, differentiation of these cells to parietal endoderm, either spontaneously (PSA-1) or by treatment with retinoic acid and dibutyryl cAMP (F9), resulted in expression of the 1.4-kilobase PLP message. Undifferentiated F9 cells displayed negligible specific binding of [ 12S l]PLP-(1-34)amide. When F9 cells were induced to differentiate to parietal endoderm, specific binding sites for [ 125 I]PLP-(1-34)amide were expressed in parallel with PLPresponsive adenylate cyclase. These receptors, like those in classical PTH target tissues, displayed identical affinity (K d = 5.2 niu) for bPTH-(1-34) and hPLP-(1-34)amide; with binding capacity (B max) of 6.6 x 10 4 sites/cell. In the presence of retinoic acid, exogenous PLP substituted for dibutyryl cAMP in a concentration-dependent fashion in promoting the differentiation of F9 cells to parietal endoderm. Thus, both PLP mRNA and PLP receptors coupled to adenylate cyclase are expressed during the differentiation of mouse embryonal carcinoma cells. Increased cAMP levels produced by autocrine stimulation of PLP receptors by PLP may contribute to differentiation of embryonal carcinoma cells into parietal endoderm.
BoneKEy osteovision, Oct 1, 2006
BoneKEy osteovision, Jul 1, 2005
One of the strongest areas of debate concerning low bone mass associated with low body size/under... more One of the strongest areas of debate concerning low bone mass associated with low body size/underweight at a younger age is whether bone mass in this case is well adapted and/or whether it is a hallmark of bone fragility. This paper is of interest because it compares BMD and microstructure as determined by high-resolution QCT at distal radius and tibia in young women with constitutional leaness (BMI < 16.5) and no hormonal disturbances to women with anorexia nervosa and controls. BMD and microstructural parameters were similarly decreased in lean women and those with longstanding anorexia nervosa, and the calculated breaking strength was also decreased.
Elsevier eBooks, 2001
Page 299. CHAPTER 1 7 Physiologic Actions of PTH and PTHrP V. Epidermal, Mammary, Reproductive, a... more Page 299. CHAPTER 1 7 Physiologic Actions of PTH and PTHrP V. Epidermal, Mammary, Reproductive, and Pancreatic Tissues JOHN “IYSOLMERSKI Yale University School of Medicine, New Haven, Connecticut 06520 ANDREW ...
Advances in Health Sciences Education, Jan 25, 2020
We conducted a study to compare medical school experiences, values, career paths, and career sati... more We conducted a study to compare medical school experiences, values, career paths, and career satisfaction of under-represented in medicine (URiM) and non-URiM physicians approximately 15 years after medical school, guided by the Theory of Planned Behavior and the concept of stereotype threat. The sample consisted of four graduating classes, 1996–1999, of Harvard Medical School, 20% of whom were URiM. URiM respondents came from families of lower educational attainment and graduated with more debt. As students, they reported a greater experience of stereotype threat and, and at graduation they showed a tendency to place a higher value on avoiding a career that places them under constant pressure. Concerning their current status, URiM respondents expressed a lower level of satisfaction with their career progress. Multivariable analyses indicated that across the entire sample, URiM status was not a significant predictor of employment in academic medicine, but that being in academic medicine was predicted by mentors’ encouragement for a research career, greater intention to pursue research, and a lower value on having a financially rewarding career. Lower career satisfaction was predicted by one’s status as URiM, employment in academic medicine, greater involvement in research, and a greater value on avoiding constant pressure. The data suggest that negative student experiences in medical school, combined with the lack of mentor encouragement and financial pressures may discourage URiM medical students from pursuing academic careers, and that pressures for productivity and working in academic medicine may degrade the satisfaction derived by physicians in general.
Journal of Clinical Investigation, Feb 1, 2001
Annual Review of Medicine, Feb 1, 1990
A parathyroid hormone-like peptide that probably causes hypercalcemia associated with solid tumor... more A parathyroid hormone-like peptide that probably causes hypercalcemia associated with solid tumors was recently characterized. It is a potent hypercalcemic and hypophosphatemic factor whose production is strongly associated with hypercalcemia and whose properties account for most aspects of the clinical syndrome. Diagnostic tests for this peptide have been developed. The parathyroid hormone-like peptide as well as other cytokines, such as tumor necrosis factor-alpha, likely play a role in causing hypercalcemia in multiple myeloma and lymphomas.
SpringerReference, Jan 20, 2012
This manuscript has beon npmducld fan the microfilm muter. UMI C h s the text directly from the o... more This manuscript has beon npmducld fan the microfilm muter. UMI C h s the text directly from the original or copy submitlad. Thus, some thesis and dissertation copies am in typewriter face, while others may be horn any type of computer printer. Tho quality of this nproducdkn b dopmdent upon tho quality of thr copy 8ubmbd. Broken or indistinct print, cdored or poor quality illus~tions a d photographs, print blmdhmugh, substandard margins, a d improp8r alignment un adversely a f W mprodUdl*m. In the unlikely event tht ihe ruthor did not send UMI a complete mmuscript and there are missing w s , them will be noted. Also, if unauthorited copyright material had to be removed, a note will indicate n8 deletion. Oversize materials (e.g., maps, drawings, chrrb) am reproduced by sectioning the original, beginning at Uw upper Wt-hnd comer and continuing fmm Id! to right in equal rrclionr with small wdaps. Photographs included in ths original rnanusdpt have been reprodwad xerographically in this copy. Higher qwlity 8" x 9" blKk and white photographic prints are availabb for my photographs or illustratkmt-ring in this copy for an additional chargo. Contact UMI dimtly to m r .
Journal of Bone and Mineral Research, Dec 3, 2009
A parathyroid hormone-related protein (PTHrP) is the probable cause of humoral hypercalcemia in m... more A parathyroid hormone-related protein (PTHrP) is the probable cause of humoral hypercalcemia in malignancy, but its normal physiologic role remains unknown. Since current evidence suggests that PTHrP may have a role in embryonic development, we cloned a genomic fragment that encodes chicken PTHrP (cPTHrP) and studied the expression of PTHrP in developing chick embryos. Blot hybridization of chicken genomic DNA with a cPTHrP genomic DNA probe showed a single band, suggesting that a single-copy gene encodes cPTHrP. By screening a chicken genomic library with the human probe an open reading frame was identified that corresponds to the human PTHrP (hPTHrP) exon IV. Compared to the human sequence the 5' splice junction is highly conserved and the two predicted propeptide residues are identical. The sequence predicts a mature peptide of 139 amino acids; all of the first 21 and 94 of the first 112, but only 8 of the final 27 residues of cPTHrP are identical to the human sequence. The structural features required for PTH receptor binding and activation are highly conserved between chicken and hPTHrP. Poly(A)-enriched RNA from 3-15 day chicken embryos was surveyed by hybridization to the chicken probe. A hybridizing band of 1.45 kb was found in tissues derived from all three germ layers, including brain, heart, lung, liver, gizzard, intestine, chorioallantoic membrane, yolk sac, and skeletal muscle. An additional 1.2 kb hybridizing band was found in some (issues. The conservation of the PTHrP sequence between chicken and mammals supports the view that PTHrP has an important physiologic role. The presence of PTHrP mRNA in early embryos suggests that this role may be in embryonic development.
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Papers by gordon strewler