Digital radiology departments could benefit from the ability to integrate and visualize data (e.g... more Digital radiology departments could benefit from the ability to integrate and visualize data (e.g. information reflecting complex workflow states) from all of their imaging and information management systems in one composite presentation view. Leveraging data warehousing tools developed in the business world may be one way to achieve this capability. In total, the concept of managing the information available in this data repository is known as Business Intelligence or BI. This paper describes the concepts used in Business Intelligence, their importance to modern Radiology, and the steps used in the creation of a prototype model of a data warehouse for BI using open-source tools.
Background: Glutamine is a critical amino acid for the metabolism of enterocytes, lymphocytes, an... more Background: Glutamine is a critical amino acid for the metabolism of enterocytes, lymphocytes, and other proliferating cells. Although supplementation with glutamine has been suggested for growing infants, its effect on protein metabolism has not been examined. Objective: The objective was to examine the effect of enteral glu- tamine or glycine on whole-body kinetics of glutamine, phenylala- nine, leucine, and urea
To study end-user attitudes and preferences with respect to radiology scheduling systems and to a... more To study end-user attitudes and preferences with respect to radiology scheduling systems and to assess implications for retention and extension of the referral base. A study of the institution's historical data indicated reduced satisfaction with the process of patient scheduling in recent years. Sixty physicians who referred patients to a single, large academic radiology department received the survey. The survey was designed to identify (A) the preferred vehicle for patient scheduling (on-line versus telephone scheduling) and (B) whether ease of scheduling was a factor in physicians referring patients to other providers. Referring physicians were asked to forward the survey to any appropriate office staff member in case the latter scheduled appointments for patients. Users were asked to provide comments and suggestions for improvement. The statistical method used was the analysis of proportions. Thirty-three responses were received, corresponding to a return rate of 55%. Twenty-six of the 33 respondents (78.8%, P < .01) stated they were willing to try an online scheduling system; 16 of which tried the system. Twelve of the 16 (75%, P < .05) preferred the on-line application to the telephone system, stating logistical simplification as the primary reason for preference. Three (18.75%) did not consider online scheduling to be more convenient than traditional telephone scheduling. One respondent did not indicate any preference. Eleven of 33 users (33.33%, P < .001) stated that they would change radiology service providers if expectations of scheduling ease are not met. On-line scheduling applications are becoming the preferred scheduling vehicle. Augmenting their capabilities and availability can simplify the scheduling process, improve referring physician satisfaction, and provide a competitive advantage. Referrers are willing to change providers if scheduling expectations are not met.
Transgenic animals expressing genes capable of repairing DNA may be a valuable tool to study the ... more Transgenic animals expressing genes capable of repairing DNA may be a valuable tool to study the effect of DNA-damaging agents on tissue- specific carcinogenesis. For this reason, we constructed a chimeric gene consisting of the promoter-regulatory region of the phosphoenolp) ruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) gene linked to the Esche- richia coli oda gene coding for O'-alkylguanine-DNA alkyltransferase and
PURPOSE We have previously reported inpatient imaging utilization trends at our institution from ... more PURPOSE We have previously reported inpatient imaging utilization trends at our institution from fiscal years (FY) 1984 through 2002. In this study, we assessed the trends in imaging utilization for inpatients from FY 2003 through 2012. METHOD AND MATERIALS In this institutional review board-approved, retrospective study performed at a 793-bed tertiary care academic institution, we reviewed imaging utilization in adult inpatients from October 1, 2002 through September 30, 2012 (FY 2003 through 2012) and recorded the gross number of imaging studies coded by modality (conventional [plain films and fluoroscopy], sonography, nuclear medicine [NM], CT, and MRI) and associated relative value units (RVUs). We used linear regression to assess trends in number of imaging studies and RVUs per case-mix-adjusted admissions (CMAA). RESULTS The total number of imaging studies as well as CT, NM and conventional studies adjusted for CMAA decreased (p=0.02, p=0.0006, p=0.0008 and p=0.001 respectivel...
... In the Northern Sierra terrane between latitudes 39°N and 40°N, which is the subject of this ... more ... In the Northern Sierra terrane between latitudes 39°N and 40°N, which is the subject of this paper, the Jurassic arc sequence is typified by an abundance of basaltic to andesitic volcanic rock deposited in marine environments ( [Harwood, 1992 and Hanson et al ... [Lowe, 1982]). ...
Although some information is available concerning the physiological alterations in vivo associate... more Although some information is available concerning the physiological alterations in vivo associated with spontaneous bovine ketosis, a broad study of pathways and possible changes of enzyme activities has not been carried out. To this aim, liver samples were taken from spontaneously ketotic cows, from the same cows when normal, and when starved for 96 hours. Measurements were made to ascertain
Background: To assess patterns of use of abdominal imaging in the emergency department (ED) from ... more Background: To assess patterns of use of abdominal imaging in the emergency department (ED) from 1990 to 2009. Methods: We retrospectively reviewed data on adult ED patients treated between 1990 and 2009 at our universityaffiliated quaternary care institution. Examinations were coded by abdominal imaging modality: x-ray, sonography, CT, or MRI. Proportional costs for each imaging modality were evaluated using relative value units (RVUs). Chisquare tests were used to assess for significant trends. Results: The intensity of abdominal imaging per 1,000 ED visits increased 19.3% from 1990-2009 (p = 0.0050). The number of abdominal CT scans per 1,000 ED visits increased 17.5-fold (p < 0.0001). Similarly, the number of abdominal MRIs per 1,000 ED visits increased from 0 to 1.0 (p < 0.0001), and the number of abdominal sonographs per 1,000 ED visits increased 51.6% (p = 0.0198). However, the number of x-ray examinations per 1,000 ED visits decreased 81.6% (p < 0.0001). Abdominal imaging RVUs per 1,000 ED visits increased 2.7-fold (p < 0.0001), due primarily to CT imaging, which accounted for 14% of RVUs in 1990 and 76% of RVUs in 2009. Conclusions: The intensity of abdominal imaging examinations per 1,000 ED visits and the number of abdominal imaging RVUs increased significantly over a 20-year period. CT replaced x-ray as the most common abdominal imaging modality for evaluation of ED patients. In light of these increasing costs as well as the increased radiation exposure of CT, clinical decision rules and computerized decision support may be needed to ensure appropriate utilization of abdominal CT in the ED.
Transgenic mice, containing the chimeric gene obtained by linking the promoter-regulatory region ... more Transgenic mice, containing the chimeric gene obtained by linking the promoter-regulatory region of P-enolpyruvate carboxykinase (PEPCK) gene to the bovine growth hormone structural gene (bGH), were used to investigate the long-term effects of bGH on glucose metabolism. Expression of the PEPCK/bGH gene was markedly enhanced by feeding a diet high in protein and inhibited by a high carbohydrate diet. All
The metabolic function of PEPCK-C is not fully understood; deletion of the gene for the enzyme in... more The metabolic function of PEPCK-C is not fully understood; deletion of the gene for the enzyme in mice provides an opportunity to fully assess its function. The gene for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK-C) was deleted in mice by homologous recombination (PEPCK-C-/- mice) and the metabolic consequences assessed. PEPCK-C-/- mice became severely hypoglycemic by day two after birth and then died with profound hypoglycemia (12 mg/dl). The mice had milk in their stomachs at day two after birth and the administration of glucose raised the concentration of blood glucose in the mice but did not result in an increased survival. PEPCK-C-/- mice have two to three times the hepatic triglyceride content as control littermates on the second day after birth. These mice also had an elevation of lactate (2.5 times), beta-hydroxybutyrate (3 times) and triglyceride (50%) in their blood, as compared to control animals. On day two after birth, alanine, gl...
We have developed, for the Case 3D Cryo-imaging system, a specialized, multiscale visualization s... more We have developed, for the Case 3D Cryo-imaging system, a specialized, multiscale visualization scheme which provides color-rich volume rendering and multiplanar reformatting enabling one to visualize an entire mouse and zoom in to organ, tissue, and microscopic scales. With this system, we have anatomically characterized, in 3D, from whole animal to tissue level, a transgenic mouse and compared it with its control. The transgenic mouse overexpresses the cytosolic form of phosphoenolpyruvate carboxykinase (PEPCK-C) in its skeletal muscle and is capable of greatly enhanced physical endurance and has a longer life-span and reproductive life as compared to control animals. We semiautomatically analyzed selected organs such as kidney, heart, adrenal gland, spleen, and ovaries and found comparatively enlarged heart, much less visceral, subcutaneous, and pericardial adipose tissue, and higher tibia-to-femur ratio in the transgenic animal. Microscopically, individual skeletal muscle fibers...
Transgenic animals provide a comprehensive model for investigating genes encoding inducible enzym... more Transgenic animals provide a comprehensive model for investigating genes encoding inducible enzymes involved in metabolism, since the molecular mechanisms regulating gene transcription can be studied in the whole animal. Studies on the promoters of the genes encoding two key enzymes in the gluconeogenic and glycolytic pathways--phosphoenol-pyruvate carboxykinase and pyruvate kinase are described as examples of this approach. Work on the phosphoenolpyruvate carboxykinase promoter using transgenic mice has been particularly informative: the cis-acting elements involved in hormonal regulation, tissue specificity and developmental inhibition of gene expression have been identified and their function in vivo examined.
Receptor-mediated gene transfer is an attractive method for therapeutically correcting human gene... more Receptor-mediated gene transfer is an attractive method for therapeutically correcting human genetic diseases since it permits the targeting of DNA to cellular receptors in specific tissues of adult animals. Genes introduced by this technique have been shown to be expressed in the target tissue for varying periods. However, to be useful for gene therapy, it is critical that both the chemical properties and physical interactions of the reagents involved in the design of the DNA delivery vehicle be rigorously characterized. In this review, we discuss the critical steps in the preparation of the DNA-ligand complex and the factors involved in the delivery and regulated expression of a transgene in animal tissues. The feasibility of using this technique for the therapeutic delivery of genes to mammalian tissues will also be evaluated.
We show that intraplate magmatism occurred 1106 to 1112 million years ago over an area of two mil... more We show that intraplate magmatism occurred 1106 to 1112 million years ago over an area of two million square kilometers within the Kalahari craton of southern Africa, during the same magnetic polarity chron as voluminous magmatism within the cratonic core of North America. These contemporaneous magmatic events occurred while the Rodinia supercontinent was being assembled and are inferred to be parts of a single large igneous province emplaced across the two cratons. Widespread intraplate magmatism during Rodinia assembly shows that mantle upwellings required to generate such provinces may occur independently of the supercontinent cycle.
Proceedings of the National Academy of Sciences, 1986
Livers from newborn mice homozygous for either one of the lethal deletions c14CoS or c3H in chrom... more Livers from newborn mice homozygous for either one of the lethal deletions c14CoS or c3H in chromosome 7 have drastically reduced levels of cytosolic phosphoenolpyruvate carboxykinase (GTP) [GTP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32] activity when compared with normal littermates. The structural gene for the enzyme maps on chromosome 2 and appears intact and not grossly rearranged in deletion homozygotes. These mice also have negligible levels of hepatic mRNA encoding this enzyme. Studies of the transcription rate of the gene showed that it was reduced to 25-50% of normal in hepatic nuclei obtained from mice homozygous for either deletion. We suggest that, in addition to the reduction in the level of transcription, the deletions in chromosome 7 may also cause alterations in messenger stability, processing, or transport from the nucleus.
Proceedings of the National Academy of Sciences, 2002
Regulation of the turnover of triglycerides in adipose tissue requires the continuous provision o... more Regulation of the turnover of triglycerides in adipose tissue requires the continuous provision of 3-glycerophosphate, which may be supplied by the metabolism of glucose or by glyceroneogenesis, the de novo synthesis of 3-glycerophosphate from sources other than hexoses or glycerol. The importance of glyceroneogenesis in adipose tissue was assessed in mice by specifically eliminating the expression of the cytosolic form of phosphoenolpyruvate carboxykinase (PEPCK-C), an enzyme that plays a pivotal role in the pathway. To accomplish this, we mutated the binding site for the peroxisome proliferator-activated receptor ␥ (PPAR␥) called the peroxisome proliferator-activated receptor element (PPARE), in the 5 flanking region of the PEPCK-C gene in the mouse by homologous recombination. The mutation abolished expression of the gene in white adipose tissue and considerably reduced its expression in brown adipose tissue, whereas the level of PEPCK-C mRNA in liver and kidney remained normal. Epididymal white adipose tissue from these mice had a reduced triglyceride deposition, with 25% of the animals displaying lipodystrophy. There was also a greatly reduced level of lipid accumulation in brown adipose tissue. A strong correlation between the hepatic content of triglycerides and the size of the epididymal fat pad in PPARE ؊/؊ mice suggests that hepatic triglyceride synthesis predominantly utilizes free fatty acids derived from the adipose tissue. Unlike other models, PPARE ؊/؊ mice with lipodystrophy did not exhibit the lipodystrophy-associated features of diabetes and displayed only moderate hyperglycemia. These studies establish the importance of the PPARE site for PEPCK-C gene expression in adipose tissue and the role of PEPCK-C in the regulation of glyceroneogenesis, a pathway critical for maintaining the deposition of triglycerides in adipose tissue.
Proceedings of the National Academy of Sciences, 1979
A recombinant plasmid containing a DNA segment complementary to rat liver albumin mRNA has been c... more A recombinant plasmid containing a DNA segment complementary to rat liver albumin mRNA has been constructed, cloned, and used to examine the organization of albumin gene. The 18S fraction of total liver poly(A)-containing
Digital radiology departments could benefit from the ability to integrate and visualize data (e.g... more Digital radiology departments could benefit from the ability to integrate and visualize data (e.g. information reflecting complex workflow states) from all of their imaging and information management systems in one composite presentation view. Leveraging data warehousing tools developed in the business world may be one way to achieve this capability. In total, the concept of managing the information available in this data repository is known as Business Intelligence or BI. This paper describes the concepts used in Business Intelligence, their importance to modern Radiology, and the steps used in the creation of a prototype model of a data warehouse for BI using open-source tools.
Background: Glutamine is a critical amino acid for the metabolism of enterocytes, lymphocytes, an... more Background: Glutamine is a critical amino acid for the metabolism of enterocytes, lymphocytes, and other proliferating cells. Although supplementation with glutamine has been suggested for growing infants, its effect on protein metabolism has not been examined. Objective: The objective was to examine the effect of enteral glu- tamine or glycine on whole-body kinetics of glutamine, phenylala- nine, leucine, and urea
To study end-user attitudes and preferences with respect to radiology scheduling systems and to a... more To study end-user attitudes and preferences with respect to radiology scheduling systems and to assess implications for retention and extension of the referral base. A study of the institution&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s historical data indicated reduced satisfaction with the process of patient scheduling in recent years. Sixty physicians who referred patients to a single, large academic radiology department received the survey. The survey was designed to identify (A) the preferred vehicle for patient scheduling (on-line versus telephone scheduling) and (B) whether ease of scheduling was a factor in physicians referring patients to other providers. Referring physicians were asked to forward the survey to any appropriate office staff member in case the latter scheduled appointments for patients. Users were asked to provide comments and suggestions for improvement. The statistical method used was the analysis of proportions. Thirty-three responses were received, corresponding to a return rate of 55%. Twenty-six of the 33 respondents (78.8%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .01) stated they were willing to try an online scheduling system; 16 of which tried the system. Twelve of the 16 (75%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05) preferred the on-line application to the telephone system, stating logistical simplification as the primary reason for preference. Three (18.75%) did not consider online scheduling to be more convenient than traditional telephone scheduling. One respondent did not indicate any preference. Eleven of 33 users (33.33%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) stated that they would change radiology service providers if expectations of scheduling ease are not met. On-line scheduling applications are becoming the preferred scheduling vehicle. Augmenting their capabilities and availability can simplify the scheduling process, improve referring physician satisfaction, and provide a competitive advantage. Referrers are willing to change providers if scheduling expectations are not met.
Transgenic animals expressing genes capable of repairing DNA may be a valuable tool to study the ... more Transgenic animals expressing genes capable of repairing DNA may be a valuable tool to study the effect of DNA-damaging agents on tissue- specific carcinogenesis. For this reason, we constructed a chimeric gene consisting of the promoter-regulatory region of the phosphoenolp) ruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) gene linked to the Esche- richia coli oda gene coding for O'-alkylguanine-DNA alkyltransferase and
PURPOSE We have previously reported inpatient imaging utilization trends at our institution from ... more PURPOSE We have previously reported inpatient imaging utilization trends at our institution from fiscal years (FY) 1984 through 2002. In this study, we assessed the trends in imaging utilization for inpatients from FY 2003 through 2012. METHOD AND MATERIALS In this institutional review board-approved, retrospective study performed at a 793-bed tertiary care academic institution, we reviewed imaging utilization in adult inpatients from October 1, 2002 through September 30, 2012 (FY 2003 through 2012) and recorded the gross number of imaging studies coded by modality (conventional [plain films and fluoroscopy], sonography, nuclear medicine [NM], CT, and MRI) and associated relative value units (RVUs). We used linear regression to assess trends in number of imaging studies and RVUs per case-mix-adjusted admissions (CMAA). RESULTS The total number of imaging studies as well as CT, NM and conventional studies adjusted for CMAA decreased (p=0.02, p=0.0006, p=0.0008 and p=0.001 respectivel...
... In the Northern Sierra terrane between latitudes 39°N and 40°N, which is the subject of this ... more ... In the Northern Sierra terrane between latitudes 39°N and 40°N, which is the subject of this paper, the Jurassic arc sequence is typified by an abundance of basaltic to andesitic volcanic rock deposited in marine environments ( [Harwood, 1992 and Hanson et al ... [Lowe, 1982]). ...
Although some information is available concerning the physiological alterations in vivo associate... more Although some information is available concerning the physiological alterations in vivo associated with spontaneous bovine ketosis, a broad study of pathways and possible changes of enzyme activities has not been carried out. To this aim, liver samples were taken from spontaneously ketotic cows, from the same cows when normal, and when starved for 96 hours. Measurements were made to ascertain
Background: To assess patterns of use of abdominal imaging in the emergency department (ED) from ... more Background: To assess patterns of use of abdominal imaging in the emergency department (ED) from 1990 to 2009. Methods: We retrospectively reviewed data on adult ED patients treated between 1990 and 2009 at our universityaffiliated quaternary care institution. Examinations were coded by abdominal imaging modality: x-ray, sonography, CT, or MRI. Proportional costs for each imaging modality were evaluated using relative value units (RVUs). Chisquare tests were used to assess for significant trends. Results: The intensity of abdominal imaging per 1,000 ED visits increased 19.3% from 1990-2009 (p = 0.0050). The number of abdominal CT scans per 1,000 ED visits increased 17.5-fold (p < 0.0001). Similarly, the number of abdominal MRIs per 1,000 ED visits increased from 0 to 1.0 (p < 0.0001), and the number of abdominal sonographs per 1,000 ED visits increased 51.6% (p = 0.0198). However, the number of x-ray examinations per 1,000 ED visits decreased 81.6% (p < 0.0001). Abdominal imaging RVUs per 1,000 ED visits increased 2.7-fold (p < 0.0001), due primarily to CT imaging, which accounted for 14% of RVUs in 1990 and 76% of RVUs in 2009. Conclusions: The intensity of abdominal imaging examinations per 1,000 ED visits and the number of abdominal imaging RVUs increased significantly over a 20-year period. CT replaced x-ray as the most common abdominal imaging modality for evaluation of ED patients. In light of these increasing costs as well as the increased radiation exposure of CT, clinical decision rules and computerized decision support may be needed to ensure appropriate utilization of abdominal CT in the ED.
Transgenic mice, containing the chimeric gene obtained by linking the promoter-regulatory region ... more Transgenic mice, containing the chimeric gene obtained by linking the promoter-regulatory region of P-enolpyruvate carboxykinase (PEPCK) gene to the bovine growth hormone structural gene (bGH), were used to investigate the long-term effects of bGH on glucose metabolism. Expression of the PEPCK/bGH gene was markedly enhanced by feeding a diet high in protein and inhibited by a high carbohydrate diet. All
The metabolic function of PEPCK-C is not fully understood; deletion of the gene for the enzyme in... more The metabolic function of PEPCK-C is not fully understood; deletion of the gene for the enzyme in mice provides an opportunity to fully assess its function. The gene for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK-C) was deleted in mice by homologous recombination (PEPCK-C-/- mice) and the metabolic consequences assessed. PEPCK-C-/- mice became severely hypoglycemic by day two after birth and then died with profound hypoglycemia (12 mg/dl). The mice had milk in their stomachs at day two after birth and the administration of glucose raised the concentration of blood glucose in the mice but did not result in an increased survival. PEPCK-C-/- mice have two to three times the hepatic triglyceride content as control littermates on the second day after birth. These mice also had an elevation of lactate (2.5 times), beta-hydroxybutyrate (3 times) and triglyceride (50%) in their blood, as compared to control animals. On day two after birth, alanine, gl...
We have developed, for the Case 3D Cryo-imaging system, a specialized, multiscale visualization s... more We have developed, for the Case 3D Cryo-imaging system, a specialized, multiscale visualization scheme which provides color-rich volume rendering and multiplanar reformatting enabling one to visualize an entire mouse and zoom in to organ, tissue, and microscopic scales. With this system, we have anatomically characterized, in 3D, from whole animal to tissue level, a transgenic mouse and compared it with its control. The transgenic mouse overexpresses the cytosolic form of phosphoenolpyruvate carboxykinase (PEPCK-C) in its skeletal muscle and is capable of greatly enhanced physical endurance and has a longer life-span and reproductive life as compared to control animals. We semiautomatically analyzed selected organs such as kidney, heart, adrenal gland, spleen, and ovaries and found comparatively enlarged heart, much less visceral, subcutaneous, and pericardial adipose tissue, and higher tibia-to-femur ratio in the transgenic animal. Microscopically, individual skeletal muscle fibers...
Transgenic animals provide a comprehensive model for investigating genes encoding inducible enzym... more Transgenic animals provide a comprehensive model for investigating genes encoding inducible enzymes involved in metabolism, since the molecular mechanisms regulating gene transcription can be studied in the whole animal. Studies on the promoters of the genes encoding two key enzymes in the gluconeogenic and glycolytic pathways--phosphoenol-pyruvate carboxykinase and pyruvate kinase are described as examples of this approach. Work on the phosphoenolpyruvate carboxykinase promoter using transgenic mice has been particularly informative: the cis-acting elements involved in hormonal regulation, tissue specificity and developmental inhibition of gene expression have been identified and their function in vivo examined.
Receptor-mediated gene transfer is an attractive method for therapeutically correcting human gene... more Receptor-mediated gene transfer is an attractive method for therapeutically correcting human genetic diseases since it permits the targeting of DNA to cellular receptors in specific tissues of adult animals. Genes introduced by this technique have been shown to be expressed in the target tissue for varying periods. However, to be useful for gene therapy, it is critical that both the chemical properties and physical interactions of the reagents involved in the design of the DNA delivery vehicle be rigorously characterized. In this review, we discuss the critical steps in the preparation of the DNA-ligand complex and the factors involved in the delivery and regulated expression of a transgene in animal tissues. The feasibility of using this technique for the therapeutic delivery of genes to mammalian tissues will also be evaluated.
We show that intraplate magmatism occurred 1106 to 1112 million years ago over an area of two mil... more We show that intraplate magmatism occurred 1106 to 1112 million years ago over an area of two million square kilometers within the Kalahari craton of southern Africa, during the same magnetic polarity chron as voluminous magmatism within the cratonic core of North America. These contemporaneous magmatic events occurred while the Rodinia supercontinent was being assembled and are inferred to be parts of a single large igneous province emplaced across the two cratons. Widespread intraplate magmatism during Rodinia assembly shows that mantle upwellings required to generate such provinces may occur independently of the supercontinent cycle.
Proceedings of the National Academy of Sciences, 1986
Livers from newborn mice homozygous for either one of the lethal deletions c14CoS or c3H in chrom... more Livers from newborn mice homozygous for either one of the lethal deletions c14CoS or c3H in chromosome 7 have drastically reduced levels of cytosolic phosphoenolpyruvate carboxykinase (GTP) [GTP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32] activity when compared with normal littermates. The structural gene for the enzyme maps on chromosome 2 and appears intact and not grossly rearranged in deletion homozygotes. These mice also have negligible levels of hepatic mRNA encoding this enzyme. Studies of the transcription rate of the gene showed that it was reduced to 25-50% of normal in hepatic nuclei obtained from mice homozygous for either deletion. We suggest that, in addition to the reduction in the level of transcription, the deletions in chromosome 7 may also cause alterations in messenger stability, processing, or transport from the nucleus.
Proceedings of the National Academy of Sciences, 2002
Regulation of the turnover of triglycerides in adipose tissue requires the continuous provision o... more Regulation of the turnover of triglycerides in adipose tissue requires the continuous provision of 3-glycerophosphate, which may be supplied by the metabolism of glucose or by glyceroneogenesis, the de novo synthesis of 3-glycerophosphate from sources other than hexoses or glycerol. The importance of glyceroneogenesis in adipose tissue was assessed in mice by specifically eliminating the expression of the cytosolic form of phosphoenolpyruvate carboxykinase (PEPCK-C), an enzyme that plays a pivotal role in the pathway. To accomplish this, we mutated the binding site for the peroxisome proliferator-activated receptor ␥ (PPAR␥) called the peroxisome proliferator-activated receptor element (PPARE), in the 5 flanking region of the PEPCK-C gene in the mouse by homologous recombination. The mutation abolished expression of the gene in white adipose tissue and considerably reduced its expression in brown adipose tissue, whereas the level of PEPCK-C mRNA in liver and kidney remained normal. Epididymal white adipose tissue from these mice had a reduced triglyceride deposition, with 25% of the animals displaying lipodystrophy. There was also a greatly reduced level of lipid accumulation in brown adipose tissue. A strong correlation between the hepatic content of triglycerides and the size of the epididymal fat pad in PPARE ؊/؊ mice suggests that hepatic triglyceride synthesis predominantly utilizes free fatty acids derived from the adipose tissue. Unlike other models, PPARE ؊/؊ mice with lipodystrophy did not exhibit the lipodystrophy-associated features of diabetes and displayed only moderate hyperglycemia. These studies establish the importance of the PPARE site for PEPCK-C gene expression in adipose tissue and the role of PEPCK-C in the regulation of glyceroneogenesis, a pathway critical for maintaining the deposition of triglycerides in adipose tissue.
Proceedings of the National Academy of Sciences, 1979
A recombinant plasmid containing a DNA segment complementary to rat liver albumin mRNA has been c... more A recombinant plasmid containing a DNA segment complementary to rat liver albumin mRNA has been constructed, cloned, and used to examine the organization of albumin gene. The 18S fraction of total liver poly(A)-containing
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Papers by Richard Hanson