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Biomedical subjects

C C White

Publications and source records attributed to C C White.

At least 19 recordsLinked to original sources
PubMed2006

Neurotoxicity of domoic Acid in cerebellar granule neurons in a genetic model of glutathione deficiency.

This study investigated the role of cellular antioxidant defense mechanisms in modulating the neurotoxicity of domoic acid (DomA), by using cerebellar granule neurons (CGNs) from mice lacking the modifier subunit of glutamate-cysteine ligase (Gclm). Glutamate-cysteine ligase (Glc) catalyzes the first and rate-limiting step in glutathione (GSH) biosynthesis. CGNs from Gclm (-/-) mice have very low levels of GSH and are 10-fold more sensitive to DomA-induced toxicity than CGNs from Gclm (+/+) mice. GSH ethyl ester decreased, whereas the Gcl inhibitor buthionine sulfoximine increased DomA toxicity. Antagonists of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors and of N-methyl-D-aspartate (NMDA) receptors blocked DomA toxicity, and NMDA receptors were activated by DomA-induced l-glutamate release. The differential susceptibility of CGNs to DomA toxicity was not due to a differential expression of ionotropic glutamate receptors, as evidenced by similar calcium responses and L-glutamate release in the two genotypes. A calcium chelator and several antioxidants antagonized DomA-induced toxicity. DomA caused a rapid decrease in cellular GSH, which preceded toxicity, and the decrease was primarily due to DomA-induced GSH efflux. DomA also caused an increase in oxidative stress as indicated by increases in reactive oxygen species and lipid peroxidation, which was subsequent to GSH efflux. Astrocytes from both genotypes were resistant to DomA toxicity and presented a diminished calcium response to DomA and a lack of DomA-induced L-glutamate release. Because polymorphisms in the GCLM gene in humans are associated with low GSH levels, such individuals, as well as others with genetic conditions or environmental exposures that lead to GSH deficiency, may be more susceptible to DomA-induced neurotoxicity.

Animals↗
PubMed2002

The effects of Neotrofin on septodentate sprouting after unilateral entorhinal cortex lesions in rats.

PURPOSE: Recent research on the purine derivative of hypoxanthine Neotrofin (4-[[3-(1,6-dihydro-6-oxo-9-purin-9-yl)-1-oxopropyl]amino]benzoic acid; AIT-082) has indicated that Neotrofin treatment elevates the mRNA levels of various neurotrophic factors, including nerve growth factor (NGF), in the CNS. Several previous studies have indicated that NGF may regulate septodentate sprouting after entorhinal cortex lesions in rats. Thus, the objective of this investigation was to determine whether Neotrofin treatment would enhance lesion-induced septodentate sprouting from 4 to 15 days postlesion. METHODS: Sham-operated rats or rats with EC lesions were injected (i.p.) with either Neotrofin (30 mg/kg) or saline (0.9%) immediately after surgery and every day thereafter until the end of the treatment regimen. Septodentate sprouting, as indicated by intensity of acetylcholinesterase (AChE) label in the dentate gyrus, was assessed with optical densitometry. RESULTS: We observed that Neotrofin elevated the AChE-label in the outer molecular layer of the ventral dentate gyrus at 4 days postlesion and of the dorsal dentate gyrus at 15 days postlesion. CONCLUSIONS: Neotrofin appears to have exerted limited stimulatory effects on lesion-induced sprouting by a cholinergic pathway.

Alzheimer Disease↗
PubMed2001

Tissue specific changes in the expression of glutamate-cysteine ligase mRNAs in mice exposed to methylmercury.

Glutamate-cysteine ligase (GLCL), the rate-limiting enzyme in glutathione (GSH) synthesis is composed of two subunits, a catalytic (GLCLc) and a regulatory subunit (GLCLr). These two subunits are known to be differentially regulated in vitro, in different cell types and in response to various xenobiotic exposures. In this study, we examined whether these two subunits can also be differentially regulated in vivo. We found that GLCLc and GLCLr are differentially regulated at the transcriptional level in a tissue-dependent manner in female mice treated with methylmercury (MeHg). MeHg caused a downregulation of both subunit mRNAs in the liver, upregulation of both subunit mRNAs in the kidney and upregulation of only the catalytic subunit mRNA in the small intestine of female mice treated with a single dose of MeHg (6 mg/kg) by intraperitoneal injection. These results suggest that GLCLc and GLCLr can be differentially regulated in vivo, and that this regulation is tissue dependent in the mouse.

Animals↗
PubMed2001

A model for predicting chloride concentrations in river water in a relatively unpolluted catchment in north-east Scotland.

The River Dee is an oligotrophic soft water system, in the NE of Scotland, with a catchment area of approximately 2100 km2. The river rises in the Cairngorm Mountains and enters the North Sea at Aberdeen, approximately 140 km from its source. Water chemical quality data was collected every 2 weeks over 12 months for 59 sites distributed throughout the catchment. River water chloride concentrations increased significantly from west to east. In depth investigation of the relationship with distance from the coast revealed the significant difference in spatial distribution of river water chloride concentrations between upland and lowland/agricultural areas, suggesting the possible importance of agricultural practices to streamwater chloride concentrations. Thirty of the sample sites are independent and have been used to develop a simple model for prediction of streamwater Cl- concentration throughout the catchment. The model has been validated using data from the remaining sub-catchments. The model shows that mean Cl- concentration may be reliably predicted from distance from the coast and the percentage of improved grassland and arable land cover in each sub-catchment (r2 = 0.98). It is postulated that the land use effects may be partly due to the evolved link between landuse and catchment altitude characteristics, rather than just the direct effect of applied potassium chloride fertiliser on agricultural land. It was noted that there was insufficient forestry within the River Dee Catchment to reliably include % forest cover in the model.

Agriculture↗
PubMed2001

Enhanced acetaminophen hepatotoxicity in transgenic mice overexpressing BCL-2.

Mitochondria play an important role in the cell death induced by many drugs, including hepatotoxicity from overdose of the popular analgesic, acetaminophen (APAP). To investigate mitochondrial alterations associated with APAP-induced hepatotoxicity, the subcellular distribution of proapoptotic BAX was determined. Based on the antiapoptotic characteristics of BCL-2, we further hypothesized that if a BAX component was evident then BCL-2 overexpression may be hepatoprotective. Mice, either with a human bcl-2 transgene (-/+) or wild-type mice (WT; -/-), were dosed with 500 or 600 mg/kg (i.p.) APAP or a nonhepatotoxic isomer, N-acetyl-m-aminophenol (AMAP). Immunoblot analyses indicated increased mitochondrial BAX-beta content very early after APAP or AMAP treatment. This was paralleled by disappearance of BAX-alpha from the cytosol of APAP treated animals and, to a lesser extent, with AMAP treatment. Early pathological evidence of APAP-induced zone 3 necrosis was seen in bcl-2 (-/+) mice, which progressed to massive panlobular necrosis with hemorrhage by 24 h. In contrast, WT mice dosed with APAP showed a more typical, and less severe, centrilobular necrosis. AMAP-treated bcl-2 (-/+) mice displayed only early microvesicular steatosis without progression to extensive necrosis. Decreased complex III activity, evident as early as 6 h after treatment, correlated well with plasma enzyme activities at 24 h (AST r(2) = 0.89, ALT r(2) = 0.87) thereby confirming a role for mitochondria in APAP-mediated hepatotoxicity. In conclusion, these data suggest for the first time that BAX may be an early determinant of APAP-mediated hepatotoxicity and that BCL-2 overexpression unexpectedly enhances APAP hepatotoxicity.

Acetaminophen↗
PubMed2000

Modulation of glutathione and glutamate-L-cysteine ligase by methylmercury during mouse development.

The antioxidant tripeptide glutathione has been proposed to be important in defense against oxidative stress and heavy metal toxicity. We evaluated alterations in glutathione regulation and synthesis associated with low-level chronic methylmercury (MeHg) exposure in the developing mouse fetus. Female C57Bl/6 mice were given 0, 3, or 10 ppm MeHg in the drinking water for 2 weeks prior to breeding and throughout pregnancy. Fetuses were collected on gestational days (gd) 12 and 16. Total glutathione, reduced glutathione (GSH), oxidized glutathione (GSSR), and glutamate-L-cysteine ligase (Glcl) activity were assessed in yolk sacs and fetuses at gd 16. Western and Northern blots for Glcl-catalytic (Glclc) and Glcl-regulatory (Glclr) subunits were performed on gd 12 and gd 16 fetuses. There were no changes in total glutathione in gd 16 mouse fetuses with exposure, but there were dose-related decreases in GSH and increases in GSSR. In contrast, visceral yolk sacs exhibited an increase in total glutathione in the low-dose groups, but no changes in the high-dose group. There were no changes in Glcl activity in fetuses, but there was a 2-fold increase in Glcl activity in yolk sacs from both low-dose and high-dose groups. There was a 2-fold induction in GLCLC: mRNA and protein in the gd 16 yolk sacs at both 3 and 10 ppm MeHg. No treatment-related changes in Glclr protein in either gd 12 or gd 16 yolk sacs or fetuses were found. Thus, the yolk sac is capable of up-regulating Glclc and GSH synthetic capacity in response to MeHg exposure. This increase appears to be sufficient to resist MeHg-induced GSH depletion in the yolk sac; however fetal glutathione redox status is compromised with exposure to 10 ppm MeHg.

Animals↗
PubMed1999

Induction of glutamate-cysteine ligase (gamma-glutamylcysteine synthetase) in the brains of adult female mice subchronically exposed to methylmercury.

Methylmercury (MeHg) is widely known for its potent neurotoxic properties. One proposed mechanism of action of MeHg relates to its high affinity for sulfhydryl groups, especially those found on glutathione (GSH) and proteins. Previous studies have shown that acute MeHg exposure results in an increase in the mRNA for the rate-limiting enzyme in GSH synthesis, glutamate-cysteine ligase (GLCL) (also known as gamma-glutamylcysteine synthetase). In this study, we evaluated the effects of subchronic (12-week) MeHg exposure at 0, 3 or 10 ppm in the drinking water on GSH levels, GLCL catalytic (GLCLC) and regulatory subunit mRNA and protein levels, and GLCL activity in brain, liver and kidney tissue of C57B1/6 female mice. Contrary to previous findings in rats, there were no changes in GSH concentration in any of the tissues examined. However, there was an increase in GLCLC protein in the brain, which was accompanied by a 30% increase in GLCL activity. We conclude that up-regulation of GSH synthetic capacity in the brains of mice is a sensitive biomarker of subchronic MeHg exposure.

Animals↗
PubMed1999

The role of intracellular glutathione in methylmercury-induced toxicity in embryonic neuronal cells.

Previous studies indicate that the ability of cells to up-regulate levels of intracellular glutathione (GSH) synthesis may determine their sensitivity to MeHg exposure. The purpose of the current study is two-fold. First, we determined whether the vulnerability of the developing central nervous system (CNS) to MeHg lies in its intracellular GSH content. The intracellular GSH content and the activity of gamma-glutamyl cysteine synthetase (GCS) were determined with and without MeHg exposure in primary cultures of rat embryonic CNS cells. In addition, the effect of GSH modulation on MeHg-induced cytotoxicity was determined. Second, we characterized the mechanism of GCS regulation, initially by studying the GCS heavy chain subunit (GCS-HC). Primary embryonic limb bud cells were used as a reference cell type for comparing the response of CNS cells. The results indicate that constitutive intracellular GSH content, GCS activity, and GCS-HC mRNA and protein levels of CNS cells were approximately ten-, two-, five-, and ten-fold higher, respectively, than those in limb bud cells. A dose-dependent increase in GSH levels and GCS activity was observed in CNS and limb bud cells following 1 and 2 microM MeHg exposure for 20 hr. Further characterization of GCS up-regulation in CNS cells showed that the increase in GCS activity following MeHg exposure, unlike limb bud cells, was not accompanied by an elevation of GCS-HC mRNA and protein levels. Pretreatment with N-acetylcysteine led to a significant increase in intracellular GSH, while L-buthionine-(S,R)-sulfoximine (BSO) resulted in decreased GSH levels, however neither pretreatment had a significant impact on MeHg-induced cytotoxicity in either cell type. Our results suggest that although oxidative stress may mediate aspects of MeHg toxicity, disruption of GSH homeostasis alone is not responsible for the sensitivity of embryonic CNS cells to MeHg.

Acetylcysteine↗
PubMed1998

Functions of the Caenorhabditis elegans regulatory myosin light chain genes mlc-1 and mlc-2.

Caenorhabditis elegans contains two muscle regulatory myosin light chain genes, mlc-1 and mlc-2. To determine their in vivo roles, we identified deletions that eliminate each gene individually and both genes in combination. Functions of mlc-1 are redundant to those of mlc-2 in both body-wall and pharyngeal muscle. mlc-1(0) mutants are wild type, but mlc-1(0) mlc-2(0) double mutants arrest as incompletely elongated L1 larvae, having both pharyngeal and body-wall muscle defects. Transgenic copies of either mlc-1(+) or mlc-2(+) rescue all defects of mlc-1(0) mlc-2(0) double mutants. mlc-2 is redundant to mlc-1 in body-wall muscle, but mlc-2 performs a nearly essential role in the pharynx. Approximately 90% of mlc-2(0) hermaphrodites arrest as L1 larvae due to pharyngeal muscle defects. Lethality of mlc-2(0) mutants is sex specific, with mlc-2(0) males being essentially wild type. Four observations suggest that hermaphrodite-specific lethality of mlc-2(0) mutants results from insufficient expression of the X-linked mlc-1(+) gene in the pharynx. First, mlc-1(0) mlc-2(0) double mutants are fully penetrant L1 lethals in both hermaphrodites and males. Second, in situ localization of mlc mRNAs demonstrates that both mlc-1 and mlc-2 are expressed in the pharynx. Third, transgenic copies of either mlc-1(+) or mlc-2(+) rescue the pharyngeal defects of mlc-1(0) mlc-2(0) hermaphrodites. Fourth, a mutation of the dosage compensation gene sdc-3 suppresses hermaphrodite-specific lethality of mlc-2(0) mutants.

Animals↗
PubMed1996

From the archives of the AFIP. Malignant pleural mesothelioma: radiologic-pathologic correlation.

Malignant pleural mesothelioma (MPM) is a rare malignant neoplasm that typically affects individuals occupationally exposed to asbestos through a variety of industries. The patients experience an insidious onset of symptoms, including dyspnea, chest pain, cough, malaise, and weight loss. The pathologic diagnosis of MPM is difficult, and special stains or immunohistochemical or ultrastructural analysis may be required to differentiate MPM from metastatic adenocarcinoma. The tumor affects both the parietal and visceral pleural surfaces and progresses to encase the lung and invade the lung, mediastinum, and chest wall. Radiologically, MPM manifests as unilateral pleural effusion, pleural nodules, or pleural masses. Imaging studies are useful for diagnosis and staging in patients who are potential surgical candidates. Although a variety of multimodality therapies are available and radical surgical procedures have been developed, the prognosis remains dismal.

Aged↗
PubMed1995

Zonal differences in DNA synthesis activity and cytochrome P450 gene expression in livers of male F344 rats treated with five nongenotoxic carcinogens.

Both increased cell proliferation and "altered" CYP gene expression are prominent phenomena associated with liver tumor promotion by nongenotoxic carcinogen treatment. To further characterize these two responses, groups of rats were kept on powdered rat chow diet containing 0.05% phenobarbital (PB) or 0.025% ciprofibrate (Cip) for 8 days or given 8 daily doses by gavage of pregnenolone 16 alpha-carbonitrile (PCN, 150 mg/kg/ml corn oil), 3,3',4,4'-tetrachlorobiphenyl (PCB-MC, 3 mg/kg/ml corn oil) or 2,2',4,4'-tetrachlorobiphenyl (PCB-PB, 7.5 mg/kg/ml corn oil). A minipump was implanted in the rat abdominal cavity to release bromodeoxyuridine (BRDU) 5 days after the start of nongenotoxic carcinogen treatment and the experiment was terminated 3 days later. BRDU-labeled parenchymal nuclei were observed primarily in the periportal area independent of nongenotoxic carcinogen treatment. Treatment with each of the 5 nongenotoxic carcinogens resulted in profound alterations in CYP gene expression at both the transcriptional and translational levels. Expression of CYP1A1, 1A1/2, 3A1, 2B1/2, and 4A immunoproteins demonstrated nongenotoxic carcinogen-specific patterns in both magnitude and zonal distribution. In agreement with the CYP immunoprotein data, treatment with each of the five nongenotoxic carcinogens resulted in a unique composition of mRNAs of CYP2B1, 2B2, 2C6, 2C11, 3A1, 3A2, and 4A1, which were variably increased or decreased relative to the untreated control livers, depending on the treatment. Similarly, the rate and pattern of CYP enzyme-mediated hydroxylation toward testosterone, 17 beta-estradiol, corticosterone, and lauric acid were greatly altered by nongenotoxic carcinogen treatment. According to the zonal distribution patterns of CYP immunoproteins, each hepatocyte in the cell plate from the periportal triad to the central vein has a characteristic and nongenotoxic carcinogen-specific composition of CYP enzymes. Because many endogenous substrates are modulators of DNA and RNA synthesis, intracellular kinetics of endogenous substrates of CYP enzymes in the corresponding hepatocytes could contribute, at least in part, to the differences in gene expression, differentiation, and cell proliferation among the hepatocytes in the cell plate.

Animals↗
PubMed1994

Inhibition of cell proliferation by ciprofibrate in glutathione S-transferase P1-1-positive rat hepatic hyperplastic nodules.

Previous studies have demonstrated that short-term treatment with a peroxisome proliferator (PP) decreased the size and number of genotoxic carcinogen-induced hepatic hyperplastic lesions identified by gamma-glutamyl transpeptidase (GGT) or glutathione S-transferase P1-1 (rGSTP1-1) staining. However, longer-term PP treatment of animals bearing similar hepatic hyperplastic lesions produced an increase in both the size and number of liver tumors. To characterize the hepatic hyperplastic lesions which are inhibited or promoted by PP, a unique double labeling technique was developed to determine the relative rate of cell division (e.g., DNA synthesis) in rGSTP1-1-positive nodules before and after ciprofibrate (Cip) treatment. rGSTP1-1-positive nodules were induced with the Solt-Farber resistance protocol (diethylnitrosamine-2-acetylaminofluorene partial hepatectomy). Eleven weeks after diethylnitrosamine initiation, 3 groups of rats were maintained on a control chow diet or switched to a powdered chow diet containing 0.025% Cip or 0.05% phenobarbital (PB) for the last 8 days of the experiment. A minipump implanted in the abdominal cavity released [methyl-3H]thymidine continuously for 72 h and was then removed prior to CIp or PB treatment. A second minipump was then implanted which released bromodeoxyuridine to the abdominal cavity 5 days after the start of Cip or PB administration and lasted for 72 h until the termination of the experiment. Both the [methyl-3H]thymidine and bromodeoxyuridine labeling indices (LIs) were determined in the same group of cells within individual rGSTP1-1-positive nodules in the right posterior lobes of livers. PB treatment increased both the average number of persistent GGT-positive nodules and the ratio of persistent GGT-positive to rGSTP1-1-positive nodules/cm2. In contrast, Cip treatment greatly decreased the average number and area of persistent GGT-positive nodules, as well as the ratio between persistent GGT-positive and rGSTP1-1-positive nodules/cm2. Cip treatment also resulted in a 40% decrease in the average LI in the rGSTP1-1-positive nodules. In some rGSTP1-1-positive nodules, the LI was decreased from > 40% prior to Cip treatment to < 5% afterward, suggesting that Cip treatment interrupted progression in these nodules. Such drastic changes in the LI before and after treatments were not observed in either PB- or vehicle-treated (control) animals. A number of small nodules with a high bromodeoxyuridine LI but with no or very few [methyl-3H]thymidine-labeled nuclei and negative GGT and rGSTP1-1 staining were detected only in the Cip group.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Enhancement of glutathione content in glutathione synthetase-deficient fibroblasts from a patient with 5-oxoprolinuria via metabolic cooperation with normal fibroblasts.

Fibroblasts from patients with the disease 5-oxoprolinuria have reduced glutathione synthetase activity and are thus glutathione (GSH) deficient. In this study, 5-oxoprolinuria fibroblasts (GM3877 cells) contained less GSH than normal diploid fibroblasts as determined by biochemical analysis and by flow cytometry using monochlorobimane. They also contained lower gamma-glutamylcysteine synthetase activity than normal cells. However, cocultures of GM3877 cells and normal cells displayed either normal or slightly elevated GSH content, depending upon the assay used. When differentially labeled with fluorescent beads, cocultured, and then isolated by fluorescence-activated cell sorting, both GM3877 cells and normal cells had GSH content similar to that of sorted normal cells cultured alone, whereas sorted GM3877 cells cultured alone showed depressed GSH content. GM3877 cells had detectable levels of gamma-glutamylcysteine (gamma-GC) when cultured alone, but gamma-GC was undetectable in these cells when they were cocultured with normal cells, indicating that it was efficiently metabolized to GSH by the normal cells. These changes in low-molecular-weight thiols were likely to have been mediated by metabolic cooperation across gap junctions because they were dependent upon confluency and because media conditioned by either cell type failed to significantly alter the GSH content of the other cell type. Cocultures exposed to moderate levels of hydrogen peroxide showed less depletion of GSH than GM3877 cells cultured alone, suggesting that the sharing of low-molecular-weight thiols or other reductants via metabolic cooperation can protect cells from oxidative stress.

Amino Acid Metabolism, Inborn Errors↗
PubMed1993

The effect of 1-chloro-2,4-dinitrobenzene exposure on antigen receptor (CD3)-stimulated transmembrane signal transduction in purified subsets of human peripheral blood lymphocytes.

The intracellular low-molecular-weight thiol glutathione (GSH) is an important scavenger of free radicals and plays a role in the maintenance of the redox status of protein sulfhydryl groups. We have previously shown that human peripheral blood lymphocytes sorted on their basal GSH content proliferate proportionately to their GSH levels, and that an early event in lymphocyte activation appeared to be dependent on GSH. We have now analyzed transmembrane signal transduction in cells treated with 1-chloro-2,4-dinitrobenzene (CDNB), a GSH-depleting agent. Transmembrane signal transduction was measured as changes in intracellular free calcium and in protein tyrosine phosphorylation after stimulation with anti-CD3 monoclonal antibody. The results show a CDNB dose-dependent reduction in GSH content, the magnitude of intracellular free calcium mobilization, and the extent of tyrosine phosphorylation of several proteins, including phospholipase C-gamma 1. This suggests a role for GSH and/or protein thiol redox status in one of the earliest events controlling the ability of lymphocytes to respond to important proliferative signals in their environment and implies that agents which deplete lymphocyte GSH may be immunosuppressive through effects on CD3/T cell receptor-dependent transmembrane signal transduction.

Antibodies, Monoclonal↗
PubMed1993

Decreased expression of cytochrome P450 mRNAs and related steroid hydroxylation activities in hepatic hyperplastic nodules in male F344 rats.

To explore the mechanism(s) underlying the relationship between expression of cytochrome P450 (CYP) enzymes and growth of hepatic hyperplastic nodules, mRNA of CYP1A1, 1A2, 2B1, 2B2, 2C6, 2C11, and 3A1, and CYP enzyme-mediated hydroxylation of testosterone (T), 17 beta-estradiol (E), and corticosterone (C) were determined in a group of selected large nodules from livers of male F344 rats given the modified Solt-Farber resistance protocol and compared with control and surrounding tissue. Slot-blot analysis with specific oligonucleotides showed little or no mRNA of CYP2B1, 2B2, and 2C6 in nodules, surrounding tissue, and control liver without PB treatment. Constitutive expression of CYP1A2, 2C11, and 3A1 in nodules was from 2 to 10 times less in nodules than in control liver. BP treatment increased mRNA of CYP2B1, 2B2, 2C6, 2C11, and 3A1 in control and surrounding tissue substantially, but was 3 to 11 times less in the nodules than in the control liver. Messenger RNA of CYP1A1 was not detected in either nodules or control livers independent of PB treatment. HPLC determination demonstrated a general pattern of a decrease in CYP enzyme-mediated hydroxylation of T, E, and C in the nodules relative to the surrounding tissue and control liver. The differences between nodules and control liver were usually 3 to 10-fold for the 12 metabolites detected although smaller decreases were observed for a few metabolites in some nodules. PB increased the rate of hydroxylation for 11 of the 12 metabolites and resulted in 2 additional metabolites of both T and E in control liver and some nodules. However, the general pattern of lower hydroxylation activities in the nodules relative to the surrounding tissue remained the same as that in the non-PB group. These observations are consistent with the hypothesis that intracellular kinetics of endogenous CYP enzyme substrates may differ in some nodules, relative to the surrounding tissue, as a result of decreased expression of CYP genes. This difference in CYP expression pattern in turn may contribute to the selective growth and progression to cancer of certain nodules, as many endogenous CYP enzyme substrates are modulators of DNA and RNA synthesis and cellular growth and differentiation.

Animals↗
PubMed1990

Longitudinal change and interstate variability in the size of residential facilities for persons with mental retardation.

Changes in the size and type of operation of residential facilities for persons with mental retardation in the United States over the past 2 decades were discussed and current (June 30, 1988) interstate variability in residential services along these same dimensions examined. Considerable progress was noted nationally in securing relatively small, community-based residential opportunities for persons with mental retardation. However, this progress has not been uniformly realized in all states or for all types of facilities. Standards for federal policy that would make the official national commitment to community-based services more consistent among all the states were considered.

Health Facility Size↗