The molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in French families; report of two novel mutations.
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Base Sequence↗
Biomedical subjects
G Liu
Publications and source records attributed to G Liu.
Mouse models dissect the role of p53 in cancer and development.
Mice lacking one or two copies of the p53 gene have provided invaluable insight into the process of tumorigenesis. The importance of apoptosis in suppression of tumorigenesis in vivo became evident from analysis of these mice. Moreover, the timing and kinds of tumors that develop in these mice are altered by the presence of additional inherited mutations, by strain differences, and by food intake. Developmental abnormalities are also visible in mice with loss of p53 and with overexpression of p53 suggesting that p53 levels are critical for normal cellular processes. While mice do not necessarily recapitulate all the tumor types found in inherited cancers, they offer the unique opportunity to decipher the critical pathways in tumorigenesis. These findings can then be applied to humans.
Animals↗
Bone mass and structure at the hip in men and women over the age of 60 years.
Bone mass and structure at the proximal femur are important predictors of hip fracture. The aims of this study were to compare in a large sample of elderly men and women the precision of measurements of bone mass and structure at multiple sites at the proximal femur, to examine their interrelationships, to establish their relationships with age and body size, and to examine criteria for defining geometric and architectural variables in bone structure. Women (n = 336) and men (n = 141) over the age of 60 years were studied cross-sectionally. Bone mineral density (BMD) and content (BMC) at the proximal femur were measured in duplicate by dual-energy X-ray absorptiometry (DXA). Shaft and total upper femur (hip) sites in addition to femoral neck, Ward's triangle and trochanter were measured. Structural variables, measured from radiographs and from DXA images, including cortical thickness at calcar femorale, lateral cotex and midfemur, width of the femur and medulla, Singh grade, hip and femoral axis length, femoral head and neck width and the center of mass of the femoral neck. BMD and BMC had high reproducibility and there were significant differences in reproducibility across sites. Among sites, total upper femur and shaft had the highest reproducibility. Duplicate measurements substantially improved reliability of the measurement and are recommended when the value is close to a diagnostic level or when it will be used to establish rates of change. Reproducibility of structural variables was also high except for the lateral cortex, center of mass and Singh grade. Variance due to measurement error did not change with either age or gender. Women were significantly different from men, after controlling for differences in body size, in all variables except Singh grade and medulla width. BMD and BMC were negatively related to age and positively to body size. Structural variables examined in relation to age and body size fell into two categories. The first comprised variables that were not age-related but were body-size-related suggesting that they could be classified as geometric variables. The second comprised variables that were both body-size-related and age-related, suggesting that they could be classified as architectural variables. Using these criteria, calcar and lateral cortex were architectural variables, whereas shaft width, hip and femoral axis length, femoral head and neck width, and center of mass were geometric in both men and women. In women, shaft cortex width and medulla width were age-related, whereas in men they were not. Singh grade showed no consistent pattern with age or body size in women and men.
Absorptiometry, Photon↗
Age-related changes in serum undercarboxylated osteocalcin and its relationships with bone density, bone quality, and hip fracture.
The effect of the degree of carboxylation of osteocalcin (OC) on the properties of bone is unclear. The aim of this study was to relate serum concentrations of total OC (tOC) and undercarboxylated OC (ucOC), measured with a two-site immunoassay, to bone mineral density (BMD) at the femoral neck and ultrasonic transmitted velocity (UTV) at the os calcis in 257 women aged 60-99 years, 22 of whom had sustained a hip fracture. There was an increase in tOC (r = 0.19, P = 0.003) and ucOC (r = 0.20, P = 0.002) with age. No significant difference in tOC or ucOC between subjects with and without hip fracture was found. Serum tOC was negatively correlated with femoral neck BMD (r = -0.23, P = 0.0001) and os calcis UTV (r = -0.29, P = 0.0001) and partial correlations indicated that these relationships were independent of age. Serum ucOC also correlated negatively with os calcis UTV (r = -0.21, P = 0.001) and less strongly with femoral neck BMD (r = -0.13, P = 0.052). After adjusting for age, only the relationship between ucOC and os calcis UTV remained significant (r = -0.16, P = 0.017). It is concluded that in women over 60 years, the increase in tOC reflects an age-related rise in bone remodeling, whereas the increase in ucOC reflects an age-related fall in vitamin K status. The stronger relationship of ucOC with UTV than BMD suggests that the rise in ucOC may perhaps relate more to changes in bone quality than mineral content. Higher serum ucOC concentrations in subjects with a history of hip fracture could not be confirmed.
Age Factors↗
Role of superoxide anion on the proliferation and c-Ha-ras or p53 expression in prostate cancer cell line PC3.
The purpose of this study was to investigate the role of superoxide anion (02-*) in the regulation of p53 or c-Ha-ras expression and proliferation in the prostate cancer cell line PC3. Cell proliferation was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in the presence of O2-*, basic fibroblast growth factor (bFGF) or their combination. p53 or C-Ha-ras expression in the cells treated with O2-* was assayed by fluorescence in situ hybridization (FISH). The proliferation was significantly inhibited by O2-* in a concentration-dependent manner ranging from 9 to 36 micromol/l nicotinamide adenine dinucleotid (NADH) combined with 2-8 micromol/l N-methylphenazonium methyl sulfate (PMS). Enhancement of proliferation by 2 ng/ml bFGF was significantly inhibited by O2-*. Although O2-* was not able to alter c-Ha-ras gene expression, O2-* at the concentrations of 18 micromol/l NADH and 4 micromol/l PMS upregulated the expression of p53. O2-* may modulate proliferation and gene expression in PC3 cells.
Anions↗
The cenpB gene is not essential in mice.
Centromere protein B (CENP-B) is a centromeric DNA-binding protein that binds to alpha-satellite DNA at the 17 bp CENP-B box sequence. The binding of CENP-B, along with other proteins, to alpha-satellite DNA sequences at the centromere, is thought to package the DNA into heterochromatin subjacent to the kinetochore of mitotic chromosomes. To determine the importance of CENP-B to kinetochore assembly and function, we generated a mouse null for the cenpB gene. The deletion removed part of the promoter and the entire coding sequence except for the carboxyl-terminal 35 amino acids of the CENP-B polypeptide. Mice heterozygous or homozygous for the cenpB null mutation are viable and healthy, with no apparent defect in growth and morphology. We have established mouse embryo fibroblasts from heterozygous and homozygous cenpB null littermates. Microscopic analysis, using immunofluorescence and electron microscopy of the cultured cells, indicated that the centromere-kinetochore complex was intact and identical to control cells. Mitosis was identical in fibroblasts derived from cenpB wild-type, heterozygous and null animals. Our studies demonstrate that CENP-B is not required for the assembly of heterochromatin or the kinetochore, or for completion of mitosis.
Animals↗
Randomized, double-blind, placebo-controlled trial of oral enalapril in patients with neurally mediated syncope.
BACKGROUND: The purpose of this study was to study the effect of enalapril on neurally mediated syncope (NMS). Several agents (except for angiotensin-converting enzyme [ACE] inhibitors) have been used to treat patients with NMS. It is unknown whether ACE inhibitors have beneficial effects on NMS. METHODS AND RESULTS: Thirty subjects who had reproducible NMS induced with head-up tilt table test (HUT) were randomly assigned and divided in double-blind fashion into placebo and enalapril (an ACE inhibitor) groups. Hemodynamics and plasma catecholamine concentrations were studied. Before administration of enalapril, syncope induced by HUT was associated with vigorous hypotension and bradycardia. Plasma catecholamine concentrations were significantly elevated during NMS compared with the supine position before tilt. Oral enalapril rather than placebo produced a marked reduction in diastolic blood pressure during supine positioning before tilt. Administration of enalapril prevented HUT-induced NMS and increase of plasma catecholamine concentrations in all patients examined. Conversely, placebo had no effect in the majority of patients with NMS (12 of 15 subjects). Follow-up data showed that NMS disappeared in 14 (93%) of 15 patients treated with enalapril. CONCLUSIONS: This study demonstrates that ACE inhibitors may efficiently prevent NMS, presumably through inhibition of sympathetic system activation and peripheral hypotensive effect.
Administration, Oral↗
Modulation of cytokine production following intranasal administration of antigenic peptide.
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Administration, Intranasal↗
Restricted expression of oncofetal fibronectin mRNA in thyroid papillary and anaplastic carcinoma: an in situ hybridization study.
Restricted expression of oncofetal fibronectin mRNA in the tissues of thyroid papillary and anaplastic carcinoma has recently been shown by both Northern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR). Oncofetal fibronectin mRNA can be a target of gene diagnosis and targeted gene therapy, provided it is expressed in all cancer cells in the tissues. To investigate this criterion in thyroid cancer tissues, we measured their expression of oncofetal fibronectin mRNA using in situ hybridization. An abundant expression of oncofetal fibronectin mRNA was found in all the observed cancer cells of six papillary carcinomas and an anaplastic carcinoma, but not in the tissues of normal thyroid, Graves' disease, adenomatous goitre, follicular adenoma, follicular carcinoma or medullary carcinoma. This result encourages us to establish gene diagnosis of thyroid papillary and anaplastic carcinomas by detecting oncofetal fibronectin mRNA in biopsies.
Antigens, Neoplasm↗
The effects of ceftiofur sodium (Naxcel) on bovine oocyte and preimplantation embryonic development assessed by in vitro embryo production techniques.
Ceftiofur sodium is a third-generation cephalosporin antibiotic with broad spectrum bactericidal activity against Gram-positive and Gram-negative bacteria including the beta-lactamase producing strains. In this study, we use in vitro techniques to examine the effects of low and high levels of ceftiofur sodium on the development of bovine oocytes/embryos during oocyte maturation, oocyte fertilization and embryo culture. A total of 8590 oocytes was used in six independent experiments, each in a randomized complete block design. Each replication within each experiment consisted of oocytes from the same abattoir collection of ovaries. There was no difference in embryo development when oocytes were exposed to ceftiofur sodium during oocyte maturation or fertilization at low (10 and 50 micrograms/mL) or high (100 and 200 micrograms/mL) concentrations. However, when fertilized oocytes were exposed to concentrations > or = 50 micrograms/mL during culture, ceftiofur sodium significantly retarded embryo development (e.g. the numbers of ova developing to the morula and blastocyst stages were reduced, and a large proportion of embryos were blocked at the 8-cell stage). We conclude that ceftiofur sodium does not appear to have detrimental effects on oocyte maturation and fertilization. However, long term exposure to high dosages of ceftiofur sodium during post-fertilization culture adversely affects embryo development in vitro.
Animals↗
FtsK is a bifunctional protein involved in cell division and chromosome localization in Escherichia coli.
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Cell Division↗
Comparison of active treatment and placebo in older Chinese patients with isolated systolic hypertension. Systolic Hypertension in China (Syst-China) Collaborative Group.
BACKGROUND: Isolated systolic hypertension occurs in around 8% of Chinese people aged 60 years or older. In 1988, the Systolic Hypertension in China (Syst-China) Collaborative Group started to investigate whether active treatment could reduce the incidence of stroke and other cardiovascular complications in older patients with isolated systolic hypertension. METHODS: All patients were initially started on masked placebo. After stratification for centre, sex and previous cardiovascular complications, alternate patients (n=1253) were assigned nitrendipine at 10-40 mg daily, with the addition of captopril at 12.5-50.0 mg daily or hydrochlorothiazide at 12.5-50.0 mg daily, or both, if a sufficient blood pressure fall was not obtained. In the remaining 1141 control patients, matching placebos were administered similarly. RESULTS: At entry, sitting blood pressure averaged 170.5 mmHg systolic and 86.0 mmHg diastolic, age averaged 66.5 years and total serum cholesterol was 5.1 mmol/l. After 2 years of follow-up, sitting systolic and diastolic blood pressures had fallen by 10.9 mmHg and 1.9 mmHg in the placebo group and by 20.0 mmHg and 5.0 mmHg in the active treatment group. The intergroup differences were 9.1 mmHg systolic (95% confidence interval 7.6-10.7 mmHg ) and 3.2 mmHg diastolic (95% confidence interval 2.4-4.0). Active treatment reduced total strokes by 38% (from 20.8 to 13.0 endpoints per 1000 patient-years, P=0.01), all-cause mortality by 39% (from 28.4 to 17.4 endpoints per 1000 patient-years, P=0.003), cardiovascular mortality by 39% (from 15.2 to 9.4 endpoints per 1000 patient-years, P=0.03), stroke mortality by 58% (from 6.9 to 2.9 endpoints per 1000 patient-years, P=0.02), and ail fatal and nonfatal cardiovascular endpoints by 37% (from 33.3 to 21.4 endpoints per 1000 patient-years, P=0.004). CONCLUSIONS: Antihypertensive treatment prevents stroke and other cardiovascular complications in older Chinese patients with isolated systolic hypertension. Treatment of 1000 Chinese patients for 5 years could prevent 55 deaths, 39 strokes or 59 major cardiovascular endpoints.
Aged↗
Inhibitory effect of enalapril on neurally mediated syncope in elderly patients.
A dramatic increase in catecholamine (CA) concentration is believed to be a primary trigger of the neurally mediated syncope (NMS) in elderly subjects. The hypercontractile state of the heart might be alleviated by angiotensin-converting enzyme (ACE) inhibitor through depression of CA release from the sympathetic nerve ending. Thus ACE inhibitor might have positive effect on the prevention of NMS. In this study, 24 elderly subjects who had reproducible NMS induced with head-up tilt test (HUT) were randomized and double-blind divided into placebo and ACE-inhibitor groups. The plasma CA concentration [norepinephrine (NE) and epinephrine (E)] were measured during HUT, and the effects of enalapril on NMS were observed in the two groups. Before administration of enalapril, plasma CA concentrations were significantly increased during HUT compared with those in the supine position; In contrast, administration of the enalapril (10 mg/day) for >1 year inhibited the concentration of plasma CA increase and prevented syncope in all 12 patients (p < 0.05); however, placebo had no effect on plasma CA concentrations and syncope disappeared in only two of 12 patients after administration of placebo. From this study, we conclude that enalapril can prevent NMS in patients, presumably because of its part in the inhibition of CA release from sympathetic nerve endings.
Aged↗
Lipid second messengers derived from glycerolipids and sphingolipids, and their role in smooth muscle function.
The processes that link activation of an external receptor to the internal mechanisms that elicit a physiological response have been the subject of extensive investigation. It has been established that rather than just being an inert barrier to protect the cell from environmental damage, there are populations of phospholipids located within the plasma membrane that act as a reservoir for signalling molecules and when a receptor binds its appropriate activating ligand a chain of events is initiated which leads to the breakdown of these lipids and the release of second messengers. Such processes are rapid enough for physiological responses to be effected. The purpose of this review is to examine the profile of lipid second messengers derived from glycerophospholipids and sphingolipids. In the former class are included phosphoinositide and phosphatidylcholine and the latter includes sphingomyelin. Hydrolysis of such parent compounds is mediated by phospholipases and the profile of metabolites appears to be agonist specific and modulated by a number of mechanisms including heterotrimeric G-protein subunits, small G-proteins, alterations in intracellular calcium concentration, protein kinase C and tyrosine kinases. The recent interest in sphingolipids, particularly in vascular smooth muscle cells, has been provoked by the observation that ceramide and sphingoid base formation is observed in response to vasoconstrictor hormones.
Animals↗
Impact of pharmacist consultations provided to patients with diabetes on healthcare costs in a health maintenance organization.
We conducted a study to assess the impact on healthcare utilization and costs of pharmacist consultations provided to patients with diabetes. Data for this study were derived from a larger study conducted by Kaiser Permanente and the University of Southern California that evaluated three alternative models of pharmacist consultations (control, state, and Kaiser). Computerized data were available for patient demographic characteristics and healthcare utilization. We used medication data to classify patient cohorts as insulin only or oral antidiabetics +/- insulin. We estimated hospitalization costs based on diagnostic related group and medication costs based on average wholesale price; office visits were estimated at $70 each. In the insulin only cohort, total costs for patients who had their prescriptions filled at a state model pharmacy were 7.8% less than those for patients filling prescriptions at a control model pharmacy (P = 0.008). In the oral +/- insulin cohort, total costs for patients filling new prescriptions at a Kaiser model pharmacy were 21.9% less than those for patients using a control model pharmacy (P = 0.0001). The state model also was negatively correlated (beta coefficient, -0.0997) with total costs (P = 0.0001). These data suggest that pharmacist consultations provided to patients with diabetes can decrease total healthcare costs in a health maintenance organization.
Adult↗
[Subtype and sequence analysis of the C2-V3 region of gp120 genes among HIV-1 strains in Sichuan province].
Nine DNA fragments of HIV-1 env gene were amplified by PCR from uncultured peripheral blood mononuclear cells (PBMCs) obtained from HIV-1 sero-positive intravenous drug users (IDUs) in Sichuan province, in mid 1996. Their C2-V3 region (about 450 bp) was sequenced. Sequence analysis showed that there were two HIV-1 subtypes B and C, with 1.4% and 2.6% gene divergence inside each subtype, in Sichuan. The 5 subtype B strains, when comparing with sequences of several reference HIV-1 strains, were found similar to these identified in Thailand, Myanma and Yunnan province. The nucleotide sequence divergence between them was ranged from 3.6% to 4.3%. Meanwhile, the 4 subtype C strains except sc3, were most close to those found in India as well as in Yunnan province, and both their nucleotide sequence divergence was 3.1%. The sc3 strain belonged to subtype C but had larger genetic distance, between 10.1%-17.2%. Above results suggested a recent epidemic of both subtype HIV-1 strains in Sichuan provine and they were very close to those identified in Yunnan province: The subtype C strain of sc3 is special and its source remains not clear.
China↗
Effectiveness of the analogue of natural Schisandrin C (HpPro) in treatment of liver diseases: an experience in Indonesian patients.
OBJECTIVE: To determine the effect of dimethyl-4,4'-dimethoxy-5,6, 5',6-dimethylene dioxybiphenyl-2,2'-dicarboxylate (HpPro) on patients with acute and chronic liver diseases. METHODS: An open trial and a prospective randomized and controlled study were performed. The open trial consisted of 56 cases (16 cases of acute hepatitis, 20 cases of chronic hepatitis, 14 cases of liver cirrhosis and 6 cases of fatty liver). Controlled study consisted of 20 cases of Child A chronic hepatitis which were randomly treated with either HpPro or a mixture of known drugs which used as a liver protective agent in Indonesia as control for one week. The patients were then crossed over those two drugs in the next week. RESULTS: In the open trial, after 4 weeks' treatment with HpPro 7.5 mg orally three times daily, acute hepatitis, chronic hepatitis and fatty liver cases showed rapid decrease of SGOT and SGPT. In the liver cirrhosis cases, SGOT and SGPT were decreased slowly. In the controlled trial, nine patients received HpPro 7.5 mg three times daily orally and eleven were treated with a mixture of known drugs as the controls. After one week treatment, HpPro group clinically showed significant decrease of SGPT and SGOT levels compared to control group (P = 0.035). At the second week, HpPro group showed significant decrease of SGOT compared to control group (P = 0.038) but the decrease of SGPT was not significant (P = 0.096). CONCLUSION: Treatment with HpPro is effective to reduce liver impairment in acute and chronic liver diseases on Indonesian patients. No side effect of HpPro was observed.
Adolescent↗
[A study on HBV DNA pre C region A83 mutation in patients with hepatitis B].
Mismatched polymerase chain reaction (MPCR) and restriction fragment length polymorphism assay(RFLP) were performed to detect the HBV DNA pre core A83 mutation in 97 patients with chronic HBV infection in Hunan. HBV DNA pre core A83 mutation were detected in 37 out of 97 patients (37/97,38.1%). It was found that the prevalence of HBV DNA pre core A83 mutation of the patients with severe hepatitis and with CAH(chronic active hepatitis) were significantly higher than those with CPH(chronic persistent hepatitis) and carriers of HBV, and the patients with elevated transaminase (ALT > 70U) or positive HBeAb were significantly higher than those with normal transaminase (ALT < 70U) and with positive HBeAg, respectively. The results suggest that the HBV DNA pre core A83 mutation is associated with active and severe liver tissue in patients with hepatitis B.
Adolescent↗