Biomedical subjects

L Jin

Publications and source records attributed to L Jin.

At least 163 records · Page 9Linked to original sources

PubMed2000

p27kip1 expression distinguishes papillary hyperplasia in Graves' disease from papillary thyroid carcinoma.

In most cases, the histopathologic and cytologic distinction between Graves' disease and papillary thyroid carcinoma is relatively easy, but on occasion Graves' disease may simulate a thyroid papillary carcinoma. For example, papillary fronds with fibrovascular cores may be present in both Graves' disease and papillary carcinoma. p27kip1 (p27) is a cyclin-dependent kinase inhibitory protein that has been shown to be an independent prognostic factor in a variety of human tumors. Our previous studies of p27 expression in hyperplastic and neoplastic endocrine lesions showed that the level of p27 was quite different in these two conditions. To determine if this distinction could also be made between Graves' disease and papillary carcinoma, we analyzed expression of p27 and other cell cycle proteins in a series of cases of Graves' disease with papillary hyperplasia and a series of papillary thyroid carcinomas. Formalin-fixed paraffin-embedded tissues from 61 randomly selected patients with thyroid disease, including 29 cases of Graves' disease with papillary architectural features and 32 cases of papillary carcinoma, were analyzed for expression of p27, Ki-67, and DNA topoisomerase II alpha (topo II alpha) by immunostaining. The distribution of immunoreactivity was analyzed by quantifying the percentage of positive nuclei that was expressed as the labeling index (LI) plus or minus the standard error of the mean. The papillary hyperplasia of Graves' disease had a p27 LI of 68.2 +/- 3.1 (range, 24 to 88), whereas papillary carcinomas had a LI of 25.6 +/- 2.5 (range, 12 to 70) (P < .0001). No significant differences in Ki-67 or topo II alpha expression were identified between papillary hyperplasia in Graves' disease and papillary carcinoma. These results indicate that p27 protein expression is significantly higher in papillary hyperplasia of Graves' disease compared to papillary carcinoma, which may be diagnostically useful in difficult cases.

Adult↗

PubMed2000

Endothelial nitric oxide synthase is a site of superoxide synthesis in endothelial cells treated with glyceryl trinitrate.

Tolerance to glyceryl trinitrate (GTN) involves superoxide (O(2)(*-)) production by endothelial cells. Nitric oxide synthase (NOS) produces O(2)(*-) when L-arginine (L-arg) is limited. The purpose of this study was to test the hypothesis that GTN stimulates NOS to increase O(2)(*-) synthesis in endothelial cells when L-arg is limited. Production of O(2)(*-) by bovine aortic endothelial cells (BAEC, passages 3 - 5) was determined by spectrophotometrically measuring superoxide dismutase-inhibited reduction of ferricytochrome C to ferrocytochrome C. Cells were incubated in buffer without L-arg. O(2)(*-) production was measured using BAEC either untreated or treated with L-NAME or L-arg alone or following treatment with GTN (10(-9) to 10(-6) M) for 30 min or DPTA NONOate (10(-7) and 10(-6) M) alone or with GTN or DPTA NONOate after pretreatment with nitro-L-arginine methyl ester (L-NAME), L-arg or their inactive enantiomers, D-NAME or D-arg (all 5 x 10(-4) M) (n=6 - 7/group). L-NAME alone produced a 69% reduction in O(2)(*-) levels. Treatment with L-arg alone had no effect. Cells treated with GTN alone exhibited an increase in O(2)(*-). This effect was prevented by pretreatment with either L-NAME or L-arg, and was unaffected by D-NAME or D-arg. We observed a dose-response relationship in O(2)(*-) production to GTN over a range of 10(-9) to 10(-7) M. The NO donor, DPTA-NONOate, unlike GTN, did not have a significant effect on O(2)(*-) production. In conclusion, endothelial NOS is a site of O(2)(*-) synthesis in endothelial cells activated by GTN.

Animals↗

PubMed2000

Distribution of three HIV-1 resistance-conferring polymorphisms (SDF1-3'A, CCR2-641, and CCR5-delta32) in global populations.

Chemokine receptors (CCR5, CXCR4 and CCR2) have been shown to be important co-receptors for HIV infection. Mutations at CCR5 (CCR5-delta2), CCR2 (CCR2-641), and stromal-derived factor SDF1 (SDF1-3'A), a primary ligand for CXCR4, are known to have protective effects against HIV-1 infection and the onset of AIDS symptoms. We studied the three-locus genotype frequency distributions in 70worldwide populations from a sample of 2341 individuals without any known history of HIV-1 infection and AIDS symptoms. From these data, we estimated the risk of AIDS onset (relative hazard, RH) of each population. This survey shows that the substantial allele frequency differences of each of these mutations translate into an extensive variation in relative hazards for AIDS in worldwide populations. However, no evidence of natural selection against the mutant gene carriers is detected. Finally, the combined three-locus genotype data predict the highest relative hazard (RH) in South-East Asia and Africa where AIDS is known to be more prevalent.

Chemokine CXCL12↗

PubMed2000

A novel electrochemical microsensor for the determination of NO and its application to the study of the NO donor S-nitrosoglutathione.

A novel electrochemical microsensor for the determination of NO based on an electropolymerized film of tetraaminophthalocyaninecopper [Cu(TAPc)] was prepared. Its response to NO and its application to the study of an NO donor (S-nitrosoglutathione; GSNO) are also described. The microsensor exhibited an electrocatalytic effect on NO oxidation and showed a low detection limit, high sensitivity and selectivity for NO determination. The oxidation current (measured by differential pulse amperometry) was linear for NO concentrations ranging from 6.2 x 10(-9) to 3.0 x 10(-5) mol L-1 with a calculated detection limit of 4.0 x 10(-9) mol L-1 (S/N = 3) and a linear coefficient of 0.9984. Some endogenous electroactive substances in biological tissues, such as dopamine, 5-hydroxytryptamine and nitrite, at concentrations higher than those in biological systems did not interfere with NO determination. The sensor shows promise for the possible in vivo determination of NO. Using the microsensor, the NO release from the NO donor (GSNO) was successfully monitored. This work sets a foundation for the study of the pharmacology and the biological effects in vivo of S-nitrosothiols.

Electrochemistry↗

PubMed2000

Measurement of nitric oxide released in the rat heart with an amperometric microsensor.

Nitric oxide (NO) plays an important role in various physiological processes, acting either as an intra- and intercellular messenger or as a toxic agent. The detection and quantification of NO have been accomplished by a variety of methodologies. In the present study, real-time production of NO in the rat heart was continuously measured by using a novel copper-platinum microparticle-modified NO electrochemical microsensor. The linearity range of the microsensor is between 8.0 x 10(-8) and 4.8 x 10(-6) mol L-1 and the detection limit is 3.0 x 10(-8) mol L-1. NO release from the rat heart stimulated by the agonists L-arginine and acetylcholine was observed, and the responses were decreased by the NO synthase inhibitor L-N omega-nitroarginine. In addition, the effect of sodium nitroprusside (SNP), a NO donor, was also studied. SNP increases the concentration of NO in the rat heart. The experiments showed that electrochemical detection is suitable for detecting and quantifying NO in biological systems.

Acetylcholine↗

PubMed2000

Variations in the care of elderly persons with diabetes among endocrinologists, general internists, and geriatricians.

BACKGROUND: The American Diabetes Association (ADA) clinical practice recommendations have been widely promoted, but they lack a geriatric-specific approach to care. We aimed to determine the style of care that endocrinologists, general internists, and geriatricians provided to their elderly patients with diabetes and to what extent these medical professionals adhered to the ADA standards. METHODS: We performed a retrospective cohort study of a stratified sample of 531 diabetic patients aged 65 years and older from the endocrinology, general internal medicine, and geriatrics clinics of an urban academic medical center. RESULTS: Patients of geriatricians were older, had higher comorbidity, and were more likely to be demented. The average number of diabetic complications was similar across the specialties, although patients of endocrinologists had higher prevalence of neuropathy and retinopathy compared with patients of geriatricians. Endocrinologists were more likely to use insulin, multiple types of insulin, and combined oral hypoglycemic and insulin therapies. Most patients had hemoglobin A1c measured, and average values were similarly high across specialties at 8.6%. Blood pressures were above 130/85 mm Hg in 85% of the patients. All specialties rarely measured urine microalbumin; geriatricians seldom performed fractionated cholesterol tests, and ophthalmology visits occurred in only half of the patients. CONCLUSION: Endocrinologists had the most aggressive, complex diabetes treatment regimens, although geriatricians had older patients with more dementia and lower prevalence of microvascular complications. Average hemoglobin A1c levels and blood pressures were higher than recommended among patients of all three specialties. Screening for diabetic complications and hyperlipidemia was lower than advised.

Aged↗

PubMed2000

Vascular and endothelial actions of inhibitors of substance P amidation.

Formation of mature active neuropeptides such as substance P (SP) from their glycine extended precursors entails alpha-amidation of peptide precursors by the sequential enzymatic action of peptidylglycine alpha-monooxygenase (PAM) and peptidylamidoglycolate lyase (PGL). We reported that these two enzymes that can produce mature active neuropeptides are present in cultured bovine aortic endothelial cells (BAECs). We hypothesize that alpha-amidation of peptides occurs in endothelial cells and that these peptides are critically involved in the overall regulation of cardiovascular function. In this study, this hypothesis was tested using specific amidation inhibitors to determine their effects on the actions of SP and its glycine-extended precursor (SP-Gly). We have found that SP and SP-Gly are equipotent in stimulating nitric oxide (NO) release by BAECs. At 10(-5) M, the specific inhibitors of PAM (4-phenyl-3-butenoic acid; PBA) and PGL (5-acetamido-2,4-diketo-6-phenyl-hexanoic acid and its methyl ester) reduced NO basal release by 40, 34, and 45%, respectively. They also reduced the production of NO induced by SP-Gly by 63, 68, and 69%, respectively, but had no effect on NO production in response to either SP or acetylcholine. SP and SP-Gly also were equipotent in relaxing rat aortic segments. The vasorelaxation to SP-Gly was endothelium dependent and inhibited by the NOS antagonist L-nitroarginine methyl ester (L-NAME), but it was not affected by inhibition of prostaglandin synthesis. Inhibitors of both PAM and PGL significantly reduced the vasorelaxing actions of SP-Gly, whereas responses to SP were not affected. A cumulative infusion of PBA into the femoral artery of rabbits, at final concentrations of 2.4, 24, and 240 microM for 20 min each, increased the vascular resistance (VR), indicating the tonic production of vasodilating amidated peptide(s). This effect was maximum at 60 min after infusion (20.5 +/- 4.7 vs. 8.2 +/- 0.7 mm Hg/ml/min; p < 0.05). These results suggest that endothelial cells can produce mature SP from its SP-Gly precursor and that a product of peptide alpha-amidation tonically stimulates endothelial cell NO release to control vascular tone.

Amidine-Lyases↗

PubMed2000

Identification of the pseudorabies virus promoter required for latency-associated transcript gene expression in the natural host.

Expression of the latency-associated transcript (LAT) gene is a hallmark of alphaherpesvirus latency, and yet its control and function remain an enigma. Resolution of this problem will require verification and subsequent elimination or disabling of elements regulating LAT gene transcription so that the influence of the resultant RNA can be evaluated. Toward this end, we generated a novel pseudorabies virus (PrV) recombinant in which a 282-bp region containing the LAP1 (first latency-active promoter) consensus sequence was replaced by a reporter cassette. Despite this substitution, replication of the recombinant was comparable to that of the parental and rescuant viruses both in cultured mammalian cells and in the natural host, swine. Furthermore, production of the LAT gene-associated 2.0- and 8.0-kb RNAs during an in vitro lytic infection of cultured neuronal cells was unaffected. However, the otherwise constitutively produced and processed 8.4-kb LAT was not detected in porcine trigeminal ganglia latently infected with this novel recombinant, although the viral genome was shown to be present. Therefore, LAP1 is apparently the basal promoter for PrV LAT gene expression during viral latency but is not required for such activity during an in vitro lytic infection of neuronal cells. More importantly, the ability of PrV to persist in a latent state in the absence of LAT suggests that other factors are responsible for this event in the natural host.

Animals↗

PubMed2000

The haplotype linkage disequilibrium test for genome-wide screens: its power and study design.

The focus of human genetics continues to shift toward the dissection of complex phenotypes. Integral to these endeavors is the development of powerful analytical tools. To this end, we propose a novel method designated the haplotype linkage disequibrium (LD) test for identifying diseases genes. The basic structure of the haplotype test statistic is a chi-square in which haplotypes, as opposed to individual marker data, are compared between cases and controls. Specifically, we performed power calculations and demonstrate that the use of haplotypes improves the power of mapping disease genes. We show that this approach can be used for initial genome-wide screens in mapping disease genes. Furthermore, we investigated the factors influencing statistical power of the method and discussed basic principals underlying study design. Published data from the Hereditary Hemochromatosis region was used to illustrate the utility of the haplotype test. Also discussed is its relationship with linkage disequibrium.

Alleles↗

PubMed2000

Effects of NO donors and synthase agonists on endothelial cell uptake of L-Arg and superoxide production.

It is commonly believed that the activity of NO synthase (NOS) solely controls NO production from its substrates, L-Arg and O(2). The Michaelis-Menten constant (K(m)) of NOS for L-Arg is in the micromolar range; cellular levels of L-Arg are much higher. However, evidence strongly suggests that cellular supply of L-Arg may become limiting and lead to reduced NO and increased superoxide anion (O(-)(2)*) formation, promoting cardiovascular dysfunction. Uptake of L-Arg into cells occurs primarily (approximately 85%) through the actions of a Na(+)-independent, carrier-mediated transporter (system y(+)). We have examined the effects of NOS agonists (substance P, bradykinin, and ACh) and NO donors (S-nitroso-N-acetyl-penicillamine and dipropylenetriamine NONOate) on transport of L-Arg into bovine aortic endothelial cells (BAEC). Our results demonstrate that NOS agonists increase y(+) transporter activity. A rapidly acting NO donor initially increases L-Arg uptake; however, after longer exposure, L-Arg uptake is suppressed. Exposure of BAEC without L-Arg to substance P and a Ca(2+) ionophore (A-23187) increased O(-)(2)* formation, which was blocked with concurrent presence of L-Arg or the NOS antagonist N(omega)-nitro-L-arginine methyl ester. We conclude that factors including NO itself control y(+) transport function and the production of NO and O(-)(2)*.

Animals↗

PubMed2000

Leptin and leptin receptor expression in rat and mouse pituitary cells.

Leptin is a circulating hormone secreted mainly by adipose tissue. Recent studies have shown leptin production by other tissues, including the placenta, stomach, and mammary tissues. Various reports have suggested that the anterior pituitary may have a role in the regulatory effects of leptin. We recently localized leptin in the human anterior pituitary, but analysis of leptin in rodent pituitary has not been previously reported. In this study we examined rat and mouse pituitary tissues and various cell lines for leptin by RT-PCR, immunohistochemistry, and Western blotting. Leptin receptor messenger RNA was also examined in these tissues by RT-PCR. Leptin was present in a small percentage of rat (4.8 +/- 0.7%) and mouse (7 +/- 2%) pituitary cells. Colocalization studies with leptin and pituitary hormones showed leptin expression mainly in TSH cells (24 +/- 2% of TSH cells in the rat pituitary and 31 +/- 1% of TSH cells in the mouse pituitary). A folliculo-stellate (FS) cell line, TtT/GF, also expressed leptin. The long isoform of leptin receptor (OB-Rb) was present in normal pituitary and in various pituitary cell lines, including FS, GH3, and alphaT3-1 cells. Treatment of GH3 and FS cells with leptin (1 x 10(-8) M) inhibited cell proliferation assessed by [3H]thymidine incorporation in GH3, but not in FS, cells. These findings show for the first time that leptin is expressed in rat and mouse anterior pituitaries mainly by TSH cells and by a mouse FS cell line. The finding of leptin and of the long isoform of leptin receptor in normal rat and mouse pituitaries and in various cell lines implicates an autocrine/paracrine loop in the production and regulation of leptin and leptin receptor in the rodent pituitary.

Animals↗

PubMed2000

Aberrant DNA methylation of cyclin D2 and p27 genes in rodent pituitary tumor cell lines correlates with specific gene expression.

We previously reported that increased DNA methylation was an important mechanism of silencing the p27 gene in some pituitary tumor cell lines [1]. DNA methylation correlated inversely with p27 gene expression. The p27 and cyclin D2 genes are located in the same region of mouse chromosome 6, rat chromosome 4, and human chromosome 12p13. Because both genes are located in the same gene cluster, we investigated whether methylation was a principal mechanism regulating cyclin D2 as well as p27 expression in rodent pituitary cell lines. Bisulfite genomic sequencing showed that the normally unmethylated cytosines of the p27 gene in normal pituitary (NP) were extensively methylated in GH3 and GHRH-CL1 cells, but not in AtT 20, alphaT3-1 and LbetaT2 cells; but cyclin D2 was extensively inactivated in various pituitary tumor cell lines by increased DNA methylation. These abnormalities of methylation in p27 and cyclin D2 genes occurred with different frequencies in five pituitary tumor cell lines with 100% (5/5) methylation of the cyclin D2 gene and 40% (2/5) methylation of the p27 gene. Treatment with the methyl transferase inhibitor 5'-aza-2'-deoxycytidine (AZAdC) increased expression of cyclin D2 and p27 in GH3 and GHRH-CL1 pituitary tumor cells. There was a correlation between hypermethylation and gene expression. GH3 tumors implanted into Wistar-Furth rats in vivo did not change the methylation status of the p27 and cyclin D2 genes. These data indicate a coordinately reduced expression of these two linked genes in most rodent pituitary tumor cell lines and suggest that methylation of cyclin D2 and p27 might occur in a "hot spot" in this gene-rich cluster.

Journal Article↗

PubMed2000

Interleukin-8 and granulocyte elastase in gingival crevicular fluid in relation to periodontopathogens in untreated adult periodontitis.

BACKGROUND: This study aimed to determine the relationships among interleukin (IL)-8 and granulocyte elastase levels in gingival crevicular fluid (GCF) and the concomitant presence of periodontopathogens in untreated adult periodontitis. METHODS: GCF and subgingival plaque samples were collected from 16 patients with untreated adult periodontitis and 10 healthy control subjects. IL-8 levels were determined by enzyme-linked immunosorbent assay (ELISA). Granulocyte elastase was analyzed with a neutrophilic granulocyte-specific, low molecular weight and chromogenic substrate, L-pyroglutamyl-L-prolyl-L-valine-p-nitroanilide, and the maximal rate of elastase activity (MR-EA) was calculated. Five DNA probes were used to detect the presence of A. actinomycetemcomitans (A.a.), B. forsythus (B.f.), P. gingivalis (P.g.), P. intermedia (P.i.), and T. denticola (T.d.). RESULTS: Lower IL-8 concentrations and higher granulocyte elastase activities were found in patients than in healthy controls as well as in diseased conditions co-infected with B.f., P.g., P.i., and T.d. as compared to healthy conditions without the target species (P <0.05). IL-8 concentrations were positively correlated with MR-EA levels in the periodontitis conditions co-infected with B.f., P.g., P.i., and T.d. (P <0.05). A wide range of IL-8 concentrations was found among 15 patients when the periodontitis condition was characterized by co-infection with B.f., P.g., P.i., and T.d. MR-EA levels in the high IL-8 group of subjects were significantly higher than those in the low IL-8 group of subjects (P <0.01). CONCLUSIONS: The present study shows that the local host-bacteria interactions in untreated periodontitis are diverse in terms of the intensity of inflammatory responses measured by IL-8-related granulocyte elastase activity in GCF. This might reflect different phases of the inflammatory response due to shifts in host-bacteria interactions and therefore be indicative of a range of periodontal disease activity levels.

Actinobacillus Infections↗

PubMed2000

Quality of diabetes care in community health centers.

OBJECTIVES: This study assessed the quality of diabetes care in community health centers. METHODS: In 55 midwestern community health centers, we reviewed the charts of 2865 diabetic adults for American Diabetes Association measures of quality. RESULTS: On average, 70% of the patients in each community health center had measurements of glycosylated hemoglobin, 26% had dilated eye examinations, 66% had diet intervention, and 51% received foot care. The average glycosylated hemoglobin value per community health center was 8.6%. Practice guidelines were independently associated with higher quality of care. CONCLUSIONS: Rates of adherence to process measures of quality were relatively low among community health centers, compared with the targets established by the American Diabetes Association.

Adult↗

PubMed2000

Computational methods for gene expression-based tumor classification.

Gene expression profiles may offer more or additional information than classic morphologic- and histologic-based tumor classification systems. Because the number of tissue samples examined is usually much smaller than the number of genes examined, efficient data reduction and analysis methods are critical. In this report, we propose a principal component and discriminant analysis method of tumor classification using gene expression profile data. Expression of 2000 genes in 40 tumor and 22 normal colon tissue samples is used to examine the feasibility of gene expression-based tumor classification systems. Using this method, the percentage of correctly classified normal and tumor tissue was 87.0%. The combined approach using principal components and discriminant analysis provided superior sensitivity and specificity compared to an approach using simple differences in the expression levels of individual genes.

Analysis of Variance↗

PubMed2000

Mumps outbreak confined to a religious community.

One hundred and forty-four cases of mumps were notified in a religious community in London between July 1998 and April 1999 and the infection was confirmed in 82% of those who underwent saliva testing (51/62). Half of the clinical and half of the confirme

Journal Article↗

PubMed2000

[Information behavior of microsatellite loci in genome scanning].

OBJECTIVE: To determine the heterozygosity and polymorphism information content of 139 microsatellite loci in Han population. METHODS: Multiplex approach was used to analyze the 139 loci. The amplified fragments were subjected to electrophoresis in PAGE gel and analyzed with Genescan( TM) and Genotyper(TM). RESULTS: The heterozygosities are between 0.35 to 0.89, with the heterozygosities of 88% loci >0.60. PICs are in the range of 0.32 and 0.88, with PICs of 95% loci >0.50. CONCLUSION: The polymorphism information content of microsatellite loci is very high and their distribution varies in different races and populations.

Aged↗

PubMed2000

Medical and psychosocial services in drug abuse treatment: do stronger linkages promote client utilization?

OBJECTIVE: To examine the extent to which linkage mechanisms (on-site delivery, external arrangements, case management, and transportation assistance) are associated with increased utilization of medical and psychosocial services in outpatient drug abuse treatment units. DATA SOURCES: Survey of administrative directors and clinical supervisors from a nationally representative sample of 597 outpatient drug abuse treatment units in 1995. STUDY DESIGN: We generated separate two-stage multivariate generalized linear models to evaluate the correlation of on-site service delivery, formal external arrangements (joint program/venture or contract), referral agreements, case management, and transportation with the percentage of clients reported to have utilized eight services: physical examinations, routine medical care, tuberculosis screening, HIV treatment, mental health care, employment counseling, housing assistance, and financial counseling services. PRINCIPAL FINDINGS: On-site service delivery and transportation assistance were significantly associated with higher levels of client utilization of ancillary services. Referral agreements and formal external arrangements had no detectable relationship to most service utilization. On-site case management was related to increased clients' use of routine medical care, financial counseling, and housing assistance, but off-site case management was not correlated with utilization of most services. CONCLUSIONS: On-site service delivery appears to be the most reliable mechanism to link drug abuse treatment clients to ancillary services, while referral agreements and formal external mechanisms offer little detectable advantage over ad hoc referral. On-site case management might facilitate utilization of some services, but transportation seems a more important linkage mechanism overall. These findings imply that initiatives and policies to promote linkage of such clients to medical and psychosocial services should emphasize on-site service delivery, transportation and, for some services, on-site case management.

Ambulatory Care Facilities↗