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Biomedical subjects

L Jin

Publications and source records attributed to L Jin.

At least 109 records · Page 6Linked to original sources

Inactivation of the p16 gene in human pituitary nonfunctioning tumors by hypermethylation is more common in null cell adenomas.

Recent studies have shown that methylation of the CpG island within the p16/CDKN2A/MTS1 (p16) gene is associated with loss of expression of p16 protein in pituitary tumors. We analyzed a series of 21 pituitary adenomas and three normal pituitaries along with a human pituitary cell line (HP75) for methylation of exon 1 by methylation-specific PCR, immunohistochemistry, and Western blotting. PCR analysis showed that 5/7 (71%) of null cell adenomas, but only 2/7 (29%) gonadotroph tumors were hypermethylated. In addition,1 of 2 ACTH tumors but no GH (n = 4) or PRL (n = 1) adenoma examined were hypermethylated. Immunostaining and Western blot analysis of protein expression supported the methylation-specific PCR analyses. These results show that p16 gene silencing by hypermethylation is more common in null cell adenomas compared to other nonfunctioning adenomas such as gonadotroph tumors and that the role of p16 in the pathogenesis of pituitary adenomas is restricted to specific tumor subtypes.

Adenoma↗

Pathologic features and expression of insulin-like growth factor-2 in adrenocortical neoplasms.

We analyzed a series of adrenocortical neoplasms to compare the clinicopathologic features and the expression of insulin-like growth factor-2 (IGF-2) in adrenocortical adenomas and carcinomas. IGF-2 is a growth factor commonly expressed in many tumors including adrenal cortical and medullary neoplasms. Formalin-fixed paraffin-embedded tissues from 64 adrenocortical adenomas and 67 adrenocortical carcinomas were analyzed. The carcinomas were histologically graded from 1 to 4 based on mitotic activity and necrosis. Tumor weight, size, and follow-up information were obtained by chart review. Expression of IGF-2 was detected by immunohistochemistry with the avidin-biotin-peroxidase complex method and a monoclonal antibody against IGF-2. Adrenocortical carcinomas were larger (mean: 13.1 cm, 787 g) than adenomas (mean: 4.2 cm, 52 g) (p < 0.001). Inpatients with adrenocortical carcinomas, high tumor grade (3 or 4) (p = 0.01) was associated with decreased survival. Expression of IGF-2 was higher in adrenocortical carcinomas than in adenomas (p < 0.001). These results show that tumor size and weight along with expression of IGF-2 protein are useful features to assist in distinguishing between adrenocortical adenomas and carcinomas, and that high tumor grade is a predictor of survival in adrenocortical carcinomas. However, single immunohistochemical markers such as IGF-2 or single histopathologic features cannot by themselves separate adrenocortical adenomas from carcinomas, and a combination of clinical, gross, and microscopic features are needed to establish the diagnosis in difficult cases.

Adolescent↗

Soluble CD14 levels in gingival crevicular fluid of subjects with untreated adult periodontitis.

BACKGROUND: This study determined soluble CD14 (sCD14) levels in gingival crevicular fluid (GCF) and their potential relationship to periodontal conditions in adult periodontitis. METHODS: GCF was collected from 15 patients with untreated adult periodontitis. sCD14 levels were determined by ELISA and presented as total amount (ng/site) and concentration (microg/ml). The periodontal examination consisted of plaque index (PI), bleeding index (BI), probing depth (PD), and clinical attachment level (CAL). PD and CAL were measured with an electronic probe. RESULTS: sCD14 was detected in all 15 subjects and was found in 59% (62/105) of the sampled sites. The percentage of sites with sCD14 varied greatly, ranging from 14% to 100%. The mean total amount of sCD14 was 1.71+/-0.40, range 0.03 to 5.41 ng/site; the concentration of sCD14 was 14.04+/-4.15, range 0.16 to 51.74 microg/ml. No significant difference in clinical data was found between the sites with and without detectable levels of sCD14. However, on the basis of the individual profile of sCD14 levels, i.e., those individuals with >50% of the sites containing sCD14 and mean levels of sCD14 >5.0 microg/ml, the 15 subjects were divided into a high sCD14 group (9 subjects) and a low sCD14 group (6 subjects). Compared to the high group, the low group showed greater mean PD and a higher percentage of sites with PD > or = 5.0 mm (P <0.05). Consistent with this, sCD14 concentrations showed a negative correlation with PD (r(s) = -0.636, P = 0.0174). CONCLUSIONS: The present study shows that sCD14 levels in GCF varied greatly among subjects with untreated adult periodontitis. Individuals with higher levels of sCD14 in GCF and more sites containing sCD14 had fewer deep pockets. The negative correlation between GCF sCD14 levels and probing depth implies a crucial role of sCD14 in bacterially induced periodontal destruction. The relationship between GCF sCD14 levels and probing depth warrants further investigations.

Adult↗

Melting curve analysis of SNPs (McSNP): a gel-free and inexpensive approach for SNP genotyping.

High-throughput methods for assaying DNA variation require two important steps: (i) discriminating the variation and (ii) detecting the signal. In this report, we describe a novel SNP genotyping method that we refer to as melting curve analysis of SNPs (McSNP). McSNP combines a classic approach for discriminating alleles, restriction enzyme digestion, with a more recent method for detecting DNA fragments, melting curve analysis. Melting curve analysis is performed by slowly heating DNA fragments in the presence of the dsDNA-specific fluorescent dye SYBR Green I. As the sample is heated, fluorescence rapidly decreases when the melting temperature of a particular fragment is reached. We show that it is possible to determine the composition of simple mixtures of DNA fragments, such as those that result from restriction enzyme digestions of short PCR products. McSNP is well suited for high-throughput genotyping because 96 samples can be analyzed and automatically scored in 20 min. Our results clearly demonstrate that McSNP is a simple, inexpensive, and accurate means of genotyping SNP variation.

Genotype↗

Barriers to providing diabetes care in community health centers.

OBJECTIVE: We aimed to identify barriers to improving care for individuals with diabetes in community health centers. These findings are important because many such patients, as in most other practice settings, receive care that does not meet evidence-based standards. RESEARCH DESIGN AND METHODS: In 42 Midwestern health centers, we surveyed 389 health providers and administrators about the barriers they faced delivering diabetes care. We report on home blood glucose monitoring, HbA1c tests, dilated eye examinations, foot examinations, diet, and exercise, all of which are a subset of the larger clinical practice recommendations of the American Diabetes Association (ADA). RESULTS: Among the 279 (72%) respondents, providers perceived that patients were significantly less likely than providers to believe that key processes of care were important (overall mean on 30-point scale: providers 26.8, patients 18.2, P = 0.0001). Providers were more confident in their ability to instruct patients on diet and exercise than on their ability to help them make changes in these areas. Ratings of the importance of access to care and finances as barriers varied widely; however, >25% of the providers and administrators agreed that significant barriers included affordability of home blood glucose monitoring, HbA1c testing, dilated eye examination, and special diets; nonproximity of ophthalmologist; forgetting to order eye examinations and to examine patients' feet; time required to teach home blood glucose monitoring; and language or cultural barriers. CONCLUSIONS: Providers in health centers indicate a need to enhance behavioral change in diabetic patients. In addition, better health care delivery systems and reforms that improve the affordability, accessibility, and efficiency of care are also likely to help health centers meet ADA standards of care.

Blood Glucose Self-Monitoring↗

Sharing learning through narrative communication.

This paper examines key aspects of the learning experiences of ten speech and language therapy (SLT) students on clinical placements, as revealed by an analysis of 102 narrative accounts. We argue that when students on placements tell stories of their learning experiences the process of recounting them can help them to reflect on and consolidate what they have learned and to have this learning validated by peer, clinician or tutor audiences. Thus, sharing learning through narrative communication is itself further learning from the original experience. We show how students evaluate their learning experiences, how their growing confidence is mediated by clinicians and how such narratives are shared in normal student interaction. Tutors might use the insights from narrative learning to raise students' awareness of their own learning, and thus to improve it.

Education↗

Students' expectations of learning key skills and knowledge.

Students' expectations of the key skills and knowledge they acquire and how their perceptions of these change during the four year period of their speech and language therapy (SLT) degree programme are explored. This is important because students are central to the teaching and learning process so their expectations of learning have to be taken into account in order to best help them to achieve the required learning outcomes. Over 100 De Montfort University (DMU) SLT under-graduate students from the four years were surveyed by questionnaire. The research findings are discussed to examine the significance of differences between and within year cohorts. The outcomes of this research will provide a basis for recommendations for DMU and other universities' SLT programmes, and for the improvement of student learning guidance.

Health Knowledge, Attitudes, Practice↗

P450 interaction with HIV protease inhibitors: relationship between metabolic stability, inhibitory potency, and P450 binding spectra.

More than 60 human immunodeficiency virus protease inhibitors were examined for the structure-activity relationship between metabolic stability, CYP3A4 inhibitory potency, and substrate-induced binding spectra with a ferric form of P450 in human liver microsomes. A positive relationship was found between CYP3A4 inhibitory potency and metabolic stability; namely, compounds that were more potent for the CYP3A4 inhibition generally were more metabolically stable. In addition, the compounds formed two clusters defined by the distinct type of substrate-induced P450 binding spectra: the compounds with type II binding spectra were more stable metabolically and more potent for the CYP3A4 inhibition than those with type I binding spectra. The structure-activity relationship suggested that the presence and position of heterocyclic nitrogen on the pyridine moiety play an important role in determining the manner of interaction with P450 and the magnitude of CYP3A4 inhibition/metabolic stability in the series of structurally related human immunodeficiency virus protease inhibitors under development.

Anti-HIV Agents↗

[Single nucleotide polymorphism in beta2-adrenoceptor gene and the distribution in Chinese Han ethnic group].

OBJECTIVE: The study was conducted to investigate single nucleotide polymorphism(SNP) in beta2-adrenoceptor(beta2-AR) gene and the distribution of these identified SNPs in Chinese Han ethnic group. METHODS: beta2-AR gene was sequenced to detect SNPs by fluorescent labeling automatic sequencing method in 80 unrelated samples from territory of Dabie Mountain in Anhui province. RESULTS: A total of 8 SNPs were identified in length of 3.8 kb, including 5 SNPs in code region, 3 SNPs in regulatory region. Although the variations, -468C to G, -367T to C, -47C to T,-20T to C, +79C to G, +100G to A, +491C to T, +1098T to C have been identified in other ethnic groups, they have not been found in our study. The allele distribution of SNPs is in good unity with the Hardy-Weinberg equilibrium. CONCLUSION: The distribution of SNPs in beta2-AR gene is not equable and the SNPs in different ethnic groups differ greatly. The allele distribution of SNPs conforms well to the Hardy-Weinberg equilibrium.

Alleles↗

[Genotype polymorphism and its implications of mannose-binding protein allele in 5 Chinese nationalities].

OBJECTIVE: To detect the genotypes and sequences of the exon 1 of human mannose-binding protein (MBP) allele in 5 Chinese nationalities. METHODS: The genotypes of MBP gene of 5 Chinese nationalities were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The exon 1 of the MBP gene of 22 Chinese Hans was analyzed by using ABI 310 genetic analyzer. RESULTS: The DNA sequences of exon 1 of Chinese MBP gene were acquired. The allele frequencies of the codon 54 of the MBP gene (MBP-54) of 5 Chinese nationalities were 0.181(Hans), 0.128(Uygurs), 0.181(Mongols), 0.179(Tibetans) and 0.181(Yis). The allele distribution for MBP-54 mutation of 5 Chinese nationalities was in good agreement with Hardy-Weinberg equilibrium. Compared with the Hans, Uygurs had a lower MBP-54 mutation rate. There were no differences in the allele frequencies between the chronic hepatitis B patients and health controls in Chinese Hans. The mutations of the codons 52 and 57 were not detected in this study. CONCLUSION: A higher prevalence of MBP-54 mutation was found in 5 Chinese nationalities, MBP-54 mutation was not associated with the persistence of hepatitis B.

Adolescent↗

[High polymorphism at the human P gene locus in Chinese Han and Tibetan populations].

OBJECTIVE: The authors studied two synonymous sites polymorphism (A355A, G780G) and one intervening sequence polymorphism(IVS13-15) of human P gene in 181 and 171 individuals sampled from Chinese Han and Tibetan populations respectively. METHODS: Genomic DNA was extracted from the ACD-blood specimens collected from 352 healthy unrelated individuals by phenol-chloro methods. The amplification of three fragments was performed using PCR technique; the product was digested with restricted enzyme. Agarose electrophoresis was used for typing the PCR product. RESULTS: There were two alleles at each exon variety locus; the allele frequencies in both A355A and G780G were of significant differences between the two populations ( chi(2)=24.54,chi(2)=37.05,P>0.001). No significant difference was found in allele frequency in IVS13-15 locus between the two populations (chi(2)=2.06,P>0.05). And in each of the populations, no significant difference was noted in the genotype frequency between the male and the female. The test for Hardy-Weinberg equilibrium showed that the genotype distributions observed in the two populations were correspondent with the expected. CONCLUSION: There is a remarkable difference in the distribution of allele frequencies at P gene locus between Chinese Han and Tibetan populations, which is related to the variation in skin pigmentation of these two Chinese population.

Adolescent↗

[Genotyping of HIV resistant alleles in indigenous Tibetan ethnic group of China: low frequency of CCR5triangle32 and high frequency of CCR2b-64I alleles].

OBJECTIVE: To investigate the allelic polymorphism of CCR5triangle32, CCR5m303, CCR2b-64I and SDF1-3'A in Tibetan population in Lasa area of China. METHODS: The genomic DNA samples from 330 Tibetan subjects' whole blood samples were purified by use of QIAgen Blood Kit and identified by PCR or PCR-RFLP analyses. RESULTS: The mutation frequencies of CCR5triangle32 and CCR5m303 alleles were lower than 0.15%, and those of CCR2 b-64I and SDF1-3'A alleles were 29.42% and 19.24% respectively in the study samples. The allelic polymorphisms of the four alleles of Tibetan population were similar to those of Chinese Han population. Genotype distribution of the four alleles was in accordance with Hardy-Weinberg equilibrium. The above results suggest that Tibetan population may be relatively susceptive to HIV-1. CONCLUSION: The Chinese Tibetan may have a lower frequency of CCR5triangle32 and a higher frequency of CCR2b-64I allele, compared with Caucasian.

Adolescent↗

[A simple and rapid new method for SNP typing by single-tube bi-directional allele specific amplification].

OBJECTIVE: To establish a new method for single nucleotide polymorphism(SNP) typing based on allele specific PCR: single-tube bi-directional amplification (SB-ASA), and study the influence on specific extension by introducing a mismatch at the third 3'terminal base of allele specific primers. METHODS: Two allele specific primers, with a mismatch introduced at the third 3'terminal base, were both included in PCR system; they extended in opposite directions and amplified two allele specific fragments different in size. The genotype was determined by observing the length of amplified fragments after agarose electrophoresis. The proper ranges of annealing temperature (Ta) under which primers can specifically extend were achieved by observing the amplification status at different temperatures. RESULTS: SB-ASA was successfully used to type 36 samples for four different kinds of SNPs. Typing results were completely consistent with those by directional sequencing. Proper Ta ranges of two primers were expanded respectively from 64-69 degrees centigrade to 46-66 degrees centigrade and from 60-62 degrees centigrade to 56-61 degrees centigrade by introducing a mismatch at the third 3'terminal base. CONCLUSION: SB-ASA is a simple, rapid and efficient new method for SNP typing. During allele specific PCR reaction, specific primers with a mismatch at the third 3'terminal base have more power to identify two alleles.

Alleles↗

[Genetic relationships among six Chinese populations revealed by analysis of 30 autosomal STRs].

30 autosomal STRs of 6 Chinese populations (Bai, Naxi, Tu, Sala, Han in Shandong, She) were amplified by multiplex PCRs using fluerescein-labelled primers. Shriver's Dsw was estimated on the basis of the results of the genescanning and genotyping after running unnatural PAGE of the PCRs' products on ABI 377 sequencer. Phylogenetic trees were constructed by using Neighbor-Joining and UPGMA method based on Dsw, and then the genetic relationships among them were analyzed referring to some relative informations. Our results indicated that the genetic distance between Sala and Tu is near, 0.033. But the distances between Sala and other four populations are far, over 0.12; Tu is close to Naxi and Shandong Han, and the distances are 0.038, 0.063 respectively; The distance between Bai and Han is the nearest, 0.007, but there is a distance, 0.075, between Bai and Naxi, and a far distance, 0.112, between Bai and Tu; The distance between Naxi and Han is 0.100 and the distances between She and other 5 populations are all over 0.12. In both of the NJ and UPGMA phylogenetic trees, Naxi, Tu and Sala is one cluster and Bai and Han is another cluster. She is a single branch. These results, basically consistent with 6 Chinese populations' geographic distribution and histories, can provide some genetic information to comprehensively study their origin, migration, formation and development with their historical records and archaeological evidence.

Asian People↗

Pharmacokinetics and metabolism of a RAS farnesyl transferase inhibitor in rats and dogs: in vitro-in vivo correlation.

Compound I (1-(3-chlorophenyl)-4-[(1-(4-cyanobenzyl)-1H-imidazol-5-yl)methyl]piperazin-2-one) is a potent and selective inhibitor of farnesyl-protein transferase (FPTase). The pharmacokinetics and metabolism of compound I displayed species differences in rats and dogs. After oral administration, the drug was well absorbed in dogs but less so in rats. Following i.v. administration, compound I was cleared rapidly in rats in a polyphasic manner with a terminal t(1/2) of 41 min. The plasma clearance (CL(p)) and volume of distribution (V(dss)) were 41.2 ml/min/kg and 1.2 l/kg, respectively. About 1% of the dose was excreted in rat bile and urine as unchanged drug over a period of 24 h, suggesting that biotransformation is the major route of elimination of compound I. Using liquid chromatography (LC)-tandem mass spectometry, nineteen metabolites of compound I were identified in urine and bile from dogs and rats. Structures of two major metabolites were confirmed by LC-NMR. N-Dealkylation and phase II metabolism were the major metabolic pathways. Animal and human liver microsomal intrinsic clearance values were scaled to predict hepatic clearance and half-life in humans, and the predicted values were in good agreement to the in vivo data.

Algorithms↗

Genotypes and polymorphisms of mutant CCR5-delta 32, CCR2-64I and SDF1-3' a HIV-1 resistance alleles in indigenous Han Chinese.

OBJECTIVE: To evaluate the frequencies and polymorphisms of CCR5-delta 32, CCR2-64I and SDF1-3' A alleles conferring resistance to HIV-1 infection in Chinese population from Han ethnic origin. METHODS: This cohort was comprised of 1251 subjects (915 men and 336 women) aged 15-80 years and none was HIV-1 positive. Genotyping of allelic CCR5-delta 32, CCR2-64I and SDF1-3' A variants was performed using PCR or PCR/RFLP assay, and further confirmed by direct DNA sequencing. RESULTS: Our finding shows that the delta 32 deletion mutation in the CCR5 gene does occur in this population and can be inherited in a Mendelian fashion in indigenous Han Chinese at a very low frequency of 0.00119 (n = 1254). The frequencies of mutant CCR2-64I and SDF1-3' A alleles were 0.20023 (n = 1251) and 0.2873 (n = 893), in this population, which are higher than those found in American Caucasians. Furthermore the polymorphisms of CCR2-64I and SDF1-3' A alleles in the Han Chinese population were different from those in American Caucasians. Statistical analysis showed that the genotype distribution of CCR5-delta 32, CCR2-64I and SDF1-3' A alleles was in equilibrium according to the Hardy-Weinberg equation. CONCLUSION: The CCR5-delta 32 mutation may not be a major resistant factor against HIV-1 infection in indigenous Han Chinese. The significance of higher frequencies of CCR2-641 and SDF1-3' A alleles (0.20023 and 0.2791) in the Han population remains to be clarified in HIV-1-positive carriers and AIDS patients.

Acquired Immunodeficiency Syndrome↗

[Changes of plasma level of neuropeptide Y in patients with pregnancy induced hypertension].

OBJECTIVE: To investigate the changes and its clinical significance of plasma neuropeptide Y (NPY) concentration in patients with pregnancy induced hypertension (PIH). METHODS: Plasma NPY levels were detected by radioimmunoassay in 30 patients with PIH, 20 normal non-pregnant women and 23 normal pregnant women. The PIH group was subdivided into mild, moderate and Severe subgroups, and the NPY concentration was also measured in these subgroups respectively at admission and one week after delivery. RESULTS: The plasma NPY levels in patients with PIH [(164.16 +/- 68.32) ng/L] were significantly higher than those of normal non-pregnant women and normal pregnancies [(86.60 +/- 20.65) ng/L, (82.42 +/- 12.46) ng/L, P < 0.01, respectively]. There was significant difference among plasma NPY levels among the patients with mild, moderate, and severe PIH at admission (P < 0.01). At one week after delivery the concentrations of plasma NPY were significantly decreased in the moderate and severe subgroups compared with the value measured at admission (P < 0.01). Moreover, the NPY levels in patients with severe PIH after delivery were still higher than those of normal non-pregnant women. CONCLUSIONS: The results suggested that the level of NPY in plasma is increased in women with PIH. Elevated plasma NPY levels may play a key role in the development of PIH.

Adult↗

[The change of plasma von Willebrand factor and endothelin levels in patients with pregnancy induced hypertension].

OBJECTIVE: To study the association of plasma von willebrand factor (vWF) and endothelin-1 (ET-1) levels in patients with pregnancy induced hypertension (PIH). METHODS: Plasma vWF and ET-1 were studied by ELISA method and immunoradiological method respectively in 36 patients with PIH, 18 normal pregnant women and 19 normal non-pregnant women. RESULTS: Circulation levels of vWF and ET-1 were increased with increasing severity of the PIH. In mild PIH patients, the levels of plasma vWF [(135.9 +/- 30.9)%, (P > 0.05)] weren't significantly higher than those in healthy pregnant women [(131.6 +/- 39.2)%, (P > 0.05)], but the levels of ET-1 [(63.7 +/- 4.8) pg/L] were significantly higher than those in healthy pregnant women [(47.1 +/- 4.7) pg/L, (P < 0.01)]. There were significant differences between groups of moderate-severe PIH [vWF (174.4 +/- 35.4)%, ET-1 (92.6 +/- 19.1) pg/L]. There was a positive correlation between the plasma vWF level and ET-1 level. CONCLUSION: The results suggested that plasma vWF and ET-1 concentration could be used as indicators for the severity of PIH.

Adult↗