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Analysis of differentiation-induced expression mechanisms of thyrotropin receptor gene in adipocytes.

Rat adipose tissue, as well as differentiated 3T3-L1 cells, has been shown to express TSH receptor (TSHR) mRNA in amounts approaching those in the thyroid. We investigated the molecular mechanisms of TSHR gene expression in adipose cells. Primer extension and cloned cDNA sequences showed that transcription of the TSHR gene in rat adipose tissue was from multiple start sites clustered between -89 to -68 bp and almost identical to those in FRTL-5 thyroid cells. By transient expression analysis, we localized, between -146 and -90 bp, a positive regulatory element, the activity of which was markedly increased after the differentiation of 3T3-L1 cells. Deoxyribonuclease I protection showed that nuclear extracts from differentiated 3T3-L1 cells strongly protected two sequences, from -146 to -127 bp, including a cAMP response element-like sequence and from -112 to -106 bp containing a putative Ets-binding sequence. In differentiated 3T3-L1 cells, disruption or deletion of either sequence was found to result in the loss of enhancer activity, suggesting both elements may synergistically activate the TSHR promoter. Electrophoretic mobility shift analysis revealed the induction of new protein/DNA complexes formed either with the cAMP response element-like site or with putative Ets elements after the differentiation into adipocytes. In contrast, nuclear proteins, whose binding to DNA was diminished after the differentiation of 3T3-L1 cells, were found to interact with the site contiguous to the 5'-end of the putative Ets-binding sequence. Mutations of this binding site, which reduced the protein/DNA complex formation, increased TSHR promoter activity in undifferentiated cells. These observations suggested that differentiation-induced diminution of suppressor interactions may allow the enhancers to synergistically activate the transcription of TSHR gene in adipocytes.

Adipocytes↗

Lymphomas with follicular and monocytoid B-cell components. Evidence for a common clonal origin from follicle center cells.

We investigated the clonal relationship between follicular center cell and monocytoid B-cell components of non-Hodgkin lymphoma by isolating the components and comparing the nucleotide sequences of the complementarity-determining region (CDR)3 of the rearranged immunoglobulin heavy chain (IgH) gene. Paraffin blocks from 4 cases with amplifiable DNA using the polymerase chain reaction (PCR) were identified. Multiple representative cell clusters of the 2 components were obtained by microdissection, and the IgH CDR3 was amplified using a seminested PCR. Most of the PCR products obtained from both tumor components in each case had identical lengths when analyzed with polyacrylamide gel electrophoresis (PAGE) and identical migratory patterns on denaturing gradient gel electrophoresis (DGGE). These findings indicate sequence identity of the IgH CDR3 of both tumor components. Sequence analysis showed that point mutations were responsible for bands from the same case that had nonidentical migratory patterns by DGGE. The components in each of the 4 cases studied have the same clonal origin. Intraclonal sequence variations in the IgH gene were observed in 2 cases, consistent with the presence of continued somatic hypermutation after establishment of the clone. The expression of CD10 and bcl-2, as well as the detection of bcl-2 rearrangements in 2 cases, indicate that these lymphomas are of follicular center cell origin.

B-Lymphocytes↗

Human circadian time structure in subjects of different gender and age.

Most human variables exhibit rhythms with an about 24 hour (circadian) period. Each rhythm can be characterized by its acrophase (calculated peak time of the cosine curve best fitting to the data), its amplitude and rhythm adjusted mean (MESOR). The sequential array of the rhythms' acrophases represents the temporal order of the human time structure. In the present work we used circadian rhythms of 24 chemical and 15 hormonal variables extracted from published studies which were done in a defined area of southeastern Europe (Romania). All studies had a comparable experimental design and were analyzed biochemically and statistically in the same laboratory. The acrophases of these rhythms obtained from both genders of different age groups (from the 2nd to the 9th decade of age) were subjected to multiple correlation test, cluster and principal coordinates analyses. The results show that the temporal order is affected both by gender and age, and evaluate the degree of the effect, offer a "chronbiologic fingerprint" for the examined groups and assist in dissecting rhythm variability among populations.

Adult↗

Genotype x environment interaction for milk production in Guernsey cattle.

International genetic evaluations that use national genetic evaluation results as input need to acknowledge country boundaries. The current model for international evaluation treats each country as a genetically separate trait, i.e., assumes milk production to be similar within country, but different between countries. The use of cow performance records does not require such restriction, and allows for other statistical models to consider genotype x environment interaction. First-lactation records from 40,000 Guernsey cows in four countries (Australia, Canada, United States, and South Africa) were used to detect and describe genotype x environment interaction for milk production traits. Five statistical models were considered: single-trait across-county (ST), single-trait across-country with heterogeneous residual variance (SThet), multiple-trait across-country (MT), multiple-trait herd cluster model (HC), and reaction norm model (RR). For the herd cluster model, herds were clustered into groups based on information on herd management, genetic composition, and climate. Reaction norms describe the phenotype expressed by a genotype as a function of the environment, and was modeled by random regression on the herd average for peak milk yield as the descriptor of production environment. Gibbs sampling was used to make inferences about the parameters of interest, and models were compared based on goodness of fit and deviance information criterion. Posterior mode of the heritability for the single-trait model was 0.32, and ranged from 0.15 to 0.53 for models SThet and MT. Posterior mode of the genetic correlations between countries estimated with model MT were generally high (0.78 to 0.90). However, posterior SD were high (up to 0.15 for Australia-South Africa), and values near unity for the genetic correlations were not unlikely. Model HC gave more precise inferences but lower goodness of fit compared with model MT. Results from model RR provided evidence for heterogeneity of genetic variances. This model was least supported by the data, probably because heterogeneity of residual variances was not considered. Among the models in this study, the one with homogeneous genetic and heterogeneous residual variances across countries fitted best to the data, and we expect a model for which the assumption of homogeneous genetic variance is relaxed to show an even better fit to the data.

Animals↗

[Exploration on statistical method for calculating intensity of the infection in residents in nationwide sampling survey of schistosomiasis].

AIM: To set up statistical methods for calculation of intensity of schistosome infection in residents in nationwide sampling survey of schistosomiasis. METHODS: Based on the epidemiological survey of schistosomiasis and according to the medical statistics for multiple stratifying and clustering random sampling, the calculation method on intensity of schistosome infection was inferred. RESULTS AND CONCLUSION: Nine formulas were worked out for the calculation of the intensity of schistosome infection in different endemic provinces with different ecotypes. These formulas are of practical value.

China↗

[Mining microarray gene expression data of metastatic colorectal cancer by literature profiling].

OBJECTIVE: To search new metastatic colorectal cancer-related genes. METHODS: Metastatic colorectal cancer microarray gene expression data was mined by literature profiling, which was based on the analysis of literature profiles generated by extracting the frequencies of certain terms from the abstracts in the Medline literature database. The terms are then filtered on the basis of both repetitive occurrence and co-occurrence among multiple gene entries. Clustering analysis was subsequently performed on the retained frequency values, shaping a coherent picture of the functional relationship among the heterogeneous genes identified in the long lists. The clustering result was analyzed against the result of document analysis and experiment. RESULTS AND CONCLUSION: Two new genes (TIAM1 and NM23H1) with potential relation to metastatic colorectal cancer were identified.

Colorectal Neoplasms↗

[A prospective study of relationship between blood pressure and 10-year cardiovascular risk in a Chinese cohort aged 35-64 years].

OBJECTIVE: To provide epidemiological data for the revision of The National Guideline for Prevention and Treatment of Hypertension through the analysis of the association between blood pressure (BP) and the risk of cardiovascular diseases (CVD) in a cohort aged 35-64 years. METHODS: A prospective study was carried out in 11 provinces from 1992 to 2002. The association between BP and CVD (CHD and stroke) was analyzed in 31728 subjects aged 35 - 64 years. RESULTS: (1) Compared with BP < 110/75 mmHg, the risk of CVD increased 1 time (RR=2.09), 2 times (RR=3.23), and 10 times (RR=11.81) when BP was 120-129/80-84 mmHg, 140-149/90-94 mmHg, and > or = 180/110 mm Hg, respectively. (2) The risk of acute CHD for subjects with stage 2 hypertension was 2.3 times of those with optimal BP, whereas the risk of ischemic stroke and hemorrhagic stroke was 4.9 times and 11.7 times, respectively. (3) 36.1% of all CVDs, 44.0% of the acute stroke and 23.7% of the acute CHD were attributable to hypertension. (4) In each BP level, the 10-year risk of CVD increased with the increased number of other risk factors. CONCLUSIONS: The risk of CVD increases with BP continuously from BP of 110/75 mmHg. Therefore, the cutpoint of the diagnostic criteria for hypertension is arbitrary. Comprehensive intervention for multiple risk factor clustering should be strengthened to reduce the overall risk of CVD.

Adult↗

[Epidemiological survey of prevalence of fatty liver and its risk factors in a general adult population of Shanghai].

OBJECTIVE: To investigate the prevalence and major risk factors of fatty liver among adult residents in Shanghai. METHODS: A cross-sectional survey with multiple-stage stratified cluster and random sampling was performed. All residents aged 16 and above were invited to participate in the survey; they came from four communities of Yangpu District and Pudong New District. Questionnaire, physical examination, serum lipid-profile, and 75 gram oral glucose tolerance test and ultrasonographic examination of liver were undertaken. Analysis of data was performed through SPSS 11.0 for Windows statistical package. RESULTS: A total of 3175 residents took part in the survey, which was 75% of adult residents of the investigated communities and 2.26/10 000 of Shanghai municipal residents. Of the 3175, 1218 were males and 1957 were females. The mean age of the participants was 52.4+/-15.1 years and ranged from 16 to 88 years. Fatty liver was detected with ultrasound examination in 661 participants (20.82%), among which 3.48% had alcoholic fatty liver, 4.08% had suspected alcoholic fatty liver, and 92.43% had nonalcoholic fatty liver. The age-adjusted, sex-adjusted prevalence of fatty liver in Shanghai adult residents was 17.29%, the prevalence of alcoholic fatty liver, suspicious alcoholic fatty liver, and nonalcoholic fatty liver in Shanghai adult residents were 0.79%, 1.15%, and 15.35%, respectively. The prevalence of fatty liver was increased with aging in males and in females. Among participants younger than 50 years old, the prevalence of fatty liver in males was significantly higher than that in females, but in participants older than 50 years the case was just the opposite, higher in females. The mean age (years), body mass index (BMI), waist circumference, blood pressure, fasting and two hour serum glucose level, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and the presence of obesity, diabetes mellitus, hypertension, dyslipidemia, and gallstones in the fatty liver group was significantly higher than those in the group without fatty liver, but the high-density lipoprotein cholesterol (HDL-C) level and the educational level were both lower in the fatty liver group. Logistic regression analysis demonstrated that the prevalence of fatty liver was only positively correlated to nine risk factors, including male sex, educational level, waist circumference, BMI, fasting glucose level, HDL-C, TG, hypertension and diabetes mellitus. In heavy drinkers, obesity increased the risk for fatty liver by 4.8-fold, but heavy drinking only increased the risk for fatty liver 1.5-fold (95% CI 0.9-2.6, P=0.1685). CONCLUSION: There is a high prevalence of fatty liver among adult residents in Shanghai, and nonalcoholic fatty liver is the major type. Metabolic disorders such as obesity and diabetes mellitus, hypertension and hyperlipidemia are more closely associated with fatty liver than heavy drinking in Shanghai.

Adolescent↗

Outbreak of Kawasaki syndrome in Denver, Colorado: association with rug and carpet cleaning.

Between October 1984 and January 1985, the largest outbreak of Kawasaki syndrome reported to date in the continental United States (62 cases) occurred in the Front Range of the Rocky Mountains, extending from Colorado Springs, Colorado, to Cheyenne, Wyoming. Fifty-two (84%) of these Kawasaki syndrome patients lived in the Denver metropolitan area. A case-control study revealed that 16 (62%) of 26 Kawasaki syndrome patients compared with 10 (20%) of 49 matched control subjects had a history of exposure to shampooed (19%) or spot-cleaned (81%) rugs or carpets within 30 days of the Kawasaki syndrome onset date (odds ratio = 5, P less than .01). The time of exposure to shampooed or spot-cleaned rugs or carpets for 9 of 10 Kawasaki syndrome patients who had a single exposure and for all 6 Kawasaki syndrome patients who had multiple exposures were clustered within an interval 13 to 30 days before the onset of illness. Although the reason for this unusually large outbreak remains obscure, it is the third in which a statistically significant association between Kawasaki syndrome and rug or carpet cleaning has been found.

Case-Control Studies↗

[The establishment of hemorheological data base and its applications].

This hemorheological data base was established with an Apple II computer. The covering technique was applied to deal with its lacks of memories. This data base had a mutual administration system and complete managing functions including inputting, inquiring, printing, transferring, revising functions and so on. More than twenty hemorheological parameters involving apparent viscosities of whole human blood, plasma viscosity, viscoelasticity and thixotropy indices, were saved in the way of paging mode. Meanwhile, this data base had a common mathematical statistics system in recently medical use. It included monovariable linear and nonlinear regressions, t-test, multiple linear regression, cluster analysis etc. Therefore, this data base can be conveniently utilized to analyze the hemorheological data comprehensively. Besides the establishment of normal hemorheological indices, this data base equipped a primary method of quantitative diagnosis through hemorheological indices, it gave a new method to diagnose some diseases and to observe their curing process.

Blood Viscosity↗

[Psychosocial variables associated to housing conditions colonized by the vector of Chagas' disease].

The Venezuelan unfinished housing that prevails in the rural areas (palm roof and unfinished walls) is the main factor for the settlement of the Chagas' Disease vector in the country. This research had as principal objective: to explore the social behavior variable that maintain housing in such condition. It was carried out in the Municipality of Tinaquillo, Cojedes State, an endemic zone of this disease. The research was based on a previous study on the same subject. The sample used in that study was revised and improved and the analysis methods were changed. A rural sample was obtained applying the following technics: multivariable analysis, factorial analysis of multiple correspondence and cluster analysis. The results show the existence of four social behavioral types which are associated to the housing condition. The 2/4 group represents a majority group (55.93% of the individuals). In this group the reinitiation of the disease transmission cycle is more feasible due to the existence of a higher number of negative conditions, objective and subjective, associated to the unfinished housing.

Animals↗

Quantitative analyses of the binding of soluble complement-fixing antibody/dsDNA immune complexes to CR1 on human red blood cells.

We have used direct binding isotherm analyses to measure the association constant (Ka) and number of binding sites for the binding of prepared complement-fixing antibody (Ab)/dsDNA immune complexes (IC) to human red blood cells (RBC). In order to generalize this study we have examined the binding reaction for a number of different anti-dsDNA Ab (from systemic lupus erythematosus plasmas), complement sources, RBC donors, and dsDNA sizes. The affinity of the IC for the RBC is quite high, and the Ka values fall within a narrow range (5 to 14 X 10(10) liter/mol). Similarly, the limiting stoichiometries for the number of IC bound per RBC were between 40 and 91. The very high affinity and limiting stoichiometries both suggest that the IC bind to the RBC via multiple contacts with clusters of complement receptor type 1 (CR1). Furthermore, we have used three specific monoclonal AB (mAb) to quantitate CR1 on human RBC in the presence and absence of bound IC. One of these Ab, mAb 1B4, is blocked from binding to the RBC if IC are previously bound, and we have used this observation to verify the multivalent nature of the interaction of complement-fixing IC with CR1 on human RBC.

Antibodies, Antinuclear↗

[Evaluating the health of the elderly and well-being of relatives caring for the elderly].

Facilitating a realistic appraisal of physical and psychiatric health parameters of a diseased family member has shown to be most important in counseling families with frail elder relatives. It is a prerequisite for adequate coping strategies to reduce caregiver burden, e.g. for the relief available using professional help. Data of a study on 140 families with a diseased elder relative (Bruder et al.) (1) are used to identify 6 types of families that differ maximally with regard to estimation of the old person's state of health (denial, realistic view or aggravation of disease by the caregiver and/or by the old person) by means of cluster analysis. A multiple regression of "caregiver wellbeing" on the elderly's "objective health status", on "family type" and on an interaction term "objective health status" by "family type" accounts for roughly 33% of the variance of caregiver wellbeing. A highly significant effect of the interaction term proves denial and/or aggravation of the elder person's state of disease to be detrimental to caregiver wellbeing given a certain grade of disease of the old person. A negative effect of the patient's disease on caregiver wellbeing is found especially for families a) with old person and caregiver misjudging physical deficits in opposite directions and b) with caregivers denying organic brain deterioration in their frail relative. A concept for counseling families reaching from information, support during the process of grieving about loss of the elder's capacities up to psychotherapeutically oriented help for family members is briefly described.

Adaptation, Psychological↗

[Correlation study of cancer mortality and food consumption].

The geographical relationships between cancer mortality and food consumption were analyzed by means of extensive uses of correlation coefficiencies, factor analysis, multiple regression analysis, cluster analysis and path analysis. The results for the countries in the world varied broadly due to selection of the countries analyzed. The results for prefectures in Japan showed differences between males and females especially with regard to stomach cancer. The present study shows the importance of careful selection of geographical and other variables when making correlation studies.

Alcohol Drinking↗

[Units of DNA replication in S-phase human cells].

Current methods of physical mapping allow the estimation of genomic distances (i.e. DNA contents) from linear distances between DNA markers in interphase nuclei, and in this study we estimated the size of focal centers of DNA replication in cultured S-phase human cells. Our results indicate that the conformation of S-phase chromosome fibres in the range of contour lengths 0.1-3.0 microns fits the random walk model and, therefore, the quantitative methods of interphase mapping can be applied to the estimation of sizes of replication units. The obtained data show the existence of multiple non-clustered small units less than 150 kb in size, equivalent to small replicons detected by fiber DNA radioautography, and also a significant fraction of big units more than 500 kb in size, representing groups of small replicons and/or big replicons. These big units are detected as chains of small replication foci, probably reflecting the structural chromatin organization in well-known loop domains, since the experimentally induced decrease of replicons to the average size 12 kb does not lead to any change in the pattern of indicated chains.

Adenocarcinoma↗

Is there a role for dietary fish oil in the treatment of hypertension?

Hypertension and atherosclerosis are highly prevalent disorders which contribute substantially to the burden of premature morbidity and mortality at significant cost to the economy. Hypertension, abdominal obesity and risk factor clustering represent complex regulatory disorders which probably reflect an interaction of multiple genetic and environmental factors. Information has been summarised which indicates that fish oil, obtained either as a dietary supplement or by the consumption of more fish products, represents a relatively simple and comparatively inexpensive dietary intervention which may lower BP, especially in combination with a low salt diet, and favourably alter multiple risk factors in the cluster. This summary also indicates that multiple significant gaps in our knowledge about fish oil remain. Closing these gaps through further clinical and basic research may lead to greater acceptance and more appropriate therapeutic use of fish oil for health maintenance and disease prevention.

Animals↗

Use of computer simulation to evaluate a putative cluster of genetic or teratologic outcomes: adjustment for "multiple hypotheses" and application to a reported excess of Down's syndrome.

The identification of an apparent excess of a genetic outcome in a particular area and/or a particular time often provokes considerable public alarm about the presence of an environmental mutagen. It is often difficult to determine in any particular case whether the observation, whatever its nominal statistical significance, is due to chance concatenation of events or to an environmental factor. Statistical evaluation is made more difficult by the profuse number of possible hypotheses that could have triggered concern about an excess. This renders it difficult to calculate the actual probability of the observation (or one more extreme). By attempting to identify similar types of outcomes that could have provoked an apparent excess and then undertaking computer simulations assuming random deviations from a constant rate, one may attempt to adjust for the problem of multiple hypotheses. We apply this approach to a reported excess of Down's syndrome in Norway in 1985-1986 in younger mothers, and conclude that there is a high probability that it arose by chance.

Adolescent↗

A survey of homozygous deletions in human cancer genomes.

Homozygous deletions of recessive cancer genes and fragile sites are known to occur in human cancers. We identified 281 homozygous deletions in 636 cancer cell lines. Of these deletions, 86 were homozygous deletions of known recessive cancer genes, 17 were of sequenced common fragile sites, and 178 were in genomic regions that do not overlap known recessive oncogenes or fragile sites ("unexplained" homozygous deletions). Some cancer cell lines have multiple homozygous deletions whereas others have none, suggesting intrinsic variation in the tendency to develop this type of genetic abnormality (P < 0.001). The 178 unexplained homozygous deletions clustered into 131 genomic regions, 27 of which exhibit homozygous deletions in more than one cancer cell line. This degree of clustering indicates that the genomic positions of the unexplained homozygous deletions are not randomly determined (P < 0.001). Many homozygous deletions, including those that are in multiple clusters, do not overlap known genes and appear to be in intergenic DNA. Therefore, to elucidate further the pathogenesis of homozygous deletions in cancer, we investigated the genome landscape within unexplained homozygous deletions. The gene count within homozygous deletions is low compared with the rest of the genome. There are also fewer short interspersed nuclear elements (SINEs), long interspersed nuclear elements (LINEs), and low-copy-number repeats (LCRs). However, DNA within homozygous deletions has higher flexibility. These features may signal the presence of currently unrecognized zones of susceptibility to DNA rearrangement. They may also reflect a tendency to reduce the adverse effects of homozygous deletions by minimizing the number of genes removed.

Cell Line, Tumor↗