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Biomedical subjects

R Jenkins

Publications and source records attributed to R Jenkins.

At least 73 records · Page 4Linked to original sources
PubMed1999

Epithelial integrity, cell death and cell loss in mammalian small intestine.

In recent years, the different mechanisms of epithelial cell loss which occur in mammalian and avian small intestine have been re-investigated. Information is now available for a variety of mammalian types and mechanisms can be divided into two major classes: [i] those preserving epithelial integrity by maintaining intercellular tight junctions throughout early-to-late stages of cell extrusion; and [ii] those which compromise integrity by introducing breaches in epithelial continuity. Both classes are associated with the activity and/or proximity of non-epithelial cells (mainly lymphocytes and mononuclear phagocytes) located in the epithelium or underlying lamina propria. Intraepithelial lymphocytes may be involved in enterocyte targetting and killing whilst lamina propria (LP) macrophages sequester cell debris. Where epithelial integrity is maintained, two types of loss can be identified. In the first (type 1), complete cells are extruded into the lumen. In the second (type 2), only anucleate apical cell fragments pass into the lumen. There are two variants of type 2 loss distinguishable by the fate of the nucleated basal portions of cells. One variant (type 2a) creates large intercellular spaces extending from the preserved apical cap to the basal lamina and containing enterocyte debris for phagocytosis. The second (type 2b) involves the gradual shrinkage of individual cells (which become more electron-dense) and in situ degeneration of their nucleated subapical portions in increasingly narrower intercellular spaces between adjacent healthy enterocytes. The mechanism of removal of these fragments is unclear but may be via macrophages or surrounding enterocytes. Apoptosis has been implicated in both type 1 and type 2 extrusion. In contrast, type 3 loss involves morphological changes in enterocytes which are reminiscent of those seen in necrosis and is accompanied by breaks in epithelial continuity following cell swelling, a decrease in cell electron density and total or subtotal degradation of organelles and membranes. It ends in loss of either an abnormal cell apex (with subsequent exposure of the degraded cell contents and their spillage into the lumen) or a complete cell remnant (extruded into the lumen before total disintegration of plasma membranes).

Animals↗
PubMed1999

Production of a family of kinase-inhibiting lactones from fungal fermentations.

During the course of our screening for natural products from fungi, extracts of several cultures were found to make a family of related resorcylic acid lactone compounds, which are potent inhibitors of MEK kinase. Comparative and empirical studies of fermentation conditions improved the titers of the compounds of interest. Striking changes in the ratios and amounts of the major and minor compounds in some cases were achieved by manipulations of media composition.

Culture Media↗
PubMed1999

Frequent deletions within FRA7G at 7q31.2 in invasive epithelial ovarian cancer.

We previously showed that FRA7G, an aphidicolin-inducible common fragile site at 7q31.2, colocalized with the common region of loss of heterozygosity (LOH) in a number of different tumors. Based on the sequence analysis of 150 Kb in the FRA7G region, we identified four new polymorphic microsatellite markers. In this article, we have used these four microsatellite markers and eight additional markers from 7q22-32 to analyze the breakage and loss of the region surrounding FRA7G in 49 invasive epithelial ovarian cancers and three borderline ovarian tumors. No allelic loss was detected in the ovarian tumors of borderline malignancy, but 71% (35/49) of the invasive tumors showed LOH at one or more loci in the region analyzed. Of the 12 markers analyzed, most of the markers exhibiting a high frequency of LOH were within FRA7G, and the highest frequency of LOH was seen with the new marker 7G14 (37%, 15/41). Breakpoint analysis in tumors with LOH demonstrated that the frequent loss of DNA sequences seen within the FRA7G region was due to frequent small interstitial deletions and not a result of loss of the whole fragile site region. These findings indicate that FRA7G does play a role in the breakage and loss of 7q sequences in invasive ovarian cancer. In addition, the newly identified markers enable us to further delineate a smallest common region of loss in invasive ovarian tumors to a 150-Kb region flanked by markers D7S486 and 7G14.

Carcinoma↗
PubMed1998

Socioeconomic status, standard of living, and neurotic disorder.

BACKGROUND: Evidence on the association between socioeconomic status and the prevalence of neurotic disorder is contradictory. We studied the association between three elements of socioeconomic status and the prevalence of neurotic psychiatric disorder in a representative sample of adults aged 16-64 living in private households in the UK. METHODS: A cross-sectional survey of 10,108 adults aged 16-65 resident in private households in the UK was selected by a multi-stage, clustered, random-sampling design. Neurotic disorders were defined using a standardised interview, the revised clinical interview schedule (CIS-R). Data for 9570 people were available for this study. FINDINGS: We used housing tenure and access to cars as measures of standard of living; both were associated with the prevalence of neurotic disorder even after adjustment for other socioeconomic and demographic variables, including Registrar General's Social Class and educational attainment. Those people with no access to a car had an odds ratio for neurotic disorder of 1.4 (95% CI 1.1-1.7), compared with those who had access to two or more cars. People who rented their homes were also at increased risk (1.3 [1.1-1.5]). We estimated that about 10% of the neurotic disorder in the UK could be attributed to the increased prevalence of those without cars who rented their homes. There was a complex interaction between Registrar General's Social Class and sex, and there was no independent association with educational attainment. INTERPRETATION: There is an independent association between low standard of living and the prevalence of neurotic psychiatric disorder. The UK has experienced one of the largest increases in income inequality within western market economies over the past 20 years, and this inequality may have had adverse consequences for the mental health of the population.

Adolescent↗
PubMed1998

Genomic organization and mutation analysis of p73 in oligodendrogliomas with chromosome 1 p-arm deletions.

p73, a protein having substantial structural and functional similarity to p53, has recently been identified and demonstrated to be a potential tumor suppressor. Its location on human chromosome 1p36.33 implicates p73 as a candidate for neuroblastoma. Like neuroblastoma, oligodendrogliomas also show a high frequency of deletions in chromosome 1p36.3. To determine whether p73 is a potential tumor suppressor gene involved in the development of oligodendrogliomas, we performed mutation analysis of p73 in oligodendrogliomas with chromosome 1 p-arm deletions. We first determined the genomic organization and the intron-exon boundary sequences of the p73 gene by long PCR, vectorette PCR, and Southern hybridization. This gene spans about 65 kb with a large first intron. Primer pairs for the amplification of each of the 13 p73 encoding exons were designed in corresponding introns. The amplicons were then analyzed using the denaturing high-performance liquid chromatography system for mutations in the p73 gene. Twenty oligodendroglioma samples with 1p36.3 deletions were screened, but no mutations were detected except for several polymorphisms. It is thus clear that p73 is not a candidate gene for oligodendroglioma despite its location in the frequently deleted 1p36.3 region.

Chromosomes, Human, Pair 1↗
PubMed1998

FRA7G extends over a broad region: coincidence of human endogenous retroviral sequences (HERV-H) and small polydispersed circular DNAs (spcDNA) and fragile sites.

FRA7G is an aphidicolin-inducible common fragile site at human chromosomal band 7q31.2. This region is frequently altered in a number of different tumor types including prostate, breast, and ovarian cancer. It has also been hypothesized that this region contains an important tumor suppressor gene which is mutated during the development of these cancers or an oncogene which is amplified. We previously used a FISH-based approach to isolate YAC clones which spanned FRA7G. In this report, we describe the isolation and restriction endonuclease mapping of three overlapping P1 clones which cover FRA7G and the region frequently altered in the different cancers. FISH-based analysis of these clones reveals that aphidicolin-induced breakage in the FRA7G region occurs over a region of at least 300 Kb in length. We have also localized a previously sequenced BAC clone to this region. The sequence obtained from this clone reveals the presence of an endogenous retroviral sequence (HERV-H) in the midst of the FRA7G region as well as sequences with homology to small polydispersed circular DNAs (spcDNAs). Thus for the first two cloned common fragile sites, FRA7G and FRA3B, there is an association with both spcDNAs and hot-spots for viral integration.

Base Sequence↗
PubMed1998

Frequent homozygous deletions in the FRA3B region in tumor cell lines still leave the FHIT exons intact.

FRA3B at human chromosomal band 3p14.2 is the most active common fragile site in the human genome. The molecular mechanism of fragility at this region remains unknown but does not involve expansion of a trinucleotide or minisatellite repeat as has been observed for several of the cloned rare fragile sites. Deletions and rearrangements at FRA3B have been observed in a number of distinct tumors. The recently identified putative tumor suppressor gene FHIT spans FRA3B, and various groups have reported identifying deletions in this gene in different tumors. Using a high density of PCR amplifiable markers within FRA3B searching for deletions in the FRA3B region, we have analysed 21 tumor cell lines derived from renal cell, pancreatic, and ovarian carcinomas. We found a commonly deleted region in the renal cell and ovarian carcinoma cell lines located in the middle of an HPV16 viral integration site. Despite the presence of deletions in the FRA3B region in most of the cell lines, we did not detect alterations in FHIT exons in any of the cell lines examined. Thus, deletions of 3p14.2 in these carcinoma cell lines may simply reflect instability of the FRA3B region during tumor progression.

Carcinoma, Renal Cell↗
PubMed1998

Influence of race on the prediction of cardiac events with stress technetium-99m sestamibi tomographic imaging in patients with stable angina pectoris.

The prognostic value of myocardial perfusion imaging in African-Americans is unknown. This study compared the prediction of cardiac events of stress technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) imaging in symptomatic Caucasian and African-American patients. Prospectively collected stress Tc-99m sestamibi tomographic imaging data from 4 medical centers, with follow-up information in 1,086 Caucasian and African-American patients, were analyzed in a core statistical laboratory. Primary events of cardiac death and nonfatal myocardial infarction and secondary events of all-cause mortality were analyzed using Kaplan-Meier survival analysis and Cox proportional-hazards multivariable model. Normal images in both African-Americans and Caucasians were associated with a low-annual cardiac event rate, whereas abnormal images were significantly associated with a higher cardiac event rate. The highest predictor of cardiac events was multivessel abnormality in both races. Use of this technique could identify patients at high risk and potentially reduce the high-cardiac event rate in African-Americans by utilizing appropriate therapies.

Aged↗
PubMed1998

The influence of age and sex on the prevalence of depressive conditions: report from the National Survey of Psychiatric Morbidity .

BACKGROUND: Women are consistently reported to have a greater prevalence of depressive disorders than men. The reason for this is unclear, and is as likely to be social as biological. There is some evidence that the excess of depression is greater during women's reproductive lives. Data from the National Survey of Psychiatric Morbidity were used to test the hypothesis that the excess disappeared in the post-menopausal years and that obvious social explanations for this were inadequate. METHOD: Subjects (N = 9792) from a random sample of the British population provided data for the analysis. Psychiatric assessment was carried out by lay interviewers using the CIS-R. Subjects with ICD-10 depressive episode or mixed anxiety/depression were compared with the remainder. Social variables that were likely to contribute to a post-menopausal decline in depressive disorders were controlled in logistic regression analyses. RESULTS: There was a clear reversal of the sex difference in prevalence of depression in those over age 55. This could not be explained in terms of differential effects of marital status, child care, or employment status. CONCLUSIONS: This large and representative survey adds considerably to the increasingly held view that the sex difference in prevalence of depression is less apparent in later middle age. This may be linked to the menopause, and our attempts to explain it in terms of obvious conditions among social variables were not successful. More specific studies are required to clarify the finding.

Adolescent↗
PubMed1998

The Checklist of Challenging Behaviour and its relationship with the Psychopathology Inventory for Mentally Retarded Adults.

The Checklist of Challenging Behaviour (CCB) was developed to survey the prevalence of challenging behaviour among people with intellectual disability. It describes 32 behaviours, and data are collected on the frequency, management difficulty and severity of these states. The present paper reports on the relationship between challenging behaviour (as measured by the CCB) and mental health (as measured by the Psychopathology Inventory for Mentally Retarded Adults). In addition, it discusses the differences between the two groups of clients used in the study, i.e. hospital and community subject groups, in terms of challenging behaviour and mental health.

Adult↗
PubMed1998

Potential for suicide prevention in primary care? An analysis of factors associated with suicide.

BACKGROUND: General practitioners (GPs) need to be aware of the risk factors for suicide. GP records may provide clues to identifying the relative importance of such risk factors. AIMS: To identify, in suicide cases and matched controls, the patterns of consultation, diagnosis, and treatment of mental illness, and recording of risk factors for suicide. To examine the usefulness of data routinely collected by GPs in computerized databases to investigate treatment of patients in general practice prior to suicide. METHOD: Case control study using GP records from the General Practice Research Database (GPRD). Three controls selected for each case, matched for age, sex, and duration of registration with practice. Information extracted of the prevalence of major disease; diagnosis of, and treatment, or referral for, mental illness; frequency of recording of recent life events; and consultations with the GP in the 12 months prior to death. RESULT: Of the 339 suicide cases recorded, 80% were male, which is similar to the national percentage for this age group. Females were more likely than males to have a history of mental illness and to have been diagnosed and treated for mental illness in the 12 months before death (59% versus 35%), and women were more likely to have previously attempted suicide (47% versus 27%). There was no significant difference between males and females in period of time since last contact with GP practice, but females consulted more frequently. Twenty-nine per cent of cases had not consulted their GP in the six months prior to death. In multivariate analysis, the following were identified as independent risk factors: history of attempted suicide; untreated serious mental illness (odds ratio > 20); recent (past 12 months) marital life event; alcohol abuse; frequent consultations with GP; and previous mental illness. Recording of life events by GPs was poor. CONCLUSIONS: Females at risk of suicide are more likely than males to have been diagnosed and treated for mental illness. It is likely that GPs are under-diagnosed and under-treating males at risk. Data from the GPRD give comparable results to those from other studies. The GPRD is a potentially useful tool for research into relatively uncommon events in general practice.

Adolescent↗
PubMed1998

Prognostic significance of allelic imbalance of chromosome arms 7q, 8p, 16q, and 18q in stage T3N0M0 prostate cancer.

Frequent allelic imbalance of polymorphic markers mapped to regions of the 7q, 8p, 16q, and 18q arms has been reported in prostate cancer. To better define the clinical significance of these genetic alterations, we undertook a retrospective analysis of systemic progression and survival in patients with a single stage of prostate cancer. We ascertained all 227 patients from the Mayo Clinic Radical Prostatectomy Registry who had a histologic high-grade, pathologic stage C (pT3N0M0) tumor surgically removed between 1966 and 1987. The mean follow-up of this population of patients was 7.7 years. DNAs were extracted from cancer lesions identified in 5-micron paraffin-embedded tumor sections. Control DNAs were obtained from surgically removed lymph nodes. Paired DNA samples of 153 patients were available for analysis using 16 polymorphic microsatellite markers mapped to 7q31, 8p22-p21, 16q23-qter, and 18q21-q22. The frequencies of allelic imbalance for at least one marker mapped to 7q31, 8p22-p21, 16q23-qter, and 18q21-q22 were 30, 58, 53, and 45% of all informative cases, respectively. Allelic imbalance at 7q31 strongly correlated with systemic cancer progression and to a slightly lesser extent with cancer-specific death. Eight-year systemic cancer progression-free rates were 58 and 81% for cases with and without 7q31 allelic imbalance, respectively (P < 0.001). Eight-year prostate cancer-specific survival rates were 70 and 85% with and without 7q31 allelic imbalance, respectively (P = 0.019). Multivariate analysis indicated that allelic imbalance at 7q31 is a significant independent predictor of systemic progression (P < 0.001) and possibly prostate cancer death (P = 0.029). In addition, allelic imbalance of the specific loci D7S522 (7q31.1) and D8S258 (8p22-p21.3) was strongly associated with systemic progression (P < 0.001 and P = 0.010, respectively) and with prostate cancer death (P < 0.001 and P = 0.009, respectively). The results suggest that a gene or genes mapped to 7q31.1 and possibly 8p22-p21.3 play an important role in tumor progression, and that allelic imbalances at these regions are markers for poor prognosis in prostate carcinoma.

Aged↗
PubMed1998

Gene amplification as a prognostic factor in primary and secondary high-grade malignant gliomas.

The purpose of this study was to examine the incidence of gene amplification in patients with primary (de novo) and secondary high-grade gliomas (gliomas evolving from lower grade malignancies) and to assess its prognostic significance. A total of 186 prospectively collected frozen surgical specimens were analyzed. Extracted DNA was examined by Southern blot using probes corresponding to the EGFR, CDK4, MDM2, n-MYC, CYCD1, PDGFR-alpha, MET, c-MYC oncogenes. Complete clinical data regarding age, sex, tumor size, extent of surgical resection, postoperative therapy and patient survival were collected. We showed that EGFR followed by CDK4 were the most frequent oncogene amplifications. Oncogene amplification events were significantly more frequent in grade 4 than in grade 3 astrocytomas, mixed gliomas or oligodendrogliomas (P<0.001). With respect to EGFR, there was a significant difference in the frequency of amplification between primary and secondary gliomas (P=0.001); however, no difference in the amplification frequency of the other oncogenes was observed. There was no apparent correlation between the occurrence of gene amplification and patient survival, possibly because the genes amplified in human gliomas are part of larger signaling pathways.

Adolescent↗
PubMed1997

Issues of empowerment for nurses and clients.

Consumer empowerment is a complex issue especially when people with learning disabilities are involved. The word 'empowerment' is ambivalent, implying vulnerability on the part of the client. Those who apparently need to be empowered are those who often cannot be. This article explores these contradictions in relation to people with a learning disability.

Consumer Advocacy↗