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Biomedical subjects

H Jenkins

Publications and source records attributed to H Jenkins.

At least 19 recordsLinked to original sources

Comparative epidemiology of Chlamydia trachomatis infection among men attending sexually transmitted disease clinics with and without indication for testing.

Understanding the epidemiology of Chlamydia trachomatis infection in men without indication for testing (without symptoms, signs, or a report of sexual contact with an infected partner) is of crucial importance to reduce the heavy burden of this infection, particularly because this group of men is not usually offered testing in different clinical settings. Using electronic medical records of two STD clinics in Connecticut, 2000-02, this study identified the risk factors of C. trachomatis infection in men with and without indication for testing. In both groups, men who were younger than 30, African-American, or had a prior history of C. trachomatis infection were significantly more likely to be infected. Since a system for routine reproductive health care of young men does not currently exist, health-care providers need to promote an increased awareness of C. trachomatis infection among their male patients who are at increased risk of infection.

Adult↗

Condom effectiveness for prevention of Chlamydia trachomatis infection.

BACKGROUND/OBJECTIVES: A growing body of evidence is increasingly demonstrating the effectiveness of condoms for sexually transmitted infection (STI) prevention. The purpose of the present analysis was to provide a disease specific estimate for the effectiveness of condoms in preventing Chlamydia trachomatis infection while controlling for known exposure to infection. METHODS: Condom effectiveness for C trachomatis was estimated using a medical record database from a public sexually transmitted disease clinic (n = 1455). Clients were classified as having known exposure to C trachomatis if they presented to the clinic as a contact to an infected partner. RESULTS: Among clients with known exposure, 13.3% of consistent condom users were diagnosed with C trachomatis infection compared to 34.4% of inconsistent condom users (adjusted odds ratio = 0.10; 95% CI: 0.01 to 0.83). Among clients with unknown exposure, there was no observed protective effect of condoms. CONCLUSIONS: This study provides further evidence that condoms are effective in preventing C trachomatis infection by reporting a disease specific estimate and restricting analyses to individuals with known exposure.

Adult↗

Variation in the CTLA4/CD28 gene region confers an increased risk of coeliac disease.

Susceptibility to coeliac disease involves HLA and non-HLA-linked genes. The CTLA4/CD28 gene region encodes immune regulatory T-cell surface molecules and is a strong candidate as a susceptibility locus. We evaluated CTLA4/CD28 in coeliac disease by genetic linkage and association and combined our findings with published studies through a meta-analysis. 116 multiplex families were genotyped across CTLA4/CD28 using eight markers. The contribution of CTLA4/CD28 to coeliac disease was assessed by non-parametric linkage and association analyses. Seven studies were identified that had evaluated the relationship between CTLA4/CD28 and coeliac disease and a pooled analysis of data undertaken. In our study there was evidence for a relationship between variation in the CTLA4/CD28 region and coeliac disease by linkage and association analyses. However, the findings did not attain formal statistical significance (p = 0.004 and 0.039, respectively). Pooling findings with published results showed significant evidence for linkage (504 families) and association (940 families): p values, 0.0001 and 0.0014 at D2S2214, respectively, and 0.0008 and 0.0006 at D2S116, respectively. These findings suggest that variation in the CD28/CTLA4 gene region is a determinant of coeliac disease susceptibility. Dissecting the sequence variation underlying this relationship will depend on further analyses utilising denser sets of markers.

Abatacept↗

Prospective survey of childhood inflammatory bowel disease in the British Isles.

The incidence of inflammatory bowel disease in children in western countries may be rising. Since there is no prospective national data on the incidence of inflammatory bowel disease in the UK and Republic of Ireland (ROI), we undertook a prospective survey to determine this incidence. The incidence during 1998 and 1999 was 5.2/100,000 per year in children aged younger than 16 years. Those from an Asian background were over-represented and more likely to have ulcerative colitis.

Adolescent↗

Contribution of the MHC region to the familial risk of coeliac disease.

Susceptibility to coeliac disease is genetically determined by possession of specific HLA-DQ alleles, acting in concert with one or more non-HLA linked genes. The pattern of risk seen in sibs and twins in coeliac disease is most parsimonious with a multiplicative model for the interaction between the two classes of genes. Based on a sib recurrence risk for coeliac disease of 10% and a population prevalence of 0.0033, the sib relative risk is 30. To evaluate the contribution of the MHC region to the familial risk of coeliac disease, we have examined haplotype sharing probabilities across this region in 55 coeliac disease families. Based on these probabilities the sib relative risk of coeliac disease associated with the MHC region is 3.7. Combining these results with published data on allele sharing at HLA, the estimated sib relative risk associated with the MHC region is 3.3. Therefore, the MHC genes contribute no more than 40% of the sib familial risk of coeliac disease and the non-HLA linked gene (or genes) are likely to be the stronger determinant of coeliac disease susceptibility.

Celiac Disease↗

The relationship between staff burnout/distress and interactions with residents in two residential homes for older people.

OBJECTIVE: The main hypothesis was that staff burnout/distress would be negatively associated with the quantity and quality of social interactions between staff and residents. The subsidiary hypothesis hypothesis was that 'perceived involvement in decision-making' among staff would be positively associated with the quantity and quality of staff-resident interactions. DESIGN: Cross-sectional and within-group. Standardized self-report questionnaires completed by staff; and non-participant, time-sampling observation and coding of staff-resident interactions. SETTING. Two independent (not-for-profit) residential care homes for older people in the UK. PARTICIPANTS: 18 out of 24 residential workers completed questionnaires. MEASURES: The 12-item General Health Questionnaire (GHQ-12); the Maslach Burnout Inventory (MBI); the Perceived Involvement Personal Questionnaire (PIPQ); and the Quality of Interactions Schedule (QUIS). RESULTS: Staff who reported higher levels of personal accomplishment (ie lower levels of burnout on the personal accomplishment subscale) exhibited significantly more staff-resident interactions; and staff who perceived more involvement in decisions relating to their work showed significantly fewer negative staff-resident interactions. Staff distress, emotional exhaustion and depersonalization were not found to be significantly related to the quantity or quality of staff resident interactions. CONCLUSIONS: The results provide some support for the hypotheses. It appears that levels of personal accomplishment and perceived involvement in decision-making among staff may significantly influence the quantity and quality of staff-resident interactions in residential settings. However, the causal relationships are uncertain, and replication of these findings is required in other contexts.

Adult↗

GST-lamin fusion proteins act as dominant negative mutants in Xenopus egg extract and reveal the function of the lamina in DNA replication.

A cDNA encoding Xlamin B1 was cloned from a whole ovary mRNA by RT-PCR. GST-lamin fusion constructs were generated from this cDNA by first creating convenient restriction sites within the Xlamin B1 coding sequence, using PCR directed mutagenesis, and then sub-cloning relevant sequences into pGEX-4T-3. Two expression constructs were made, the first, termed delta 2+ lacked sequences encoding the amino-terminal 'head domain' of lamin B1 but included sequences encoding the nuclear localization signal sequence (NLS). The second expression construct, termed delta 2-, lacked sequences encoding the amino-terminal 'head domain' as well as sequences encoding the NLS. Purified fusion proteins expressed from these constructs, when added to egg extracts prior to sperm pronuclear assembly, formed hetero-oligomers with the endogenous lamin B3. The delta 2+ fusion protein prevented nuclear lamina assembly but not nuclear membrane assembly. The resulting nuclei were small (approximately 10 microns in diameter), did not assemble replication centers and failed to initiate DNA replication. When the delta 2- fusion protein was added to egg extracts prior to sperm pronuclear assembly, lamina assembly was delayed but not prevented. The resulting nuclei although small (approximately 12 microns), did form replication centers and initiated DNA replication. When added to egg extracts after sperm pronuclear assembly was completed delta 2+, but not delta 2-, entered the pre-formed nuclei causing lamina disassembly. However, the disassembly of the lamina by delta 2+ did not result in the disruption of replication centers and indeed these centres remained functional. These results are consistent with the hypothesis that lamina assembly precedes and is required for the formation of replication centers but does not support those centers directly.

Animals↗

Building a virtual reality temporal bone dissection simulator.

The temporal bone is one of seven bones that comprise the human skull, and has an intimate relationship with many vital structures. Anatomically, its three-dimensional relationships make it one of the most challenging areas for surgeons to understand and master. In addition, the temporal bone contains minute structures that are among the most sophisticated and delicate in the human body. These structures include the cochlea and vestibular organs, which are responsible for hearing and balance; the middle ear, including the ossicles, which conduct acoustic energy to the cochlea; and the facial nerve, which is responsible for controlling the muscles of facial expression, and contributes to the sensation of taste. Additionally, the temporal bone forms a major portion of the skull base, and has intimate relationships to vital structures including the carotid artery, jugular vein, cerebral cortex, brainstem, and cranial nerves. Surgical procedures performed on the temporal bone include: procedures to eradicate chronic and acute infections; procedures to remove malignant and benign tumors within the temporal bone, from the skull base, or from the posterior cranial fossa; procedures to restore the hearing mechanism; procedures to eliminate balance disorders; and procedures to correct congenital anomalies. For surgeons-in-training, and even surgeons-in-practice, mastery of the anatomy of the temporal bone and the many complex approaches necessary to treat patients takes years of focused endeavor. This is typically accomplished through the dissection of human cadaver temporal bones, which are scarce, and require a dedicated laboratory facility. Efforts are currently underway to develop a realistic simulator for temporal bone procedures. Users immersed in the simulator will interact with a three-dimensional temporal bone, derived from patient-specific data, using a haptic interface to simulate traditional surgical procedures. Feedback from experts in otologic surgery will be built into the system for additional instruction. This presentation will include an overview of the application being developed, a report of its current state of development, and plans for the future.

Computer Simulation↗

Carcinoma of the tonsil: prognostic factors.

OBJECTIVES: This study was conducted to provide a review of the prognostic factors of tonsillar carcinoma. DESIGN: A retrospective analysis. SETTING/PATIENTS: Patients with squamous cell carcinoma of the tonsil, treated in Northern Alberta, at the Cross Cancer Institute from 1975 to 1995 were analyzed using a population-based, head and neck cancer registry. There were 102 patients, 73 male and 29 female, ranging in age from 35 years to 83 years, with a mean of 60 years. The clinical stages were T1: 5 patients; T2: 27 patients, T3: 33 patients; T4: 11 patients; and Tx: 3 patients. The nodal stages were N0: 33 patients, N1: 26 patients; N2: 34 patients, N3: 7 patients; Nx: 2 patients. METHOD: The patients were treated with various modalities: surgery alone: 2 patients; surgery plus radiation: 26 patients; radiation treatment alone: 61 patients; and others: 13 patients. Patients were classified according to the UICC TNM 1992 criteria. The overall 5-year Kaplan-Meier survival in our series was 39%. The cause-specific 4-year survival was 57%. Various prognostic factors and their impact on survival were studied. RESULTS: On univariate analysis, the following factors were found to be significant. Age < 50 vs. > 50 (p = .02); endophytic growth pattern vs. exophytic growth of the primary (p = .01); ulcerated lesions vs. nonulcerated lesions (p = .000); various T stages (p = .003); clinical extension vs. no extension of primary disease (p = .02); combined modality of treatment (surgery and radiation treatment) had the best chance of survival compared to radiation treatment alone (p = .03). Nodal stages N0 vs. N+ disease (p = .2); sex of the patient, female vs. male (p = .83); and dose of radiation treatment < 5000 cGy vs. > 5000 cGy (p = .41) were found not to be significant. When the above significant factors were stratified according to the stage of the disease, only two were significant; ulcerated lesions vs. nonulcerated lesions (p = .04), and the modality of treatment chosen (e.g., radiation alone vs. radiation plus surgery) (p = .02). CONCLUSIONS: In this series of patients, combined-modity approach using surgery and radiation treatment was found to be the best way to treat carcinoma of the tonsil. However, each treatment strategy should be individualized taking into account various prognostic factors.

Adult↗

Nuclear lamina and nuclear matrix organization in sperm pronuclei assembled in Xenopus egg extract.

Nuclear lamina and matrices were prepared from sperm pronuclei assembled in Xenopus egg extracts using a fractionation and extraction procedure. Indirect immunofluorescence revealed that while chromatin was efficiently removed from nuclei during the extraction procedure, the distribution of lamins was unaffected. Consistent with this data, the amount of lamin B3, determined by immunoblotting, was not affected through the extraction procedure. Nuclear matrices were visualised in DGD sections by TEM. Within these sections filaments were observed both at the boundary of the nucleus (the lamina) and within the body of the nucleus (internal nuclear matrix filaments). To improve resolution, nuclear matrices were also prepared as whole mounts and viewed using field emission in lens scanning electron microscopy (FEISEM). This technique revealed two distinct networks of filaments. Filaments lying at the surface of nuclear matrices interconnected nuclear pores. These filaments were readily labelled with monoclonal anti-lamin B3 antibodies. Filaments lying within the body of the nuclear matrix were highly branched but were not readily labelled with antilamin B3 antibodies. Nuclear matrices were also prepared from sperm pronuclei assembled in lamin B3 depleted extracts. Using FEISEM, filaments were also detected in these preparations. However, these filaments were poorly organised and often appeared to aggregate. To confirm these results nuclear matrices were also observed as whole mounts using TEM. Nuclear matrices prepared from control nuclei contained a dense array of interconnected filaments. Many (but not all) of these filaments were labelled with anti-lamin B3 antibodies. In contrast, nuclear matrices prepared from "lamin depleted nuclei' contained poorly organised or aggregated filaments which were not specifically labelled with anti-lamin B3 antibodies.

Animals↗

Management of infantile polyposis syndrome.

A boy with generalised infantile polyposis syndrome is reported to highlight the difficulties in management. Despite attempts to reduce polyp mass by regular endoscopic polypectomy, daily transfusions of blood products, and a trial of the non-steroidal anti-inflammatory agent sulindac, his condition gradually deteriorated and he died of septicaemia.

Anti-Inflammatory Agents, Non-Steroidal↗

Xenopus lamin B3 has a direct role in the assembly of a replication competent nucleus: evidence from cell-free egg extracts.

Xenopus egg extracts which assemble replication competent nuclei in vitro were depleted of lamin B3 using monoclonal antibody L6 5D5 linked to paramagnetic beads. After depletion, the extracts were still capable of assembling nuclei around demembranated sperm heads. Using field emission in lens scanning electron microscopy (FEISEM) we show that most nuclei assembled in lamin B3-depleted extracts have continuous nuclear envelopes and well formed nuclear pores. However, several consistent differences were observed. Most nuclei were small and only attained diameters which were half the size of controls. In a small number of nuclei, nuclear pore baskets, normally present on the inner aspect of the nuclear envelope, appeared on its outer surface. Finally, the assembly of nuclear pores was slower in lamin B3-depleted extracts, indicating a slower overall rate of nuclear envelope assembly. The results of FEISEM were confirmed using conventional TEM thin sections, where again the majority of nuclei assembled in lamin B3-depleted extracts had well formed double unit membranes containing a high density of nuclear pores. Since nuclear envelope assembly was mostly normal but slow in these nuclei, the lamin content of 'depleted' extracts was investigated. While lamin B3 was recovered efficiently from cytosolic and membrane fractions by our procedure, a second minor lamin isoform, which has characteristics similar to those of the somatic lamin B2, remained in the extract. Thus it is likely that this lamin is necessary for nuclear envelope assembly. However, while lamin B2 did not co-precipitate with lamin B3 during immunodepletion experiments, several protein species did specifically associate with lamin B3 on paramagnetic immunobeads. The major protein species associated with lamin B3 migrated with molecular masses of 102 kDa and 57 kDa, respectively, on one-dimensional polyacrylamide gels. On two-dimensional O'Farrell gels the mobility of the 102 kDa protein was identical to the mobility of a major nuclear matrix protein, indicating a specific association between lamin B3 and other nuclear matrix proteins. Nuclei assembled in lamin B3-depleted extracts did not assemble a lamina, judged by indirect immunofluorescence, and failed to initiate semi-conservative DNA replication. However, by reinoculating depleted extracts with purified lamin B3, nuclear lamina assembly and DNA replication could both be rescued. Thus it seems likely that the inability of lamin-depleted extracts to assemble a replication competent nucleus is a direct consequence of a failure to assemble a lamina.

Animals↗