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Biomedical subjects

N Wright

Publications and source records attributed to N Wright.

At least 19 recordsLinked to original sources

Definition of dendritic cell subpopulations present in the spleen, Peyer's patches, lymph nodes, and skin of the mouse.

Dendritic cells (DC) are highly efficient antigen-presenting cells (APC) that have an essential function in the development of immune responses against microbial pathogens and tumors. Although during the past few years our understanding of DC biology has remarkably increased, a precise characterization of the different DC subpopulations remains to be achieved with regard to their phenotype and lineage relationships. In this report, we have extensively studied the DC subpopulations present in the thymus, spleen, Peyer's patches, lymph nodes (LN) and skin of the mouse. Thymus DC and 60% spleen DC have a lymphoid DC phenotype, ie, CD8(+) DEC-205(high) Mac-1(low), whereas 40% spleen DC have a myeloid DC phenotype, ie, CD8(-) DEC-205(low) Mac-1(high). Both CD8(+) and CD8(-) DC are leukocyte function-associated antigen-1 (LFA-1)high and highly adherent. Within Peyer's patches the majority of DC correspond to the CD8(+) DEC-205(high) Mac-1(low) lymphoid category. In the LN, together with CD8(+) and CD8(-) DC, an additional nonadherent CD8(int) LFA-1(int) subpopulation with lymphoid DC characteristics is described. Finally, in the skin both epidermal Langerhans cells (LC) and dermal DC are CD8(-)DEC-205(high) Mac-1 (high), and do not express LFA-1. Interestingly, LC migration experiments indicate that LC underwent the upregulation of CD8 and LFA-1 upon migration to the LN, supporting the hypothesis that LC belong to the CD8(+) lymphoid lineage.

Animals

Functional and phenotypic analysis of thymic B cells: role in the induction of T cell negative selection.

The phenotype of mouse thymic B cells and their capacity to induce T cell negative selection in vitro were analyzed. Thymic B cells expressed B cell markers such as IgM, Fc gamma receptor, CD44, heat-stable antigen, LFA-1 and CD40. In addition, they were positive for the activation molecule CD69 and displayed high levels of B7-2. Although thymic B cells expressed CD5 on their surface, no CD5-specific mRNA was detected. Moreover, thymic B cells induced a stronger deletion of TCR-transgenic (TG) thymocytes than splenic B cells, which had low CD69 and B7-2 levels. Interestingly, CD40-activated splenic B cells up-regulated CD69 and B7-2 and acquired a capacity to induce T cell deletion comparable to that of thymic B cells. Moreover, thymic B cells from CD40-deficient mice displayed lower CD69 and B7-2 levels than control thymic B cells, and lower capacity to induce the deletion of TCR TG thymocytes. These results support the hypothesis that CD40-mediated activation of thymic B cells determines a high efficiency of antigen presentation, suggesting that within the thymus B cells may play an important role in the elimination of autoreactive thymocytes.

Animals

A bronchogenic cyst in an infant causing tracheal occlusion and cardiac arrest.

A 3-month-old infant treated for 3 weeks for suspected bronchiolitis, developed episodes of profound desaturation. A lateral X-ray showed displacement and compression of the trachea. Respiratory arrest, from which she was successfully resuscitated, occurred just before MRI scan. The mass was removed at thoracotomy and a histological diagnosis of a bronchogenic cyst was made. Mediastinal masses in babies are relatively rare, and the situation in which they present with acute respiratory distress may prove extremely challenging to the anaesthetist. Bronchogenic cysts are difficult to diagnose pre-operatively and awareness may assist in the peri-operative management of these infants.

Anesthesia, General

Assessment of patients with memory problems using a nurse-administered instrument to detect early dementia and dementia subtypes.

BACKGROUND: With the development of pharmacological treatments for Alzheimer's disease there will be an increase in the numbers of patients requiring assessment from specialist services. Could the role of the specialist clinician be supported by other health professionals screening those who might benefit from treatment? METHOD: Sixty-four consecutive referrals to the Leicester University Memory Clinic were assessed at home by a community psychiatric nurse using a semi-structured interview. The nurse then reported her findings to a psychiatrist and a diagnosis was agreed. This diagnosis was then compared to the Memory Clinic diagnosis and a standardized (ICD-10) diagnosis recorded by another psychiatrist examining the clinic records. RESULTS: The nurse assessment procedure performed well in detecting dementia, with a kappa statistic (k) of 0.75 when compared to the standardized and Memory Clinic diagnoses. There was, however, only moderate concordance between the ICD-10 diagnosis and nurse (k = 0.46) and the Memory Clinic and nurse (k = 0.60) for Alzheimer's disease. The relatively low k value for Alzheimer's disease was principally a result of difficult in differentiating vascular dementia. CONCLUSIONS: A single supervised community psychiatric nurse, using a structured assessment instrument, can adequately detect early dementia in a sample of patients referred with memory problems. Subtypes of dementia are not, however, accurately differentiated.

Adult

Role of spasmolytic polypeptide in healing of stress-induced gastric lesions in rats.

Stress is known to induce gastric ulcerations but the mechanism of their healing has been little studied. This paper describes the studies on mucosal expression and the effect on ulcer healing of spasmolytic peptide (SP), one of the members of the trefoil peptide family. Gastric ulcerations were induced in rats by the exposition to 3.5 h of water immersion and restraint stress. It was found that the number of these lesions gradually declined at 4, 8 and 12 h after stress and this spontaneous healing was significantly accelerated by s.c. infusion of human recombinant SP in a constant dose of 50 micrograms kg-1 h-1. The healing of the stress-induced ulcerations was accompanied by a gradual restoration of gastric mucosal blood flow and the decrease in gastric acid and pepsin secretion towards the normal values. The expression of SP in rats (rSP) was detected by RT-PCR in the intact mucosa and during all tested time periods reaching a peak at 4 h after the stress. Immunostaining for rSP in the intact mucosa was confined to the mucous neck cells, but following the exposure to stress it was significantly enhanced and occurred also in the cells of the basal region of gastric glands, reaching a peak at 4 h after the stress. We conclude that SP plays an important role in healing of stress-induced gastric lesions possibly by the acceleration of the mucosal repair, the enhancement of mucosal blood flow and the inhibition of gastric secretion.

Animals

Evaluation of a quantitative competitive PCR assay for measuring herpes simplex virus DNA content in genital tract secretions.

Previous studies have shown an association between the approximate titer of herpes simplex virus (HSV) DNA in clinical specimens and the ability to isolate HSV from genital secretions. To control for variance in amplification conditions, we developed a competitive quantitative PCR (QC PCR) for the detection of HSV DNA. The assay accurately measured from 10 to 10(6) copies of HSV DNA. We compared the QC PCR with our previous semiquantitative detection method and found concordance for 61 of 63 positive specimens. We also evaluated the HSV DNA content from individual swabs of genital secretions obtained from individual sites of the genital tract (cervix, vulva, and rectum) with that from one swab with secretions from all three sites. The concordance for detecting HSV DNA was 91%; for only 4 of 143 collection days was there a > 1 log difference between the two collection methods. A single swab with secretions from all three genital sites and evaluated in a QC PCR format can accurately measure the frequency of subclinical and clinical shedding of HSV and the titer of HSV shed from the genital region. Such an approach should be very useful in the evaluation of antiviral chemotherapy for HSV.

Base Sequence

Downgaze paresis following severe head trauma in a child.

A 4 1/2-year-old girl developed a downgaze paresis following severe head trauma. Magnetic resonance imaging showed evidence of peri-aqueductal lesions in the rostral midbrain in the region of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). Twenty five weeks following the injury, the downgaze paresis remained unchanged but she developed convergence retraction nystagmus on attempted upgaze. Repeat imaging did not show any change in the lesions in the rostral midbrain. This report provides further evidence for the riMLF in the control of downgaze, and a synkinesis is postulated for the development of the convergence retraction nystagmus.

Child, Preschool

Expression of trefoil peptides in the gastric mucosa of transgenic mice overexpressing transforming growth factor-alpha.

Overexpression of transforming growth factor-alpha (TGF-alpha) in the gastric mucosa of metallothionein-TGF alpha (MT-TGF alpha) transgenic mice leads to a marked alteration in the ontogeny of the fundic cellular lineages. Induction of the transgene leads to the over-production of mucous cells with a concomitant diminution in the development of parietal cell and chief cell lineages. We have sought to define more precisely the mucous cell lineages involved in the mucous cell hyperplasia in MT-TGF alpha mice by investigating the expression of trefoil peptides in MT-TGF alpha mice. MT-TGF alpha mice and their non-transgenic littermates were treated with cadmium sulfate beginning at 13 days of age. Animals were then sacrificed at intervals over the following 2 weeks and gastric mucosa was examined for expression of trefoil peptides and TGF alpha by immunohistochemistry and in situ hybridization. No TGF alpha mRNA expression could be demonstrated by in situ hybridization in non-transgenic mice. In MT-TGF alpha mice, in situ grains for TGF alpha mRNA were detected at the base of fundic glands in 13 day old animals, whereas the expression was observed more widely in the mucosa of older animals (28 days). TGF alpha immunoreactivity was observed in foveolar mucous cells and residual parietal cells in MT-TGF alpha mice at all ages. By in situ hybridization, pS2 mRNA was detected in the surface mucous cells in normal gastric mucosa. In MT-TGF alpha mice, pS2 mRNA was found throughout the expanded foveolar region. By in situ hybridization, spasmolytic peptide (SP) expression was observed in the region of the progenitor zone in both groups of mice. By immunohistochemistry, SP expression was noted in a broad band of mucous neck cells deep to the progenitor zone. No gastric expression of intestinal trefoil factor (ITF) was noted in either group of mice. The results demonstrate that the expansion of the foveolar mucous cell compartment in MT-TGF alpha mice is due to the hyperplasia of normal surface cells expressing their particular mucin-associated trefoil peptide, pS2.

Animals

Dynamics of risk behavior for HIV infection among young Thai men.

The objective of this investigation was to analyze the dynamics of risk for HIV-1 infection among young men in Thailand. We conducted a prospective study in a cohort (n = 1,236) of young men, aged 19-23 years at conscription into the Royal Thai Army and Air Force from six provinces in northern Thailand in May 1991 who were followed until their discharge in April 1993. The outcome measure was change since conscription in the frequency of self-reported sex with female commercial sex workers (CSW) during military service. Although 42% of conscripts reported no visit to a female CSW in the year prior to conscription, most had a visit during military service. Men who visited female CSWs infrequently at baseline increased their visits somewhat over time, whereas those with high initial rates of CSW visits decreased. Based on an assumed stable distribution over time, change from baseline was not statistically significant. Only marital status and high baseline CSW visit rates were associated with diminished visit frequency in multivariate analysis. No differences were seen in patterns of change in CSW visits by HIV-1 serostatus. More aggressive preventive interventions are needed to reduce the frequency of CSW visits in northern Thailand, a setting where 40-80% of all female CSWs working in brothels are now HIV seropositive.

Adult

Automatism re-visited: post-traumatic automatism as a defence to a serious criminal charge.

A case is described of a policeman who assaulted the man he was arresting after receiving a concussive blow to the head. The defence argued he was suffering from post-traumatic automatism and after juries were unable to agree a verdict in two trials he was acquitted. Aspects of post-traumatic automatism in English law are described and theories of the neurology of concussion and aggressive behaviour are discussed. Guidelines are proposed for the evaluation of cases of post-traumatic automatism.

Automatism

Trefoil peptides. Coming up clover.

Now that information on trefoil domain structure is available from X-ray crystallographic and nuclear magnetic resonance spectroscopy studies, we can begin to understand the functions of these unusual protein motifs.

Amino Acid Sequence

Seroprevalence of HIV antibodies and risk factors in healthy young males from upper north Thailand.

In the Spring of 1991 a random sample of young men from Upper Northern Thailand (mean age = 21 years) was interviewed by trained medical students from Chiang Mai University, serum samples were obtained and analyzed for prevalence of HIV-1 antibodies and for syphilis, and risk factors for HIV infection were assessed. It was found that Commercial Sex Workers (CSW) were the principal risk factor, that consistent condom use is rare, and the rates of HIV infection are rising rapidly. Sociodemographic background, homosexual behavior, drug use, and history of STD's were found to be not significant risk factors. The conclusions are that the education campaigns should be intensified to reduce the frequency of contact with CSW and to encourage consistent use of condoms.

Adult

Risk factors for HIV infection among young adult men in northern Thailand.

OBJECTIVE: To determine the sociodemographic and behavioral risk factors associated with human immunodeficiency virus (HIV) infection in two cohorts of young men selected for military service in northern Thailand. DESIGN: Military conscripts were studied cross-sectionally after conscription in May 1991 and November 1991. Risk factors were assessed by interview with trained nonmilitary interviewers. SETTING: Two military training bases in Chiang Mai, Thailand. PARTICIPANTS: A total of 2417 young men aged 19 to 23 years (mean age, 21 years) conscripted by lottery into military service in the Royal Thai Army or Royal Thai Air Force from six provinces in northern Thailand. MAIN OUTCOME MEASURES: Human immunodeficiency virus seroprevalence by enzyme-linked immunosorbent assay confirmed by Western blot and univariate and multivariate analyses of sociodemographic and behavioral risk factors associated with HIV seroprevalence. RESULTS: Overall, 289 (12.0%) of 2417 men were HIV-seropositive at baseline. The strongest associations with being HIV positive were heterosexual activities. History of sex with a female commercial sex worker (CSW) was frequent (96.5% of men who were HIV-positive and 79.0% of men who were HIV-negative) and strongly associated with HIV infection on univariate and multivariate analyses (adjusted odds ratio, 1.60 to 2.07, depending on the frequency of CSW contact). Also, sexually transmitted diseases were common and associated with HIV infection in both univariate and multivariate analyses (adjusted odds ratio, 3.36). Sex with other males and injection drug use were uncommon and not associated with HIV infection. Condom use was reported in 61.5% of men at last sex with a CSW but was not shown to be protective of prevalent HIV infection. CONCLUSION: The epidemic of HIV infection has spread widely among young men in northern Thailand, despite reported frequent and recent use of condoms during sex with female CSWs. Control of HIV infection in this population will probably require more regular and effective use of condoms, prevention and treatment of sexually transmitted diseases, and reduction in the frequency of CSW contact.

Adult