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Biomedical subjects

J Kent

Publications and source records attributed to J Kent.

At least 37 records · Page 2Linked to original sources
PubMed1997

The reticulocalbin gene maps to the WAGR region in human and to the Small eye Harwell deletion in mouse.

We describe the localization of the gene encoding reticulocalbin, a Ca2+-binding protein of the endoplasmic reticulum, on human chromosome 11p13 midway between the WT1 and the PAX6 genes and show that it is hemizygously deleted in WAGR individuals. The mouse reticulocalbin gene is also shown to map to the region of conserved synteny on mouse chromosome 2 and to be deleted in the Small eye Harwell (SeyH) mutation. Loss of the reticulocalbin gene could contribute to the early lethality of SeyH and SeyDey homozygotes.

Abnormalities, Multiple↗
PubMed1997

Influenza vaccination in patients with asthma: effect on peak expiratory flow, asthma symptoms and use of medication.

This pilot study was undertaken to examine whether killed influenza vaccine causes exacerbations in asthmatic adults. Thirty-three stable asthmatics recorded peak expiratory flow (PEF), asthma symptoms, and use of asthma medication for 2 weeks, and then received killed influenza vaccine. Thereafter they recorded PEF, asthma symptoms and use of medication for a further 2 weeks. Comparison of recordings during the 2 weeks before and after vaccination revealed that influenza vaccine was not associated with reduction in PEF (P = 0.76), increase in asthma symptoms (P = 0.17) or use of asthma medication (P = 0.58). Similar results for PEF (P = 0.49), asthma symptoms (P = 0.17), and asthma medication (P = 0.16) were obtained when the analysis was restricted to the 2 days before and after vaccination.

Adult↗
PubMed1997

Myxoedematous madness and grievous bodily harm.

Psychosis is a rare but recognized complication of hypothyroidism (otherwise known as 'myxoedematous madness'). This is the report of a man charged with attempted murder who was found to be suffering from myxoedematous madness. The case illustrates several problems in the law relating to mental disorder and criminal responsibility. He was interviewed in the absence of an appropriate adult and this led to the inadmissibility of the police interviews. However, to have laid the basis for a defence of insanity the ideal evidence would have been what he told the investigating police officers about his state of mind at the material time, under caution and possibly with the assistance of an appropriate adult. As it was, although he was clearly mentally ill at the material time, the insanity defence was not open to him as he did not satisfy the MacNaughton Rules and his mental state did not fulfill the criteria for automatism. By the time he stood trial he was fully recovered from his psychosis and this faced the judge with a difficulty in sentencing him. The case is used to discuss proposed changes to the law concerning insanity.

Journal Article↗
PubMed1997

Hypothalamic substance P release. Attenuated angiotensin responses in mRen2(27) transgenic rats.

Increases in arterial pressure and paraventricular nucleus vasopressin release in response to intracerebroventricular injections of angiotensin peptides are blunted in mRen2(27) renin transgenic [TG(+)] rats. Intraventricular injections of tachykinin peptides mimic several of the actions of angiotensin peptides, and angiotensin peptides evoke substance P release from hypothalamic brain slices. The present study assessed whether diminished substance P release occurs in response to angiotensin peptides in TG(+) rats. Systolic blood pressure at 8 to 12 weeks of age averaged 197 +/- 4 mm Hg (n = 20; P < .05) in TG(+) rats compared with 123 +/- 4 mm Hg in normotensive control [TG(-)] rats (n = 18). Body weight was lower in hypertensive than in normotensive rats (305 +/- 14 versus 344 +/- 13 g, respectively; P < .05). Brain slices from hypothalamus were perfused at 37 degrees C with oxygenated Krebs' bicarbonate buffer. Substance P was measured before (basal) and during perfusion with either Krebs' buffer (control) or 2 mumol/L angiotensin-(1-7) or angiotensin II. Basal substance P release was 92 +/- 10 pg/g wet tissue in TG(+) and 98 +/- 12 pg/g in TG(-) rats (P > .05). Angiotensin-(1-7) and angiotensin II significantly increased substance P release from hypothalamus of TG(-) rats (82% and 70% above control: P < .05) but not TG(+) rats. These studies further support the hypothesis that the cardiovascular effects of angiotensin peptides are mediated in part by substance P and that this relationship is blunted in a hypertensive model that results from excess tissue production of angiotensins.

Angiotensin I↗
PubMed1996

Risk factors for lower respiratory complications of rhinovirus infections in elderly people living in the community: prospective cohort study.

OBJECTIVE: To assess the role of rhinoviruses in elderly people living in the community. DESIGN: Prospective community based surveillance of elderly people, without intervention. Subjects were telephoned weekly to identify symptomatic upper respiratory tract infections. Symptoms and impact of illnesses were monitored, and specimens were collected for diagnostic serology and human rhinovirus polymerase chain reaction. SETTING: Leicestershire, England. SUBJECTS: 533 subjects aged 60 to 90. MAIN OUTCOME MEASURES: Symptoms, restriction of activity, medical consultations, and antibiotic use during 96 rhinovirus infections. Adjusted odds ratios for lower respiratory syndromes with respect to smoking and health status. RESULTS: A viral cause was established in 211 (43%) of 497 respiratory illnesses; rhinoviruses were identified in 121 (24%) and as single pathogens in 107. The median duration of the first or only rhinovirus infection in the 96 people with 107 rhinovirus infections was 16 days; 18 of the 96 patients were confined to bed and 25 were unable to cope with routine household activities. Overall, 60 patients with rhinovirus infections had lower respiratory tract syndromes; 41 patients consulted their doctor, 31 of them (76%) receiving antibiotics. One patient died. Logistic regression analysis showed that chronic medical conditions increased the estimated probability of lower respiratory rhinovirus illness by 40% (95% confidence interval 17% to 68%) and smoking by 47% (14% to 90%). There were almost six times as many symptomatic rhinovirus infections as influenza A and B infections. CONCLUSIONS: Rhinoviruses are an important cause of debility and lower respiratory illness among elderly people in the community. Chronic ill health and smoking increase the likelihood of lower respiratory complications from such infections. The overall burden of rhinovirus infections in elderly people may approach that of influenza.

Aged↗
PubMed1996

Regulation of the Wilms' tumor gene during spermatogenesis.

Spermatogenesis is the process by which male germ cells develop and mature, a pathway that includes a transition from a mitotic to a meiotic cell cycle. Throughout this pathway, the germ cells are in close contact with their nurturing cells, the Sertoli cells. Sertoli-germ cell interactions are difficult to study in mammals due to the complex cellular organization of their seminiferous tubules. The urodele amphibian testis, however, provides a unique system to study the process of germ cell maturation; it is organized in a gradient-like cystic structure, in which synchronized germ cells can be found within the same cyst. The Wilms' tumor gene (WT1) has been shown to be an essential gene for the formation of the gonads in mice, and it has been implicated in a variety of differentiation processes. The WT1 gene is thus a good candidate for the study of the differentiation processes involved in the maturation of the male germ cells. By using a probe for the urodele WT1 homologue in in situ hybridization studies, as well as an antibody against the WT1 protein in immunohistochemistry studies, we determined that WT1 gene expression in Sertoli cells depends on the stage of maturation of the associated germ cell. Thus, WT1 mRNA was detected only in Sertoli cells of cysts that contained early spermatogonia. No mRNA expression was observed in cysts containing late spermatogonia, germ cells undergoing meiosis, or germ cells going through spermiogenesis. Immunohistochemistry studies confirmed that WT1 protein was strongly expressed in Sertoli cells associated with early spermatogonia but not in late ones. The protein was also found in Sertoli cells associated with germ cells that undergo the subsequent stages of meiosis and spermiogenesis. These results suggest that WT1 could be involved in the regulation by Sertoli cells of germ cell maturation and possibly in the progression from a mitotic to a meiotic cell cycle.

Ambystoma↗
PubMed1996

Effects of upper respiratory tract infections in patients with cystic fibrosis.

BACKGROUND: The polymerase chain reaction has improved the detection of picornaviruses and rhinoviruses and our understanding of their role in reversible airways disease. The effects of colds on lower respiratory morbidity and bacterial colonisation in cystic fibrosis remain uncertain. METHODS: Children with cystic fibrosis were evaluated regularly in the clinic and the parents notified the investigators when their child developed a cold. Nasopharyngeal specimens were collected at the start of the infection for polymerase chain reaction, bacteriology was also undertaken and again three weeks later, and pulmonary function was measured in children aged > or = 6 years at four day intervals for three weeks. The effects of colds on rate of progression of cystic fibrosis were assessed by pulmonary function, Shwachman scores, and radiology. RESULTS: Thirty eight children suffered 147 colds over 17 months. Picornaviruses were detected in 51 (43%) of 119 nasopharyngeal specimens, and 21 of the 51 were further identified as rhinoviruses. Pulmonary dysfunction was similar following picornavirus and non-picornavirus infections; the mean change from baseline in forced expiratory volume in one second (FEV1) was -16.5% and -10.3% at 1-4 days and 21-24 days, respectively, after onset of a cold. Children who experienced more colds than average had evidence of disease progression with reduction in Shwachman score, increasing Chrispin-Norman score, and greater deterioration in FEV1 per annum. Ten of 12 new bacterial infections were associated with a cold. CONCLUSIONS: Picornavirus and non-picornavirus colds are associated with pulmonary function abnormalities and disease progression in patients with cystic fibrosis, and predispose to secondary bacterial infection and colonisation.

Adolescent↗
PubMed1996

A male-specific role for SOX9 in vertebrate sex determination.

Mutation analyses of patients with campomelic dysplasia, a bone dysmorphology and XY sex reversal syndrome, indicate that the SRY-related gene SOX9 is involved in both skeletal development and sex determination. To clarify the role SOX9 plays in vertebrate sex determination, we have investigated its expression during gonad development in mouse and chicken embryos. In the mouse, high levels of Sox9 mRNA were found in male (XY) but not female (XX) genital ridges, and were localised to the sex cords of the developing testis. Purified fetal germ cells lacked Sox9 expression, indicating that Sox9 expression is specific to the Sertoli cell lineage. Sex specificity of SOX9 protein expression was confirmed using a polyclonal antiserum. The timing and cell-type specificity of Sox9 expression suggests that Sox9 may be directly regulated by SRY. Male-specific expression of cSOX9 mRNA during the sex determination period was also observed in chicken genital ridges. The conservation of sexually dimorphic expression in two vertebrate classes which have significant differences in their sex determination mechanisms, points to a fundamental role for SOX9 in testis determination in vertebrates. Sox9 expression was maintained in the mouse testis during fetal and adult life, but no expression was seen at any stage by in situ hybridisation in the developing ovary. Male-specific expression was also observed in the cells surrounding the Müllerian ducts and in the epididymis, and expression in both sexes was detected in the developing collecting ducts of the metanephric kidney. These results suggest that SOX9 may have a wider role in the development of the genitourinary system.

Animals↗
PubMed1996

The treatment of chronic benign pain syndrome in capitated health care.

Developing specialized services for the management of chronic benign pain syndrome offers enhanced patient care and reduced costs. The evolution of a behavioral medicine/health psychology department to provide these services in a large HMO is described. Operational aspects and implementation challenges are discussed.

Attitude of Health Personnel↗
PubMed1995

The evolution of WT1 sequence and expression pattern in the vertebrates.

WT1 is a Wilms' tumour predisposition gene, encoding a protein with four C-terminal Kruppel-type zinc fingers, which is also a major regulator of kidney and gonadal development. To pinpoint key regulatory domains involved in development and evolution of the vertebrate genitourinary system, we have isolated WT1 orthologues from all gnathostome classes. Partial nucleotide sequence from chick, alligator, Xenopus laevis and zebrafish reveals extensive conservation. Both the zinc fingers and the transregulatory domain exhibit a high level of similarity in all the species examined. However, of the two alternatively spliced regions only one, the three amino acid KTS insertion between zinc fingers 3 and 4, is found in species other than mammals. The 17 amino acid insertion at the C-terminal end of the transregulatory domain is present only in mammals. Residues with reported human pathological mutations are also unaltered across species, underlining their structural significance. Studies in chick and alligator reveal that the mammalian intermediate mesoderm expression pattern is conserved in birds and reptiles. A wider role in mesodermal differentiation is suggested by expression in some paraxial and lateral mesoderm derivatives.

Alligators and Crocodiles↗
PubMed1995

Human CD8+ T lymphocyte clones specific for T cell receptor V beta families expressed on autologous CD4+ T cells.

CD8+ T cells control immune responses, and recent studies suggest that this regulation is, in part, specifically directed towards TCR structures expressed by CD4+ cells. To develop a system to study the role of the TCR in regulatory interactions, we isolated clones of CD4+ cells expressing identified TCR V beta chains. These CD4+ clones were used to stimulate and expand autologous CD8+ cells, which kill the inducing CD4+ clone as well as independently isolated autologous CD4+ clones sharing the same TCR V beta as the inducing cell but not CD4+ T cells expressing different V beta TCRs. This V beta-specific cytotoxicity is dependent on the state of activation of the target cells and is not inhibited by an anti-class I monoclonal antibody, W6/32. We envision that V beta-specific CD8+ T cells of this type may regulate immune responses by direct interaction with antigen-activated CD4+ cells.

CD4-Positive T-Lymphocytes↗
PubMed1995

Multidrug-resistant Mycobacterium tuberculosis in an HIV dental clinic.

OBJECTIVE: To investigate possible transmission of multidrug-resistant tuberculosis (MDR-TB) in a dental setting. DESIGN: A retrospective, descriptive study of dental workers (DWs), patients, and practice characteristics. PATIENTS: Two dental workers (DW1 and DW2) with acquired immunodeficiency syndrome and MDR-TB. SETTING: A hospital-based (Hospital X) human immunodeficiency virus (HIV) dental clinic in New York City. METHODS: To identify dental patients with tuberculosis (TB), patients treated in the dental clinic at Hospital X during 1990 were cross-matched with those listed in the New York City Department of Health Tuberculosis Registry. Mycobacterium tuberculosis isolates from both DWs and from dental patients with TB were tested for antimicrobial susceptibility and typed by restriction fragment length polymorphism (RFLP) analysis. Infection control practices were reviewed. RESULTS: M tuberculosis isolates infecting DW1 and DW2 were resistant to isoniazid and rifampin and had identical RFLP patterns. DW1 and DW2 worked in close proximity to each other in a small HIV dental clinic in Hospital X during 1990. Of 472 patients treated in the dental clinic in 1990, 41 (8.7%) had culture-proven M tuberculosis infection. Of these 41, 5 had isolates with resistance patterns similar to both DWs; however, for four available isolates, the RFLP patterns were different from the patterns of the DWs. Sixteen of the 41 patients received dental treatment while potentially infectious. Dental patients were not routinely questioned about TB by dental staff, nor were all dental staff screened routinely for TB. No supplemental environmental measures for TB were employed in the dental clinic in 1990. CONCLUSIONS: Our investigation suggests that MDR-TB transmission may have occurred between two DWs in an HIV dental clinic. Opportunities for transmission of TB among dental staff and patients were identified. TB surveillance programs for DWs and appropriate infection control strategies, including worker education, are needed to monitor and minimize exposure to TB in dental settings providing care to patients at risk for TB.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Epidemiology of Creutzfeldt-Jakob disease in the United States, 1979-1990: analysis of national mortality data.

The trends and current incidence of Creutzfeldt-Jakob disease (CJD) was examined by using a unique and potentially high sensitive source for case ascertainment. We analyzed death certificate information for 1979-1990 from US multiple-cause-of-death mortality data, compiled by the National Center for Health Statistics, Centers for Disease Control and Prevention. We evaluated death certificate data for US residents for whom CJD was listed as one of the multiple causes of death on the death certificate (046.1) from the International Statistical Classification of Diseases, Injuries, and Causes of Death (9th revision). Age-adjusted and age-specific CJD death rates by gender, race, and region were calculated to measure the disease incidence because of the rapidly fatal course of the disease for most patients with CJD. We identified 2,614 deaths with CJD listed on the death certificates. The average annual age-adjusted mortality rate was 0.9 deaths per million persons (range 0.8-1.1). The mean age at death was 67 years. CJD-related deaths were uncommon among persons younger than 50 years of age (4.3% of all deaths). The highest average annual mortality rate was for those persons aged 70-74 years (5.9 deaths per million persons). A slight majority (53.0%) of the deaths was in females, but the age-adjusted mortality rate was 1.2 times higher for males. Most deaths (94.8%) were in whites; the mortality rate for blacks was only 40% of that for whites. The age-adjusted CJD mortality rate in the United States is similar to published estimates of the crude incidence of CJD worldwide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Consultant views on the use of aspirin in acute cerebrovascular disease: implications for clinical trials.

A questionnaire was sent to all 155 consultant physicians and geriatricians in the Yorkshire region who routinely admit patients with acute stroke in order to ascertain: (a) current opinion regarding the prescription of aspirin to patients with various manifestations of cerebrovascular disease, in particular the timing of initial treatment; and (b) the perceived role of computed tomography (CT) scans in relation to such therapy. The response rate was 81% (126/155). Aspirin was reported to be prescribed routinely by 75% (95/126) of physicians for patients with completed stroke. Amongst those prescribing aspirin, treatment was reported to be initiated routinely within 48 hours of the onset of symptoms by 63% (60/95). Only 10% (6/60) of these physicians reported that they would withhold aspirin therapy until the result of a cranial CT scan was known, although 43% (26/60) thought a CT scan was desirable. Our survey, which for logistical reasons is one of opinion rather than actual practice, suggests that aspirin is probably being prescribed acutely (less than 48 hours) after stroke to a significant number of patients and often without a pretreatment CT scan. As with patients who have had a CT scan, the balance of risks and benefits of this practice are unknown. We conclude that it would be ethical for acute treatment trials to allow randomization to aspirin without prior CT scan.

Acute Disease↗
PubMed1994

Lung and chest wall mechanical properties before and after cardiac surgery with cardiopulmonary bypass.

From measurements of airway and esophageal pressures and flow, we calculated the elastance and resistance of the total respiratory system (Ers and Rrs), chest wall (Ecw and Rcw), and lungs (EL and RL) in 11 anesthetized-paralyzed patients immediately before cardiac surgery with cardiopulmonary bypass and immediately after chest closure at the end of surgery. Measurements were made during mechanical ventilation in the frequency and tidal volume ranges of normal breathing. Before surgery, frequency and tidal volume dependences of the elastances and resistances were similar to those previously measured in awake seated subjects (Am. Rev. Respir. Dis. 145: 110-113, 1992). After surgery, Ers and Rrs increased as a result of increases in EL and RL (P < 0.05), whereas Ecw and Rcw did not change (P > 0.05). EL and RL exhibited nonlinearities (i.e., decreases with increasing tidal volume) that were not seen before surgery, and RL showed a greater dependence on frequency than before surgery. The changes in RL or EL after surgery were not correlated with the duration of surgery or cardiopulmonary bypass time (P > 0.05). We conclude that 1) frequency and tidal volume dependences of respiratory system properties are not affected by anesthesia, paralysis, and the supine posture, 2) open-chest surgery with cardiopulmonary bypass does not affect the mechanical properties of the chest, and 3) cardiac surgery involving cardiopulmonary bypass causes changes in the mechanical behavior of the lung that are generally consistent with those caused by pulmonary edema induced by oleic acid (J. Appl. Physiol. 73: 1040-1046, 1992) and decreases in lung volume.

Adult↗
PubMed1994

Wilms' tumour--a case of disrupted development.

Wilms' tumour is a paediatric kidney malignancy that arises through aberrant differentiation of nephric stem cells. We are studying the role of one Wilms' tumour predisposition gene, WT1. This is a tumour suppressor gene whose function is required for normal development of the genitourinary system. WT1 encodes a putative transcriptional repressor of the zinc finger family. Here we discuss how one of the normal functions of WT1 may be to suppress myogenesis during kidney development. Furthermore, we describe how we are proposing to use YAC (yeast artificial chromosome) transgenesis to analyse WT1 regulation and function in mice. We also discuss the evolution of the WT1 gene amongst different vertebrate classes and how this may provide insights into genitourinary evolution.

Animals↗
PubMed1993

Respiratory viruses and exacerbations of asthma in adults.

OBJECTIVE: To study the role of respiratory viruses in exacerbations of asthma in adults. DESIGN: Longitudinal study of 138 adults with asthma. SETTING: Leicestershire Health Authority. SUBJECTS: 48 men and 90 women 19-46 years of age with a mean duration of wheeze of 19.6 years. 75% received regular treatment with bronchodilators; 89% gave a history of eczema, hay fever, allergic rhinitis, nasal polyps, or allergies; 38% had been admitted to hospital with asthma. MAIN OUTCOME MEASURES: Symptomatic colds and asthma exacerbations; objective exacerbations of asthma with > or = 50 l/min reduction in mean peak expiratory flow rate when morning and night time readings on days 1-7 after onset of symptoms were compared with rates during an asymptomatic control period; laboratory confirmed respiratory tract infections. RESULTS: Colds were reported in 80% (223/280) of episodes with symptoms of wheeze, chest tightness, or breathlessness, and 89% (223/250) of colds were associated with asthma symptoms. 24% of 115 laboratory confirmed non-bacterial infections were associated with reductions in mean peak expiratory flow rate > or = 50 l/min through days 1-7 and 48% had mean decreases > or = 25 l/min. 44% of episodes with mean decreases in flow rate > or = 50 l/min were associated with laboratory confirmed infections. Infections with rhinoviruses, coronaviruses OC43 and 229E, influenza B, respiratory syncytial virus, parainfluenza virus, and chlamydia were all associated with objective evidence of an exacerbation of asthma. CONCLUSIONS: These findings show that asthma symptoms and reductions in peak flow are often associated with colds and respiratory viruses; respiratory virus infections commonly cause or are associated with exacerbations of asthma in adults.

Adult↗