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Biomedical subjects

C Thompson

Publications and source records attributed to C Thompson.

At least 109 records · Page 6Linked to original sources

Bacterial SOS checkpoint protein SulA inhibits polymerization of purified FtsZ cell division protein.

Cell division of Escherichia coli is inhibited when the SulA protein is induced in response to DNA damage as part of the SOS checkpoint control system. The SulA protein interacts with the tubulin-like FtsZ division protein. We investigated the effects of purified SulA upon FtsZ. SulA protein inhibits the polymerization and the GTPase activity of FtsZ, while point mutant SulA proteins show little effect on either of these FtsZ activities. SulA did not inhibit the polymerization of purified FtsZ2 mutant protein, which was originally isolated as insensitive to SulA. These studies define polymerization assays for FtsZ which respond to an authentic cellular regulator. The observations presented here support the notion that polymerization of FtsZ is central to its cellular role and that direct, reversible inhibition of FtsZ polymerization by SulA may account for division inhibition.

Bacterial Proteins↗

Contraceptive needs of women attending a genitourinary medicine clinic for the first time.

OBJECTIVE: To assess the need for, and potential uptake of, a contraceptive service within a genitourinary medicine (GUM) clinic. METHODS: 544 women, median age 17 years (range 13-54) including 142 teenagers, attending the Fife GUM clinics serving a semirural population of 350,000 for the first time in the 12 month period from 1 September 1995 to 31 August 1996 were interviewed. RESULTS: Contraception was required by 353, of whom only 5% (29) were at risk of unplanned pregnancy, although half (15) of these were teenagers. 23 of 29 (79%) stated that they would access contraception at a GUM clinic if it were available. Of women using contraception, 67% (217/324) were taking the oral contraceptive pill (OCP), of whom 177 obtained supplies from their general practitioners and were happy with this. However, 92/177 (52%) stated that they would access the OCP at GUM clinics if it were available. Overall, of the 243 women who stated that they would access contraception at the GUM clinic, 23 of whom were currently at risk of an unplanned pregnancy, the demand was principally for condoms and the OCP. CONCLUSION: The majority of women attending GUM clinics for the first time are using contraception, or have deliberately chosen not to do so. Only 5% were at risk of unplanned pregnancy. In general, the women using contraception were happy with their current source of contraception, but about two thirds would use a contraceptive service at GUM clinics if it were available at the time they were attending the clinic. It was found that teenagers accounted for half of those women at risk of unwanted pregnancy. However, the majority of teenagers requiring contraception would consider obtaining it from GUM clinics.

Adolescent↗

Audit of diagnostic criteria for Trichomonas vaginalis in a genitourinary medicine clinic.

A comparison between high vaginal swab (HVS) wet prep examination within the genitourinary medicine (GUM) clinic and that made from an HVS transported in Amies charcoal medium to the laboratory for the diagnosis of Trichomonas vaginalis was made in a prospective study. Clinic wet prep compared with Amies had a sensitivity of 68% and specificity of nearly 100%. Using the clinic wet prep alone, 9/30 (30%) cases would have been missed.

Animals↗

Osmoregulation in clinical disorders of thirst appreciation.

Thirst and drinking are essential components of normal osmoregulation in healthy man. Abnormalities of thirst appreciation, in particular hypodipsia, have profound implications for water homeostasis. The combination of cranial diabetes insipidus and hypodipsia can have particularly serious consequences, with the potential for life-threatening hyponatraemia. Although the tools for measuring thirst are subjective and lack true specificity, their use in clinical research has contributed greatly to our understanding of the physiology of thirst appreciation and the abnormal control of thirst in osmoregulatory disorders. The precise neural control of thirst appreciation remains unknown, and perhaps as a result of this, satisfactory therapies for the treatment of disorders of thirst have not yet been developed; behavioural modification and retraining of drinking habits remain the rather limited cornerstones of management.

Adult↗

Polyvalent binding to carbohydrates immobilized on an insoluble resin.

Numerous studies have established that polyvalency is a critical feature of cell surface carbohydrate recognition. Nevertheless, carbohydrate-protein interactions are typically evaluated by using assays that focus on the behavior of monovalent carbohydrate ligands in solution. It has generally been assumed that the relative affinities of monovalent carbohydrate ligands in solution correlate with their polyvalent avidities. In this paper we show that carbohydrate ligands synthesized directly on TentaGel beads interact with carbohydrate-binding proteins in a polyvalent manner. The carbohydrate-derivatized beads can, therefore, be used as model systems for cell surfaces to evaluate polyvalent carbohydrate-protein interactions. By using a combinatorial approach to synthesize solid-phase libraries of polyvalent carbohydrates, one can rapidly address key issues in the area of cell surface carbohydrate recognition. For example, studies reported herein demonstrate that there is an unanticipated degree of specificity in recognition processes involving polyvalent carbohydrates. However, the correlation between polyvalent avidities and solution affinities is poor. Apparently, the presentation of carbohydrates on the polymer surface has a profound influence on the interaction of the ligand with the protein receptor. These findings have implications for how carbohydrates function as recognition signals in nature, as well as for how polyvalent carbohydrate-protein interactions should be studied.

Carbohydrate Metabolism↗

Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial.

OBJECTIVE: To determine whether long-term supplementation with vitamin E enhances in vivo, clinically relevant measures of cell-mediated immunity in healthy elderly subjects. DESIGN: Randomized, double-blind, placebo-controlled intervention study. SETTING AND PARTICIPANTS: A total of 88 free-living, healthy subjects at least 65 years of age. INTERVENTION: Subjects were randomly assigned to a placebo group or to groups consuming 60, 200, or 800 mg/d of vitamin E for 235 days. MAIN OUTCOME MEASURES: Delayed-type hypersensitivity skin response (DTH); antibody response to hepatitis B, tetanus and diphtheria, and pneumococcal vaccines; and autoantibodies to DNA and thyroglobulin were assessed before and after supplementation. RESULTS: Supplementation with vitamin E for 4 months improved certain clinically relevant indexes of cell-mediated immunity in healthy elderly. Subjects consuming 200 mg/d of vitamin E had a 65% increase in DTH and a 6-fold increase in antibody titer to hepatitis B compared with placebo (17% and 3-fold, respectively), 60-mg/d (41% and 3-fold, respectively), and 800-mg/d (49% and 2.5-fold, respectively) groups. The 200-mg/d group also had a significant increase in antibody titer to tetanus vaccine. Subjects in the upper tertile of serum alpha-tocopherol (vitamin E) concentration (>48.4 micromol/L [2.08 mg/dL]) after supplementation had higher antibody response to hepatitis B and DTH. Vitamin E supplementation had no effect on antibody titer to diphtheria and did not affect immunoglobulin levels or levels of T and B cells. No significant effect of vitamin E supplementation on autoantibody levels was observed. CONCLUSIONS: Our results indicate that a level of vitamin E greater than currently recommended enhances certain clinically relevant in vivo indexes of T-cell-mediated function in healthy elderly persons. No adverse effects were observed with vitamin E supplementation.

Aged↗

CD28/B7 costimulation regulates autoimmune diabetes induced with multiple low doses of streptozotocin.

Insulin-dependent diabetes mellitus is believed to occur as a result of a T cell-mediated destruction of the islets of Langerhans. The factors that regulate the T cell responses, in particular the costimulatory signals required for the T cell activation, which result in islet cell destruction, are still unclear. CD28/B7 interactions have been shown to be important in the regulation of T cell immune responses. We, therefore, have examined the role of CD28/B7 interactions in a model of insulin-dependent diabetes mellitus in which T cell-dependent insulitis and hyperglycemia occur over a brief period, following multiple low doses of streptozotocin (multidose streptozotocin (STZ)-induced diabetes mellitus). Expression of CD28 was necessary for diabetes because CD28 -/- C57BL/KsJ animals developed neither hyperglycemia nor insulitis, and did not express IFN-gamma mRNA following STZ, unlike CD28 +/- C57BL/KsJ mice. The expression of B7-1 (CD80) and B7-2 (CD86) molecules was closely regulated during development of the disease. Expression of both CD80 and CD86 increased on cells in pancreatic lymph nodes in STZ-treated C57BL/KsJ mice. Expression of only CD86 increased on islet cells in diabetic mice. In wild-type animals, treatment with mAb against CD86 prevented, whereas treatment with mAb against CD80 exacerbated, insulitis and hyperglycemia, indicating that mAbs against these molecules differentially affect development of disease. We conclude that CD28 signal transduction is required for development of diabetes in multidose STZ-induced diabetes mellitus. CD80 and CD86 molecules, the CD28/CTLA4 ligands, may have different roles in regulation of the disease and affect T cell function at steps beyond differentiation into mature phenotypes.

Animals↗

Seasonality prevalence and incidence of depressive disorder in a general practice sample: identifying differences in timing by caseness.

A total of 2225 consecutive consulting general practice patients attending a North London Health Centre over the course of a year were screened and interviewed for the presence of psychiatric disorder using the GHQ and SADS; 196 patients suffering from RDC depressive disorders were identified and followed up for a further 12 months. A difference in prevalence incidence and recovery time was identified between major and minor depression. Various associations between season of onset and a range of variables were observed. Logistic modelling identified interactions between some of these variables some of which have not been explored in previous studies.

Bipolar Disorder↗

Polymorphism at codons 114, 116, 145, and 163 muddle the typing of HLA-B*1304.

Genetic exchanges often muddle the typing of HLA class I molecules, this is also the case for HLA-B*1304. Serologic and molecular DNA class I typing report a B15/B55 type for cell 847, whereas DNA sequencing finds B*5501/B*1304. HLA-B*1304 differs by no more than four amino acids from other HLA-B13 molecules, a comparative analysis of the B13 and B15 families was therefore performed to determine why serologic and molecular DNA approaches report a B15 type for B*1304. Comparisons demonstrate that limited differences individuate the B15 and B13 molecules such that the genetic recombination of codons 145 and 163 in the class I heavy chain's alpha 2 alpha helix prompt B*1304 to exhibit a B15X21 pattern of serologic cross-reactivity. Molecular DNA class I typing approaches are also swayed by genetic recombinations to type B*1304 as a B15 molecule: B15-like nucleotide sequences encoding residues 114, 116, and 145, lead B*1304 to exhibit a B15 PCR amplification pattern. Thus, genetic exchanges encoding key amino acids in the class I heavy chain lead molecular and serologic typing approaches to categorize HLA-B*1304 as a member of the B15 family.

Alleles↗

Lifestyle intervention in people with insulin-dependent diabetes mellitus (IDDM).

OBJECTIVE: To investigate the impact of intensive lifestyle education on dietary practices, exercise and metabolic measurements in people with insulin-dependent diabetes mellitus (IDDM). DESIGN: Sixty-one volunteer subjects with IDDM were randomised to intensive (Group 1) or standard (Group 2) education programmes for six months. During a second six month period of observation Group 1 subjects received routine surveillance for their condition and those in Group 2 were given intensive advice (phase 2). Current insulin regimens were modified to optimise glycaemic control before the start of the intervention phase. Nutrient intakes, weight, blood pressure, glycated haemoglobin (HbA1), plasma lipids, lipoproteins and maximal oxygen consumption (VO2 max) were measured at the time of recruitment and at three monthly intervals during the trial and phase 2. SETTING: Department of Human Nutrition at the University of Otago. RESULTS: Glycated haemoglobin decreased significantly in both groups between recruitment and randomisation, the improvement being sustained during the six months of the randomised trial and for group 1 during the six months of post trial observation. A further decrease was seen in Group 2 during the second six month period when they were given intensive advice. Comparable changes were seen with total and low density lipoprotein (LDL) cholesterol in Group 1 during the trial, but significant decreases were only seen in Group 2 in association with intensive intervention (phase 2). These changes occurred in parallel with increases in intakes of carbohydrate and monounsaturated fatty acids, a reduction in intakes of total and saturated fat, and an improvement in maximum oxygen consumption. CONCLUSIONS: A lifestyle programme for people with IDDM results in modest changes in diet and exercise habits sufficient to improve measures of glycaemic control and lipoprotein mediated risk of coronary heart disease independent of changes in insulin regime. More innovative approaches to achieve lifestyle changes are required to meet current recommendations which in turn are likely to produce even greater beneficial changes than those observed here.

Adult↗

The Hampshire Depression Project: development and piloting of clinical practice guidelines and education about depression in primary health care.

This paper describes the development and piloting of a comprehensive educational programme about recognition and management of depressive illness in primary care. Full evaluation of the effectiveness of the programme is currently underway in a randomized controlled trial, the Hampshire Depression Project (HDP), involving 56 general practices. The programme consists of clinical practice guidelines, practice-based seminars and follow-up sessions. Each part of the programme has been designed to be flexible, clinically oriented and relevant to all members of the multidisciplinary primary care team. The pilot study established the need for a systematic approach to the access of practices and practice teams, and the organization and process of the seminars. Application of this approach was associated with excellent attendance in the main programme.

Depression↗

A comparison of bactericidal/permeability-increasing protein variant versus recombinant endotoxin-neutralizing protein for the treatment of Escherichia coli sepsis in rats .

OBJECTIVE: To compare a recombinant bactericidal/permeability-increasing protein variant and a recombinant endotoxin-neutralizing protein. DESIGN: Randomized, blinded, controlled study, using a rat model of sepsis. SETTING: Animal research facility. SUBJECTS: Male Wistar rats. INTERVENTIONS: An inoculum of 1.5 x 10(7) to 1.8 x 10(8) Escherichia coli O18ac K1, implanted in the peritoneum, produced bacteremia in 95% of animals after 1 hr. One hour after E. coli challenge, animals received recombinant bactericidal/permeability-increasing protein variant, recombinant endotoxin-neutralizing protein, or saline intravenously, followed by ceftriaxone and gentamicin intramuscularly. MEASUREMENTS AND MAIN RESULTS: Twenty-four (85.7%) of 28 animals receiving recombinant endotoxin-neutralizing protein (p < .001 vs. control) survived 7 days compared with nine (33.3%) of 27 recombinant bactericidal/permeability-increasing protein variant-treated (p < .001 vs. control) and two (6.5%) of 31 control animals. CONCLUSIONS: Both recombinant endotoxin-neutralizing protein and recombinant bactericidal/permeability-increasing protein variant improved survival. Recombinant endotoxin-neutralizing protein was superior to recombinant bactericidal/permeability-increasing protein variant in its protective effect at the doses tested. Our results suggest that both proteins may be useful in the treatment of human Gram-negative sepsis.

Animals↗

Compliance to exercise therapy in older participants with knee osteoarthritis: implications for treating disability.

This investigation examined predictors of compliance with exercise therapy in a clinical trial involving older adults with knee osteoarthritis (OA). The study sample was partitioned into tertiles by level of compliance to determine its effect on several clinical outcome measures in the trial (i.e., knee pain, difficulty with activities of daily living, and performance-related disability). The participants (N = 439) first completed all baseline assessments and were then randomly assigned to one of three treatment conditions: health education control, aerobic exercise, or resistance exercise. The two exercise treatments involved a 3-month center-based phase and a 15-month home-based phase. Variables in five categories (i.e., demographic, fitness, health-related quality of life, performance-related disability, and prior exercise behavior) were entered as predictors of attendance and time spent exercising during each session for three different periods of time across the course of the study. Results of these analyses revealed that it was possible to explain more variance for time spent exercising (approximately 40%) during the first 3 months than for attendance (approximately 10%). Furthermore, once participants completed the first 3 months of their training, prior behavior was the strongest predictor of exercise compliance. In most cases, the regression models accounted anywhere from 26 to 46% of the variance in attendance or time spent exercising (7 of the 8 P values < 0.01). In general, demographic, fitness, psychosocial, and disability-related measures did not predict compliance with any consistency across the various phases of the trial. Analysis of the dose-response data suggest that, in the use of aerobic exercise to deter disability in older people with knee OA, consideration should be given to prescribing frequent bouts of activity (at least 3 times each week) of moderate duration (approximately 35 min).

Activities of Daily Living↗

Haemophilus influenzae type b-specific antibody in infants after maternal immunization.

OBJECTIVE: To study the kinetics of Haemophilus influenzae type b (Hib)-specific antibody in infants born to mothers immunized with an Hib polysaccharide or one of two Hib conjugate vaccines. STUDY DESIGN: Serum antibody to the polyribosylribitol (PRP) moiety of Hib was measured by radioimmunoassay and enzyme-linked immunosorbent assay at birth and at 2 and 6 months of age in infants born to women immunized with Hib polysaccharide or conjugate vaccine (PRP-D and HbOC). A subset of infants > or = 6 months of age was immunized with Hib conjugate vaccine after licensure of this vaccine for infants. A comparison group of 18 infants born to unimmunized women received the same Hib conjugate vaccine on a similar schedule. RESULTS: Total PRP antibody concentrations were 1.50, 14.4 and 20.4 microg/ml in 2-month-old infants born to mothers immunized with polysaccharide, PRP-D and HbOC vaccines, respectively, and 2.54, 1.35 and 2.46 microg/ml in 6-month-old infants. Infants born to mothers immunized with polysaccharide vaccine had significantly less PRP antibody at 2 months of age but similar antibody concentrations at 6 months of age. Persistence or increases in total PRP antibody during 6 months were noted in 21 of 47 (44.6%) study infants. A subset of study and comparison infants was immunized with a mean of 2.6 doses of Hib vaccines between 6 months and 2 years of age, and all infants had total PRP antibody concentrations > or = 0.15 microg/ml. CONCLUSION: Conjugate Hib vaccines administered during the last trimester of pregnancy resulted in significantly higher PRP antibody titers in infants at birth and 2 months of age than did polysaccharide vaccine. A subset of infants born to immunized mothers was subsequently immunized with Hib conjugate vaccine and had antibody concentrations similar to those in infants born to nonimmunized women.

Antibodies, Bacterial↗

Microalbuminuria: a marker to increased renal and cardiovascular risk in diabetes mellitus.

The presence of persistent microalbuminuria in IDDM is strongly predictive of the future development of end stage renal failure and of cardiovascular disease to a lesser extent. Screening for microalbuminuria is an essential component of modern diabetes practice, as effective antihypertensive therapy, and particularly, the use of angiotensin converting enzyme inhibitors is of proven benefit in retarding progression of renal disease. Cost benefit analysis justifies the expense of microalbuminuria screening programmes and early intervention. It has been estimated that the use of angiotensin converting enzyme inhibitors in microalbuminuric IDDM will save 5200 Pounds-11,000 Pounds per year of life saved. Angiotensin converting enzyme inhibitors are not free of side-effects, and it is therefore essential, given the intrinsic variability of the albumin excretion rate, and the regression to normoalbuminuria of a significant proportion of patients, to confirm the diagnosis of microalbuminuria by repeated measurements prior to the commencement of treatment. The value of intensive glycaemic control is unproven, and further prospective studies are required. There are no proven therapies for the prevention of macrovascular disease in IDDM, although the value of cessation of smoking and aggressive blood pressure control are undoubted in the non-diabetic population. Controversy persists about the value of lipid lowering therapy, especially in young patients, although even in this group there is an increased risk of cardiovascular disease. Microalbuminuria is the strongest known predictor of cardiovascular disease in NIDDM; in contrast to the situation in the non-diabetic population, active lipid lowering therapy is not of proven cardiac benefit, but intervention seems justifiable when taken in the context of the very high prevalence of cardiovascular disease. Microalbuminuria is also predictive of end stage renal disease in NIDDM. Although intervention with angiotensin converting enzyme inhibitors has not been proven to prevent end stage renal disease, stabilisation of albumin excretion rate and creatinine clearance have been demonstrated in normotensive NIDDM, and it seems likely that longer term follow-up studies will confirm the benefit of angiotensin converting enzyme inhibitors in the prevention of end-stage renal disease. The observed predictive power of microalbuminuria as regards both cardiac and renal risk in NIDDM when considered in conjunction with the preliminary results of the benefits of angiotensin converting enzyme inhibition lend further support to the employment of microalbuminuria screening in NIDDM.

Albuminuria↗

Effects of morning phototherapy on circadian markers in seasonal affective disorder.

BACKGROUND: The suppression of melatonin by light at 00.30 hours has been shown to be greater in winter than in summer on patients with seasonal affective disorder (SAD) but not in matched normal controls. METHOD: In this study 12 patients with SAD and 12 matched normal controls were exposed to morning light therapy in the winter. Melatonin profiles and sensitivity to light were measured before and after treatment. RESULTS: The SAD but not the normal group showed a phase advance of melatonin rhythms in response to phototherapy. There was an association between phase position and phase shift in the SAD but not in the normal group. CONCLUSIONS: There may be instability of circadian rhythms in SAD mediated by a high-amplitude phase response curve, rather than a fixed phase abnormality as had been previously suggested. This instability may be secondary to impaired serotoninergic function in the afferent pathways to the suprachiasmatic nuclei.

Adult↗