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Biomedical subjects

J Wheeler

Publications and source records attributed to J Wheeler.

At least 19 recordsLinked to original sources
PubMed1995

Antigen-binding B cells and polyreactive antibodies.

The present experiments were initiated to see if cells capable of binding antigens could make polyreactive antibodies. Fluorescein isothiocyanate-labeled self and non-self antigens were incubated with B cells from normal individuals. Antigen-binding cells were separated from non-antigen-binding cells by flow cytometry, immortalized with Epstein-Barr virus and analyzed at the clonal level for their capacity to make polyreactive antibodies. Four to six times more cells making polyreactive antibodies were found in the B cell subset that bound antigens than in the B cell subset that did not bind antigens. The majority of the polyreactive antibodies were of the immunoglobulin (Ig)M isotype. Immunoflow cytometry revealed that cell lines making polyreactive antibodies bound a variety of antigens (e.g., insulin, IgGFc and beta-galactosidase), whereas cell lines making monoreactive antibodies bound only a single antigen. The binding of antigens to B cell lines that made polyreactive antibodies could be inhibited (range, 28%-57%) by both homogeneous and heterogeneous antigens. Both CD5+ and CD5- antigen-binding B cells made polyreactive antibodies, but the frequency was slightly higher in the CD5+ antigen-binding (85%) as compared to the CD5- antigen-binding (50%) population. Comparison of CD5+ B cells that bound antigens with CD5+ B cells that did not bind antigens showed that approximately 86% of the former, but only 15% of the latter, made polyreactive antibodies. It is concluded that cells capable of binding a variety of different antigens can make polyreactive antibodies and that antigen binding is a good marker for identifying polyreactive antibody-producing cells.

Antibody Formation↗
PubMed1995

A pilot study of infectious intestinal disease in England.

Pilot studies to test methods to determine the incidence, agents, risk factors and socioeconomic costs of infectious intestinal disease (IID) in England were carried out as recommended by the Committee on the Microbiological Safety of Food (the Richmond Committee) by eight general practices. There were case control and enumeration studies of patients presenting to general practice with IID, a population-based prospective cohort study, and a survey of socioeconomic costs of cases of IID. Information on risk factors was obtained by questionnaire (self-administered compared with interview) and a stool sample was requested on all cases and controls. Response rates in the GP case control study were 75% for case questionnaires and 74% for stools; for controls the figures were 70% and 68% respectively. The acceptance rate into the cohort study was 49%; this was significantly higher where phone contact was made. The rate was similar if recruitment was by individual or household. Follow-up of the cohort by negative reporting was complete for up to 6 months. Direct postage by subject was required to obtain fresh stool specimens. Estimates were obtained of presentation rates of IID and the distribution of risk factors which were used to plan the main study. The pilot study demonstrated that it is possible to undertake a national study based in general practice to determine the incidence of IID in the population and presenting to GPs and its agents, risk factors and costs.

Adolescent↗
PubMed1995

Anti-glomerular basement membrane glomerulonephritis in the mouse: the role of macrophages.

An immunohistochemical study was undertaken on fixed, paraffin-embedded mouse kidney in order to elucidate the role and significance of infiltrating macrophages in a mouse model of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). Tissue was available representing the full gamut of histological features seen in this model. The mouse macrophage-specific antigen F4/80 was detected in tissue sections of glomerulonephritic kidney and the pattern and extent of staining was compared with normal mouse kidney. In glomerulonephritic kidney, an increase in the number of F4/80-positive cells was evident in close proximity to and surrounding Bowman's capsule of those glomeruli which were severely damaged, with extensive fibrin deposition and well developed cellular crescents. F4/80-positive cells did not feature in the glomerular tuft or in the region of the parietal epithelium of Bowman's capsule even when extensive cellular crescents were present. Breaks in Bowman's capsule were not demonstrated. We conclude that F4/80-positive macrophages are not a major constitutive cell type of developing crescents in this mouse model of anti-GBM GN but, by virtue of their peri-glomerular localization, may be involved in the destructive process, perhaps producing signalling molecules which contribute to the inflammatory reaction.

Animals↗
PubMed1994

In vivo production of tumour necrosis factor-alpha and interleukin-6 in BALB/c mice inoculated intranasally with a high dose of respiratory syncytial virus.

Intranasal administration of an inoculum of 10(7) focus-forming units (FFU) of respiratory syncytial (RS) virus induced disease in BALB/c mice with signs of anorexia, cachexia, ruffled fur, and pneumonia. Mice displayed mild signs of illness on day 1 postinoculation (PI), followed by a transient recovery phase of 3 days. Disease rapidly reappeared on day 5 PI and worsened on subsequent days, with mortalities by day 7 PI. Mice inoculated with 5 x 10(6) FFU exhibited milder signs of disease, while those inoculated with 2 x 10(6) FFU and control mice given only Hep-2c cell suspension exhibited no noticeable signs of illness. High levels of bioactive tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were detected in both lungs and sera of mice inoculated with 10(7) FFU of virus. Peak levels of both cytokines were detected at day 1 PI but remained detectable throughout the 7 day period studied postinoculation. Cytokine levels were much lower or were undetectable in control mice. These results suggest that the macrophage is stimulated in vivo to produce inflammatory cytokines in response to RS virus infection.

Animals↗
PubMed1994

Steroid sulfation by expressed human cytosolic sulfotransferases.

The human cytosolic sulfotransferases (STs), dehydroepiandrosterone sulfotransferase (DHEA-ST) and the phenol-sulfating form of phenol sulfotransferase, (P-PST), have been expressed in bacteria and used to investigate the ability of the cloned enzymes to conjugate steroids and related compounds. DHEA-ST was capable of sulfating all of the 3-hydroxysteroids, testosterone and estrogens tested as substrates. The 3-hydroxysteroids, androsterone, epiandrosterone and androstenediol, were conjugated at 50-60% of the rate of DHEA. Of the steroids tested, P-PST was capable of conjugating only the estrogens. The catechol estrogens, 2-hydroxyestradiol, 4-hydroxyestradiol and 4-hydroxyestrone, and compounds with estrogenic activity such as 17 alpha-ethynyl-estradiol and trans-4-hydroxytamoxifen, were also tested as substrates. DHEA-ST showed little or no sulfation activity with these compounds; however, all of these compounds were sulfated by P-PST. These results indicate that the expressed human STs are valuable in analyzing the overlapping substrate specificities of these enzymes and that P-PST may have an important role in the metabolism of estrogens and estrogenic compounds in human tissues.

Amino Acid Sequence↗
PubMed1994

In vitro bromodeoxyuridine labelling of renal biopsy specimens: correlation between labelling indices and tubular damage.

AIMS: To examine the correlation between bromodeoxyuridine (BrdU) labelling indices (LI) and tubular damage in renal biopsy specimens; to evaluate the diagnostic and prognostic potential of measuring cell proliferation in a variety of renal lesions. METHODS: In vitro BrdU labelling of renal biopsy specimens was undertaken and labelled cells were detected in routinely fixed, paraffin wax embedded sections by immunohistochemistry. The BrdU LI were calculated as percentages for the three types of tubular cells--proximal and distal convoluted tubules and medulla (LI/PCT, LI/DCT, LI/Med)--and a total tubular BrdU LI (LI/Tub) was also calculated for each biopsy specimen. Histological features indicative of tubular damage were also scored and a total tubular damage score obtained for each biopsy specimen. RESULTS: The one hour labelling process did not affect tissue morphology or impede subsequent diagnosis. Four biopsy specimens were obtained from three renal transplant recipients. Diagnosis of 19 non-transplant biopsy specimens revealed a variety of renal lesions. Total tubular damage scores ranged from 0 to 25 and the LI/Tub ranged from 0 to 3.68% in all 23 biopsy specimens. Analyses of variance showed highly significant correlations between the total tubular damage score and both LI/Tub (p = 0.004) and LI/PCT (p = 0.004); a weaker correlation was found between the total tubular damage score and LI/DCT (p = 0.013). CONCLUSIONS: A correlation was found between tubular damage and BrdU LI. This was most clearly seen in the proximal tubules. However, as the study was limited to a few examples of specific forms of glomerular or interstitial disease, firm conclusions about the value of BrdU labelling in routine diagnosis and prognosis could not be drawn.

Biopsy, Needle↗
PubMed1994

Timing of the endometrial biopsy may be critical for the accurate diagnosis of luteal phase deficiency.

OBJECTIVE: To determine the optimal time to perform the endometrial biopsy for the detection of "out-of-phase" endometrium. DESIGN: Two endometrial biopsies were performed during a single menstrual cycle in each subject. The patient's chronological day was determined by counting forward from the midcycle LH surge, as assessed by urinary LH detection. The "early" biopsy was done on day LH + 7.4 +/- 0.8, and the "late" biopsy on day LH + 11.6 +/- 0.7. Each biopsy was independently read by two pathologists and was considered out of phase if the histologic date was > or = 3 days delayed compared with the chronological date. SETTING: Infertility practice of an academic teaching hospital. PATIENTS: Thirty-three ovulatory women seeking evaluation for infertility. MAIN OUTCOME MEASURE: Number of patients with out-of-phase endometrium detected by the early versus the late biopsy. RESULTS: There was a significantly greater detection rate for out-of-phase endometrium using the early biopsy (12.1% to 18.2% incidence depending on the observer) compared with the later biopsy (6.1% to 9.1% incidence). A majority of the early out-of-phase biopsies corrected by the time of the later biopsy. CONCLUSION: Our findings indicate that an endometrial biopsy performed in the midluteal phase may detect a greater number of women with delayed endometrial maturation during the temporal window of embryo implantation. The observation that most of the women with out-of-phase midluteal biopsies had normal late luteal endometrium may represent a cryptic form of luteal phase deficiency.

Adult↗
PubMed1993

Perceptions of VA chiefs of staff on total quality management implementation.

A national survey of United States Veterans Affairs (VA) Medical Centers (n = 167) chiefs of staff was conducted. The survey solicited feedback of the attitudes and perceptions of respondents toward planning, implementation, and monitoring of the Total Quality Management (TQM) process in their facilities. A Likert scale type of responses were collected and analyzed to measure the degree of agreement or disagreement of the respondents to survey statements on TQM. The survey included responses to three sections of the questionnaire: 25 statements on TQM, information on the TQM process status in the facility, and demographics of respondents and their facilities. The results of the survey indicate a considerable involvement of responding chiefs of staff in the TQM process and indicated their willingness to support it. Respondents agreed that TQM requires time and commitment of top management, and, again, they indicated their willingness to devote the time necessary for the process to succeed. They were, however, cautious in endorsing the statement that TQM will decrease health care costs (fiscal and human). The survey provides information that should prove valuable to administration in planning TQM and Continuous Quality Improvement efforts.

Adult↗
PubMed1992

Bioactivation of 7-hydroxymethyl-12-methylbenz[a]anthracene by rat liver bile acid sulfotransferase I.

The bioactivation of 7-hydroxymethyl-12-methylbenz[a]anthracene (HMBA) to an electrophilic sulfuric acid ester metabolite has been shown to be catalyzed by rat liver bile acid sulfotransferase I (BAST I). The sulfation and activation of HMBA by BAST I was determined by the ability of sulfated HMBA to form DNA adducts. The BAST I was also shown to react with rabbit anti-human dehydroepiandrosterone sulfotransferase antisera and to represent a major form of hydroxysteroid/bile acid sulfotransferase in female rat liver cytosol. Higher levels of BAST I activity and immunoreactivity as well as HMBA-DNA adduct formation were detected in female rat liver cytosol than in male rat liver cytosol. The bioactivation of HMBA by pure BAST I was dependent on the presence of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) in the reaction and was inhibited by dehydroepiandrosterone, a physiological substrate for BAST I. Glutathione, a cellular nucleophile with important protective properties, decreased DNA adduct formation in the HMBA sulfation reaction in the absence of glutathione S-transferase activity. These results indicate the usefulness of BAST I to investigate the sulfation and activation of HMBA and probably other hydroxymethylated polyaromatic hydrocarbons to electrophilic and mutagenic metabolites under defined reaction conditions.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Impact of self-management education on the functional health status of older adults with heart disease.

This paper presents findings from the evaluation of a self-management education program based on self-regulation principles. Older men and women (N = 324) were randomly assigned to program and control groups. Outcomes were measured using the Sickness Impact Profile. Twelve months following baseline data collection, psychosocial functioning of program participants was significantly better than that of controls. Different program effects were noted when results were analyzed by participant gender.

Activities of Daily Living↗
PubMed1991

Corrections in counting paired nuclei labelled with bromodeoxyuridine in tissue sections.

Bromodeoxyuridine is finding increasing use as an alternative to, or in conjunction with, tritiated thymidine for labelling nuclei in DNA synthesis. Precise identification of labelled nuclei is possible, even when there is considerable overlap between neighbouring nuclei. In the sparsely labelled renal cortex of the normal male mouse, 'flash labelling' with bromodeoxyuridine shows single labelled nuclei at 1 h. At 24, 48 and 72 h after injection of bromodeoxyuridine, some labelled cells are seen to lie adjacent and such labelled pairs are presumed to be the result of cell division. Single labelled nuclei at 24, 48 and 72 h might indicate arrest in DNA synthesis or a prolonged G2 period, but it is important to recognize that a correction must be made for paired labelled nuclei in which one member is out of the plane of section. The factors involved in making such a correction are discussed and a correction table calculated. In the normal male mouse renal cortex, we show that nearly all cells labelled at 1 h had divided by 72 h.

Animals↗
PubMed1991

Efficacy and safety of ethynodiol diacetate, 1 mg, with ethinyl estradiol, 35 micrograms, with an emphasis on contraceptive efficacy. A phase IV trial.

A phase IV trial evaluated the efficacy and safety of a monophasic oral contraceptive formulation, ethynodiol diacetate, 1 mg, plus ethinyl estradiol, 35 micrograms (EDA 1 mg with EE 35 micrograms) (Demulen 1/35). Nine hundred eighty-three community-based obstetrician-gynecologists treated a total of 7,759 patients with EDA 1 mg with EE 35 micrograms for one to eight months. Clinical evaluation forms on 6,382 patients were amenable to analysis for safety (including breakthrough bleeding, ovarian cyst formation and complexion changes); 5,412 patients were evaluable for efficacy (prevention of pregnancy), with a total of 21,440 cycles recorded. The study results were interpreted in terms of the impact on clinical management of oral contraceptive users and the methods, strengths and weaknesses of phase IV trials, particularly as they relate to confirmation of the results reported here.

Adolescent↗
PubMed1990

In vivo bromodeoxyuridine incorporation in normal mouse kidney: immunohistochemical detection and measurement of labelling indices.

A method is reported for in vivo bromodeoxyuridine incorporation in mice and its subsequent visualization in kidney by immunohistochemistry. Following formal-sublimate fixation of the kidney, bromodeoxyuridine labelled nuclei were detected in paraffin sections with a monoclonal antibody and visualized by an immunoperoxidase technique. This rapid and unequivocal method was used to measure labelling indices in tubules, glomerular tuft and Bowman's capsule in normal male T70 (Beige) mice, at intervals up to 72h after labelling. Significant differences were found between the labelling indices of these three populations of cells, which appeared to show different cell kinetic behaviour.

Animals↗
PubMed1990

Weight cycling in female rats subjected to varying meal patterns.

The effect of weight cycling on energy balance was examined in female rats. Two groups of adult female rats were subjected to three bouts of weight cycling, each bout consisting of 8 days of food restriction (9 g/day or approximately 50% of usual intake) followed by 16 days of refeeding. During refeeding animals were given 22.8 g/day of food so that they were offered, during the 24-day cycle, the same amount of food offered to control rats that were not subjected to weight cycling. One group of weight-cycled rats (gorgers) was given its daily intake in a few large meals (i.e., allowed to gorge). The other weight-cycled group (nibblers) was fed by automated feeders in several small meals during each 24-h period (i.e., prevented from gorging). Neither weight-cycled group displayed an increased food efficiency or an increased body fatness compared with noncycled controls. Weight-cycled rats allowed to gorge did have an increased food efficiency and a greater carcass energy content compared with weight-cycled rats not allowed to gorge. These results suggest a pattern of gorging promoted food efficiency and body energy gain compared with a pattern of nibbling, but gorging during refeeding cannot account for reports of increased food efficiency in weight-cycled rats.

Adipose Tissue↗
PubMed1990

Anti-glomerular basement membrane (GBM) glomerulonephritis in the mouse: development of disease and cell proliferation.

In a mouse model of anti-glomerular basement membrane (GBM) glomerulonephritis, associated with the nephrotic syndrome, a wide range of morphological and proliferative responses was seen in the renal corpuscle, at 6 days. The severity of the damage could be assessed by measuring the average daily weight gain between days 0 and 3 (DWG) of the animal. Those animals with a high DWG showed capsular proliferation, whereas animals with a low DWG showed predominantly tuft cell proliferation. Capsular cell birth rate increased with DWG whilst tuft cell birth rate was negatively related. A computer simulation suggests that the results are compatible with the induction of successive but overlapping waves of tuft and capsular cell proliferation.

Animals↗
PubMed1989

Sporozoite antibodies and malaria in children in a rural area of The Gambia.

Sporozoite antibody levels were measured in a group of children aged one to nine years resident in a rural area of The Gambia, using an ELISA to the repeat peptide (NANP)40. The prevalence and titre of antibodies varied with age but not with sex or ethnic group. Significant variations in prevalence were recorded within a group of adjacent villages. Children who were seropositive at the beginning of the dry season had higher spleen and parasite rates both at this time and at the end of the subsequent rainy season than did seronegative children, suggesting that they were exposed more frequently to infection. However, seropositive children had fewer episodes of fever accompanied by high levels of parasitaemia than did seronegative children, suggesting that they had a greater degree of clinical immunity. No differences were found in seroprevalence rates or in mean antibody titres between children who slept under conventional or Permethrin treated bed nets and those who did not, even though bed nets significantly reduced the number of bites by vector mosquitoes.

Age Factors↗