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Biomedical subjects

J Wheeler

Publications and source records attributed to J Wheeler.

At least 55 records · Page 3Linked to original sources

Tissue distribution of amyloid P component as defined by a monoclonal antibody produced by immunization with human glomerular basement membranes.

A monoclonal antibody reactive against amyloid P component (NCL-AMP) has been developed following immunization of mice with partially-purified human glomerular basement membranes (GBM) and standard hybridization and cloning techniques. The antibody reactivity was evaluated by enzyme-linked immunosorbent assay (ELISA) and by the indirect immunoperoxidase technique on sections of frozen and fixed human kidney and other tissues. The distribution of amyloid P component in various normal tissues is described and the possible co-localization with the Goodpasture antigen is discussed. In addition, the suitability of the antibody for detection of amyloid deposits in renal amyloidosis is demonstrated and its potential for use in other pathological conditions is considered.

Animals↗

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↗

Multidisciplinary treatment results for patients with isolated cleft palate.

Fifty-eight patients with cleft palate only who had received treatment in the Department of Otolaryngology-Head and Neck Surgery at the University of Iowa were examined for treatment results. Forty-one (70.7 percent) of the 58 patients showed a syndrome or suggestive factors. An unusually high percentage (36 percent) of the 58 patients required secondary surgery for velopharyngeal dysfunction or showed indications for surgery at examination. Some but not all of the relatively low success rate appears related to surgical experience. Speech proficiency, hearing acuity, and dental status were within normal limits or nearly so. The 20 patients with pharyngeal flap surgery were doing well, with minimal indications of functional obstruction.

Adolescent↗

Anti-glomerular basement membrane glomerulonephritis (anti-GBM GN) in the mouse: BrdU-labelling indices and histological damage.

In-vivo BrdU incorporation and visualization by immunohistochemistry, previously reported in normal mouse kidney, were applied to a mouse model of anti-GBM GN, induced by immunization with rabbit anti-mouse GBM antiserum, to assess the contribution of capsular cell proliferation in the development of crescents. A significant increase (P = 0.003) in the BrdU-labelling index (LI) for capsular cells was observed, as compared to normal mice (5.76 +/- 1.1 vs 0.70% +/- 0.12%). Elevated LI were also observed for tuft and tubular cells but these increases were not statistically significant. It was concluded that, in this model, capsular cell proliferation is a major contributory factor to the formation of cellular crescents. In addition, other pathological features, indicative of glomerular damage, were assessed semi-quantitatively alongside numbers of labelled capsular cells per glomerulus. It was found that podocyte vacuolation is strongly associated with, and may precede, proliferation, suggesting some common causative factor. Fibrin, when present, was confined within the tuft capillary loops and was only weakly associated with either podocyte vacuolation or capsular cell proliferation. It was concluded that this protein does not play a major role in the initiation of pathological damage. Finally, glomerular lesions were found to be randomly distributed. Thus, the idea of intraglomerular signalling, resulting in 'clustering' of damaged glomeruli, is not supported.

Animals↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Routine and rapid enzyme linked immunosorbent assays for circulating anti-glomerular basement membrane antibodies.

Microtitre plate modifications of the original tube enzyme linked immunosorbent assay (ELISA) of Wheeler and Sussman were used for the routine and rapid assays of anti-glomerular basement membrane antibodies in human sera. In a prospective study of 238 sera from 200 patients, the routine assay (about 24 hours) detected circulating antibodies in seven sera from three patients with active anti-glomerular basement membrane disease. The remaining sera, from patients with a variety of other glomerulonephropathies, were negative by the assay. The rapid assays took less than four hours, and in a retrospective study, detected anti-glomerular basement membrane antibodies in a range of 15 positive sera, with a level of discrimination similar to that observed in the routine assay and with no false positive/negative results.

Antibodies↗

Carbon dioxide-insufflated colonoscopy: an ignored superior technique.

Colonoscopy and barium enema are complementary studies in the diagnosis of the cause of lower intestinal bleeding. The air usually insufflated during colonoscopy often makes it impossible to perform a good barium enema on the same day. As a possible solution to this problem, we studied the quality of barium enemas performed immediately following carbon dioxide-insufflated colonoscopy. All 15 patients who underwent unsuccessful total colonoscopies using carbon dioxide insufflation were able to have barium enemas performed the same day in contrast to only one out of 15 patients who had air-insufflated colonoscopy. In a survey of all hospitals in Illinois with 150 beds or more, we found only 15 of 146 hospitals used carbon dioxide for colonoscopy insufflation. We recommend the routine use of carbon dioxide for colonoscopic insufflation not only for greater safety and comfort for the patient, but also for the convenience and cost savings.

Adult↗