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Biomedical subjects

M Pearce

Publications and source records attributed to M Pearce.

At least 37 records · Page 2Linked to original sources
PubMed1994

Bladder neck mobility and the outcome of surgery for genuine stress urinary incontinence. A logistic regression analysis of lateral bead-chain cystourethrograms.

Bladder neck position, as determined by preoperative and postoperative resting and straining lateral bead-chain cystourethrograms, was analyzed by logistic regression analysis in 94 women undergoing 98 operations for genuine stress incontinence. A total of 384 roentgenograms were analyzed in an attempt to build a model that would predict the likelihood of surgical success in a given patient based on the preoperative films and explain a successful surgical outcome based on the characteristics of the postoperative films. The most important predictors of success were the number of previous incontinence operations, a large distance between the bladder neck and the pubic symphysis at rest, and increased mobility of the bladder neck before surgery. Successful surgery appeared to be related most closely to decreasing mobility of a previously hypermobile bladder neck.

Female↗
PubMed1993

Dystrophin and related proteins.

During the past year significant progress has been made in understanding how dystrophin deficiency leads to muscle cell necrosis in Duchenne muscular dystrophy and Becker muscular dystrophy. Dystrophin interacts with a glycoprotein complex spanning the muscle sarcolemma, effectively linking the actin cytoskeleton to the extracellular matrix. The carboxyl terminus of dystrophin is required for glycoprotein binding. Interestingly, at least three mRNAs transcribed from the distal end of the DMD gene in tissues other than muscle have been shown to encode this domain. Deficiency of a second component of the dystrophin-associated glycoprotein complex has been shown to occur in another muscle-wasting disorder, severe childhood autosomal recessive muscular dystrophy. Sequence analysis of the entire cDNA for the autosomal dystrophin-related protein utrophin has shown that dystrophin and utrophin are closely related. Furthermore, both of these proteins have been shown to bind to the same or a similar glycoprotein complex in muscle.

Animals↗
PubMed1993

The utrophin and dystrophin genes share similarities in genomic structure.

Utrophin and dystrophin are highly homologous proteins which are reciprocally expressed in DMD (Duchenne muscular dystrophy) muscle. The remarkable similarity of these proteins suggests that they may play a similar cellular role in some circumstances; if this were the case then utrophin may be capable of replacing dystrophin in DMD patients. In this paper we show that the genomic structure of the utrophin gene is similar to the dystrophin gene, further exemplifying the relatedness of the two genes and their gene products. We have constructed a 1.25 Mb contig of eight yeast artificial chromosome (YAC) clones covering the utrophin gene located on chromosome 6q24. Utrophin is encoded by multiple small exons spanning approximately 900 kb. The distribution of exons within the genomic DNA has similarities to that of the dystrophin gene. In contrast to dystrophin, the utrophin gene has a long 5' untranslated region composed of two exons and a cluster of unmethylated, rare-cutting restriction enzyme sites at the 5' end of the gene. Similarities between the genomic structure suggest that utrophin and dystrophin arose through an ancient duplication event involving a large region of genomic DNA.

Base Sequence↗
PubMed1993

Removal of inhaled plutonium and americium from the rat by administration of ZnDTPA in drinking water.

This study has examined the efficacy of ZnDTPA administered in drinking water for removing 238Pu and 241Am from the rat after their simultaneous inhalation as nitrates; the dosage used was 95 mumol kg-1d-1. The continuous administration of ZnDTPA over a 14 d interval, commencing 1 h after exposure, reduced the lung and total body contents of 238Pu to, respectively, 11% and 18% of those in untreated rats; the corresponding values for 241Am were 11% and 14%. After the continuous administration of 95 mumol kg-1 from 4 d to 28 d post exposure, the lung and total body contents of 238Pu were, respectively, 5% and 16% of those in controls; the corresponding values for 241Am were 7% and 19%. Further reductions in the actinide contents of body tissues were found when treatment was extended to 52 d or 76 d. These regimens were as effective as twice weekly injections of 30 mumol kg-1 ZnDTPA commencing at 4 d. After the continuous administration of 95 mumol kg-1 d-1 for 72 d, some pathological changes to the gastrointestinal tract were observed but these were considered to be reparable. It was concluded that further work is required to evaluate the toxicity of the ligand and to establish the optimal treatment regimen.

Administration, Inhalation↗
PubMed1992

The efficacies of 3,4,3-LIHOPO and DTPA for enhancing the excretion of plutonium and americium from the rat: comparison with other siderophore analogues.

With DTPA as a comparison, the siderophore analogue code named 3,4,3-LIHOPO has been tested for its ability to remove 238Pu and 241Am from rats after their inhalation or intravenous injection as nitrate. The most effective treatment regimen for inhaled Pu was the repeated administration of 30 mumol kg-1 3,4,3-LIHOPO. By 7 days after exposure, the Pu contents of the lungs and total body were reduced respectively to 2 and 4% of those in untreated animals. These values were six and three times less than when DTPA was administered using the same protocol. For inhaled Am, 3,4,3-LIHOPO and DTPA were considered equally effective, the lung and total body contents being reduced respectively to 13 and 10% of those in controls. Some animals showed slight degenerative changes in the liver and proximal tubules of the kidneys after the repeated administration of 30 mumol kg-1 of 3,4,3-LIHOPO; however these changes were less marked than after DTPA treatment. After the intravenous injection of Pu, the most effective regimen was the single administration of 3 mumol kg-1 3,4,3-LIHOPO. The body content at 7 days was reduced to 7% controls compared with 19% after the repeated administration of 30 mumol kg-1 DTPA. At a dosage of 30 mumol kg-1, 3,4,3-LIHOPO was less effective owing to the higher retention of Pu in the liver. With repeated dosages of 30 mumol kg-1 3,4,3-LIHOPO was more effective than DTPA for the decorporation of Am; the body contents were 16 and 31% of those in controls respectively. Importantly, the body content was still reduced to 28% of control after a single administration of 3 mumol kg-1. The ligand 3,4,3-LIHOPO, which is also superior to other siderophore analogues, could represent a most significant development in the decorporation of Pu and Am.

Administration, Inhalation↗
PubMed1992

Anti-IL-6 antibodies suppress myeloid cell production and the generation of CFU-c in long-term bone marrow cultures.

Interleukin 6 (IL-6) is one of several hemopoietic growth factors produced by stromal cell lines derived from the adherent layer of long-term bone marrow cultures (LTBMCs). To evaluate the potential role of IL-6 in stromal cell-dependent myelopoiesis, we established LTBMCs and verified that IL-6 mRNA is transcribed by heterogeneous adherent cell layers and that IL-6 protein is present in culture supernatants. Established LTBMCs were then depleted of IL-6 by using a specific neutralizing monoclonal antibody (mAb). Cultures treated for 2-3 weeks with anti-IL-6 mAb showed decreased production of maturing myeloid cells and colony-forming progenitor cells (colony-forming units in culture, CFU-c) but not stem cells (spleen colony-forming units, CFU-s). In parallel experiments, it was also found that the addition of IL-6 to LTBMCs stimulated a marked increase in total cell production, CFU-c, and day-8 CFU-s. In sum, it appears that endogenous production of IL-6, although limiting, is essential for the normal level of myelopoiesis associated with stromal cell function in LTBMCs.

Animals↗
PubMed1990

Role of endogenously produced interleukin-6 as a second signal in murine thymocyte proliferation induced by multiple cytokines: regulatory effects of transforming growth factor-beta.

Previous studies have demonstrated that murine thymocytes proliferate in the presence of submitogenic concentrations of phytohemagglutinin-P (PHA-P) and various cytokines such as interleukin-1 (IL-1), interleukin-4 (IL-4), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). We report that C3H/HeJ thymocytes stimulated with PHA-P and IL-1, IL-4, or TNF-alpha secrete significant levels of IL-6 as determined on B9 hybridoma cells. The possibility that thymocyte proliferation induced by these cytokines was mediated through IL-6 was investigated utilizing a neutralizing monoclonal antibody against murine IL-6, MP5 20F3.1. The results demonstrate that MP5 20F3.1 inhibited the proliferative response of thymocytes and B9 hybridoma cells to recombinant MuIL-6 (but not HuIL-6) and neutralized the endogenous IL-6 produced in the thymocyte cultures, but did not have any measurable effects on the proliferative responses induced by IL-1, IL-4, or TNF-alpha. Although the level of endogeneously produced IL-6 did not play a measurable role in the proliferative response induced by TNF-alpha, the addition of higher concentrations of IL-6 augmented the proliferation of murine thymocytes induced by rMu TNF-alpha. In addition, recombinant human transforming growth factor-beta 1 (rHu TGF-beta 1) significantly inhibited thymocyte proliferation induced by HuIL-1, rMuIL-4, rMuIL-6, and rMuTNF-alpha. The studies suggest that IL-1, IL-4, or TNF-alpha mediate a proliferative signal on murine thymocytes independent of IL-6 and that the proliferative signals provided by these cytokines as well as IL-6 are inhibitable by rHu TGF-beta 1.

Animals↗
PubMed1990

Production of cytokines by mouse B cells: B lymphomas and normal B cells produce interleukin 10.

We have examined a panel of murine Ly-1+ B lymphomas and purified normal murine peritoneal B cells separated into subsets on the basis of expression of the Ly-1 surface antigen, for their ability to produce cytokines. Where possible, we have used a combination of cytokine detection methods in order to compensate for differences in sensitivity and specificity, and the possibility of inhibitors masking an activity. All the lymphomas tested were shown to constitutively express TGF-beta and CSIF/IL-10. In addition, varying levels of IL-6, TNF-alpha and TNF-beta, and G-CSF, were demonstrable in most of the lymphomas, and variants of one lymphoma (CH12) additionally produced varying levels of IL-3, IL-4, and GM-CSF. FACS purified normal Ly-1+ and Ly-1- peritoneal B cells, were also shown to express RNA encoding CSIF/IL-10, IL-6, TNF-alpha and TNF-beta, and very low levels of G-CSF, following stimulation with LPS. These data were supported by the detection of IL-6 and CSIF/IL-10 in supernatants from LPS-stimulated Ly-1+ and Ly-1- B cells using specific immunoassays. None of the lymphomas or B cell preparations produced IL-1 alpha, IL-2, IL-5, IL-7, or IFN-gamma. The purity of our normal B cell populations was assessed by phenotypic analysis on the FACS and also by the disappearance of certain mRNA transcripts after purification, e.g. CD4, c-fms, GM-CSF, and IFN-gamma, most of which could be detected in LPS-stimulated total peritoneal cell populations. This suggested that our B cell purification method had reduced, to a level undetectable in our assays, contaminating T cells (CD4), macrophages (c-fms, GM-CSF), and NK cells (IFN-gamma). Absence of IL-3, IL-4, IL-5, and GM-CSF expression by LPS-stimulated Ly-1+ and Ly-1- B cells reduced the concern that contaminating peritoneal mast cells could account for the observed cytokine production. We therefore believe our data provide strong support for production of a subset of cytokines by LPS-stimulated normal B cells. Both the Ly-1+ B lymphomas and normal Ly-1+ and Ly-1- B cells appear capable of expressing IL-6, TNF-alpha, TNF-beta, and CSIF/IL-10.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Comparison of ultrasound and lateral chain urethrocystography in the determination of bladder neck descent.

Several methods exist to determine the position of the bladder neck, an important mechanism of urinary continence. Radiologic screening is widespread but involves irradiation and may be imprecise. We compared perineal ultrasound scanning and radiologic scanning of the bladder neck by use of a chain and catheter and found good correlation between the two techniques. Ultrasound scanning is preferred, as it avoids irradiation, is accurate, is portable, and is readily available in most gynecologic departments.

Catheterization↗
PubMed1989

Program on the Surgical Control of the Hyperlipidemias (POSCH): design and methodology. POSCH Group.

The Program on the Surgical Control of the Hyperlipidemias (POSCH) is a prospective, randomized, controlled, multi-center, secondary, atherosclerosis intervention trial. POSCH addresses the therapeutic arm of the lipid-atherosclerosis theory, i.e. whether lowering of plasma cholesterol is directly related to a reduction in atherosclerosis risk. In this trial, lipid modification is accomplished by the partial ileal bypass operation. Between 1975 and 1983, 838 patients were randomized into this study. All patients were between 30 and 64 years of age, had survived one and only one electrocardiogram and enzyme-documented myocardial infarction, and had a total plasma cholesterol of at least 220 mg/dl or a low density lipoprotein (LDL)-cholesterol of at least 140 mg/dl if the total plasma cholesterol was between 200 and 219 mg/dl after a minimum of 6 weeks of dietary fat and cholesterol restriction. The primary response variable in POSCH is overall mortality. Secondary endpoints include fatal and non-fatal myocardial infarctions, serial electrocardiographic changes, and, most importantly, sequential coronary arteriography changes. The minimum follow-up is currently planned to be 7 years. Study analyses will be made primarily on the "intention to treat" basis. This paper is the first detailed presentation of POSCH design and methodology. Included are descriptions of study design, implementation, and data collection, including data processing, quality assurance/quality surveillance, and patient safety monitoring. POSCH seeks to demonstrate a significant reduction in overall mortality by lipid modification and to validate the use of coronary arteriographic change as a surrogate endpoint for change in coronary heart disease risk.

Adult↗
PubMed1988

Using a symbiotic man/machine approach to evaluating visual clinical research data.

Some candidate medical expert system applications have a significant visual component. Knowledge engineers usually dismiss such task domains as potential expert systems applications. Our success in developing ESCA, a system for evaluating serial coronary angiograms, shows that such task domains should not be dismissed so quickly. We used a symbiotic approach between man and machine, where technologists provide the visual skills with an expert system imitating the conceptual skills of the expert, to produce a partially automated system that is more consistent and cost effective than one that is fully manual. The agreement between the system's conclusions and that of a panel of experts is good. The expert system actually has a slightly higher agreement rate with the expert panel than the agreement rate between two expert panel teams evaluating the same film pair.

Angiocardiography↗
PubMed1988

Frequency of in vitro resistance of Pseudomonas aeruginosa to cefepime, ceftazidime, and cefotaxime.

The selection frequencies of cefepime (BMY 28142), ceftazidime, and cefotaxime resistance among Pseudomonas aeruginosa strains were determined. Cefepime-resistant mutants were not selected by cefepime (frequency, less than 10(-11)). Ceftazidime- and cefotaxime-resistant mutants were isolated at frequencies of 10(-5) to 10(-10) and were often cross-resistant. However, cefepime resistance among ceftazidime- and cefotaxime-resistant mutants was rare. Selected mutants resistant to cefepime constitutively produced 40- to 450-fold more beta-lactamase than did the parent strain.

Cefepime↗
PubMed1987

Ultrasound scanning in women with raised serum alpha fetoprotein: short term psychological effect.

Thirty pregnant women with raised serum alpha fetoprotein (AFP) were interviewed before and after they received real-time ultrasound scanning to further diagnose fetal abnormalities. Thirty pregnant mothers receiving routine ultrasound scanning for dates served as the controls. The 'at risk' group were more anxious and concerned about the fetus before the scan. There was a greater reduction of state-anxiety following scanning in the raised AFP group than for the controls. Similar changes were found in the attitude towards the fetus, pregnancy and fetus' health between the risk and control subjects.

Adaptation, Psychological↗