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Biomedical subjects

J Murray

Publications and source records attributed to J Murray.

At least 217 records · Page 12Linked to original sources
PubMed1996

Mode of pulsatile follicle-stimulating hormone secretion in gonadal hormone-sufficient and -deficient women--a clinical research center study.

To test the hypothesis that FSH is secreted at least in part within discrete secretory bursts in women and that the characteristics of episodic FSH secretion are altered within differing gonadal hormone environments, we measured FSH by immunoradiometric assay every 10 min for 24 h in premenopausal women during the early follicular (EF), late follicular (LF), and midluteal (ML) phases of the menstrual cycle and in postmenopausal (PM) women (n = 8 in each group). Secretory events were evaluated using multiparameter deconvolution. FSH was secreted in an episodic manner, with the number of secretory bursts (per 24 h; mean +/- SEM) detected in LF (20 +/- 0.79) and PM (20 +/- 0.90) women being greater than that in EF (16 +/- 0.88) and ML (14 +/- 0.93) women. FSH secretory burst mass (milliinternational units per mL) was significantly higher in PM (12 +/- 1.6) than in EF (1.8 +/- 0.21), LF (3.1 +/- 1.3), or ML (0.8 +/- 0.11) women and primarily reflected a relative increase in the maximal secretory rate rather than increased burst half-duration. The estimated half-life (minutes) of endogenous FSH in LF women (155 +/- 18) was shorter than those calculated in EF (251 +/- 24), ML (277 +/- 38), and PM (231 +/- 18) women. Cross-correlation analysis showed strongly positive associations between successively paired serum FSH and LH concentrations in all four groups of women. Deconvolution of simultaneously obtained LH concentration-time series revealed statistically significant concordance (13-25%) between FSH and LH secretory episodes at a lag time of 0 min in EF, LF, and PM women and when LH secretory bursts led FSH secretory bursts by 10 min in ML phase women. However, as 75-87% of FSH and LH secretory pulses were discordant, we infer the operation of distinct control mechanisms in the generation of FSH and LH release episodes. In summary, these results suggest that FSH is secreted within discrete secretory bursts in women, that the mass and frequency of FSH secretory bursts differ in women exhibiting various gonadal hormone environments, and that FSH and LH secretory bursts occur coincidentally at a higher rate than expected on the basis of chance alone, but at such a low overall rate of concordance that distinct mechanisms probably operate to direct episodic FSH and LH secretory activity.

Adult↗
PubMed1996

Use of large databases for resolving critical care problems.

Large databases allow for rapid access to large volumes of data. To convert raw data to information, large numbers of data points must be correlated into a descriptive pattern that can be interpreted by the user. Databases must be constructed so as to allow reliable extraction of the raw data into a format that supports analysis of events in a meaningful, objective, and reproducible manner. Databases must be responsive to a variety of users. They must not demand unrealistic amounts of effort on those responsible for data entry. Standard protocols in various stages of development will make databases easier to use and more reliable. Database management tools such as the Internet and the National Library of Medicine will become more integrated into the practice of critical care medicine at all levels, including administration, clinical care, and research. This article provides an overview of the capabilities and difficulties associated with large databases. The major areas of use of large databases in the hospital setting are administration, bibliographic, patient care, research, and education. Each of these areas has different requirements and is supported by different types of databases. The advantages and disadvantages of linear, relational, and object-oriented databases are discussed. Issues relating to methods of data entry and the accuracy and reliability of data are discussed. The challenges involving integration of various sources of data and the interfacing of devices are reviewed.

Critical Care↗
PubMed1995

Intracellular localisation of herpes simplex virus type 1 ribonucleotide reductase subunits during infection of cultured cells.

We have analysed the intracellular localisation of herpes simplex virus type 1 ribonucleotide reductase during infection of cultured cells by indirect immunofluorescence using polyclonal and monoclonal antibodies specific for the R1 and R2 subunits. Three different viruses were used to infect cells, wild-type strain 17+ and two temperature-sensitive mutants, ts 1222, which produces R1 only, and ts 1207, which expresses a normal R2 and an altered R1 that fails to interact with R2 at the nonpermissive temperature because of an amino acid substitution in R1. R1 was detected 2 hr postinfection with all three viruses and remained evenly distributed throughout the cytoplasm. R2 was not observed until 4 hr postinfection and, in contrast to the even distribution of R1, was localised in discrete cytoplasmic foci close to the nucleus. In double-labelling experiments both R1 and R2 were found in these foci where they presumably associate to form the active enzyme. As expected R2 was not detectable in cells infected with ts 1222. In ts 1207-infected cells it formed wild-type-like foci, indicating that interaction with R1 is not required for R2 focus formation. R1 was present in a twofold excess over R2 in wild-type-infected cells. We suggest that the uncomplexed R1 could perform a role associated with the protein kinase present in the N-terminal domain.

Amino Acid Sequence↗
PubMed1995

The superficial femoral vein. A potentially lethal misnomer.

OBJECTIVE: To assess the potential for error in interpretation of venous duplex reports that use the term "superficial femoral vein." DESIGN: Three surveys conducted by mail. SETTING: Three multispecialty medical groups, anatomy departments of all US medical schools, and vascular laboratories. PARTICIPANTS: A total of 46 family practitioners and general internists, 95 chairpersons of departments of anatomy, and 85 laboratory directors. MAIN OUTCOME MEASURES: Proposed treatment of a patient with leg pain and an acute thrombosis of the superficial femoral vein; what nomenclature(s) for the deep thigh veins is (are) felt to be correct, what are acceptable alternatives, what is taught to students and which is preferred; and what terminology is being used in lower limb venous duplex reports. RESULTS: Only 24% (11/46) of the respondents would have administered anticoagulants to the patient as described. Only 3% (3/95) of anatomists felt the term "superficial femoral vein" was correct, 22% (21/95) felt it was an acceptable alternative (though only 9% [9/95] taught it to medical students), and only 7% (7/95) of anatomists felt the term was preferred for everyday use. The term "superficial femoral vein" is used by 93% (79/85) of vascular laboratories in lower limb venous duplex reports. CONCLUSION: Although the overwhelming majority of vascular laboratories use the term "superficial femoral vein" in venous duplex reports, the use of this term is potentially hazardous to patients. Most primary care physicians have not been taught and are not aware that the superficial femoral vein is a deep vein and that acute thrombosis of this vessel is potentially life threatening.

Family Practice↗
PubMed1995

A multicenter, double-blind, placebo-controlled trial of aprotinin for reducing blood loss and the requirement for donor-blood transfusion in patients undergoing repeat coronary artery bypass grafting.

BACKGROUND: Aprotinin is a serine protease inhibitor that reduces blood loss and transfusion requirements when administered prophylactically to cardiac surgical patients. To examine the safety and dose-related efficacy of aprotinin, a prospective, multicenter, placebo-controlled trial was conducted in patients undergoing repeat coronary artery bypass graft (CABG) surgery. METHODS AND RESULTS: Two hundred eighty-seven patients were randomly assigned to receive either high-dose aprotinin, low-dose aprotinin, pump-prime-only aprotinin, or placebo. Drug efficacy was determined by the reduction in donor-blood transfusion up to postoperative day 12 and in postoperative thoracic-drainage volume. The percentage of patients requiring donor-red-blood-cell (RBC) transfusions in the high- and low-dose aprotinin groups was reduced compared with the pump-prime-only and placebo groups (high-dose aprotinin, 54%; low-dose aprotinin, 46%; pump-prime only, 72%; and placebo, 75%; overall P = .001). The number of units of donor RBCs transfused was significantly lower in the aprotinin-treated patients compared with placebo (high-dose aprotinin, 1.6 +/- 0.2 U; low-dose aprotinin, 1.6 +/- 0.3 U; pump-prime-only, 2.5 +/- 0.3 U; and placebo, 3.4 +/- 0.5 U; P = .0001). There was also a significant difference in total blood-product exposures among treatment groups (high-dose aprotinin, 2.2 +/- 0.4 U; low-dose aprotinin, 3.4 +/- 0.9 U; pump-prime-only, 5.1 +/- 0.9 U; placebo, 10.3 +/- 1.4 U). There were no differences among treatment groups for the incidence of perioperative myocardial infarction (MI). CONCLUSIONS: This study demonstrates that high- and low-dose aprotinin significantly reduces the requirement for donor-blood transfusion in repeat CABG patients without increasing the risk for perioperative MI.

Aged↗
PubMed1995

pH regulation of the F-actin binding properties of Dictyostelium elongation factor 1 alpha.

ABP50, an F-actin bundling protein from Dictyostelium, is also the protein synthesis co-factor, elongation factor 1 alpha (EF1 alpha). Concomitant with cAMP stimulation in Dictyostelium is a cytoplasmic alkalinization (Aerts, R. J., DeWit, R. J. W., and Van Lookeren Campagne, M. M. (1987) FEBS Lett. 220, 366-370) and a redistribution of EF1 alpha (Dharmawardhane, S., Demma, M., Yang, F., and Condeelis, J. (1991) Cell Motil. Cytoskel. 20, 279-288). In addition, others have shown a correlation between intracellular pH and the level of protein synthesis in Dictyostelium (Aerts, R. J., Durston, A. J., and Moolenaar, W. H. (1985) Cell 43, 653-657). The present study investigates the relationship between pH and the F-actin binding properties of EF1 alpha. We found that increasing pH over the physiological range 6.2-7.8 causes a loss of EF1 alpha-mediated F-actin bundling and single filament binding, with corresponding increases in the amount of free EF1 alpha in vitro. Similar results also were obtained by cell fractionation and confocal immunofluorescence microscopy. The EF1 alpha binding constant (Kd) for F-actin is increased from 0.2 microM to > 2.2 microM over the same pH range. In addition, EF1 alpha-induced actin bundle formation is freely reversible by changes in pH. Thus, pH may be a potent modulator of cytoarchitecture in Dictyostelium and may also influence mRNA translation rates by modifying the interactions between the protein synthetic machinery and the actin cytoskeleton.

Actins↗
PubMed1995

DNA and RNA content analysis by flow cytometry in the pathobiologic assessment of bone tumors.

Studies of simultaneous DNA and RNA contents by flow cytometry in hematologic and some solid neoplasms have been shown to provide information that may be useful in the pathobiological evaluation of these neoplasms. We contend that similar analysis may be equally valuable in assessing bone tumors. Our data revealed significant statistical differences in DNA ploidy and proliferative fraction between benign and malignant bone neoplasms. Benign tumors manifested predominantly DNA diploidy and low proliferative activity, whereas the majority of malignant tumors were DNA aneuploid and showed high proliferation rate. No significant difference in the RNA content between different histopathologic categories was found. We observed, however, a distinct and consistently high RNA content pattern in giant cell tumors, aneurysmal bone cysts, and chondroblastomas that may be useful in their differential diagnosis. Analysis of different prognostic factors in malignant tumors indicated that histologic grade and DNA content are a significant prognostic factors. Further analysis of malignant tumors showed that a correlation between the proliferative activity and the clinical outcome in the low grade category and between RNA content and patients' survival in osteosarcomas. Our study also showed that preoperative treatment significantly impacted on the extent of the proliferative fraction in malignant tumors. We conclude that DNA/RNA analysis of bone tumor may assist in: (1) the differential diagnosis of certain bone tumors, (2) evaluation of treatment response, and (3) the biological assessment of osteosarcomas.

Acridine Orange↗
PubMed1995

Prospective evaluation of a composite scoring system for mammographically detected cytologically assessed impalpable breast abnormalities.

The aim of all breast screening programmes is a reduction in deaths from the disease. It is hoped that this can be achieved with minimal intervention in the patient cohort who do not have cancer. In this study we have assessed the efficacy of a combination of mammographic and cytological scoring systems in the evaluation of 208 women with screen-detected non-palpable breast lesions. All mammograms were scored 1-5 and those with a score of 3 or more required needle localization. A cytology score of 1 to 5 was generated for each patient according to a similar system and an aggregate score for each patient was achieved by the addition of the mammographic and cytology score. Ninety-three of the 208 patients had malignancy--the positive predictive value for mammography alone in this series was 45%. All 58 patients who had an aggregate score of 8 or greater had cancer. The 60 patients who had an aggregate score of 4 had benign disease on excision biopsy. We suggest that a 'wait and repeat mammogram' approach is appropriate in patients with grade 3 mammography and benign (grade 1) cytology. Patients with an intermediate aggregate score of 5-7 should have an excision biopsy and those with an aggregate score of 8 could have definitive surgery rather than excision biopsy. Application of this aggregate scoring technique would enhance the delivery of more appropriate surgery to a majority of patients with screen-detected breast abnormalities.

Biopsy↗
PubMed1995

Beta spectrin PRAGUE: a truncated beta spectrin producing spectrin deficiency, defective spectrin heterodimer self-association and a phenotype of spherocytic elliptocytosis.

Spherocytic elliptocytosis is a phenotypic hybrid between hereditary spherocytosis (HS) and hereditary elliptocytosis (HE) characterized by the presence of spheroovalocytes and spherocytes which exhibit increased osmotic fragility, indicating a deficiency of surface area. Both the spherocytic red cell morphology and the increased osmotic fragility distinguish this clinical entity from common HE. In contrast to common HE, the molecular basis of spherocytic elliptocytosis is unknown. Here we describe two members of a family who both have the characteristic features of spherocytic HE. We show that the underlying defect involves a G to C transversion at the -1 position of the acceptor splice site upstream of exon X of beta spectrin leading to skipping of exon X from the mutant beta spectrin mRNA allele. The mutant mRNA is present in reticulocytes in similar amounts as the normal mRNA. Pulse-labelling of erythroblasts prepared from peripheral blood in a two-phase liquid-culture system reveals a decreased synthesis of the truncated beta spectrin, a finding which is likely to underlie the moderately severe spectrin deficiency in the two patients. In addition, this mutant spectrin, similar to the previously reported spectrins, is defective in spectrin heterodimer self-association. The spectrin deficiency, which represents a common finding in the majority of patients with HS, together with weakened spectrin heterodimer self-association, as found in the majority of patients with common HE, provides a molecular explanation for the phenotype of spherocytic elliptocytosis in this kindred and, most likely, in other patients carrying similar beta spectrin mutations.

Base Sequence↗
PubMed1995

Molecular basis of spectrin deficiency in beta spectrin Durham. A deletion within beta spectrin adjacent to the ankyrin-binding site precludes spectrin attachment to the membrane in hereditary spherocytosis.

We describe a spectrin variant characterized by a truncated beta chain and associated with hereditary spherocytosis. The clinical phenotype consists of a moderate hemolytic anemia with striking spherocytosis and mild spiculation of the red cells. We describe the biochemical characteristics of this truncated protein which constitutes only 10% of the total beta spectrin present on the membrane, resulting in spectrin deficiency. Analysis of reticulocyte cDNA revealed the deletion of exons 22 and 23. We show, using Southern blot analysis, that this truncation results from a 4.6-kb genomic deletion. To elucidate the basis for the decreased amount of the truncated protein on the membrane and the overall spectrin deficiency, we show that (a) the mutated gene is efficiently transcribed and its mRNA abundant in reticulocytes, (b) the mutant protein is normally synthesized in erythroid progenitor cells, (c) the stability of the mutant protein in the cytoplasm of erythroblasts parallels that of the normal beta spectrin, and (d) the abnormal protein is inefficiently incorporated into the membrane of erythroblasts. We conclude that the truncation within the beta spectrin leads to inefficient incorporation of the mutant protein into the skeleton despite its normal synthesis and stability. We postulate that this misincorporation results from conformational changes of the beta spectrin subunit affecting the binding of the abnormal heterodimer to ankyrin, and we provide evidence based on binding assays of recombinant synthetic peptides to inside-out-vesicles to support this model.

Ankyrins↗