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Biomedical subjects

D Murray

Publications and source records attributed to D Murray.

At least 271 records · Page 15Linked to original sources

Immunocytochemistry of renin in renal tumours.

We used a panel of two polyclonal antisera and two monoclonal antibodies to human renin to assess the tissue distribution of immunoreactive renin in a range of tumours and normal human tissues. The only tissue showing positive staining for renin was kidney and all four antisera stained the myoepithelioid cells in the renal cortex. In the survey of tumours we found immunoreactive renin only in renal tumours, namely, renal cell carcinoma, and nephroblastoma (Wilms' tumour). The renin-positive cells were sparse and distributed mainly along the course of the tumour blood vessels. They stained positively with all four antibodies and, in pairs of serial sections, we showed that the same cell reacted with two different antisera. This suggests that renal cell carcinoma and nephroblastoma have within them cells which contain renin.

Antibodies, Monoclonal↗

Pulsed Doppler and two-dimensional echocardiography: comparison of halothane and isoflurane on cardiac function in infants and small children.

The combination of two-dimensional and pulsed Doppler echocardiography was used to measure determinants of cardiac function in 20 ASA physical status I infants and small children (9 days-32 months of age) during equipotent halothane (n = 10) or isoflurane (n = 10) anesthesia in oxygen. Five sets of cardiovascular data were recorded in each patient. In the awake, unmedicated state prior to induction, at three different anesthetic levels, 0.75, 1.0, and 1.25 MAC (corrected for age) and a final measurement repeated at 1.25 MAC after the intravenous infusion of 15 ml X kg-1 of Lactated Ringers solution. The study was completed prior to intubation and surgery. Results are expressed as mean +/- SEM. Isoflurane and halothane decreased mean blood pressure from the awake level (isoflurane 76.6 +/- 2.3 to 60.6 +/- 3.1 mm, halothane 72.2 +/- 3.9 to 60.6 +/- 3.1 mm at 1.25 MAC). Isoflurane increased heart rate at all anesthetic levels (128.7 +/- 4.2 to 142.5 +/- 6.0 beats/min at 0.75 MAC). Halothane decreased heart rate at 1.25 MAC (124.6 +/- 4.6 to 119.4 +/- 3.5 beats/min). Isoflurane and halothane decreased cardiac index at 1.25 MAC. Stroke volume index decreased at 1.0 and 1.25 MAC with both isoflurane (36.9 +/- 3.8 to 30.2 +/- 3.5 ml/m2) and halothane (32.7 +/- 2.5 to 28.9 +/- 2.5 ml/m2). Ejection fractions also decreased significantly at 1.0 and 1.25 MAC in both groups of patients (22 +/- 6% at 1.25 MAC halothane and 28 +/- 8% at 1.25 MAC isoflurane).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Differential repair of gamma-ray-induced DNA strand breaks by various cellular subpopulations of mouse jejunal epithelium and bone marrow in vivo.

We have examined the induction and repair of gamma-ray-induced DNA strand breaks in different subpopulations of cells in mouse jejunal epithelium and bone marrow using a modification of the alkaline elution methodology whereby different populations of cells are selectively labeled with radioactive DNA precursors. Mice were labeled by intraperitoneal injection with between 0.5 and 2.0 mu Ci/g of [3H]thymidine at various times prior to irradiation with 10 Gy of gamma rays. In the studies with jejunal epithelium, the timing of the injection of the radiolabel relative to the irradiation was varied between 6 and 72 h, depending on the cell population of interest. The DNA damage and repair characteristics representative of both the total cell population and the radiolabeled fraction of these cells were then measured. Little difference was noted in the amount of initial damage induced in these different populations of cells. However, for both the jejunum and bone marrow, cells that incorporated the radiolabel within 6 h after injection (i.e., rapidly proliferating cells) repaired their strand breaks more rapidly than did the remainder of the population. In the case of jejunum, the repair capacity of the radiolabeled cell population progressively diminished as the cells matured and differentiated so that cells that contained the radiolabel 72 h after injection (i.e., mature villus cells) actually repaired their strand breaks more slowly than did the bulk cells.

Animals↗

Effect of 3-aminobenzamide on DNA strand-break rejoining and cytotoxicity in CHO cells treated with hydrogen peroxide.

The influence of the nuclear ADP-ribosyltransferase inhibitor 3-aminobenzamide on the DNA strand-break rejoining kinetics and cytotoxicity in Chinese hamster ovary cells following H2O2 treatment was investigated. For the DNA damage studies, cells were treated on ice with H2O2 (0-20 microM) for 1 h in serum-free medium, after which the H2O2 was removed and the cells were allowed to repair their damage in complete medium at 37 degrees C in the presence or absence of 3-aminobenzamide (5 mM) for periods up to 2 h. The DNA strand breaks remaining as a function of time were then estimated by alkaline elution. A linear relationship between the H2O2 concentration and the initial level of DNA single-strand breaks (zero time allowed for repair) was observed. No double-strand breaks or DNA-protein cross-links were detected at these doses. The rejoining of single-strand breaks after H2O2 (20 microM) alone was characterized by a single exponential process with a t1/2 of approx. 5 min. However, in the presence of 3-aminobenzamide, rejoining was much slower and biphasic, with t1/2 of approx. 10 and 36 min. The inhibitory action of 3-aminobenzamide was concentration-dependent and completely reversible in that, when the 3-aminobenzamide was removed from the treated cultures, the strand-break rejoining kinetics rapidly returned to the t1/2 of 5 min typical of H2O2 alone. Considerably higher concentrations of H2O2 (up to 600 microM) were required for cell killing compared to the DNA damage studies. Cell killing by H2O2 alone was characterized by a shoulderless, exponential survival curve (D0 = 880 microM). The cytotoxicity was potentiated when the cells were treated with 3-aminobenzamide (5 mM) for 1 h after the H2O2 treatment; the survival curve with 3-aminobenzamide also assumed a biphasic character (D0 of 212 microM and 520 microM). These results are consistent with the theory that OH.-induced single-strand breaks do not normally represent lethal lesions to the cell because of their rapid, efficient repair. However, interference with these repair processes (in this case by 3-aminobenzamide) can alter this relationship, possibly allowing lesion fixation.

Animals↗

Central haemodynamics in acute myocardial infarction in relation to mortality and peak enzyme activity.

The relation of central haemodynamic changes to subsequent mortality and peak enzyme activity was investigated in 190 patients with acute myocardial infarction. The mean delay time from onset of symptoms to the haemodynamic study was 7.2 hours. Major exclusion criteria were heart rate less than 65 beats min-1, systolic blood pressure less than 105 mmHg and lung rales to a distance of greater than 10 cm above the lung bases. Nine patients (4.7%) died within 15 days and 16 patients (8.4%) within 90 days after the infarction. Compared to survivors, non-survivors were characterized by baseline depression of cardiac index, stroke volume index and left ventricular stroke work index, while pulmonary capillary wedge pressure and peripheral resistance were increased. However, a wide overlap between survivors and non-survivors makes the predictive value low in the individual patient. Peak serum aspartate aminotransferase (S-ASAT) activity was weakly related to baseline pulmonary capillary wedge pressure (r = 0.28; P less than 0.001) and stroke volume index (r = -0.22; P less than 0.01). The correlation to pulmonary capillary wedge pressure was only found in anterior (r = 0.34) infarcts. Peak serum lactate dehydrogenase (LD1) was not correlated with baseline haemodynamics.

Aged↗

Growth factor and cytogenetic abnormalities in cultured nevi and malignant melanomas.

It has been proposed that benign nevi that fail to differentiate normally may undergo stepwise growth and morphologic changes resulting in progression toward dysplastic nevi, which in some cases progress into malignant melanoma. In this study, we sought to determine the relationship between production of endogenous growth factors and the appearance of chromosomal abnormalities in cultured nevi and melanomas. Newly established cultures from 8 nevi with benign histology and 6 malignant melanomas, and 2 malignant melanoma cell lines were studied. Assays for mitogenic growth factors were based on stimulation of [3H]thymidine incorporation into DNA in Hs0294 malignant melanoma cells, produced by serum-free conditioned medium from nevus or melanoma cultures. Karyotypes were examined in cultures of an equivalent passage. Three of the 8 nevus cultures were mitogen-negative and displayed normal karyotypes; one nevus culture was mitogen-positive and had a normal karyotype, although the biopsied tissue demonstrated histologic evidence of benign melanocytic proliferation; one was mitogen-negative initially, but had an extra chromosome 8 in 2 of 50 cells; 3 were mitogen-positive and chromosomally abnormal. Each of the cultures in this latter group exhibited reciprocal translocation (rcpt) as the only identifiable abnormality [rcpt(6;15), rcpt(10;15), rcpt(15;20)], or a constitutional rcpt(4;5). Thus, there was direct correlation between growth factor production and chromosome abnormality in 6 of 8 benign nevus cultures. In the newly established melanoma cultures there was also concordance between growth factor and chromosomal status; conditioned media from 4 of 6 were mitogen-positive by at least one assay, and all 4 of the mitogen-positive cultures had chromosomally abnormal cell populations. Of the 2 melanoma cultures negative for growth factors, one was also negative for chromosome abnormality; the other had chromosomal change consisting of increased polyploidy. Both melanoma cell lines had abnormal karyotypes and were mitogen-positive. Though numerous chromosome changes were noted in the karyotypically abnormal melanoma cells, 6 of the 8 cultures exhibited abnormalities in chromosomes 1, 6, and/or 7. These data suggest that steps in the progression from benign nevi toward dysplastic nevi or malignant melanoma include: proliferation resulting from altered production of endogenous mitogenic growth factors; and development of specific chromosomal abnormalities.

Cells, Cultured↗

Population strategies to enhance physical activity: the Minnesota Heart Health Program.

A population-wide, community-based program in cardiovascular disease prevention, the Minnesota Heart Health Program (MHHP), has been designed to promote more frequent and vigorous physical activity in North American communities, along with improved eating and smoking patterns. The physical activity component of this broad-based education strategy is based on the facilitation which physical activity provides to lowering of other risk characteristics for heart disease and its enhancement of other healthy behaviors and on the potential for prevention of elevated risk in the first place. The rationale for a population strategy to complement medical approaches to prevention is that exercise patterns are largely socially learned and culturally determined. The MHHP Physical Activity Program is implemented through three major education strategies: direct education, community organization, and mass communications. Early results from this 10-year project indicate that it is feasible to enter U.S. communities and to involve their leadership actively in MHHP activities of health promotion. Moreover, attitudes, knowledge, awareness, participation, and behaviors related to exercise and eating patterns appear to be changed by the program. Nevertheless, there are problems in the design, implementation, analysis and interpretation of population changes in physical activity and other health behaviors in community demonstration programs. These issues, along with their solutions, should provide useful information for medical science and for the public health about population strategies of disease prevention and health promotion.

Adolescent↗

Microscopic peliosis of pancreatic islets in a woman with MEN-1 syndrome.

We report herein a case of histologically identified peliosis of pancreatic islets in the surgically removed portion of the pancreas of a 30-year-old woman with multiple endocrine neoplasm, type 1 (MEN-1) syndrome. In addition to microscopic peliosis, the pancreas contained multiple endocrine tumors producing insulin, glucagon, somatostatin, and growth hormone-releasing factor and showed evidence of widespread nesidioblastosis. It is uncertain whether peliosis of pancreatic islets and MEN-1 syndrome were coincidental or whether the two diseases were causally related. Since hormonal factors can result in hepatic peliosis, it is tempting to speculate that the endocrine imbalance secondary to MEN-1 syndrome might have played a role in the genesis of peliosis in this case. Although no direct proof of vascular damage was encountered, it is conceivable that escape of red blood cells from the circulation and their accumulation in tissue spaces was due to abnormal islet blood flow and increased capillary permeability.

Adult↗

Cell cycle-dependent cytotoxicity of alkylating agents: determination of nitrogen mustard-induced DNA cross-links and their repair in Chinese hamster ovary cells synchronized by centrifugal elutriation.

Chinese hamster ovary cells were synchronized into the different phases of the cell cycle by centrifugal elutriation and treated with nitrogen mustard (HN2) in order to investigate the role of DNA damage and repair processes in the cell cycle-dependent cytotoxicity of this alkylating antitumor agent. In agreement with previous studies, cell populations enriched in G1 were the most sensitive to HN2, and those enriched in late S phase-G2 were more resistant, as determined by clonogenic assay. Although the variation in surviving fraction through the cell cycle in response to a single dose (3 micrograms/ml; 1.0 h) of HN2 was as great as a factor of 10, complete dose-response curves generated for the most sensitive and most resistant elutriator fractions indicated that such changes could be accounted for by a ratio of D0 values of only 1.4 Cells synchronized by this same method were also analyzed for their relative levels of HN2-induced DNA cross-linking using the sensitive technique of alkaline elution. There was no significant difference in the levels of either DNA interstrand or DNA-protein cross-links induced in the two elutriator fractions described above immediately after the HN2 treatment. When the amount of DNA cross-linking in the two fractions was measured 6 h after treatment, considerable repair had occurred; however, there was no measurable difference in the rate of repair of either type of cross-link (i.e., DNA interstrand and DNA-protein) in the different phases. Differences in DNA damage and repair processes could not therefore be resolved within the confidence limits of available assays and probably cannot account for the differential cytotoxicity of HN2 towards cells in the different cell cycle phases.

Alkylating Agents↗

[Primary prevention of hypertension in childhood (the population approach)].

A substantial prevalence of clinical hypertension with a large portion of the adult population requiring daily antihypertensive medication makes this disease an important public health problem. The known and unknown side effects of life-long pharmacologic therapy directs searches for methods of prevention. Because the origins of high blood pressure are found in children, at a point in life where health habits are established, preventive programs directed to youth seem particularly relevant. Increased sodium intake is the most widespread nutritional factor related to the development of high blood pressure. The prevalence of hypertension and the ubiquitous nature of sodium in many processed foods, well in excess of that needed for life seem to indicate the need for a broad public health approach. A test of this approach in school children is described below. The overall goals are to better understand the nature of health education and nutrition education in this age and, if successful, evaluate the effect of moderate sodium reduction on blood pressure.

Adolescent↗

[Prevention and treatment of hypertension at the population level: the Minnesota Heart Health Program].

The Minnesota Heart Health Program is a ten year research and demonstration trial for the primary prevention of coronary heart disease. Community wide prevention and control of hypertension is among the major goals of this study. Systematic population screening for hypertension, mass media campaigns, adult and youth education programs, physician and health professional programs, and community organization efforts are part of the multiple strategy approach to prevention. Replication in three sites, annual risk factor surveys and morbidity/mortality surveillance will provide evidence for the value of this community wide approach at the end of ten years.

Adolescent↗

Atypical carcinoid tumor of the small bowel complicating celiac disease.

An atypical carcinoid tumor of the small bowel in a patient with celiac disease is described. Although an increased incidence of malignancy has been observed in celiac disease, this seems to be the first report of a carcinoid tumor of the small intestine associated with this condition. Although the significance of this association is unclear, the implications with regard to gastrointestinal endocrine cell proliferation and tumor histogenesis are discussed.

Carcinoid Tumor↗

Hemodynamic effects of metoprolol in acute myocardial infarction. A randomized, placebo-controlled multicenter study.

The central hemodynamic effects of metoprolol in acute myocardial infarction have been studied in a multicenter, double-blind, randomized trial. One hundred and ninety patients with acute myocardial infarction not previously on beta blockers with heart rate greater than 65 beats/min and blood pressure greater than 105 mm Hg and without clinical signs of serious heart failure were included. After insertion of a pulmonary artery catheter, patients were randomized to metoprolol, 15 mg intravenously, and 50 mg 4 times a day orally (n = 95) or placebo (n = 95) with a mean delay of 7.2 hours. Hemodynamic measurements were made at baseline and repeatedly during 24 hours. Heart rate, systolic blood pressure and cardiac index were all immediately reduced by 10 to 20% in the metoprolol group and the difference compared with placebo was maintained throughout the 24 hours (p less than 0.001). Pulmonary capillary wedge pressure (PCWP) in the metoprolol group increased from 13.7 +/- 6.7 to a peak of 15.5 +/- 5.5 mm Hg 30 minutes after injection. The difference compared with placebo was maintained for 8 hours (p less than 0.01). This increase was seen only in the patient group with initial PCWP below the median of 13 mm Hg. In patients with initial PCWP above the median a continuous decrease was observed in both the placebo and metoprolol groups. Thus high initial PCWP was not associated with intolerance to metoprolol. Based on hemodynamic measurements tolerance to metoprolol was good.

Aged↗

DNA damage in normal and neoplastic mouse tissues after treatment with misonidazole in vivo.

Alkaline elution has been used to examine the integrity of DNA isolated from various tissues from mice treated with misonidazole (MISO). High doses (1-3 mg/g) of MISO caused extensive DNA strand breakage in cells isolated from two fibrosarcoma tumors that were known to contain hypoxic cells, and also in cells from certain normal tissues (liver and kidney in particular). The incidence of strand breaks gives further support to the suggestion that MISO can be metabolically nitroreduced beyond the singly reduced nitro radical-anion in some normal tissues as well as in hypoxic tumor cells, generating DNA-reactive species. Nitroreductases must therefore be able to compete successfully with molecular oxygen for the MISO nitro radical-anion in such tissues.

Animals↗

Aseptic meningitis in a neonate with an oral vesicular lesion.

Enteroviruses may be responsible for severe, life-threatening diseases, such as meningitis, within the neonatal period. Differentiation of an enteroviral etiology from that of herpes simplex virus may be difficult initially. We describe a case of aseptic meningitis in which the use of a viral blood culture was helpful.

Coxsackievirus Infections↗

Effects of fluorescein on tear breakup time and on tear thinning time.

A simple, noninvasive method of in vivo precorneal tear film stability analysis is described. The method involves observing the first catoptric (first Purkinje) image. The effect of fluorescein on the results and the relation with standard tear breakup time (BUT) are presented.

Adult↗