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Biomedical subjects

R Brown

Publications and source records attributed to R Brown.

At least 19 recordsLinked to original sources
PubMed1992

Binding of human single-stranded DNA binding protein to DNA damaged by the anticancer drug cis-diamminedichloroplatinum (II).

The chemotherapeutic drug cis-diamminedichloroplatinum (II) covalently binds to DNA resulting in a variety of adducts and cross-links which are thought to be responsible for the toxicity of the drug. We have used the gel mobility shift assay to detect proteins which bind to DNA treated in vitro with cis-diamminedichloroplatinum (II) and have identified two complexes which bind with increased affinity to cis-diamminedichloroplatinum (II)-damaged DNA. Using monoclonal antibodies we have shown that one complex, B1, contains human single-stranded DNA binding protein, a protein known to be involved in the in vitro repair synthesis assay of mammalian excision repair.

Antibodies, Monoclonal↗
PubMed1992

Glutathione depletion in chronic lymphocytic leukemia B lymphocytes.

Glutathione (GSH) content may be the major determinant of a cell's sensitivity to cytotoxic alkylating agents. In the present study, the GSH concentration was determined in lymphocytes isolated from the blood of normal subjects and patients with chronic lymphocytic leukemia (CLL). Comparable levels were found in both types of cells. Incubation for 20 hours led to a decrease in GSH to 51% of baseline values in CLL B cells. Under the same conditions, normal B- or T-lymphocyte GSH content remained constant. GSH depletion was shown to be a characteristic of the B-CLL B lymphocyte. It was not found in the T cells of patients with B-CLL or in cells from patients with T-CLL. Chlorambucil (CLB) contributes to the decrease in GSH in B-CLL lymphocytes; after incubation with the drug, lower levels of GSH were found than in the normal B or T lymphocytes, B-CLL T cells, or T-CLL (CD4 or CD8) cells. GSH depletion of CLL B lymphocytes may be related to the greater therapeutic efficacy of CLB in B-CLL than in T-CLL.

B-Lymphocytes↗
PubMed1992

Immunochemiluminometric assays (ICMA) specific for growth hormone releasing hormone 1-44 NH2 and 1-40 OH.

We describe specific two-site immunochemiluminometric assays able to directly measure human growth hormone-releasing hormone 1-44 NH2 and 1-40 OH concentrations in unextracted plasma. A common N-terminal antibody was purified from polyclonal rabbit antisera to growth hormone-releasing hormone 1-44 NH2 on a growth hormone-releasing hormone 1-29 NH2 linked affinity column and labelled with chemiluminescent acridinium ester. C-terminal specific monoclonal antibodies to growth hormone-releasing hormone 1-44 NH2 and 1-40 OH were raised in Balb/C mice and used as solid phase antibodies. Assay of fasting specimens from normal individuals gave medians (and ranges) of 23 pg/ml (2-200) and 30 pg/ml (3-134) for growth hormone-releasing hormone 1-44 NH2 and 1-40 OH, respectively. Samples from a series of acromegalics showed that most have values in the normal range though median values were higher, 56 pg/ml for growth hormone-releasing hormone 1-44 NH2 (P < 0.001) and 52 pg/ml for 1-40 OH (P < 0.001). Using these assays it will be possible for the first time to directly study the physiology and pathophysiology of these two peptides.

Acromegaly↗
PubMed1992

Autoantibodies to thrombomodulin: development of an enzyme immunoassay and a survey of their frequency in patients with the lupus anticoagulant.

In order to investigate the possibility that autoantibodies to thrombomodulin (TM) may exist in patients with the lupus anticoagulant (LA) and perhaps be implicated in the pathogenesis of recurrent thrombosis seen in such patients, we developed an enzyme-immunoassay to screen serum samples for anti-human TM activity. The major technical problem encountered in developing this assay was to reduce the non-specific binding of serum components from both the LA positive and the negative population. Considerable reduction of non-specific binding was achieved by use of a phosphate/citrate buffer at pH 8.0 and the use of an optimal sample dilution of 1/40. In addition, samples were always tested in parallel in blank wells and results are expressed as an OD ratio. Samples from 113 patients with the LA were assayed and compared to 78 patients referred for LA testing but found to be negative. The mean OD values for the LA positive patients (+/- SD) was 1.36 (0.44) with a range of 0.78-2.57. This was virtually identical to the values for the LA negative population (1.38 +/- 0.40, range 0.76-2.77). The results of this study indicate that there is no evidence for the presence of a significant autoantibody activity to TM in patients with the LA when compared to LA negative patients. If such autoantibodies do exist their frequency must be quite low.

Autoantibodies↗
PubMed1992

Characteristics of peak aerobic capacity in symptomatic and asymptomatic subjects with left ventricular dysfunction. The Studies of Left Ventricular Dysfunction (SOLVD) Investigators.

Expired gas analysis was used to determine the aerobic exercise performance of subjects with depressed left ventricular (LV) systolic function and congestive heart failure (CHF). To determine whether subjects with no or minimal CHF have better aerobic exercise performance than do those with overt CHF, oxygen consumption (VO2) at anaerobic threshold (AT) and peak exercise was measured in 184 subjects with LV ejection fraction less than or equal to 0.35 who participated in the Studies of Left Ventricular Dysfunction. Subjects were divided into those with overt CHF needing treatment (treatment trial; n = 20) and those who had neither overt CHF nor treatment for CHF (prevention trial; n = 164). Treatment trial subjects had a lower LV ejection fraction (0.25 +/- 0.07) than did prevention trial ones (0.29 +/- 0.05; p = 0.001), but there were no differences in age, gender, body weight, resting heart rate and blood pressure. Treadmill exercise testing was performed after 2 to 3 weeks of placebo (no angiotensin-converting enzyme inhibitor) treatment. Treatment trial subjects exercised for a shorter time (493 +/- 160 seconds) and attained a lower peak VO2 (13 +/- 4 ml/kg/min) and VO2 at AT (11 +/- 4 ml/kg/min) than did prevention trial ones (842 +/- 277 seconds, and 20 +/- 6 and 16 +/- 5 ml/kg/min, respectively). Analysis of covariance showed that the differences in peak VO2 and VO2 at AT were statistically significant between the 2 trials after adjusting for age, gender, LV ejection fraction and New York Heart Association functional class.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Role of congenital hypertrophy of the retinal pigment epithelium in the predictive diagnosis of familial adenomatous polyposis.

A study was carried out to evaluate congenital hypertrophy of the retinal pigment epithelium (CHRPE) as a disease marker in a defined population with familial adenomatous polyposis (FAP). Indirect ophthalmoscopy was performed on 75 individuals from 25 known families with FAP, of whom 32 were known to be affected and 43 were at a 50 per cent prior risk of developing the disease. A further ten individuals from five families with hereditary non-polyposis colorectal cancer (HNPCC) were also tested. CHRPE was seen in 28 of the 32 affected individuals, 27 of whom met the criteria for a positive examination. Three individuals at risk of FAP also had positive examinations. Five individuals from the families with HNPCC also had CHRPE, although none met the criteria for a positive examination. Of four types of CHRPE analysed, one (small pigmented dots) was found to be more frequent in older family members (P = 0.012), suggesting that this type of lesion may proliferate with age. Compliance with ophthalmic screening was 97 per cent in families with FAP. Using a combined set of diagnostic criteria, CHRPE identified affected individuals with a specificity of at least 94 per cent and a sensitivity of 84 per cent. Results argue for a combined screening programme for FAP of DNA analysis, indirect ophthalmoscopy and bowel examination.

Adenomatous Polyposis Coli↗
PubMed1992

Amplification of the topoisomerase II alpha gene in a non-small cell lung cancer cell line and characterisation of polymorphisms at the human topoisomerase II alpha and beta loci in normal tissue.

DNA was prepared from normal tissue and 19 lung cancer cell lines. Using probes which detect restriction fragment length polymorphisms at both the topoisomerase II alpha and beta loci, heterozygosity was detected at a frequency of 0.17 and 0.37 for the alpha and beta loci, respectively. Southern blot analysis of DNA extracted from lung cancer cell lines detected amplification of both the topoisomerase II alpha and ERBB2 genes in the adenocarcinoma line Calu3. These results indicate that topoisomerase II alpha and ERBB2 may be closely linked on chromosome 17 and coamplified during adenocarcinoma progression. Since topoisomerase II is a target for several anticancer drugs, it will be of interest to study alterations to topoisomerase II genes during tumour development, as these may in part determine the response of the tumour to chemotherapy.

Adenocarcinoma↗
PubMed1992

Reliability and validity of a health-related quality of life battery for evaluating outpatient antidepressant treatment.

This study was designed to evaluate the reproducibility, validity and responsiveness of a health-related quality of life (HRQOL) battery that was assembled for the evaluation of antidepressant therapy. The Montgomery-Asberg Depression Rating Scale was used to measure severity of depression. The HRQOL battery contained measures of energy and fatigue, social behaviour, cognitive function, home and work role function, and general well-being (i.e., health perceptions, life satisfaction) selected from previously developed and validated instruments. The clinical investigators and research nurses reported on difficulty in using the HRQOL battery. Most patients were able to complete the questionnaire without problems within 10 min. Reproducibility was very good with intraclass correlation coefficients ranging from 0.74 to 0.97. The HRQOL scales showed evidence of good concurrent validity. The scales were moderately correlated with MADRS scores (r = 0.30-0.62). The magnitude of these correlations indicate that HRQOL scales are related to depression measures, but they are not alternative measures of depression. Changes in MADRS scores were associated with changes in all scales, except for work behaviour, indicating that improvements in depression ratings also resulted in improvements in health status and well-being. The HRQOL scales included in this study were found to be reliable, reproducible, and valid and no appreciable burden was placed on patients or investigators participating in the study. With the exception of the Work Behaviour scale, the HRQOL scales were very responsive to changes in depression severity. This brief HRQOL instrument can provide a comprehensive assessment of the outcomes of antidepressant treatment.

Adult↗
PubMed1992

Sleep deprivation-induced hyperthermia following antigen challenge due to opioid but not interleukin-1 involvement.

Eight hours total sleep deprivation does not affect colonic temperature. The combination of a subpyrogenic challenge of sheep red blood cells with sleep loss however, can produce a significant rise in colonic temperature that peaks during the third hour of the sleep deprivation vigil. The regulation of this increase in colonic temperature appears to be opioid in nature and not because of the release of the cytokine interleukin-1. It would appear that the combination of sleep loss and low dose antigen challenge, both manipulations of themselves nonpyrogenic, produces a synergistic rise in colonic temperature. The implication of a psychologically-derived stress response via the opioid system may explain this finding.

Animals↗
PubMed1992

Ventilatory and P0.1 response to hypercapnia in quadriplegia.

Unlike individuals with comparable degrees of respiratory muscle weakness from other causes, quadriplegic patients have a blunted ventilatory and P0.1 response to hypercapnia. This suggests that the diminished response in quadriplegia is due, in part, to an alteration in respiratory drive. We measured the hypercapnic response in 9 subjects with chronic quadriplegia (Q) and 8 normal controls (N). Ventilatory muscle strength, maximum voluntary ventilation (MVV), and lung volumes were measured in all subjects. The ventilatory response (HCVR) in Q was significantly less than in N (0.73 +/- 0.37 vs 2.95 +/- 0.4 L.min-1.mmHg-1; P less than 0.001), even when normalized for indices of respiratory muscle performance (e.g., vital capacity, MVV). There was no significant change in the HCVR in Q after the administration of naloxone. We also serially studied 2 subjects with acute quadriplegia, and found that despite progressive improvement in respiratory muscle performance, there was no accompanying increase in the response to hypercapnia. These data suggest that muscle weakness alone cannot explain the blunted hypercapnic response in quadriplegia, and are consistent with the hypothesis that these subjects have a reduced ventilatory drive.

Adult↗
PubMed1992

Reduced tidal volume increases 'air hunger' at fixed PCO2 in ventilated quadriplegics.

The act of breathing diminishes the discomfort associated with hypercapnia and breath-holding. To investigate the mechanisms involved in this effect, we studied the effect of tidal volume (VT) on CO2-evoked air hunger in 5 high-level quadriplegic subjects whose ventilatory capacity was negligible, and who lacked sensory information from the chest wall. Subjects were ventilated at constant frequency with a hyperoxic gas mixture, and end-tidal PCO2 was maintained at a constant but elevated level. VT was varied between the subjects' normal VT and a smaller VT. Subjects used a category scale to rate their respiratory discomfort or 'air hunger' at 30-40 sec intervals. In 4 of 5 subjects there was a strong inverse relationship between breath size and air hunger ratings. The quality of the sensation associated with reduced VT was nearly identical to that previously experienced with CO2 alone. We conclude that afferent information from the lungs and upper airways is sufficient to modify the sensation of air hunger.

Adult↗
PubMed1992

Are sense-antisense peptide interactions between HIV-1 (gp120), CD4, and the proto oncogene product p56lck important?

The finding that codons for hydrophobic and hydrophilic amino acids are generally complemented by codons for hydrophilic and hydrophobic amino acids respectively has led to a novel observation. The antisense peptides coded for by the complementary DNA strand of biologically active peptides are able to bind their active sense counterparts with high specificity. Sense-antisense relationships have been observed in several peptide species as well as in receptor-ligand interactions. The idea that sense-antisense interactions are biologically relevant and indeed feasible among complex molecules prompts the examination of virus-host cell interactions. We propose such a sense-antisense interaction exists between the HIV glycoprotein gp120 and the intracellular domain of the HIV receptor CD4. This interaction is at a site which may be occupied by the proto oncogene product p56lck.

Amino Acid Sequence↗
PubMed1992

Length-based endotracheal tube and emergency equipment in pediatrics.

HYPOTHESIS: Pediatric endotracheal (ET) tubes can be accurately selected based on body length using a specialized emergency tape. POPULATION: Derivation set: Two hundred five children undergoing elective surgery. Validation set: Two hundred thirteen children undergoing elective surgery. Each child served as his or her own control. METHODS: Derivation phase: Two hundred twenty-one children undergoing ET intubation for elective surgery had their body length and leak pressures measured. The 205 children who had leak pressures between 10 and 40 cm H2O constituted the derivation set. The body length for a given ET tube size was derived from the interquartile range of patient lengths in this derivation set. Sizes for other resuscitative equipment items were chosen by a panel of experts using a modified Delphi technique. This information was placed by length on a color-coded tape. Validation phase: The tape was validated by using it to select ET tube size in another group of 203 children undergoing elective surgery. Criteria for acceptable fit in this group included leak pressure as above and the anesthesiologists' decision to accept the tube size or to retintubate. In the validation phase, length-based ET tube selections were compared with age-based rules: (age + 16)/4, and (age + 18)/4. RESULTS: The tape selected the appropriate ET tube size by leak pressure criterion in 77% of the cases and was within +/- 0.5 mm of the "correct" size 99% of the time. This was significantly better (P less than .005) than two widely used age-based rules, which gave the correct initial size in only 47% and 9% of these cases, and were within +/- 0.5 mm for 86% and 59%. The anesthesiologists chose to continue with the tape-sized tube rather than to reintubate in 89% of cases. CONCLUSION: A system for length-based selection of emergency equipment represents a significant adjunct to emergency physicians and paramedics who must deal with critically ill children. Length-based ET tube selection is clearly superior to age-based rules, which are difficult to remember and require accurate estimation of a patient's age.

Body Height↗
PubMed1992

The effect of malnutrition on insulin binding to rat erythrocytes.

Insulin binding to erythrocyte receptors was compared in malnourished and control rats. Percentage specific insulin binding to malnourished rat erythrocytes was significantly lower than to control erythrocytes (P less than 0.001). The low insulin binding in the malnourished rat erythrocytes was accompanied by low insulin receptor affinity (P = 0.035).

Animals↗