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Biomedical subjects

R Brown

Publications and source records attributed to R Brown.

At least 433 records · Page 24Linked to original sources

Survival of cancer patients on therapy with coenzyme Q10.

Over ca. 25 years, assays in animal models established the hematopoietic activities of coenzyme Q's in rhesus monkeys, rabbits, poultry, and children having kwashiorkor. Surprisingly, a virus was found to cause a deficiency of CoQ9. Patients with AIDS showed a-"striking"-clinical response to therapy with CoQ10. The macrophage potentiating activity of CoQ10 was recorded by the carbon clearance method. CoQ10 significantly increased the levels of IgG in patients. Eight new case histories of cancer patients plus two reported cases support the statement that therapy of cancer patients with CoQ10, which has no significant side effect, has allowed survival on an exploratory basis for periods of 5-15 years. These results now justify systematic protocols.

Aged↗

Isolation, characterization and localization of annexin V from chicken liver.

Annexin V has been purified from chicken liver; 40 mg of annexin V was obtained per kg of tissue. In contrast with mammalian liver, very little annexin VI was obtained. Surprisingly, chicken liver annexin V resembles mammalian annexin IV in its M(r) (32,500) and its isoelectric point (5.6), but amino-acid-sequence analysis demonstrates identity with chicken annexin V (anchorin CII). It binds to phospholipids in a Ca(2+)-dependent manner with free-Ca2+ concentrations for half-maximal binding to phosphatidylserine and phosphatidic acid of 10 microM; phosphatidylethanolamine of 32 microM and phosphatidylinositol of 90 microM. No binding to phosphatidylcholine was observed at Ca2+ concentrations up to 300 microM. In isolated liver membranes a significant proportion of annexin V was not extractable with EGTA but could only be extracted with Triton X-100, suggesting the existence of a tightly membrane-associated form of annexin V. A specific antiserum to chicken annexin V was used to localize the protein in adult and embryonic chicken liver. In the adult, annexin V was highly concentrated in epithelial cells lining the bile ducts, and along the bile canaliculi. In embryonic liver, strong staining of the bile-duct epithelial cells was again evident, and in addition, endothelial cells were strongly immunoreactive.

Amino Acid Sequence↗

Binding activities of cis-platin-damage-recognition proteins in human tumour cell lines.

Proteins can be detected by South-western analyses of human tumour-cell extracts binding to double-stranded oligonucleotide DNA treated in vitro with the chemotherapeutic drug cis-diamminedichloroplatinum (II) (CDDP), but not to untreated DNA. The relative molecular masses of proteins binding to the CDDP-treated double-stranded oligonucleotide are 25, 48 and 97 kDa. The binding activity of 2 of the CDDP-damage-recognition proteins, of relative molecular mass 48 and 97 kDa, is greater in a CDDP-resistant human ovarian tumour cell line than in the parental sensitive line. South-western analysis of a panel of human bladder cell lines and CDDP-sensitive testicular cell lines show consistent patterns of CDDP-damage-recognition proteins within each cell type, however with differences between the 2 cell types. Binding of the proteins to CDDP-damaged DNA and the altered binding activity detected in tumour cell lines suggests that alteration in damage-recognition proteins could play a role in tumour response to CDDP.

Base Sequence↗

Insuring Latinos against the costs of illness.

OBJECTIVE: To examine the determinants of health insurance coverage for Latinos in the United States and how different targeted strategies for health care reform differentially affect the country's major ethnic groups, focusing on the implications for the Latino population. DESIGN: Data from the 1980 and 1990 Current Population Surveys were used to compare the insurance status of nonelderly (< 65 years) Latinos with the Anglo (non-Hispanic white), black, and Asian and other populations by estimating the attributable fraction for selected covariates. The effects of health care reform strategies on the coverage of the major ethnic groups were simulated from these data. MAIN OUTCOME MEASURES: Percentage uninsured, percentage insured by Medicaid, and attributable fraction for covariates. RESULTS: Latinos have the worst health insurance coverage of any ethnic group in the country. Approximately 39% of Latinos are uninsured compared with 13.8% for the Anglo and 24% for the black population. Providing coverage to all the poor could reduce the uninsured rate for Anglos by about 23%, whereas the reduction among Latinos could be about 37% and among blacks about 42%. Similar reductions could be achieved by covering all workers and their minor dependents. Regardless of the approach to reform, however, Latinos would remain with high absolute rates of uninsured. CONCLUSIONS: Differences in Medicaid eligibility, labor force characteristics, and family composition between Latinos and other ethnic groups suggest that policy initiatives may affect Latinos differently. Targeted strategies, such as employer mandates, "pay-or-play" programs, or Medicaid expansions, can improve coverage, but many Latinos could still remain uninsured.

Adolescent↗

In situ correlation of synthesis and storage of parathormone in parathyroid gland disease.

The distribution and expression of parathyroid hormone (PTH) were investigated in normal and abnormal parathyroid tissue. PTH was detected using a monoclonal antibody with specificity for the 44-68 region of the PTH molecule. Prominent reactivity for PTH was seen in normal parathyroid with a granular pattern of staining. Active parathyroid tissue (adenoma and hyperplasia) showed much less reactivity for PTH, although there was prominent reactivity in the normal tissue around adenomas. Comparison of expression of PTH with that of parathormone mRNA showed a reciprocal pattern in normal tissue and, to a less marked extent, in abnormal tissue. Parathyroid carcinoma in particular had coinciding areas of PTH and PTH mRNA expression. Oxyphil cells had little or no PTH expression, except in the associated 'colloid' in some cases. The findings indicate an inverse relationship between storage and cellular synthesis of PTH, this being more marked in physiological than in pathological conditions of the parathyroid.

Adenoma↗

Exercise endurance in rats: roles of type I and II corticosteroid receptors.

Intact and adrenalectomized (ADX) rats were mildly food deprived and administered dexamethasone (type II agonist), aldosterone (type I agonist), corticosterone (mixed agonist), or vehicle 24 and 2 h prior to forced exercise in a treadmill. The endurance of intact animals was unaffected by hormone treatments. Adrenalectomy greatly advanced the onset of fatigue, and aldosterone exacerbated the effect of adrenalectomy. Corticosterone improved endurance in ADX rats, and dexamethasone was even more potent in this respect. Aldosterone slowed deprivation-induced weight loss in ADXs, while corticosterone and especially dexamethasone accelerated loss. Thus, endurance was directly related to body weight loss, and presumably to the fuels released by such loss. The results extend the type I-type II functional dichotomy to the delivery of utilizable energy for metabolically active tissues.

Adrenal Glands↗

Co-amplification of erbB2, topoisomerase II alpha and retinoic acid receptor alpha genes in breast cancer and allelic loss at topoisomerase I on chromosome 20.

The DNA topoisomerase enzymes are targets for the cytotoxic effects of a number of anticancer agents termed topoisomerase inhibitors. We have analysed breast cancer biopsy specimens for genetic alterations at and around topoisomerase loci in order to obtain molecular insight into factors which may determine how tumours respond to chemotherapy. We show that of 50 tumours examined, the topoisomerase II alpha locus is co-amplified in 3 cases out of 6 with erbB2 amplification and that amplification can be accompanied by high expression of topoisomerase II alpha. In our attempts to distinguish amplification from aneuploidy and define the limits of amplification, we also observed co-amplification of the retinoic acid-alpha receptor with erbB2 and topoisomerase II alpha in the same three samples. At the topoisomerase I locus on chromosome 20, we observed allelic loss in two out of 17 samples. Genetics abberations at topoisomerase loci, therefore, appear to be relatively common in breast cancer.

Aged↗

Cisplatin-DNA damage recognition proteins in human tumour extracts.

Enhanced repair of DNA adducts may be a cause of cis-diamminedichloroplatinum(II) resistance in solid malignancies. Binding of specific damage recognition proteins to the sites of DNA damage may be involved in the initial steps of DNA repair, or alternatively may block access of repair proteins to damaged DNA. Proteins which bind specifically to CDDP-modified DNA were identified in cell extracts from human ovarian carcinoma cell lines by two assays, the gel mobility shift assay and the southwestern blot. In the first assay, proteins complexed with CDDP-modified oligonucleotide and produced two retarded bands, B1 and B2. The B2 complex was partially purified from an ovarian cell extract by anion exchange FPLC, and was shown to bind to DNA damaged by CDDP but not by transDDP or UV irradiation. Using the southwestern blot, proteins of 97, 48, and 25 kD were identified; each of these bound to CDDP-modified but not undamaged oligonucleotide. The partially purified B2 protein fraction contained both the 97 and the 25 kD damage recognition proteins. A human ovarian carcinoma cell line selected in vitro for CDDP-resistance (OV1P/DDP), which is 5-fold more resistant to CDDP than the parental line (OV1P), showed an increase in binding of the 97 and 48 kD damage recognition proteins compared with the parental line. Twelve ovarian cell lines differed by up to 3-fold in their expression of these proteins, but there was no correlation between the amount of damage recognition protein in a cell extract and the cellular sensitivity to CDDP. Damage recognition proteins were also demonstrated in extracts prepared from biopsies of human ovarian, cervical, and testicular malignancies, but there was no apparent difference in the binding activity in extracts from tumours of different CDDP-sensitivity. The functional role of these damage recognition proteins remains to be established.

Base Sequence↗

Expression of topoisomerase II alpha and beta in an adenocarcinoma cell line carrying amplified topoisomerase II alpha and retinoic acid receptor alpha genes.

Human topoisomerase II enzymes are targets for a number of widely used anticancer agents. We have analysed a lung adenocarcinoma cell line CALU3, which has co-amplified topoisomerase II alpha and ERBB2 sequences, for the structure of the amplicon and for expression of both topoisomerase II alpha and beta. The region of chromosome 17q amplified in CALU3 also includes the retinoic acid receptor alpha locus and is therefore similar to the amplicon observed in breast cancers carrying amplified topoisomerase II alpha and retinoic acid receptor sequences. The use of fluorescence in situ hybridisation localises the amplified topoisomerase II alpha sequences to a cluster on one chromosome with single copies localised to others. CALU3 express high levels of topoisomerase II alpha is determined by Western blot, immunofluorescence and enzyme activity. The enzyme activity extracted from CALU3 is sensitive to inhibition by the topoisomerase II poison etoposide. Topoisomerase II beta expression was observed in three lung cancer cell lines including CALU3 and was confined to the nucleoli. Thus, the CALU3 cell line is an ideal model to study the amplification and expression of topoisomerase II alpha in adenocarcinomas.

Blotting, Western↗

Hyperparathyroidism, platelet intracellular free calcium and hypertension in chronic renal failure.

To investigate possible relationships between hyperparathyroidism, alterations in intracellular free calcium concentration ([Ca2+]i) and hypertension in chronic renal failure, serum concentrations of intact parathyroid hormone (PTH) were measured by two-site immunometric assay, and platelet ([Ca2+]i) was assessed using the fluorescent indicator fura-2. Thirty-six patients with chronic renal failure were studied, 10 with normal serum PTH concentrations (mean 8.0 +/- 0.6 pmol/liter), 17 with elevated serum PTH (35.0 +/- 7.2 pmol/liter) and 9 patients with elevated PTH (36.2 +/- 5.9 pmol/liter) who were receiving nifedipine. Platelet [Ca2+]i was increased in patients with elevated PTH, compared with those in whom PTH was normal (138 +/- 16 vs. 83 +/- 7 nmol/liter, P < 0.01). A linear relation was observed between serum PTH and platelet [Ca2+]i in these patients (r = 0.818, P < 0.001). In contrast, platelet [Ca2+]i was not elevated (84 +/- 9 nmol/liter) in the patients with elevated PTH who were receiving nifedipine. A linear relation was also present between both serum PTH (r = 0.616, P < 0.001) and platelet [Ca2+]i (r = 0.576, P < 0.005) and mean blood pressure. Nine patients with hyperparathyroidism were restudied after treatment with the vitamin D analogue alfacalcidol. This resulted in significant decreases in serum PTH (P < 0.01), platelet [Ca2+]i (P < 0.02), and mean blood pressure (P < 0.05). These studies indicate that [Ca2+]i may be increased early in renal failure, and that this increase occurs in association with both hyperparathyroidism and hypertension. Furthermore, treatment of hyperparathyroidism with alfacalcidol may result in reductions in both [Ca2+]i and blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Spirometry--acceptability and reproducibility in spinal cord injured subjects.

The American Thoracic Society (ATS) has formulated guidelines for spirometry. We hypothesized that individuals with SCI (SCI), as a result of weak respiratory muscles, would exhibit poor test acceptability and reproducibility. Seventy-eight SCI subjects (39 with complete SCI) answered a respiratory questionnaire and performed spirometry. Of those with complete SCI, the proportion of subjects which met ATS criteria decreased with higher levels of injury. Poor test performance was not associated with age, respiratory symptoms or muscle fatigue. The most common reason for failing to meet ATS criteria for acceptability was excessive back extrapolated volumes (EBEV). Individuals with efforts that were acceptable except for EBEV and/or for exhalation of less than six seconds had values for forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) that were reproducible. If ATS criteria for acceptable spirometry were used in studying subjects with SCI, individuals producing otherwise reproducible values for FVC and FEV1 would be excluded. We found reproducibility similar to what has been reported in other cohorts and conclude that longitudinal study of respiratory function in SCI is feasible.

Adult↗

A controlled trial of weighing with the Direct Recording Scales by the mothers in a village based growth monitoring programme in Ghana.

The Direct Recording Scales from Teaching aids at low cost (TALC) have been designed to overcome some of the deficiencies in present growth monitoring programmes. This is the full account of the first controlled trial of their use by 38 mothers for 6 months in a rural West African village. The mothers found weighing with the Direct Recording Scales easier to perform and more accurate than the control group using the dial scales. Their understanding of growth monitoring significantly improved as assessed by a questionnaire. Additionally, the mothers were proud to actively participate in the village--based weighing, which allowed more time for full discussions of their child's growth while leaving time free for the visiting health worker to spend on other aspects of Primary Health Care.

Body Weight↗