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Biomedical subjects

A Brown

Publications and source records attributed to A Brown.

At least 469 records · Page 26Linked to original sources
PubMed1986

Association of antigen expression and DNA ploidy in human colorectal tumors.

Fifty colorectal tumors were screened by indirect immunofluorescence and flow cytometry for antigen expression using a panel of monoclonal antibodies that recognize determinants preferentially expressed on tumor cells (carcinoembryonic antigen, Y haptenic blood group, 791T/36 defined antigen 791T-P72). Fifty % of the tumors expressed all three antigens, 41%, two, and 9%, one. Over a third reacted strongly with at least one monoclonal antibody, although the majority of tumors stained with a moderate intensity. Extranuclear membranes from tumors showed similar antigen expression to disaggregated tumor cells and were particularly useful for providing the relative tumor:normal tissue binding ratios. The carcinoembryonic antigen specific monoclonal antibody showed the strongest tumor selectivity with a tumor:normal tissue ratio of 24 +/- 7:1. Lack of correlation between expression of the three antigens suggested that the monoclonal antibodies recognizing them may have potential as a "cocktail." One-third of the tumors contained cells with an aneuploid DNA content and expressed elevated levels of carcinoembryonic antigen and Y haptenic blood group antigen when compared to tumors with diploid DNA content. Aneuploid cells within a tumor were also preferentially stained with all of the monoclonal antibodies.

Adenocarcinoma↗
PubMed1985

A quantitative method for assessing the extent of experimental gastric erosions and ulcers.

Evaluation of acute gastric erosions and ulcers induced by chemicals such as ethanol or aspirin is difficult because these lesions are predominantly multiple and irregularly shaped. A commercially available, relatively inexpensive microprocessor-linked planimeter (Micro-Plan II) with a stereomicroscope was used to measure the area of gastric mucosa damaged following intragastric administration of various doses of ethanol or aspirin. An enlarged image of rat glandular stomach was projected from the stereomicroscope onto a planimeter on which the perimeter of the entire glandular stomach and each lesion was traced with an electronic cursor. An attached printer recorded the area of stomach assessed, the number of lesions, the surface area of each lesion and the total area of mucosal damage. The technique was compared with semiquantitative methods used previously to assess experimentally induced gastric mucosal damage. The quantitative morphometric method was sufficiently sensitive to demonstrate a dose-response effect of ethanol and aspirin. The stereomicroscope--planimeter combination provides a sensitive method to quantitate either a few small, or numerous large, regularly or irregularly shaped hemorrhagic and nonhemorrhagic gastric mucosal lesions.

Animals↗
PubMed1985

Psychological normality and abnormality in persistent headache patients.

One hundred and three patients referred to a neurological outpatient clinic were examined to assess the relationship between persistent headache, not due to significant physical illness, and emotional disturbance. Overall, the patients showed slightly more evidence of emotional disturbance than a general practice population but less than psychiatric outpatients. Thus, with cut-off points of 4/5 and 9/10 on the General Health Questionnaire (GHQ 28) the whole group had 52% or 20% of psychiatric 'cases' respectively. On the Crown-Crisp Experiential Index the 70 females had mean total scores of 37.19 +/- 11.11 and the 33 males had scores of 31.79 +/- 11.36. In addition the childhood experiences measured by the Parental Bonding Instrument appeared to be normal. Seven patients had significant depressive illness, according to the Levine-Pilowsky Depression Questionnaire. Statistically significant differences in psychological state did not emerge between the diagnoses of cluster headache, classical migraine, common migraine, tension headache or combined headache. However, negative correlations were found between the duration of illness and measures of anxiety. It is concluded that although the emotional state contributes to the development of pain and headache in some patients, there are others in whom comparable headaches are unlikely to be due to emotional factors. Selection effects are held to be important and some of the emotional changes will vary at different phases of a chronic disorder. A new symptom may initially cause anxiety but when a condition persists some patients will be increasingly concerned or depressed whilst others develop tolerance for the situation.

Adolescent↗
PubMed1985

Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat.

The hypothesis that vascular injury contributes to the development of hemorrhagic erosions after intragastric administration of ethanol has been examined in the rat using vascular tracers. Extravasation of intravenously injected Evans blue into the gastric wall and into gastric contents was used as an indicator of vascular permeability. India ink and monastral blue, which label damaged blood vessels, were used to demonstrate vascular injury morphologically. Intragastric instillation of 75% and 100% ethanol induced increased vascular permeability within 1-3 min and resulted in monastral blue labeling of vessels in 13% and 17%, respectively, of the glandular mucosa within 1 min. After 1 h of 100% ethanol exposure, the areal density of monastral blue-stained blood vessels did not increase compared with that seen at 1 min, but the areal density of grossly visible hemorrhagic lesions increased strikingly and approximated that of vessel staining. The hemorrhagic erosions consistently occurred in regions of glandular mucosa where vessels were stained with monastral blue. Pretreatment with prostaglandin F2 beta or cysteamine reduced ethanol-induced Evans blue extravasation and monastral blue staining of mucosal blood vessels but did not reduce histologic evidence of gastric surface cell damage in the glandular mucosa. As increased vascular permeability and morphologically detectable vascular lesions consistently preceded the development of grossly visible hemorrhagic erosions in the glandular mucosa, we suggest that vascular injury is an early pathogenetic factor in the development of ethanol-induced gastric hemorrhagic erosions. The data also indicate that the degree of vascular damage, unlike the injury to surface epithelial cells, is reduced by pretreatment with prostaglandin F2 beta or the sulfhydryl cysteamine.

Animals↗
PubMed1985

Reduction of anti-inflammatory drug costs with newer aspirin formulations.

Anti-inflammatory/analgesic drugs account for a large proportion of prescriptions and prescribing costs, particularly for ambulatory patients. Although aspirin is highly effective, 95% of anti-inflammatory/analgesic prescriptions have been for the newer, more expensive alternatives. Recently two newer aspirin formulations were made available on our hospital's formulary. Subsequently aspirin prescribing rose from 5% to 14.5% (P less than 0.0005), and mean pharmacy costs for anti-inflammatory analgesics fell 5.9% over a 7-month period (P less than 0.025). This decline in costs interrupted a historic trend toward increased prescription costs and was accomplished with minimal effort or hospital resources. Increased availability and familiarity with these newer aspirin formulations may substantially reduce costs for the health care system.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1985

Cross-reactive target antigen in cell-mediated cytolysis of cells infected with a temperature-sensitive mutant of Sindbis virus.

Cytotoxic T lymphocytes (CTL) against alphavirus-infected L929 cells were generated in mice by two in vivo immunizations of one virus or by in vivo immunization followed by in vitro stimulation of splenocytes with infected peritoneal exudate cells or splenocytes. These CTL caused specific H-2-restricted cytolysis equally well with homologous, heterologous or Sindbis virus ts20 mutant-infected cells. Thus, specific CTL appear to be cross-reactive components in normal immunity to alphaviruses and the E1 glycoprotein is implicated as the target antigen.

Animals↗
PubMed1985

Leprosy associated with HLA-DR2 and DQw1 in the population of northern Thailand.

A study of the frequency of HLA-DR2 and DQw1 was performed in leprosy patients and controls in northern Thailand. HLA-DR2 was found in 100% (17/17) of patients with sporadic tuberculoid leprosy and in over 90% (30/32) of all tuberculoid leprosy patients, as compared to 62% (20/32) of controls (p = .02). These strong associations had relative risks of 21.4 for sporadic and 7.4 for all tuberculoid leprosy, and etiologic fractions of 1.0 and 0.84, respectively. There was also a statistically significant and strong association between tuberculoid leprosy and DQw1. These data add to the growing body of evidence that products of HLA class II determinants or closely linked genes may play a role in determining the clinical manifestations of M. leprae infection.

Adult↗
PubMed1985

Detection of immunologically cross-reacting capsid protein of alphaviruses on the surfaces of infected L929 cells.

Hyperimmune, but not normal immune, monospecific antiserum made to capsid protein of Sindbis virus (SIN) was found to cause cytolysis equally well of both SIN- and Semliki Forest virus-infected L929 cells in antibody-dependent, complement-mediated cytotoxicity assays. The cell surface reactivity of the hyperimmune antiserum was also demonstrated by solid-phase radioimmune assays with unfixed infected cells or infected cells fixed with low concentrations of glutaraldehyde (0.025%) before reactivity with antisera. Higher concentrations of glutaraldehyde lowered the sensitivity of detection. Purified SIN capsid protein specifically inhibited antibody-dependent, complement-mediated cytotoxicity by the monospecific anti-capsid protein serum on SIN- and Semliki Forest virus-infected target cells. That hyperimmune anti-SIN serum also cross-reacts with capsid protein on the surface of Semliki Forest virus-infected cells was suggested by the fact that capsid protein inhibited cross-cytolysis in the antibody-dependent, complement-mediated cytotoxicity assay. The latter antiserum was collected after repeated injections of purified virions over a 9-month period. The results suggest that hyperimmune monospecific antisera made to SIN capsid protein or hyperimmune antisera to SIN or Semliki Forest virions detect homologous and cross-reacting capsid protein determinants on the surface of infected cells.

Animals↗
PubMed1985

Leukemia in breast cancer patients following adjuvant chemotherapy or postoperative radiation: the NSABP experience.

Since 1971, 8,483 women with primary breast cancer participated in seven trials evaluating adjuvant chemotherapy. Leukemia occurred in only three of 2,068 patients treated by operation alone. The cumulative risk was 0.06% after 10 years in those free of metastases or a second primary tumor, and 0.27% in those with tumor. Thus, leukemia is not an important factor in the natural history of breast cancer. Five of 646 women receiving postoperative regional radiation developed leukemia, an overall risk of 1.39 +/- .49% at 10 years. Twenty-seven cases of leukemia (0.5%) and seven of myeloproliferative syndrome (0.1%) were recorded in 5,299 patients who received L-phenylalanine mustard (L-PAM)-containing regimens. The maximum cumulative risk of leukemia in chemotherapy recipients (leukemia of any type and myeloproliferative syndrome) was 1.68 +/- .33% at 10 years following operation. The risk excluding those with myeloproliferative syndrome was 1.29 +/- .28%. The risk of leukemia in patients free of metastases or a second primary was 1.11 +/- .30% at 10 years, and when combined with myeloproliferative syndrome, it was 1.54 +/- .36%; risks not significantly greater than observed following radiation (P = .58 and .29). No cases of leukemia were observed during the 2 years of chemotherapy and none have occurred after the seventh postoperative year. Comparisons with the surveillance, epidemiology, and end results tumor registries (SEER) data indicate an increased relative risk of acute myelogenous leukemia following postoperative regional radiation (P less than .01) and adjuvant chemotherapy (P less than .001). The findings indicate that hematologic disorders are side effects of both radiation and alkylating agents used in the adjuvant treatment of primary breast cancer. The risk of such events is lower than that reported following treatment of other solid tumors and hematologic malignancies by chemotherapy. The benefit from adjuvant chemotherapy for breast cancer exceeds the risk of leukemia. Since chemotherapy is not uniformly beneficial, efforts should be directed toward identifying responders so that only those who will benefit are exposed to the risk.

Actuarial Analysis↗
PubMed1985

Duodenal ulcer induced by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine).

Experiments in rats revealed that the parkinsonian drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) given in multiple daily doses either per os (p.o.) or subcutaneously (s.c.) induced in a dose-dependent manner solitary or double ("kissing") duodenal ulcers in the rat. MPTP also diminished cerebral concentrations of DOPAC and the duodenal ulcers were prevented by pretreatment with dopamine agonists (e.g., bromocriptine, lergotrile) or monoamine oxidase inhibitors (e.g., pargyline, 1-deprenyl). High doses of MPTP also caused gastric erosions and motility changes resembling parkinsonism (e.g., akinesia, rigidity, forward bending of trunk). This chemical decreased gastric secretion of acid and pepsin, as well as pancreatic bicarbonate, trypsin and amylase. Thus, MPTP causes duodenal ulcers that are possibly associated with impaired defense in the duodenal bulb (e.g., decreased availability of duodenal and pancreatic bicarbonate).

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1984

Immunohistochemical localization of Y hapten and the structurally related H type-2 blood-group antigen on large-bowel tumours and normal adult tissues.

The monoclonal antibody C14/1/46/10 which defines the Y hapten carbohydrate antigen (Brown et al., 1983) was shown, by the indirect immunoperoxidase technique, to stain tissue sections of 96% of colo-rectal adenocarcinomas and 100% of colo-rectal adenomas. In contrast, a monoclonal antibody defining the related H type-2 blood-group antigen was found to stain 86% of adenocarcinomas and 32% of adenomas. In adenocarcinomas the percentage of cells stained for both antigens was, on average, greater in group O than in group A patients. In adenomas a focal pattern of expression was observed, for both Y hapten and H type-2 antigen, that was characteristic of group A but not group O adenocarcinomas. In the normal mucosa of the distal colon, whilst H type-2 antigen was absent, Y hapten was found in the immature cells of the crypt bases. A comparison of the cellular phenotypes present in adenocarcinomas, adenomas and normal mucosa of the distal colon supports the adenoma-carcinoma sequence hypothesis for the genesis of colo-rectal carcinomas. In normal adult tissues Y hapten was predominantly found on epithelial cells whilst nervous tissues, muscles and connective tissues were negative. The expression of Y hapten in several positive tissues was dependent upon secretor status. A comparison of the expression of Y hapten and H type 2 antigen on normal adult tissues revealed that all of the permutations of expression of these two structurally related antigens were possible.

ABO Blood-Group System↗