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Biomedical subjects

A Brown

Publications and source records attributed to A Brown.

At least 451 records · Page 25Linked to original sources
PubMed1987

Passive protection across subgroups of alphaviruses by hyperimmune non-cross-neutralizing anti-Sindbis serum.

Extended hyperimmunization of rabbits with Sindbis (SIN) or Semliki Forest (SF) viruses causes the production of antisera that are cross-reactive with virus-infected cells in antibody-dependent, complement-mediated cytotoxicity assays but that do not cross-neutralize viruses in vitro. C3H/HeJ mice given gamma globulin fractionated from the extended hyperimmune antiserum against SIN, but not control sera, were protected from challenge by 100 LD50 of SF, a virus which is in a different subgroup than SIN. All mice survived if the gamma globulin was given 24 hr before challenge virus and partial protection occurred if the globulin was given 24 hr after the virus. Cobra venom factor treatment of normal C3H mice challenged with SF did not reduce the protection, suggesting that complement was not involved. Methyl palmitate (40 mg/mouse) given before gamma globulin and virus challenge suppressed macrophage activity and reduced the level of protection 23% in females and 70% in males. Silica treatment (3 mg/mouse) reduced the protection equally in both males and females by 92%. In vitro experiments were done to test if it were possible that cross-antibody-dependent cellular cytotoxicity (ADCC) could account for the passive cross-protection observed in this system. Cross-ADCC could be demonstrated in vitro at high dilutions of antiserum (1:25,600). On the basis of the in vitro and in vivo results presented, we suggest that cross-ADCC against SF-infected target cells is one of the likely mechanisms to explain the passive cross-protection observed.

Animals↗
PubMed1987

Prevention of ethanol-induced vascular injury and gastric mucosal lesions by sucralfate and its components: possible role of endogenous sulfhydryls.

We tested the hypothesis that sucralfate, which contains eight sulfate and aluminum molecules on a sucrose and its other components might decrease ethanol-induced vascular injury and hemorrhagic mucosal lesions through a sulfhydryl (SH)-sensitive process. Experiments performed in rats revealed that the entire sucralfate molecule is not a prerequisite for protection against ethanol-induced mucosal vascular injury and erosions. It appears that sulfate and sucrose octasulfate are potent components of sucralfate, although an equimolar amount of sucralfate is at least twice as effective in gastroprotection than its components. The SH alkylator N-ethylmaleimide abolished the gastroprotection by sucralfate, suggesting SH-sensitive process in the mucosal protection which seems to be associated with the prevention of rapidly developing vascular injury in the stomach of rats given ethanol.

Aluminum↗
PubMed1987

Prolonging tamoxifen therapy for primary breast cancer. Findings from the National Surgical Adjuvant Breast and Bowel Project clinical trial.

OBJECTIVE: To determine whether prolonging the duration of tamoxifen administration beyond the cessation of a combined chemotherapy regimen benefits patients with primary breast cancer with positive findings in axillary nodes who benefit initially from the combined regimen. DESIGN: Nonrandomized, nonconcurrent cohort study. SETTING: National Surgical Adjuvant Breast and Bowel Project, conducted in 68 institutions in North America. PATIENTS: Women were included if they had breast cancer with positive nodes and were aged 49 years or less with both estrogen and progesterone receptor levels of 10 fmol or more, aged 50 to 59 years with progesterone receptor levels of 10 fmol or more, or aged 60 to 69 years. Two cohorts were compared: patients who were randomly assigned to the tamoxifen arm of the adjuvant chemotherapy trial (randomized patients) and women who were added to this arm after randomization had ceased (registered patients). Three hundred seventy-seven women in each group who were disease free at the end of the initial 2-year treatment period were followed for an additional 3 years. INTERVENTIONS: All received melphalan, fluorouracil, and tamoxifen (10 mg twice daily by mouth) for 2 years. Registered patients (but not randomized patients) were offered tamoxifen for a third year after the initial 2-year treatment period, and 273 (72%) agreed. MEASUREMENTS AND MAIN RESULTS: Women receiving a third year of tamoxifen had a better disease-free survival rate (odds ratio, 1.54; 95% confidence interval, 1.14 to 2.07; p = 0.004) and survival rate (odds ratio, 1.56; 95% Cl, 1.02 to 2.37; p = 0.04) through their fifth postoperative year. Women aged 50 years or more benefited, but those aged 49 years or less did not. CONCLUSIONS: The benefit of tamoxifen given to tamoxifen-responsive patients in conjunction with melphalan and fluorouracil appears to be enhanced when the tamoxifen treatment is continued beyond cessation of treatment with these agents.

Actuarial Analysis↗
PubMed1987

Microenvironmental cytokines and expression of erythroid heme metabolic enzymes.

In this study, we demonstrated that benzene and its metabolites, phenol and hydroquinone, were toxic to human burst-forming unit-erythroid (BFU-E) growth, hydroquinone being the most toxic. Phenol (10(-4) M) was also found to have a marked toxicity on stromal cell colony formation. BFU-E binding with human-tumor necrosis factor (rHu-TNF) was linear with the number of BFU-E colonies. Recombinant rHu-TNF suppressed BFU-E growth in a dose-dependent manner and this was reversed with anti-TNF antibody. Binding studies of rHu-TNF for human K562 cells indicated that K562 cells have a binding constant of approximately 1075 per cell. The heme pathway enzymes, uroporphyrinogen deaminase, and heme oxygenase activities were measured in BFU-E cultures exposed to iron, interleukins (1 and 2), and various lymphocyte and macrophage-conditioned media with or without hemin. In most instances, hemin was found to stimulate the heme synthetic pathway in the presence of these agents. Iron and adherent (macrophage) cell conditioned media (CM) were found to stimulate heme oxygenase activity. Macrophage CM was found to suppress erythropoiesis in contrast to phytohemagglutinin-stimulated leukocyte (PHAL)-CM, which enhanced erythroid growth. In addition, porphobilinogen deaminase levels were greater in 14-day cultures containing hemin plus PHAL-CM as compared with hemin alone. These results are discussed with respect to the generation of hematopoietic inhibitory-stimulatory factors by the marrow microenvironment and their effects on heme synthesis and degradation.

Ammonia-Lyases↗
PubMed1987

Effect of dopamine-related drugs on duodenal ulcer induced by cysteamine or propionitrile: prevention and aggravation may not be mediated by gastrointestinal secretory changes in the rat.

Dose- and time-response studies have been performed with dopamine agonists and antagonists using the cysteamine and propionitrile duodenal ulcer models in the rat. The experiments demonstrate that the chemically induced duodenal ulcer is prevented by bromocriptine, lergotrile and reduced by apomorphine or L-dopa. Aggravation of cysteamine-induced duodenal ulcer was seen especially after (-)-butaclamol, (-)-sulpiride, haloperidol and, less effectively, after other dopaminergic antagonists. The duodenal antiulcerogenic action of dopamine agonists was more prominent after chronic administration than after a single dose, whereas the opposite was found concerning the proulcerogenic effect of dopamine antagonists. In the chronic gastric fistula rat, both the antiulcerogens bromocriptine or lergotrile and the proulcerogens haloperidol, pimozide or (-)-N-(2-chlorethyl)-norapomorphine decreased the cysteamine- or propionitrile-induced gastric secretion. No correlation was apparent between the influence of these drugs on duodenal ulcer development and gastric and duodenal (pancreatic/biliary) secretions. In the chronic duodenal fistula rat, decreased acid content was measured in the proximal duodenum after haloperidol, and diminished duodenal pepsin exposure was recorded after bromocriptine. Furthermore, the aggravation by dopamine antagonists of experimental duodenal ulcer probably involves a peripheral component. The site of dopamine receptors and physiologic effects which modulate experimental duodenal ulcer remain to be identified, but their elucidation may prove to be an important element in the pathogenesis and treatment of duodenal ulcer.

Animals↗
PubMed1986

Squid neurofilaments. Phosphorylation and Ca2+-dependent proteolysis in situ.

Three major polypeptides co-purify with neurofilaments from squid (Loligo forbesi) axoplasm: P60 (apparent Mr 60,000), P200 (apparent Mr 200,000) and Band 1 (apparent Mr 400,000). Anti-IFA, a monoclonal antibody that recognizes an epitope common to all classes of intermediate filaments, binds to P200 and P60. When axoplasm is incubated with [32P]Pi, the major phosphorylated polypeptides are P200 and Band 1. We have investigated Ca2+-dependent proteolysis of [32P]phosphorylated axoplasm in order to localize the major sites of phosphorylation and to probe the arrangement of the polypeptides in the filament. The proteinase preferentially cleaves P200 and Band 1, liberating the phosphorylated domains. Analysis of proteolysed filaments by electron microscopy and gel electrophoresis shows that most of P200 and Band 1 can be cleaved while still maintaining intact filaments. We suggest that P200 is initially cleaved within a single highly sensitive region, generating two major fragments called P100p (apparent Mr 100,000) and P110s (apparent Mr 110,000). P100p contains the Anti-IFA epitope and co-sediments with filaments, whereas P110s is highly phosphorylated and does not sediment with filaments. Band 1 is cleaved to produce a soluble high-Mr fragment that is phosphorylated and that represents a major portion of the undigested component, whereas P60 is relatively resistant to limited proteolysis. Thus proteolysis appears to define two major filament domains: a conserved core that forms the backbone of the filament, and a highly phosphorylated peripheral region that is not essential for filament integrity.

Animals↗
PubMed1986

Idiopathic deep vein thrombosis in an apparently healthy patient as a premonitory sign of occult cancer.

An association between migratory venous thrombosis or acute pulmonary embolism and occult cancer has been previously suggested. The relationship between the commoner deep venous thrombosis (DVT) in an otherwise healthy individual and occult cancer is not known. The incidence of cancer in 35 otherwise healthy patients with idiopathic DVT (group A) was compared to 48 patients with DVT due to a known etiology, excluding cancer (group B). In 12 patients of group A (34%), a diagnosis of cancer was established 4-68 months after the DVT episode, compared to 2 patients of group B (4%) (P = 0.001). The origin of the earliest discovered cancer (up to 8 months) was the reproductive organs (ovary, endometrium, prostate, breast), while the later discovered malignancies were of colon, pancreas, lung and a lymphoma. At the initial idiopathic DVT episode, patients found subsequently to have cancer, were older than the control group (P less than 0.01), had hemoglobin concentration lower than 12.4 g/dl (P less than 0.02), and had eosinophil counts higher than 3% (P less than 0.01). A score devised from these parameters could identify 83% of the patients with cancer and 91% of those without malignancy (P = 0.00003). These findings indicate that there is a correlation between idiopathic DVT and occult cancer and that the majority of the patients at risk may probably be identified early by the score devised.

Age Factors↗
PubMed1986

Isolation and partial characterization of endothelial cell extracellular complexes.

Human endothelial cells release components into the growth medium that stimulate cell-substratum adhesion. Several macromolecular components were isolated by ultracentrifugation of the endothelial cell conditioned medium. The components were heterogeneous, consisting of several sizes when examined by sedimentation velocity and gel filtration. When the extracellular components were evaluated by electron microscopy, structurally discrete particles were observed. The extracellular components and the complexes mediated cell-substratum adhesion to both human umbilical and arterial endothelial cells. The majority of the extracellular components that promote endothelial cell adhesion were pelleted by ultracentrifugation. Although the complexes contained fibronectin, antibodies to fibronectin did not inhibit cell adhesion to the complexes. Significant inhibition of endothelial cell adhesion was observed in the presence of heparin and heparan sulfate. The supernatant fraction following ultracentrifugation of the growth medium contained a component that suppressed endothelial cell adhesion to culture dishes coated with fibronectin, type I collagen, and endothelial cell complexes. SDS-polyacrylamide gel electrophoresis indicated that the complexes contained several components, and the majority of the large-molecular-weight components were pelleted by ultracentrifugation. The conditioned medium from human endothelial cells contains specific complexes that promote cell-substratum adhesion and components that suppress cell-substratum adhesion.

Antigens, Surface↗
PubMed1986

Tumor nuclear grade, estrogen receptor, and progesterone receptor: their value alone or in combination as indicators of outcome following adjuvant therapy for breast cancer.

Previous reports by us have shown that the outcome of breast cancer patients who have received systemic adjuvant therapy is influenced by tumor estrogen or progesterone receptor (ER or PR) content or by nuclear grade. This publication provides information regarding the relative merit of those three markers. Findings from patients receiving L-PAM plus 5-FU (PF) or PF plus tamoxifen (PFT) indicate that the disease-free survival and survival within each regimen was almost identical when related to either ER, PR, or nuclear grade. Those having tumors with either of the receptors greater than or equal to 10 fmol or a good nuclear grade had a better outcome through five postoperative years than did those with ER or PR 0-9 fmol or poor nuclear grade. The magnitude of the difference was similar for each of the three discriminants. Since they were found to be of equal predictive value, one marker might well serve as a substitute for another. Cox regression analyses, however, clearly indicate that ER, PR, and nuclear grade have an independent influence on outcome and that a more accurate assessment of outcome is obtained when more than one marker is employed. Thus, information should be obtained on as many markers as possible. This conclusion is supported by observations presented which indicate that nuclear grade in combination with either or both of the receptors is a better predictor than either marker alone and that, as indicated by life table probability values and relative odds ratios, an increasing number of favorable tumor prognostic indicators results in a better patient outcome particularly in PFT-treated patients. A possible explanation is considered for why the separation of receptor/nuclear grade categories is more orderly and pronounced in PF-treated patients receiving tamoxifen than in those given PF alone.

Aged↗
PubMed1986

Spontaneous loss of HBeAg and the prevalence of HTLV-III/LAV infection in a cohort of homosexual hepatitis B virus carriers and the implications for antiviral therapy.

The future design of controlled trials of antiviral therapy which might include homosexual hepatitis B virus (HBV) carriers requires base-line data on the spontaneous rate of loss of HBeAg and the prevalence of human T-lymphotropic virus III (HTLV-III/LAV) infection. Fifty-one untreated HBsAg and HBeAg-positive homosexual HBV carriers were followed for a median HBeAg-positive time of 23.5 months (range 6-85.5). Ten lost HBeAg, giving an annual rate of spontaneous loss of HBeAg of 10%. This rate is considerably higher than the apparent rate in a previous report and has considerable implications for the interpretation of previous, and the design of future, controlled trials in this population. A rapid rise in the prevalence of anti-HTLV-III/LAV amongst HBV carriers was demonstrated from 1981 such that by 1984 over 60% of HBV carriers were anti-HTLV-III-positive. HBV-DNA polymerase levels were not significantly different in asymptomatic anti-HTLV-III/LAV-positive compared to anti-HTLV-III/LAV-negative HBV carriers. Nevertheless, since chronic HTLV-III/LAV infection in its later stages may potentiate HBV replication, it is a factor that will need to be considered together with many others in any trial stratification procedure.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Focal loss of anterior horn cells in the cervical cord in motor neuron disease.

In a three-dimensional study of the distribution of anterior horn cells in the C8 segment of the human spinal cord we have recognized lateral and medial zones of motor neuron groupings, but have not been able to recognize subgroups of neurons within these groupings resembling the anatomical columns described by earlier investigators. This observation does not invalidate the concept of functional groupings within these anterior horn cell pools. In studies of the same segment in cords obtained at autopsy from patients with motor neuron disease, zones of focal loss of motor neurons were identified, without consistent severity or distribution at different sectional levels. These findings imply varying resistance to the disease in different pools of motor neurons.

Aged↗
PubMed1986

Effects of intensified practitioner-patient communication on control of diabetes mellitus.

Control of diabetes mellitus requires active participation of patients in self-care and ongoing support from medical professionals. This study examines the hypothesis that control of diabetes can be improved by more frequent communication between patients and medical professionals. We instructed 233 insulin-requiring diabetic patients to mail the results of home blood glucose monitoring to the physician's office at least every two weeks. Feedback from office nurse practitioners followed receipt of these reports, providing frequent two-way communication between regularly scheduled office appointments. In the group of patients who mailed reports more than 26 weeks during the year, the mean glycosylated hemoglobin (GHb) value was 10.4% at baseline, and there was a mean decrease in GHb of 1.0% during the succeeding year (P = .001). In patients who mailed reports less than 26 weeks during the year, mean GHb was 10.2% at baseline, and there was no significant change during the succeeding year. Since mean GHb was virtually identical in the two groups at baseline, mailing the reports of home-determined blood glucose levels and receiving feedback between office visits resulted in improved control of diabetes.

Blood Glucose↗
PubMed1986

RASM, a "new' low-frequency blood group antigen.

A 'new' low-frequency red cell antigen, RASM, was found in 3 generations of a Caucasian family. It is inherited as a Mendelian dominant character. The propositus, a newborn, had a positive direct antiglobulin test; overt haemolytic disease of the newborn was not present.

Antigens, Surface↗
PubMed1986

Restriction endonuclease activities in the legionellae.

Fifteen legionellae isolates were studied for the presence of restriction endonucleases. At least three different specificities were found in nine of these isolates. One particular activity was present in two groups of isolates isolated from widely separated geographic areas.

Bacteriophage lambda↗
PubMed1986

Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial.

In this National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial, 1,891 women with primary operable breast cancer and positive axillary nodes were randomized between Jan, 1977 and May 1980 to receive L-phenylalanine mustard (L-PAM) and 5-fluorouracil (5-FU) either with or without tamoxifen (TAM)-PFT. This report presents life table probabilities, cumulative odds ratios, and P values for disease-free survival (DFS) and survival at yearly intervals through 5 years of observation (mean time on study, 72 months). When patients were examined overall without regard for any discriminant associated with outcome, ie, age, number of positive nodes, or tumor receptor status, there was a significant prolongation of DFS (P = .002), but not survival through the fifth postoperative year. The benefit was almost entirely restricted to those greater than or equal to 50 years with greater than or equal to 4 positive nodes. In that group there was a 66% greater chance of remaining disease free if PFT was received (P less than .001), and there was also a significant survival benefit (P = .02). The advantage from PFT was found to be associated with tumor estrogen receptor (ER) and progesterone receptor (PR) as well as patient age and nodal status. Overall there was a significant improvement in DFS from PFT in those having tumors with an ER or PR level greater than or equal to 10 femtomole (fmol) (P = .01 and .009, respectively). No significant benefit in DFS or survival has been observed in patients less than or equal to 49 years old related either to nodes or tumor receptor status. Survival continues to be adversely affected by TAM in those patients (less than or equal to 49 years old), particularly when their tumors have a PR of 0 to 9 fmol (P = .007). In patients greater than or equal to 50 years old with four or more positive nodes, a significant DFS benefit persisted through the fifth year of observation in those having tumor ER or PR levels greater than 10 fmol (P less than .001 and .002). The advantage was observed in patients 50 to 59 years old as well as those 60 to 70. Women in the older decade demonstrated some advantage from PFT when their tumor ER or PR was 0 to 9 fmol. The most likely explanation for this finding is analytical error in receptor analyses.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1986

The int-1 proto-oncogene.

The int-1 proto-oncogene is the first cellular gene discovered and implicated in tumorigenesis solely on the basis of repeated insertional mutations that activate transcription of the gene. The gene is silent in most tissues but expressed in the embryonic central nervous system, in the late (post-meiotic) stages of spermatogenesis, and in a high proportion of mouse mammary tumor virus-induced carcinomas, when a provirus is inserted upstream or downstream of the coding domain. The functional significance of int-1 in the oncogenic process is supported by the demonstration that murine leukemia virus-based vectors carrying the gene can alter the morphology and growth properties of an established line of mammary epithelial cells. The predicted primary protein product of the int-1 gene is 370 amino acids in length and cysteine-rich; immunoprecipitation with anti-peptide antibodies reveals multiple species of int-1 protein, due to asparagine-linked glycosylations and probable cleavage of a signal peptide. However, the active product of the gene and its biochemical behavior during normal development and mammary tumorigenesis are not known.

Animals↗