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D Brown

Publications and source records attributed to D Brown.

At least 703 records · Page 39Linked to original sources
PubMed1991

Differential exposure of epitopes on the human red cell antigen D (Rh).

The D polypeptide of the human Rh blood group system has a number of different epitopes on its surface. It is also known that there is considerable variation in the number of D antigen sites available to different human monoclonal anti-D antibodies. For instance, certain monoclonal antibodies recognise only a small number of sites on the red cell surface (about 9,000 sites/red cell on R1R2 cells) whereas other antibodies recognise a high number (about 20,000-30,000 sites/red cell). It has been found that cholesterol enrichment of the red cell membrane increases the number of sites available to those antibodies which recognize only a few sites but has no effect on those recognising many sites. The results are consistent with the view that access to some of the D epitopes is partially hindered by neighbouring molecules in the membrane and that alteration of the lipid content of the membrane changes it in such a way as to allow increased access to these obstructed epitopes.

Antibodies, Monoclonal↗
PubMed1991

The role of affiliative loss in the recruitment of helper cells among insulin-dependent diabetics.

The study was undertaken to determine whether affiliative loss might play a role in the development of insulin-dependent diabetes by increasing the percentage of helper-inducer T cells when diabetics were reminded of the loss. It was found that diabetics who had experienced the recent death of a loved one showed a marked increase in helper cells, in contrast to diabetics who had not experienced a recent death, after both groups viewed a film about a happy, but doomed, love affair. The diabetics who had experienced a recent death also showed more affiliative distress after viewing the film. This increase in distress was associated with a physiological sign of increased activation, namely, increased plasma cortisol output, which in turn was associated with gains in helper-cell percentages. This suggests that frequent reminders of severe affiliative disturbances during the pre-onset histories of such diabetics may result in physiological activation, which leads to periodical recruitment of helper cells, which could augment the immune attack on the insulin-producing cells in the pancreas. None of these results was obtained with controls, which suggests that the diabetics were unusually sensitive to affiliative distress.

Adult↗
PubMed1991

Localization of the protein product of the immediate early growth response gene, Egr-1, in the kidney after ischemia and reperfusion.

Egr-1 is an "immediate early" gene that is induced by growth factors and agents that induce differentiation and encodes a protein with a "zinc-finger" motif. This protein is believed to be involved in transcriptional regulation. Because the fate of the kidney, and hence the organism, after an ischemic insult is dependent upon cellular repair, differentiation, and proliferation, we examined whether there was expression of the Egr-1 protein after an ischemic insult to the rat kidney. We have previously reported that Egr-1 mRNA accumulates to high levels in mouse kidneys after 30 min of ischemia and 1 h of reperfusion. In the present study, performed in rats, we show that Egr-1 mRNA transiently accumulates to very high levels after 40 min of ischemia and 1 h of reperfusion, is decreased by 3 h, and is nondetectable by 24 h of reperfusion. Reperfusion is required for Egr-1 protein accumulation to occur. The Egr-1 protein was localized by immunohistochemical techniques primarily to the nuclei of the thick ascending limbs and principal cells of the collecting ducts in the cortex and medulla. The subcellular localization was exclusively nuclear. There was some staining of the glomerular tuft and staining was particularly prominent in the parietal epithelial cells. In parallel to the accumulation of Egr-1 mRNA, the expression of the protein was transient and was no longer apparent after 5 h of reperfusion. The Egr-1 protein may play an important role in regulation of the response to ischemia of those segments of the nephron that are highly susceptible to oxygen deprivation and have a high level of intrinsic plasticity. It is possible that this protein may modulate cellular processes important for the ultimate ability of these critical nephron segments to recover from an ischemic insult.

Animals↗
PubMed1991

Evaluation of a test based on baculovirus-expressed glycoprotein G for detection of herpes simplex virus type-specific antibodies.

An immunoblot assay for discrimination of antibodies to herpes simplex virus (HSV) types 1 and 2 was devised using extracts of recombinant-baculovirus-infected insect cells expressing HSV-1 or -2 glycoprotein G (gG1 or gG2). The assay was evaluated by comparing its results with those obtained by using an immunodot assay based on gG immunopurified from HSV-1- and HSV-2-infected cells. Each of 110 human serum specimens was tested blindly and independently three times. At a serum dilution of 1:20, the maximum specificities were 96% and 100% and the maximum sensitivities were 100% and 92% for gG1 and gG2, respectively. Reproducibility was 99% among readers and 95% among individually tested samples of each specimen. Results obtained in two laboratories from a different set of 15 serum specimens were in complete agreement, indicating the assay is accurate and reproducible. The ease of antigen production should allow the test to become widely available.

Animals↗
PubMed1991

The validity of lecturer ratings by students and trained observers.

This study sought to determine to what degree student ratings of specific lecturer characteristics relate to trained observer ratings of such characteristics and to identify the distinguishing delivery characteristics of highly rated lecturers. The 15 lowest-rated lecturers and the 15 highest-rated lecturers, based on the mean ratings of students from two consecutive years (1982 and 1983) in a large multi-instructor course, served as the target group. Blinded non-student raters observed the lectures in 1984 (two per lecture) and completed quantitative and qualitative forms. For all six subscores from the quantitative form, statistically significant differences between the lecturers given the highest and lowest ratings were obtained. It is concluded that the students' ratings were stable across the three years; the independent observers discriminated between the lecturers the students rated the highest and the lowest; voice presentation characteristics discriminated the most effectively; and nonmedical non-student observers are potentially a useful source of information regarding faculty teaching skills.

Education, Medical, Undergraduate↗
PubMed1991

Optimization of the liposomes encapsulating a new lipopeptide CGP 31362 for efficient activation of tumoricidal properties in monocytes and macrophages.

The purpose of this study was to optimize a suitable liposomal carrier for CGP 31362, a new synthetic lipopeptide analogue of gram-negative bacterial cell walls. CGP 31362 was inserted into the membranes of different liposomes with different phospholipid composition. We determined the ability of these liposomes to activate tumoricidal properties in mouse peritoneal and bone marrow macrophages, and in human monocytes. The ideal liposome carrier for CGP 31362 consisted of phosphatidylcholine and phosphatidylserine in a 7:3 molar ratio. Subsequent to efficient binding and endocytosis, CGP 31362 in liposomes of this composition rendered mouse macrophages and human monocytes highly tumoricidal. Moreover, even in the absence of interferon-gamma, human monocytes released significant levels of tumor necrosis factor and interleukin-1. These data show that in a suitable liposomal carrier, the new synthetic lipopeptide in liposomes is a potent activator of tumoricidal properties in macrophages.

Animals↗
PubMed1991

Alexithymic characteristics and metabolic control in diabetic and healthy adults.

Diabetes has long been identified as a disease with possible psychological components. Alexithymia--an inability to express emotions verbally, operational thinking, and a lack of fantasy life--is found in a high proportion of psychosomatic patients. We therefore tested the hypothesis that diabetics would be more alexithymic than controls. In addition, the lack of awareness of affect was hypothesized to have negative consequences for the management of diabetes, as reflected in metabolic glucose control (HbA1). The number of emotion words produced in six imaginative (Thematic Apperception Test) stories was used as the measure of alexithymia, with few words reflecting alexithymic characteristics. Diabetics were found to be significantly more alexithymic than controls. Further, fewer emotion words (alexithymia) was associated with poorer metabolic control. These data suggest that alexithymic characteristics may interfere with a diabetic's ability to manage their illness, and support previous research showing that the suppression of emotions can lead to a difficulty in regulating glucose levels.

Adolescent↗
PubMed1991

Influence of mild cold on the components of 24 hour thermogenesis in rats.

1. The influence of two weeks' acclimation to either 28 degrees C (thermal neutrality) or 21 degrees C (mild cold) on 24 h heat production and motor activity has been investigated in male Wistar rats. Food intake was controlled and provided as a single meal of approximately 170 kJ per day. Mathematical modelling was used to relate metabolic rate to measured movement and time of day. 2. For animals at thermal neutrality it was clear that metabolic rate increased during periods of substantial measured movement and returned to baseline during periods of minimal activity. Total heat production could therefore be divided into two components: underlying and movement-induced thermogenesis. 3. At 21 degrees C, a more complex model was needed. During periods of substantial activity, the relation between metabolic rate and movement was similar to that at 28 degrees C and total heat production could be divided into the same two components of underlying and movement-induced thermogenesis. However, during periods of prolonged inactivity, a different model was required, which included a component of extra metabolic activity, termed supplementary thermogenesis. By fitting this model to data at 28 and 21 degrees C, it was possible to partition 24 h heat production into the three possible sources of underlying, movement-induced and supplementary thermogenesis. 4. Total 24 h heat production was approximately 25% higher for rats at 21 compared with 28 degrees C (P less than 0.01) and underlying thermogenesis was approximately 20% higher for those in the mild cold (P less than 0.01). Measured movement was significantly reduced in the mild cold (P less than 0.05) although it was energetically less efficient since there was no difference in movement-induced thermogenesis, which accounted for 18 and 15% of total heat production at 28 and 21 degrees C respectively. Supplementary thermogenesis was observed only in the mild cold and it accounted for approximately 6% of 24 h heat production, while the peak value accounted for 20% of total heat production. Circadian variations in thermogenesis were also different at 28 compared with 21 degrees C. Possible mechanisms accounting for the components of underlying thermogenesis and supplementary thermogenesis are discussed.

Animals↗
PubMed1991

Heterogeneous localization of G protein alpha-subunits in rat kidney.

The Gs alpha and Gi alpha 1-3 subunits of GTP-binding proteins were localized in sections of rat kidney using antibodies against unique synthetic decapeptides from the different G alpha subunits. All of the G alpha subunits were found to have a polarized distribution on renal tubule epithelial cells, and staining was typically found on either basolateral or apical membranes in a given cell type. Gi alpha 1 was localized to the apical pole of both thick ascending limb cells and cells forming the papillary epithelium, Gi alpha 2 labeled the basolateral plasma membrane and the cytoplasm of collecting duct principal cells, and Gi alpha 3 was most abundant in the apical region of proximal tubule cells of the S1 segment, where it was concentrated in sub-brush-border invaginations. It was also found in the perinuclear Golgi complex in these cells. Gs alpha was heavily concentrated on the basolateral plasma membranes of thick ascending limb cells and both principal and intercalated cells of the collecting duct. Less intense subapical staining of G alpha s was also found in proximal tubule cells. The cells of the macula densa had a unique G protein distribution that was distinct from the surrounding cells of the thick ascending limb of Henle. Antibodies specific for the Gi alpha 1 and Gi alpha 3 subunits both stained intracellular vesicles clustered at the basal pole of the cell. A heterogeneous distribution of G alpha subunits was also found by Western blotting on isolated cortical membrane fractions.

Amino Acid Sequence↗
PubMed1991

Effect of aerosolized pentamidine prophylaxis on the diagnosis of Pneumocystis carinii pneumonia by induced sputum examination in patients infected with the human immunodeficiency virus.

This study assessed the effect of aerosolized pentamidine prophylaxis on the clinical presentation and diagnostic sensitivity of induced sputum examination for Pneumocystis carinii pneumonia. Between January 1, 1988 and October 27, 1990, 348 induced sputum examinations were performed as the initial diagnostic procedure for P. carinii pneumonia in patients infected with the human immunodeficiency virus (HIV). Medical records were reviewed for all induced sputum examinations, and the study group consisted of patients who either had not received prophylactic therapy (n = 193) or had received aerosolized pentamidine prophylaxis (n = 126). A total of 29 induced sputum examinations in patients receiving either other prophylactic regimens or ongoing therapy for previously documented P. carinii pneumonia were excluded from the study group. A total of 72 consecutive episodes of P. carinii pneumonia were subsequently documented by induced sputum examination (n = 54), bronchoalveolar lavage (n = 16), thoracocentesis (n = 1), or autopsy (n = 1). A total of 44 episodes occurred in patients who had not received antipneumocystis prophylaxis, and 28 episodes occurred in patients who had received aerosolized pentamidine. Of patients capable of producing a sputum specimen for analysis, induced sputum examination had a significantly lower diagnostic yield of 64.3% in patients who had received aerosolized pentamidine prophylaxis compared with 92.3% in patients who did not receive prophylaxis (p less than 0.02, Fisher's exact test). When the data were analyzed on an intention to treat basis, although there was a trend suggesting a lower overall yield in the aerosolized pentamidine patients, the difference was not statistically significant (64.3 versus 81.8%, p = 0.17, Fisher's exact test).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1991

Mild head injury as a source of developmental disabilities.

The hospital-reported incidence of mild head injury among children indicates a prevalence of 2% to 3% in high-school-aged adolescents (14 to 18 years). Yet, our survey of 616 high school adolescents suggests that light and mild head injury (not necessarily leading to hospital admission) is almost 10 times this level. Despite the common notion that such injury is generally benign, we found significant relationships in our sample between reported head injury and hyperactivity, stuttering, mixed handedness, and dislike of mathematics.

Adolescent↗
PubMed1991

An H3-H4 histone gene pair in the marine copepod Tigriopus californicus, contains an intergenic dyad symmetry element.

Histone genes are one of the most widely studied multigene families in eucaryotes. Over 200 histone genes have been sequenced, primarily in vertebrates, echinoderms, fungi and plants. We present here the structure and genomic orientation of an H3-H4 histone gene pair from the marine copepod, Tigriopus californicus. These histone gene sequences are the first to be determined for the class Crustacea and among the first to be determined for protostomes. The H4 and H3 genes in Tigriopus are shown to be adjacent, to have opposite polarity, and to contain a 26 bp region of dyad symmetry centrally located within the spacer region between the two genes. A similarly located dyad element has been found in yeast which contributes to the coordinated cell cycle control of the adjacent histone genes. The Tigriopus H3-H4 histone gene pair is clustered with one H2A and two H2B histone genes on a 15 kb genomic Bam H1 fragment. The H4 gene sequence predicts an H4 protein with an unusual serine to threonine substitution at the amino terminal residue. The H3 gene sequence predicts an H3 protein which is identical to the vertebrate H3.2 histone.

Amino Acid Sequence↗
PubMed1991

Colchicine-induced redistribution of proton pumps in kidney epithelial cells.

In kidney medulla, intercalated cells (ICs) all have an apical proton-pumping ATPase, but in the cortex, ICs with apical (type A cells) and basolateral (type B cells) proton pumps coexist. Proton pumps in proximal-tubule epithelial cells are located in a band of apical membrane at the base of the brush border. To determine the effect of microtubule disruption on proton-pump polarity in these cell types, we immunolocalized proton pumps in normal and colchicine-treated rat kidneys. In addition, NEM-sensitive ATPase was measured in brush-border (BBMV) and basolateral membrane vesicles from kidney cortex. Rats were injected with colchicine, and kidneys were fixed 4-24 h later. In both cortical and medullary IC, proton pumps were localized on vesicles that were scattered throughout the cell. A- and B-type ICs were no longer distinguishable on the basis of proton-pump polarity. In the medulla, no concentration of proton pumps at the basolateral pole of ICs was detectable. In proximal tubules, pumps were also scattered on vesicles throughout the cytoplasm. NEM-sensitive ATPase was reduced by over 60% in BBMV, and was also reduced in basolateral membranes, indicating no increased insertion of NEM-sensitive ATPase into basolateral membranes after colchicine treatment. We conclude that a change in the polymerization state of microtubules is not sufficient to account for the differential targetting of proton pumps in subpopulations of intercalated cells.

Adenosine Triphosphatases↗
PubMed1991

Loss of antigens associated with the apical endocytotic pathway in proximal tubules from rats with heymann nephritis.

In addition to the glomerular lesions associated with Heymann nephritis, a rat model of human membranous nephritis, proximal tubule damage, and a perturbation of proximal tubule function also have been reported to occur in this disease. The aim of the present study was to examine in more detail the nature of the apical plasma membrane damage in proximal tubules using specific antibodies directed against clathrin, gp330, and a proton-pumping adenosine triphosphatase, all of which are components of the apical endocytotic apparatus of these epithelial cells. Immunocytochemical studies revealed a marked reduction in staining for all three antigens in proximal tubules from rats with active Heymann nephritis. Furthermore endocytotic uptake of intravenously injected FITC-dextran was considerably lower in diseased animals than in normal rats. Gp330 and rat IgG were identified as components of the luminal debris that accumulated during the course of Heymann nephritis. These results show that perturbation of proximal tubule endocytosis occurs in Heymann nephritis together with a loss of three apical antigens that are normally localized on membrane domains associated with the apical endocytotic pathway in these cells. The results also suggest that antibody-antigen complexes may be shed from the plasma membrane in both the glomerulus and the proximal tubule in this disease.

Adenosine Triphosphatases↗
PubMed1991

In situ activation of mouse lung macrophages by coadministration of liposomes containing the lipopeptide CGP 31362 and interleukin 2 involves interaction with T lymphocytes and natural killer cells.

These studies were undertaken to determine the mechanism for augmented tumoricidal activity of alveolar macrophages (AM) in mice injected intravenously with multilamellar liposomes containing a lipopeptide analogue of Gram-negative bacteria cell wall (MLV-CGP 31362) and intraperitoneally with interleukin 2 (IL-2). BALB/c mice were injected into the kidney with syngeneic renal carcinoma cells. Ten days later, this kidney was resected, and the mice were treated intravenously with MLV-CGP 31362 and/or intraperitoneally with IL-2. Treatment with MLV-CGP 31362 led to a reduction in the number of lung metastases, whereas treatment with IL-2 alone did not. The coadministration of intravenous liposomes and intraperitoneal IL-2 produced significant eradication of lung metastases. MLV-CGP 31362 (iv) and IL-2 (ip) were injected both into control immune-competent and nude mice or into mice whose natural killer (NK) cells had been depleted by systemic administration of anti-asialo GM1 antibodies. MLV-CGP 31362 activated tumoricidal properties in AM of all groups of mice. The additive tumoricidal activation of AM by IL-2 was associated with its effects on both T cells and NK cells.

Animals↗
PubMed1991

Lack of effect of N-acetylcysteine on the release of oxygen radicals from neutrophils and alveolar macrophages.

N-acetylcysteine (NAC) is rapidly de-acetylated in vivo to cysteine (CYSH), a precursor of glutathione (GSH) which is an antioxidant in cells and body fluids. We investigated the effect of oral administration of N-acetyl cysteine for 5 days on the spontaneous and stimulated generation of hydrogen peroxide (H2O2) and superoxide anion (O2-) from human and rat phagocytic leucocytes. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL) in control rats and rats given NAC in their drinking water. Neutrophils (PMNL) were harvested from whole blood in normal nonsmoking volunteers before and after NAC was given by mouth. The stimulated release of H2O2 and O2 from both rat AM and human PMN was not changed by administration of NAC. However, a small but significant increase was observed in both the spontaneous generation of O2- from rat AM and the spontaneous generation of H2O2 from human PMNL. Administration of NAC significantly increased cysteine levels in human plasma and rat BAL, but the levels in human PMNL and rat AM after NAC did not differ from control levels. GSH levels were not altered significantly by NAC.

Acetylcysteine↗