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Biomedical subjects

D Brown

Publications and source records attributed to D Brown.

At least 757 records · Page 42Linked to original sources
PubMed1990

Reduction of vinblastine neurotoxicity in mice utilizing a collagen matrix carrier.

Vinblastine sulfate (VLB) suspended within a collagen matrix (CM) as a diffusion limiting drug delivery vehicle was examined in vitro, as well as in mouse subcutaneous and brain tumor models. Against RIF-1 and KHT subcutaneous tumors, there was enhancement of antitumor activity with intratumoral (i.t.) delivery of VLB when it was combined with CM and/or epinephrine (epi) provided as a vasoactive agent to limit diffusion of VLB away from the injection site. Furthermore, in pharmacokinetic studies an 3-fold enhancement of tumor exposure to drug (AUC) with the CM-formulation was observed relative to the administration of free VLB i.t. Craniotactic injection of VLB into mouse brain in doses from 0.2 to 2 mg/kg revealed that the CM association markedly reduced the acute toxicity of VLB in normal mouse brain. Furthermore, mice with stereotactically implanted KHT brain tumors treated with 0.2 mg/kg VLB in CM had less tumor present in the brain histologically compared to the free VLB and untreated control groups.

Animals↗
PubMed1990

Treatment of condyloma acuminatum with three different interferon-alpha preparations administered parenterally: a double-blind, placebo-controlled trial.

One hundred seventy-eight patients were enrolled in a placebo-controlled trial to evaluate three interferon-alpha preparations administered parenterally for the treatment of condyloma acuminatum. When all interferon groups were combined and compared with placebo, interferon recipients had greater rates of complete, 75%, 50%, and 25% lesion resolution than did placebo recipients (P = .21, P = .14, P = .02, and P = .02, respectively). Rates of lesion resolution were higher among women than among men, and women were more likely than men to respond to interferon. Virologic measurements in paired lesion biopsies did not correlate with interferon treatment or disease outcome. Although interferon toxicity was observed frequently, no participant withdrew from the study because of side effects, and dosage alterations were not required. Parenterally administered interferon-alpha is more effective than placebo in treating condyloma acuminatum, although rates of complete response are low. Different regimens, including combination therapy, should be evaluated for treatment of this common sexually transmitted disease.

Adult↗
PubMed1990

Skin grafting: dermal components in inhibition of wound contraction.

The inhibition of wound contraction by skin grafting is widely accepted but poorly understood. We used an experimental model of contraction to study the effect of dermal organization, cellularity, and collagen matrix on contraction inhibition. Wound beds covered with inverted and collagen matrix grafts contracted at the same rate as full-thickness grafts. Heat denaturation diminished this ability. Partial-thickness grafts derived from papillary or reticular dermis inhibited contraction to an equal degree. Inhibition of contraction appears to relate to the amount of intact dermal collagen matrix transferred, and not to another component of a full-thickness graft.

Animals↗
PubMed1990

New developments in the Life Table Analysis System of the National Institute for Occupational Safety and Health.

In the 1970s, the National Institute for Occupational Safety and Health developed a Life Table Analysis System to analyze occupational cohort studies. We have updated the original system by adding two new features: direct standardization with a test for linear trend, and analyses by lagged exposure (either duration of exposure or cumulative exposure). We have also updated US reference rates through 1989. The updated systems and documentation (version F) are available upon request. In collaboration with the National Cancer Institute, we have also developed multiple cause-of-death rate files, which consider contributory as well as underlying cause. These files (also available upon request) will enable investigators to derive the expected prevalence of diseases at death, which can then be compared with the observed prevalence in an exposed cohort. Work is currently underway to produce a personal computer version of the Life Table Analysis System.

Cause of Death↗
PubMed1990

The combined effect of incubation temperature, pH and sorbic acid on the probability of growth of non-proteolytic, type B Clostridium botulinum.

It has been reported that non-proteolytic strains of Clostridium botulinum will grow at 3.3 degrees C, and they are therefore of concern in relation to certain chilled foods. The effects of combinations of inhibitory factors may be used to reduce the risk of growth of these bacteria in foods. The combined effect of pH values between 4.8 and 7.0, temperatures between 6 degrees and 30 degrees C, and sorbic acid concentrations up to 2270 mg/l on the probability of growth from a single spore of non-proteolytic, type B strains in a culture medium has been determined. A mathematical model has been developed that enables the effect of varying combinations of these factors on the probability of growth of non-proteolytic, type B Cl. botulinum to be predicted.

Clostridium botulinum↗
PubMed1990

The localization of somatostatin-like immunoreactivity in the alimentary tract of the sheep with observations on the effect of an infection with the parasite Haemonchus contortus.

Cells containing somatostatin immunoreactivity were localized in the alimentary tract of parasite-free sheep by indirect immunocytochemistry, using an antiserum raised to ovine somatostatin. Nerve fibres showing somatostatin-like immunoreactivity were identified in the oesophagus, reticulum wall and groove, rumen pillar and wall, omasum sulcus and abomasum. Varicose fibres were found in the myenteric plexuses of the duodenum, jejunum, ileum and colon. The greatest distribution of endocrine cells (99 cells mm-2) was found in the antrum of the abomasum with 47, 29, 12 and 6 cells mm-2 respectively in the fundus, the first part of the duodenum, mid-jejunum and ileum. Some of the parasite-free sheep which had never experienced infection with larvae of the abomasal nematode, Haemonchus contortus, were paired with similar sheep in an experiment to investigate the effect of parasitism on nitrogen metabolism in the small intestine. The protocol of this experiment required observations before and after parasite infection, with final observations 2 weeks after removal of the infection by treatment with an anthelmintic drug. The sheep were then killed and tissues taken from each paired animal. Tissues from the recently parasitized sheep showed increases of D cells in the fundus and antrum of the abomasum. At present it is not clear if these increases were related to parasitism, per se, or were the post-treatment indicators of healing and recovery from infection with parasite larvae.

Animals↗
PubMed1990

Brush-border membrane alkaline phosphatase activity in mouse Peyer's patch follicle-associated enterocytes.

1. Using a new method of quantitative cytochemistry to determine alkaline phosphatase activity, it was possible to identify M cells and distinguish two further types of enterocytes present in mouse Peyer's patch follicle-associated epithelial tissue. 2. A quantitative description of these three cell types was provided by making direct absorbance measurements of enzyme reaction product on the luminal surface of individual follicle-associated enterocytes. M cells having a negligible alkaline phosphatase activity had a mean absorbance of 6 +/- 2 arbitrary units. The other two populations of enterocytes had overlapping but significantly different mean absorbances of 20 +/- 2 and 30 +/- 3 arbitrary units. 3. M cells accounted for 3.2 +/- 1% of the total number of cells present in the apical part of the follicle-associated epithelium. This percentage is a minimum value describing an extreme example of cells having M cell-like characteristics. The remaining epithelial cells were divided equally between those having high and low alkaline phosphatase activities in their brush-border membranes. A small percentage of cells having low alkaline phosphatase activities could perform M cell functions. 4. Results obtained suggest that reduced alkaline phosphatase activity and brush-border membrane Cl- conductance can both be used as differentiation markers to identify a large population of poorly differentiated enterocytes present in mouse follicle-associated epithelial tissue.

Alkaline Phosphatase↗
PubMed1990

Antibody to hepatitis C virus in multiply transfused patients with thalassaemia major.

Seventeen of 73 (23.3%) multiply transfused patients with thalassaemia major (age range, 1-39 years) tested positive for antibody to hepatitis C virus (anti-HCV). Eleven of the 24 patients regularly transfused in countries outside Britain were anti-HCV seropositive; only six of the 49 regularly transfused in Britain were seropositive. The incidence of anti-HBs and anti-HBc was similar to that of anti-HCV in both the British and foreign patients. The anti-HCV seropositive patients showed significantly higher plasma aspartate aminotransferase activities (AST), mean (SD) 10.2 (70.3) U/l, and serum ferritin concentrations, 4067 (2708) micrograms/l, than the anti-HCV seronegative patients (AST, 33.9 (15.6) U/l; serum ferritin 2051 (2092) U/l), respectively. Among the 36 patients who had earlier undergone liver biopsy 10 of 21 with histological features of chronic active hepatitis or cirrhosis, or both, were seropositive for anti-HCV whereas only one of 15 without histological evidence of chronic viral hepatitis was seropositive for anti-HCV. It is concluded that HCV is a major cause of chronic hepatitis in patients with thalassaemia major and is associated with raised AST activity and serum ferritin concentration compared with patients seronegative for anti-HCV.

Adolescent↗
PubMed1990

FITC-dextran as a probe for endosome function and localization in kidney.

Fluorescein isothiocyanate (FITC)-labeled endosomes were localized in kidney epithelial cells after tissue fixation and sectioning, and specific membrane transport properties of isolated endocytic vesicles were measured using the same probe. Rats were infused intravenously with 10 kDa FITC-dextran, and kidneys were fixed with paraformaldehyde lysine periodate. FITC-labeled vesicles were visualized in semithin (1 micron) frozen sections of excised tissue by epifluorescent microscopy and by electron microscopy after a photoconversion reaction. Most FITC-labeled endosomes were apically located in epithelial cells lining the urinary tubules. By immunocytochemistry the anti-lysosomal glycoprotein LGP 120 was absent from most of the FITC-labeled vesicles, although some colocalization was noted. The limiting membrane of FITC-labeled endosomes contained a vacuolar proton pump (pHmin = 6.23 +/- 0.033) and a water channel (osmotic water permeability coefficient, Pf = 0.052 +/- 0.005 cm/s) and was highly permeable to ethylene glycol and urea but relatively impermeable to glucose. Methods allowing the attribution of specific membrane functions to vesicles that can be visualized in the apical endocytic pathway of epithelial cells should be of general use for the study of endocytic pathways in a variety of systems.

Adenosine Triphosphate↗
PubMed1990

Liver glucose transporter: a basolateral protein in hepatocytes and intestine and kidney cells.

The "liver" isoform of the facilitated diffusion glucose transporter is expressed predominantly in liver, intestine, kidney, and pancreatic islet beta-cells. The apparent molecular mass of the transporter in liver, kidney, and intestine is different, as detected by Western blot analysis of membrane proteins using antipeptide antibodies. However, as assessed by Northern blot analysis and molecular cloning, the same mRNA is expressed in these tissues, indicating that there are tissue-specific posttranslational modifications of the same transporter polypeptide. As determined by immunofluorescence analysis on frozen tissue sections, the liver glucose transporter is present on the sinusoidal membrane of hepatocytes, on the basolateral membrane of fully differentiated absorptive intestine epithelial cells, and on the basolateral membrane of proximal tubule cells of the kidney nephron. This localization is consistent with the involvement of the liver glucose transporter in several key steps of glucose metabolism: glucose uptake and release by the liver and absorption or reabsorption by epithelial cells of the intestine and kidney, respectively.

Animals↗
PubMed1990

Differential localization of two glucose transporter isoforms in rat kidney.

The localization of two glucose transporter isoforms was mapped in the rat kidney: the high-Michaelis constant (Km; 15-20 mM) low-affinity "liver" transporter and the low-Km (1-2 mM) high-affinity "erythroid/brain" transporter. Both are basolateral membrane proteins, but the liver transporter was present exclusively in the S1 part of the proximal tubule, whereas the erythroid/brain transporter was expressed at variable levels in different nephron segments. Staining intensity was low in the straight proximal tubule (S3), intermediate in the medullary thin and thick ascending limbs, and highest in connecting segments and collecting ducts. In the collecting duct, the erythroid/brain glucose transporter was expressed at the highest level in intercalated cells; less was present in principal cells. In the papilla, only intercalated cells expressed this transporter isoform. These results suggest specific involvements of each transporter isoform in transepithelial glucose reabsorption by different segments of the proximal tubule. They also indicate that while the liver glucose transporter is present in gluconeogenic cells, there is a good correlation between the level of expression of the erythroid/brain glucose transporter and the glycolytic activity of the different nephron segments.

Animals↗
PubMed1990

Endocytosis of water channels in rat kidney: cell specificity and correlation with in vivo antidiuresis.

Vasopressin action in the renal collecting duct is believed to be mediated by the cycling of water channels in principal and, possibly, intercalated cells. We used 6-carboxyfluorescein (6-CF) or fluorescein-labeled dextran (FITC-dextran) to determine the location and water permeability of endocytic vesicles from papilla and inner stripe of Brattleboro rats in different states of diuresis. Fifteen minutes after FITC-dextran infusion, fluorescent vesicles were concentrated at the apical pole of principal and intercalated cells. The osmotic water permeability (Pf) of these endosomes was measured by fluorescence quenching. In papillary endosomes, Pf was high (0.04 +/- 0.004 cm/s) when rats were in physiological states of antidiuresis or after treatment with vasopressin, 1-desamino-8-D-arginine vasopressin (DDAVP), or oxytocin; endosomes isolated from these regions of untreated animals had a low Pf. The number of papillary endosomes with high Pf increased with increasing doses of DDAVP. Endosomes from the inner stripe also had a high Pf only after vasopressin treatment. Confocal microscopy of sections of papilla showed that vasopressin significantly increased endocytosis in principal cells but had no effect on intercalated cells. Our data demonstrate that the bulk of fluorescently labeled vesicles from the papilla originate from the apical membrane of principal cells and contain water channels in their limiting membrane only when the rats are in physiological states of antidiuresis. In contrast, the majority of endocytosis in intercalated cells is not involved in water channel recycling.

Animals↗
PubMed1990

Na+(Li+)-H+ exchange in rat renal cortical vesicles with endosomal characteristics.

Preparations of rat renal cortical endocytic vesicles, loaded with fluorescein isothiocyanate-labeled dextran (FITC-dextran) in vivo had an ATP-dependent N-ethylmaleimide (NEM)-sensitive H+ pump and, in addition, showed a limited activity of an electroneutral Na(+)-H+ and Li(+)-H+ exchanger. However, the majority of FITC-dextran-containing vesicles possessed only the H+ pump. The H+ pump and the electroneutral Na+(Li+)-H+ antiporter colocalized in only a small proportion of FITC-dextran-containing vesicles. These vesicles also exhibited marked electrically coupled Na+, Li+, and H+ movement due to conductances in the vesicle membrane for these cations. As measured by the acridine orange fluorescence quench method, the electroneutral Na(+)-H+ exchange in endosomal preparations obeyed hyperbolic kinetics with an apparent Michaelis constant (Km) for Na+ of 5.9 mM and resembled that of brush-border membrane vesicles (BBMV) isolated from the same tissue (Km for Na+, 3.7 mM). The endosomal Na+(Li+)-H+ exchange was not affected by the presence or absence of ATP or NEM. However, Li+, added before or simultaneously with Na+, inhibited the endosomal Na(+)-H+ antiporter. The Na+(Li+)-H+ antiporter was insensitive to extravesicular amiloride but was partially inhibited by intravesicular amiloride. Acidic buffers stimulated the activity of the electroneutral exchanger. We found that vesicles with similar characteristics contaminate preparations of right-side-out BBMV. We conclude that the vesicles with endosomal characteristics, which contain both a vacuolar-type H+ pump and the Na+(Li+)-H+ antiporter, are either a special pool of endocytic vesicles responsible for the trafficking of the exchanger between intracellular and luminal membranes or are inside-out BBMV that form during the homogenization of the tissue.

Amiloride↗
PubMed1990

Polarization of gelsolin and actin binding protein in kidney epithelial cells.

Vasopressin regulates transepithelial osmotic water permeability in the kidney collecting duct and in target cells in other tissues. In the presence of hormone, water channels are inserted into an otherwise impermeable apical plasma membrane and the apical surface of these cells is dramatically remodelled. Because cytochalasin B and D greatly reduce the response of these cells to vasopressin, actin filaments are believed to participate in the events leading to an increase in transepithelial water permeability. Modulation of the actin filamentous network requires the concerted action of specific actin regulatory proteins, and in the present study we used protein A-gold immunocytochemistry to localize two important molecules, gelsolin and actin binding protein (ABP), in epithelial cells of the kidney inner medulla. Gelsolin and, to a lesser extent, ABP were concentrated in clusters in the apical cell web of principal cells of the collecting duct. Aggregates of gold particles were often associated with the cytoplasmic side of plasma membrane regions forming surface extensions or microvilli. The basolateral plasma membrane was labeled to a much lesser extent than the apical plasma membrane. In the thin limbs of Henle, ABP was localized over the apical plasma membrane in ascending limbs, but gelsolin labeling was weak in these cells. In thin descending limbs, the pattern of labeling was completely reversed, with abundant apical gelsolin labeling but only weak ABP immunolabeling. Although the significance of the distribution of actin regulatory proteins in thin limbs is unknown, the abundance and the predominantly apical polarization of both ABP and gelsolin in principal cells of the collecting duct is consistent with a role of the actin cytoskeleton in the mechanism of vasopressin actin.

Animals↗
PubMed1990

Differential release of TNF-alpha, IL 1, and PGE2 by human blood monocytes subsequent to interaction with different bacterial derived agents.

The purpose of these studies was to determine whether the tumoricidal phenotype of human blood monocytes would be affected by different activation signals. Human monocytes obtained by elutriation of buffy coats were cultured in vitro in medium containing LPS, muramyltripeptide phosphatidylethanolamine (MTP-PE), or a lipopeptide analogue of gram-negative bacteria cell wall. These immunomodulators were added to monocytes in the presence or absence of IFN-gamma. Incubation with LPS, lipopeptide, and MTP-PE rendered the monocyte cytotoxic against allogeneic melanoma cells. Monocytes treated with LPS and lipopeptide (in the absence of IFN-gamma) secreted IL 1, TNF, and PGE2. In contrast, monocytes incubated with MTP-PE (in the absence of IFN-gamma) secreted only TNF. When the monocytes were coincubated with IFN-gamma (human but not mouse) and the immunomodulators, IL 1, TNF, and PGE2 were secreted at all test groups. These data show that some immunomodulators can regulate the release of TNF independently of IL 1 and that not all "activated tumoricidal macrophages" share identical phenotypes.

Acetylmuramyl-Alanyl-Isoglutamine↗