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Biomedical subjects

D M Brown

Publications and source records attributed to D M Brown.

At least 199 records · Page 11Linked to original sources
PubMed1989

Inflammation generating potential of long and short fibre amosite asbestos samples.

Previous studies have shown that long thin asbestos fibres are more pathogenic in in vivo and more active in in vitro assays than short fibre samples. In the present study a long fibre amosite asbestos sample and a short fibre sample prepared from it were tested for ability to cause inflammation in the peritoneal cavity of the mouse; a UICC sample intermediate in fibre size and an inert compact dust, TiO2, were also tested. The ability of the dust samples to cause inflammation, as judged by macrophage and neutrophil recruitment, was ranked in the order long fibre greater than UICC greater than short fibre greater than TiO2. Ability of amosite samples to cause inflammation was therefore related to the proportion of long fibres. The enhanced ability of long fibres to cause inflammation and cause macrophage activation is probably a key factor in the ability of long fibres to cause pulmonary fibrosis and may also be important in fibre carcinogenesis.

Animals↗
PubMed1989

Release of glomerular heparan-35SO4 proteoglycan by heparin from glomeruli of streptozocin-induced diabetic rats.

Abnormalities in the incorporation of heparan sulfate proteoglycan into the glomerular basement membrane have been implicated in the pathogenesis of various proteinuric states, including diabetes mellitus. To understand further the interactions between proteoglycans and glomerular extracellular matrices, glomeruli were isolated from normal and streptozocin-induced diabetic rats after in vivo exposure to 35S-labeled sulfate and were treated with heparin in vitro. Heparin treatment released a unique heparan sulfate proteoglycan from glomerular cell surface or extracellular matrix proteoglycan receptors. Another, smaller heparan sulfate proteoglycan was the most abundant proteoglycan released into medium and was released constitutively in medium with or without added heparin. While the two heparin-extracted proteoglycans copurified on anion-exchange and gel-filtration chromatographic columns, they were resolved by composite 0.6% agarose--1.8% polyacrylamide gel electrophoresis. Glomeruli from diabetic rats contained decreased proportions of the heparin-releasable heparan sulfate proteoglycan and more constitutively released heparan sulfate proteoglycan. The apparent molecular weight and intrinsic charge of the heparin-released proteoglycan mixture and the apparent molecular weight and sulfation pattern of their 35S-labeled glycosaminoglycan chains after nitrous acid deaminative cleavage were similar in the two groups. A brief trypsin digestion of heparin-treated glomeruli released proportionately less integral membrane and extracellular matrix 35S-labeled proteoglycans and 35S-labeled glycopeptides from diabetic glomeruli than form control glomeruli. Elution of these 35S-labeled macromolecules from anion-exchange columns and migration in agarose-polyacrylamide gels were similar in the two groups. Abnormalities in proteoglycan-matrix interactions or proteoglycan processing may account for changes in the proportions of heparin- and trypsin-extracted proteoglycan compartments in diabetes.

Animals↗
PubMed1989

Effects of sorbinil on glomerular structure and function in long-term-diabetic rats.

We investigated the role of the aldose reductase pathway in the pathogenesis of the nephropathy of rats with sever (non-insulin-treated) streptozocin-induced diabetes of 6 mo duration. The initial experiment included four groups of rats: diabetic and control animals on a 20% protein diet, which were untreated or treated with sorbinil (an aldose reductase inhibitor). Food intake was increased by diabetes but was uninfluenced by sorbinil, whereas urinary urea nitrogen excretion was increased and body weight was decreased by both variables. Glomerular basement membrane (GBM) width was increased by diabetes and decreased by sorbinil. No other structural changes were noted. We speculated that sorbinil could have slowed the abnormal rate of GBM thickening in diabetic rats and the normal increase in GBM width in control rats by inducing a mild catabolic state. The second experiment also involved four groups of rats: diabetic and control animals on a 50% protein diet, which were untreated or treated with sorbinil. In these studies, diabetes was again associated with reduced body weight, but sorbinil had no influence on urinary urea nitrogen. Urinary albumin excretion, which was increased by diabetes, was not affected by sorbinil. GBM width was increased by diabetes, but in contrast to animals on 20% protein diets, the animals on 50% protein diets and treated with sorbinil did not have reduced GBM widths. Mesangial volume fraction was greater in diabetic animals than in controls, and sorbinil largely prevented mesangial expansion in them. Surprisingly, the control animals on the 50% protein diet and given sorbinil had increased mesangial volume fraction compared with control rats on the same diet not given the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1989

Ileal duplication cyst: repeated spontaneous decompression delays diagnosis.

A duplication cyst of the ileum was initially observed in a fetus at 26 weeks gestation on prenatal ultrasonography. Repeated spontaneous resolution of the cyst by decompression into the adjacent bowel lumen delayed diagnosis and management until the child was 9 months of age. The child experienced two episodes of hemorrhage from the cyst as a result of the delay in diagnosis.

Cysts↗
PubMed1988

Effect of morphine and nalmefene on energy balance in diabetic and non-diabetic rats.

Male rats made diabetic by intravenous injection of streptozotocin were used to evaluate the effect of the diabetic state on morphine- and nalmefene-induced changes in food intake and body weight. Morphine increased 4 hour food intake in non-diabetic rats after an initial injection, but increased intake in diabetic rats only after repeated injections. Unlike short term measurements, morphine decreased food intake when measured over 24 or more hours in both groups. Chronic injection of morphine decreased body weight only in non-diabetic rats. Feed efficiency data suggest that morphine had a more potent effect on energy balance in the non-diabetic rats. The opioid antagonist, nalmefene, did not alter body weight in either group and only altered food intake in the diabetic animals. These data are in concert with other reports indicating that the diabetic state renders animals less responsive to the effects of morphine on nociception and smooth muscle contraction.

Animals↗
PubMed1988

Ureteral duplication with lower pole ectopia to the epididymis.

We report a unique case of a duplex ureter with ureteral ectopia. A 30-year-old man presented with a coliform infection of the epididymis and excretory urography revealed, in addition to a normal-appearing right renal collecting system, a second right ureter that arose from an inferior calix, penetrated the lower pole parenchyma and drained directly into the ipsilateral epididymis. The radiological evaluation and surgical management are discussed, and several embryological explanations for this anomaly are offered.

Adult↗
PubMed1988

Glomerular basement membrane proteoglycans are derived from a large precursor.

The basement membrane heparan sulfate proteoglycan produced by the Englebreth-Holm-Swarm (EHS) tumor and by glomeruli were compared by immunological methods. Antibodies to the EHS proteoglycan immunoprecipitated a single precursor protein (Mr = 400,000) from [35S]methionine-pulsed glomeruli, the same size produced by EHS cells. These antibodies detected both heparan sulfate proteoglycans and glycoproteins in extracts of unlabeled glomeruli and glomerular basement membrane. The proteoglycans contained core proteins of varying size (Mr = 150,000 to 400,000) with a Mr = 250,000 species being predominant. The glycoproteins are fragments of the core protein which lack heparan sulfate side chains. Antibodies to glomerular basement membrane proteoglycan immunoprecipitated the precursor protein (Mr = 400,000) synthesized by EHS cells and also reacted with most of the proteolytic fragments of the EHS proteoglycan. This antibody did not, however, react with the P44 fragment, a peptide situated at one end of the EHS proteoglycan core protein. These data suggest that the glomerular basement membrane proteoglycan is synthesized from a large precursor protein which undergoes specific proteolytic processing.

Animals↗
PubMed1988

Quantitative management techniques in dietetics: improving practice through technology transfer.

A content analysis of articles appearing chronologically in the Journal of The American Dietetic Association since its inception in 1925 reveals the breadth and depth of management practice in the dietetic profession. This historical review highlights the introduction, demonstration, and adoption of management tools and techniques in the profession, with particular emphasis on quantitative management science techniques. Seven classifications of management science techniques were used for the content analysis. Although applications of forecasting, simulation, linear programming, and queuing models have been reported in the Journal, a gap is evident between the demonstration of management science techniques and operational use of these techniques in dietetic practice. Dietetic researchers, practitioners, and educators have vital roles in facilitating the transfer of quantitative management science technology into operational dietetic practice. Assessment of the state-of-the-art of dietetic management practice relative to proven quantitative management science techniques reveals the need for improved technology transfer to enhance professional ability in both tactical and strategic decision making.

Dietetics↗
PubMed1988

Improvement of differential toxicity between tumor and normal tissues using intratumoral injection with or without a slow-drug-release matrix system.

The therapeutic effects of cisplatin on tumor and normal tissues were assessed when the drug was given by different administration routes either as free drug or associated with a collagen-based matrix. Tumor response was assessed by growth delay of the murine RIF1 tumor, grown subcutaneously in female C3H/km mice. Normal tissue responses were assessed by plasma clearance of [51Cr]EDTA (giving an estimate of kidney damage), by the drop in peripheral white blood cells, and by a loss in mouse body weight. Intraperitoneal injections of cisplatin were the most toxic to the normal tissues for a given drug dose. Intratumoral injections of matrix-associated drug were the least toxic. Comparison of tumor growth delays for a given normal tissue damage demonstrated the superiority of all intratumoral schedules over the ip route.

Animals↗
PubMed1988

Response of murine tumors to matrix-associated cisplatin intratumoral implants.

The response to collagen matrix-associated cisplatin (cis-DDP-CM) implanted intratumorally into KHT and RIF-1 fibrosarcomas grown sc in C3H mice was studied. The effects on tumor growth as well as body weight and animal survival were assessed. The effect of cis-DDP-CM (8 mg/kg) on the growth of KHT tumor was assessed by determining the number of days required for tumors to grow to three times the pretreatment volume of 100-150 mm3. When cisplatin (cis-DDP) was administered ip, the number of days required for threefold growth was 11.1 +/- 2.5 SE. Administration of cis-DDP-CM intratumorally resulted in a value of 17.2 +/- 1.7 days. Epinephrine (0.1-5.0 mg/kg) was also added to the matrix as a vasoconstrictor to further localize the activity of cis-DDP. This resulted in enhanced antitumor activity and, presumably, lower systemic exposure to cis-DDP. For cis-DDP administered ip, the dose required to kill 50% of the test group at 10 days after injection was approximately 14 mg/kg. When cis-DDP-CM was administered intratumorally in doses less than or equal to 30 mg/kg, no mice died. Loss in mouse body weight (greater than 3 g) was detected with ip doses of cis-DDP at 8 mg/kg, but no weight loss was detected for mice treated with matrix implant delivering cis-DDP doses less than or equal to 25 mg/kg.

Animals↗
PubMed1988

Effects of matrix-associated chemotherapy in combination with irradiation in vivo.

Delay of tumor growth in RIF-1 fibrosarcomas in C3H mice was studied, comparing ip delivery of 5-fluorouracil (5-FU) or cisplatin (cis-DDP) versus collagen matrix-associated intratumoral delivery of drug with and without irradiation to a total dose of 1,500 cGy. For cis-DDP (6 mg/kg), the number of days required for treated tumors to attain three times their original treatment volume was 6.2 +/- 1.6 SE for ip drug and 7.0 +/- 1.3 for intratumoral drug matrix. The use of the vasoactive agent epinephrine (1 mg/kg) in the matrix resulted in a growth delay of 10.1 +/- 2.0 days. Irradiation given 60 minutes after drug administration enhanced the delay of tumor growth to 19.2 +/- 2.6 days for systemic drug and 16.7 +/- 2.5 days for matrix-associated drug. The delay of tumor growth for irradiation plus matrix-associated cis-DDP containing epinephrine was 33.0 +/- 5.4 days. X-rays alone caused a tumor growth delay of 11.2 +/- 1.3 days. Similar results were found for 5-FU at a dose of 50 mg/kg, although the epinephrine in the matrix was not as effective.

Animals↗
PubMed1987

The stability of oligodeoxyribonucleotide duplexes containing degenerate bases.

Oligodeoxyribonucleotides containing N4-methoxycytosine (mo4C), N4-methoxy-5-methylcytosine (mo4m5C) and other base-analogues were synthesised and used to compare the stabilities of duplexes containing mo4C.A and mo4C.G base pairs with those containing normal and mismatch pairs. The Tm values and other thermodynamic parameters are recorded. The otherwise identical duplexes containing a mo4C.A and a mo4C.G base pair have closely similar stabilities to each other and to the corresponding duplexes containing normal base pairs, considerably greater than the stabilities of those containing mismatch pairs. Corresponding observations are recorded in dot-blot experiments using M13 cloned DNA carrying an insert complementary to the oligonucleotides; approximate Td values are given.

Base Sequence↗
PubMed1987

Proteoglycan metabolism associated with mouse metanephric development: morphologic and biochemical effects of beta-D-xyloside.

Morphology and de novo incorporation of [35S]sulfate into proteoglycans were studied in fetal mouse kidneys at the onset of organogenesis. Branching morphogenesis and nephron development in organ culture and in vivo were associated with de novo synthesis of chondroitin-SO4 and heparan-SO4 proteoglycans. The role of proteoglycan metabolism in metanephrogenesis was then studied by analysis of the effects of p-nitrophenyl-beta-D-xylopyranoside (beta-D-xyloside) on renal development and proteoglycan metabolism. Incubation of fetal kidneys in beta-D-xyloside at concentrations of 1.0 and 0.5 mM, but not at 0.1 mM, caused inhibition of ureteric branching and markedly diminished synthesis of a large Mr 2.0 X 10(6) Da chondroitin-SO4 proteoglycan. Incorporation of [35S]sulfate was stimulated at all beta-D-xyloside concentrations, reflecting synthesis of xyloside initiated dermatan-35SO4 chains. In contrast to dramatic effects on chondroitin-SO4 synthesis and ureteric branching, beta-D-xyloside had no effect on heparan-SO4 synthesis or on development of the glomerulus and glomerular basement membrane. We thus characterize the proteoglycans synthesized early in the course of renal organogenesis and describe observations which suggest an association between metabolism of chondroitin-SO4 proteoglycan and development of the ureter.

Animals↗
PubMed1987

Effect of dexamethasone on fetal lung 15-hydroxy-prostaglandin dehydrogenase: possible mechanism for the prevention of patent ductus arteriosus by maternal dexamethasone therapy.

Prenatal maternal glucocorticoid treatment has been reported to reduce the incidence of patent ductus arteriosus in prematurely born infants. Patency of the ductus arteriosus is thought to be maintained primarily by the vasodilatory effect of PGE2 both in utero and in prematurely born infants, and lung is a major source of PGE2 in fetuses and neonates. 15-Hydroxy-prostaglandin dehydrogenase (15-PGDH) catalyzes the initial reaction in converting biologically active PGE2 to its inactive analogue, 15-keto-PGE2. In the present study, effect of prenatal dexamethasone treatment on the activity of fetal rat lung 15-PGDH was studied at 20, 21 and 22 days of gestation. Activity of fetal lung 15-PGDH more than doubled from 20 to 22 days of gestation. Dexamethasone treatment at 0.4 mg/kg and 0.8 mg/kg significantly increased the activity of 15-PGDH in both 20- and 21-day fetuses but had no effect on 22-day fetuses. We speculate that the clinical observation that prenatal glucocorticoid treatment reduces the incidence of patent ductus arteriosus in premature infants may in part be due to the stimulatory effect of glucocorticoid on the activity of 15-PGDH in fetal and neonatal lung and possibly other organs.

Animals↗
PubMed1986

Partial characterization of heparan and dermatan sulfate proteoglycans synthesized by normal rat glomeruli.

Rat glomerular heparan sulfate (HS) and dermatan sulfate (DS) proteoglycan synthesis was studied in vitro and in vivo. Incorporation of [35S]sulfate into macromolecules was linear over 16 h in vitro, and DS was the predominant glycosaminoglycan (GAG), while HS dominated in vivo incubations. Proteoglycans were found in the bottom 2/5 (high density) CsCl gradient fractions and eluted as two overlapping peaks from DEAE-Sephacel columns. The proportion of low density 35S-glycoproteins and 35S-proteoglycans increased with time. Two high buoyant density HS proteoglycans were extracted from glomeruli and eluted in DEAE peak I. The first, HS-tIA, had an Mr of 130 X 10(3) with Mr 12.5 X 10(3) GAG chains. This proteoglycan was released from the tissue by trypsin and was partially displaced by heparin treatment. In addition, it was rapidly released into the medium of label-chase experiments after which it migrated slightly more rapidly than HS-tIA in gels, with HS chains similar in length to its tissue counterpart. The second, HS-tIB, had an Mr of 8.6 X 10(3) with little or no attached protein. This proteoglycan was characterized as intracellular as it resisted release by trypsin treatment or heparin extraction in medium and was not detected in the medium of label-chase experiments. Two tissue DS proteoglycans were characterized. The first, DS-tIA, co-purified with HS-tIA and was the predominant proteoglycan synthesized during 4-h in vitro incubations. Like HS-tIA, it was rapidly released into medium and displaced from cell surfaces or tissue "receptors" by heparin or trypsin treatments. A second, Sepharose CL-6B-excluded DS proteoglycan from DEAE peak II, DS-tII, accumulated in tissue over 16 h in vitro. This proteoglycan was self-associating and contained clusters of iduronic acid residues along its Mr 26 X 10(3) DS chains. It resisted extraction from the tissue with heparin, trypsin, and detergent. No DS-tII was detected in the incubation medium. Instead, medium proteoglycans eluted as single Sepharose CL-6B-included peaks. DS chains from medium proteoglycans were shorter (Mr 18 X 10(3)) and had more regularly spaced iduronic acid residues than GAGs from DS-tII. The length and sulfation patterns of DS-mII GAG were similar to GAG from DS-tIA. Thus, glomeruli rapidly synthesized and released Sepharose CL-6B-included heparin-displaceable DS and HS proteoglycans while retaining a Sepharose CL-6B-excluded self-associating DS proteoglycan and an intracellular HS.

Animals↗
PubMed1986

Histamine stimulates prostaglandin E production by rheumatoid synovial cells and human articular chondrocytes in culture.

Histamine stimulates prostaglandin E (PGE) production by cultures of adherent rheumatoid synovial cells and human articular chondrocytes. When subcultured synovial fibroblasts or human articular chondrocytes were "primed" by preincubation with conditioned media from primary adherent rheumatoid synovial cell cultures (synovial factor), each produced even higher PGE levels upon histamine exposure. This histamine stimulation was prevented by histamine H1, but not H2, antagonists and was more marked if serum was absent from the culture media. Thus, histamine-induced PGE production by these cells is mediated via H1 receptor activation and subsequent arachidonic acid liberation.

Arthritis, Rheumatoid↗