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Biomedical subjects

D M Brown

Publications and source records attributed to D M Brown.

At least 181 records · Page 10Linked to original sources
PubMed1990

Partial characterization of proteoglycans synthesized by human glomerular epithelial cells in culture.

Confluent adult and fetal human glomerular epithelial cells were incubated for 24 h in the presence of [3H]-amino acids and [35S]sulfate. Two heparan-35SO4 proteoglycans were released into the culture medium. These 35S-labeled proteoglycans eluted as a single peak from anion exchange chromatographic columns, but were separable by gel filtration on Sepharose CL-6B columns. The larger heparan-35SO4 proteoglycan eluted with the column void volume and at a Kav of 0.26 from Sepharose CL-4B columns. The most abundant medium heparan-35SO4 proteoglycan was a high buoyant density proteoglycan similar in hydrodynamic size (Sepharose CL-6B Kav 0.23) to those previously described in glomerular basement membranes and isolated glomeruli. Heparan-35SO4 chains from both proteoglycans were 36 kDa. A smaller proportion of Sepharose CL-6B excluded dermatan-35SO4 proteoglycan was also synthesized by these cells. The predominant protein cores of both medium heparan-35SO4 proteoglycans were approximately 230 and 180 kDa. A hybrid chondroitin/dermatan-heparan-35SO4 proteoglycan with an 80-kDa protein core copurified with the smaller medium heparan-35SO4 proteoglycan. This 35S-labeled proteoglycan appeared as a diffuse, chondroitinase ABC sensitive 155-kDa fluorographic band in sodium dodecyl sulfate-polyacrylamide gels after the Sepharose CL-6B Kav 0.23 35S-labeled proteoglycan fraction was digested with heparitinase. The heparitinase generated heparan sulfate proteoglycan protein cores and the 155-kDa hybrid proteoglycan fragment had molecular weights similar to those previously identified in rat glomerular basement membrane and glomeruli using antibodies against a basement membrane tumor proteoglycan precursor (Klein et al. J. Cell Biol. 106, 963-970, 1988). Thus, human glomerular epithelial cells in culture are capable of synthesizing, processing, and releasing heparan sulfate proteoglycans which are similar to those synthesized in vivo and found in the glomerular basement membrane. These proteoglycans may belong to a family of related basement membrane proteoglycans.

Adult↗
PubMed1990

Bile plug syndrome: successful management with a mucolytic agent.

Common bile duct obstruction, in an infant with bile plug syndrome, was relieved at surgery with a mucolytic agent, after an unsuccessful attempt at clearing the biliary tree with saline irrigation. This procedure obviated choledochotomy in this patient, and may be of use in other infants with ductal obstruction complicating the inspissated bile, associated with gut rest, parenteral nutrition, or diuretic therapy.

Acetylcysteine↗
PubMed1990

Contrasting bronchoalveolar leukocyte responses in rats inhaling coal mine dust, quartz, or titanium dioxide: effects of coal rank, airborne mass concentration, and cessation of exposure.

The aim of this study was to determine the bronchoalveolar leukocyte response to airborne coal mine dust; quartz and titanium dioxide were used as positive and negative controls, respectively. Groups of rats were exposed to airborne mass concentrations of 10 and 50 mg/m3 of the dusts for 7 hr/day, 5 days/week and their bronchoalveolar space was lavaged at time points between 2 and 75 days of exposure, to assess the leukocyte response. This study revealed time-dependent and airborne mass concentration-dependent recruitment of neutrophils and macrophages into the bronchoalveolar region with coal mine dust inhalation but no real difference in the magnitude of the response between coal mine dusts from collieries mining coal of different rank and quartz content although the maximum quartz content in the dusts used was 6%. The inflammatory response was much less than that produced by quartz, at similar airborne mass concentrations, and more than that produced by titanium dioxide which was, in general, a poor inflammogen in the rat lung. Groups of rats were exposed to the airborne dusts for 32 or 75 days, then removed from the exposure chambers, and allowed to recover by breathing room air for a further 64 days. During this recovery period there was marked progression of the leukocyte response with quartz and persistence of the response with coal mine dust. Chronic recruitment of leukocytes to the lungs of individuals inhaling coal mine dust is likely to be an important factor in the development of coal workers' pneumoconiosis.

Administration, Inhalation↗
PubMed1990

Studies of renal autoregulation in pancreatectomized and streptozotocin diabetic rats.

We studied renal autoregulation in pancreatectomized Munich-Wistar diabetic rats and in their sham-operated controls. In a second experiment we studied renal autoregulation in untreated and insulin treated streptozotocin diabetic Munich-Wistar rats and their nondiabetic controls. In the first experiment the diabetic rats had higher baseline renal blood flows (RBF). There was a fall in renal vascular resistance (RVR) and sustained RBF in both diabetic and control rats as renal perfusion pressures (RPP) was reduced from 130 and 110 mm Hg. As RPP was reduced from 110 and 80 mm Hg, there was no significant Change in RVR in control rats and RBF began to fall. Below RPP of 80 mm Hg RVR rose and RBF fell sharply in these rats. In contrast, there was a progressive fall in RVR as RPP was lowered to 60 mm Hg in the diabetic rats and, thus, RBF was much better sustained in these animals. In the second experiment the plasma glucose level was 502 +/- 52 mg/dl (X +/- SD) in the untreated diabetic rats and only modestly reduced to 411 +/- 49 mg/dl in the insulin treated animals. Untreated streptozotocin diabetic rats had moderately reduced and insulin-treated diabetic rats had mildly reduced baseline RVR and RBF. However, in these animals as in the pancreatectomized rats the increases in RVR noted in control rats at subautoregulatory RPPs were not seen. Thus, regardless of whether baseline RBFs were increased or decreased, diabetic rats sustained RBF at markedly reduced RPPs far more efficiently than did nondiabetic rats. The pathogenesis of these abnormalities in diabetic rats was not learned in these studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Complications of extracorporeal membrane oxygenation in neonates.

In cases of severe respiratory failure, cardiopulmonary bypass has been used as support until cardiac and pulmonary recovery occurs. We report the Wilford Hall USAF Medical Center experience with extracorporeal membrane oxygenation (ECMO) and its associated complications. From July 1985 to March 1989, 57 neonates were placed on membrane oxygenators. The overall survival was 79%. Technical complications encountered included catheter-related problems, mechanical complications of the pump apparatus, and hemorrhage. Hemorrhagic complications were the most frequent and devastating complications encountered. Intracranial hemorrhage accounted for six deaths associated with bypass. Extracorporeal membrane oxygenation is successful in significantly improving survival of neonates whose predicted mortality approaches 100% with conventional treatment. The rate of infant mortality using the membrane oxygenator is not affected by technical complications related to catheter position, mechanical problems with the circuit, or hemorrhage, excluding intracranial hemorrhage. The major cause of death of infants receiving extracorporeal membrane oxygenation is the underlying disease process leading to cardiopulmonary failure.

Catheterization, Central Venous↗
PubMed1990

Inflammation in the lungs of rats after deposition of dust collected from the air of wool mills: the role of epithelial injury and complement activation.

In a previous study assessing respiratory symptoms in individuals employed in wool textile mills in the north of England relations between symptoms of chronic bronchitis, breathlessness and wheeze, and rhinitis and current exposure to airborne mass concentration of dust were shown. As preliminary steps in defining the potential hazard associated with dust from the air of wool mills the ability of inspirable dust, collected from the air of wool textile mills, to cause inflammation when injected into the lungs of rats was determined. Dusts were collected from the beginning of wool processing (opening) in one factory and from the middle (combing) and late (backwinding) stages of the process in two other factories. Ability of the dusts to cause inflammation was assessed by instillation into the lungs of rats followed by bronchoalveolar lavage. All the dusts caused some inflammation which peaked on day 1 and did not persist beyond one week. A distinctive aggregation response of mononuclear cells in the lavage, however, had a different time course, peaking at day 7. An attempt was made to determine how the wool mill dusts caused inflammation and experiments showed that the dusts themselves had no inherent chemotactic activity but that they did have a pronounced ability to generate chemotaxins in serum and so could activate complement in lung fluid. In addition, dust collected from ledges in the mills had the ability to injure epithelial cells in vitro which could also contribute to inflammation. A role for endotoxin in the inflammatory activity of the dusts was not discounted and a leachate of the dust had the ability to cause inflammation when injected into the lungs of rats. Wool mill dust is likely to be a complex mixture of materials and these experiments represent a preliminary approach to understanding the biological activity of the whole unfractionated dust and further studies are in progress to define more accurately the toxic material(s) in the dust.

Animals↗
PubMed1990

Agnathia and associated malformations: a case report.

A case of a rare first branchial arch anomaly with severe hypoplasia of the mandible and fusion between the mandible and adjacent bones is presented. The patient also had intracranial, cardiac, and acral deformities. The craniofacial malformations may reflect incomplete separation of the first branchial arch into its maxillary and mandibular processes. The association between the craniofacial and other corporal anomalies is unknown.

Branchial Region↗
PubMed1990

Survey of ethical issues in dental hygiene.

The purpose of this study was to determine the types and frequency of ethical problems encountered by dental hygienists, and to determine the type of instruction they have received in ethical theory and problem solving. A 40-item questionnaire mailed to 2,251 American Dental Hygienists' Association members resulted in a stratified random sample of 1,523 (68% response rate). The three ethical dilemmas most frequently encountered in dental hygiene practice are (1) observation of behavior in conflict with standard infection control procedures (66%); (2) failure to refer patients to a specialist such as a periodontist (60%); and (3) nondiagnosis of dental disease (58%). While almost 86% of the respondents received formal instruction in ethical theory, only 51% received formal instruction in methods for solving ethical problems. More hygienists (74%) felt their ethical principles were influenced by role models rather than by formal instruction (63%). This study indicates that serious ethical dilemmas are encountered by the majority of dental hygienists and that some modification of current entry-level education, as well as of continuing professional education, should be considered to prepare dental hygienists to recognize and resolve ethical problems.

Adult↗
PubMed1990

Productivity measurement in foodservice: past accomplishments--a future alternative.

Productivity measurement, monitoring, and improvement are ongoing management responsibilities. Financial and personnel resources are limited, and foodservice managers are faced with the increasingly difficult task of efficiently and effectively meeting consumer demands. A wide variety of labor productivity measures have been reported in the foodservice literature. The most prevalent of those measures include labor minutes per meal and labor minutes per meal equivalent. A measurement technique that considers only one or a few of the resources used to produce goods and services may result in limitations and potentially inaccurate productivity measurement. A total-factor productivity model that relates organizational output to all input resources is recommended. Such a model has been used in several business firms. Aggregate and multiple partial-factor productivity ratios enabled business managers to identify the relationships and trade-offs among all resources not previously revealed in labor productivity measures. Such an expanded productivity model could be applied in food-service settings to provide additional information for enhanced decision making.

Efficiency↗
PubMed1989

Synthesis and duplex stability of oligonucleotides containing cytosine-thymine analogues.

The synthesis of the deoxynucleoside derived from the base P, 6H,8H-3,4-dihydro-pyrimido[4,5-c] [4,5-c] [1,2]oxazin-7-one, 2, and its introduction by established phosphoramidite and H-phosphonate chemistry into oligonucleotides is described. The melting transition temperatures (Tm) of a range of heptadecamer duplexes containing P/A and P/G base-pairs are compared with corresponding ones having N4-methoxycytosine (M) 1 and mismatched normal bases. P/A and P/G pairs allow closely similar duplex stabilities and have the potential to reduce the multiplicity of probes and primers based on amino acid sequences by removing the T/C degeneracy.

Amides↗
PubMed1989

Regulatory and essential light-chain-binding sites in myosin heavy chain subfragment-1 mapped by site-directed mutagenesis.

Site-directed mutagenesis of the cloned subfragment-1 (S-1) region of the unc-54 gene, encoding the myosin heavy chain B (MHC B) from Caenorhabditis elegans, has been used to locate binding sites for the regulatory and essential light chains. MHC B S-1 synthesized in Escherichia coli co-migrated with rabbit skeletal muscle myosin S-1 (Mr 90,000), was recognized by anti-nematode myosin antiserum on immunoblots, and specifically bound to 125I-labelled regulatory and essential light chains in a gel overlay assay. Deletion of 102 residues from the C terminus (mutant 655) reduced regulatory and essential light-chain binding to about 30% and 20% of wild-type levels, respectively. Similar reductions in relative binding of the two light chains were seen with mutant 534, in which 38 residues were deleted from the C terminus. Potential binding sites within 75 residues of the C terminus of S-1 were mapped by construction of five other mutant S-1 clones (398, 399, 400, 409 and 411) containing internal deletions of ten to 12 amino acid residues. These showed up to 30% reductions in their ability to bind essential light chains, but did not differ significantly from wild-type in their ability to bind regulatory light chains. Another mutant, 415, containing a deletion of a conserved acidic hexapeptide, E-D-I-R-D-E, showed enhancement of binding of regulatory and essential light chains to 150% and 165% of wild-type levels. Hence, the major binding sites for both light chains are within 38 amino acid residues of the C terminus.

Amino Acid Sequence↗
PubMed1989

Anion-cation separations on a mixed bed alumina-silica column.

Mixed bed ion-exchange (MBIE) columns containing alumina and silica were evaluated for the simultaneous separation of anion and cation analytes. At the mobile phase pH used alumina provides anion exchange sites while silica provides cation exchange sites. Since alumina and silica exhibit weak acid and base properties, their anion and/or cation exchange properties are pH dependent. Ion exchange capacities, rates of exchange and analyte ion exchange selectivities are also pH dependent. The major mobile phase parameters affecting analyte anion and cation resolution and elution order are pH and type and concentration of counter anion and counter cation, respectively. The weight ratio of the two exchangers and/or the exchange capacities of the two in the column can also be used to alter resolution and elution order. Several examples of the simultaneous separation of inorganic mono- and divalent anions and cations using a single sample injection, a single column and a single detector (conductivity) illustrate the parameters and scope of the alumina-silica MBIE column.

Aluminum Oxide↗
PubMed1989

Effects of products from inflammatory pulmonary neutrophils on alveolar macrophage chemotaxis, spreading, and thymidine incorporation.

Since macrophages and neutrophils are found together in the alveolar region of the lung during alveolar inflammation, we assessed whether neutrophil products could influence three key functions of alveolar macrophages: chemotaxis, spreading, and thymidine incorporation. Neutrophils were obtained from the lungs of rats treated by intratracheal instillation of heat-killed Corynebacterium parvum and cultured overnight, alone or in the presence of zymosan, PMA, an inert particulate (titanium dioxide), or a toxic dust, (quartz). Supernatants were collected from these cells and a lysate, obtained by freeze-thawing neutrophils, was also used. Neutrophil supernatants caused a slight reduction in chemotaxis and a significant loss of ability to spread on glass which varied depending on the in vitro treatment of the neutrophils. In addition neutrophil supernatants also had a substantial effect in stimulating uptake of thymidine which was, once again, very dependent on the treatment of the neutrophils during preparation of the supernatants, with unstimulated and TiO2-treated neutrophils producing maximum stimulation. The increases in thymidine uptake were not matched by increased proliferation, suggesting that another signal may be necessary for expanison of alveolar macrophage numbers during alveolar inflammation.

Animals↗
PubMed1989

Chondroitin sulfate proteoglycan synthesis and reutilization of beta-D-xyloside-initiated chondroitin/dermatan sulfate glycosaminoglycans in fetal kidney branching morphogenesis.

Branching morphogenesis and chondroitin sulfate proteoglycan synthesis by explanted fetal mouse kidneys were previously shown to be inhibited by p-nitrophenyl beta-D-xylopyranoside (beta-D-xyloside) while glomerular development and heparan sulfate proteoglycan synthesis were unaffected. The metabolic fate of fetal kidney explant proteoglycans was investigated to determine whether or not recovery of proteoglycan synthesis and morphogenesis occur after exposure to beta-D-xyloside. Chondroitin sulfate proteoglycan synthesis resumed within 4 hr of removal of beta-D-xyloside and was enhanced once beta-D-xyloside-initiated chondroitin/dermatan-35SO4 glycosaminoglycans (GAGs) were released from the tissue. Radioactivity incorporated into beta-D-xyloside-initiated chondroitin/dermatan-35SO4 GAGs during labeling in the presence of beta-D-xyloside was reutilized in the synthesis of chondroitin-35SO4 proteoglycan during a 24-hr chase in nonradioactive medium without beta-D-xyloside. Further, highly purified beta-D-xyloside-initiated chondroitin/dermatan-35SO4 GAGs were taken up by kidneys more avidly than was free [35S]sulfate. These 35S-GAGs were degraded and reutilized in the synthesis of chondroitin-35SO4 proteoglycan. Ureteric bud branching resumed 48 hr after beta-D-xyloside was removed from the incubation medium. These findings support the idea that both chondroitin sulfate proteoglycan synthesis and proteoglycan processing may be involved in branching morphogenesis.

Animals↗
PubMed1989

Bronchoalveolar leukocyte response in experimental silicosis: modulation by a soluble aluminum compound.

The biological properties of quartz have been related to its surface reactivity. We have addressed the role of particle surface reactivity in mediating the biological activity of quartz in mixed dusts, by treating the quartz with aluminum lactate. Intratracheal instillation of untreated quartz in rats caused a rapid, sustained alveolitis and bronchoalveolar leukocytes obtained from these animals had enhanced activity in degrading fibronectin, but reduced ability to mount a respiratory burst. Quartz pretreated with aluminum elicited a markedly reduced inflammatory response; the reduced activity of the treated quartz was also reflected in the attenuated change in the key functional parameters, oxidant production and proteolysis of fibronectin. Late intratracheal dosing with aluminum after the quartz-induced alveolitis was well established reduced the inflammatory response and abrogated the effect of quartz on the respiratory burst, but did not alter fibronectin degradation by the leukocytes. Aluminum did not affect the inflammatory response to Corynebacterium parvum and thus the effect was on the quartz particles and not on the inflammatory leukocytes. These findings have implications for the likely pulmonary responses to mixed dusts containing quartz and aluminum silicate clays.

Animals↗
PubMed1989

Effects of dietary protein content in streptozotocin-diabetic rats.

We evaluated the influence of increased dietary protein intake on glomerular structure and function in Lewis rats made diabetic with streptozotocin. We found that diabetic animals on a 20% or 50% protein diet ate approximately 50% more protein and excreted about 50% more urinary urea nitrogen than did their respective similarly-fed nondiabetic controls. The 50% protein diet was associated with higher glomerular filtration rates (GFR) and renal blood flows (RBF) at two months in both diabetic and control animals compared to their respective controls on the lower protein diet. However, GFR and RBF were not significantly higher in the diabetic animals on the 50% protein diet in the controls on the 20% diet and were slightly, albeit not significantly lower than controls on the 50% diet. Glomerular capillary pressure (PGC) tended to be lower in the diabetic compared to their respective controls, while the high protein diet was associated with higher PGC in diabetic and nondiabetic animals. The PGC in the 50% diabetic rats was not different from the PGC in the nondiabetic rats. Urinary albumin excretion (UAE) rate was greater in the diabetic than in the nondiabetic animals. UAE was greatest in the high protein diabetic animals at six months. Glomerular basement membrane thickness after six months of diabetes was increased essentially equally in both normal and high-protein fed diabetic groups and was largely uninfluenced by diet in the controls. Fractional mesangial volume was increased and relative filtration surface was decreased only in the 50%-protein diet diabetic rats at six months. Thus, high protein diet was associated with increased fractional mesangial volume in diabetic rats, but this could not be explained by increased glomerular capillary flows or pressures. The mechanism of acceleration of mesangial expansion by high protein diet in diabetic animals was not elucidated by these studies.

Animals↗
PubMed1989

Antibody producing cells in the spleens of mice treated with pathogenic mineral dust.

Experiments were carried out to assess the effect of intraperitoneal injection of the mineral dusts, titanium dioxide, quartz, or asbestos, on splenic lymphocyte antibody forming cells in immunised mice. Titanium dioxide and quartz caused similar, about one third, reductions in plaque forming cells; asbestos caused substantial reduction to about a quarter of the number found in control spleens. The inhibition of antibody forming cells in the spleen found with chrysotile was dose dependent and both chrysotile and crocidolite asbestos were similar in activity. Systemic immunomodulation after local deposition of mineral dust may be important to the development of disease.

Animals↗