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D W Brown

Publications and source records attributed to D W Brown.

At least 145 records · Page 8Linked to original sources
PubMed1990

Accessible conformations of melanin-concentrating hormone: a molecular dynamics approach.

Molecular dynamics simulations have been used to search for the accessible conformations of the melanin-concentrating hormone (MCH). The studies have been performed on native MCH and two of its peptide fragments, a cyclic MCH(5-14) fragment and a linear MCH(5-14) fragment. An analysis of the molecular dynamics trajectories of the three peptides indicates that two regions of the peptide have characteristic conformational properties that may be important for the biological activity. One is a region around Gly8, which is conformationally mobile, and the other is around Pro13, which shows unusual rigidity. The molecular dynamics simulation results are discussed in terms of backbone structural features like beta turns, side-chain interactions, and orientations of the disulfide bridge. The results of this analysis are used to suggest new analogues that will modify the conformational features of the peptide and further define the conformational requirements for activity. Finally, the results are related to nmr studies of the peptide and reveal agreements between the experimental nuclear Overhauser effect constraints and some of the accessible conformations obtained from the simulation.

Amino Acid Sequence↗
PubMed1990

Consistent associations between hepatic lesions in English sole (Parophrys vetulus) and polycyclic aromatic hydrocarbons in bottom sediment.

A consistent and statistically significant association between prevalence of hepatic neoplasms in free-living sole (Parophrys vetulus) and levels of anthropogenic polycyclic aromatic hydrocarbons in bottom sediment from sites of fish capture was documented in a series of studies conducted over a period of 7 years in Puget Sound, Washington. This result strengthens the evidence supporting a causal relationship between exposure to sediment-associated hydrocarbons and development of hepatic neoplasms in this bottom-dwelling marine fish species. Prevalences of two other distinct categories of idiopathic hepatic lesions-megalocytic hepatosis and steatosis/hemosiderosis-also showed consistent, statistically significant associations with polycylic aromatic hydrocarbon concentrations in bottom sediment, and association with prevalence of a third category (putatively preneoplastic foci of cellular alteration) approached statistical significance. On the basis of other studies, megalocytic hepatosis and foci of cellular alteration are both considered to be important precursor lesions in the stepwise histogenesis of hepatic neoplasms.

Animals↗
PubMed1990

Neural aging: speculation.

This communication attempts to explain the absence of mitosis in cortical neurons of adult mammals in terms of defective proteolysis and a hypothetical proteolysis-inhibiting factor (PIF). Highly speculative hypotheses offer an explanation for aging at the cellular level. The speculations are analyzed in terms of Sacher's action principle for mammalian longevity, which is based on encephalization, metabolic rate, and body temperature.

Animals↗
PubMed1989

High-performance liquid chromatographic method for isolating coprostanol from sediment extracts.

We report a rapid, largely automated high-performance liquid chromatographic (HPLC) method, which uses an HPLC column packed with alkylnitrile-substituted secondary alkylamine (aminocyano) bonded phase, to isolate coprostanol from interfering compounds in sediment extracts. Coprostanol is then quantitated, as the trimethylsilyl ether, by gas chromatography with flame ionization detection. Results from using the HPLC method to analyze a sediment reference material for coprostanol were statistically comparable to a previously used gravity-flow column method. We also report the coprostanol concentrations in several sediment samples from the California coast which reflect a range of sewage contamination (62-15,000 ng/g).

Cholestanol↗
PubMed1989

The influence of immune complexes, steric effects, and antigen-antigen interactions on the sensitivity of enzyme-linked immunosorbent assays.

Serum from mice hyperimmunized with 2,4,6-trinitrophenylated bovine gamma globulin (TNP-BGG) or keyhole limpet hemocyanin have been shown to have enhanced binding to several ligands unrelated to the antigen used for immunization. Addition of the immunizing antigen to the serum can result in increased binding to unrelated ligands and to the polyvinyl chloride surface of microtiter wells in solid-phase enzyme-linked immunosorbent assays. In a competitive binding assay using TNP-BGG-hyperimmune serum adsorbed to the microtiter well followed by an alkaline phosphatase conjugate of BGG in the presence or absence of TNP-BSA, substantial inhibition of BGG binding is seen. Steric hindrance appears to be the major cause of such inhibition since addition of hapten alone has little effect on BGG binding. An antigen-antigen interaction between KLH and TNP is also detectable. Immune complex formation, steric effects, and antigen-antigen interactions potentially have substantial influences on ELISA sensitivity and must be considered as possible sources of artifact in these assays.

Animals↗
PubMed1989

Influence of avian leukosis viral sequences on transmission to the egg and embryo.

Rous associated virus type-0 (RAV-0), a subgroup E replication-competent endogenous virus of chickens, is associated with a low efficiency of virus shedding into the egg albumen and failure to establish congenital transmission. In contrast, RAV-1, a subgroup A virus of exogenous origin, is efficiently shed into the albumen and readily infects the embryo. Among a series of in vitro constructed recombinants between RAV-0 and RAV-1, we have identified subgroup E recombinants that efficiently shed virus into the egg albumen but do not undergo efficient congenital transmission. The LTR region, subgroup-determining sequences in env, and sequences within a 375 bp Sacl-Xhol fragment at the 5' end of the genome each influenced the efficiency of virus shedding into the albumen. Egg inoculations with viruses differing only in env were used to confirm the low rate of congenital transmission of subgroup E viruses. These studies revealed that subgroup A envelope antigens are at least 100-fold more effective for the establishment of embryonic infection than subgroup E.

Animals↗
PubMed1988

High-performance liquid chromatographic method for isolating organic contaminants from tissue and sediment extracts.

Interest in the assessment of the anthropogenic contamination of the marine environment has accelerated in recent years. Existing methods to analyze environmental samples (e.g., sediments or tissues) for trace amounts of organic contaminants such as aromatic hydrocarbons and chlorinated compounds are tedious and costly. We report a rapid, efficient high-performance liquid chromatography (HPLC) procedure which uses a size-exclusion column to separate the analytes of interest from interfering compounds in the sample matrix. Analytical results from the HPLC method were, in general, comparable to a gravity-column method which had been used for several years. The HPLC method had several other advantages: improved precision; the ability to monitor chromatographic conditions; the potential for automating analyses; and reduced consumption of solvents and other materials.

Animals↗
PubMed1988

The antigenic diversity of rotaviruses: significance to epidemiology and vaccine strategies.

Rotaviruses are the major cause of infantile gastroenteritis world-wide. Much antigenic diversity exist amongst them. This has important implications to diagnosis, epidemiology and vaccination strategies. The nature of this diversity is now well understood. This review outlines and discussed our current knowledge of the subject from a historical perspective.

Antigens, Viral↗
PubMed1988

Role of RAV-0 genes in the permissive replication of subgroup E avian leukosis viruses on line 15Bev1 CEF.

Rous associated virus type-0 (RAV-0) is a replication-competent endogenous virus of chickens which grows more efficiently on chick embryo fibroblasts (CEFs) from line 15B chickens than on CEFs from line K28. Differences in viral growth on these two sources of cells have been attributed to an early event in the retrovirus life-cycle, at or before viral DNA synthesis. Five in vitro constructed avian leukosis viruses (ALVs) as well as RAV-0 (a subgroup E ALV), RAV-1 (subgroup A), and RAV-2 (subgroup B) have been assessed for their relative growth on 15Bev1 and K28 CEFs. More efficient replication on 15Bev1 CEFs than on K28 CEFs was determined by subgroup E-encoding sequences in env. Subgroup A and B envelope sequences as well as viral LTR, gag, and pol sequences did not obviously bias relative rates of viral replication on the two cell types. We suggest that the unusually permissive replication of subgroup E viruses on 15B CEFs is a receptor-mediated phenomenon and that the line 15B receptor for subgroup E ALVs is more efficient than that of line K28.

Animals↗
PubMed1988

Rotavirus epidemiology in Vellore, south India: group, subgroup, serotype, and electrophoretype.

Rotaviruses were detected in 163 of 916 (17.8%) specimens collected from children under 3 years of age with gastroenteritis in Vellore, South India, between August 1983 and July 1985. Rotaviruses were detected throughout the study period, with a peak prevalence in December to February (winter) and June to August (southwest monsoon season). A total of 117 rotavirus strains were tested for subgroup, serotype, and rotavirus double-stranded RNA electrophoretic migration pattern; 24.8% of the strains were subgroup I, 69.2% were subgroup II, and 6.0% were neither subgroup I nor subgroup II. Subgroup I and II strains were circulating concurrently throughout the study. Of the 117 rotavirus strains, 32 (27.4%) were serotyped; 15 were serotype 1, 3 were serotype 2, 2 were serotype 3, and 12 were serotype 4. Three serotypes were circulating concurrently during the periods of peak rotavirus prevalence. In 100 of the 117 strains (85.4%) an RNA pattern was detected. One unusual subgroup I group A rotavirus with a long migration pattern and four atypical rotaviruses serologically related to group C were also detected.

Child↗
PubMed1988

Influence of env and long terminal repeat sequences on the tissue tropism of avian leukosis viruses.

Adsorption and penetration of retroviruses into eucaryotic cells is mediated by retroviral envelope glycoproteins interacting with host receptors. Recombinant avian leukosis viruses (ALVs) differing only in envelope determinants that interact with host receptors for subgroup A or E ALVs have been found to have unexpectedly distinctive patterns of tissue-specific replication. Recombinants of both subgroups were highly expressed in bursal lymphocytes as well as in cultured chicken embryo fibroblasts. In contrast, the subgroup A but not subgroup E host range allowed high levels of expression in skeletal muscle, while subgroup E but not subgroup A envelope glycoproteins permitted efficient replication in the thymus. A subgroup B virus (RAV-2), like the subgroup E viruses, demonstrated a distinct bursal and thymic tropism, further supporting the theory that genes encoding receptors for subgroup B and E viruses are allelic. The source of long terminal repeats (LTRs) or adjacent sequences also influenced tissue-specific replication, with the LTRs from endogenous virus RAV-0 supporting efficient replication in the bursa and thymus but not in skeletal muscle. These results indicate that ALV env and LTR regions are responsible for unexpectedly distinctive tissue tropisms.

Animals↗
PubMed1988

Retrovirus-expressed hemagglutinin protects against lethal influenza virus infections.

An influenza virus hemagglutinin gene, H7, has been expressed in a replication-competent Schmidt-Ruppin Rous sarcoma virus-derived vector. This virus, P1/H7, expressed a glycosylated precursor of the H7 protein which was processed to a mature form and transported to the cell surface. The expressed H7 glycoprotein could not be detected in P1/H7 virus particles. A P1/H7 stock which expressed 5 to 10% of the level of H7 observed in influenza virus-infected chicken embryo fibroblasts was used to immunize 1-month-old chickens. This immunization resulted in low or undetectable levels of hemagglutination-inhibiting and neutralizing antibody. Despite the low serum response, challenge with a highly pathogenic H7N7 virus revealed complete protection against lethal infection.

Animals↗
PubMed1988

Long terminal repeat (LTR) sequences, env, and a region near the 5' LTR influence the pathogenic potential of recombinants between Rous-associated virus types 0 and 1.

A series of recombinants between Rous-associated virus type 0 (RAV-0), RAV-1, and a replication-competent avian leukosis virus vector (RCAN) have been tested for disease potential in day-old inoculated K28 chicks. RAV-0 is a benign virus, whereas RAV-1 and RCAN induce lymphoma and a low incidence of a variety of other neoplasms. The results of the oncogenicity tests indicate that (i) the long terminal repeat regions of RAV-1 and RCAN play a major role in disease potential, (ii) subgroup A envelope glycoproteins are associated with a two- to fourfold higher incidence of lymphoma than subgroup E glycoproteins, and (iii) certain combinations of 5' viral and env sequences cause osteopetrosis in a highly context-dependent manner. Long terminal repeat and env sequences appeared to influence lymphomogenic potential by determining the extent of bursal infection within the first 2 to 3 weeks of life. This would suggest that bursal but not postbursal stem cells are targets for avian leukosis virus-induced lymphomogenesis. The induction of neutralizing antibody had no obvious influence on the incidence of lymphoma.

Animals↗
PubMed1987

The diagnostic gap in diarrhoeal aetiology.

It is well established that rotaviruses of group A are the most important cause of severe diarrhoea in children. The causes of most cases of infectious diarrhoea still remain unidentified, however, and there must be other viruses to be found. 'Novel' rotaviruses have recently been discovered, mainly in animals (serogroups B and C in pigs and humans, D in birds, and one or more further groups in sheep and other mammals). Except for the group B virus which has caused widespread outbreaks of quite severe diarrhoea in adults in China (still not reported from outside China) these novel rotaviruses are rarities in the human and probably represent uncommon zoonotic infections. We speculate that the Chinese virus might have arisen by reassortment of genetic segments of animal group B viruses or perhaps by mutation, and so became infectious for man. The problem of identifying and determining the importance of small round viruses is reviewed. It seems likely that the group of small, round structured viruses, including Norwalk and the viruses of plainly calicivirus morphology, are all representatives of a whole group of enteric caliciviruses. Until they can be more easily cultivated it will be difficult to make diagnostic reagents available to all. Astroviruses and genuine parvoviruses have been found by many people in many countries. Astroviruses are probably more important as pathogens in lambs than in children or calves; parvoviruses can only be established as significant in epidemics. The coronavirus-like particles, first found in Vellore and Bristol, are still enigmatic and their role in diarrhoea is uncertain. Toroviridae, recently discovered as causes of diarrhoea in ungulates, do not seem to be at all important as causes of diarrhoea in humans. Possibly fruitful approaches to future searches are outlined: firstly to make more extensive use of immuno-electron microscopy; and secondly to try to improve existing tissue culture systems to make them more sensitive to enteric viruses.

Animals↗