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Biomedical subjects

D C Williams

Publications and source records attributed to D C Williams.

At least 109 records · Page 6Linked to original sources
PubMed1991

Physiological and pharmacological regulation of biological calcification.

Biological calcification is a highly regulated process which occurs in diverse species of microorganisms, plants, and animals. Calcification provides tissues with structural rigidity to function in support and protection, supplies the organism with a reservoir for physiologically important ions, and also serves in a variety of specialized functions. In the vertebrate skeleton, hydroxyapatite crystals are laid down on a backbone of type I collagen, with the process being controlled by a wide range of noncollagenous proteins present in the local surroundings. In bone, cells of the osteoblast lineage are responsible for the synthesis of the bone matrix and many of these regulatory proteins. Osteoclasts, on the other hand, are continually resorbing bone to both produce changes in bone shape and maintain skeletal integrity, and to establish the ionic environment needed by the organism. The proliferation, differentiation, and activity of these cells is regulated by a number of growth factors and hormones. While much has already been discovered over the past few years about the involvement of various regulators in the process of mineralization, the identification and functional characterization of these factors remains an area of intense investigation. As with any complex, biological system that is in a finely tuned equilibrium under normal conditions, problems can occur. An imbalance in the processes of formation and resorption can lead to calcification disorders, and the resultant diseases of the skeletal system have a major impact on human health. A number of pharmacological agents have been, and are being, investigated for their therapeutic potential to correct these defects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Insecticide susceptibility of Aedes aegypti from Santo Domingo, Dominican Republic.

The insecticide susceptibility of Aedes aegypti adults and larvae from Santo Domingo, Dominican Republic, was investigated using World Health Organization standard procedures. A field strain was more resistant to insecticides than a colony strain that originated from the same place. Larvae produced from ovitrap-collected eggs were resistant to temephos (78.2% mortality on exposure to 0.025 mg/liter). Mortality rates after exposure of adults to discriminating concentrations showed that wild populations were resistant to DDT, malathion, propoxur, permethrin and deltamethrin. The problem of resistance was considered serious enough to warrant consideration of control measures other than the use of chemicals.

Aedes↗
PubMed1991

Malaria transmission potential by Anopheles mosquitoes of Dajabon, Dominican Republic.

A field and laboratory study was conducted to determine some of the parameters relevant to malaria transmission by Anopheles mosquitoes in Dajabon Province, Dominican Republic. Although all 4 species occurring in the area, i.e., An. albimanus, An. crucians, An. grabhamii and An. vestitipennis, were included in the investigations, most of the work focused on the first and last named species because of their abundance. Gonotrophic cycles were determined to be 2.6 and 3.2 days for An. albimanus and An. vestitipennis, respectively. Mean parity rates for the 2 species were 37.3 and 20.7%, respectively, in outdoor samples. The human blood index, as determined by ELISA, was 0.08 for An. albimanus and 0.12 for An. vestitipennis. Only An. albimanus was confirmed positive for Plasmodium falciparum circumsporozoite protein, using ELISA. The vectorial capacity of An. albimanus was determined to be 0.019 and that of An. vestitipennis 0.005.

Animals↗
PubMed1990

Two subcellular locations for peripheral-type benzodiazepine acceptors in rat liver.

Subcellular fractionation of rat liver by differential centrifugation showed the mitochondrial fractions to have the greatest enrichment of 'peripheral-type' benzodiazepine acceptor. Two peaks of acceptor sites were found on isopycnic density-gradient centrifugation, one peak (rho = 1.19 g/ml) corresponding to the peak of mitochondria as judged by marker enzyme distribution and by transmission electron microscopy, and the other peak (rho = 1.17 g/ml) which is not mitochondrial as judged by the lack of mitochondrial enzyme markers. Whereas the density of the mitochondrial acceptor was sensitive to sonication and was shown to have an outer-membrane location, the density of the non-mitochondrial acceptor was insensitive to sonication. The non-mitochondrial acceptor was shown not to be associated with Golgi, lysosomes, rough endoplasmic reticular microsomes, peroxisomes, or some types of plasma membranes, as judged by differences in the distribution of marker activities. No enrichment of benzodiazepine acceptor was found in the purified nuclear fraction. Both acceptors were shown to be peripheral-type high-affinity acceptors as judged by ligand specificities and by photoaffinity labelling.

Affinity Labels↗
PubMed1990

A monoclonal anti-imipramine antibody with antidepressant binding properties similar to the muscarinic receptor.

A murine monoclonal antibody raised using imipramine conjugated to bovine serum albumin bound free imipramine with high affinity (KD = 24 nM). The antibody had a binding affinity profile for tricyclic and other uptake-inhibitor type antidepressants which correlated highly with the affinities of the same compounds for the brain acetylcholine muscarinic receptor, but not for plasma-membrane 5-hydroxytryptamine carriers. This antibody was not similar in binding properties to polyclonal antisera produced using the same antigen but was highly similar in binding properties to a monoclonal anti-nortriptyline antibody, ANT3, raised by Marulo et al. (Marulo S, Hoebeke J, Guillet JG, Andre C and Strosberg AD, J Immunol 138: 524-526, 1987) using a different antigen.

Animals↗
PubMed1990

In vitro screening for anticonvulsant-induced teratogenesis in neural primary cultures and cell lines.

To establish inherent potential for the induction of neural tube defects the ability of selected anticonvulsant agents to interfere with cell division has been established in vitro using an antiproliferative assay in clonal cell lines and a cytotoxicity assay using primary cultures of cerebral cortex neurons at different stages of development. In order to evaluate the relative toxicities of these agents their in vitro effects were determined at 2-3 times the plasma therapeutic level. By these procedures valproate and the benzodiazepines, diazepam and clonazepam, exerted a potent antiproliferative action which could not be attributed to increased cytotoxicity. In contrast phenytoin was markedly cytotoxic but was without an antiproliferative action. This cytotoxicity was most pronounced during the periods of extensive fibre outgrowth. When compared to epidemiological and animal study data, agents which inhibited cell proliferation within twice therapeutic concentration were consistently associated with major neural tube malformations. However phenytoin, found to be positive in the cell cytotoxicity assay, is not associated with neural tube malformations but rather is primarily associated with mental retardation. Thus assessment of antiproliferative activity of anticonvulsant drugs may be one criterion for identification of teratogenic potential during neurulation.

Animals↗
PubMed1990

Two affinity states for [3H]imipramine binding to the human platelet 5-hydroxytryptamine carrier: an explanation for the allosteric interaction between 5-hydroxytryptamine and imipramine.

5-Hydroxytryptamine (5-HT) showed a biphasic effect on the dissociation rate of [3H]imipramine from human platelet membranes: At low concentrations (EC50, approximately 2.5 microM), 5-HT stimulated the rate, as expected for mutually exclusive binding of 5-HT and imipramine; at higher concentrations (EC50, approximately 40 microM), 5-HT reduced this stimulated rate, a result consistent with 5-HT binding at a site that is physically distinct from both the imipramine binding site and the 5-HT transport recognition site of the 5-HT carrier. This modulatory effect could be mimicked by tryptamine, was saturable and independent of Na+ concentration, and could also be demonstrated for detergent-solubilized carriers. Monophasic association kinetics for [3H]imipramine binding were found. Heat stability experiments showed biphasic thermal inactivation curves. These results are consistent with [3H]imipramine binding to two classes of binding sites at the 5-HT carrier on human platelet membranes, with affinities three- to fivefold different. 5-HT can convert the lower-affinity state into the higher-affinity state.

Binding Sites↗
PubMed1990

Platelet 5-HT uptake in post-stroke depression.

Serotonin (5-HT) uptake into platelets is reduced in functionally depressed patients. Depression following stroke (cerebrovascular accident; CVA) is common and severe. Sixteen patients who had suffered a CVA within 6 to 12 months and who were medication-free had blood taken for measurement of platelet 5-HT uptake. Seven of these patients were depressed. These were compared with age- and sex-matched hospital controls. No difference in platelet 5-HT uptake was found across these groups.

Aged↗
PubMed1990

In vitro HIV infection of primate lymphocytes.

Peripheral blood mononuclear cells (PBMC) obtained from four different primate species were tested for their respective ability to support the "in vitro" replication of the human immunodeficiency viruses, HIV-1, and HIV-2. PBMC of Cebus apella, patas (Erythrocebus patas), green (cercopithecus aethiops sabaeus) and rhesus monkeys (Macaca mulatta) were infected "in vitro" with either HIV-1 or HIV-2. Cultures were assayed weekly for particle-associated reverse transcriptase activity. Both viruses were found to be cytolytic for all these monkey's PBMC. Low levels of HIV-1 and HIV-2 infection were observed in Cebus cells. However, productive infection was only detected in HIV-2 infected rhesus PBMC. The capacity of HIV-2 to replicate in rhesus cells may provide a useful model for evaluating antiviral drugs and vaccines.

Animals↗
PubMed1990

Studies of the susceptibility of Anopheles albimanus and Anopheles vestitipennis from Dajabon, Dominican Republic, to insecticides.

Insecticide susceptibility of Anopheles albimanus and An. vestitipennis in Dajabon Province, Dominican Republic, was investigated. Only 74.3% of An. albimanus exposed to 4% DDT for 1 h died. The mortality in this species following exposure for 1 h to 0.25% permethrin was also 74.3%. However, this species was susceptible to malathion, fenitrothion and propoxur. The mortality obtained following exposure of An. vestitipennis to 4% DDT and 0.1% propoxur, both for 1 h, was 71% and 100%, respectively. However, the number of specimens exposed to propoxur was small.

Animals↗
PubMed1990

Bionomic studies of the Anopheles mosquitoes of Dajabon, Dominican Republic.

Field studies of Dajabon Province, Dominican Republic, revealed that Anopheles albimanus and An. vestitipennis were the most abundant anopheline species followed by An. crucians and An. grabhamii. Three of the species were collected as adults and larvae whereas An. grabhamii was found only in the adult stage. Perennial ponds and rice fields were the most important larval habitats. The anophelines were predominantly exophilic and exophagic; however, outdoor resting sites could not be identified. Large numbers of mosquitoes were collected from corrals at night and also by using an animal-baited net trap and UV light traps. Man-biting collections showed an early evening peak of biting activity by An. albimanus and An. vestitipennis. Only 23% and 13% of the bites by the 2 species, respectively, occurred indoors.

Animals↗
PubMed1990

Baseline data on Aedes aegypti populations in Santo Domingo, Dominican Republic.

Baseline field studies were conducted from April 1987 to July 1988 on Aedes aegypti in Santo Domingo, an endemic area for dengue fever. Premise, container and Breteau indices were measured in one treated area and 2 nearby control areas. These indices averaged 69.6, 46.3 and 142.1, respectively. The principal larval habitats of Ae. aegypti were 208-liter (55-gal) concrete-lined drums. The estimated daily adult production was approximately 60 per house. Adult mosquito populations were monitored using oviposition traps and by sweep net collections. There was no correlation between adult abundance and the larval indices. Monitoring the natural adult densities was more efficient for evaluating the impact of ULV malathion application than the use of standard bioassay procedures.

Aedes↗
PubMed1990

Effects of controlled burning on Aedes taeniorhynchus eggs in an abandoned rice impoundment in South Carolina.

Controlled burning reduced the number of viable eggs in an Aedes population. The effectiveness of the burn was related to the amount of rainfall, surface moisture and dry vegetation. A greater reduction in viable eggs occurred when the burn was close to the ground. Variable results were achieved if the surface was moist but there was a significant reduction in the number of viable eggs, due to a heavy amount of dry vegetation accompanied by low rainfall.

Aedes↗
PubMed1990

Comparison of ground and aerial ultra-low volume applications of malathion against Aedes aegypti in Santo Domingo, Dominican Republic.

Efficacy of ground and aerial ultra-low volume (ULV) applications of 91% malathion at 438 ml/ha against Aedes aegypti in the Dominican Republic was evaluated using indoor collections, oviposition trapping and adult sentinel mortality rates. Ground compared to aerial ULV applications in this study were found to have a greater effect on Ae. aegypti when measured by the described sampling techniques. Neither application method provided the level of Ae. aegypti suppression believed necessary for control in the event of a dengue virus epidemic.

Aedes↗
PubMed1989

Antiproliferative action of benzodiazepines in cultured brain cells is not mediated through the peripheral-type benzodiazepine acceptor.

The benzodiazepines, Ro 5-4864, diazepam, clonazepam, and also PK-11195, inhibited, at micromolar concentrations, the proliferation of rat C6 glioma and mouse neuro-2A neuroblastoma cells in culture. The cells possessed high levels of "peripheral-type" high-affinity benzodiazepine binding sites as judged by binding assays and displacement potencies. However, the different potencies and specificities of compounds for the antiproliferative actions and binding affinities for the binding site suggest that the antiproliferative actions were not mediated through the peripheral-type binding site. In support of this, these compounds have also been shown to inhibit proliferation of some nonneuronal cultured cell lines, e.g., mouse SP2/O-Ag 14 hybridoma and rat NCTC epithelial cells, which have no detectable high-affinity peripheral-type benzodiazepine binding sites.

Animals↗