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Biomedical subjects

D C Williams

Publications and source records attributed to D C Williams.

At least 19 recordsLinked to original sources
PubMed1992

Long-range changes in a protein antigen due to antigen-antibody interaction.

Amide exchange kinetics were used to probe the conformation of hen egg-white lysozyme complexed with the anti-lysozyme monoclonal antibody HyHEL-5. Following the technique developed by Paterson et al. [(1990) Science 249, 755-759] we used two-dimensional NMR to measure amide exchange kinetics of the lysozyme amide protons in the lysozyme-antibody complex. A total of 15 amide protons showed altered exchange kinetics in the presence of the complex. Five of these 15 protons reside on residues that are found within the epitope as defined by X-ray crystallography. Five residues are located at the perimeter of the epitope. The remaining five residues are removed from the epitope. The perturbation of amide exchange rates at sites distant from the epitope indicates that the formation of antigen-antibody complexes can produce changes in the antigen at sites that are quite distant from the structural epitope.

Amides↗
PubMed1992

Increased osteoclast development after estrogen loss: mediation by interleukin-6.

Osteoclasts, the cells that resorb bone, develop from hematopoietic precursors of the bone marrow under the control of factors produced in their microenvironment. The cytokine interleukin-6 can promote hematopoiesis and osteoclastogenesis. Interleukin-6 production by bone and marrow stromal cells is suppressed by 17 beta-estradiol in vitro. In mice, estrogen loss (ovariectomy) increased the number of colony-forming units for granulocytes and macrophages, enhanced osteoclast development in ex vivo cultures of marrow, and increased the number of osteoclasts in trabecular bone. These changes were prevented by 17 beta-estradiol or an antibody to interleukin-6. Thus, estrogen loss results in an interleukin-6-mediated stimulation of osteoclastogenesis, which suggests a mechanism for the increased bone resorption in postmenopausal osteoporosis.

Analysis of Variance↗
PubMed1992

Regioselectivity of the insertion reactions of some aromatic diazo compound complexes with cyclomaltoheptaose.

Pyrolysis of solid complexes of aromatic diazo compounds with cyclomaltoheptaose (beta-cyclodextrin) yields either derivatives via insertion of carbene into hydroxyl groups. The distribution of the 2-, 3-, and 6-O-isomers indicates that the regioselectivity is moderate. The guest geometry is not as important as its size in determining the ratios of regioisomers. The origins of the regioselectivity are discussed.

Carbohydrate Conformation↗
PubMed1992

Stabilization of the peripheral-type benzodiazepine acceptor by specific phospholipids.

The peripheral-type benzodiazepine acceptor from rat adrenal gland was solubilized with Triton X-100. The soluble acceptor exhibited isoquinoline carboxamide and benzodiazepine binding activity only when supplemented with lipid. Phosphatidylserine and phosphatidylinositol were especially efficacious. Such selectivity may reflect a specific structural requirement for acceptor activity. The requirement for lipid for acceptor activity in fractions subsequent to solubilization was demonstrated. This stabilization of acceptor activity by the phospholipids promises to facilitate purification of the functional acceptor.

Adrenal Glands↗
PubMed1992

Intermittent administration of bovine PTH-(1-34) increases serum 1,25-dihydroxyvitamin D concentrations and spinal bone density in senile (23 month) rats.

We examined the effect of intermittent administration of bovine parathyroid hormone (1-34) (bPTH) on spinal bone mineral content (BMC) and bone mineral density (BMD), serum 1,25-dihydroxyvitamin D concentrations, and serum markers of osteoblast function in senile male and female rats (23 and 24 months of age, respectively). Sexually mature young (3 month) male rats were similarly treated for comparison. bPTH administration increased serum osteocalcin concentrations without changing serum inorganic phosphate or calcium concentrations in either group of old animals. In young animals, PTH administration increased the serum calcium and inorganic phosphate concentrations significantly (p less than 0.05), although values remained within the normal range. In the vehicle-treated male rats, serum 1,25-dihydroxyvitamin D concentrations were lower in the senile than in the young animals (18 +/- 5 versus 47 +/- 6 pg/ml, p less than 0.05). PTH administration resulted in significantly increased serum 1,25-dihydroxyvitamin D concentrations in the senile and young male animals (both, p less than 0.05) and the final mean serum 1,25-dihydroxyvitamin D concentrations were not statistically different (68 +/- 9 versus 85 +/- 6 pg/ml respectively; p = NS). Serum 1,25-dihydroxyvitamin D concentrations were significantly (p less than 0.05) higher in the PTH-treated senile female rats than the sex-matched, vehicle-treated controls. The pretreatment spinal BMC and BMD as assessed by dual-energy x-ray absorptiometry (DEXA) were significantly higher in the senile male animals than in the young animals. Spinal BMC and BMD decreased in the vehicle-treated senile male rats (p less than 0.05) over the 3 weeks of the study despite a gain in weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

First report of Ixodes (Ixodes) minor Neumann (Acari: Ixodidae) from South Carolina.

Previous reports from the literature have indicated the northernmost range of extension of Ixodes minor Neumann to be southern Georgia with the greatest number of collections having been made in the coastal regions of that state. An unpublished record in the U.S. National Tick Collection indicated that I. minor had been collected as far north as South Island, Georgetown County, S.C., as early as 1933. I. minor was collected on three separate occasions in Charleston County, S.C., between October 1990 and February 1991, thus verifying the northern extension of this tick's range and the probable existence of a stable population on the coast of South Carolina. The roof rat (Rattus rattus) is reported for the first time serving as a host for I. minor.

Animals↗
PubMed1992

17 beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens.

The effect of 17 beta-estradiol on interleukin-6 (IL-6) synthesis was examined in murine bone marrow-derived stromal cell lines, normal human bone-derived cells, and nontransformed osteoblast cell lines from mice and rats. In all these cell types IL-6 production was stimulated as much as 10,000-fold in response to the combination of recombinant interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). Addition of 17 beta-estradiol in the cultures exerted a dose-dependent inhibition of IL-1-, TNF-, and IL-1 + TNF-induced production of bioassayable IL-6. Testosterone and progesterone (but not 17 alpha-estradiol) also inhibited IL-6, but their effective concentrations were two orders of magnitude higher than 17 beta-estradiol. 17 beta-estradiol also decreased the levels of the IL-6 mRNA. In addition, estradiol inhibited both TNF-induced IL-6 production and osteoclast development in primary bone cell cultures derived from neonatal murine calvaria. The TNF-stimulated osteoclast development was also suppressed by a neutralizing monoclonal anti-IL-6 antibody. This in vitro evidence suggests, for the first time, a mechanistic paradigm by which estrogens might exert at least part of their antiresorptive influence on the skeleton.

Animals↗
PubMed1992

The effects of the peripheral-type benzodiazepine acceptor ligands, Ro 5-4864 and PK 11195, on mitochondrial respiration.

The role of the peripheral-type benzodiazepine acceptor is unclear. It has been suggested that the acceptor ligands, Ro 5-4864 and PK 11195, stimulate mitochondrial respiration by binding to the peripheral-type benzodiazepine acceptor. We determined the effect of the benzodiazepine Ro 5-4864 and of the isoquinoline carboxamide PK 11195 on the respiration rates of liver, kidney and adrenal mitochondria during coupled, uncoupled and phosphorylating respiration. These ligands inhibited uncoupled and phosphorylating respiration, but only at concentrations substantially greater than their KD values for binding to the acceptor. There was a slight stimulation of coupled respiration by these ligands at concentrations similar to their KD values for the acceptor, but this stimulation was markedly greater at higher concentrations. These results suggest that the ligands Ro 5-4864 and PK 11195 affect respiration in a non-specific way, independently of binding to the acceptor. There was no correlation between the effect of these ligands on respiration and the density of the acceptor in mitochondria from liver, kidney and adrenals. We suggest that the earlier reported alteration of respiration by these ligands was due to non-specific effects and was not mediated by the peripheral-type benzodiazepine acceptor.

Adrenal Glands↗
PubMed1992

Penetration of ultra-low volume applied insecticide into dwellings for dengue vector control.

Determinations on the penetration of ultra-low volume applied insecticide into dwellings was accomplished with a model house in Frederick, MD, USA, and native houses in Santo Domingo, Dominican Republic. Results from the model house tests show that aerosol droplets, with a volume median diameter of 4 microns, penetrated and remained suspended in low recesses of the building during the first 2 min after spraying. Similar results were found with tests in Santo Domingo, where man-made or natural obstructions were determined to be critical factors in aerosol penetration.

Aedes↗
PubMed1991

Immunological studies on the rat peripheral-type benzodiazepine acceptor.

Photoaffinity labelling of rat adrenal mitochondrial preparations with [3H]PK 14105 resulted in a single 3H-labelled band on SDS/PAGE gels with an apparent-molecular-mass peak of 18 kDa. This represents a polypeptide associated with the peripheral-type benzodiazepine-binding site. Solubilization of photoaffinity-labelled membranes with 6 M-guanidine hydrochloride, followed by gel filtration and reversed-phase h.p.l.c. of the solubilized material, resulted in the purification to homogeneity of the [3H]PK 14105-labelled polypeptide. This purified polypeptide was used to raise a rabbit polyclonal antiserum which recognized the immunogen in pure form and exclusively recognized it in a crude preparation of rat adrenal mitochondria as judged by immunoblotting. By the same analysis the antiserum identified the corresponding polypeptide from rat kidney and salivary gland, demonstrating its cross-reactivity. Subsequent immunocytochemical studies localized the polypeptide to the cortex of the adrenal gland, the distal tubules of kidney, the interstitial cells of testis, the biliary epithelium of liver and the choroid plexus and ependyma cells within the brain. This selective localization within organs may provide an insight into the physiological role of the peripheral-type benzodiazepine acceptor.

Adrenal Glands↗
PubMed1991

Binding of insulin-like growth factors to cultured rat calvarial cells with differing biologic responses.

The insulin-like growth factors (IGFs) are considered important regulators of bone metabolism affecting a number of biologic responses in vitro. Primary fetal rat calvarial cells (PRC) and a cloned adult rat calvarial cell line (C3) both exhibit a concentration-dependent IGF stimulation of [3H]thymidine incorporation into DNA, but the C3 cells show a greater sensitivity and magnitude of response. IGF-I and IGF-II were nearly equipotent in PRC cultures, but IGF-I was more than twice as active as IGF-II in the C3 cultures. This effect of the IGFs on DNA synthesis in two bone cell cultures with different culture histories has been correlated with receptor and binding protein profiles. Specific high-affinity IGF binding sites were found in both cell types. In general, the sites present on PRC cells showed a preference for binding IGF-II over IGF-I, but C3 cells displayed two types of relatively specific binding sites. In both cell types [125I]IGF-I bound primarily to a protein with IGF type I receptor characteristics. However, in PRC cells, [125I]IGF-II cross-linked specifically with proteins that had IGF type II receptor characteristics plus several sites unique to these cells; in C3 cells, [125I]IGF-II bound to a 139 kD protein that could be displaced by either IGF-I or IGF-II. Finally, IGF-II-specific 85 and 67 kD proteins were common to both cell types. From these studies, it is apparent that the IGFs bind to a variety of high-affinity binding sites in bone cells and that these sites differ between a highly responsive and a less responsive bone cell population.

Animals↗
PubMed1991

Effects of antiestrogenic compounds on avian medullary bone formation.

Administration of estradiol to male Japanese quail induced the formation of medullary bone in the marrow cavities of the bird's femora and tibiae. This was accompanied by increased serum levels of calcium, phosphorus, and alkaline phosphatase activity. We examined the effects of two structurally distinct "antiestrogens" on the estrogen-induced formation of medullary bone in this quail model. Trioxifene (LY133314) and tamoxifen are members of a group of compounds commonly referred to as antiestrogens that elicit mixed agonist-antagonist actions on estrogen target tissues. In our experiments, these compounds did not display estrogen agonist properties with respect to medullary bone formation. They also did not elicit changes in serum calcium, phosphorus, or alkaline phosphatase activity. When given concurrently with estradiol, the compounds inhibited both the estrogen-induced formation of medullary bone and the associated changes in serum parameters. Trioxifene appears to be somewhat more potent than tamoxifen in antagonizing estrogen effects in this model.

Alkaline Phosphatase↗
PubMed1991

Effects of estrogen and tamoxifen on serum osteocalcin levels in ovariectomized rats.

Serum osteocalcin levels were measured in ovariectomized rats treated for 35 days with either estrogens (ethynylestradiol administered orally or 17 beta-estradiol administered by subcutaneous injection) or the antiestrogenic compound tamoxifen (administered both orally and subcutaneously). Tamoxifen is a non-steroidal compound that has mixed agonist/antagonist actions in several biological models, but is commonly referred to as an 'antiestrogen'. Administration of tamoxifen, like estrogen, caused a reduction in the increases in animal body weight and femur length during the test period, and greater bone density in the distal femur metaphysis compared to ovariectomized control animals. Both the estrogens and tamoxifen caused a dose-dependent decrease in serum osteocalcin as compared to the levels in the serum of ovariectomized control rats; however, tamoxifen displayed both reduced potency and efficacy compared to estrogens. Serum osteocalcin levels declined in a linear fashion throughout the estrogen dose range, and at the highest doses tested (400 micrograms/kg/d ethynylestradiol; 100 micrograms/kg/d 17 beta-estradiol), osteocalcin levels were reduced by 45-50% compared to those found in ovariectomized control animals. The reduction in serum osteocalcin concentrations in tamoxifen-treated animals, on the other hand, was reduced maximally by about 30% compared to those found in the ovariectomized controls at a dose of 100 micrograms/kg/d. Further reduction in serum osteocalcin beyond this level was not observed with increasing doses of tamoxifen. We conclude that tamoxifen acts as an estrogen agonist with respect to effects on serum osteocalcin levels, but fails to reduce serum levels of osteocalcin to the extent observed with steroidal estrogens.

Animals↗
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↗