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Biomedical subjects

D C Anderson

Publications and source records attributed to D C Anderson.

At least 433 records · Page 24Linked to original sources
PubMed1983

Noninvasive carotid testing in threatened stroke. 2. Predictive performance.

The various noninvasive tests have different inherent limitations, and expectations of the tests must take these limitations into account. The tests' main value lies in cases where indications do not clearly favor surgical management nor do they contraindicate it for prophylaxis of threatened stroke. In such cases, test results may help sway the clinician's decision. Intravenous digital subtraction angiography may affect the application of the traditional noninvasive technologies in the future.

Arteriosclerosis↗
PubMed1983

The interaction between Treponema pallidum and human polymorphonuclear leukocytes.

The interaction between polymorphonuclear leukocytes (PMNLs) and Treponema pallidum was studied. Intradermal injection of greater than or equal to 10(6) T. pallidum into rabbits caused a rapid accumulation of PMNLs. Human serum released chemotaxigenic factor (C5a) during incubation in vitro with T. pallidum. Incubation of T. pallidum with human PMNLs in vitro (ratio, 100:1) stimulated chemiluminescence. These responses were dependent upon the presence of both antibody and complement and were greatest when serum from a patient with late secondary syphilis was used as a chemotaxigenic source or for opsonization. Electron microscopic studies documented the rapid uptake of T. pallidum into membrane-bound vacuoles in the human PMNLs in vitro after incubation for as little as 5 min, with leukocyte degranulation and loss of treponemal integrity observed after 4 hr. T. pallidum were found within PMNLs 3 hr after intradermal inoculation of rabbits. These data show that PMNLs are attracted to, and appear to ingest, T. pallidum, but they fail to explain why inoculation of these organisms is not followed by eradication.

Animals↗
PubMed1983

Experience with trilostane in the treatment of Cushing's syndrome.

Five patients with pituitary dependent Cushing's syndrome and two with adrenal carcinoma were treated with increasing doses of trilostane (up to 1440 mg daily). There was no consistent fall in serum cortisol levels. In addition there was no rise in the levels of precursors immediately preceding the proposed site of action of trilostane. These results suggest that trilostane does not effectively block the enzyme 3 beta-hydroxysteroid dehydrogenase delta 4,delta 5 isomerase in patients with Cushing's syndrome and that it should no longer be recommended for their treatment.

Adrenal Gland Neoplasms↗
PubMed1983

Impaired chemotaxigenesis by type III group B streptococci in neonatal sera: relationship to diminished concentration of specific anticapsular antibody and abnormalities of serum complement.

A chemotaxigenesis (CTG) assay employing adult or neonatal sera, type III group B streptococci (GBS) and polymorphonuclear leukocytes (PMNs) was designed to evaluate the role of PMN mobilization in the pathogenesis of type III GBS infection in neonates. Generation of C5a in healthy adult sera with moderate-high (3-40 micrograms/ml) or low (less than or equal to 2 micrograms/ml) levels of specific anticapsular antibody was confirmed by PMN aggregometry and by the neutralization of CTG by goat anti-human C5. CTG was significantly (P less than 0.001) greater in high as compared to low specific antibody-containing adult sera; stepwise increases in CTG occurred when specific IgG was added to untreated, but not heat-inactivated, hypogammaglobulinemic serum. Immunospecificity of CTG was shown by a failure of type III GBS to generate C5a in heterologous (type Ia) high antibody sera. Mean CTG values in three high and 16 low antibody-containing sera from healthy term neonates were 24% and 62% of high (P less than 0.001) and low (P less than 0.01) antibody adult sera, respectively. The addition of both complement and specific IgG to low antibody-containing neonatal sera was required to enhance their CTG activity to high antibody adult values. CTG by type III GBS in neonatal sera-neonatal PMN mixtures was only 25% (high antibody sera) and 14% (low antibody sera) of values for paired maternal sera mixtures reacted with adult PMNs (P less than 0.001). These studies demonstrate that CTG by type III GBS in neonatal sera is markedly diminished and that low concentrations of specific anticapsular antibody and abnormalities of complement function contribute to impaired PMN mobilization in human neonates.

Adult↗
PubMed1983

Separation of two bone cell populations from fetal rat calvaria and a study of their responses to parathyroid hormone and calcitonin.

Bone cells released from perinatal rat calvaria by digestion with clostridial peptidase were separated into two distinct populations (designated types B and C) by equilibrium density centrifugation on a two-step gradient of Percoll. They were extensively characterized by light and electron microscopy and for behaviour in culture, acid and alkaline phosphatase activity, collagen synthesis, collagenase secretion and adenylate cyclase response to parathyroid hormone (PTH) and calcitonin. Type C cells were predominantly large with up to seven nuclei and an unusual cytoplasmic appearance in cytocentrifuge preparations. They did not proliferate in culture and we have established culture conditions which prevented their overgrowth by contaminating proliferative cells. In culture these cells had low alkaline and high acid phosphatase and high aryl sulphatase activity, and synthesized little collagen. In contrast type B cells were mostly smaller and many had irregular cytoplasmic projections. In culture they became polygonal in shape, proliferated rapidly, and reached confluence in 4-5 days. These were low in aryl sulphatase and acid phosphatase, high in alkaline phosphatase activity, and synthesized labelled collagen actively with [3H]proline and ascorbic acid included in the culture medium. The two cell population were found to differ in culture in two important further respects. First, the type C cells showed an adenylate cyclase response to calcitonin but not to PTH, while the converse was true for type B cells; this was so over at least a 20-fold range of isobutylmethyl xanthine concentration. Secondly, type C cells in culture secreted an active collagenolytic enzyme. Type B cells secreted much lower levels of a predominantly latent collagenase which required activation by mersalyl. Co-culture of type C and type B cells led to a marked reduction in the content of active collagenase in the culture medium.

Animals↗
PubMed1983

Estimating the impact of management decisions on the occurrence of puberty in beef heifers.

Age and weight at puberty in beef heifers were hypothesized to be jointly dependent random variables with the joint distribution conditional upon values of exogenous variables such as breed, date of birth and postweaning rate of gain. A statistical model was specified that tested the joint dependency hypothesis and measured the impact of variation in the explanatory variables on puberty. Model parameters were estimated by two-stage least-squares procedures from data on 556 beef heifers: 190 raised at the Northern Agricultural Research Center (NARC), Havre, Montana and 366 raised at the Livestock and Range Research Station (LARRS), Miles City, Montana. Results did not support the hypothesis that age and weight at puberty were jointly dependent; weight at puberty did depend upon age at puberty, but age at puberty did not depend upon weight at puberty when postweaning level of nutrition was known. Thus, the appropriate probability distribution was a conditional univariate probability distribution on age. Results were consistent with past research in that breed and breed-cross differences existed, and heifers heavier at weaning and fed higher levels of postweaning nutrition reached puberty at an earlier age and heavier weight.

Age Factors↗
PubMed1983

Impaired polymorphonuclear leukocyte motility in malnourished infants: relationship to functional abnormalities of cell adherence.

The humoral and cellular contributions to PMN motility in vitro were studied in 37 malnourished (PCM) pediatric patients. Early-phase directed migration to BCF and to ZANS was diminished significantly (p less than 0.001) in severe PCM patients as compared to healthy adult or age-matched controls or respective nutritionally restored patients. Abnormalities were reversible after nutritional restoration and unrelated to occurrence of clinical infection. To determine the pathogenic mechanism of impaired PMN mobility in PCM, studies of cell morphology and adhesive function were performed. Abnormalities observed in severe PCM suspensions included significantly (p less than 0.001) increased baseline (unstimulated) adherence values and impaired CF modulation of adhesive function. Diminished enhancement of PMN adherence or decreased (relative to baseline) adherence values were observed in response to BCF (mean % delta = +5) or f-Met-Leu-Phe (mean % delta = -6) as compared to adult PMN values of +28% delta and +31% delta, respectively. That these abnormalities may result from in vivo CF prestimulation was suggested by findings of "activated" PMN morphology in suspensions prior to in vitro stimulation, and abnormalities of the distribution of PMN surface adhesion sites under conditions of chemotactic stimulation. Further investigations will be required to determine the underlying pathogenic mechanism(s) accounting for our observations.

Cell Adhesion↗
PubMed1983

Pharmacological characterization of the acetylcholine transport system in purified Torpedo electric organ synaptic vesicles.

A wide variety of pharmacologically active compounds was surveyed for effects on active transport of [3H]acetylcholine by synaptic vesicles isolated from the electric organ of Torpedo californica. In over 80 compounds tested, inhibitors of a wide range of potencies were found. The most potent inhibitor was 2-(4-phenylpiperidino)cyclohexanol (AH5183), which half-inhibited transport at 40 nM. This compound had been predicted by Marshall [Br. J. Pharmacol. 38:503-516 (1970)] to block acetylcholine storage by vesicles in vivo. The synaptic vesicle active transport system is shown to be pharmacologically distinct from other cholinergic systems. The site of action of AH5183 and other potent inhibitors is not certain, but the possibility of trivial action on the vesicle ATPase or a vesicle proton gradient was eliminated. The results constitute new evidence supporting vesicle exocytosis as the source of evoked acetylcholine release by nerve terminals. AH5183 appears to be the prototype for a new family of anticholinergics. The possibility that some drugs that exhibit secondary anticholinergic effects act in part by antagonizing acetylcholine storage is discussed.

Acetylcholine↗
PubMed1983

Inhibition of [3H]acetylcholine active transport by tetraphenylborate and other anions.

The effects of tetraphenylborate and other anions on the active uptake of [3H]acetylcholine by synaptic vesicles isolated from Torpedo californica electric organ were studied. Tetraphenylborate completely inhibits active uptake with a half-inhibitory concentration of 0.3 microM. Dipicrylaminate also half-inhibits at 0.3 microM, phenyldicarbaundecaborane at 14 microM, fluoride at 2 mM, thiocyanate at 3 mM, and azide at 16 mM. Tetraphenylborate had no effect on the vesicle ATPase activity or the transmembrane electric potential at low concentrations where it inhibits [3H]acetylcholine active transport. The mechanism for tetraphenylborate inhibition is uncertain, but it might be similar to that of its action as a mitochondrial uncoupler. Solubility products for the acetylcholine, choline, and potassium salts of the tetraphenylborate and dipicrylaminate anions also were measured. The inhibition results confirm the hypothesis of Marshall and Parsons [Br. J. Pharmacol. 54:333-338 (1975)] that tetraphenylborate acts on intact neuromuscular preparations to inhibit transmitter storage, and constitute new pharmacological evidence that evoked release of acetylcholine is mediated by synaptic vesicles.

Acetylcholine↗
PubMed1982

Acute disseminated fatal toxoplasmosis in a squirrel monkey.

Acute disseminated toxoplasmosis was diagnosed in an adult male squirrel monkey (Saimiri sciureus). The disease was characterized by severe pulmonary edema, diffuse interstitial pneumonia, and multifocal areas of necrosis along with Toxoplasma organisms in the lungs, liver, spleen, lymph nodes, adrenal glands, and heart. Small numbers of organisms were found in bone marrow, renal glomeruli, and renal tubular epithelial and interstitial cells. Small numbers of organisms also were associated with foci of hemorrhage in the brain. The source of the infection was not determined.

Acute Disease↗
PubMed1982

Fluorinated ligands as nuclear magnetic resonance probes of active-site nonequivalence in abortive ternary complexes of horse liver alcohol dehydrogenase.

The interactions of the dimeric horse liver alcohol dehydrogenase (LADH) with ligands in two nonreactive ternary complexes have been examined by using nuclear magnetic resonance and fluorescence techniques. One complex contains the enzyme, NADH, and the abortive alcohol substrate p-(trifluoromethyl) benzyl alcohol. The trifluoromethyl group allows the bound environment and bound to free exchange kinetics of this alcohol to be examined by using 19F NMR. Binding isotherms of the coenzyme and the abortive substrate were examined by using fluorescence. Similar measurements were made with the enzyme, NADH, and the aldehyde analogue p-(trifluoromethyl) benzamide. For both complexes there was no evidence of cooperative equilibrium binding of any ligand. Careful measurements of the exchange kinetics of the fluorinated alcohol or amide when binding to the enzyme NADH complex using NMR techniques showed that a single lifetime describes the exchange of ligands from both subunits of the protein. These results appear to rule out any site-site interactions in this system and support the notion that the observed biphasic kinetics observed in transient reactions of LADH with NAD and alcohols is a property of a single site in this system.

Alcohol Dehydrogenase↗
PubMed1982

Properties of bound trifluoroethanol complexes with horse liver alcohol dehydrogenase.

The substrate analogue 2,2,2-trifluoroethanol (TFE) has been used as a 19F NMR probe of the active site of alcohol dehydrogenase from horse liver (LADH). We are able to directly observe a single resonance assigned to TFE in its ternary complex with LADH and nicotinamide adenine dinucleotide (NAD). The chemical shift of this resonance is independent of pH between values of 6.2 and 8.9, suggesting that bound TFE does not change ionization state in this range. Both by 19F NMR self-exchange measurements and by ligand-displacement studies with pyrazole, we also find that displacement of TFE from its ternary complex with NAD is a linear function of proton concentration over a similar pH range, with more rapid desorption occurring at lower pH values. This suggests that the pK of 6.4 for this process seen previously by Kvassman and Pettersson [Kvassman, J., & Pettersson, G. (1980) Eur. J. Biochem. 103, 557] is not due to the ionization of bound TFE. These studies also show that the bound lifetime of TFE in its ternary complex with LADH and NAD is quite long (400s) at pH 8.7, suggesting the use of TFE as a kinetic trapping reagent in single-turnover stopped-flow experiments. Binding isotherms of NAD to LADH saturated with TFE at pH 8.7 or with pyrazole at pH 7.5 reveal essentially no cooperative behavior. The displacement time courses described above are all adequately fit as first-order processes, thus giving no evidence for site heterogeneity or site-site interaction in the binding of these ligands to dimeric LADH. TFE and pyrazole are used as reagents to further explore the question of site-site interaction from a kinetic point of view in the following paper [Anderson, D. C., & Dahlquist, F.W. (1982) Biochemistry (following paper in this issue)].

Alcohol Dehydrogenase↗
PubMed1982

Biphasic transient kinetics are a property of a single site in horse liver alcohol dehydrogenase.

The transient kinetics under single turnover conditions of the dimeric enzyme horse liver alcohol dehydrogenase (LADH) are often biphasic with nearly equal amplitudes in the fast and slow components of the reaction. These observations have been the basis for the suggestion that this enzyme displays half of the sites reactivity or kinetic site-site interactions in its catalytic cycle [Bernhard, S.A., Dunn, M.F., Luisi, P.L., & Shack, P. (1970) Biochemistry 9, 185]. Alternatively, the biphasic kinetics could be the result of a complex mechanistic path at a single site with no kinetic interactions between the active sites [Kvassman, J., & Pettersson, G. (1976) Eur. J. Biochem. 62, 279; Kvassman, J., & Pettersson, G. (1978) Eur. J. Biochem. 87, 417]. To resolve this question, we have prepared LADH in which one of the two active sites is occupied by the strongly bound, slowly exchanging ternary complex inhibitors NAD with trifluoroethanol or NAD with pyrazole. These half-inhibited dimers show essentially the same biphasic transient kinetics as the native enzyme. These results strongly support mechanisms in which the observed kinetics are a property of each independently functioning site of the dimer. The possibility of half of the sites reactivity or kinetic site-site interaction appears to be ruled out.

Alcohol Dehydrogenase↗
PubMed1982

Proton gradient linkage to active uptake of [3H]acetylcholine by Torpedo electric organ synaptic vesicles.

It has been confirmed that cholinergic synaptic vesicles isolated from the electric organ of Torpedo californica exhibit adenosine 5'-triphosphate (ATP) dependent active uptake of [3H]acetylcholine. Active uptake can be completely inhibited by low concentrations of the mitochondrial uncouplers carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone, nigericin, gramicidin, valinomycin, and A 23187. Under similar conditions uncouplers stimulate the vesicle adenosinetriphosphatase (ATPase) by from 40 to 80%. ATP-supported uptake of [3H]acetylcholine increases greatly as the external pH is increased from 6.6 to 7.6 and remains approximately constant from pH 7.8 to pH 8.6. The uptake also becomes more selective for [3H]acetylcholine compared to [14C]choline as the pH is increased from 6.6 to 7.6, achieving 12-fold selectively, in a manner similar to the increase in the amount of [3H]acetylcholine taken up. Bicarbonate stimulates both the amount and selectivity of [3H]acetylcholine uptake over the lower pH range, but it has no effect over the higher pH range. Exogenous ammonium ion completely inhibits active [3H]acetylcholine uptake, with lower concentrations of ammonium ion required at higher pH values in a manner consistent with ammonia being the active species. Adenosine 5'-diphosphate and a nonhydrolyzable ATP analogue do not support active [3H]acetylcholine uptake. It is concluded that an ATPase pumps protons into the cholinergic synaptic vesicle to produce an internally acidic and positively charged proton gradient that is linked to [3H]acetylcholine uptake.

Acetylcholine↗