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Biomedical subjects

A Davis

Publications and source records attributed to A Davis.

At least 343 records · Page 19Linked to original sources
PubMed1983

A role for an indoleamine other than 5-hydroxytryptamine in the hypothalamic thermoregulatory pathways of the rat.

1. Intrahypothalamic injection of either 5-hydroxytryptamine (5-HT) (20 mug) or tryptamine (1 mug) caused hypothermia and hyperthermia respectively in lightly restrained rats maintained at an ambient temperature of 20 +/- 1 degrees C.2. Both the 5-HT- and the tryptamine-sensitive sites were located within the same region of the preoptic area.3. When rats were tested at different ambient temperatures (4, 20 and 29 degrees C), intrahypothalamic injection of 5-HT caused a marked fall in core temperature (-1.3 degrees C) in rats maintained at 4 degrees C, but smaller responses were obtained at 20 and 29 degrees C (-0.9 and -0.5 degrees C respectively). Tryptamine caused a significant hyperthermia in rats kept at 20 degrees C, but had no significant effect in rats maintained at either 4 or 29 degrees C.4. The hypothermic effect of 5-HT was selectively antagonized by systemic pre-treatment with cyproheptadine (2.5 mg/kg), but not by methergoline (0.625 mg/kg) and methysergide (0.2 mg/kg). In contrast, the hyperthermic effect of tryptamine was blocked by methergoline and methysergide, but not by cyproheptadine.5. Cyproheptadine (2.5 mg/kg) reduced the ability of rats to cope with a heat load but had no effect on the response to cold. In contrast, methergoline (0.625 mg/kg) and methysergide (0.2 mg/kg) reduced the ability to cope with cold but the rats' ability to cope with a heat load remained intact.6. These results suggest the existence of two indoleamine pathways within the preoptic anterior hypothalamus involved in the control of body temperature: a serotonergic pathway mediating heat loss and a non-serotonergic pathway mediating heat gain. The non-serotonergic system may exert its effects by modulating the activity of a central serotonergic system.

Animals↗
PubMed1982

Ascorbate injury and EDTA (or manganese) protection of D2-dopamine receptors.

Ascorbic acid, EDTA, and Mn2+ modulated neuroleptic binding to membrane receptors but not to solubilized receptors. Preincubation with ascorbic acid at 22 degrees C produced a profound time-dependent decline in [3H]spiperone binding to membrane receptors (prepared in Tris-ascorbate buffer). Ascorbate had minimal effect if introduced simultaneously with [3H]spiperone in the incubation medium, and receptor binding was performed and assayed at 0 degrees C. Binding to the solubilized receptor was not ascorbate sensitive. Both EDTA and Mn2+ blocked the ascorbate effect on membrane receptors but were without effect on solubilized receptors. The preparation and incubation buffers used for [3H]spiperone binding studies should include EDTA if ascorbate is present in the buffer.

Animals↗
PubMed1982

Solubilized receptors for [3H]dopamine (D3 binding sites) from canine brain.

The objective of the present study was to solubilize the D3 site which binds [3H]dopamine, using the same digitonin method that had been successful in solubilizing the D2 dopamine receptor. Canine brain striatal membranes were solubilized by a final concentration of 1% digitonin. The specific binding of [3H]dopamine to the soluble D3 binding sites was measured using Sephadex G-50 gel filtration. The density of D3 sites was identical in the membrane and soluble preparations (82-90 fmoles/mg protein), although the dissociation constant (KD value) went from 1.2 nM in the membranes to the value of 3.4 nM in the soluble material. The concentrations of various drugs which inhibited the binding of [3H]dopamine were similar in the two preparations. The agonists [dopamine, apomorphine and (+/-)-6,7-dihydroxy-2-aminotetralin (ADTN)] all inhibited the binding of [3H]dopamine by 50% at concentrations between 2 and 20 nM in both the intact and soluble preparations. The neuroleptics were all equally weak in inhibiting the binding of [3H]dopamine, with IC50 values in the micromolar concentration range, values typical for the D3 site. Approximately 36% of the D3 sites were recovered from the original tissue. Since the densities and recoveries of the D2 and D3 sites differed upon digitonin solubilization, this provided further indirect evidence that these two sites are distinct and separate entities which might ultimately be separated.

Animals↗
PubMed1982

Comparison of soluble dopamine D2-receptors from three species.

In order to determine the species which would provide the highest yield of soluble and specific D2-type dopamine receptors, the striata from human, calf and canine brains were solubilized by 1% digitonin. The receptors were detected with [3H]spiperone, using Sephadex G-50 columns or polyethylene glycol precipitation. The soluble D2-sites from the human and canine tissue had about the same KD and rank order of drug affinities as the native membrane preparations. The binding characteristics of the calf D2-receptors were considerably altered, however, upon solubilization; the affinities for spiperone and chloropromazine were reduced 12-fold, and the non-specific binding increased from 28 to 50%. Calf caudate is a poor choice for dopamine receptor solubilization using digitonin. The solubilized canine tissue, however, provided an excellent source of D2-receptors because of its similarity to soluble human D2-receptors and its stability in solution.

Animals↗
PubMed1982

UVR radiometry of solar simulated radiation in experimental photocarcinogenesis studies.

The UVR radiometry of a long-term mouse photocarcinogenesis project is described. The methods used were (a) a phototherapy (UV-A) radiometer, (b) an electronic integrating dosimeter, (c) indirect spectroradiometry and (d) polysulphone and phenothiazine film badges for UV-B and UV-A respectively. The merits of the various methods are discussed. All but the phenothiazine film were considered to be satisfactory. The importance of reliable UVR radiometry is emphasized.

Animals↗
PubMed1982

Pretreatment behavioral profiles associated with subsequent psychosocial adjustment in radiation therapy patients: a prospective study.

A clinically derived system of judging cancer patients' engagement, reality testing and degree of arousal during a pretreatment consultation was found predictive of psychosocial problems or no problems reported by sixty cancer patients one month after starting radiation therapy. Independent ratings of psychosocial problems by the treating oncologists, nurses and radiation therapists three months after starting treatment were also found significantly associated with the pretreatment composite. Disease, treatment and demographic factors were not predictive of psychosocial problems and were not associated with the pretreatment clinical composite. Follow-up observations at six months and eighteen to twenty-four months of forty-four and twenty-four of the original patients available for study revealed there was no continuing association between their pretreatment clinical composites and psychosocial problem ratings.

Adult↗
PubMed1982

Potential for single high-dose influenza immunization in unprimed children.

High concentrations of split-product vaccine (SPV) are more immunogenic than lower concentrations. These studies were verified with another influenza strain, B/Singapore/22/79. Two ether-treated SPVs were compared in 80 children and young adults. The vaccine strains were influenza A/Bangkok/79, A/Brazil/78, and B/Singapore/79; 44 patients received a high-dose SPV containing 7, 7 and 60 micrograms each of the respective hemagglutinins (HA) and 36 received a standard dose SPV containing 7, 7, and 7 micrograms of HA, respectively. Among persons initially seronegative by hemagglutination inhibition (HAI) tests, the geometric mean titer (GMT) in 15 recipients of one high dose was 97 vs GMT of 37 in 18 recipients of one standard dose (P less than .05). Furthermore, 87% of high-dose recipients had HAI titer greater than or equal to 40 vs 44% of standard dose recipients. In initially seropositive persons, GMT in 29 recipients of one high dose was 170 vs GMT of 84 in 18 recipients of one standard dose (P less than .05). Immune response to the other two virus strains was comparable for the two vaccines. The reaction index for the high dose vaccine was 0.70 vs 0.45 for the standard dose (P = NS). An A/Bangkok epidemic struck the New York metropolitan area. The attack rate in unvaccinated matched sibling control subjects was 35% (15/43). There were no vaccine failures. In conclusions, in the small number of patients studied, a 60-micrograms HA dose of B/Singapore/79 was significantly more immunogenic than a standard 7-micrograms HA dose without an increase in reactogenicity.

Adolescent↗
PubMed1981

Assay for soluble dopamine receptors by the precipitation method.

Receptors with high affinity for neuroleptics (D2-type dopamine receptors) were solubilized from dog striatum using 1% digitonin. Soluble receptors were labelled using [3H]spiperone, and the bound 3H-ligand was separated from the free [3H]spiperone by molecular sieving on the Sephadex G-50 columns. This paper presents a polyethylene glycol (PEG) precipitation method designed to replace this column method. IC50 values for both neuroleptics and dopamine agonists, as well as dissociation constants for [3H]spiperone were similar for both methods. The precipitation method yielded a receptor density of 64 fmol/mg protein whereas the molecular sieving technique yielded a value of 194 fmol/mg protein. The qualitative similarities between the methods validates using the rapid precipitation method for monitoring the receptor during various stages of its purification.

Animals↗
PubMed1981

Further study of the conformation of nuclease-(1-126) in relation to intrinsic enzymatic activity.

Nuclease-(1-126), although containing 89% of the amino acid sequence which folds to the ordered structure of nuclease A, is disordered and highly flexible (Taniuchi, H., and Anfinsen, C. B. (1969) J. Biol. Chem. 243, 4778-4786). On the other hand, Sachs et al. (Sachs, D. H., Schechter, A. N., Eastlake, A., and Anfinsen, C. B. (1974) Nature 251, 242-244) have demonstrated intrinsic enzymatic activity for nuclease-(1-126). To attempt to learn whether or not the active population of nuclease-(1-126) has the native conformation, we have examined nuclease-(1-126) with respect to enzymatic kinetics with and without the competitive inhibitor deoxythymidine 3',5'-diphosphate (pdTp), effect of temperature on enzymatic activity, binding of pdTp in the presence of Ca2+ and intrinsic viscosity, Stokes radius, CD, and response to trypsin action in the presence and absence of pdTp and Ca2+. The results indicate that the conformation of nuclease-(1-126) bound with pdTp in the presence of Ca2+ is partially constrained but still highly flexible below 30 degrees C, outside the range of thermal transition exhibited by the ordered elements of nuclease-(1-126). Thus, formation or stabilization of active site of nuclease-(1-126) by binding with ligands is not associated with cooperative folding of the entire polypeptide chain. Considering that nuclease-(1-126) does not bind to nuclease-(127-149) but does to nuclease-(111-149), the results are consistent with the idea that the specific cooperative interactions, providing extra stabilizing energy required for maintaining the polypeptide chain in the ordered state of nuclease A, may be disrupted for nuclease-(1-126) primarily due to cleavage of the peptide bond between residues 126 and 127. Then, it may be thought that binding with ligands does not compensate for this disruption.

Circular Dichroism↗
PubMed1981

Solubilization of neuroleptic/dopamine receptors of human brain striatum.

Dopaminergic neuroleptic receptors were solubilized by digitonin from post-mortem human brain putamen. The receptors were labelled by [3H]spiperone and separated from free [3H]spiperone by sephadex chromatography. Neuroleptics and neurotransmitters had similar inhibitory and stereoselective potencies on the solubilized and intact membrane receptors. The KD for [3H]spiperone was apparently high for the solubilized receptors. Unlike the rat striatum, therefore, the human putamen can be solubilized to release neuroleptic/dopamine receptors, permitting the future development of highly sensitive methods for detecting dopamine receptors.

Antipsychotic Agents↗
PubMed1981

Hemoglobin switching in sheep. Isolation of the fetal gamma-globin gene and demonstration that the fetal gamma- and adult beta A-globin genes lie within eight kilobase segments of homologous DNA.

A recombinant DNA library of sheep genomic DNA fragments inserted into the bacteriophage vector, Charon 4A, was screened by plaque hybridization with a probe for sheep gamma-globin gene sequences. Three clones containing overlapping segments of DNA, the total length of which was 25 kb, were identified; each included all or a part of the same globin gene. Nucleotide sequencing of substantial portions of the globin gene in one clone, lambda S gamma G31, and of the gene in a previously isolated recombinant, lambda S beta AG21, established that the genes in these recombinants encoded for the gamma- and beta A-globin genes of sheep, respectively. Features characteristic of globin genes in other species that were identified in both genes included a sequence, ATAAAA, 30 nucleotides from the presumed site of initiation of transcription, a region of "capping homology," two introns at positions corresponding to amino acids 29-30 and 103-104 and the polyadenylation sequence, AATAAA, in the 3' untranslated region. Electron microscopic analysis of heteroduplexes formed between lambda S gamma G31 and lambda S beta AG21 revealed that the gamma and beta A genes of sheep lie within segments of homologous DNA at least 8 kb in length within which were identified small regions of nonhomology both 5' and 3' to the genes.

Amino Acid Sequence↗
PubMed1981

Microcephaly, microphthalmia, falciform retinal folds, and blindness. A new syndrome.

We have observed an apparently new, heritable syndrome consisting of severe microcephaly, microphthalmia, falciform retinal folds, and blindness. Two brothers were affected with these problems. The mother, while she has no ocular malformations, has severe microcephaly and mild mental retardation. The only other offspring of the parents, a boy, is normal. Laboratory evaluation of the affected sibs was uninformative. An environmental cause of this condition has been sought, but none has been identified. Possible modes of inheritance include autosomal dominant inheritance with variable expressivity, X-linked recessive inheritance with partial expression in the mother, or autosomal recessive inheritance that is etiologically unrelated to the mother's microcephaly.

Abnormalities, Multiple↗
PubMed1981

In vitro synthesis of adenovirus type 5 T antigens. I. Translation of early region 1-specific rna from lytically infected cells.

Translation of early RNA specific for the leftmost early region 1 of adenovirus type 5 DNA in a rabbit reticulocyte cell-free system resulted in the synthesis of proteins with the following molecular weights: 65,000 (65K), 54K, 42 to 34K, 29K, 25K, 19K, and 18K. All of these proteins could be immunoprecipitated with hamster antitumor serum. The 42 to 34K proteins mapped in early region 1a, and those with molecular weights of 65K, 19K, and 18K mapped in early region 1b. The gene coding for the 54K protein may be localized outside of early region 1. We could not map unambiguously the 29K and 25K proteins. The identification of a 65K protein among products synthesized in vitro suggests that this protein may be identical to the 65K major T antigen present in adenovirus type 5-infected and -transformed cells, and this indicates that it is indeed encoded by the viral genome. This protein is encoded by a 23S mRNA. The other early region 1-specific proteins appear to be encoded by mRNA of approximately 13S, except for the 19K protein, which is synthesized with RNA sedimenting at both 13S and 23S.

Adenoviruses, Human↗