Search PubMed⌕ Search

Biomedical subjects

G Thomas

Publications and source records attributed to G Thomas.

At least 721 records · Page 40Linked to original sources
PubMed1986

[Mutagenicity of urine after ingestion of saccharin in man].

In vitro tests of mutagenicity help detect carcinogenic substances. A variation of the Ames test may be used to study the mutagenicity of urine after exposition of the organism in vivo. Saccharin is a widely used artificial sweetener excreted in the urine which can induce dose-dependent tumours of the bladder in the animal. We studied the mutagenicity of the urine of healthy volunteers after the ingestion of a single dose of saccharin. The results show a mutagenic effect related to the dose ingested in two types of Salmonella typhimurium (TA 98 and TA 38). These results are difficult to interpret as saccharin is not mutagenic in vitro alone or in the presence of control urine which eliminates a direct carcinogenic or cocarcinogenic effect; we were unable to detect impurities or metabolites. This study underlines the difficulty of prophylactic detection of chemical carcinogens.

Administration, Oral↗
PubMed1985

Epidermal growth factor-mediated activation of an S6 kinase in Swiss mouse 3T3 cells.

Extracts from epidermal growth factor (EGF)-stimulated Swiss mouse 3T3 cells are up to 10 times more potent in phosphorylating ribosomal protein S6 than extracts from quiescent cells. Preparation of extracts in the absence of phosphatase inhibitors leads to a time-dependent loss of kinase activity. In order of potency, the most efficient phosphatase inhibitors in protecting the S6 kinase activity are phosphotyrosine followed by p-nitrophenyl phosphate, beta-glycerol phosphate, and phosphoserine. The kinetics of kinase activation following EGF treatment are rapid and transient. The maximum increase is observed between 15 and 30 min with only 20-30% of the activity remaining after 2 h. Phosphorylation of S6 in the intact cell follows a similar pattern of activation, reaching a maximum between 30 and 60 min and then slowly returning to basal levels by approximately 3 h. The activation of protein synthesis is also rapid; however, in contrast to the transient activation of the S6 kinase and S6 phosphorylation, it remains persistently high for at least 6 h following EGF treatment. Comparison of these events with EGF binding shows that about 50% of the cell surface binding sites are lost within 10 min of exposure to EGF, and about 25% remain after 2 h. Finally, sodium orthovanadate, which is known to mimic the mitogenic effect of EGF, also leads to activation of the S6 kinase, however, with distinct kinetics and by an apparent EGF receptor-independent pathway.

Animals↗
PubMed1985

The optical isomers of the 1,4-dihydropyridine BAY K 8644 show opposite effects on Ca channels.

The optical isomers of the 1,4-dihydropyridine BAY K 8644 were studied in isolated rabbit aorta and heart preparations. The (-)-enantiomer has the known vasoconstricting and positive inotropic properties of the Ca agonistic compound. In contrast, its antipode shows at about 10-50 times higher concentrations the vasodilating and negative inotropic effects of Ca antagonistic drugs. It is concluded that neither simple chemical nor physical actions can be responsible for the opposite effects of Ca antagonistic and Ca agonistic dihydropyridines.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

The complete sequence of the chicken delta 1 crystallin gene and its 5' flanking region.

delta-Crystallin is the principal structural protein of the embryonic chicken lens. In the chicken, there are two linked delta-crystallin genes arranged in the same transcriptional polarity (5'-delta 1-delta 2-3'). Here we have sequenced the delta 1 crystallin gene and almost 4.3 kilobases of its 5' flanking region. The delta 1 gene is 7766 base pairs in length and has 17 exons. At least one lariat branch consensus sequence has been identified in each intron. Analysis of the deduced delta-crystallin protein using a program which accounts for conservative amino acid changes shows regions of similarity within the delta 1 amino acid sequence. These suggest a rough 2-fold repeat in the protein structure.

Amino Acid Sequence↗
PubMed1985

Metabolic and immunological effects of cyclosporin in recently diagnosed type 1 diabetes mellitus.

Cyclosporin 5-10 mg/kg daily was given for 2-8 months to twelve recently diagnosed type 1 diabetics from a mean of 49 +/- SE 14 days after the start of insulin therapy, which was regulated to give near-normal blood glucose and haemoglobin A1c values. Mean insulin dosage dropped from 46 +/- 5 U/day before cyclosporin treatment to 16 +/- 4 U/day by the 7th month. Four patients had a complete remission and the insulin needs of four more were cut by half. The remaining four did not have remissions. Initial basal and glucagon-stimulated C peptide concentrations were higher in those who went into remission than in those who did not; they rose during cyclosporin treatment in the former but not in the latter. OKT4+ lymphocyte functions were suppressed in all patients and OKT4/OKT8 ratios declined. Anti-beta-cell autoimmunity, as indicated by lymphocyte-induced inhibition of insulin release from mouse islet cells, declined in all patients who went into remission. No consistent trend was observed for anti-islet cell antibodies. In forty-four similar, but non-randomised, recently diagnosed diabetics treated with insulin alone, the incidence of remission was 6%.

Adult↗
PubMed1985

The positive inotropic dihydropyridine Bay K 8644 does not affect calcium sensitivity or calcium release of skinned cardiac fibres.

BAY K 8644 is a positive inotropic dihydropyridine which concentration-dependently increased contractile force in guinea-pig atria at 10 to 1000 nmol/l. In chemically skinned cardiac fibres from guinea-pig hearts the substance did not change the tension induced by calcium. Also BAY K 8644 did not release calcium from intracellular myocardial stores like caffeine since it failed to evoke a contractile response in saponin-treated, calcium-loaded cardiac muscle. Thus, the drug exerts its effects neither by sensitizing the contractile apparatus to calcium nor by a caffeine-like action.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Host finding and feeding in Hydrotaea irritans (Diptera, Muscidae): the role of chemical senses.

Hydrotaea irritans is commonly considered to be the primary vector for the bacteria which cause summer mastitis in cattle. A behavioural physiology approach was used to investigate potential host odours (kairomones) that may be used by the fly in finding its host and to determine which substrates or sites on the host may be utilised in feeding. Attractant odours include CO2 and butyric, propionic and acetic acids: the latter three are also produced by the bacteria causing summer mastitis. When milk, slaver, nasal secretion, mastitis secretion and blood were offered to flies as feeding substrates only the last three produced significant increases in feeding duration in comparison to controls offered distilled water.

Animals↗
PubMed1985

Anti-inflammatory actions of tannins isolated from the bark of Anacardium occidentale L.

A mixture of tannins (hydrolysable and non-hydrolysable) obtained from the bark of Anacardium occidentale L., on i.p. injection, demonstrated apparent anti-inflammatory activity in carrageenan- and dextran-induced rat paw oedemas, cotton pellet granuloma test and adjuvant-induced polyarthritis in rats. At higher doses orally administered tannins also had activity in carrageenan paw oedema and adjuvant arthritis experiments. The tannins i.p. also inhibited acetic acid-induced "writhing responses" in mice and were found to antagonise the permeability-increasing effects in rats of certain mediators of inflammation and to inhibit the migration of leucocytes to an inflammatory site. While not appearing to act by the release of adrenal hormones, tannins may produce effects in a non-specific manner by their astringent properties on cell membranes thus affecting cell functions. The above results should be considered while studying the anti-inflammatory actions of plant extracts which contain tannins.

Animals↗
PubMed1985

The radiation sensitivities of R3327-H and R3327-AT rat prostate adenocarcinomas.

Dunning R3327-H and R3327-AT tumors growing subcutaneously in the flanks of Fischer X Copenhagen rats were irradiated with 137Cs gamma-rays at volumes of approximately 300 mm. The effects of various doses of radiation were estimated by measurements of subsequent tumor growth as well as by histological evaluation. The well-differentiated, hormonally-responsive R3327-H tumor was more radiosensitive than the anaplastic R3327-AT tumor. The reasons for this increased radiation sensitivity of the R3327-H tumor include a greater "apparent" radiation sensitivity of tumor cells and the absence of tumor hypoxia. The presence of hypoxic tumor stem cells was inferred from significant radiosensitization of tumor growth delay by 0.5 mg./gm. misonidazole and by a technique which utilizes radioactively-labelled misonidazole as a marker for hypoxic cells. The persistence of a mass of R3327-H tumor tissue after aggressive radiotherapy was not indicative of tumor cells. Furthermore, the rapid increase in volume of R3327-AT cells after aggressive radiotherapy was attributed to limited proliferation of tumor cells which were destined to ultimately die. Possible implications of these findings for the management of human prostatic adenocarcinoma are discussed.

Adenocarcinoma↗
PubMed1985

Threshold for lens damage during Q-switched Nd:YAG laser iridectomy. A study of rhesus monkey eyes.

Clinical and pathologic examinations were performed after 18 iridectomies had been created in six eyes of three rhesus monkeys using increasing Q-switched neodymium (Nd):YAG laser energy, pulses per burst, and number of bursts. Treatment parameters bracketed the threshold for lens damage during iridectomy. Iridectomy with one or two bursts of one or two Q-switched pulses at 5 to 6.2 mJ per pulse was achieved without lens damage. Slight increase of pulse energy or an increase to three pulses per burst (without pulse energy increase) caused local damage to the underlying lens. Marked increase of any of the treatment parameters caused slightly larger iridectomies and slightly larger, localized damage of the underlying lens. Synechiae developed between the monkey posterior iris surface at the iridectomy and the damaged area in 80% of the lens lesions. In monkeys, the small pulsed laser iridectomies created with pulses of energies up to 6.5 mJ became occluded during the healing process.

Animals↗
PubMed1985

Endothelial damage thresholds for retrocorneal Q-switched neodymium:YAG laser pulses in monkeys.

Laser pulses were focused within 1 mm of the rhesus monkey corneal endothelium using the Coherent Model 9900 laser at energies of 3, 6, 9, and 12 mJ. Sixteen slightly off-axis pulses were applied with no contact lens on the eye. Corneal damage was studied clinically and by scanning electron microscopy. Q-switched pulses of 12 mJ or less are not likely to damage the cornea if focused more than 0.75 mm from the endothelium. The retrocorneal focal distance for a 50% incidence of endothelial damage for 6, 9, and 12 mJ pulses was found to be less than 0.5 mm. For 3 mJ pulses, it was less than 0.25 mm. The severe early effect of suprathreshold pulses is edema of endothelial cells in a 0.2- to 0.6-mm diameter circular zone surrounding a small central pit through Descemet's membrane. At two months, irregular enlargement of endothelial cells surrounding and partially covering the persistent pit exists at sites of severe damage. The extent of the longer-term change is proportional to the severity of the original insult, but in no case was there clinically significant, persistent damage in the healed corneas.

Animals↗
PubMed1985

Endothelial damage from retrocorneal mode-locked neodymium:YAG laser pulses in monkeys.

Laser pulses were focused 0.85 to 1.60 mm from the rhesus monkey corneal endothelium using a mode-locked laser at 3.3 and 4.5 mJ. Sixteen slightly off-axis pulses were applied with no contact lens on the eye. Corneal damage was studied clinically and by scanning electron microscopy. The retrocorneal distance for a 50% incidence of endothelial damage (LD 50 = lesion distance, 50%) for 3.3 mJ mode-locked pulses was found to be 1.60 mm. All mode-locked pulses of 4.5 mJ focused 0.85 to 1.60 mJ from the endothelium caused damage. In comparison, Q-switched pulses of 12 mJ or less are not likely to damage the cornea if focused more than 0.75 mm from the endothelium. The severe, early effect of mode-locked pulses is edema of endothelial cells in a 0.2- to 0.3-mm diameter circular zone surrounding a 0.1-mm diameter denuded zone with a small central break of Descemet's membrane. By two months, mild and moderate lesions heal with little or no distortion of the endothelial mosaic. Irregular enlargement of endothelial cells surrounding and covering the previously denuded area of severe lesions is caused by both mode-locked and Q-switched treatment. In no case was there clinically significant, persistent damage in the healed monkey corneas.

Animals↗
PubMed1985

Histopathology of neodymium: YAG laser iridectomy in humans.

Fifteen peripheral iridectomy specimens were obtained, with informed consent, from patients with primary narrow angle glaucoma, after previous neodymium:YAG (Nd:YAG) laser iridectomy. The iridectomies were performed three hours to ten weeks after laser application. Iridectomy specimens were examined by scanning and/or transmission electron microscopy. Early effects of the Nd:YAG laser on the iris were mild hemorrhage and fibrinous aggregates. There were no inflammatory cell infiltrates. At later time intervals (up to 2 months post-laser treatment) the holes showed irregular thickness of iris pigment epithelium at the margins, and tissue atrophy limited to the immediate margins of the hole. Elsewhere the iris was structurally intact. The diameter of the holes varied from 60 to 500 microns. The larger holes corresponded to cases that had received more application shots.

Aged↗
PubMed1985

A dihydropyridine (Bay k 8644) that enhances calcium currents in guinea pig and calf myocardial cells. A new type of positive inotropic agent.

Bay k 8644 is a structural analog of nifedipine with positive inotropic activity. The mechanism of drug action was evaluated by measuring the effects of Bay k 8644 on twitch tension, action potential configuration, and calcium channel currents in myocardial cells. Bay k 8644 increases twitch tension in guinea pig atria without changing the time course of tension development. The drug does not occlude the effect of isoproterenol on twitch tension. The effects of Bay k 8644 on atrial twitch tension are highly dependent on the frequency of stimulation. Maximal inotropic effects are observed at approximately 0.5 Hz, but no inotropic effect occurs at 0.003 Hz (a rested-state contraction). Since positive inotropic effects only occur with frequent electrical stimulation, they are not due to an intracellular action or to mechanisms that elevate cell calcium in quiescent muscle, such as inhibition of the Na,K-ATPase. Bay k 8644 increases the action potential duration of calf ventricular muscle and Purkinje fibers. Effects on action potential duration are occluded by 1 microM nisoldipine, which specifically blocks calcium channels. The interaction of Bay k 8644 with calcium channels in calf Purkinje fibers was studied using the two-microelectrode voltage clamp technique. Strontium was used as a charge carrier to minimize current through calcium-activated channels and to avoid changes in calcium conductance due to changes in intracellular calcium. Bay k 8644 increases strontium currents and alters the time- and voltage-dependence of channel opening. The greatest percent increase in strontium current occurs for weak depolarizations. For strong depolarizations, strontium current is increased most at the beginning of a test pulse. The drug-induced changes in calcium channel gating are inconsistent with a calcium- or cyclic adenosine monophosphate-mediated effect, and indicate a novel mechanism of action on calcium channels. Thus, Bay k 8644 is the first positive inotropic agent shown to act specifically and directly on calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Platelet glutathione and thromboxane synthesis in diabetes.

The relationship of the reduced glutathione (GSH) content in unstimulated platelets and their capacity to synthesize thromboxane A2 (TXA2), measured by radioimmunoassay of TXB2, was investigated in diabetic and matched control subjects. The GSH content in platelets from diabetic subjects (6.52 +/- 0.73 microgram/10(9) platelets, mean +/- SD) was significantly (P less than 0.001) lower than in platelets from control subjects (10.10 +/- 1.58 microgram/10(9) platelets). When platelet-rich plasma (PRP) was stimulated with 1.65 mM arachidonic acid, significantly (P less than 0.001) more TXB2 was formed in PRP from diabetic subjects (344 +/- 87 ng/2.5 X 10(8) platelets) than in PRP from control subjects (132 +/- 35 ng/2.5 X 10(8) platelets). Furthermore, the plasma level of TXB2 was increased in diabetic subjects (522 +/- 117 pg/ml) in comparison with control subjects (187 +/- 63 pg/ml). An inverse correlation (r = 0.98) was observed between the GSH content in unstimulated platelets and their capacity to synthesize TXA2 when stimulated with 1.65 mM arachidonic acid. These data suggest that platelet GSH may have an important regulatory effect on platelet TXA2 synthesis and that increased TXA2 synthesis by platelets from diabetic subjects may be the result of low intracellular GSH levels.

Adolescent↗
PubMed1985

Experimental pyelonephritis and papillary necrosis in the Gunn rat.

Homozygous and heterozygous female Gunn rats show increased susceptibility to experimental urinary infection. The strain develops pyelonephritis after intravesical inoculation of Proteus mirabilis in numbers which fail to induce the lesion in albino rats, and severe pyelonephritis is frequently complicated by papillary necrosis. The basis for this enhanced susceptibility has not been defined, but the occurrence of the phenomenon in both homozygous and heterozygous rats indicates that it is not caused primarily by high plasma levels of unconjugated bilirubin or by the deposition of bilirubin in the tip of the renal papilla. The increased susceptibility of the homozygous Gunn rat to ascending urinary tract infection provides supporting evidence for the suggestion that infection may complicate the natural history of experimental analgesic nephropathy in this strain and is relevant to the clinical association of analgesic nephropathy and urinary infection.

Animals↗
PubMed1985

Cardiovascular effects of the calcium-agonistic dihydropyridine BAY K 8644 in conscious dogs.

The hemodynamic effects of the dihydropyridine-derivative BAY K 8644 (methyl-1,4-dihydro-2, 6-dimethyl-3-nitro-4-(2-trifluoro-methylphenyl)-pyridine-5-carboxylate), a chemical analogue of Nifedipine, were evaluated in 9 conscious, chronically instrumented dogs. Compared to Nifedipine, BAY K 8644 displays an opposite pharmacological profile. Dose-dependent hemodynamic effects are observed at doses of 4 micrograms/kg i.v. and above. With 32 micrograms/kg i.v. BAY K 8644 increases total peripheral vascular resistance by 100%. It causes a rise of both, systolic and diastolic, blood pressure up to 196/138 mm Hg at spontaneous sinus rhythm and up to 216/162 mm Hg when keeping heart rate constant at 150 beats/minute. Spontaneous heart rate reflexly drops to 52 beats/minute. Cardiac contractility as indicated by LV(dP/dt)max markedly increases from 2800 to 5600 mm Hg/s at spontaneous sinus rhythm and from 2900 to 6100 mm Hg/s while pacing at 150 beats/minute. These effects are apparently neither affected by alpha-adrenergic blockade with Phenoxybenzamine (5 mg/kg i.v.) nor by beta-blockade with Propranolol (0.5 mg/kg i.v.) but can be reserved by equivalent doses of Nifedipine. In conclusion, the Calcium-agonistic dihydropyridine BAY K 8644 due to its novel mechanism of action could be the precursor of a new class of positive inotropic or antihypotensive drugs.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗