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Biomedical subjects

J H Jones

Publications and source records attributed to J H Jones.

At least 109 records · Page 6Linked to original sources

Synthesis of (7R)-7H-indolo[3,4-gh][1,4]benzoxazines, a new class of D-heteroergolines with dopamine agonist activity.

Synthesis of several members of the 9-oxaergoline ring system is presented. Both the C/D cis and the C/D trans isomers of 4,6,6a,8,9,10a-hexahydro-7-ethyl-7H-indolo[3,4-gh] [1,4]benzoxazine were prepared, and the C/D trans isomer was resolved into its optical isomers. The enantiomer having the highest affinity for the [3H]apomorphine binding site, (-)-trans-6-ethyl-9-oxaergoline [(-)-6b], was shown to have the same absolute configuration as the natural ergolines, namely, 6aR, 10aR. In vivo and in vitro pharmacological evaluation shows these 9-oxaergolines to possess potent dopamine agonist properties.

Animals↗

Changes in blood pressure and renal function after parathyroidectomy in primary hyperparathyroidism.

Changes in blood pressure and renal function were investigated in 62 patients with primary hyperparathyroidism treated surgically, in an attempt to assess whether or not hypertension and renal impairment should be regarded as important indications for parathyroidectomy. 29% were hypertensive pre-operatively and the blood pressure remained elevated after parathyroidectomy in all of these patients. Hypertension developed for the first time after parathyroidectomy in 45% of those patients who were normotensive before surgery. Renal function was normal initially in 73% and mild renal impairment developed after surgery in 9% of these patients. At the end of the follow-up period, the prevalence of hypertension was higher in patients with renal impairment pre-operatively (88%) than in those with normal renal function (51%). We conclude that hypertension alone should not be regarded as an indication for parathyroidectomy in asymptomatic hyperparathyroidism. No firm conclusions can be reached about the importance of mild renal failure as an indication for surgery and the question is unlikely to be resolved without conducting a prospective controlled trial.

Blood Pressure↗

Potent dopamine agonist activity of a novel ergoline, 6-ethyl-9-oxaergoline (EOE).

6-Ethyl-9-oxaergoline (EOE) and its enantiomers were compared with apomorphine in a number of tests designed to measure dopamine (DA) agonist activity within the central nervous system. In rats, the tests were: interaction with DA receptors labeled with 3H-apomorphine or 3H-spiroperidol; the effects on DA synthesis as assessed by the gamma-butyrolactone procedure; turning in 6-OHDA lesioned animals; stereotypy; and, slowing of DA cell firing rates. In the mouse, locomotor activity, hypothermia and postural asymmetry in caudectomized animals were studied. Emesis in the beagle was also examined. The (-)-enantiomer of EOE was more potent than either the (+)-enantiomer or the racemate in all tests. With the exception of inducing stereotypy and the displacement of 3H-apomorphine from rat striatal membranes, (-)-EOE was equi- or more potent than apomorphine in all test procedures. (-)-EOE was effective following oral administration and exhibited a longer duration of action than apomorphine. The results indicate EOE is a potent DA agonist.

4-Butyrolactone↗

Pulmonary blood flow distribution in panting ostriches.

Ostriches (Struthio camelus) are the only birds known that can increase post-dead space ventilation during severe heat stress without experiencing hypocapnia and respiratory alkalosis. To determine whether this phenomenon occurs due to redistribution of pulmonary blood flow during panting, thus creating an extreme ventilation-perfusion (V/Q) imbalance, the distributions of pulmonary blood flow in ostriches at rest (15 degrees C) and in severe panting (45 degrees C) were determined using radioactively labeled microspheres. Blood flow distribution at rest was greatest in the neopulmo [18% greater than mean pulmonary blood flow (MPBF)] and the cranial (23% greater than MPBF) and distal (12% greater than MPBF) regions of the paleopulmo. During panting blood flow was not shunted around the lung, and flow to the neopulmo decreased to MPBF, became more homogeneous along the craniocaudal axis, and remained nonhomogeneous along the mediolateral axis. The results suggest that the observed decrease in gas exchange during panting is probably due primarily to shunting of the increased ventilation around the parabronchial exchange region rather than to alterations in the patterns of V/Q within the lung.

Animals↗

Control of air flow in bird lungs: radiographic studies.

The complex pattern of air flow in the respiratory system of birds suggests that certain sites function as valves. To examine the possibility of mechanical valving, rather than aerodynamic valving, we recorded radiographic images of the orifices where the medioventral secondary bronchi branch from the primary bronchus in resting Pekin ducks. Analysis of the images indicated that the orifices do not change size or shape during the respiratory cycle, suggesting that they function as aerodynamic rather than mechanical valves in directing air flow through the lung.

Animals↗

Worker exposure to vinyl chloride and poly(vinyl chloride).

The National Institute for Occupational Safety and Health (NIOSH) in early 1974 began industrial hygiene studies of vinyl chloride exposed workers. Three VC monomer plants, three VC polymerization plants, and seven PVC fabrication plants were surveyed. V polymerization plant workers and workers in one job category in VC monomer plants were exposed to average levels above 1 ppm. The highest average exposure was 22 ppm. NIOSH health hazard evaluation studies since these initial surveys have primarily shown nondetectable levels of vinyl chloride. A NIOSH control technology study in 1977 showed that exposure levels in VC polymerization plants had been drastically reduced but exposure levels above 1 ppm were still found in several cases.

Air Pollutants↗

A heterophile system in human renal transplantation. VIII. The morphological distribution of the antigen in rat tissues.

The morphological distribution of heterophile transplant antigen (HTA) was determined in rat tissues using an indirect immunofluorescence technique. Human anti-HTA sera were used to localize HTA in rat kidney, liver, heart, skeletal muscle, spleen, and stomach. HTA was found in basement membrane and supporting stromal elements of all tissues studied. In the kidney, HTA was demonstrated in tubular basement membrane but not glomerular basement membrane. No evidence for cell surface antigen distribution could be ascertained except for erythrocyte membranes. HTA was not found on endothelium of rat blood vessels. We know of no antigens previously implicated in histocompatibility that are stromal in location.

Animals↗

Mechanism of racemisation of histidine derivatives in peptide synthesis.

Evidence is presented to show that the racemisation of N(alpha)-benzyloxycarbonyl-N(pi)-phenacyl-L-histidine which occurs on activation with dicyclohexylcarbodiimide in dimethylformamide takes place by action of the pi-nitrogen as an intramolecular base catalyst in the O-acylisourea adduct which is in reversible equilibrium with the reactants, rather than by formation of an optically labile heterocyclic intermediate.

Chemical Phenomena↗

Synthesis of the sultam analog of 11-deoxy PGE2.

As an extension of our work on the series of N-alkylmethanesulfonamidoheptanoic acids, we have prepared the cyclic-sulfonamide (sultam) analog of 11-deoxy PGE2. Although numerous publications have described the introduction of heteroatoms into the 5-membered ring of the prostaglandins, the cyclic-sulfonamides have remained a heretofore unexplored class. The synthetic scheme for the preparation of this unique PG analog is presented in this paper.

Chemical Phenomena↗

Incidence of infectious mononucleosis at the Universities of California and Hawaii.

The observed rates of heterophil-positive infectious mononucleosis at the University of California at Davis and the University of Hawaii at Manoa were 1,212 and 37 per 100,000 students per academic year, respectively. The data collected suggest that the extraordinarily low incidence at the University of Hawaii may be due to the following factors: (1) underutilization of the student health service by students with infectious mononucleosis; (2) low proportion of Epstein-Barr virus-seronegative students; (3) high proportion of Asian students who appear to be less likely to develop heterophil-positive infectious mononucleosis; and (4) possible low efficiency in the transmission of primary Epstein-Barr virus infections.

Adolescent↗

Synthesis and biological activities of [7-(azetidine-2-carboxylic acid)]-oxytocin and -lysine-vasopressin.

[7-(Azetidine-2-carboxylic acid)]-oxytocin and -lysine-vasopressin have been synthesised by a (6 + 3) strategy using protected hexapeptide acids with preformed disulphide bridges, and their biological activities have been investigated. All activities were reduced but not to the same extent. In assays of pressor and antidiuretic activity it was observed consistently that the responses to the vasopressin analogue were of shorter duration than responses to lysine-vasopressin of the same amplitude.

Amino Acid Sequence↗

Avian cerebral blood flow: influence of the Bohr effect on oxygen supply.

To clarify the problems of altitude tolerance in birds, we studied the combined effect of hypocapnia and hypoxia on cerebral blood flow (CBF) in ducks. CBF was measured by the xenon clearance method. Normocapnic hypoxia causes CBF to increase when the arterial O2 tension (PaO2) falls below 60--70 mmHg. Hypocapnic hypoxia significantly shifts the blood flow curve so that blood flow does not increase until a lower PaO2 (50--60 mmHg) is reached. This gives the appearance that hypocapnia suppresses the hypoxia-induced increase in CBF. However, due to the Bohr effect, the hypocapnic blood contains significantly more O2 than does the normocapnic blood at the same PaO2. Therefore, when CBF is expressed as a function of O2 content, rather than PO2, CBF in the hypocapnic group does not differ significantly from the CBF in the normocapnic group. We interpret this to mean that because of the significantly greater oxygen content of the hypocapnic blood at a given PaO2, the degree of hypoxia experienced by these brains is not as severe as that experienced by the normocapnic brains.

Adaptation, Physiological↗

11,12-Secoprostaglandins. 5. 8-Acetyl- or 8-(1-hydroxyethyl)-12-hydroxy-13-aryloxytridecanoic acids and sulfonamide isosteres as inhibitors of platelet aggregation.

The synthesis of a series of 8-acetyl- (or 1-hydroxyethyl-) 12-hydroxy-13-aryloxytridecanoic acids and their sulfonamide isosteres is described. These compounds are formally derived from members of earlier reported series of modified secoprostaglandins by replacing the omega-butyl chain termini by substituted aryloxy groups. A number of these compounds are potent inhibitors of collagen-induced blood platelet aggregation in guinea pigs on oral administration.

Animals↗