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Biomedical subjects

G H Jones

Publications and source records attributed to G H Jones.

At least 127 records · Page 7Linked to original sources
PubMed1984

Synthesis of a novel class of heteroaromatic amino acids and their use in the preparation of analogues of luteinizing hormone-releasing hormone.

A novel class of heterocyclic aromatic amino acids based on the 3-(2-benzimidazolyl)alanine system has been generated by chiral synthesis from D- or L-aspartic acid. The use of variously substituted o-phenylenediamines for condensation with the beta-carboxyl function of alpha-benzyl N-(benzyloxycarbonyl)-D-aspartate has led to a series of amino acids of graded hydrophobicity with a steric bulk similar to that of tryptophan. In a similar fashion, we have prepared 3-(2-benzothiazolyl)-D-alanine from o-aminothiophenol and 3-(2-benzoxazolyl)-D-alanine from o-aminophenol. Incorporation of these amino acids into the 6-position of luteinizing hormone-releasing hormone (LH-RH) led to a series of very potent agonist analogues (up to 160 times LH-RH potency), active in doses ranging from 0.1 to 0.5 microgram by twice daily injection in a rat estrus cyclicity suppression assay designed to show the paradoxical antifertility effects of these compounds.

Alanine↗
PubMed1984

The control of chiasma distribution.

The question of recombination control has been the subject of intensive investigation over many years. This paper is restricted to an evaluation of the information obtainable from cytological studies of chiasmata, since other approaches are well represented in other papers in this volume. The advantages and disadvantages of chiasmata as means of studying recombination are discussed. Cytological observations reveal many constraints on the distribution of chiasmata, which are interpreted as outward expressions of controls operating at different levels, namely between cells, between bivalents and within bivalents. Detailed descriptions of these constraints are presented as a preliminary to discussing models and mechanisms of control. They include, at the between-bivalent level, over-dispersal of chiasma number per bivalent and the formation of an obligatory minimum of one chiasma per bivalent; and at the within-bivalent level, chiasma localization and chiasma interference. The genetical basis of these constraints is emphasized and evidence presented which suggests that chiasma distribution at different levels is subject to both separate and coordinate genetical controls. These observations lead to the consideration and evaluation of general stochastic models of chiasma control based on the modification of site probabilities for chiasma formation. While these models are a useful approach to thinking about the control of recombination, they do not give a fully satisfactory explanation of all aspects of chiasma control. Finally, specific mechanisms for chiasma distribution control are considered. In a few exceptional species, localized pairing and synaptonemal complexes lead to localized chiasma formation; details of two such cases are presented. In the majority of species, pairing is not localized or restricted and in these species the control of chiasma distribution is more conjectural. Arguments are presented which suggest that even in these cases of full pairing, the pattern of pairing initiation and progression and perhaps the timing of these events could be important factors controlling the distribution of chiasmata.

Animals↗
PubMed1983

Acceptor activity, isoacceptor profiles and function in protein synthesis of transfer RNAs from regenerating skeletal muscle.

Transfer RNAs have been prepared from control and regenerating rat skeletal muscle. The yield of tRNA is highest during the early stages of the regeneration process (5 and 8 days following the induction of regeneration) and decreases to near control values thereafter. The amino acid acceptor activity (extent of aminoacylation) of tRNA from regenerating muscle was also found to be higher for some amino acids than the activity of control tRNA, and the maximum increase in activity was observed between 5 and 8 days following the initiation of regeneration with a decrease to control levels through 15 and 30 days. The isoacceptor pattern, determined by RPC-5 chromatography, for methionyl-tRNAs from control muscle and 5-day regenerating muscle were essentially indistinguishable, while a minor peak of prolyl-tRNA was observed in the population from 5-, 8- and 15-day regenerates which was apparently absent from the control tRNA. Lysyl-tRNAs from control muscle contain two major isoacceptors while a third isoacceptor is observed in the tRNA preparations from 5-, 8- and 15-day regenerating muscle. The relative amount of this third isoacceptor is highest in the 8-day population and decreases in amount in tRNAs from 15- and 30-day regenerates. Control muscle also contains two major glutamyl-tRNA species while a third isoacceptor can be detected in regenerates. The relative amount of this species increases during the early course of the regeneration process but is present at near control levels by 30 days following Marcaine injection. Cell-free protein synthesis using muscle polyribosomes showed that tRNAs from regenerating muscle were more effective in stimulating [35S]methionine incorporation than tRNAs from control muscle.

Amino Acids↗
PubMed1982

Protein synthesis in bupivacaine (marcaine)-treated, regenerating skeletal muscle.

Skeletal muscle regeneration has been induced by injection of the myotoxic drug bupivacaine (Marcaine) into the rat tibialis anterior muscle. Doses of 1.5 and 1.0% wt/vol produce significant levels of muscle regeneration, but these doses also produce large regions of ischemic muscle. Doses of 0.75 and 0.5% bupivacaine are also effective in inducing regeneration and produce little or no ischemia. Regenerating muscle is significantly more active in the incorporation of 35S-methionine into protein than is control muscle, and the activity increase is directly proportional to the bupivacaine dose injected. Polyribosomes were isolated in greater yield from bupivacaine-treated muscles, as compared with control muscles, 5 days postinjection, and were also more active in cell-free protein synthesis than control polysomes. Again, the yield and activity of the muscle polysomes was directly proportional to the bupivacaine concentration used for injection. Polyacrylamide gel electrophoresis of polysomal cell-free reaction mixtures demonstrated the synthesis of a number of myofibrillar proteins.

Animals↗
PubMed1982

Synthesis and biological activity of some very hydrophobic superagonist analogues of luteinizing hormone-releasing hormone.

The effect of increased hydrophobicity at position 6 of luteinizing hormone-releasing hormone (LH-RH) has been investigated by the incorporation of a series of 15 very hydrophobic, unnatural D-amino acids at this position. The unnatural amino acids studied can be considered analogues of phenylalanine with carbocyclic aromatic side chains consisting of substituted phenyl (e.g., 2,4,6-trimethylphenyl, p-biphenyl) or polycyclic aromatic (e.g., naphthalene, anthracene) units. When enzymatic resolution (subtilisin Carlsberg) of the most hydrophobic amino acids failed, the racemic amino acids were incorporated, and the diastereomeric LH-RH analogues were resolved by preparative high-performance liquid chromatography. The analogues were synthesized by the solid-phase technique. All of the synthetic compounds were very potent LH-RH superagonists, but [6-(3-(2-naphthyl)-D-alanine)]LH-RH, [6-(3-(2-naphthyl)-D-alanine), 7-(N alpha-methylleucine)]LH-RH and [6-(3-(2,4,6-trimethylphenyl)-D-alanine)]LH-RH appear to be among the most potent LH-RH agonist analogues yet reported when tested in a rat estrus cyclicity suppression assay designed to show the paradoxical antifertility effects of these compounds [ED50 approximately 7 x 10(-8) g; twice daily in saline]. These analogues are twice as potent as [D-Trp6,ProNHEt9]LH-RH in this assay system (i.e., approximately 200 times the potency of LH-RH).

Amino Acids↗
PubMed1982

Preparation of messenger RNA from mature skeletal and cardiac muscle.

Messenger RNA (poly(A) + RNA) has been prepared from mature skeletal muscle of adult rats by several procedures. These procedures involved oligodT-cellulose chromatography of either muscle polyribosomes (method 1), polysomal RNA isolated by CsCl gradient centrifugation of muscle polysomes (method 2), total muscle RNA isolated by CsCl gradient centrifugation (method 3), or total muscle RNA prepared by phenol extraction (method 4). Each procedure produced RNA in significant yields which sedimented in a broad band (from 4S to greater than 28S) on sodium dodecyl sulfate--sucrose gradients. In addition, poly (A) + RNA from each procedure stimulated protein synthesis in the wheat germ cell-free system. The best combination of yield and messenger activity was obtained for poly (A) + RNA prepared from polysomal RNA by method 2. This poly(A) + RNA preparation stimulated the cell-free synthesis of a number of presumptive myofibrillar proteins, including myosin heavy chain and actin, in the wheat germ system. The presence of the latter protein among the cell-free products was confirmed by DNase I affinity chromatography of appropriate reaction mixtures. Poly(A) + RNA was also isolated from rat cardiac muscle polysomal RNA by method 2. This RNA also directed the synthesis of myofibrillar proteins in the wheat germ system. The relative amounts of the proteins synthesized in the presence of skeletal and cardiac muscle poly(A) + RNA have been compared. The data indicate that the method described is suitable for the isolation of RNA with message activity from mature mammalian muscle.

Animals↗
PubMed1982

Vascular clearance of embolic tumor cells and colloidal carbon and the levels of serum lysozyme following muramyl dipeptide administration.

Various doses of coded samples of the parent muramyl dipeptide entity and eight synthetic analogues were injected intravenously into C57BL/6J mice, and the extent of clearance of intravenously injected 5-[125I]iodo-2-deoxyuridine (125I-dUrd) radioactively labeled B16 tumor cells from the lung was measured 3 days later. The results of between one and four experiments with each compound demonstrated that five compounds, including the parent compound, produced dose-dependent increases in the loss of tumor cells from the lung. The same five compounds also caused an increase in the clearance of intravascular carbon clearance. Monitoring of serum lysozyme levels revealed no significant increases compared to controls at doses of up to 1 mg/mouse following muramyl dipeptide (MDP) administration i.v., i.p. or s.c. at any time up to 30 days after administration. Increased pulmonary tumor cell clearance did not occur after s.c. MDP administration and peaked 3 days after i.p. or i.v. MDP, reaching near normal levels by Day 7.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1981

Chiasma frequency and distribution in a sample of human males: chromosomes 1, 2, and 9.

Chiasma frequency and the distribution of chiasmata within chromosomes 1, 2, and 9 were investigated in a total of seven males with presumptively normal meiosis. With the exception of one unusual individual there was little variation among the males examined for these characteristics. The exceptional male had a reduced chiasma frequency, which, rather than being considered abnormal, was thought to represent the lower end of the normal range of variability. A statistical analysis of the histograms of chiasma distribution confirmed the impression of overall similarity, and we conclude that genetic maps of these chromosomes may now be constructed without too much disturbance from differences between individuals. The maps will be presented separately in a subsequent paper.

Analysis of Variance↗
PubMed1981

Functional tests of the corpus callosum in schizophrenia.

The corpus callosum, a cerebral commissure of 200,000,000 fibres, is thickened in chronic schizophrenia and several neuropsychological and neurophysiological techniques have suggested poor links between the two cerebral hemispheres. The interhemispheric conduction time across the corpus callosum, measured in 12 schizophrenics, using the ipsilateral/contralateral latency differences of the early somatosensory evoked response, was found to be effectively zero. It is suggested that schizophrenia is a split-brain condition akin to agenesis of the corpus callosum, unrecognized through the use of compensatory ipsilateral sensory pathways.

Adolescent↗
PubMed1980

Regression of tumors in guinea pigs after treatment with synthetic muramyl dipeptides and trehalose dimycolate.

A high incidence of tumor regression was observed in guinea pigs bearing transplantable, line-10 hepatocellular carcinomas when synthetic muramyl dipeptides combined with trehalose dimycolate in oil-in-water emulsions were injected directly into the tumors. These compounds are promising candidates to replace viable bacillus Calmette-Guérin in cancer immunotherapy in humans and animals.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Marcaine, a selective inhibitor of eucaryotic aminoacylation.

The effects of marcaine, a myotoxic drug, on the aminoacylation of transfer ribonucleic acid (rRNA) have been studied. The drug is a potent inhibitor of the acylation of rat liver tRNA with leucine and isoleucine but is only mildly inhibitory (or not inhibitory) to acylation with a number of other amino acids which were tested. Further, marcaine inhibited aminoacylation in cell-free systems using components from several mammalian tissues, including muscle, from yeast, and from wheat germ. No effect of the drug was observed in aminoacylation systems from several bacterial species which were tested. The drug inhibits acylation with leucine and isoleucine competitively but exhibited noncompetitive kinetics when the concentrations of adenosine 5'-triphosphate (ATP) and tRNA were varied. Marcaine was also a competitor of leucine in the ATP--pyrophosphate exchange reaction. Two structural analogues of marcaine, carbocaine and xylocaine, also inhibited acylation of rat liver tRNA with leucine but in a noncompetitive fashion. On a molar basis, marcaine appears to be the most effective inhibitor of the three drugs tested.

Animals↗
PubMed1979

Mammography. An aid or distractor in diagnosis?

A retrospective analysis of 155 mammograms has indicated the value of this procedure even with simple and inexpensive equipment. In women with a discrete mass requiring biopsy, mammography combined with clinical findings predicted with 100% confidence over half the cancers diagnosed. When both X-ray and clinical findings suggested a benign lump, only one in nine was a carcinoma. In the one-third of patients in whom signs and X-ray findings were in conflict or equivocal, the malignancy rate was about one in three. In women with breast signs or symptoms, but without discrete mass and with a "benign" mammography report, no cancer has been found in follow up for from 12 months to seven years.

Biopsy, Needle↗