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P M Collins

Publications and source records attributed to P M Collins.

34 records · Page 2Linked to original sources

Calcium-dependent aggregation of human serum amyloid P component. Inhibition by the cyclic 4,6-pyruvate acetal of galactose.

Serum amyloid P component is a normal plasma glycoprotein which is the precursor of amyloid P component, a minor but universal constituent of amyloid deposits. When isolated human P component is exposed to free ionised Ca2+ it aggregates and precipitates. This phenomenon is completely inhibited by the presence of 10(-4)-10(-2) M methyl 4,6-O-(1-carboxyethylidene)-beta-D-galactopyranoside, a recently synthesised specific ligand for amyloid P component. This observation suggests that the autoaggregation of human amyloid P component involves the Ca2+ dependent specific ligand binding property of P component, but does not distinguish between receptor-site-mediated and allosteric mechanisms.

Amyloid↗

Specific chemical dissociation of fibrillar and non-fibrillar components of amyloid deposits.

In systemic amyloidosis, a fatal disorder for which there is no effective treatment, the extracellular protein deposits are composed of amyloid fibrils together with a non-fibrillar glycoprotein, amyloid P component (AP). Methyl 4,6-O-(1-carboxyethylidene)-beta-D-galactopyranoside (MO beta DG), a recently identified ligand for AP, was tested for its ability to produce in-vitro elution of AP which had been laid down with amyloid fibrils in vivo. Millimolar concentrations of MO beta DG completely dissociated AP from human and murine splenic amyloid deposits. Availability of this material thus provides for the first time the opportunity for specific molecular dissection of amyloid deposits. If MO beta DG or a related substance were effective in vivo it might be of therapeutic importance.

Amyloid↗

Binding specificity of serum amyloid P component for the pyruvate acetal of galactose.

Serum amyloid P component (SAP) is a normal plasma protein that is of interest because of its presence in amyloid deposits, its presence in normal human glomerular basement membrane, and its stable evolutionary conservation. It has calcium-dependent ligand-binding specificity for amyloid fibrils, fibronectin (Fn), C4-binding protein (C4bp), and agarose. Although the binding to agarose, a linear galactan hydrocolloid derived from some marine algae, is unlikely per se to be related to the physiological function of SAP, it does provide a model system in which to explore the precise ligand requirements of SAP. We report here that the amount of SAP from human, mouse, and plaice (Pleuronectes platessa L.) serum able to bind to agarose from different sources reflect precisely their pyruvate content. Methylation with diazomethane of the carboxyl groups in the pyruvate moiety of agarose completely abolishes SAP binding to agarose. The pyruvate in agarose exists as the 4,6-pyruvate acetal of beta-D-galactopyranose. We have therefore synthesized this galactoside, using a novel procedure, established its structure by analysis of its nuclear magnetic resonance spectra, and shown that it completely inhibits all known calcium-dependent binding reactions of SAP. The R isomer of the cyclic acetal, methyl 4,6-O-(1-carboxyethylidene)-beta-D-galactopyranoside (MO beta DG) was effective at millimolar concentration and was more potent than its noncyclic analogue, while pyruvate, D-galactose, and methyl beta-D-galactopyranoside were without effect. The autologous protein ligands of SAP presumably, therefore express a structural determinant(s) that stereochemically resembles MO beta DG. Availability of this specific, well-characterized, low molecular weight ligand for SAP should facilitate further investigation of the function of SAP and its role in physiological and pathophysiological processes.

Amyloid↗

Influence of stress on adrenocortical function in the male tree shrew (Tupaia belangeri).

Adrenocortical function in the tree shrew (Tupaia belangeri) was evaluated by reference to levels of individual corticosteroids as an initial phase in the clarification of the hormonal mechanisms by which stress influences male reproductive function. Corticosteroids were separated with Sephadex LH-20 chromatography and measured by specific radioimmunoassay procedures. Corticosterone was the principal corticosteroid in the peripheral plasma and in unstressed animals the ratio corticosterone:cortisol was 4.5:1 (1000 hr samples). Basal levels of corticosterone and cortisol exhibited parallel diurnal fluctuations with a peak at 0600 hr preceding the onset of daily activity and similar to that described for other diurnally active species. Levels of corticosterone and cortisol were markedly elevated 10 min after either restraint stress applied at various times during the day or ACTH administration to both saline- and dexamethasone-pretreated animals. In each of these experimental situations cortisol showed a greater relative increase from basal levels as compared to corticosterone resulting in a decline in the ratio corticosterone:cortisol. For example, the unstressed ratio of corticosterone (9.1 +/- 0.8 ng/ml) and cortisol (2.0 +/- 0.2 ng/ml) at 1000 hr was 4.5:1. Following 10 min of restraint stress the ratio declined to 1.5:1 (corticosterone, 44.9 +/- 1.4 ng/ml; cortisol, 31.7 +/- 1.3 ng/ml). An increase in cortisol is considered to be an important component of the physiological response to stress by the tree shrew adrenal. It is concluded that the adrenal cortex of the tree shrew normally produces corticosteroids through two pathways and the secretion of both corticosterone and cortisol are responsive to acute ACTH stimulation and feedback inhibition by dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗

Genetic variation at the alcohol dehydrogenase locus in natural populations of the seaweed fly, Coelopa frigida.

Samples of the seaweed fly, Coelopa frigida, from six populations widely spaced around the English coast were collected during 1974-76 and again in 1979-80. Gene frequencies at the Alcohol dehydrogenase (Adh) locus were found not to vary significantly between sites, nor over the five year period of their study. Genotype distributions are compared with Hardy-Weinberg expectations and show consistent, mostly significant, differences. These results are interpreted in the light of an association between the Adh locus and a chromosomal inversion polymorphism. It is argued that the remarkable geographical uniformity must indicate the presence of strong selection, probably taking the form of heterokaryotypic advantage.

Alcohol Oxidoreductases↗

Anatomy and function of the reproductive tract in the captive male tree shrew (Tupaia belangeri).

The reproductive anatomy of the male tree shrew (Tupaia belangeri) was examined and compared with other Tupaiidae. The testes are located prepenially in a pigmented scrotum which is fused to the base of a pendulous penis. The terminal portion of the vas deferens is differentiated into an ampullary gland and joins the duct of the seminal vesicle to form a short ejaculatory duct. The prostate is a compact bilateral body drained by a main collecting duct. In the aggregate, these features indicate that the reproductive system in Tupaia is primate in character. Testicular function in tree shrews is affected by both social and seasonal factors. When males were housed communally, the majority exhibited testicular degeneration accompanied by a loss in the weight and fructose content of the seminal vesicles and in pigmentation of the scrotum. These changes may be due to the presence of dominant conspecifics since animals kept in isolation undergo normal sexual development. Animals captured throughout the year and isolated show seasonal fluctuations in androgenic and spermatogenic function. Reproductive capacity is maximal during the winter and minimal during the summer. Local environmental factors appear to regulate reproductive function so that the greatest number of births occur during the dry season.

Animals↗

Plasma FSH, LH and testosterone levels in the male rat during degeneration of the germinal epithelium caused by severe heat treatment or ligation of the vasa efferentia.

Rats were treated by exposure of the scrotum to a temperature of 43 degrees C for 30 min or bilateral ligation of the vasa efferentia and bled at 0, 3, 7, 14 and 21 days after treatment. In heat-treated rats FSH levels rose linearly from pretreatment levels while those in efferenticectomized animals remained unchanged for 3 days before increasing. In both groups FSH concentrations reached similar maximum values after 7 days and were significantly higher than those of intact controls at 7, 14 and 21 days. LH levels, although not generally different from those in the controls, rose from pretreatment levels in parallel with FSH. No differences were found in testosterone concentrations in any of the groups. Histological examination at 3 weeks after treatment confirmed that the germinal epithelium consisted mainly of spermatogonia and Sertoli cells. The cytoolgical appearance and lipid content of the Leydig cells of the aspermatogenic testes were indistinguishable from those of the controls and the weight and histological appearance of the accessory sex organs and the fructose content of the coagulating glands were also normal. It is concluded that the sterilizing effects of heat treatment and efferentiectomy are independent of changes in Leydig cell function and that the increase in gonadotrophin levels is related to the germ cell degeneration.

Animals↗

Larval development of silver sea bream (Sparus sarba): ontogeny of RNA-DNA ratio, GH, IGF-I, and Na(+)-K(+)-ATPase.

To ascertain some of the important biochemical and molecular events that take place during early larval development of silver sea bream (Sparus sarba), we undertook a study of changes in the morphology as well as the ontogeny of the RNA-DNA ratio, growth hormone (GH), insulin-like growth factor I (IGF-I) messenger RNA abundance, Na(+)-K(+)-ATPase subunit mRNA abundance, and Na(+)-K(+)-ATPase enzyme activity. Larvae samples were collected at 1 to 46 days posthatch (dph). At 7 dph the yolk sac was fully absorbed, and from 28 dph onward larvae underwent rapid developmental changes to the juvenile stage. The RNA-DNA ratio was highest at 1 dph, decreased to low levels between 7 and 21 dph, then increased by 28 dph, and then again by 46 dph. The ontogenetic profiles of GH, IGF-I, and Na(+)-K(+)-ATPase alpha1 and beta1 subunits were studied using reverse transcriptase polymerase chain reaction, coupled with radioisotope hybridization of immobilized DNA. Growth hormone abundance reached a constant and high level from 35 dph onward, whereas the IGF-I level reached a peak at 35 dph and then significantly decreased. Both Na(+)-K(+)-ATPase alpha1 and beta1 subunit mRNAs increased up to 35 dph, however, at 46 dph the alpha1 subunit remained high whereas the beta1 subunit decreased. Na(+)-K(+)-ATPase activity was low in 1-dph larvae but increased rapidly as development progressed. The importance of these findings is discussed within the context of larval development.

Aging↗