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Biomedical subjects

J Gauldie

Publications and source records attributed to J Gauldie.

At least 253 records · Page 14Linked to original sources

The structures of some peptides from bee venom.

The sequences are given of two peptides (secapin and melittin F) whose isolation from the venom of the common European honey bee (Apis mellifera) has previously been described [Gauldie et al. (1976) Eur. J. Biochem. 61, 369--376]. Some structural studies on the known peptide 401 (MCD peptide) are described. The positions of the two disulphide bridges in peptide 401 have been determined by (an essentially) novel method.

Amino Acid Sequence↗

Effects of active immunization of female rabbits against testosterone.

Prepubertal (immature) and mature female rabbits were actively immunized against testosterone-3-oxime-bovine serum albumin over a period of 11 weeks. The antibody titre was significant in all animals by 5 weeks. The concentration of FSH in prepubertal animals decreased significantly (P less than 0.001) between weeks 1 and 5, but no significant changes were observed in the concentration of LH at any time. After immunization for 8 weeks, there was a significant (P less than 0.05) increase in the serum concentration of androgen and the percentage of bound testosterone also increased (P less than 0.05). The serum concentration of oestradiol increased after immunization for 11 weeks, compared with values at 8 weeks (P less than 0.05) and oestradiol binding also rose by week 5 (P less than 0.01). Libido was not affected and significantly (P less than 0.005) increased numbers of ovulations were noted in immunized animals. These results suggest that immunization of the female rabbit against testosterone may disrupt the normal regulation of follicular maturation.

Animals↗

The effect of thrombocytopenia on experimental arteriosclerotic lesion formation in rabbits. Smooth muscle cell proliferation and re-endothelialization.

This study was designed to investigate the mechanisms involved in fibromusculoelastic lesion formation produced by selective de-endothelialization by the intra-arterial balloon catheter technique in thrombocytopenic rabbits. Thrombocytopenia was induced and maintained for up to 30 days by daily injections fo highly specific sheep anti-rabbit platelet sera (APS). Evidence for re-endothelialization was obtained by i.v. Evans blue dye 30 min before sacrifice. Rabbits received daily injections of APS, which reduced the mean platelet count to 5,600/cm3; control animals received identically treated normal sheep sera on the same schedule, and had mean daily platelet counts of 363,000/cm3. Evaluation of intimal thickness was assessed by counting cell layers in semithin sections. Intimal thickening in aortae from rabbits treated with APS was strikingly suppressed, in contrast to those from normal sheep sera-treated animals which showed a mean intimal thickness of 18 cell layers within 28 days often after de-endothelialization. Re-endothelialization was not affected by APS treatment. These results indicate that the proliferation of smooth muscle cells is dramatically inhibited by reduction of platelets.

Animals↗

A radioimmunoassay for serum ferritin.

We describe the development and evaluation of a serum ferritin radioimmunoassay, in which 125l-labeled ferritin and rabbit anti-ferritin antibody are used. Goat anti-rabbit gamma-globulin antibody, together with polyethylene glycol, is used as the separating reagent. The assay has a working range up to 500 mug of ferritin per litre, and a sample requirement of 75 mul of serum for assay at two dilutions. The assay requires 24 h. it has a sensitivity of 1.5 mug of ferritin per litre and a long-term precision (CV) of 13%. Reference intervals for a population of men were 18-330 mug/litre, with no marked age dependence, while those for a population of women older than 50 years were 18-200 mug/litre. Many apparently healthy women in the 20-50 year age group have much lower concentrations. Serum ferritin concentrations of less than 18 mug/litre are indicative of iron deficiency, defined as the absence of stainable iron in an aspirate of bone marrow.

Adult↗

Inhibition of injury induced thromboatherosclerotic lesions by anti-platelet serum in rabbits.

We have previously shown that repeated or continuous intimal injury caused by an indwelling aortic catheter causes a variety of lesions in rabbits maintained on a diet unsupplemented by lipid. These include fatty streaks, lipid-free fibrous plaques and lipid-rich raised thromboatherosclerotic plaques. Whether lipid-rich raised lesions are a result of injury or co-existing thrombosis or both is not clear. The present experiment was designed to answer this question. Anti-platelet serum (APS) to washed sonicated rabbit platelets was raised in sheep. PE 60 polyethylene catheters were placed in the aortas of 35 rabbits by way of a femoral artery. The animals were randomly divided into 2 groups. The experimental group (17 rabbits) received an intravascular injection of 1.0 ml of APS followed 8 hours later by a subcutaneous injection of 0.5 ml. Thereafter, 0.5 ml APS was given subcutaneously each day for 13 additional days. The control group (18 rabbits) received no APS. Platelet counts were done prior to surgery, at 5 minutes following surgery, at 4 days, 8 days and just prior to killing. Extent of lesions was estimated by photographing the opened aortas, projecting the photographs on cardboard, cutting out the areas occupied by the different lesions and weighing the cardboard. The mean weight of raised lesions in the control group was 6 to 7 times greater than in the experimental groups. Statistical analysis of this difference based on Welsh's "t" test for unequal variances was highly significant (P less than 0.001). Platelet counts in the experimental groups varied from 0 to 20,000 at 14 days. In animals with platelet counts less than or equal to 1,000 mm3 raised lesions were completely prevented. In a second experiment the effect of APS was compared with normal sheep serum (NSS). A similarly significant inhibition of raised lesions occurred in the APS group. The extent of lesions in the NSS control was similar to that in the No-APS group of the first experiment. These findings indicate that thrombosis is more important than injury in the development of lipid-rich raised lesions.

Animals↗

An approach to immunotherapy using antibody to IgE in mast cell leukemia.

Passive immunotherapy was attempted in a patient with mast cell leukemia using antibody against IgE. The results of both in vitro and in vivo studies indicate that although receptor sites for IgE were retained by the malignant mast cell, a secretory defect was present characterized by the spontaneous release of histamine and an impaired secretory response to anti-IgE antibody. Anti-IgE antibody selectively and reproducibly reduced the number of circulating mast cells probably by facilitating their permanent uptake by the reticuloendothelial system. Tolerance was not achieved with high dose deaggregated sheep IgG, nor were we able to confirm the effectivity of immunochemotherapy based on linking chlorambucil to antibody directed against the tumor-associated "antigen" IgE.

Animals↗

Thermodynamic aspects of some radioassays.

In a number of radioimmunoassays and radiotransin assays, effective equilibrium constants have been measured at different temperatures in order to define the relative contribution of changes of entropy and enthalpy to the change in free binding energy. In systems with a large enthalpy component, the lowest possible incubation temperature maximizes sensitivity, and control of temperature throughout the assay is important. Conversely, when enthalpy change is small, a high temperature allows rapid attainment of equilibrium without loss of sensitivity. At a theoretical level, the thermodynamic characteristics of binding may allow some insight into the nature of the binding process.

Angiotensin II↗

Pseudothrombocytopenia due to platelet aggregation and degranulation in blood collected in EDTA.

Three patients are described in whom platelet aggregation and/or degranulation occurred in blood collected into EDTA. These changes resulted in spurious thrombocytopenia and morphological changes similar to those observed in some thrombocytopathies. The abnormalities were dependent on the presence of EDTA and did not occur in citrate, oxalate or heparin anticoagulants. In two patients the abnormality was shown to be due to a plasma factor which was not IgG, IgM, fibrinogen or albumin. The most likely explanation is that these patients have an unidentified abnormal plasma component which, on exposure to EDTA, develops 'anti-platelet activity'. Althought relatively uncommon a prospective study of the incidence of these phenomena indicates that they are probably more common than either platelet cold agglutinins or platelet satellitism. They have practical significance with respect to the diagnosis of thrombocytopenia and also to the interpretation of abnormal platelet morphology.

Adenosine Diphosphate↗

Alteration of the HL-A antigenic site in situ.

The chemical nature of the HL-A antigenic sites on peripheral blood lymphocytes was studied by treatment of these cells with glycolytic enzymes and with sodium metaperiodate, and monitoring the residual antigen expression either by the lymphocyte cytotoxicity test or by quantitative microabsorption of monospecific anti-HL-A sera. Neither the gentle enzymatic nor the chemical treatment of lymphocytes altered expression of the HL-A antigens indicating that carbohydrates are not involved, in a major way, in the HL-A antigenic sites.

Acetylglucosaminidase↗

Purification and properties of dihydrofolate reductase from cultured mammalian cells.

Dihydrofolate reductase was purified quickly and simply from small quantities of cultured mammalian cells by affinity chromatography. On gel electrophoresis of the purified enzyme, multiple bands of activity resulted from enzyme-buffer interaction at low but not high buffer concentration. A Ferguson plot (Ferguson, 1964) showed that this heterogeneity was due to a charge difference with no alteration in the size of the enzyme. Stimulation of enzyme activity by KCl, urea and p-hydroxymercuribenzoate, and inhibition by methotrexate and trimethoprim, showed only minor differences between the various enzymes.

Cell Line↗