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Biomedical subjects

J M Stark

Publications and source records attributed to J M Stark.

At least 73 records · Page 4Linked to original sources
PubMed1989

Changes in phospholipid fatty acid composition and triacylglycerol content in mouse tissues after infection with bacille Calmette-Guérin.

Changes in the lipids of tissues from mice infected with bacille Calmette-Guérin (BCG) have been detected by gas-liquid chromatography. Infection with BCG resulted in (1) an increase in the polyunsaturated to saturated fatty acid ratio of phospholipids and (2) a decrease in the total triacylglycerol fatty acid content of spleen, liver and peritoneal macrophages. The alteration in fatty acid composition was significant in the phosphatidylethanolamine fraction of the phospholipids. The relation of these findings to an increased sensitivity to bacterial endotoxins is discussed.

Animals↗
PubMed1987

Pharmacokinetics of ciprofloxacin in the elderly.

The pharmacokinetics of ciprofloxacin, administered orally as a 250-mg tablet were compared in 10 young (age 20-30 years) and 10 elderly (age 60-73 years) healthy volunteers. The time to peak serum concentrations was about 80 min in both age groups, although the maximum concentration attained was significantly greater in the old (1.7 mg/l) than the young (1.2 mg/l). Area under the plasma concentration-time curve, corrected for body weight, was on average 48% greater in the elderly, but the mean terminal elimination half-life was not significantly different, averaging 4.3 h in the old and 3.7 h in the young. Overall 24-hour urinary recovery in both age groups was comparable. The differences may be explained by a reduced volume of distribution of ciprofloxacin in old age and do not suggest a general need for significant dose alteration in the elderly.

Administration, Oral↗
PubMed1987

Tumour cell killing by tumour necrosis factor: inhibition by anaerobic conditions, free-radical scavengers and inhibitors of arachidonate metabolism.

Previous work on the mechanism of tumour-cell killing by the macrophage product tumour necrosis factor (TNF) is consistent with a free radical-induced process. In this study, free-radical involvement was sought by (i) investigating the effects on TNF cytolysis of anaerobic conditions, free-radical scavengers and inhibitors of two potential pathways of free-radical generation (oxidative phosphorylation and arachidonate metabolism) and (ii) looking for increased malonyldialdehyde (MDA) production in TNF-treated cells (MDA is a free radical-induced lipid peroxidation product). Although TNF cytolysis of L929 cells was inhibited by anaerobic conditions, only limited effects were seen with free-radical scavengers. Suppression of arachidonate metabolism by steroids effectively inhibited TNF cytolysis but the mitochondrial poison rotenone did not. There was a marked, but late, increase in MDA production in TNF-treated cells. Overall, these results indicate that if free radicals are involved it is at a late stage in the cytolytic process. However the most striking observation in this study is that arachidonate metabolism is an essential link in the cytolytic process.

Animals↗
PubMed1983

The structure of cloned hemolysin DNA from plasmid pHly185.

The complete DNA segment coding for hemolysis on Escherichia coli plasmid, pHly185, on to the vector pBR322 has been cloned. The recombinant plasmid, pJS204, coded the production of externalized hemolysin and contained four contiguous EcoRI fragments from the original plasmid. A restriction map of pJS204 was generated with six endonucleases. Deletion mutations were constructed from the recombinant plasmid by excision with either BamHI and PstI and religation. The BamHI deletion removed a 3680-bp portion from the recombinant plasmid and prevented the synthesis of active hemolytic activity. The PstI-generated deletion removed 7800 bp from the opposite end of the Hly sequence and resulted in a plasmid coding for the production of active intracellular hemolytic activity but contained no information for the export of hemolysin. We examined the ability of the deletion mutants of pJS204 to complement each other, and Tn5 insertion mutations in the hly region of the parent plasmid, pHly185. The complementation studies indicated the presence of three separate cistrons able to complement in trans in a recA E. coli host. Two cistrons were found to be required for synthesis and one cistron for export of the hemolysin. The presence of two promoters and the directions of transcription for the synthesis of the hly gene products was also inferred from the complementation studies.

Bacterial Proteins↗
PubMed1982

Analysis of hemolytic determinants of plasmid pHly185 by Tn5 mutagenesis.

A nonconjugative hemolysin plasmid, pHly185, was isolated from Escherichia coli 185. Tn5 mutagenesis produced nonhemolytic derivatives that either expressed no hemolytic activity or did not secrete activity. These Tn5 insertions were located in three contiguous EcoRI fragments. Insertions inactivating hemolysin structural gene(s) were identified on all three EcoRI fragments. Mutations affecting the secretory function were clustered in one portion of a single EcoRI fragment.

Bacteriophage lambda↗
PubMed1981

Acute-phase C56-forming ability and concentrations of complement components in normotensive and hypertensive pregnancies.

A prospective study of 61 women who were normotensive at booking revealed an increased incidence of C56-forming ability in those who later developed hypertension. Similar changes were found before delivery in a separate group of women admitted with latent hypertension and in each of 11 women with severe pre-eclampsia and a surviving fetus. The C56-forming ability, an acute phase feature, often preceded the hypertension and the findings suggest an indirect relation between complement changes and the mechanism causing hypertension in pregnancy. Concentrations of complement components in hypertensive and normotensive pregnancies were also compared with each other and with those of normal healthy non-pregnant women. The hypertensive patients had increased total alternative pathway function and higher factor B concentrations. The C56-negative sera from hypertensive patients tended to have C7 concentrations higher than normal whereas C56-positive patients had higher C5 concentrations. The aetiological and pathological implications are discussed.

Complement Activation↗
PubMed1981

The effects of surgical removal of Peyer's patches in rat on systemic antibody responses to intestinal antigen.

A method is described for the in vivo surgical removal of all Peyer's patches from the small intestine and caecum of the rat. Over two postoperative months, this procedure had no apparent morphological effects on the small intestine or intraepithelial lymphocyte numbers, nor were the numbers of IgA producing cells in the small intestine or serum immunoglobulin levels permanently influenced. However, circulating specific antibody to human serum albumin was significantly elevated in animals without Peyer's patches 3 weeks after surgery, in comparison with a sham operated group of animals. Subsequent intestinal immunization in animals without Peyer's patches with a lipid-conjugated human serum albumin resulted in a diminished primary but a comparatively normal secondary systemic antibody response to this antigen.

Animals↗
PubMed1980

Recurrent meningococcal infections associated with a functional deficiency of the C8 component of human complement.

A patient is described who had a functional deficiency of the C8 complement component. His serum contained abnormal C8 which lacked some of the antigenic determinants of normal C8. The defect was associated with recurrent meningococcal infections due at different times to at least two strains. The patient's serum contained antibodies to meningococci and could induce phagocytosis and intracellular killing of the cocci by polymorphs. However, the serum was bactericidal only after the addition of C8-containing serum. As the patient did not give a history of susceptibility to other pyogenic organisms and has normal polymorph function, the circumstances of meningococcal infection must be unusual in that the plasma bactericidal activity critically determines the outcome: it may be that if large numbers of meningococci are not killed in the plasma, the polymorphs are overwhelmed.

Adolescent↗
PubMed1980

Endotoxin-induced appearance of peroxidase-positive cells in the white pulp of the mouse spleen.

Endotoxin (1-10 microgram intravenously) increased the number of strongly peroxidase-positive cells in the white pulp of the mouse spleen, demonstrable by the Graham-Karnovsky technique. The increase was greatest after 10 h, the cells being found most frequently around the central vessels of the white pulp. The appearance of such cells at this critical immunological site may relate to the known adjuvant activity of endotoxin in promoting immune responses against protein antigens.

Animals↗
PubMed1980

Immunogenicity of lipid-conjugated antigens. II. Anti-complementary activity and antigen trapping in the spleen.

The most immunogenic of various acylated human serum albumin (HSA) preparations also showed the greatest anti-complementary activity. This is due in part to their ability to activate the alternative pathway and consume complement components. Such molecules also adsorbed radiolabelled complement components readily and were themselves rapidly removed from the circulation after their intravenous injection. Highly lipidated C14 HSA (C14, fatty acid side-chains with 14 carbon atoms) was not itself mitogenic: unlike HSA it localized heavily to the red pulp as well as to cells of dendritic form in the splenic white pulp. The increased immunogenicity is found in lipidated HSA species which show the following features: hydrophobicity, anti-complementary activity, ability to activate complement, heavy localization in the red pulp and an unusual tendency to localize to dendritic cells of the while pulp.

Acylation↗
PubMed1980

Immunogenicity of lipid-conjugated antigens. I. The influence of chain length and degree of conjugation on induction of antibody in mice.

An experiments in mice with a range of human serum albumin (HSA) molecules acylated to various degrees with side-chains of 6--20 carbon atoms, the greatest antibody responses against HSA were induced by highly acylated HSA with side-chains of intermediate length (C10--14). Similar results were obtained in rats but in this species the highest acylations with a particular chain length more often induced a less than optimal response. Mouse sera produced in response to acylated antigens and absorbed with HSA itself did not detectably react with acylated HSA when tested by an ammonium sulphate precipitation method. Acylation of antigen may sometimes reduce immunogenicity as shown in experiments with diphtheria toxoid.

Acylation↗
PubMed1978

Disequilibrium in control of proteolysis as a cause of pre-eclampsia.

The interrelated systems which control proteolysis may go into disequilibrium during pregnancy so that a renin-like enzyme in the plasma produces effects such as the early clinical manifestations of pre-eclampsia; the overactivity of the reninlike enzyme may in turn lead to undue activity of other physiological systems including those of the coagulation and complement systems.

Antithrombins↗
PubMed1978

The ability of smooth and rough strains of Streptococcus pneumoniae to activate human complement by the alternative pathway.

Three capsulate pneumococcal strains of serotypes 1, 2 ans 3, and one non-capsulate strain of serotype 47, were found to activate human complement by the alternative pathway to a similar extent over the concentration range examined. Nevertheless, the capsulate strains, in contrast to the non-capsulate, are known to require complement attachment for phagocytosis and it is therefore postulated that the toxic by-products released cause the wave of oedema characteristic of pneumococcal lobar pneumonia.

Bacteriological Techniques↗
PubMed1978

Meningococcal infection and proteolytic control.

Cascade enzyme inhibitors (C1-esterase inhibitor, C3b inactivator, antithrombin III) and other major proteolytic enzyme inhibitors (alpha 1 trypsin inhibitor, alpha 1 chymotrypsin inhibitor, inter-alpha-trypsin inhibitor, alpha 2 macroglobulin) as well as C3 and alpha 1 acid glycoprotein, have been examined in the sera of Nigerian patients suffering from meningococcal infection of varied severity. Patients with meningococcaemia had lower serum concentrations of important inhibitors than did patients with localised meningitic infection. Within the coccaemic group, those who died had the lowest values, notably of antithrombin III and alpha 2 macroglobulin (and also of C3). The clinical end-result of meningococcal infection may be related to the degree of disequilibrium of the linked system of proteolytic control induced by the meningococcal endotoxin.

Antithrombin III↗