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Biomedical subjects

J F Martin

Publications and source records attributed to J F Martin.

At least 325 records · Page 18Linked to original sources
PubMedDate not supplied

Normal fasting-state levels of serum cholyl-conjugated bile acids in Gilbert's syndrome: an aid to the diagnosis.

Fasting levels of cholic acid conjugates were determined by radioimmunoassay in the serum of 24 patients with extensively documented Gilbert's syndrome and in 98 healthy controls without unconjugated hyperbilirubinemia. The Gilbert's syndrome patients studied included all three subtypes, as determined from studies of the plasma disappearance kinetics of sulfobromophthalein and indocyanine green. Although patients with structural liver disease severe enough to produce hyperbilirubinemia almost invariably have elevated fasting serum levels of cholic acid conjugates, values were normal in each of the Gilbert's syndrome patients, including patients with metabolic abnormalities in sulfobromophthalein and indocyanine green transport. It is concluded that the measurement of fasting serum levels of cholic acid conjugates is a useful adjunct to the diagnosis of Gilbert's syndrome.

Cholic Acids↗
PubMedDate not supplied

Clusters of genes for the biosynthesis of antibiotics: regulatory genes and overproduction of pharmaceuticals.

In the last decade numerous genes involved in the biosynthesis of antibiotics, pigments, herbicides and other secondary metabolites have been cloned. The genes involved in the biosynthesis of penicillin, cephalosporin and cephamycins are organized in clusters as occurs also with the biosynthetic genes of other antibiotics and secondary metabolites (see review by Martín and Liras [65]). We have cloned genes involved in the biosynthesis of beta-lactam antibiotics from five different beta-lactam producing organisms both eucaryotic (Penicillium chrysogenum, Cephalosporium acremonium (syn. Acremonium chrysogenum) Aspergillus nidulans) and procaryotic (Nocardia lactamdurans, Streptomyces clavuligerus). In P. chrysogenum and A. nidulans the organization of the pcbAB, pcbC and penDE genes for ACV synthetase, IPN synthase and IPN acyltransferase showed a similar arrangement. In A. chrysogenum two different clusters of genes have been cloned. The cluster of early genes encodes ACV synthetase and IPN synthase, whereas the cluster of late genes encodes deacetoxycephalosporin C synthetase/hydroxylase and deacetylcephalosporin C acetyltransferase. In N. lactamdurans and S. clavuligerus a cluster of early cephamycin genes has been fully characterized. It includes the lat (for lysine-6-aminotransferase), pcbAB (for ACV synthase) and pcbC (for IPN synthase) genes. Pathway-specific regulatory genes which act in a positive (or negative) form are associated with clusters of genes involved in antibiotic biosynthesis. In addition, widely acting positive regulatory elements exert a pleiotropic control on secondary metabolism and differentiation of antibiotic producing microorganisms. The application of recombinant DNA techniques will contribute significantly to the improvement of fermentation organisms.

Acyltransferases↗
PubMedDate not supplied

Stem cells and repair of the heart.

Stem-cell therapy provides the prospect of an exciting and powerful treatment to repair the heart. Although research has been undertaken in animals to analyse the safety and efficacy of this new approach, results have been inconclusive. The mechanism by which stem cells could improve cardiac function remains unclear. We describe the background to the concept of natural repair and the work that has been done to establish the role of stem cells in cardiac repair. Controversies have arisen in interpretation of experimental data. The important issues surrounding the application of stem-cell therapy to man are discussed critically. We discuss the future of this pioneering work in the setting of growing concerns about clinical studies in man without understanding the biological mechanisms involved, with the difficulties in funding this type of research.

Animals↗
PubMedDate not supplied

Inbreeding and developmental stability in a small human population.

Inbreeding coefficients are reported for all members of the isolated Havasupai tribe of northern Arizona (USA), based upon pedigrees which are as deep as eight generations. Because inbreeding has been repeatedly shown to reduce developmental homeostasis in a large number of species, we ask if the degree of inbreeding in the Havasupai is associated with reduced developmental stability. Fluctuating asymmetry in two dermatoglyphic traits suggests that inbreeding significantly compromises developmental homeostasis in this population.

Analysis of Variance↗
PubMedDate not supplied

Hormonal and behavioral determinants of the secondary sex ratio.

The timing of insemination relative to ovulation and the frequency of insemination appear prominently in analyses of variations in human secondary sex ratios. Explanations invoking these variables are shown to be inadequate. A new synthetic model of sex determination is proposed in which the sex of offspring is powerfully determined by the state of the cervical mucus. The cervical state is then shown to be a function of hormonal factors endogenous to the female in interaction with the effects of previous inseminations.

Adolescent↗
PubMedDate not supplied

Consequences of the introduction of the new inactivated poliovirus vaccine into the Expanded Programme on Immunization.

Use of the oral poliovirus vaccine in the Expanded Programme on Immunization (EPI) demands that the children vaccinated be seen four times during the first 10 months of life. In practice, this necessity presents considerable difficulties, which are expressed in particular by the high drop-out rate. Introduction of the new inactivated poliovirus vaccine (IPV) into the vaccination program enables children to be effectively protected against the six diseases of the EPI in only two visits. Vaccination coverage is thus very significantly increased. At the same time, by reducing the number of visits, both the running costs and the investment costs can be decreased. However, the cost of the vaccines is going to rise noticeably because the production of the new IPV will remain a great deal more costly than the production of the live vaccine. An outline is provided of the likely price of the new concentrated and purified IPV. The efficacy/cost ratio, measured by the cost of completely vaccinating a child, will, nevertheless, be considerably improved. The new IPV therefore increases the feasibility of the EPI under most satisfactory economic conditions.

Community Health Services↗
PubMedDate not supplied

Lymphomatoid granulomatosis with cerebral involvement.

We report the case of a 26-year-old man who suffered from lymphomatoid granulomatosis. The light microscopical features of a biopsy from involved cerebral tissue are described and for the first time the cytological findings on a brain smear are illustrated. The results of immunological and electronmicroscopical investigations are consistent with the suggestion that this disease may be a disorder of T lymphocytes. It is suggested that the smear technique may be used to confirm the presence of cerebral disease in patients with an established diagnosis, and to investigate suspected patients who present with extrapulmonary manifestations.

Adult↗
PubMedDate not supplied

Nitric oxide and prostacyclin. Divergence of inhibitory effects on monocyte chemotaxis and adhesion to endothelium in vitro.

Monocyte-endothelial interactions are of fundamental importance in determining the movement of monocytes from the blood stream into the vessel wall. This study reports that two endothelium-derived factors, nitric oxide and prostacyclin, alter in vitro monocyte behavior. Nitric oxide (greater than 10(-5) M) inhibited monocyte adhesion to porcine aortic endothelial cell monolayers, whereas prostacyclin (10(-9) to 10(-5) M) had no effect. Both nitric oxide and prostacyclin inhibited monocyte chemotaxis stimulated by N-formyl-methionyl-leucyl-phenylalanine and induced dose-dependent increases in intracellular cyclic guanosine monophosphate and cyclic adenosine monophosphate concentrations, respectively. The cell surface expression of the CD11b/CD18 adhesion receptor, a glycoprotein complex known to mediate monocyte intracellular adhesion, was not altered by either nitric oxide or by prostacyclin. Thus, endothelium-derived nitric oxide and prostacyclin may have a physiological role in modulating monocyte-vascular wall interactions. Alterations in this system may contribute to the increased monocyte emigration from the blood stream into the vessel wall observed in atherogenesis.

Animals↗
PubMedDate not supplied

Platelet and megakaryocyte changes in cholesterol-induced experimental atherosclerosis.

Rabbits were fed either 2 g cholesterol in 10 ml olive oil daily with normal diet (n = 5) or normal diet alone (n = 5). After 12 weeks, the cholesterol-fed animals had developed fatty plaques involving 24% +/- 4% of the surface area of the aorta; the control animals had none. Mean platelet volume was significantly smaller (p less than 0.04) in the cholesterol-fed animals (4.1 +/- 0.3 fl) compared with the controls (4.8 +/- 0.4 fl). The heterogeneity of the average volume distributions of the two groups, characterized by the statistical parameters of the coefficient of variation, skewness, and kurtosis, was also significantly different. Platelet count was significantly higher (p less than 0.001) in the cholesterol-fed group (7.48 +/- 1.06 x 10(11) platelets/liter blood) compared to the control group (4.86 +/- 0.60 x 10(11) platelets/liter blood). Mean megakaryocyte cytoplasmic volume was significantly larger (p less than 0.001) in the cholesterol-fed rabbits (12,262 +/- 1485 fl) compared with controls (6,814 +/- 761 fl). The range of cytoplasmic volumes was also significantly increased in the cholesterol-fed rabbits. A significant (p less than 0.01) increase in mean megakaryocyte nuclear volume in the cholesterol-fed animals was accompanied by a nonsignificant increase in mean nuclear DNA content: 30.2 +/- 3.7 N compared with a control value of 23.6 +/- 4.0 N. This evidence indicates that a high cholesterol diet in rabbits is associated with changes in platelet production from megakaryocytes as well with as the development of atherosclerosis.

Animals↗