Search PubMed⌕ Search

Biomedical subjects

P Jones

Publications and source records attributed to P Jones.

At least 19 recordsLinked to original sources
PubMed1992

The human glutathione S-transferases: comparison of isoenzyme expression in normal and astrocytoma brain.

We describe expression of alpha, mu and pi class glutathione S-transferases (GST) in brain tissue from 21 controls and uninfiltrated and tumour tissue from 17 glioma patients. GST were sequentially resolved by chromatofocusing into the GST2, GST1, GST5, GST2 (5.5), GST3, GST6 sets and the contribution of each to total activity determined. The immunological identity of these isoforms was studied using immunoblotting. The pi class GST3 isoform was the major contributor to activity in control tissue (70.9%) and, uninfiltrated (75.1%) and tumour samples (82.4%). Expression was significantly greater in the tumours (P less than 0.05). Expression of alpha isoforms GST2 and GST2 (5.5) was variable with most subjects demonstrating no detectable GST2 (B1 and B2 chromatofocused monomers). An isoform termed GST2 (5.5) chromatofocussed at pH 5.5 and cross-reacted with antisera to B1. It was detected in most control and glioma patients and comprised about 5% of total activity. The contribution of GST2 and GST2 (5.5) to activity was similar in control, uninfiltrated and tumour tissue. Two mu class enzymes, GST1 and GST5, were identified. GST1 isoforms were detected in 9 of 21 control samples, the phenotype of these and matched liver samples were identical. GST1 isoforms were detected in 4 of 16 tumour samples, a significantly lower incidence than in a previously established control group. GST5 was expressed in most samples, the contribution of this locus to activity was significantly reduced in the tumours (5.2%) compared with control samples (14.5%).

Astrocytoma↗
PubMed1992

Increased sympathetic nervous activity and the effects of its inhibition with clonidine in alcoholic cirrhosis.

OBJECTIVE: To study disturbances in sympathetic nervous system function in patients with alcoholic cirrhosis and the effect of clonidine on such disturbances. DESIGN: Cross-sectional physiologic and neurochemical evaluation of patients with cirrhosis and of healthy controls; an uncontrolled trial of intravenous clonidine in the cirrhotic patients. PATIENTS: Forty-four hospitalized patients with biopsy-proven alcoholic cirrhosis and 31 healthy controls. INTERVENTIONS: Intravenous clonidine. MAIN OUTCOME MEASURES: Radiotracer-derived measures of norepinephrine release to plasma, central hemodynamics, wedge hepatic vein pressure, and measures of renal function. MAIN RESULTS: In patients with cirrhosis, clonidine reduced previously elevated norepinephrine overflow rates for the whole body, kidneys, and hepatomesenteric circulation. This sympathetic inhibition was accompanied by the following potentially clinically beneficial effects: the lowering of renal vascular resistance (median reduction, 24%; 95% CI, 14% to 31%), the elevation of glomerular filtration rate (median increase, 27%; CI, 14% to 39%), and the reduction of portal venous pressure (median reduction, 25%; CI, 18% to 32%). The norepinephrine and hemodynamic responses to graded clonidine dosing (1, 2, and 3 micrograms/kg body weight intravenously) indicated that the sympathetic outflow to the hepatomesenteric circulation was more sensitive to pharmacologic suppression with clonidine than was the sympathetic outflow to the systemic circulation. CONCLUSIONS: The sympathetic nerves to the kidneys, heart, and hepatomesenteric circulation are stimulated in patients with cirrhosis. Clonidine inhibits these activated sympathetic outflows differentially, which could possibly provide a basis for the selective pharmacologic treatment of portal hypertension in patients with cirrhosis.

Adult↗
PubMed1992

Genes, viruses and neurodevelopmental schizophrenia.

Recent neuroimaging and neuropathological studies suggest a developmental origin for schizophrenia. Some cases may, therefore, be caused by a genetic defect in the specification of brain development. Early environmental hazards such as obstetric complications, and maternal exposure during pregnancy to influenza epidemics, have also been found to increase the risk of later schizophrenia. The relationship between the prevalence of influenza and birth date has been found more consistently for female than male schizophrenics. Female schizophrenia is also associated with a higher risk of schizophrenia in first degree relatives. This raises the question of whether part of the genetic predisposition to schizophrenia may comprise an abnormal reaction to maternal influenza.

Brain Damage, Chronic↗
PubMed1992

Free radical yields from the homolysis of peroxynitrous acid.

A recent study reports discordant results for maximal free-radical yields from the decomposition of peroxynitrous acid using different assay reagents and a puzzling decrease (to zero) of the radical yields with increasing pH. An assay method using 2,2,'azino-bis(3-ethyl-benzthiazoline sulphonate) (ABTS) has been tested using stopped-flow kinetic studies, and the results imply that the assay is satisfactory when [HOONO] much greater than [-OONO] but that reactions involving peroxynitrite anion interfere at higher pH. Evidence is presented that peroxynitrite was an interfering species in the earlier studies.

Benzothiazoles↗
PubMed1992

Limiting dilution analysis in leprosy.

Peripheral blood mononuclear cells (PBM) obtained from leprosy patients and healthy controls were cultured with Mycobacterium leprae and the control antigens, BCG and SKSD. Parallel cultures were supplemented with additional interleukin-2 (IL-2). On the basis of the level of response to M. leprae, leprosy patients could be divided into low, intermediate and high responders. The addition of IL-2 resulted in enhanced proliferation to antigen only by cells from intermediate responders. This effect was neither antigen specific nor was it confined to cells from leprosy patients. When limiting dilution analyses were performed on cells from 26 patients across the leprosy spectrum, no M. leprae-reactive lymphocytes were detected in cells from subjects with lepromatous disease. The precursor frequency for cultures containing M. leprae plus IL-2 was no greater than that of cultures containing IL-2 alone, thereby excluding the possibility of clonal anergy reversible with IL-2. This was observed in both untreated patients and those on long-term treatment, which made sequestration of antigen-reactive cells within leprosy lesions an unlikely explanation. On the other hand, M. leprae-reactive lymphocytes were detected in patients with tuberculoid and borderline tuberculoid disease and in two subjects with borderline lepromatous leprosy in type I reversal reaction. IL-2 reactive cells were detected in all patients regardless of clinical classification. Three 'suppressor' curves were obtained but were not confined to cells from lepromatous patients. Taken together, these findings suggest that the non-responsiveness to M. leprae characteristic of the great majority of multibacillary patients is due to an absence of antigen-sensitive T cells.

Antigens, Bacterial↗
PubMed1992

Structure of a 16 kDa integral membrane protein that has identity to the putative proton channel of the vacuolar H(+)-ATPase.

A 16 kDa protein has been isolated in a homogeneous form as the major component of a paracrystalline paired membrane structure closely resembling the gap junction. The primary structure of this protein from arthropod and vertebrate species has been determined by protein and cDNA sequencing. The amino acid sequences are highly conserved and virtually identical to the amino acid sequence of the proteolipid subunit of the vacuolar H(+)-ATPases. The disposition of the protein in the membrane has been studied using proteases and the N,N'-dicyclohexylcarbodiimide reactive site identified. These data, together with secondary structure predictions, suggest that the 16 kDa protein is for the most part buried in the membrane, arranged in a bundle of four hydrophobic alpha-helices. Using computer graphics, a model has been constructed based on this arrangement and on the electron microscopic images of the paracrystalline arrays.

Amino Acid Sequence↗
PubMed1992

Effect of post-delivery care on neonatal body temperature.

A prospective observational study of post-delivery care and neonatal body temperature, carried out at Kathmandu Maternity Hospital, was followed by a randomized controlled intervention study using three simple methods for maintaining body temperature. There were 500 infants in the initial observation study and 300 in the intervention study. In the observation study, 85% (420/495) of infants had temperatures < 36 degrees C at 2 h and nearly 50% (198/405) had temperatures < 36 degrees C at 24 h (14% were < 35 degrees C). Most of the infants who were cold at 24 h had initially become cold at the time of delivery (only seven infants had been both well dried and wrapped). In the intervention study, all infants were dried and wrapped before random assignment to one of the three methods: the "kangaroo" method, the traditional "oil massage" or a "plastic swaddler". All three were found to be equally effective. Overall, 38% (114/298) of the infants had temperatures < 36 degrees C at 2 h and 18% (41/231) at 24 h (when none was < 35 degrees C).

Body Temperature↗
PubMed1992

Haemophilia home therapy.

Within the past 20 years, home therapy has become an accepted treatment for the majority of people with severe haemophilia in the developed world. The intravenous administration of blood products by suitably trained patients or their relatives has proved to be safe and effective. It allows for the early treatment of bleeding episodes before the appearance of physical signs. It results in reduced morbidity, especially in terms of reduction in long-term arthropathy, and in reduced socio-economic handicap. It is cost effective both in terms of savings in time previously lost from school or work and reduction of reliance on expensive hospital facilities. Home therapy forms a vital part of the overall comprehensive care of people with haemophilia and their families.

Adult↗
PubMed1992

Effects of pimobendan (UDCG 115) on renal function in healthy volunteers.

A phase I, double-blind, single-dose, randomized, two-period crossover study was conducted to investigate the effects of pimobendan on renal function to assess whether renal events were a contra-indication to its administration. Results in eight healthy volunteers indicated no significant adverse events on renal plasma flow, glomerular filtration rate, or laboratory safety screens; side-effects were also found to be minimal. Further studies are indicated to assess whether, in the proposed treatment group, i.e. patients with heart failure (in whom compromised renal function is common), pimobendan similarly elicits no serious adverse renal effects.

Adult↗
PubMed1992

Glomerular injury induced by hydrogen peroxide: modifying influence of ACE inhibitors.

The sensitivity of isolated glomeruli from normotensive (Wistar-Kyoto, WKY) and spontaneously hypertensive (SHR) strains to oxidant stress was studied by determining the incidence of pyknosis, karyohexis and karyolysis after incubation with different concentrations of hydrogen peroxide (H2O2) (4.7 x 10(-9) - 10(-3) M). Even though the proportion of glomeruli containing nuclei that demonstrated these features increased progressively with increasing concentrations of H2O2, the number of severely damaged glomeruli was relatively small even at concentrations of 4.7 x 10(-3) M. Examination of the surface epithelial cells of glomeruli using scanning electron microscopy revealed no evidence of disturbance of the macroscopic or podocyte structure or, of increased blebbing after H2O2-treatment. These data suggest damage to nuclei is an early result of ROS stress on glomeruli. Preincubation of WKY glomeruli with captopril or lisinopril resulted in a significant drop in the proportion of WKY glomeruli demonstrating structural damage after oxidant stress. In contrast, preincubation of SHR glomeruli with lisinopril had no effect on oxidant-induced changes in the morphology of SHR glomeruli, whereas captopril effected a significant increase in the proportion of glomeruli demonstrating damage at all concentration of H2O2.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

[Access to root canals].

Both for the future of the residual dental crown and in order to work efficiently in the canals, preparation of the pulp chamber should be regarded as more than a mere stage. Although it is only a transitory stage, it is essential that the pulp chamber should be clean and well cleared without wasting healthy dental tissue. A good access, without excess, will increase the chances of success.

Dental Caries↗
PubMed1992

Serological response to purified mycobacterial phosphatidylinositol mannoside in healthy controls and in patients with tuberculosis and leprosy.

The serological response to a monoclonal antibody-defined phosphatidylinositol mannoside (L4-PIM) present in all mycobacteria was examined in patients with various mycobacterial diseases and healthy subjects from different populations. IgG but not IgM antibodies were detected in most patients with untreated lepromatous (84%) or borderline lepromatous (65%) leprosy, but in only a minority of those with disease at the tuberculoid end of the leprosy spectrum (< 17% positive). The response to L4-PIM was correlated with the IgM response to disaccharide octyl-bovine serum albumin (dBSA), and decreased with successful treatment. On the other hand, the test proved to be of little value in the diagnosis of untreated tuberculosis (4/15 positive) or atypical mycobacterial infection in patients with AIDS (0/11 positive). IgG antibodies to L4-PIM were also found in a significant proportion of healthy individuals, irrespective of their Mantoux status. These antibodies were shown to be specific for L4-PIM on immunoblotting, and their incidence increased with age in random donors from both urban Australia and rural Papua New Guinea. Despite the limited value of the assay in diagnosis of any particular mycobacterial disease, the presence of antibodies to L4-PIM appears to be a sensitive indicator of subclinical infection with environmental mycobacteria in subjects with an intact immune system.

Acquired Immunodeficiency Syndrome↗