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Biomedical subjects

O James

Publications and source records attributed to O James.

At least 19 recordsLinked to original sources
PubMed1992

Thrombin, epidermal growth factor, and phorbol myristate acetate stimulate tubulin polymerization in quiescent cells: a potential link to mitogenesis.

Previous studies suggest that alterations in the microtubule (MT)-tubulin equilibrium during G0/G1 affect mitogenesis. To determine the effect of growth factors on the MT-tubulin equilibrium, we developed a radioactive monoclonal antibody binding assay (Ball et al.: J. Cell. Biol. 103:1033-1041, 1986). With this assay, 3H-Ab 1-1.1 binding to cytoskeletons in confluent populations of cultured cells is proportional to the number of tubulin subunits polymerized into MTs. We now show that purified alpha-thrombin increases 3H-Ab 1-1.1 binding to cytoskeletons of serum-arrested mouse embryo (ME) fibroblasts from 1.5- to 3-fold. This stimulation is dose-dependent and correlates with concentrations of thrombin required for initiation of DNA synthesis. Other mitogenic factors, epidermal growth factor (EGF) and phorbol 12-myristate 13-acetate (PMA), also stimulate MT polymerization. Addition of colchicine (0.3 microM) eight hours after growth factor addition, blocks stimulation of 3H-thymidine incorporation by thrombin, EGF, or PMA, suggesting that tubulin polymerization or subsequent events triggered by MT polymerization are required for cells to enter a proliferative cycle. Consistent with models for autoregulation of tubulin synthesis, thrombin, EGF, and PMA all increase tubulin synthesis 9 to 15 hr after growth factor addition, raising the possibility that the decrease in free tubulin and subsequent stimulation of tubulin synthesis is linked to progression of cells into a proliferative cycle. Colchicine addition to these cells also stimulates DNA synthesis, but colchicine-stimulated cells enter S phase 6 to 8 hr later than those stimulated by growth factors. This delayed stimulation may be related to the time required for degradation of tubulin-colchicine complexes below a critical level. These data suggest that regulation of cell proliferation may be linked to increased MT polymerization and the resulting decrease in free tubulin pools.

Animals↗
PubMed1992

Expression and characterization of genetically engineered human immunodeficiency virus-like particles containing modified envelope glycoproteins: implications for development of a cross-protective AIDS vaccine.

Noninfectious human immunodeficiency virus type 1 (HIV-1) viruslike particles containing chimeric envelope glycoproteins were expressed in mammalian cells by using inducible promoters. We engineered four expression vectors in which a synthetic oligomer encoding gp120 residues 306 to 328 (amino acids YNKRKRIHIGP GRAFYTTKNIIG) from the V3 loop of the MN viral isolate was inserted at various positions within the endogenous HIV-1LAI env gene. Expression studies revealed that insertion of the heterologous V3(MN) loop segment at two different locations within the conserved region 2 (C2) of gp120, either 173 or 242 residues away from the N terminus of the mature subunit, resulted in the secretion of fully assembled HIV-like particles containing chimeric LAI/MN envelope glycoproteins. Both V3 loop epitopes were recognized by loop-specific neutralizing antibodies. However, insertion of the V3(MN) loop segment into other regions of gp120 led to the production of envelope-deficient viruslike particles. Immunization with HIV-like particles containing chimeric envelope proteins induced specific antibody responses against both the autologous and heterologous V3 loop epitopes, including cross-neutralizing antibodies against the HIV-1LAI and HIV-1MN isolates. This study, therefore, demonstrates the feasibility of genetically engineering optimized HIV-like particles capable of eliciting cross-neutralizing antibodies.

AIDS Vaccines↗
PubMed1991

Production of immunogenic HIV-1 viruslike particles in stably engineered monkey cell lines.

A proviral fragment from human immunodeficiency virus type 1 (HIV-1) (LAV-1BRU) containing only protein-coding information, was expressed in COS cells using constitutive promoters in transient and stable transfection experiments. The presence of viruslike particles in cell supernatants was verified by Western blot analysis, density gradient centrifugation, and electron microscopy. Transfection of Vero cells with a similar construct employing the human metallothionein promoter led to the isolation of stable cell lines exhibiting inducible viruslike particle expression in response to cadmium chloride treatment. Induction ratios for viruslike particle expression were in excess of 1000-fold with production levels of p24 core antigen as high as 0.6 mg/L per 24 h. HIV-1 viruslike particles were immunogenic in mice, leading to strong envelope and core-specific humoral responses after two immunizations. The development of stable cell lines expressing significant quantities of HIV-1 viruslike particles offers an alternative to the use of live virus vectors for the production and evaluation of particle-based AIDS vaccines.

Animals↗
PubMed1991

The effect of age on glucuronidation and sulphation of paracetamol by human liver fractions.

Glucuronidation and sulphation were studied in vitro in human liver samples from 22 subjects aged 40-89 years using paracetamol as substrate. There was no significant correlation with age for the activity of either enzyme pathway. These results provide further evidence that age per se does not have a major effect on the activities of hepatic metabolising enzymes.

Acetaminophen↗
PubMed1990

Prevalence of reactive serological tests for syphilis in the Jamaican population.

Serological tests for syphilis (STS) were performed on sera from 15,876 members of the general adult population, 3,039 pregnant women and 1,029 children, in order to assess the prevalence and value of reactive STS in Jamaicans; 2.7% of sera from the general adult population, 4.7% from pregnant women and 2.2% from children were reactive in the Venereal Disease Research Laboratory (VDRL) test. Reactive Fluorescent Treponemal Absorption (FTA-ABS) tests occurred in significantly higher frequency in pregnant women (4%) than in the general population (2.2%; p less than 0.001). The prevalence of reactive STS in children did not differ significantly from that of the general adult population. The predictive value of a reactive VDRL test in pregnant women (85%) was higher than that of the general population (79%). These results suggest that adequate screening with the inexpensive VDRL test would enable the early detection and treatment of syphilis, and could prevent increasing incidence of congenital syphilis in Jamaica.

Adult↗
PubMed1988

Global ratings of stress in the elderly.

The properties of four global ratings of life stress were investigated using data from 237 elderly subjects interviewed using the Brown & Harris life event and difficulties schedule. The global ratings had high one-year test-retest reliability and inter-rater reliability agreement. A summary measure of Adversity (based on contextual rating of all events and difficulties) may be reliably derived when a single index of life stress is desired. In the elderly sample Adversity was more closely related to chronic difficulties than to life-events.

Adaptation, Psychological↗
PubMed1986

Cloned helper T cell for IgE: characterization of T cells cloned from an atopic donor with a high serum IgE.

T cells cloned from nonatopic and atopic donors were examined for the ability to help IgE production in vitro. Experiments with clones from nonatopic donors were unsuccessful in spite of isolation of four clones that promoted IgM and IgG when these were mixed with B cells from nonatopic donors and pokeweed mitogen. We reasoned that T cells regulating IgE might be found with greater frequency in atopic donors with very high serum IgE. Two T cell clones from an atopic donor with a serum IgE of 3000 IU/ml were found to drive atopic B cells to produce up to 10,000 pg/ml of IgE in vitro. This promotion of IgE secretion occurred in the absence of mitogen stimulus and appeared to decrease with higher ratios of T cells:B cells. One of the clones (A-H4) also promoted the production of IgM and IgG in addition to the IgE; however, when this clone was carried in culture for several months, this activity for IgM and IgG fell markedly, whereas help for IgE decreased less. We have speculated that these two T cell clones, with unusual activation properties, may be representative of a subset of atopic T cells responsible for maintaining the circulating B cells that spontaneously secrete IgE in vitro in patients with high serum IgE.

B-Lymphocytes↗
PubMed1986

Primary hepatocellular carcinoma localised by a radiolabelled monoclonal antibody.

A rat monoclonal antibody, YPC2/38.8, was selected from a panel of antibodies derived by immunising rats with fresh human colorectal carcinoma. It was found to bind to a 30 000 dalton protein present on the cell surface of normal colon and liver. This protein was increased 10-fold on primary hepatocellular carcinoma (PHC) cells. After labelling with 131I, YPC2/38.8 was shown to localise human PHCs grown as xenografts in immunosuppressed mice. Sixteen patients with PHC were given 1 mg of purified antibody labelled with 1 mCi of 131I by slow intravenous injection. In 8 out of 9 patients with PHC arising in non-cirrhotic livers, good tumour images were obtained on gamma camera or rectilinear scans, but in 7 patients who had developed PHC on the background of established hepatic cirrhosis, no tumour images were seen. Subsequent studies revealed that the 30K antigen recognised by this antibody was present in increased quantity on PHC cells and the regenerating liver cells in cirrhosis. We conclude that YPC2/38.8 may have potential for diagnostic localisation and possibly thence for the selective targeting of drugs or toxins in patients with PHC arising in a liver unaffected by significant parenchymal disease.

Adolescent↗
PubMed1986

Rating reliability for life events and difficulties in the elderly.

The inter-rater reliability of Brown's measure of ongoing difficulties ('severity') is shown to be comparable with that of the measure of life events ('long-term threat') when using data from an elderly subject pool. Test-retest reliabilities for both the life event and difficulty measures are shown to be adequate if based on 'consensus' ratings. The question is raised of generalizability of the concepts of 'threat' and 'severity' across the lifespan.

Adaptation, Psychological↗
PubMed1986

The life satisfaction index--well-being: its internal reliability and factorial composition.

The internal consistency and factorial composition of the eight-item Life Satisfaction Index--Well-being, adapted for use with elderly British samples, were examined. Cross-validation was carried out with a randomly drawn community sample of 155 rural people aged 65-89 years. The scale was found to have acceptable internal reliability, but may require modification.

Aged↗
PubMed1985

Immunoglobulin and C3 levels in maternal and cord blood in Jamaica.

IgG, IgM, IgA and C3 were estimated by radial immunodiffusion (RID) in one hundred paired maternal and cord blood samples. The mean maternal IgG, and IgM, and IgA were 2112 mg/dl, 118 mg/dl and 251 mg/dl, respectively, while in corresponding infants, the mean levels were 2194 mg/dl, 36 mg/dl and 19 mg/dl. Mean cord serum C3 levels was 113 mg/dl, approximately half the maternal level (203 mg/dl). Variation in the gestational age, birth weight, duration of labour and maternal pre-eclamptic toxaemia did not significantly affect the immunoglobulin levels. Seven out of 36 (16%) cord blood with IgM level greater than 36 mg/dl showed either fourfold rise or high antibody titres against one of the TORCH (toxoplasma, rubella, cytomegalovirus and herpes simplex virus) agents. Screening of cord serum for IgM levels can be of particular value in detection of newborn infants with clinically apparent or inapparent intrauterine infections.

Complement C3↗
PubMed1979

Intestinal perforation in ascariasis--case reports.

Two cases of intestinal perforation in association with ascariasis are described. In both cases adult ascarids were found either in the gut or lying free in the peritoneal cavity. Neither patient had typhoid fever, one had Hodgkin's lymphoma. The authors believe that the perforation were directly caused by the ascarids. Both patients died.

Adult↗
PubMed1979

Clinical evaluation of computer processing of liver gamma camera scans.

A prospective study to assess the clinical usefulness of computer processing of liver scans has been carried out on 203 patients. All patients have had six months follow up to confirm the diagnostic accuracy of the scan results. Four presentations have been studied using ROC analysis: (i) original gamma-camera pictures; (ii) processed images obtained using a non-stationary filter; (iii) images processed using nine-point smoothing; (iv) images obtained by linear interpolation at 25 isocount levels of display. It is concluded that pictures obtained by use of a non-stationary filter at 25 isocount levels are superior to a conventional gamma-camera pictures and displays obtained by linear interpolation only. All three are considerably superior to the images obtained by nine-point smoothing in detection of focal space-occupying lesions. Based on the results obtained, a strategy for the rational use of computer processing of gamma-camera liver scans is proposed.

Computers↗