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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↗
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↗
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↗
PubMed1978

The spectrum of paracetamol (acetaminophen) overdose: clinical and epidemiological studies.

In a regional survey of paracetamol overdose, 201 patients were admitted to hospital over 12 months. Chronic alcoholism was present in 10% of cases. Over 25% of patients were females aged 20 years or less. Initial blood paracetamol levels were in the toxic range in 16% and histologically severe liver damage eventually found in 20% of those biopsied. This finding corresponded to a serum aspartate aminotransferase of 600 i.u./l or more. Renal failure severe enough to require peritoneal dialysis developed in 1%. Elevated serum amylase was recorded in 22% of a 108-patient subset. Evidence of myocardial damage was found in 11.6% of an eighty-six patient subset. An unfavourable prognosis was indicated by a prothrombin ratio of 20% or less and hepatic coma, the overall mortality being 3.5%. The apparent safety of this useful analgesic is compromized by its widespread employment in parasuicide. This, the insidious and delayed onset of toxicity in overdose and ineffectiveness of late treatment argues for controlling availability to the general public.

Acetaminophen↗
PubMed1977

Bacterial overgrowth syndrome without "blind loop": A cause for malnutrition in the elderly.

Probable bacterial contamination of the small bowel without an anatomical sump occurred in 5 elderly patients (age 68--94). They presented with severe general deterioration in health rather than with obvious features of malabsorption. This syndrome has not been clearly described before. Bacterial deconjugation of bile salts was indentified by the 14C-glycocholic-acid breath test. Investigations for other causes of malabsorption, including small-bowel biopsy and pancreatic scan, revealed no abnormality. After prolonged ill-health despite an adequate diet in hospital, all 5 subjects made a striking recovery after treatment with antibiotics. This condition may be quite common, particularly in malnourished elderly people.

Age Factors↗
PubMed1977

Occupational vitiligo induced by p-tert-butylphenol, a systemic disease?

Vitiligo, morphologically indistinguishable from true vitiligo, was detected in 54 of 198 men exposed to p-tert-butylphenol (P.T.B.P.) during its manufacture. There is evidence that P.T.B.P. caused vitiligo by a systemic mechanism and that the severity of the disease was related to the intensity of exposure. No association with autoimmune disease was found. Screening for other possible associated disorders revealed mildly abnormal liver-function tests in 6 workers: liver biopsy confirmed liver damage. Of the 144 men exposed to P.T.B.P. who did not have vitiligo, only 2 had any abnormal liver-function tests. It seems possible that the liver damage is related to P.T.B.P.

Chemical Industry↗
PubMed1977

Hepatic drug acetylation and oxidation: effects of aging in man.

The half lives of acetanilide and isoniazid ("model" substrates for oxidation and acetylation respectively) were measured in populations of young (aged 20-35 years) and elderly (aged over 65 years) people. Whereas acetanilide half lives were significantly longer in the elderly, isoniazid half lives were distributed similarly in both populations. The results suggest that liver function does not decline uniformly with age and that heterozygotes for acetylation do not possess survival advantages during their middle years of life.

Acetanilides↗