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Biomedical subjects

J Grange

Publications and source records attributed to J Grange.

At least 19 recordsLinked to original sources
PubMed2001

Tuberculosis in disadvantaged groups.

Tuberculosis remains predominantly a disease of the disadvantaged and marginalized. The incidence of the disease is increasing in many industrially developed countries, particularly among the poor, ethnic minorities, prisoners and other institutionalized persons, and the socially isolated and hard to reach groups. Strengthening of the tuberculosis services is required to care for these groups. Millions of people in the developing nations are disadvantaged by poverty and inequity, and recent health sector reforms have not always been entirely in their interest. A further serious problem is the HIV/AIDS pandemic, which not only facilitates the spread of tuberculosis but, by its associated stigma, leads to delayed treatment seeking and poor adherence to therapy. In recent times, emphasis has moved away from didactic principles of tuberculosis "control" to community-and patient-centered health services, based on analysis of local factors affecting case finding and adherence to therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Tuberculosis.

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Antitubercular Agents↗
PubMed1995

Anti-HIV activity of the combination of didanosine and hydroxyurea in HIV-1-infected individuals.

HIV is known to be present in massive amounts in both resting and actively replicating cells in infected individuals. We tested the combination of didanosine and hydroxyurea, known to suppress viral production in vitro in both of these cell types, in a small number of asymptomatic patients. After 3 months of well tolerated treatment, we observed a large reduction of viral load in the peripheral blood of all 12 patients, down to nonquantifiable levels in 7 of 12 as measured by infectious virus titer, and 6 of 12 as measured by plasma HIV-RNA. In this subgroup of 6 patients, whose baseline HIV-RNA was below 14,000 copies/ml, the median increase in CD4+ count after 90 days of treatment was 244 cells/mm3.

Adult↗
PubMed1994

Therapeutic effects of D-aspartic acid beta-hydroxamate (DAH) on Friend erythroleukemia.

D-aspartic acid beta-hydroxamate (DAH), an aspartic acid analogue, exerts anti-tumoral activity against murine leukemia L5178Y both in vitro and in vivo. We show here that DAH displays activity against Friend leukemia cells (FLC) in vitro: a concentration of 2 mM results in a total inhibition of cell growth. DAH is also active in vivo against Friend virus (FV-P)-induced erythroleukemia. Treatment with DAH, given for 95 days as a single daily i.p. injection to DBA/2 mice 3 days following FV-P inoculation, induced a marked increase of 212% in the mean survival time (MST) of treated animals. Since FV-P-induced erythroleukemia is characterized by the proliferation of mature erythroid precursors, we examined the effect of DAH treatment on erythroid colony-forming cells (CFU-E) and observed that the number of CFU-E per spleen was 30 times lower in DAH-treated mice than in the controls. To gain further insight into the early effects of DAH treatment on the early phase of Friend disease, we examined the effects of short DAH treatment on spleen size, hematocrit and viremia in FV-P-infected mice. DAH treatment initiated 3 days post infection (p.i.) inhibited splenomegaly, prevented virus-induced polycythemia, and reduced serum viremia. Late DAH treatment (18 days p.i.) induced regression of FVP-induced disease as evidenced by reduction of spleen weight.

Animals↗
PubMed1994

Antiproliferative effect of D-aspartic acid beta-hydroxamate (DAH) on Friend virus-infected erythropoietic progenitor cells.

D-aspartic beta-hydroxamate (DAH), an aspartic acid analog, exerts antitumoral activity on murine leukemia L5178Y, both in vitro and in vivo. In this study, we show that DAH is also active in vivo against Friend virus (FV-P)-induced erythroleukemia, and we report the effects of DAH in vivo an in vitro on FV-P target cells, i.e. the mature erythroid colony-forming cells (CFU-E). DAH treatment (2 g/kg/day) given for 95 days as a single daily i.p. injection to DBA/2 mice either 3 or 12 days following inoculation with a high dose (10(3) plaque-forming units) of FV-P resulted in a marked increase in the mean survival time of treated animals (212 and 191%, respectively). Since FV-P elicits spleen enlargement and polycythemia, we examined the effects of DAH on spleen size, spleen-nucleated cell number, and hematocrit, in normal and FV-P infected mice, at different times in the course of continuous DAH treatments. DAH treatment initiated 3 days after viral infection inhibits the virus-induced splenomegaly, with at day 26 p.i. 1.15 x 10(8) and 12.6 x 10(8) nucleated cells per spleen observed in DAH-treated mice and untreated mice respectively, whereas only 1.03 x 10(8) nucleated cells were observed in uninfected mice. Furthermore, DAH prevents virus-induced polycythemia: on day 26, an hematocrit of 39% was measured in DAH-treated mice as compared to 60% in untreated mice. DAH treatment initiated 12 days after viral infection reduces splenomegaly, the number of nucleated spleen cells and the hematocrit of infected mice. DAH treatment initiated 3 days after viral infection prevents the tremendous increase of CFU-E in the spleen of infected mice: on day 11, the spleen of infected mice contained 4.6 x 10(6) CFU-E, while the spleen of treated mice only contained 26 x 10(3) CFU-E, and on day 26 the spleen CFU-E numbers were 45.4 x 10(6) and 1.5 x 10(6) in untreated and treated infected mice, respectively. In control uninfected mice, DAH treatment induced a transient decrease in spleen CFU-E followed by a rebound phenomenon. In vitro, preincubation with DAH inhibits colony formation by FV-P infected CFU-E, at doses starting at 3 mM, as compared to uninfected CFU-E. These data show that DAH inhibits the expression of the retroviral infection, and appears to preferentially inhibit the proliferation of infected target cells (CFU-E) in vivo.

Animals↗
PubMed1993

Comparison between direct binding, competition and agglutination assays in the characterization of polyclonal anti-idiotypes against anti-HBs human monoclonal antibodies.

Polyclonal anti-idiotypic antibodies to human monoclonal anti-HBs antibodies (MoAb1) were raised in rabbits and designated Ab2-H1 and Ab2-H2. These Ab2 were characterized using three assays. A direct binding ELISA evaluated specificity towards a panel of human monoclonal antibodies and gamma globulins. Competition radioimmunoassay (CRIA) revealed Ab2 specificities towards Ab1 antigen binding sites by inhibition of HBsAg/Ab1 binding. Ab2-H1 and Ab2-H2 had comparable reactivities in ELISA and CRIA, whereas, using affinity purified Ab2, a fast (10 min) agglutination test (Spherotest) revealed different Ab1/Ab2 binding properties. Ab2-H1 reacted in this Spherotest with the Ab1 against which it was known to be specific (Ab1-H1), whereas in the same assay Ab2-H2 showed no activity towards the variable regions of the Ab1 used for its production (Ab1-H2). When injected into rabbits Ab2-H1 induced anti-HBs Ab3 antibodies but Ab2-H2 did not, thereby confirming the assay results.

Agglutination Tests↗
PubMed1993

Production and characterization of a monoclonal antibody directed against HTLV-1 p19: use in a specific capture enzyme immunoassay.

An enzyme immunoassay (EIA) was developed for detection of Human T-cell Leukemia Virus antigen in culture supernatants and cell lysates. The assay used a mouse monoclonal antibody against HTLV-I p19 major core protein as capture antibody. It has a sensitivity of 1 microgram/ml of HTLV-I protein, 250 pg/ml of purified recombinant p19 and detected p19 in an 10(-2) diluted supernatant of MT2 infected cell and in a 100 MT2 cells lysate (10(6) cells taken at day 7 of culture). The assay enable us to discriminate between HTLV-I and HTLV-II antigens and is reproducibly negative for supernatants and cell lysates of uninfected cells and of HIV-1 infected cells. The assay was found to be more specific and 10 times more sensitive than the reverse transcriptase (RT) assay, and the EIA test became positive three days earlier than RT assay for the HTLV-I cell lines supernatants.

Animals↗
PubMed1992

Monitoring of urinary excretion of modified nucleosides in cancer patients using a set of six monoclonal antibodies.

Monoclonal antibodies were produced and characterized in order to allow the monitoring of the urinary excretion of six modified nucleosides. The specificity of each antibody was determined and competitive solid-phase enzyme-linked immunoassays were designed, the sensitivity of which lay in the pmol range. Detection and quantitation of 5-methylcytidine (5-MeCyd), 4-acetylcytidine (4-AcCyd), 1-methylinosine (1-MeIno), 1-methyladenosine (1-MeAdo), 7-methylguanosine (7-MeGuo) and pseudouridine (psi-Urd) can be performed in small volumes (70 microliters) of untreated urine. Results can be obtained from as many as 20 different samples, for one molecule, within 3 h. With this technique, values observed for three commonly measured nucleosides in urine from healthy subjects (psi-Urd, 1-MeAdo and 1-MeIno) are in good agreement with those reported by other authors after analysis by high performance liquid chromatography. Results obtained in urine from cancer patients show significantly increased levels of the six haptens quantitated by this immunoassay.

Adult↗
PubMed1991

Anti-tumoral activity of L and D isomers of aspartic acid beta-hydroxamate on L5178Y leukemia.

D and L isomers of aspartic acid beta-hydroxamate (respectively DAH and LAH) were compared for their in vitro and in vivo activity against the murine leukemia L5178Y and their tolerance in vivo in DBA/2 mice. DAH and LAH displayed comparable cytotoxic activity against L5178Y leukemia in vitro. Death of leukemia cells was observed at concentrations above 1.2 mM for both DAH and LAH. High concentrations of L-asparagine partially reversed the growth-inhibitory effects of DAH and LAH on L5178Y cells for concentrations of DAH and LAH lower than 0.6 mM. Intraperitoneal administration of DAH and LAH to mice showed that the LD10, LD50 and LD90 of DAH was 3- to 4-fold greater for DAH than for LAH. DAH was able to eradicate L5178Y tumors in mice without inducing toxic deaths, whereas LAH at comparable doses killed all the animals treated.

Animals↗
PubMed1991

Creatine kinase BB produced by murine hybridomas but not by parental cells.

Creatine kinase BB is the main CK isoenzyme expressed in murine hybridoma cells as assessed by agarose gel electrophoresis whereas it was found neither in splenocytes nor in myeloma cells. The presence of CK BB is a constant finding in all 10 murine hybridomas examined to date irrespective of the specificity of the secreted antibodies.

Animals↗
PubMed1987

Association between Km1 immunoglobulin allotype and pulmonary tuberculosis in Indonesians.

Allotypes were determined in 121 cases of smear-positive pulmonary tuberculosis and 33 healthy controls from Indonesia. It was found that the occurrence of Km1 was significantly lower in patients than in controls (p = 0.011), and that phenotypes lacking G1m (17) and G3m(21) as well as Km1 occurred much more frequently among patients than controls (p = 0.0025). Some evidence for an allotypic influence on the antibody response to mycobacterial antigens was found. A lack of G1m(17) or G3m(21) was associated with increased antibody levels in the IgG2 subclass in control subjects and a lack of Km1 with decreased antibody levels in the IgG4 subclass in patients.

Antibodies, Bacterial↗
PubMed1986

Subdivision of daughter strains of bacille Calmette-Guérin (BCG) according to secreted protein patterns.

In order to identify proteins secreted by live organisms, daughter strains of the Bacillus Calmette-Guérin (BCG) were grown for 4-7 d in a defined medium containing [35S]methionine. Secreted components were then separated by polyacrylamide gel electrophoresis under both denaturing and non-denaturing conditions, and analysed by autoradiography and in an Ambis beta-scanner. The results indicate that BCG daughter strains can be subdivided into two groups according to their secretion of a 46 kDa protein dimer consisting of two similar 23 kDa subunits. High-producer strains (Japanese, Brazilian and Russian) secrete very large quantities of this material, which constitutes approximately 23% of all secreted protein. These findings correlate with earlier studies in which degradation products of the protein dimer may have been identified, and with the data from patterns of cell wall lipids.

Bacterial Proteins↗
PubMed1982

Bacteriological survey of tuberculous lymphadenitis in South-east England: 1973-80.

During the eight years 1973-80 the Public Health Laboratory Service Regional Centre for Tuberculosis Bacteriology received cultures of mycobacteria from 2339 patients with tuberculous lymphadenitis. Of these, 2272 were M tuberculosis (2207 human and 65 bovine strains) and 67 were other mycobacterial species, usually M avium and its intracellulare variant. Disease due to the human strains of M tuberculosis occurred most often in young women of Asian ethnic origin. Many bovine strains isolated from Asian patients differ from the classical bovine type in being sensitive to pyrazinamide: the origin of these strains, whether from other people or from cattle, is unknown. Lymphadenitis due to bovine strains tended to occur in an older age group than the human strains and probably include relatively more cases of reactivation diseases. Infection caused by the other mycobacterial species occurred mainly in young children of European origin. Tuberculosis, therefore, remains an important cause of lymphadenopathy in Britain.

Adolescent↗