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Biomedical subjects

M J Newman

Publications and source records attributed to M J Newman.

88 records · Page 5Linked to original sources

Two closely linked loci and one apparently independent locus code for bovine lymphocyte antigens.

Twenty different antigens have been detected on bovine lymphocytes. Family studies suggested that 19 of the antigens were under the control of two closely-linked loci. The remaining antigen was apparently coded for by an independent locus. The distribution of the antigens in the population also suggested that three loci control the expression of lymphocyte antigens. A co-capping study on two antigens which were inherited together on one haplotype showed that these antigens were expressed on different molecules on the lymphocyte membrane, providing further evidence for the existence of two linked loci.

Animals↗

Purification and reconstitution of functional lactose carrier from Escherichia coli.

The lactose carrier protein of Escherichia coli was purified by a simple procedure employing differential solubilization and ion-exchange chromatography and reconstituted into liposomes by octylglucoside dilution. The proteoliposomes exhibited both membrane potential-driven lactose transport and lactose counterflow. Furthermore, the purified protein was identified as the product of the lac y gene. These and other results demonstrate that the lactose carrier is the only polypeptide species essential for energy-coupled lactose transport and counterflow.

Amino Acids↗

Production of foetally stimulated lymphocytotoxic antibodies by multiparous cows.

Serum samples were collected monthly from second gestation cows and examined for the presence of lymphocytotoxic antibodies. Of 25 cows studied 16 (64%) raised antibodies during or immediately after second gestation. Ten of these cows (40%) raised antibodies during gestation, some as early as 5 months before parturition. Reactors which had had first-gestation reactivity responded earlier, but had peak antibody titers no higher than cows without observable first gestation reactions. Cows with antibodies of similar specificity in the first two gestations responded earlier than those with different antibody specificities. Regardless of the time of first antibody detrection, peak titers were usually achieved during the first month postpartum. Antibody persistence increased with parity. Among cows of all ages sampled at random times, there was a linear relationship of serum reactivity to cow age.

Animals↗

Allogeneic antibody response in cattle.

Antibody responses following immunization with allogeneic bovine lymphocytes, goose red blood cells (GRBC), and ovalbumin (given IV) were studied in 20 heifers. Antibody to GRBC was detectable by 4 to 9 days in all heifers and followed the characteristic pattern of a low-titer primary response which was predominantly immunoglobulin (Ig) M, whereas a high titer IgG secondary response was observed. The dose of ovalbumin used failed to elicit a detectable antibody response. An immune response to allogeneic lymphocytes was observed, but it differed from the GRBC response. Cytotoxic antibody directed against lymphocytes was detectable by day 14 in 5 of the heifers. Five others responded by days 17 to 24 after secondary immunization. The responses were of low titer and predominantly IgM, after both primary and secondary immunizations. The time of antibody appearance and titers varied between heifers and was not dependent on differences at the major histocompatibility complex (BoLA) between heifers and immunizing lymphocytes. Cytotoxic antibody reacted with both B and T lymphocytes and appeared to recognize the serologically defined BoLA antigens. Noncytotoxic alloantibody was detected in the serum of 1 heifer and appeared to be directed against a subpopulation of lymphocytes, possibly those bearing Ia-like antigens.

Animals↗

Stimulation of maternal anti-lymphocyte antibodies by first gestation bovine fetuses.

Serum samples were taken from first-calf dairy heifers, twice weekly, for a period of 4 weeks, starting 2 weeks before the estimated date of parturition and continuing for 2 weeks post partum. Samples from each heifer were incubated with lymphocytes from the respective calf when possible, and from a 36-cow donow panel, in the presence of complement. Of the 31 heifers tested, 11 (35%) raised detectable lymphocytotoxic antibodies against fetal antigens; 3 had detectable, but weak, antibody titres as early as 10 days before parturition while the others had stronger antibody reactivity which was detectable 4--12 days post partum. The titres of these post-partum antibodies peaked 4--7 days after they were first detected. Sephadex G-200 fractionation of the sample taken at 2 weeks post partum showed that 11 responding cows had antilymphocytic activity in the IgG fraction while 8 also had IgM antibody activity.

Animals↗

Analysis of alloantisera against bovine lymphocytes. Joint report of the 1st International Bovine Lymphocyte Antigen (BoLA) workshop.

The results and agreements of the 1 international BoLA workshop, held in Edinburgh, Scotland in August 1978, are reported. Most of these concern the results from a comparison test of 249 alloantisera to bovine lymphocytes, the antisera being contributed by 9 laboratories. These sera were compared directly in Edinburgh on a panel of lymphocytes from 130 cattle of 21 breeds. In the microlymphocytotoxicity test used 75% of the sera reacted. Sixty eight of these sera were grouped into clusters according to their reaction patterns against the lymphocyte panel. Eleven of these clusters were clearly defined and were given workshop BoLA designations. In addition 22 sera were assigned to subgroups of the agreed clusters. There was no evidence that the method of production of the sera had any effect on their specificity. Although genetic data was not available, the phenotypes of the test panel of lymphocytes are consistent with the clusters detecting antigens controlled by multiple alleles at a single autosomal locus. It was agreed to name the genetic region where this putative locus is located BoLA (bovine lymphocyte antigen).

Animals↗

Production of foetally stimulated lymphocytotoxic antibodies by primiparous cows.

Serum samples from groups of heifers at different pregnancy-related stages (preconception, month of pregnancy, and postpartum) were examined for the presence of lymphocytotoxic antibodies. Only a few weak and transitory antibodies were observed before or during the first pregnancy. These did not appear to be foetally stimulated. Strong or medium strength antibodies were detected in first or second month postpartum samples from 8 of 27 heifers (30%). The reactive sera were in every case reactive with the offspring of the cows from which the respective sera were collected.

Animals↗

Permease-specific mutations in Salmonella typhimurium and Escherichia coli that release the glycerol, maltose, melibiose, and lactose transport systems from regulation by the phosphoenolpyruvate:sugar phosphotransferase system.

Several carbohydrate permease systems in Salmonella typhimurium and Escherichia coli are sensitive to regulation by the phosphoenolpyruvate:sugar phosphotransferase system. Mutant Salmonella strains were isolated in which individual transport systems had been rendered insensitive to regulation by sugar substrates of the phosphotransferase system. In one such strain, glycerol uptake was insensitive to regulation; in another, the maltose transport system was resistant to inhibition; and in a third, the regulatory mutation specifically rendered the melibiose permease insensitive to regulation. An analogous mutation in E. coli abolished inhibition of the transport of beta-galactosides via the lactose permease system. The mutations were mapped near the genes which code for the affected transport proteins. The regulatory mutations rendered utilization of the particular carbohydrates resistant to inhibition and synthesis of the corresponding catabolic enzymes partially insensitive to repressive control by sugar substrates of the phosphotransferase system. Studies of repression of beta-galactosidase synthesis in E. coli were conducted with both lactose and isopropyl beta-thiogalactoside as exogenous sources of inducer. Employing high concentrations of isopropyl beta-thiogalactoside, repression of beta-galactosidase synthesis was not altered by the lactose-specific transport regulation-resistant mutation. By contrast, the more severe repression observed with lactose as the exogenous source of inducer was partially abolished by this regulatory mutation. The results support the conclusions that several transport systems, including the lactose permease system, are subject to allosteric regulation and that inhibition of inducer uptake is a primary cause of the repression of catabolic enzyme synthesis.

Biological Transport↗

Direct transfer of the phosphoryl moiety of mannitol 1-phosphate to [14C]mannitol catalyzed by the enzyme II complexes of the phosphoenolpyruvate: mannitol phosphotransferase systems in Spirochaeta aurantia and Salmonella typhimurium.

Spirochaeta aurantia possesses a phosphoenolpyruvate:mannitol phosphotransferase system which catalyzes the transmembrane transport and phosphorylation of mannitol. In vitro studies showed that both phosphoenolpyruvate and mannitol 1-phosphate could serve as phosphate donors. The phosphoenolpyruvate-dependent reaction required two soluble proteins, Enzyme SI and HPr, and an integral membrane complex, Enzyme SII. Only Enzyme SII was required for the mannitol 1-phosphate-dependent reaction. Enzyme II-dependent transphosphorylation of sugars was also demonstrated in eubacterial extracts. The results lead to the suggestion that the Enzyme II complexes of bacterial phosphotransferase systems possess nonoverlapping binding sites for sugar and sugar phosphate.

Edetic Acid↗

Vaginal flora of first time urban family planning attendants in Accra, Ghana.

OBJECTIVE: To determine the vaginal flora of first time urban Family Planning clients at Korle-Bu Teaching Hospital and to assess its implications for the contraceptive choices made. DESIGN: A cross sectional study. METHODS: A standardized questionnaire surveying the sociodemographic characteristics and the choice of Family Planning method was administered to 100 clients at the Korle Bu Teaching Hospital between March and September 2001. High vaginal and endocervical swabs were also taken during the inspection of the vagina and cervix using a sterile bivalve speculum. The specimens were transported in Amies transport medium to the Microbiology laboratory for processing. RESULTS: The age range of the clients was 19-48 years with a modal age of 28 years. Ninety-six percent of them were married while 86% lived in urban slums. Sixty-three percent were sure of their last menstrual period. Potential pathogens were isolated from culture in 56% of the clients. Organisms causing bacterial vaginosis were the most prevalent in their genital tract. The intrauterine contraceptive device (IUCD) was the most common Family Planning method chosen, followed by the Norplant and the Depo-Provera injections. Potential pathogens were isolated from culture in 50% of those who chose the IUCD. CONCLUSION: Potential pathogens were isolated from culture in 56% of these first-time clients and organisms causing bacterial vaginosis were the most prevalent in the genital tract. It is suggested that Family Planning clients who screened positive for potential pathogens and opt for the IUCD should be considered for prophylactic antibiotics at insertion.

Adult↗

Multiple-resistant Salmonella group G outbreak in a neonatal intensive care unit.

An outbreak of nosocomial infection due to multiple-resistant Salmonella Group "G' infection in a neonatal intensive care unit in a temporary ward is reported. It started with five cases of Septicaemia and one case of meningitis over a period of about six weeks. Investigation of the outbreak resulted in isolation of a multiple-resistant Salmonella Group G from the rectal swab of 21 out of 72 babies (29%). Surveillance culture from staff yielded two fully-sensitive salmonella species. Stool culture from mother of colonised babies were all negative. Environmental cultures from the nursery grew multiple-resistant Salmonella Group G from three of four incubator mattresses and also from the radiant warmer. Institution of strict aseptic measures, followed by closure of the ward was able to stop the epidemic.

Cross Infection↗

The reversal of multidrug resistance in multicellular tumor spheroids by SDZ PSC 833.

Multidrug resistance (MDR) is a major impediment to the effective treatment of cancer. We have used multicellular tumor spheroids (MTS) as a model to investigate whether MDR can be reversed in a three dimensional structure. MTS are tightly associated aggregates of tumor cells that exhibit many of the properties of solid tumors. A human MDR breast carcinoma cell line was selected by exposure to taxol under monolayer conditions. The sensitive (parental) and drug-resistant phenotypes were retained when the cells were grown as MTS. Thus, the three dimensional conditions in this novel model system did not affect the MDR phenotype. SDZ PSC 833 is an efficient MDR reversing agent as determined under monolayer conditions and is currently being evaluated in clinical trials. Resistance to taxol and doxorubicin of the MDR cells grown as MTS was almost completely reversed by SDZ PSC 833. Our results suggest that SDZ PSC 833 has the potential to reverse the MDR phenotype in solid tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗