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Biomedical subjects

J Thompson

Publications and source records attributed to J Thompson.

At least 631 records · Page 35Linked to original sources

Methylation of 16S ribosomal RNA and resistance to the aminoglycoside antibiotics gentamicin and kanamycin determined by DNA from the gentamicin-producer, Micromonospora purpurea.

When DNA fragments from Micromonospora purpurea (the producer of gentamicin) were cloned in Streptomyces lividans, a gentamicin-resistant strain was obtained in which the ribosomes were highly resistant both to gentamicin and to kanamycin. Reconstitution analysis revealed that such resistance resulted from some property of their 16S RNA. Extracts from the clone contained methylase activity which acted on 16S RNA within E. coli 30S ribosomal subunits and rendered them resistant to gentamicin and kanamycin.

DNA, Bacterial↗

Role of granulocytes and monocytes in the prevention and therapy of experimental Staphylococcus epidermidis endocarditis in rabbits.

Rabbits with endocarditis caused by Staphylococcus epidermidis were studied to determine the parts played by granulocytes and monocytes in the prevention or outcome of therapy with cloxacillin. Both monocytes and granulocytes influenced prophylaxis with cloxacillin. The amount of cloxacillin needed to prevent infection in 50% of the rabbits was significantly less in control rabbits than in those selectively depleted of monocytes, as it was also in rabbits selectively depleted of monocytes compared with those that had both granulocytopenia and monocytopenia. Granulocytes strongly potentiated the effect of cloxacillin during prophylaxis, whereas the contribution of monocytes was merely additive. Monocytes also contributed to the effect of therapy with cloxacillin, partially via a cloxacillin-independent mechanism and partially by potentiation of the effect of cloxacillin. Granulocytes did not appear to affect cloxacillin therapy. Results of this study suggest that currently used regimens for prophylaxis and treatment of S. epidermidis endocarditis may need to be adjusted for neutropenic patients.

Animals↗

Simultaneous administration of live, attenuated influenza A vaccines representing different serotypes.

Two live, attenuated cold-adapted influenza A vaccines representing current H1N1 and H3N2 serotypes were simultaneously administered intranasally to doubly seronegative children. No clinical illness resulted. Characterization of virus shedding demonstrated shedding of both original vaccine strains and of reassortant virus with the H3N1 and H1N2 phenotype. A serum immune response to both serotypes was demonstrated. The successful simultaneous administration of two influenza A vaccine strains enhances the potential usefulness of this approach to influenza prophylaxis.

Antibodies, Viral↗

Monoclonal antibodies as probes of epithelial membrane polarization.

Monoclonal antibodies directed against antigens in the apical plasma membrane of the toad kidney epithelial cell line A6 were produced to probe the phenomena that underlie the genesis and maintenance of epithelial polarity. Two of these antibodies, 17D7 and 18C3, were selected for detailed study here. 17D7 is directed against a 23-kD peptide found on both the apical and basolateral surfaces of the A6 epithelium whereas 18C3 recognizes a lipid localized to the apical membrane only. This novel observation of an apically localized epithelial lipid species indicates the existence of a specific sorting and insertion process for this, and perhaps other, epithelial plasma membrane lipids. The antibody-antigen complexes formed by both these monoclonal antibodies are rapidly internalized by the A6 cells, but only the 18C3-antigen complex is recycled to the plasma membrane. In contrast to the apical localization of the free antigen, however, the 18C3-antigen complex is recycled to both the apical and basolateral surface of the epithelium, which indicates that monoclonal antibody binding interferes in some way with the normal sorting process for this apical lipid antigen.

Animals↗

Use of influenza A virus vaccines in seronegative children: live cold-adapted versus inactivated whole virus.

We report the safety and antigenicity of influenza A vaccines in seronegative children one to seven years of age. A natural H1N1 challenge that occurred shortly after completion of the vaccination program permitted an evaluation of efficacy. Twenty-eight subjects were inoculated with live cold-adapted (ca) influenza A/Washington/897/80 (H3N2), 29 with ca influenza A/California/10/78 (H1N1), 24 with inactivated whole-virus influenza A/Bangkok/79 (H3N2), and 30 with a placebo. The ca vaccines were well tolerated, whereas the inactivated vaccine caused adverse reactions in about one-third of the children. Fifty-seven percent of the ca H1N1 recipients showed serological responses, contrasted with 84% and 100% of subjects receiving the ca or inactivated H3N2 vaccines, respectively. None of the 16 children with induced H1N1 antibody developed clinically apparent influenza-like illness, compared with eleven of the 51 initially seronegative children who did not receive the ca H1N1 vaccine and with four of the 12 who failed to respond. Results of the efficacy field trial suggest protection against infection and symptomatic illness in children inoculated with ca H1N1, despite its failure to stimulate high levels of hemagglutinin-inhibiting antibody.

Antibodies, Viral↗

Factors influencing the diagnosis of mental disorder among primary care patients.

Understanding the role primary care physicians play in the recognition and management of mental disorder among their patients is a research topic that has assumed considerable importance because of the high prevalence combined with low recognition of mental morbidity in primary care settings. Patient characteristics that influence diagnostic patterns have been one important focus of this research. This paper presents data from a study in two primary care departments in a large comprehensive health care clinic in central Wisconsin. During a 3-month period, 1,452 attenders at these clinics were assessed using a brief psychiatric screening scale, and special study forms were completed by the primary care clinicians. Consistent with previous research, reason for visit, psychiatric symptoms, and prior knowledge of the patient are significant predictors of physician diagnosis of mental disorder. Additionally, pattern of physician practice, as represented by differences between the two types of clinics, was a strong predictor of both diagnosis and treatment. The lack of significant effects of sex and previous medical utilization is contrary to previous research. Key words: mental disorders; diagnosis; primary care.

Adult↗

Lactose metabolism in Streptococcus lactis: studies with a mutant lacking glucokinase and mannose-phosphotransferase activities.

A mutant of Streptococcus lactis 133 has been isolated that lacks both glucokinase and phosphoenolpyruvate-dependent mannose-phosphotransferase (mannose-PTS) activities. The double mutant S. lactis 133 mannose-PTSd GK- is unable to utilize either exogenously supplied or intracellularly generated glucose for growth. Fluorographic analyses of metabolites formed during the metabolism of [14C]lactose labeled specifically in the glucose or galactosyl moiety established that the cells were unable to phosphorylate intracellular glucose. However, cells of S. lactis 133 mannose-PTSd GK- readily metabolized intracellular glucose 6-phosphate, and the growth rates and cell yield of the mutant and parental strains on sucrose were the same. During growth on lactose, S. lactis 133 mannose-PTSd GK- fermented only the galactose moiety of the disaccharide, and 1 mol of glucose was generated per mol of lactose consumed. For an equivalent concentration of lactose, the cell yield of the mutant was 50% that of the wild type. The specific rate of lactose utilization by growing cells of S. lactis 133 mannose-PTSd GK- was ca. 50% greater than that of the wild type, but the cell doubling times were 70 and 47 min, respectively. High-resolution 31P nuclear magnetic resonance studies of lactose transport by starved cells of S. lactis 133 and S. lactis 133 mannose-PTSd GK- showed that the latter cells contained elevated lactose-PTS activity. Throughout exponential growth on lactose, the mutant maintained an intracellular steady-state glucose concentration of 100 mM. We conclude from our data that phosphorylation of glucose by S. lactis 133 can be mediated by only two mechanisms: (i) via ATP-dependent glucokinase, and (ii) by the phosphoenolpyruvate-dependent mannose-PTS system.

Biological Transport↗

Intracellular phosphorylation of glucose analogs via the phosphoenolpyruvate: mannose-phosphotransferase system in Streptococcus lactis.

The bacterial phosphoenolpyruvate:sugar-phosphotransferase system (PTS) mediates the vectorial translocation and concomitant phosphorylation of sugars. The question arises of whether the PTS can also mediate the phosphorylation of intracellular sugars. To investigate this possibility in Streptococcus lactis 133, lactose derivatives have been prepared containing 14C-labeled 2-deoxy-glucose (2DG), 2-deoxy-2-fluoro-D-glucose (2FG), or alpha-methylglucoside as the aglycon substituent of the disaccharide. Two of the compounds, beta-O-D-galactopyranosyl-(1,4')-2'-deoxy-D-glucopyranose (2'D-lactose) and beta-O-D-galactopyranosyl-(1,4')-2'-deoxy-2'-fluoro-D-glucopyranose (2'F-lactose), were high-affinity substrates of the lactose-PTS. After translocation, the radiolabeled 2'F-lactose 6-phosphate (2'F-lactose-6P) and 2'D-lactose-6P derivatives were hydrolyzed by P-beta-galactoside-galactohydrolase to galactose-6P and either [14C]2FG or [14C]2DG, respectively. Thereafter, the glucose analogs appeared in the medium, but the rates of sugar exit from mannose-PTS-defective mutants were greater than those determined in the parent strain. Unexpectedly, the results of kinetic studies and quantitative analyses of intracellular products in S. lactis 133 showed that initially (and before exit) the glucose analogs existed primarily in phosphorylated form. Furthermore, the production of intracellular [14C]2FG-6P and [14C]2DG-6P (during uptake of the lactose analogs) continued when the possibility for reentry of [14C]2FG and 2DG was precluded by addition of mannose-PTS inhibitors (N-acetylglucosamine or N-acetylmannosamine) to the medium. By contrast, (i) only [14C]2DG, [14C]2FG, and trace amounts of [14C]2FG-6P were found in cells of a mannose-PTS-defective mutant, and (ii) only [14C]2FG and [14C]2DG were present in cells of a double mutant lacking both mannose-PTS and glucokinase activities. We conclude from these data that the mannose-PTS can effect the intracellular phosphorylation of glucose and its analogs in S. lactis 133.

Biological Transport↗

Characterization of a membrane-regulated sugar phosphate phosphohydrolase from Lactobacillus casei.

One of the key components of the futile xylitol cycle of Lactobacillus casei Cl-16 is a phosphatase which dephosphorylates xylitol 5-phosphate to xylitol prior to the expulsion of the pentitol from cells. This enzyme has been partially purified and characterized. The phosphatase is active against a variety of four-, five-, and six-carbon sugars and sugar alcohols phosphorylated at the terminal 4, 5, and 6 positions, respectively, but exhibits little or no affinity for substrates phosphorylated at the C-1 position. The enzyme has an apparent molecular weight of 62,000 and a pH optimum between 5.5 and 6, and it requires a divalent cation (Mg2+) for maximal activity. A single protein band, exhibiting phosphatase activity, was excised from polyacrylamide gels and used to prepare antiphosphatase sera in rabbits. The antiserum was used to detect the enzyme on polyacrylamide gels and to determine the molecular weight of the monomer on sodium dodecyl sulfate-polyacrylamide gels. With a subunit molecular weight of 32,000, the native enzyme appears to be a dimer. Phosphatase activity and substrate specificity are regulated by some component associated with the cytoplasmic membrane.

Cell Membrane↗

Rectal temperature after marathon running.

Rectal temperature was measured in 62 male runners who competed in the 1983 Dundee marathon race: all measurements were made immediately after the race. Competitors' times were noted at 5, 10, 15 and 20 miles (8.0, 16.1, 24.1, 32.2 km) and at the finish (26.2 miles, 42.2 km). Mean finishing time of the group was 3 hr 33 min +/- 48 min (mean +/- S.D.; range = 2 hr 17 min-5 hr 11 min). Mean running speed of the group decreased progressively as the distance covered increased. Mean post-race rectal temperature was 38.7 +/- 0.9 degrees C (range 35.6-40.3 degrees C). The post-race temperature was correlated (p less than 0.01) with the time taken to cover the last 6.2 miles (10 km) of the race, but not with the overall finishing time (p greater than 0.05). Only the fastest runners were able to maintain an approximately constant pace throughout the race, whereas the slower runners slowed down progressively. The runners with the highest post-race temperature, although not necessarily the fastest runners, also tended to maintain a steady pace throughout. The runners with the lowest post-race temperature slowed down markedly only over the last 6.2 mile section of the race. The results clearly indicate that runners forced by fatigue or injury to slow down in the latter stages of races held at low ambient temperatures may already be hypothermic or at serious risk of hypothermia.

Adult↗

Changes in circulating immune complex concentrations and antibody titres during treatment of Q fever endocarditis.

Serum samples from 20 patients with Q fever endocarditis were tested for the presence of circulating immune complexes to see whether their concentrations correlated with antibody titres during treatment and whether they could be used to monitor the response to antimicrobial treatment. Circulating immune complexes were found in all 20 patients. The concentrations in 15 patients correlated with either or both of the Q fever phase 1 and phase 2 antibody titres obtained during treatment. In the other five patients no correlation with the antibody titres was found. There was no association between circulating immune complex concentrations and clinical response to treatment.

Adult↗

Exercise training and "ventilation threshold" in elderly.

Dynamic exercise training of the elderly increases maximal O2 uptake (VO2max); however, the effects of training on the ventilation threshold (VET) have not been studied. VET was identified as the final point before the ventilatory equivalent for O2 (VE/VO2) increased, without an increase in the ventilatory equivalent for CO2 (VE/VCO2). Inactive elderly males (mean age, 62 yr) were randomly assigned to a control (C, n = 44) or activity (A, n = 45) group. VO2max and VET were determined from an incremental treadmill test. Initial VO2max was not different between the C (2.34 +/- 0.42 l X min-1) and A (2.28 +/- 0.44 l X min-1) groups, nor was there a significant difference in the VO2 at the VET (C = 1.39 +/- 0.26 l X min-1; A = 1.31 +/- 0.23 l X min-1). The activity group trained for 30 min/day, 3 days/wk at an intensity of approximately 65-80% of VO2max. After 1 yr of training the activity group exhibited an 18% increase in VO2max (A = 2.70 +/- 0.54 l X min-1), but the change in VET was not significant (A = 1.39 +/- 0.28 l X min-1). There was no significant change in VO2max (C = 2.45 +/- 0.68 l X min-1) or VET (C = 1.38 +/- 0.31 l X min-1) in the control group. VET/VO2max declined significantly in the activity group (from 58 to 52% of VO2max). Change in VET/VO2max with training was not correlated with the initial VO2max value. We conclude that increases in aerobic capacity are more readily effected than alterations of the VET in elderly subjects.

Humans↗

Cisplatin combination chemotherapy versus chlorambucil in advanced ovarian carcinoma: mature results of a randomized trial.

A randomized study to compare the efficacy of combination chemotherapy (cisplatin, doxorubicin, cyclophosphamide: PACe) with chlorambucil (CB) in International Federation of Gynecology and Obstetrics (FIGO) stage III and IV ovarian carcinoma was conducted between May 1979 and October 1983. Patients failing initial CB were subsequently eligible for treatment with PACe. Eighty-nine patients were randomized and 85 were eligible for analysis; as of date, 72 of these patients have died. The majority of patients in this study had bulky residual disease after their initial laparotomy (76%). Complete response (CR) was documented by a second laparotomy after five cycles of combination therapy or 6 to 12 months alkylating agent therapy. The overall response rate (CR plus partial response [PR]) for the combination (PACe, 68%) was significantly higher (P = .0004) than that for the chlorambucil (CB, 26%). However, the median survival was not improved (PACe, 13 months; CB, 11 months) and the survival curves were not significantly different (log rank test P = .25). The results of this study are comparable to preliminary data reported from other similar randomized studies. PACe, as administered in this study, is not indicated as routine therapy in patients with bulky residual ovarian carcinoma.

Actuarial Analysis↗

Bluetongue virus-induced interferon in cattle.

Calves were inoculated IV with bluetongue virus (BTV), serotype 10. Titers of interferon (IFN) in serum and BTV in peripheral blood were determined. All inoculated calves produced circulating IFN that persisted for 2 to 4 days. Highest titers of BTV in peripheral blood were present after serum IFN was no longer detected. The persistence of BTV in peripheral blood, as compared with the transient IFN response, indicated that IFN was most important in the initial antiviral response of cattle to BTV infection. Bluetongue virus is probably not a suitable model inducer of circulating IFN in cattle because the profound neutropenia that accompanied BTV infection may predispose cattle to infections with other agents.

Animals↗

Adenovirus infections in young children.

The importance of adenovirus in initiating respiratory disease in young children is stressed in this report. The incidence, clinical illness, asymptomatic carriage, and serologic response of acute adenovirus-associated infection are described in a carefully followed cohort of normal children cultured with each episode of febrile respiratory illness. During a 6-year period, 8.2% of 1,416 nasal washings obtained from sick infants and children less than 7 years of age yielded adenovirus. Adenoviruses were isolated from only 1/174 (0.6%) cultures taken from well children. Typing of 98 isolates showed 81% to be types 1 or 2. A greater than or equal to fourfold rise in neutralizing titer was seen in 45/59 (76%) sampled. In a subset of the cohort observed for 2-week periods in a day care setting, 14 of 21 well children (67%) exposed to symptomatic children with adenovirus infection developed febrile respiratory symptoms and shedding of the same serotype within 2 weeks of exposure. This study confirms that adenovirus has a high attack rate and causes significant respiratory disease in young children.

Adenoviridae Infections↗

A multicenter study of the epidemiology of hepatitis B in anesthesia residents.

Practicing anesthesiologists are at high risk of hepatitis B infection, but the risk for anesthesia residents has not been assessed. Anesthesia residents at seven universities were surveyed to study the epidemiology of hepatitis B in these trainees. Hepatitis B virus markers in serum were measured and data from questionnaires were used to determine characteristics of anesthetic practice, effectiveness of strategies for hepatitis B virus infection control, and nonvocational hepatitis B risk factors. Of 267 participants, 12.7% (range of the seven centers, 8.7%-22.7%) had serum markers for hepatitis B virus. The seropositivity (17.8%) in anesthesia residents who had completed more than 12 months of nonanesthesia postgraduate clinical training, or who had practiced medicine in another specialty prior to anesthesia, was greater than in the other trainees (9.4%). Based on their risk and the ineffectiveness of current control measures, anesthesia residents who lack hepatitis B virus immunity should be vaccinated prior to or as early as possible in their training.

Anesthesiology↗