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Biomedical subjects

J F Brown

Publications and source records attributed to J F Brown.

At least 73 records · Page 4Linked to original sources
PubMed1988

Effects of murine recombinant interleukin 1 alpha on the host response to bacterial infection.

The effects of exogenously administered rIL-1 alpha on elimination of viable listeriae from the liver and spleen during the course of a primary Listeria monocytogenes infection was studied. Similar numbers of L. monocytogenes were recovered from rIL-1 alpha-treated and control mice at up to 24 h after infection; however, by 48 h after infection more than 1 log10 fewer viable L. monocytogenes were recovered from the spleens of rIL-1 alpha-treated mice than from Listeria-infected controls. The difference in bacterial burden between IL-1 alpha-treated and control mice increased with time; by 7 days after infection viable L. monocytogenes had been eliminated from most rIL-1 alpha-treated mice, whereas control mice still harbored 10(4) to 10(5) L. monocytogenes per spleen and liver. Histopathologic examination confirmed that rIL-1 alpha-treated mice suffered considerably less damage to the spleen, liver, lung, and brain than did control mice. To determine whether rIL-1 alpha-mediated protection indirectly by augmenting the release of other cytokines, we determined serum levels of colony-stimulating activity and IFN activity in rIL-1 alpha-treated and control Listeria-infected mice. Treatment with rIL-alpha elicited an early burst of serum colony-stimulating activity as compared with sera from Listeria-infected control mice. These data suggest that exogenous administration of rIL-1 initiates release of colony-stimulating activity, and perhaps other cytokines, that accelerate the protective response of the infected host. Prophylactic augmentation of antimicrobial resistance by administration of rIL-1 alpha may be worthy of further evaluation.

Animals↗
PubMed1987

Purified human and recombinant murine interleukin-1 alpha induced accumulation of inflammatory peritoneal neutrophils and mononuclear phagocytes: possible contributions to antibacterial resistance.

Interleukin-1 (IL-1) mediates a number of proinflammatory biological responses that are thought to contribute to antibacterial resistance. In the present study we examined the ability of IL-1 to recruit inflammatory neutrophils and mononuclear phagocytes in vivo; a function that has been reported to be closely related to antibacterial resistance. Intraperitoneal injection of small amounts (1-10 LAF units) of purified human or recombinant murine IL-1 alpha (rIL-alpha) resulted in an increased influx of inflammatory neutrophils into the peritoneal cavity that peaked at 4-14 h after IL-1 injection. A small but consistent increase in peritoneal macrophages also was observed at 72 h after rIL-1 alpha injection. The ability of rIL-1 alpha to induce neutrophil accumulation was uninfluenced by polymyxin B, was sensitive to heat treatment (100 degrees C for 1 h), and was observed after i.p. injection into LPS-nonresponsive C3H/HeJ mice. These three lines of evidence suggested that contaminating LPS did not contribute substantially to rIL-1 alpha induced accumulation of neutrophils. Treatment of mice with indomethacin or nordihydroguaiaretic acid did not abrogate rIL-1 alpha induced neutrophil accumulation. Mice injected i.p. with increasing amounts of rIL-1 alpha demonstrated a corresponding enhancement of their resistance to an i.p. L. monocytogenes challenge 4 h later, thus suggesting that IL-1 mediated inflammatory phagocyte accumulation may contribute in part to nonspecific antibacterial resistance.

Animals↗
PubMed1987

Extensive degradation of Aroclors and environmentally transformed polychlorinated biphenyls by Alcaligenes eutrophus H850.

We have isolated and characterized a strain of Alcaligenes eurtrophus, designated H850, that rapidly degrades a broad and unusual spectrum of polychlorinated biphenyls (PCBs) including many tetra- and pentachlorobiphenyls and several hexachlorobiphenyls. This strain, which was isolated from PCB-containing dredge spoils by enrichment on biphenyl, grows well on biphenyl and 2-chlorobiphenyl but poorly on 3- and 4-chlorobiphenyl. Capillary gas-chromatographic analysis showed that biphenyl-grown resting cells of H850 degraded the components of 38 of the 41 largest peaks of Aroclor 1242 and 15 of the 44 largest peaks of Aroclor 1254, resulting in an overall reduction of PCBs by 81% for Aroclor 1242 (10 ppm) and 35% for Aroclor 1254 (10 ppm) in 2 days. Furthermore, H850 metabolized the predominantly ortho-substituted PCB congeners that resulted from the environmental transformation of the more highly chlorinated congeners of Aroclor 1242 by the upper Hudson River anaerobic meta-, para-dechlorination agent system C (J. F. Brown, R. E. Wagner, Jr., D. L. Bedard, M. J. Brennan, J. C. Carnahan, R. J. May, and J. J. Tofflemire, Northeast Environ. Sci. 3:167-179, 1984). The congener selectivity patterns indicate that a two-step process consisting of anaerobic dechlorination followed by oxidation by H850 can effectively degrade all of the congeners in Aroclor 1242 and possibly all those in Aroclor 1254.

Alcaligenes↗
PubMed1987

"Haemophilus somnus," a facultative intracellular pathogen of bovine mononuclear phagocytes.

We have reported previously that bovine neutrophils are unable to kill the bovine respiratory pathogen "Haemophilus somnus." In the present study we expanded our efforts and examined the interaction of bovine mononuclear phagocytes with this important veterinary pathogen. Bovine alveolar macrophages and blood monocytes ingested but did not kill opsonized "Haemophilus somnus" in vitro, whereas these same cells ingested and killed opsonized Escherichia coli. Because this suggested that "H. somnus" was a facultative intracellular pathogen, we developed an assay to monitor the intracellular fate of ingested "H. somnus" within bovine monocytes. Our results indicated that ingested "H. somnus" multiplied within bovine monocytes (1- to 2-log10 increase in 4 h); equivalent intracellular growth was noted for both a laboratory strain and a recent field isolate of "H. somnus." Bovine monocytes killed ingested E. coli (1- to 2-log10 decrease in 4 h) under the same assay conditions that were used to follow intracellular growth of "H. somnus," thus indicating that the assay conditions did not induce a generalized defect in monocyte antibacterial activity. Light and electron microscopic examination of "H. somnus"-infected monocytes confirmed that intracellular growth had occurred. We did not observe an obvious correlation between the release of superoxide anion from bovine mononuclear phagocytes that had ingested opsonized "H. somnus" and E. coli and the subsequent intracellular survival of the bacteria. The results of this study suggest that infected mononuclear phagocytes sustain "H. somnus" infections in cattle and thus contribute to the subacute to chronic clinical course that has been reported.

Animals↗
PubMed1987

Recombinant murine interleukin-1 alpha enhancement of nonspecific antibacterial resistance.

In this study we report that treatment with recombinant murine interleukin-1 alpha (rIL-1 alpha) significantly enhanced the resistance of mice to infection by the facultative intracellular pathogen Listeria monocytogenes. The greatest level of protection was observed at a dose of 1,000 lymphocyte-activating factor units (approximately 0.17 micrograms) of rIL-1 alpha per mouse. Although rIL-1 alpha enhanced antibacterial resistance when administered either intravenously or intraperitoneally, greater protection was observed when the rIL-1 alpha and the L. monocytogenes challenge were given by the same parenteral route. When the intravenous route was used, antibacterial resistance was maximal when the rIL-1 alpha and L. monocytogenes were injected concomitantly. In contrast, intraperitoneal administration of rIL-1 alpha was most effective when given 48 h before an intraperitoneal L. monocytogenes challenge. Based on the following lines of evidence, we concluded that contaminating lipopolysaccharide (LPS) was unlikely to be responsible for the enhanced antibacterial resistance that was observed: (i) LPS was not detectable (less than 0.2 ng/ml by the lysate assay) at the concentration of rIL-1 alpha that was injected; (ii) polymyxin B did not abrogate rIL-1 alpha-enhanced antibacterial resistance; (iii) rIL-1 alpha treatment enhanced the antibacterial resistance of LPS-nonresponsive C3H/HeJ mice; and (iv) injection of up to 10 micrograms of LPS per mouse (calculated to be greater than 50,000 times the concentration of LPS in the rIL-1 alpha administered) failed to duplicate the marked enhancement of antibacterial resistance that was mediated by rIL-1 alpha. These data provide evidence for the beneficial role of IL-1 in nonspecific antibacterial resistance.

Animals↗
PubMed1987

Dual regulation of anti-bacterial resistance and inflammatory neutrophil and macrophage accumulation by L3T4+ and Lyt 2+ Listeria-immune T cells.

Adoptive transfer of anti-Listeria resistance by Listeria-immune spleen T cells was markedly reduced by pretreatment of the cells with monoclonal anti-Lyt 2.2 and complement (Lyt 2+C); pretreatment of cells with monoclonal anti-L3T4 and complement (L3T4+C) had a lesser effect on their ability to transfer resistance. Lyt 2+C-treated and L3T4+C-treated Listeria-immune T cells were undiminished in their immediate ability to transfer enhanced accumulation of inflammatory peritoneal neutrophils and macrophages in response to Listeria antigens. When L3T4+C- and Lyt 2+C-treated Listeria-immune spleen cells were cultured in vitro before transfer, however, it became apparent that the L3T4+ subset was particularly important for mediating in vivo accumulation of inflammatory phagocytes. Listeria-immune spleen T cells produced soluble factors during in vitro culture that, when injected i.p., were able to recruit inflammatory neutrophils and macrophages to the peritoneal cavities of recipient mice. Pretreatment of Listeria -immune spleen cells with L3T4+C before culture markedly diminished their ability to produce soluble factors that were capable of attracting neutrophils and macrophages in vivo. The results of this study indicate substantial roles for both Lyt 2+ and L3T4+ T-cell subsets in the dual regulation of inflammation and anti-bacterial resistance; Lyt 2+ T cells appear to be the principal mediator of anti-bacterial resistance, whereas L3T4+ T cells augment the recruitment of inflammatory phagocytes in vivo.

Animals↗
PubMed1986

New clinical roles for pharmacists: a study of role expansion.

This study assessed the legitimacy of expanded roles for pharmacists with different status audiences. Pharmacy is a profession in transition and is characterized by considerable ambiguity and uncertainty concerning its status as a health care profession. Significant changes have occurred within the profession of pharmacy in the past few decades which have led to loss of function, social power and status. The response of the profession has been a movement toward a patient-oriented, clinical role for pharmacists. Hypotheses concerning level of support for expanded roles were derived from two conflict-based models of professionalization: a power model which focuses on conflict between professions and the central role of power in defining occupational territory; and a process model which focuses on conflict of interest and diversity within a profession and the development of 'segments' which struggle for control of a profession's direction. Data were collected by self-administered questionnaires sent to California pharmacists, physicians and nurses. Respondents were asked to indicate level of support for 20 role activities for pharmacists working in two practice settings (community and hospital). Pharmacy faculty were the most supportive of the clinical role activities, followed by practicing pharmacists, nurses and physicians. Physicians and nurses were more antagonistic toward clinical activities in the community than hospital practice setting, and were most antagonistic toward role activities which require independent judgement or autonomous action relevant to patient care on the part of the pharmacist. Differences were also noted in support for clinical role activities within the pharmacists' group. The effect of experience in working with a clinical pharmacist on support for clinical role activities is also discussed.

Adult↗
PubMed1986

The relative difference in anti-Listeria resistance of C57BL/6 and A/J mice is not eliminated by active immunization or by transfer of Listeria-immune T cells.

In this study, we examined the effects of active and adoptive immunization on the anti-Listeria resistance of innately resistant C57BL/6 and innately susceptible A/J mice. Although active immunization with a sublethal dose of viable Listeria monocytogenes markedly enhanced the anti-Listeria resistance of both C57BL/6 and A/J mice, the 100-fold difference between the two strains in innate anti-Listeria resistance was not diminished. Following immunization with an equivalent sublethal dose (0.1 LD50) of L. monocytogenes, both C57BL/6 and A/J mice generated T cells that could transfer significant and comparable protection to syngeneic recipients that were challenged with up to a 10 LD50 dose of L. monocytogenes. When the absolute number of viable Listeria was compared, however, it was clear that T cells from immunized C57BL/6 mice were capable of transferring protection to syngeneic recipients at Listeria challenge doses that were more than 100-fold greater than could T cells from Listeria-immunized A/J mice. Both active immunization and adoptive transfer of syngeneic Listeria-immune T cells enhanced the accumulation of inflammatory neutrophils and macrophages in C57BL/6 and A/J mice. More inflammatory neutrophils were recovered from actively immunized C57BL/6 than from A/J mice, whereas more inflammatory macrophages were obtained from adoptively immunized C57BL/6 than from A/J mice. These results provide further evidence for the beneficial role of inflammation in genetically determined innate resistance and T-cell mediated resistance to listeriosis. These data also suggest that some mechanism in addition to inflammatory responsiveness may be responsible for limiting the expression of acquired anti-Listeria resistance in genetically susceptible A/J mice.

Animals↗
PubMed1985

Phagocytes from flora-defined and germfree athymic nude mice do not demonstrate enhanced antibacterial activity.

In this study we directly compared the in vitro antibacterial activities of resident and inflammatory phagocytes obtained from athymic (nu/nu) and euthymic (nu/+) mice. Resident peritoneal macrophages obtained from flora-defined nu/nu and nu/+ mice both demonstrated little ability to restrict the growth of Listeria monocytogenes in vitro. Inflammatory peritoneal neutrophils and macrophages obtained from flora-defined nu/nu and nu/+ mice did not differ in their ability to kill L. monocytogenes in vitro. Likewise, inflammatory peritoneal neutrophils obtained from germfree nu/nu and nu/+ mice killed equivalent numbers of listeria. In marked contrast, however, inflammatory macrophages obtained from germfree nu/nu and nu/+ mice demonstrated very limited antilisteria activity in vitro. The reduced antilisteria activity of macrophages from germfree nu/nu and nu/+ mice was associated neither with reduced phagocytosis of L. monocytogenes nor with an inability to generate an oxidative response. Unlike those of previous reports, these data suggest that resident and inflammatory phagocytes obtained from athymic mice that were maintained under conditions such that they were not subjected to underlying infections are not constitutively activated for enhanced antibacterial activity. Furthermore, these data suggest that stimulation of macrophages by products of the bacterial flora is required for the expression of macrophage antibacterial activity.

Animals↗
PubMed1985

Effects of PCB exposure on biochemical and hematological findings in capacitor workers.

Certain former operations in capacitor manufacturing resulted in extensive direct contact of the workers with electrical grade polychlorinated biphenyls (PCBs). A study group of 194 such individuals, all exposed to Aroclor 1016 and many previously exposed to Aroclors 1242 and/or 1254, was examined before (1976) and after (1979) discontinuance of PCB use in the operations (1977). At the two examinations, the approximate geometric mean serum levels (in ppb) and 5 to 95% ranges were for lower PCBs (LPCB), 363 (57-2270) and 68 (12-392); and for higher PCBs (HPCB), 30 (6-142) and 19 (4-108), respectively. The statistical associations among 42 measured clinical chemical and hematological parameters, five different measures of PCB exposure, and seven confounding variables observed in the two examinations were determined by three regression procedures. Similar regressions were performed with DDE, which was present at background levels. The principal statistical findings were a depression in serum bilirubin and elevations in serum GGTP and lymphocyte levels at the time of the first examination, and only an elevation in monocytes at the second. Appraisal of the results suggested an induction of microsomal enzymes which appeared to be subsiding after the cessation of direct exposure to PCBs. The statistical association between serum levels of PCBs and lipids reported by others was confirmed, but shown to be explained by the partitioning behavior of PCB in the body, rather than to changes in liver function. No evidence for health impairment related to PCBs was found, despite the high serum levels of PCBs in the study population.

Adipose Tissue↗
PubMed1984

Antigenic and pathogenic relationships of three bovine rotaviruses and a porcine rotavirus.

The antigenic relationships between three bovine rotaviruses, UK, CP-1 and PP-1, and a porcine rotavirus were investigated; their pathogenicity for piglets was also assessed. After propagation and cloning in cell culture, the four viruses were used to produce convalescent and hyperimmune antisera in gnotobiotic animals. For the UK and PP-1 viruses, reciprocal virus neutralization tests gave ratios of homologous to heterologous titres in the range 57 to greater than 2300. Taking a 20-fold difference in titre to be the criterion of heterogeneity, these two viruses could be regarded as separate serotypes. The third bovine virus, CP-1, was identical to PP-1 in reciprocal neutralization tests but gave a one-way cross-reaction with UK convalescent sera, i.e. it appeared to be intermediate between the two serotypes. UK and CP-1 differed antigenically from the porcine virus as shown by homologous: heterologous neutralization titre ratios of 30 to 12 600. The bovine virus, PP-1, however, had a closer relationship with the porcine virus, the homologous: heterologous ratios ranging from 4 to 110. Oral inoculation of piglets with the bovine viruses revealed differences in their pathogenicity. Isolates UK and CP-1 caused no clinical disease and could not be passaged. However, on the first and second passages in pigs, the bovine virus PP-1 and the porcine virus produced clinical disease, excretion of virus in the faeces and sero-conversion. The results suggest that PP-1 may be a natural hybrid between a bovine and a porcine rotavirus.

Animals↗
PubMed1984

Characterization of a calici-like virus (Newbury agent) found in association with astrovirus in bovine diarrhea.

A bovine calici-like virus and astrovirus, present in the same fecal sample from an outbreak of diarrhea, were separated from each other by calf passage. The calici-like virus (Newbury agent SRV-1) caused anorexia, diarrhea, and xylose malabsorption in gnotobiotic calves aged 17 to 60 days, whereas the bovine astrovirus was nonpathogenic in similar calves. The calici-like virus was shown to be antigenically distinct from a previously described isolate (Newbury agent SRV-2) by two-way cross-protection experiments in calves; calves immune to homologous challenge became clinically ill and excreted virus when challenged with the heterologous virus.

Animals↗
PubMed1983

Clinical, computed tomographic, and histopathologic characteristics of juvenile ossifying fibroma with orbital involvement.

A 9-year-old boy who had had painless progressive proptosis of the right eye for 18 months, initially diagnosed as fibrous dysplasia, was found to have a circumscribed mass involving the frontal bone in the roof of the orbit. Biopsy of the mass led to the diagnosis of juvenile ossifying fibroma and the tumor was removed by a craniotomy approach. One year after surgery, the child appeared to be healthy. Ossifying fibroma can sometimes be differentiated from fibrous dysplasia both clinically and by computed tomography. Ossifying fibroma usually appears between the ages of 7 and 28 years and produces slowly progressive proptosis and displacement of the globe in a direction that depends on the original site of the tumor. Fibrous dysplasia usually develops during the first decade of life and produces facial asymmetry, proptosis, and displacement of the globe. An ossifying fibroma characteristically has well-defined margins, is round or ovoid, is usually monostotic, and produces expansion of the involved bone. Fibrous dysplasia is usually sclerotic and expands the bone throughout its length rather than in a localized fashion. Its borders are poorly defined and the lesion is often polyostotic.

Child↗
PubMed1983

Molecular characterization of rotaviruses with distinct group antigens.

Comparative serological and nucleic acid studies were carried out on rotavirus isolates, with and without the original group antigen. Indirect immunofluorescence allowed the atypical isolates to be divided into two groups each with its own distinct group antigen hence giving a total of at least three distinct rotavirus groups. Genome profile analysis of the atypical isolates again divided them into two groups which corresponded with those obtained by immunofluorescence and within which the overall pattern of genome segments was similar. A more rigorous examination of the degree of difference between the three virus groups was carried out using single-dimension terminal fingerprint analysis. This indicated that the viruses in the three groups did not carry any genome segments in common with each other. Therefore, experimental criteria have been established which allow the division of rotaviruses into three groups. Analysis of further atypical isolates, as they become available, will establish whether the division of rotaviruses into a number of separate groups, of the type seen in influenza virus, is justified.

Animals↗
PubMed1982

The effects of physical exercise on metabolic rate and dietary-induced thermogenesis.

1. The energy metabolism of ad lib.-fed adult male Wistar rats receiving daily running exercise (0.9 km/d; 8 degrees incline) on a motor-driven treadmill, over a period of 56 d, was compared with that of sedentary ad lib.-fed rats and sedentary restricted-fed rats of similar body-weight (approximately 420 g). 2. The metabolizable energy of the diet (Oxoid 41 B) was 11.44 +/- 0.05 kJ/g. This value was not affected by restricted feeding (70% ad lib.), exercise training or exercise itself. 3. Exercise-trained rats ate 5% more food than the sedentary ad lib.-fed rats but their equilibrium body-weight was 60 g lower than that of the latter group. 4. Resting metabolic rate, measured over 22 h in a respiration chamber was increased by 10% in exercise-trained animals. 5. Feeding increased energy expenditure (dietary-induced thermogenesis) and this effect was potentiated by performance of an exercise task. 6. Exercise-trained rats exhibited anticipatory rises in energy expenditure (approximately 40%) when placed on a stationary treadmill. 7. Treadmill work increased energy expenditure by a factor of 1.9-2.4. 8. The energy cost of the exercise, determined by respiration calorimetry was 66-80 J/g per km. These energy costs did not account for all the differences observed in food energy consumption of exercise-trained and sedentary rats of equal body-weight. 9. It is concluded that regular physical exercise increases energy expenditure by factors additional to the energy requirement directly related to the physical work. These factors include an increased resting metabolic rate in exercise-trained rats, increased dietary thermogenesis induced by exercise and anticipatory increases in energy metabolism during the period preceding exercise.

Animals↗