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Biomedical subjects

B C Johnson

Publications and source records attributed to B C Johnson.

At least 19 recordsLinked to original sources
PubMed1992

The effects of dietary restriction on immune function and development of autoimmune disease in BXSB mice.

Chronic energy intake restriction (CEIR) prolonged the median life span and inhibited autoimmunity and development of autoimmune disease in BXSB mice, as has been established for mice of several other autoimmune-prone, short-lived strains. Whether imposed just after weaning or delayed until manifestations of disease had appeared, CEIR inhibited or reversed development of autoimmunity and immune complex-based renal disease in male BXSB mice. CEIR also prevented the formation of anti-DNA antibodies and prevented the increase in circulating immune complex levels that is typically observed in male mice of this strain. Moreover, CEIR inhibited development of splenomegaly and prevented the normal age-associated decline of a number of immunological functions, including interleukin 2 production, cell-mediated cytotoxic responses, and mixed lymphocyte reactivity. The observed improvement in cell-mediated immune responses was attributed largely to the capacity of CEIR to inhibit development of the splenomegaly that occurs concomitant with expansion of a non-T, non-B lymphoid cell population. These findings emphasize that CEIR, even when imposed relatively late in life in BXSB mice, can influence expression of autoimmunities and autoimmune diseases of different genetic origins and presumed pathogenetic bases.

Age Factors↗
PubMed1992

Nutrient intake as a time signal for circadian rhythm.

In considering nutrition and circadian rhythms, time-of-eating behavior is an inherited, genetically controlled pattern that can be phase-shifted by conditioning or training. In addition, there are metabolic responses to meal eating, such as entrainment of a number of enzyme levels, hormone concentrations and other metabolic and physiologic activities. To separate truly inherent rhythms from entrained responses, it is necessary to determine which oscillations continue their circadian rhythms under completely free-running conditions of no zeitgeber, such as darkness vs. light or meal eating vs. fasting. Where meal eating provides a time signal to a biological clock experiment, healthy animals-not starving but constantly receiving nutrition to avoid an eating time signal-should be used. The ability to determine which daily rhythms are not genetically inherent, but rather are responses to a particular time signal, requires the elimination of all but this time signal. By using free-running conditions that are totally without time-giving signals, entrainment by (response to) meal feeding is readily separated from inherited endogenous circadian rhythm. Both types of daily rhythm exist and both involve the biological clock mechanisms . A method by which to identify each is proposed.

Animal Nutritional Physiological Phenomena↗
PubMed1992

Lacrimal and salivary gland inflammation in the C3H/Ipr autoimmune strain mouse: a potential mode for Sjögren's syndrome.

Sjögren's syndrome is an autoimmune inflammatory disease that affects the lacrimal and salivary glands. To identify a potential animal model for study of Sjögren's syndrome, an evaluation was made of lacrimal and salivary glands in the C3H/Ipr autoimmune strain mouse at ages before (2 months) and after (5 months) systemic autoimmune disease onset at 3 to 4 months. Quantitative and qualitative analyses of C3H/Ipr lacrimal and salivary (parotid, submandibular, and sublingual) gland histopathology were performed using age-matched C3H/HeJ nonautoimmune mice to control for inflammation of nonautoimmune origin. No lacrimal or salivary gland inflammation was seen in either of the strains at 2 months of age and measures of systemic autoimmune disease were negative. At 5 months of age, the nonautoimmune C3H/HeJ controls showed a slight increase in lacrimal gland inflammation, but this was not significantly different from the 2 month old controls. A significant increase in lacrimal gland inflammation was found in the 5 month old C3H/Ipr autoimmune mice in a histologic pattern similar to that of Sjögren's syndrome in human beings. Furthermore, the degree of inflammation was positively correlated with serum immune complexes and spleen weight. Sporadic inflammation of the submandibular gland was seen in both autoimmune and control mice, but this was neither statistically significant nor correlated with measures of autoimmunity. No significant inflammation was seen in the parotid or sublingual glands.

Animals↗
PubMed1992

Effects of calorie restriction on immunologic functions and development of autoimmune disease in NZB mice.

Chronic energy (calorie) intake restriction (CEIR) prolonged life, inhibited autoimmune disease, and influenced immunologic and hematologic parameters in NZB mice. Abnormalities in numbers and proportions of T and B cells populations were corrected. Deficient responses to phytomitogens, mixed lymphocyte reactions, formation of plaque-forming cells to sheep red blood cells in vitro, production of cytotoxic T lymphocytes after in vitro stimulation, and interleukin 2 production were also corrected. CEIR prevented the extreme splenomegaly that normally occurs with age in NZB mice. This influence was associated with reduction of a greatly expanded non-T, non-B lymphoid cell population. Calorie restriction also prevented in NZB mice the rapid decrease in total numbers of colony-forming B cells in bone marrow that is also characteristic of mice of this strain. The influences of CEIR on immune parameters and hematopoiesis were generally less marked in non-autoimmune-prone DBA/2 mice than in autoimmune-prone NZB mice. CEIR has been shown to produce profound influences on several strains of autoimmune-prone mice (NZB x NZW)F1, MRL/lpr, BXSB, and NZB herein). In each of these strains, the pathogenesis and manifestations of autoimmune disease are dissimilar. Therefore, it seems likely that calorie restriction acts on an as yet elusive mechanism that operates to foster development of the diseases associated with aging common to each of these autoimmune strains as well as autoimmune-resistant mice and rats. Further investigation of the molecular and cellular bases of the benefits of CEIR seems urgent.

Animals↗
PubMed1991

Transplacental transport of N-acetylcysteine in an ovine model.

STUDY OBJECTIVE: Acetaminophen freely crosses the placenta, and acetaminophen ingestion is the most frequent intentional overdose in pregnancy. Although most patients do well after maternal treatment with the antidote N-acetylcysteine (NAC), fetal death with massive hepatic necrosis has occurred. It has never been shown whether NAC crosses the placenta to yield fetal plasma levels equal to those associated with hepatoprotective effects in human beings. Our study objective was to evaluate this in a widely accepted large animal model for maternal-fetal research. DESIGN AND TYPE OF PARTICIPANTS: A nonblinded experiment was performed using four domestic sheep at near-term gestation. INTERVENTIONS: NAC 150 mg/kg IV was administered to the ewe over 15 minutes. After induction of anesthesia, the fetal head was delivered surgically and a neck vein cannulated for blood sampling. Maternal and fetal blood samples were obtained at the end of NAC infusion, at 30- and then at 60-minute intervals for four hours. Plasma NAC levels were determined by gas chromatography/mass spectroscopy (detection limit, 2 micrograms/mL; quantification limit, 5 micrograms/mL). RESULTS: Maternal peak plasma NAC levels were 619, 631, 1,757, and 2,512, micrograms/mL, respectively, within 30 minutes of infusion. However, NAC was only minimally detectable in plasma of two fetal animals and transiently reached quantifiable levels in two others. None of the fetal animals attained serial plasma NAC levels that equalled those associated with therapeutic dosing or hepatoprotective effects in human beings. CONCLUSION: Transplacental transport of NAC is clinically insignificant in a mammalian model resembling the human being. These findings suggest that the human fetal liver is not protected from acetaminophen toxicity by maternal NAC therapy.

Acetylcysteine↗
PubMed1989

Health care workers' knowledge and attitudes concerning AIDS.

This paper reports the results of a study performed to address the many unresolved issues concerning health care workers and their treatment of patients with AIDS. A survey was developed to measure knowledge, attitudes and opinions, and other information of health care workers. The survey was administered to all employees of a 200 bed hospital. The authors provide a description of the study, indicating methods, subjects, and procedures. They report that the study identified problem areas in the educational/training of participants. According to the authors, the study indicates that there will be no AIDS-related staffing problems in health care organizations in the future. Additional findings concerning AIDS and health care workers are reported.

Acquired Immunodeficiency Syndrome↗
PubMed1988

The vitamin K dependent reaction.

The vitamin K's are 2-methyl-1,4-naphthoquinones. The vitamin is required for the post-translational gamma-carboxylation of glutamyl residues in precursor polypeptides. The vitamin K step in this carboxylation, however, requires not the quinone but the hydroquinone plus oxygen. Thus, the vitamin K-dependent step is a "mixed function" oxidation requiring a reducing compound plus molecular oxygen to provide a form of oxidant (e.g., a free radical, a hydroperoxide) capable of abstracting a particular, slightly labile hydrogen from a glutamyl residue, leaving this position free to accept a carbon dioxide molecule. This oxidation appears similar to that of other mixed function oxidants such as cytochrome P450 plus oxygen, ascorbic acid (with traces of ferrous iron) plus oxygen, ferrous iron plus oxygen, and a number of other systems which function in a wide variety of oxidation. Inhibition by spin-trapping agents suggests a free radical step in the vitamin K hydroquinone-dependent reaction, similar to other mixed function oxidations.

Vitamin K↗
PubMed1987

Crucial dietary factors in maximizing life span and longevity in autoimmune-prone mice.

When the energy intake of (NZB X NZW)F1 female mice was reduced to 60% of the intake of simultaneously ad libitum-fed mice, the early death associated with autoimmune-based renal disease in this strain was greatly delayed. The length of prolongation of disease-free life depended not only on the decreased energy intake but also on the energy source. In the group of mice with 60% intake of a carbohydrate-free (i.e., high fat) diet, mean longevity was doubled as compared to that of ad libitum-fed mice. However, when the nonprotein energy was supplied by carbohydrate (sucrose and glycerol) the mean longevity was three times that of the ad libitum-fed groups, although survival times varied widely. With ad libitum feeding the nonprotein energy source did not significantly affect longevity. Clearly, although energy intake restriction provides significant influence on longevity, very high fat diets do not give the same protection as do high carbohydrate diets. The basis for this difference is not entirely clear and several explanations are possible.

Animals↗
PubMed1987

Influence of extremes of protein and energy intake on survival of B/W mice.

Energy restriction increases longevity and life span of B/W mice as it does in mice of other long-lived or short-lived strains. Mice of autoimmune-prone strains that develop certain diseases of aging experience an increase in median longevity when energy intake is restricted early in life. The present experiments analyze the influence of restricting energy intake while feeding constant, adequate and greatly excessive amounts of protein, and constant amounts of minerals and vitamins. The experiments assess the influence of excess protein intake in mice fed ad libitum versus those restricted in energy intake. Ad libitum feeding of diets with protein composition ranging from 15 to 50% did not alter longevity or onset and manifestations of renal disease in B/W mice. In mice consuming a restricted energy intake of a diet providing identical amounts of protein to those consumed by ad libitum-fed mice, whether the protein intake was very high or normal, longevity was equally greatly prolonged. Ad libitum feeding of diets of greatly differing protein content is well tolerated by B/W mice. Both the 15 and 50% protein diets, when ad libitum fed, permitted expression of autoimmune disease and glomerulonephritis in B/W mice but did not adversely influence development or progression of disease. Restriction of energy intake of either the normal protein diet or the high protein diet greatly prolonged the life of mice of the autoimmune-prone, glomerulonephritis-prone B/W strain.

Animals↗
PubMed1986

Calories versus protein in onset of renal disease in NZB x NZW mice.

Autoimmunity-prone (NZB x NZW)F1 (B/W) female mice are used as a model of human lupus erythematosus. When full-fed, these mice die of glomerulonephritis between 7 and 11 (average 9) months of age. When food intake is restricted to 60% of calories, the onset of this disease is delayed and the mice live greatly prolonged lives free of disease. Since high protein intake is commonly associated with acceleration of kidney damage in humans and experimental animals, the current experiments were designed to employ diets in which protein concentration was as high as possible. The observations demonstrate clearly that with this model of autoimmune disease, total calorie intake (from whatever source) exerts an overriding influence on life span. A higher calorie intake leads to early death and restricted-calorie intake leads to an increased life span. When B/W mice are full-fed, with respect to calories, feeding diets of greatly differing protein composition did not influence life span significantly. By contrast, calorie restriction of diets, even of very high protein content or of lower protein content, greatly prolonged life of B/W mice. Even with exceedingly high protein intake (greater than 83% of the calories) it is not protein per se but the total calorie intake that exerts the greatest influence that determines length of life in mice of this autoimmunity- and glomerulonephritis-prone strain.

Animals↗
PubMed1984

Calorie source, calorie restriction, immunity and aging of (NZB/NZW)F1 mice.

It is frequently stated that high fat diets are harmful with respect to nutrition and disease development. Herein, (NZB/NZW)F1 autoimmune-prone mice were compared under the influence of different calorie intakes and different calorie sources. Decreased calorie intake prolonged life and delayed onset of glomerulonephritis. This influence of restriction of energy intake was greater than any influences of dietary energy source. Parameters affected strictly by restricted calorie intake were: 1) longevity, 2) delayed onset of glomerulonephritis, 3) greatly decreased circulating immune complexes, 4) decreased production of anti-DNA antibodies, 5) increased thymocyte proliferation in response to exogenous Interleukin-2 (IL-2), 6) increased IL-2 production by spleen cells stimulated by concanavalin A and 7) marked increase of mixed lymphocyte reaction of spleen cells. Parameters affected both by restriction of calorie intake and by high sucrose content in full-fed mice and not obviously related to longevity and protection from glomerulonephritis were: 1) plaque-forming cell response to sheep red blood cells in vitro and 2) cytotoxic cell-mediated immune response generated by in vitro exposure to allogenic antigen.

Aging↗
PubMed1984

Comparison of fetal and adult retinol and retinoic acid binding proteins in bovine serum and pigment epithelium.

Cellular retinol binding protein (CRBP) and cellular retinoic acid binding protein (CRABP) were assayed in bovine eye pigment epithelium (PE) cytosol from both early fetal and young adult animals. Both fetal and adult PE contain CRBP but only fetal PE contains CRABP. Blood retinol binding protein (RBP) was also assayed in serum from fetal and adult animals. Both fetal and adult serum contain RBP. A novel albumin adsorption technique (Affi-Gel Blue) combined with refinements of the sucrose gradient centrifugation technique provide a better assay method for retinoid receptors than polyacrylamide disc gel electrophoresis. Our findings support the hypothesis that retinoid receptors may cause or be the consequence of differentiation in animal tissues.

Adsorption↗
PubMed1979

Purification of a new high activity form of glucose-6-phosphate dehydrogenase from rat liver and the effect of enzyme inactivation on its immunochemical reactivity.

A new form of cytoplasmic glucose-6-phosphate dehydrogenase (E.C.1.1.1.49) was purified from rat liver by protamine sulfate precipitation, ammonium sulfate fractionation, ion exchange chromatography with diethylaminoethyl cellulose, and affinity chromatography with Cibacron blue agarose and NADP agarose. This form of the enzyme has a specific activity of over 600 units/mg of protein and gives essentially a single band by polyacrylamide gel electrophoresis. The form of the enzyme isolated by this purification method is 3 times more active than the form purified from liver by previously reported procedures. The relative mass of this pure glucose-6-phosphate dehydrogenase enzyme was determined by disc gel electrophoresis to be 269,000. This high activity glucose-6-phosphate dehydrogenase enzyme, after inactivation by reaction with palmityl-CoA, was no longer precipitated by specific rabbit and goat antisera to this purified enzyme. Thus, the possibility still exists that starved fat-refed animals contain glucose-6-phosphate dehydrogenase (G6PD) enzyme protein in an inactivated form no longer detectable by either enzyme activity or immunoprecipitation.

Animals↗
PubMed1979

Unique amanitin resistance of RNA synthesis in isolated nuclei from Amanita species accumulating amanitins.

In order to understand the basis upon which amanitin-accumulating species of Amanita are able to develop in the presence of these specific inhibitors of RNA synthesis, the in vitro RNA synthesizing activities of nuclei isolated from amanitin-accumulating species. Amanita hygroscopica (culture, derived from amanitin-accumulating carpophore) and A. suballiacea (carpophore), and from the non-accumulating species A. solitaria (culture) and A. brunnescens (carpophore) were tested for their sensitivities to alpha-amanitin inhibition. The nuclear RNA synthesizing activities obtained from both carpophores and cultures of non-accumulating organisms displayed significant sensitivities to alpha-amanitin, whereas those obtained from accumulating organisms displayed remarkable resistance to alpha-amanitin. The observed relationship between levels of amanitins in carpophores and resistance of the RNA synthesizing activities to inhibition by alpha-amanitin supports the hypothesis that amanitins may function as regulators of mRNA transcription in Amanita species.

Agaricales↗