[Clinical usefulness of X-ray CT for diagnosis of emphysema as demonstrated by correlation with lung function and selective alveolobronchography].
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Aged↗
Biomedical subjects
C Kubo
Publications and source records attributed to C Kubo.
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↗
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↗
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↗
Effects of genetic diabetes and zinc nutriture on in vivo cell-mediated immunity in the mouse.
To examine whether an abnormal zinc status contributes significantly to the impaired in vivo cell-mediated immunity of the genetically diabetic C57BL/KsJ db/db mouse, we measured specific cytotoxicity of spleen cells from db/db and heterozygous (db/m) and homozygous (m/m) control mice fed either zinc-deficient (2 mg/kg) or zinc-adequate (20 mg/kg) semipurified diets. Low serum and femur zinc concentrations were seen after 4 wk in all mice fed the zinc-deficient diet, but impaired cytotoxicity was not seen until later in control mice fed that diet. In contrast, db/db mice fed zinc-adequate diets had diminished spleen weights and markedly impaired cytotoxicity by 4 wk. These mice had normal serum and only mildly decreased femur zinc concentrations. We, therefore, found no evidence to suggest that the mildly altered zinc status of db/db mice fed zinc-adequate diets is a major factor contributing to their markedly impaired in vivo cell-mediated immunity.
Animals↗
[Respiratory failure secondary to mycoplasma pneumoniae infection].
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Acute Disease↗
[Superiority of home care proven by a clinical experience].
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Adult↗
Effects of immunization of mothers on the immune reaction of their offspring. II. Significance of enhanced antigen elimination by maternal antibodies on the suppression of the offspring.
In the offspring of sheep erythrocyte (SRBC)- or chicken erythrocyte (CRBC)-immunized mothers, generation of cytotoxicity and plaque forming cells (PFC) were suppressed, while delayed-type hypersensitivity (DTH) was not. We performed experiments to analyse the mechanism of this suppression. Antigen specific antibodies, which enhanced opsonization or antibody-dependent cell-mediated cytotoxicity (ADCC), might have a close relation to the suppression (1). The suppression was weakened by a high-dose of antigen challenge or macrophage blockade with colloidal carbon, while enhanced by macrophage activation with Corynebacterium parvum. In contrast, secondary immune responses in the offspring showed the same amplitude as in normal mice. Therefore, the suppression in the offspring might be a result from the early antigen elimination by enhanced opsonization or ADCC due to passive antibodies. But, generation of memory cells or effector cells of DTH might not be affected in the presence of passively transferred antibodies.
Animals↗
Influence of early or late dietary restriction on life span and immunological parameters in MRL/Mp-lpr/lpr mice.
Reduced food intake doubles and even triples the life span of (NZB X NZW)F1 (B/W) mice and greatly influences of food intake while keeping vitamin and mineral intake constant in mice of the MRL/Mp-lpr/lpr (MRL/l) strain. Restriction of food intake greatly prolongs life. This influence also was seen when dietary restriction was imposed later in life. Dietary restriction inhibited development of lymphoproliferative disease and greatly decreased the numbers of cells in thymus, lymph nodes, and spleen. It also delayed development of glomerulonephritis and maintained certain immunological responses. Proliferative responses to phytohemagglutinin, pokeweed mitogen, or allogeneic spleen cells were maintained in the mice fed a low-calorie diet from 6 wk. Imposing diet at 12 wk had a lesser influence than earlier restriction. These dietary influences did not depress formation of anti-DNA antibodies or circulating immunocomplexes. MRL/l mice show an apparently extremely low production of interleukin 2, and dietary restriction increased the capacity of lymph node cells but not spleen cells to produce this immunomodulator.
Aging↗
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↗
Effects of immunization of mothers on the immune reaction of their offspring: inhibition of immune responses of offspring caused by antibody imported through the milk.
Effects of immunization of pregnant AKR mice with nucleated chicken erythrocytes (CRBC) on immune responses of their offspring were examined. Antigen-specific reduction of generation of cytotoxicity and plaque forming cells (PFC) was demonstrated in the offspring at 8 weeks after birth, and lasted for 15 weeks. Cross-fostering experiments and cell transfer experiments showed that such suppression would be induced by antibody contained in the milk of immunized mothers rather than suppressor cells. Activities to enhance opsonization and to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) were demonstrated in the serum of such offspring before challenge with CRBC. Delayed footpad reaction (DFR) was maintained at the normal level in such offspring of immunized mice.
Animals↗
Differences in thymus dependency among the alloreactive T-cell subpopulations in their development: graft-versus-host reaction appears to be mediated by delayed-type hypersensitivity of tuberculin type.
The effects of thymectomy at various times after birth, 1 and 7 days (Tx-1, Tx-7), on delayed footpad reactions, cell-mediated cytotoxicity (CMC), production of migration inhibitory factor (MIF), and graft-versus-host reactions (GVHR) against allogeneic antigens were determined by experiments with 8-week-old mice. Delayed footpad reactions were detected in Tx-1 mice, but CMC, production of MIF, and the ability to raise GVHR were not detected in such mice. CMC was detected in Tx-7 mice. However, the ability to raise GVHR and to produce MIF was abolished by thymectomy at 7 days after birth. These results suggest that the effector mechanism to mount a GVHR might be mediated by delayed-type hypersensitivity of tuberculin type rather than CMC to host antigens.
Age Factors↗
Thymus-dependent increases in splenic T-cell population by indomethacin.
After administration of indomethacin, an inhibitor of prostaglandin synthesis, the number of splenic T cells increased in normal mice but not in adult-thymectomized or athymic nude mice. The enlarged T-cell population consisted mainly of Lyt-1+2+ cells. This thymus-dependent increase in T-cell population augmented in vivo antibody response to sheep erythrocytes, a T-dependent antigen. The increased T-cell population also included suppressor cells that were eliminated by treatment with anti-Lyt-2 antibody plus complement. These results suggest that increased T cells in the spleen were recruited from the thymus by an indomethacin-mediated mechanism and participated in immune responses as regulator cells.
Animals↗
Development of immunity against Listeria monocytogenes in athymic nude versus neonatally thymectomized mice.
The thymus requirement for the development of immunological responsiveness was determined by estimation of immune responses raised to Listeria monocytogenes in athymic nude, neonatally thymectomized, and sham-operated mice at 6 weeks of age. Not only sham-operated mice, but also neonatally thymectomized mice could completely eliminate the bacteria from the spleen and liver, while athymic nude mice could not eliminate them and showed a persistent form of infection. A strong delayed footpad reaction and acquired cellular resistance could be raised in neonatally thymectomized mice just as well as in sham-operated mice, but not in athymic nude mice. The delayed footpad reaction could be induced in neonatally thymectomized mice without an accompanying ability to inhibit macrophage migration. These results suggest that T cells responsible for immunity against listerial infection require the presence of the thymus for only a very short period in their development.
Animals↗
Delayed type skin response to myelin basic protein in chronic relapsing experimental allergic encephalomyelitis.
The skin response to myelin basic protein (MBP) was studied in chronic relapsing experimental allergic encephalomyelitis (EAE) using strain 13 guinea pigs. The delayed type skin response showed a monophasic curve; it gradually increased after immunization, reached maximum levels around 80 days post-immunization, and decreased thereafter. Relapses were more frequent while it was at high levels although it did not correlate directly in individuals with the clinical stage. The skin response was also high in MBP-immunized animals which had recovered from acute EAE. Our results suggest that delayed type hypersensitivity to MBP is involved but is not sufficient by itself to cause relapsing EAE.
Animals↗
Differentiation and maturation of thy-1 negative bone marrow cells. I. Effects of the thymus and radioresistant helper functions on the maturation of precursor cells specific for heterologous erythrocytes.
The effects of adult thymectomy (ATx) and preimmunization on the differentiation of cells responsible for delayed footpad reaction (DFR), plaque forming cells (PFC) and cell mediated lympholysis (CML) were examined in lethally irradiated and thy-1 negative bone marrow cell reconstituted C57BL/6 recipients. ATx reduced the degrees of immune responses in irradiated and reconstituted mice. When the recipients had been preimmunized, all of DFR, PFC and CML became detectable even in irradiated and reconstituted ATx mice. Preimmunization also evoked early maturation of precursor cells for CML. Therefore, it was suggested that radioresistant helper effects, presumably in the presence of antigens, could promote the differentiation and maturation of T cell precursors in bone marrow in the absence of the thymus. We also demonstrated differences in restoration periods of such responses after lethal irradiation and reconstitution. One or two weeks following irradiation and reconstitution, DFR was first detectable. On the other hand, the generation of PFC was detected later than 2 weeks after bone marrow cell reconstitution, and it took over 4 weeks for thy-1 negative bone marrow cells to raise CML. T cells responsible for DFR may have lower dependency on the thymus than those for PFC and CML.
Allergy and Immunology↗
The mechanism of reduction of cell-mediated cytotoxicity in neonatally thymectomized mice.
The effect of neonatal thymectomy at various times after birth (Tx-1, Tx-7) on effector and suppressor T cells responsible for cell-mediated cytotoxicity (CMC) for allogenic antigens was determined. Following in-vitro primary mixed lymphocyte cultures, in the absence of T-cell growth factor (TCGF), alloreactive CMC was not detected in spleen cells of Tx-1 mice, but was detected in spleen cells of Tx-7 mice at as high levels as in those of sham-operated mice. However, in the presence of TCGF, as much alloreactive CMC was detected in spleen cells of Tx-1 mice as in those of Tx-7 mice. Furthermore, TCGF production was not detected in spleen cells of Tx-1 mice but was detected in those of Tx-7 mice. In in-vivo experiments, inhibition of allogeneic tumour growth and CMC in spleen cells showed the same pattern as in in-vitro experiments. These results support the concept that the reduction of CMC in Tx-1 mice might be due to a defect in helper function (TCGF-producing capacity) rather than to a defect in cytotoxic T lymphocytes and/or cytotoxic T lymphocyte precursors. Alloreactive suppressor T cells could not be induced in spleen cells of Tx-1 mice but were induced in spleen cells of Tx-7 mice. Therefore, it was suggested that alloreactive suppressor T cells require the presence of the thymus for 7 days after birth in their development.
Animals↗
Analysis of the mechanism of allograft rejection and cell-mediated immunity. II. Divergent effect of CY pretreatment on the generation of cytotoxic activity in the draining lymph nodes and spleen.
CY pretreatment augmented the generation of cytotoxicity in the draining lymph node cells in mice after subcutaneous immunization with allogeneic spleen cells, or in the non-adherent peritoneal exudate cells after intraperitoneal immunization with these cells. Marginal cytotoxicity in the spleen cells after this immunization was suppressed by CY pretreatment. Similar divergent effect of CY pretreatment on the generation of cytotoxic activity in the draining lymph nodes and the spleen was also observed after immunization with allogeneic tumour cells which can induce high degrees of cytotoxicity without CY pretreatment. These results indicate that cytotoxic T lymphocyte (CTL) generation at the site of direct graft rejection appears to have a nature different from that related to CTL generation in the spleen. A discussion is made as to the role of CTL in the peripheral site and the spleen in cases of in vivo allograft rejection.
Animals↗