The effect of repetitive mild hyperthermia on body temperature, the autonomic nervous system, and innate and adaptive immunity.

The effect of repetitive mild hyperthermia on body temperature, the autonomic nervous system, and innate and adaptive immunity was investigated using a new hyperthermia treatment system, nanomist sauna (NMS). Six healthy volunteers participated and the concentration of catecholamines and cortisol, and the frequency and function of leukocytes in the peripheral blood were investigated before and after successive 7 days of hyperthermia treatment (20 min/day, 40°C, 100% relative humidity). After treatment, the blood level of adrenaline and cortisol on the 7th day was decreased compared with the 1st day, indicating the suppression of the sympathetic nervous system activity.

Reactivity of autoantibodies against not only erythrocytes but also hepatocytes in sera of mice with malaria.

In order to further examine the reactivity of autoantibodies, mice were infected with a non-lethal strain of Plasmodium yoelii. Parasitemia appeared between days 10 and 21. During this period, hyperglycemia and hypothermia were serially obeserved and this phenomenon resembled stress-associated responses.

On/off switching of capillary vessel flow controls mitochondrial and glycolysis pathways for energy production.

Capillary vessel flow in the base of the fingernail can be observed by microscopy. This flow is switched off under some conditions, such as coldness, surprise, and anger and is switched on again under other conditions, such as warming, relaxation, and mild exercise. In other words, capillary vessels perform two functions: switching flow on and off.

Research on stress-induced apoptosis of natural killer cells and the alteration of their killing activity in mouse liver.

Aim: To investigate the stress-induced apoptosis of natural killer (NK) cells and the changes in their killing activity in mouse livers.

Methods: A restraint stress model was established in mice. Flow cytometry was employed to measure the percentage of NK cells and the changes in their absolute number in mouse liver.

Sequential shift of energy production pathways at the fetal stage and during lifetime.

As eukaryotes, human beings spend their lifetime using two different pathways for energy production: the anaerobic glycolysis pathway and aerobic mitochondria pathway. Energy produced using the glycolysis pathway is utilized for cell division and prompt force of white fiber muscles whereas that produced by the mitochondria pathway is utilized for suppression of cell division and continuous force of red fiber muscles. Herein, it is proposed that there exists a sequential shift of energy production pathways at the fetal stage and during the lifetime.

Skin rubdown with a dry towel, 'kanpu-masatsu' is an aerobic exercise affecting body temperature, energy production, and the immune and autonomic nervous systems.

Skin rubdown using a dry towel (SRDT) to scrub the whole body is a traditional therapy for health promotion. To investigate its mechanism, 24 healthy male volunteers were studied. Body temperature, pulse rate, red blood cells (RBCs), serum levels of catecholamines and cortisol, blood gases (PO(2), sO(2), PCO(2) and pH), lactate and glucose, and the ratio and number of white blood cells (WBCs) were assessed before and after SRDT.

Acute stress induces the modification of the lymphocyte proteins of mouse liver.

We studied the effect of acute stress on mouse immune system and found that the stress modified the proteins existing in the lymphocytes of liver. Performing SDS-polyacrylamide gel electrophoresis (SDS-PAGE), we got the result that the proteins existing in the lymphocytes were different between stressed liver and non-stressed liver, whereas we could not find any detectable differences in the lymphocyte proteins between stressed spleen and non-stressed spleen. In stressed liver lymphocytes, we found thirteen clear bands in the stained gel that were not prominent in non-stressed liver lymphocytes.

Extracellular ATP-stimulated macrophages produce macrophage inflammatory protein-2 which is important for neutrophil migration.

Macrophages are the major source of the chemokines macrophage inflammatory protein-2 (MIP-2) and keratinocyte-derived chemokine (KC), which play a major role in neutrophil migration to sites of inflammation. Although extracellular ATP from inflammatory tissues induces several immune responses in macrophages, it is unclear whether ATP-stimulated macrophages affect neutrophil migration. Therefore, the aim of the present study was to investigate the role of ATP-induced MIP-2 production by macrophages.

Biology of autoreactive extrathymic T cells and B-1 cells of the innate immune system.

Cumulative evidence has shown that extrathymic T cells can be autoreactive and that B-1 cells may produce autoantibodies. These T and B-1 cells, which form part of the innate immune system, tend to be activated simultaneously when conventional T and B cells are in a suppressive state, for example, when thymic atrophy occurs by stress or involution with aging. In other words, autoreactive T cells and autoantibody-producing B cells are different from thymus-derived T cells and bone marrow-derived B cells.

Induction of ssDNA-binding autoantibody secreting B cell immunity during murine malaria infection is a critical part of the protective immune responses.

Although it has been hypothesized that autoimmune-like phenomena may play a critical role in the protective immune responses to both human and animal malaria, there are still no evidence-based data to support this view. In this study we demonstrate that the majority of anti-single stranded (ss) DNA autoantibody secreting B cells were confined to B220(+)CD21(+)CD23(-) cells and that these cells expanded significantly in the spleen of C57BL/6 mice infected with Plasmodium yoelii 17X non-lethal (PyNL). To determine the role of ssDNA-binding autoantibody secreting B cell responses in murine malaria, we conjugated generation 6 (poly) amidoamine dendrimer nanoparticles with ssDNA to deplete ssDNA-binding autoreactive B cells in vivo.

Natural killer T cells suppress zymosan A-mediated granuloma formation in the liver by modulating interferon-γ and interleukin-10.

Wild-type (WT) and CD1d(-/-) [without natural killer (NK) T cells] mice were treated with zymosan A to induce granuloma formation in the liver. Increased granuloma formation was seen in NKT-less mice on days 7 and 14 after administration. WT mice showed limited granuloma formation, and zymosan A eventually induced NKT cell accumulation as identified by their surface marker (e.

Cytokine profile of murine malaria: stage-related production of inflammatory and anti-inflammatory cytokines.

Balance between inflammatory and anti-inflammatory cytokines may be important in malaria presentation and outcome. To clarify cytokine interactions that produce pathology of malaria and control infection, C57BL/6 mice were infected with 10(4) parasitized RBCs from a non-lethal strain of Plasmodium yoelii. Kinetics was monitored showing the course of parasitemia, and cytokines were determined by RT-PCR from liver and spleen tissues.

Coincidence of autoantibody production with the activation of natural killer T cells in α-galactosylceramide-mediated hepatic injury.

Natural killer T (NKT) cells are known to be specifically activated by α-galactosylceramide (α-GalCer) via their interaction with CD1d. At that time, NKT cells mediate autoreactivity and eventually induce hepatic injury. As these immune responses resemble acute autoimmune hepatitis, it was examined whether autoantibody production and the activation of autoantibody-producing B-1 cells were accompanied by this phenomenon.

"Senobi" stretch ameliorates asthma symptoms by restoring autonomic nervous system balance.

The number of asthmatic patients is increasing in Japan. It is conceivable that changes in lifestyle (eg, lack of exercise and high-energy diet) may be associated with this phenomenon. The resulting factor seems to be altered activity of autonomic nervous system of these patients.

Those with the habit of going to sleep early show a higher ratio of lymphocytes while those with the habit of staying up late show a higher ratio of granulocytes.

In this study, we examined the effect of the difference in time of going to sleep on the numerical values of leukocyte subsets and various hormones. Subjects consisted of 26 healthy adults (15 men, 11 women) with a mean age of 37.6 years.

Identification and characterization of autoantibody-producing B220(low) B (B-1) cells appearing in malarial infection.

Mice with malaria showed unique immunological responses, including the expansion of NK1.1(-)TCR(int) cells (extrathymic T cells). Since TCR(int) cells with autoreactivity and autoantibody-producing B cells (B-1 cells) are often simultaneously activated under autoimmune conditions, it was examined whether B-1 cells were activated in the course of malarial infection.

Co-appearance of autoantibody-producing B220(low) B cells with NKT cells in the course of hepatic injury.

Severe hepatic injury is induced by Concanavalin A (Con A) administration in mice, the major effector cells being CD4(+) T cells, NKT cells and macrophages. Since autologous lymphocyte subsets are associated with tissue damage, Con A-induced hepatic injury is considered to be autoimmune hepatitis. However, it has remained to be investigated how autoantibodies and B-1 cells are responsible for this phenomenon.

Bone marrow large B cell lymphoma bearing cyclin D3 expression: clinical, morphologic, immunophenotypic, and genotypic analyses of seven patients.

We report seven large B cell lymphoma patients showing the involvement of tumor cells with cyclin D3 (CCND3) expression in bone marrow (BM) at the initial diagnosis. All patients presented with B symptoms, splenomegaly, and anemia/thrombocytopenia lacking hemophagocytosis in the BM. Five of the seven patients had suffered from immunological diseases or cancers.

Resistance and augmentation of innate immunity in mice exposed to starvation.

Mice were exposed to starvation for 3 days. Body temperature and various parameters were examined. By starvation, body temperature, blood glucose and ACTH decreased, especially on days 2 and 3.

Acute stress augments innate immunity in the liver and increases hyaluronan levels in the tissues and blood of mice.

The effect of acute stress on the immune system was examined in mice. Restraint stress decreased the number of lymphocytes in the liver, whereas the number of lymphocytes remained unchanged in the spleen and thymus. In the liver, the decrease in number appeared at 1.

Association of glucocorticoid with stress-induced modulation of body temperature, blood glucose and innate immunity.

To know the details of the mechanism on stress-associated responses, attention was first focused on body temperature and blood glucose after stress. Mice were exposed to restraint stress for 6 h. Under this condition, hypothermia (39 degrees C --> 33 degrees C) and hyperglycemia (150 mg/dl --> 350 mg/dl) were induced.

Alkalization of blood pH is responsible for survival of cancer patients by mild hyperthermia.

The effect of mild hyperthermia on venous blood pH was examined in 6 cancer patients. Mild hyperthermia was induced by continuation of a rectal temperature of 39.5 degrees C for 30 min.

Proposal of alternative mechanism responsible for the function of high-speed swimsuits.

Since many top swimmers wearing Speedo LZR Racer swimsuits have broken world records, it is considered that the corset-like grip of suit supports the swimmers to maintain flexibility of movement and reducing water resistance. We propose an alternative mechanism to explain this phenomenon. The suits are so tight that the blood circulation of swimmers is suppressed.

NKG2A inhibits invariant NKT cell activation in hepatic injury.

Activation of invariant NKT (iNKT) cells in the liver is generally regarded as the critical step for Con A-induced hepatitis, and the role of NK cell receptors for iNKT cell activation is still controversial. In this study we show that blockade of the NKG2A-mediated inhibitory signal with antagonistic anti-NKG2A/C/E mAb (20d5) aggravated Con A-induced hepatitis in wild-type, Fas ligand (FasL)-mutant gld, and IL-4-deficient mice even with NK cell and CD8 T cell depletion, but not in perforin-, IFN-gamma-, or IFN-gamma- and perforin-deficient mice. Consistently, 20d5 pretreatment augmented serum IFN-gamma levels and perforin-dependent cytotoxicity of liver mononuclear cells following Con A injection, but not their FasL/Fas-dependent cytotoxicity.

Role of alpha-adrenergic stimulus in stress-induced modulation of body temperature, blood glucose and innate immunity.

Mice were exposed to restraint stress for 3h. During this period, low body temperature (hypothermia, 39 degrees C-->less than 37 degrees C) and high blood glucose levels (hyperglycemia, 150 mg/dl-->up to 220 mg/dl) were simultaneously induced. Reflecting a stress-induced phenomenon, blood levels of catecholamines increased at that time.