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Biomedical subjects

C Kubo

Publications and source records attributed to C Kubo.

At least 55 records · Page 3Linked to original sources
PubMed1998

alpha2-Adrenoceptor-mediated potassium currents in acutely dissociated rat locus coeruleus neurones.

1. The noradrenaline (NA)-activated response was investigated in neurones acutely dissociated from the rat locus coeruleus (LC) using nystatin-perforated, conventional whole-cell and inside-out patch recording modes under current- and voltage-clamp conditions. 2. Under current-clamp conditions, NA hyperpolarized the LC neurones, abolishing the spontaneous action potentials. In voltage-clamp studies, NA induced an inwardly rectifying K+ current (INA) in a concentration-dependent manner with a half-maximum effective concentration of 2.2 x 10(-7) M. 3. INA was mimicked by the alpha2-agonist UK14304 but was inhibited by either the alpha2B/alpha2C antagonist ARC239 or the alpha1- and alpha2B/alpha2C antagonist prazosin, suggesting the contribution of alpha2B/alpha2C adrenoceptors. 4. INA was inhibited by the intracellular application of GDPbetaS but fully activated by intracellular perfusion of GTPgammaS. 5. In the inside-out recording mode, the application of GTP to the cytoplasmic side of the patch membrane markedly enhanced the open probability of the NA-activated single channels which represented the inwardly rectifying properties. 6. These results indicate that the activation of alpha2B/alpha2C adrenoceptors coupled with GTP-binding protein directly activates the inwardly rectifying K+ currents in rat LC neurones, thus resulting in a decrease in the spontaneous firing activities.

4-Aminopyridine↗
PubMed1998

Treating nonulcer dyspepsia considering both functional disorders of the digestive system and psychiatric conditions.

Nonulcer dyspepsia (NUD) is a common syndrome, but the optimal treatments have yet to be established. This study was performed to determine the most effective treatment for NUD. Subjects were recruited through the Department of General Internal Medicine at the Kyushu University Hospital because of their somatic symptoms. When no organic lesions were found, the patients were directed to consult our department (Psychosomatic Medicine); 194 consecutive NUD patients were studied. All subjects were assessed psychiatrically with the Structured Clinical Interview for DSM-III-R(SCID). Patients with serious NUD were hospitalized, and randomly divided into control (N = 42) and experimental groups (N = 86). The controls were treated with physical treatment alone. The experimental group received psychiatric treatment in addition, based on the results of SCID. The experimental group showed a significant improvement compared with the controls (P < 0.0001). The treatment for NUD taking into consideration both the physical and psychiatric conditions is highly effective.

Adult↗
PubMed1998

A study of intestinal dysfunction induced by restraint stress in rats.

BACKGROUND: The pathogenesis of intestinal dysfunction induced by stress has not been established. We tried to clarify possible causal mechanisms of irritable bowel syndrome. METHODS: An experimental model of intestinal dysfunction was designed using loading restraint stress in rats. A cannula was inserted into the origin of the duodenum or colon, with the other end leading to the skin. To provide intestinal content, a semi-solid colored marker was used for monitoring intestinal transit. After 1 week the marker was injected into the intestine through the cannula under unanesthetized wakefulness. RESULTS: Under restraint stress, transit in the small intestine was suppressed, but actual suppression took place only in the upper half, where the contents normally moved fast. Transit time in the colon was reduced by restraint stress. This reduction was attributed to the disappearance of the stagnant region, which was present under normal conditions. CONCLUSIONS: These results suggested that restraint stress affects the function of the pacemaker site of the intestine.

Animals↗
PubMed1997

Biphasic modulation in the trigeminal nociceptive neuronal responses by the intracerebroventricular prostaglandin E2 may be mediated through different EP receptors subtypes in rats.

To determine which prostaglandin E2 (PGE2) receptor subtypes are involved in the brain-derived PGE2-induced changes in nociception, we injected synthetic EP1, EP2 and EP3 receptor agonists (0.01 fmol to 10 nmol) into the lateral cerebroventricle (LCV) of urethane-anesthetized rats and observed the changes in the responses of the wide dynamic range (WDR) neurons in the trigeminal nucleus caudalis to noxious pinching of facial skin. The enhancement and suppression of the nociceptive responses of the WDR neurons were observed after the LCV injection of MB28767 (an EP3 receptor agonist) at a low dose range (1-100 fmol) and 17-phenyl-omega-trinor PGE2 (an EP1 receptor agonist) at high doses (1-10 nmol), respectively. Furthermore, the suppression of nociceptive neuronal responses after the LCV injection of PGE2 (1 nmol) was completely blocked by SC19220 (an EP1 receptor antagonist, 300 nmol). On the other hand, butaprost (an EP2 receptor agonist) at any doses tested (0.1 fmol to 1 nmol) had no effect on the nociceptive responses. The LCV injection of MB28767 (10 fmol) and 17-phenyl-omega-trinor PGE2 (1 nmol), which respectively enhanced and suppressed the nociceptive neuronal responses, did not affect the responses of the low threshold mechanoreceptive neurons to innocuous tactile stimuli. These results provide electrophysiological evidence that brain-derived PGE2 induces mechanical hyperalgesia and hypoalgesia through EP3 and EP1 receptors, respectively, in the rat.

Analgesics↗
PubMed1997

The requirement of intestinal bacterial flora for the development of an IgE production system fully susceptible to oral tolerance induction.

The role of intestinal bacterial flora in oral tolerance induction to the IgE response was investigated using germfree (GF) mice. When GF mice were orally administered 20 mg of OVA as tolerogen before a systemic challenge with OVA, the Th1-mediated responses, such as the production of IgG2a and IFN-gamma, were abrogated, while the Th2-mediated immune responses, such as the production of IgE, IgG1, and IL-4, were maintained. Moreover, the basal level of IL-4 production in vitro was significantly higher in the GF mice than that of IL-4 in specific pathogen-free mice when challenged systemically with OVA. On the other hand, both Th1 and Th2 responses were fully sensitive to such tolerance induction in specific pathogen-free mice. The reconstitution of intestinal flora of GF mice with Bifidobacterium infantis, one of the predominant bacteria in the intestinal flora, restored the susceptibility of these Th2 responses to oral tolerance induction; however, this was only effective when such reconstitution was performed in neonates, but not in mice at an older age. These results thus suggested that intestinal bacterial flora play a crucial role in generating a Th2 cell population whose size and response are adequately regulated and, consequently, fully susceptible to oral tolerance induction, probably by affecting the development of gut-associated lymphoid tissue at the neonatal stage.

Administration, Oral↗
PubMed1997

Restraint stress-induced elevation of endogenous glucocorticoid suppresses migration of granulocytes and macrophages to an inflammatory locus.

It has been reported that restraint stress gives rise to various immunosuppressive events. In the present study, we focused our interest on an early stage of the host-defense system in which granulocytes, macrophages and natural killer (NK) cells are involved. We observed that an elevation of endogenous glucocorticoid levels in mice induced by 24 h-restraint stress (acute stress) did not significantly reduce the NK activity of the spleen cells but profoundly suppressed the migration of macrophages and granulocytes into peritoneal cavities of the mice at 24 h after an intraperitoneal injection of proteose peptone. The reduced number of the migrated granulocytes and macrophages corresponded to a down-regulated gene expression of such chemotactic factors as MCP-1/JE in the peritoneal exudate cells of the stress-loaded mice. The stress-loaded mice recovered from such a suppressive state upon treatment with the glucocorticoid antagonist, RU-486, or upon adrenalectomy, suggesting that the elevated level of endogenous glucocorticoid is responsible for these suppressive effects of acute stress.

Adrenalectomy↗
PubMed1997

The restraint stress-induced reduction in lymphocyte cell number in lymphoid organs correlates with the suppression of in vivo antibody production.

In this study, we examined the effects of restraint stress on some immune parameters such as the in vivo antibody levels, cytokine production, and lymphocyte cell number in the spleen or mesenteric lymph node (MLN). BALB/c mice were thus injected intraperitoneally 2-times with OVA absorbed into alum on days 0 and 21. Before the first injection, the animals were either restrained for 12 h (stress group) or returned to their home cage (control group). Exposure to stress resulted in a reduction in the serum levels of anti-OVA IgE, IgG1, and IgG2a. In addition, stress also caused a decrease in the IL-4 and IFN-gamma levels in the spleen or mesenteric lymph node cell culture supernatants. Furthermore, exposure to stress resulted in a decrease in the splenic and mesenteric lymphocyte cell number when examined immediately after the cessation of stress. This decrease persisted for at least 12 h after the termination of stress and thereafter disappeared 24 h after stress. The stress-induced reductions in antibody and cytokine production occurred only when antigen was given either immediately or 6 h after stress, but not when antigen was given 24 h post stress. These results thus suggest that the restraint stress-induced change in lymphocyte cell number in the spleen or MLN closely correlates with the altered antibody and cytokine levels.

Animals↗
PubMed1997

Improved prognosis of solid-type poorly differentiated colorectal adenocarcinoma: a clinicopathological and immunohistochemical study.

AIMS: We rarely encounter solid-type poorly differentiated colorectal carcinoma, and their histogenesis and biological behaviour are not fully disclosed. METHODS AND RESULTS: A review of 60 poorly differentiated carcinomas of the colorectum was undertaken, 36 (59%) of which were located in the right side of the colorectum. Although, on the basis of the World Health Organization (WHO) classification solid carcinomas are included among undifferentiated carcinomas, the poorly differentiated carcinomas were divided into four types; 27 solid carcinomas (Sol.), 17 poorly differentiated adenocarcinomas (PDA), six signet-ring cell carcinomas (Sig,) and 10 mucinous carcinomas (Muc.). Solid carcinomas revealed a solid alveolar growth of fairly uniformly sized tumour cells with occasional mitotic figures. This type of tumour had a relatively lower percentage of lymphatic permeation and lymph node metastasis compared with the other three types. The 5-year survival rates were 31% for all poorly differentiated carcinomas, 47% for the Sol. type, 32% for the PDA type, and 0% for both the Sig. and the Muc. types, with a rate of 72% for well-differentiated adenocarcinomas selected as controls. Immunohistochemically, bcl-2 protein expression was demonstrated in 38% of the Sol. type, but in only 12% of the other three non-solid types, this difference being significant (P < 0.05). CONCLUSIONS: These findings suggest that solid carcinomas of the colorectum should be regarded as a distinct type of poorly differentiated carcinoma, leading to a good prognosis.

Adenocarcinoma↗
PubMed1997

Oral administration of a unicellular green algae, Chlorella vulgaris, prevents stress-induced ulcer.

Oral administration of dry powder of Chlorella vulgaris (CVP) showed clear prophylactic effects in water-immersion restraint stress-induced and in cysteamine-induced peptic ulcer models, but not in Shay's rat model. Drugs that enhance the protective factors of ulcer formation are effective in the first two models. CVP may prevent ulcer formation mainly through the "immune-brain-gut" axis and protection of gastric mucosa by its own characteristics.

Administration, Oral↗
PubMed1997

Alterations in lymphocyte subsets and pituitary-adrenal gland-related hormones during fasting.

We investigated changes in the immunoendocrine system during fasting. Ten hospitalized patients aged 14-46 y with psychosomatic disorders fasted for 7 or 10 d. Blood samples were collected before and on days 3 and 7 of the 7-d fasts. When fasting continued to 10 d, an additional sample was taken on day 10. We measured blood cellularity (white blood cells and total lymphocytes), the total number and percentage of lymphocyte subsets (CD2, CD3, CD4, CD8, and CD19), natural killer (NK) cell activity, cytokines (interleukin 1 beta, interleukin 2, interleukin 6, granulocyte-macrophage colony stimulating factor, tumor necrosis factor alpha, and interferon gamma), and soluble interleukin 2 receptors. Corticotropin, cortisol, and dehydroepiandrosterone sulfate (DHEAS) concentrations were also determined. Although the total number of lymphocytes decreased during fasting, NK cell activity increased significantly. Plasma cortisol and DHEAS concentrations also increased significantly whereas changes in corticotropin concentrations were not significant. The total number and percentage of CD4 cells decreased significantly during fasting but no other lymphocyte subsets changed significantly. The percentage of CD4 cells was negatively correlated with cortisol concentrations during fasting. No detectable changes occurred in cytokines or soluble interleukin 2 receptors during the study. All measured immunoendocrine values that changed during fasting returned to prefasting values during the refeeding period. These findings indicate that fasting affects immune variables such as T cell subsets and NK cell activity at least in part through changes in adrenal gland-related hormones.

Adolescent↗
PubMed1996

Extracellular ATP activates mast cells via a mechanism that is different from the activation induced by the cross-linking of Fc receptors.

In this study, the extracellular ATP (ATPo)-induced biochemical events were elucidated by comparing them with either the Fc epsilon RI- or Fc gamma R-induced events in the mouse mast cell line MC9. The omission of extracellular Ca2+ almost completely abolished the elevation of intracellular Ca2+ ([Ca2+]i) in the ATPo-stimulated cells, but only suppressed the second phase of the increase of [Ca2+]i in FcR-stimulated cells, thus suggesting that the ATPo-induced elevation of [Ca2+]i is totally dependent on the entry of extracellular Ca2+. Pretreatment with genistein, which inhibits protein kinases, especially protein tyrosine kinase, inhibited the FcR-triggered increase of [Ca2+]i, but not the ATPo-triggered one; however, such pretreatment did suppress both ATPo- and FcR-mediated beta-hexosaminidase release. An immunoblot analysis revealed that both ATPo and the cross-linking of FcRs led to tyrosine phosphorylation of 44- and 110-kDa proteins, which thus suggested that these tyrosine-phosphorylated proteins are involved in a modulation of the degranulation process following an elevation of [Ca2+]i. Pretreatment with PMA inhibited the FcR-induced [Ca2+]i increase, while not inhibiting the ATPo-induced one, thus suggesting that ATPo can mobilize [Ca2+]i even when protein kinase C (PKC) has already been activated. Pretreatment of calphostin C, a specific PKC inhibitor, had little effect on the ATPo-mediated beta-hexosaminidase secretion, thus indicating that the ATPo-induced degranulation is not mediated by PKC. Taken together, these results demonstrate that ATPo activates MC9 mast cells by a mechanism that is different from the activation induced by the cross-linking of FcRs.

Adenosine Triphosphate↗
PubMed1996

Antibody-dependent cell-mediated cytotoxicity (ADCC) in HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP)

Defects in immune surveillance mechanisms may allow increased replication of human T-lymphotropic virus type I (HTLV-I) in peripheral blood mononuclear cells in HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). To explore this possibility, antibody-dependent cell-mediated cytotoxicity (ADCC) against HTLV-I infected cells in HAM/TSP and in asymptomatic HTLV-I-seropositive carriers (SPC), was studied. ADCC activity was significantly depressed in HAM/TSP compared to SPC subjects (p < 0.025) and was due to specific reduction in ADCC effector activity. On the other hand, there was no difference in antibody component of anti-HTLV-I ADCC (ADCC-Ab) activities between HAM/TSP and SPC, although patients with more severe forms of disease tended to have higher anti-HTLV-I ADCC-Ab activity. In HAM/TSP, depressed ADCC activity against HTLV-I due to reduced ADCC-effector activity may allow increased replication of HTLV-I which may implicate the development of inflammatory neuropathologic lesions of HAM/TSP.

Adult↗
PubMed1996

Graves'disease after the onset of panic disorder.

BACKGROUND: It is still unknown whether anxiety disorders observed in Graves' disease are a consequence of increased thyroid hormone levels or precede the onset of Graves' disease. METHODS: Two case reports are described. RESULTS: In 2 patients Graves' disease occurred in the setting of previously established euthyroid panic disorder. The interval between the onset of panic disorder and that of hyperthyroidism was 4 and 5 years, respectively. Antithyroid drug treatment reduced psychiatric symptoms, but only to a partial degree. CONCLUSION: The findings indicate that panic disorder may not only be a consequence of Graves' disease but may precede its onset and potentially predispose to its development.

Alprazolam↗