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Biomedical subjects

C Kubo

Publications and source records attributed to C Kubo.

At least 19 recordsLinked to original sources
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↗
PubMed1995

Selective tumorigenesis in non-parenchymal liver epithelial cell lines by hepatocyte growth factor transfection.

Hepatocyte growth factor (HGF) has been recently suggested to contribute to tumorigenesis by an autocrine mechanism in fibroblast cells overexpressing its receptor, the MET/HGFR protein. Since epithelial cells represent the primary physiologic target of HGF, we investigated whether inappropriate expression of HGF by epithelial cells which normally express MET/HGFR may also contribute to tumorigenesis. We have transfected a full length rat HGF gene into three mouse epithelial cell lines, one derived from breast (MM55) and two (BNL CL.2 and NMuLi) representing liver non-parenchymal epithelial cells (NPEC). We confirmed the presence of the transfected gene by Southern blot analysis, the production of HGF protein by immunofluorescence, and the preservation of HGF biologic activity by bio-assay. In comparison to untransfected cells, all three HGF-transfected cell lines displayed high level MET/HGFR autophosphorylation and increased ability to proliferate in media containing low serum. The two HGF-transfected liver NPEC lines, but not the HGF-transfected mammary cell line, displayed loss of cell contact growth-inhibition and acquired a markedly increased ability to form colonies in soft agar. Furthermore, the NPEC HGF-transfected cell lines formed much larger tumors in nude mice than the untransfected counterparts, with extensive invasion and sporadic lung metastases. These results demonstrate that overexpression of HGF in at least some epithelial cells contribute to tumorigenesis, and furthermore suggest a possible role for the HGF-MET/HGFR system in the progression of certain epithelial tumors.

Animals↗
PubMed1995

A study of untreated Graves' patients with undetectable TSH binding inhibitor immunoglobulins and the effect of anti-thyroid drugs.

OBJECTIVE: We previously reported the clinical characteristics of Graves' disease with undetectable TSH binding inhibitor immunoglobulins (TBII) at first visit, but a study of the prognosis of untreated TBII negative patients with anti-thyroid drug medication has never been undertaken. The aim of this paper is to study the difference between negative and positive TBII Graves' disease in relation to the effect of anti-thyroid drug treatment. PATIENTS: From January 1986 to April 1991, 1545 patients with untreated Graves' disease were referred to Kuma Hospital, Kobe, Japan. Of these, 94 TRAb negative patients were identified. Another 83 TRAb positive patients were randomly selected from the other Graves' disease patients and served as a comparison group. Fifty-six of the 94 patients in the TBII negative group and 52 of the 83 patients in the TBII positive group completed treatment with methimazole only. MEASUREMENTS: The trial was conducted as a retrospective study with a maximum treatment period of 36 months and a follow-up period of a further 12 months. From the original pool of patients, we classified 56 TBII negative patients into two groups according to the clinical course taken; Group A in whom TBII remained undetectable throughout methimazole treatment (9 men and 34 women, age 37.2 +/- 2.2 years), and Group B who became TBII positive (4 men and 9 women, 31.2 +/- 4.4 years). Fifty-two TBII positive patients served as the comparison Group C (8 men and 44 women, age 38.1 +/- 2.0 years). RESULTS: Serum free T4 and free T3 levels in groups A and B were significantly lower before treatment than those of Group C (P < 0.001). The thyroid volumes of Group A and B patients were significantly smaller than those of Group C (P < 0.01). The level of TBII in Groups A and B was significantly lower than that in Group C (8.3 +/- 0.7 and 8.8 +/- 1.1 vs 57.0 +/- 2.8%, respectively, P < 0.001). The level of thyroid stimulating antibody (TSAb) in Groups A and B was significantly lower than that in Group C (478 +/- 71.0 and 761 +/- 140.3 vs 2143 +/- 280%, respectively, P < 0.01), and there were no significant differences in TSAb activities between Groups A and B. The remission rates in Groups A, B and C were 77.4, 36.4 and 36.5%, respectively. These data indicate that Group A has a good prognosis, but Group B has the same prognosis as Group C. CONCLUSION: We conclude that patients in whom TSH binding inhibitor immunoglobulins remained negative have a much better prognosis than TSH binding inhibitor immunoglobulins positive patients or those who become TSH binding inhibitor immunoglobulins positive, having been initially negative.

Adult↗
PubMed1994

Against-the-rule astigmatism judged at one week after phacoemulsification and aspiration procedures.

To determine the characteristics of astigmatism 1 week postoperatively or whether the final astigmatism is predictable from that present 1 week postoperatively, we analyzed 544 postcataract against-the-rule (AR) cases of astigmatism among 1,649 standard phacoemulsification cataract operations, all utilizing 10-0 Mersilene in double-running fashion. Postoperative AR astigmatism < or = 1.0 dpt increased markedly 1 week postoperatively (2.72 +/- 0.09 dpt) but decreased 6 months postoperatively. However, in postoperative AR astigmatism > 2.0 dpt, the increase 1 week postoperatively was not as great (2.16 +/- 0.13 dpt) but tended to continue to increase even 6 months postoperatively, with a flatter corneal curvature being the responsible factor. Eyes with less astigmatism 1 week postoperatively showed exacerbation of final astigmatism 6 months postoperatively. This course was different from that of small incision cataract surgery.

Aged↗
PubMed1994

[A depressive disorder in patients with irritable bowel syndrome and non-ulcer dyspepsia].

The relationships between psychiatric disorders and the symptoms of both irritable bowel syndrome (IBS) and non-ulcer dyspepsia (NUD) are herein investigated and discussed. Functional disorders of the small and large intestine induce irritable bowel syndrome. NUD is a syndrome that displays symptoms that might originate in the upper digestive system despite the absence of any organic disorder. In addition, it has also been suggested that the occurrence of NUD is based on a functional disorder of the upper digestive systems. Based on our studies of serious cases with both NUD and IBS, in approximately 50% of the NUD patients as well as about 50% of the IBS cases, a depressive disorder was found to be most closely related to the onset and continuance of the symptoms of either NUD or IBS. According to the evaluations of NUD and IBS as functional disorders and psychiatric disorders, the patients underwent treatment and all demonstrated a good response to the various treatment regimens. It is thus considered that NUD and IBS should be evaluated as both functional digestive disorders and psychiatric disorders.

Colonic Diseases, Functional↗
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

Involvement of prejunctional alpha 2-adrenoceptor in bovine ciliary muscle movement.

The effects of adrenergic agents on bovine ciliary muscle were studied in vitro. Norepinephrine, phenylephrine, or isoproterenol did not affect the muscle tone. High concentrations of guanethidine (10(-5) M) partly inhibited the nerve-mediated contractions of the muscle. The nerve-mediated contractions also were inhibited in the following order: norepinephrine > epinephrine >> isoproterenol. The inhibition was blocked by yohimbine or phentolamine, but not by optimum concentrations of prazosin, moxisylyte, propranolol, and carteolol. Usual concentrations of phosphodiesterase inhibitors markedly inhibited the nerve-mediated and carbachol-induced contractions. These results suggest that an adrenergic alpha 2 receptor located at the nerve terminals inhibits the contraction of cholinergically innervated ciliary muscle. Adrenergic innervation seems to play an inhibitory role in the muscle tissue when the muscle tone is elevated.

Animals↗
PubMed1992

Consumption of milk from cows immunized with intestinal bacteria influences age-related changes in immune competence in mice.

Milk was obtained from nonimmunized cows and cows immunized with a mixture of various human gut bacteria. Each milk was administered orally to 2-mo-old C57BL/6 mice at a dose of 150 g.kg-1.d-1 for either 6 or 16 mo. The study group had fewer enteric bacteria and a lower concentration of the serum antibodies against enteric bacteria compared with the control group at 8 and 18 mo of age. Furthermore, the study group at 18 mo old had a higher redirected cytotoxicity of intestinal intraepithelial lymphocytes, a higher proliferative response of mesenteric lymph nodes cells against mitogenic or alloantigenic stimulation and a greater ability of the spleen cells to produce anti-sheep erythrocytes IgG antibody after systemic immunization with sheep erythrocytes. A lower level of autoantibodies was observed at 8 mo and 18 mo of age in the study group compared with the control group. These results suggest that the senescence of the murine immune system may be delayed by consumption of milk from immunized cows.

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↗
PubMed1992

[Two cases of vocal cord dysfunction and bronchial asthma indicated contrary course of bronchial responsiveness based on astography].

We encountered two cases of patients who showed vocal cord dysfunction and bronchial asthma. By using an ++astograph , we found that bronchial responsiveness of these ailments differed. In the case of vocal cord dysfunction, bronchial responsiveness to methacholine indicated a false high level by adduction of the vocal cord. Therefore other evaluations including pulmonary function and bronchoscopy were required to distinguish it from bronchial asthma. On the other hand, in the case of bronchial asthma, bronchial responsiveness to methacholine was mild, but life threatening asthmatic attack occurred after inhalation of methacholine. Psychological factors were not neglected in considering both of these cases. Therefore we must consider these results and psychological factors when evaluating bronchial responsiveness.

Adolescent↗
PubMed1992

[Graduated psychosomatic treatment and quality of life in asthmatics].

We investigated the quality of life (QOL) in 72 patients with bronchial asthma who are under our gradational psychosomatic treatment (GPT) by means of an 11-item questionnaire. The results were summarized as follows: 1) Ninety-two percent of the subjects showed a good understanding of mind-body relations and modified their stressful adaptive patterns. 2) Asthmatic symptoms improved in 86 percent of the subjects. Other symptoms also improved in 72 percent of the subjects. 3) In 81 percent of the subjects, their daily life improved. Furthermore 96 percent of the subjects obtained some advantages through GPT. 4) There were various improvements in psychological states, personal relations and life style in most of the subjects. 5) The attitudes of their families toward the patients improved in 46 percent of the subjects, however 71 percent of the families developed a better understanding of the cause of asthma from the psychosomatic point of view. 6) Most of the subjects with moderate or severe symptoms were considered to have reduced the grade of severity of their symptoms from the doctor's standpoint.

Adult↗
PubMed1992

[A case of vocal cord dysfunction diagnosed as bronchial asthma, that was improved by psychosomatic therapy].

A 19-year-old psychologically disturbed female was admitted to our hospital because of intractable dyspnea and wheezing for twenty two months. She had been diagnosed as having asthma and had received several medications including steroids before admission to our hospital. According to our clinical observations, she was considered not to have asthma because neither FEV1.0 nor PaO2 was decreased during the periods of wheezing and FEV1.0 was not changed by inhalation of bronchodilators, although she had a family history of allergy and false bronchial hyperreactivity by asthograph. On physical examination, diffuse wheezing was heard mainly over the larynx during inspiration at the times of dyspnea. There was flattening of the inspiratory flow-volume loop during wheezing. Bronchoscopy performed during an attack confirmed that wheezing was due to adduction of the vocal cords throughout the respiratory cycle. Therefore, this case was diagnosed as vocal cord dysfunction. Her symptom was considered to be a form of conversion reaction derived from her unhappy past history. Following psychosomatic therapy, all of her medications became unnecessary. She understood the mind-body relationship of her condition, and learned to achieve self-control.

Adult↗
PubMed1991

Cellular immune surveillance against HTLV-I infected T lymphocytes in HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP).

To investigate the cellular immune surveillance against HTLV-I infected T lymphocytes in HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP), we studied the cytotoxic T lymphocytes (CTL) activity against an HTLV-I infected human T cell line (MT-2) and the natural killer (NK) cell activity in 15 HAM patients, 6 HTLV-I carriers, and 15 controls. The activity of CTL against MT-2 cells was found to be significantly elevated in HAM compared with that in the controls. This cytotoxicity in HAM was higher than in HTLV-I carriers, although the difference was not statistically significant. There was an HLA class I restriction in this CTL activity against MT-2 cells in HAM. On the other hand, NK cell activity was significantly lower in HAM than in controls. Cold target inhibition studies suggested that NK cells could not lyse MT-2 cells effectively. There was a positive correlation between the CTL activity against MT-2 cells and the serum antibody titers to HTLV-I in HAM.

Adult↗
PubMed1991

Influence of intake of skim milk from cows immunized with intestinal bacterial antigens on onset of renal disease in (NZB x NZW)F1 mice fed ad libitum or restricted in energy intake.

Autoimmune disease-prone (NZB x NZW)F1 (B/W) female mice are a model of human lupus erythematosus. Immune milk, obtained from cows immunized with various intestinal bacterial antigens, was given to B/W mice as a component of diets beginning at 8 wk of age. Diets were fed ad libitum or restricted to 60% of ad libitum energy intake. Controls were fed commercial skim milk. In B/W mice fed ad libitum, the titers of anti-single-stranded DNA antibodies were significantly lower in immune milk-fed mice at 4 and 6 mo of age. Onset of proteinuria was delayed and life span was significantly prolonged by immune milk feeding. Surface phenotypes of the T cells and levels of the responsiveness of lymphocytes to mitogens were not changed by immune milk feeding. The B/W mice restricted to 60% of ad libitum energy intake, which preserved immune responsiveness, had not developed proteinuria by 14 mo of age, irrespective of immune milk feeding or control milk feeding. However, at 10 mo of age, the level of plasma antibodies against intestinal bacteria was significantly higher in energy-restricted mice fed control milk than in those fed immune milk or in mice fed ad libitum.

Animals↗
PubMed1991

[Psychosomatic study of inhalation therapy in patients with bronchial asthma. I. Evaluation by questionnaire].

We investigated the use of metered-dose beta agonist inhalers (MDIs) by means of 17-item questionnaires from the standpoint of psychosomatic medicine in 56 subjects with bronchial asthma. The results can be summarized as follows: 1) Many asthmatics with neurotic characters used MDIs frequently; Thirteen percent of them suffered adverse effects. The number of times the inhalers were used increased in proportion to the severity and the duration of illness. Fifteen percent of the subjects used MDIs frequently because of anxiety. 2) Fifty percent of the subjects, most of them had neurotic or alexithymic characters, used MDIs without suffering from dyspnea or wheezes; the subjects who used MDIs because of anxiety increased in proportion to the duration of illness. 3) Seventy eight percent of the subjects were anxious about asthmatic attack when they did not carry any MDI; sixty two percent of the subjects, most of them had neurotic or alexithymic characters, actually experienced asthmatic attack. 4) Seventy three percent of the subjects used MDIs secretly; sixty percent of the subjects did not like to inhale in the presence of others. 5) There were some subjects who acted incorrectly on or after asthmatic attack when MDIs were not effective.

Adolescent↗
PubMed1991

[Psychosomatic study of inhalation therapy in patients with bronchial asthma. II. Relationship between subjective self assessment of dyspnea and peak expiratory flow rates].

The degree of dyspnea when using metered-dose inhalers (MDIs), and the relationship between subjective self assessments and objective peak expiratory flow rates were examined by means of visual analogue scales and mini wright peak flow meters in 16 subjects with asthma. Three subjects who were neurotic in character were found to have a poor perception of the degree of airway obstruction after inhalation compared with objective changes in their condition. Two subjects, one neurotic and one alexithymic, assessed the degree of dyspnea to be worse after inhalation, when objectively there were few changes. However, one neurotic subject perceived an improvement in his condition when, in fact, there was little change. Furthermore, some severe cases used MDIs in the rogressive state of airway obstruction. In conclusion, we must pay attention to patients' characters when determining treatment in order to prevent overuse of MDIs or delays in treatments including the use of MDIs.

Adult↗
PubMed1990

Prevention of immunosuppression in stressed mice by neurotropin(NSP).

It is well known that the immune function can be compromised by stress. To investigate immune function in mice stressed by experimental restraint or unavoidable and opioid dependent stress, we evaluated the changes in total body weight and in organ weights (liver, spleen and thymus) of these animals, as well as the phagocytic activity of macrophages, the cytotoxicity of T cells and inhibitory effects on tumor growth and changes in T cell subset populations. At the same time we evaluated the effects of Neurotropin (NSP), a substance extracted from the inflamed skin of rabbits inoculated with the vaccinia virus and which appears to possess neuroimmunomodulating activity. The experimentally stressed group exhibited a reduction of phagocytic activity of macrophages, cytotoxicity of T cells and inhibitory effects on tumor growth. In addition there were changes in the population of T cell subsets. In those animals pretreated with NSP, the immunosuppression induced by stress was ameliorated. As compared with several agents which influence phagocytosis, neurotropin exhibited effects similar to that of agents that blocked the adrenaline receptor and an opioid antagonist rather than tranquilizer (diazepam) and a cholinergic receptor blocker. The pharmacologic effects of neurotropin support a relationship between the actions of the central nervous system and the immune system.

Animals↗