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Biomedical subjects

K Kamata

Publications and source records attributed to K Kamata.

At least 199 records · Page 11Linked to original sources
PubMed1989

Inotropic effect of phenylephrine and myocardial alpha-adrenergic receptor in newborn and adult animals.

Developmental changes in the myocardial alpha-receptor density were studied using rabbit, rat and dog hearts. In all species studied, alpha-receptor density in the newborn was greater than in the adult. The inotropic effect of phenylephrine was measured using the isolated arterially perfused heart preparation of rabbit and rat. The heart was stimulated electrically at 40/min. In the presence of propranolol, phenylephrine caused a significant positive inotropic effect which was significantly less in the newborn than in the adult. Since alpha-adrenergic stimulation activates protein kinase C, the inotropic effect of protein kinase C activation was studied in the rabbit and rat using phorbol myristate acetate (PMA). PMA caused a negative inotropic effect and the decrease in contractile function in the newborn was greater than in the adult. These data suggest that myocardial alpha-receptor density decreases and the positive inotropic effect of alpha-agonist increases with development. The reasons for this discrepancy remain unclear but there may be developmental differences in the signal transduction processes of alpha-stimulation. The greater negative inotropy of protein kinase C activation in the premature heart may be one of the mechanisms of the reduced inotropy of alpha-agonist in this age group.

Animals↗
PubMed1989

Pharmacological action of the phospholipase A2 from the venom of Trimeresurus flavoviridis on the smooth muscle of the rat stomach.

Phospholipase A2 (PLA2) from the venom of the snake Trimeresurus flavoviridis produced an increase in resting tension of isolated strips of rat stomach fundus. The contractions of the fundus strips induced by the PLA2 were significantly inhibited by treatment with 10(-6) M indomethacin and in Ca2+-free medium, while treatment of the fundus strips with nordihydroguaiaretic acid caused a marked potentiation of the PLA2-induced contraction. Atropine (10(-6) M), chlorpheniramine (10(-6) M) and methysergide (10(-6) M) had no effects on the contractions induced by PLA2, while tetrodotoxin (10(-6) M) significantly potentiated the contraction. From these results, it appears that exogenously applied PLA2 may cause contraction of the rat stomach fundus through the liberation of endogenous arachidonic acid which may then be transformed into prostaglandins.

Animals↗
PubMed1989

Characterization of a polyreactive monoclonal antibody to dsDNA, F x 1A, and heparan sulfate generated from BALB/c mice immunized with rat renal homogenates.

Monoclonal antibodies (MoAb) were prepared by fusing spleen cells from BALB/c mice immunized with rat renal cortical homogenates to the mouse myeloma cell. One of them, designated MoAb26-3, revealed a positive antinuclear activity by screening an indirect immunofluorescence test on kidney cryostat sections. The reactivity of MoAb26-3 with double-stranded deoxyribonucleic acid (dsDNA) was confirmed by the Crithidia luciliae assay. The isotype of MoAb26-3 was determined to be IgM-kappa. To test the nephritogenicity of MoAb26-3, the hybridomas were grafted intraperitoneally into BALB/c mice. A deposition of IgM was observed along the base of the epithelial foot processes and on the luminal surface of the endothelium by immunoelectron microscopy. By direct enzyme-linked immunosorbent assay (ELISA), MoAb26-3 was shown to react not only with dsDNA but also with fraction 1A of renal cortical supernatant (F x 1A) and heparan sulfate. On the basis of inhibition ELISA, the dsDNA inhibited F x 1A and heparan sulfate binding of MoAb26-3 and F x 1A blocked the reactivity of Mo26-3 with dsDNA and heparan sulfate, while heparan sulfate showed a less inhibition on the binding of MoAb26-3 with F x 1A, dsDNA, and even with heparan sulfate. Using immunoprecipitation with radiolabeled F x 1A, MoAb26-3 was shown to react with MW 330,000, 440,000, and 700,000 bands which were the same with those which polyclonal Heymann nephritis serum could react. An intravenous injection of MoAb26-3 to rats resulted in the deposition of IgM along the glomerular capillary wall, but resulted in an only transient appearance of proteinuria.

Animals↗
PubMed1989

Impairment of endothelium-dependent relaxation and changes in levels of cyclic GMP in aorta from streptozotocin-induced diabetic rats.

1. Acetylcholine (ACh)-induced relaxation of aortic strips with endothelium and production of cyclic GMP between streptozotocin-induced diabetic and age-matched control rats were compared. 2. The concentration-response curve for ACh-induced relaxation was shifted to the right in diabetic rats. IC50 values for ACh were 4.57 +/- 0.67 x 10(-8) M and 1.00 +/- 0.87 x 10(-7) M in aortic strips from age-matched control and diabetic rats, respectively (n = 6, P less than 0.05). 3. Relaxations produced by atrial natriuretic peptide (ANP) in diabetic aortae were similar to those in age-matched vessels. 4. Relaxations produced by sodium nitroprusside (SNP) in diabetic aortae were similar to those in age-matched vessels. 5. Basal levels of cyclic GMP and ACh-induced production of cyclic GMP were significantly decreased in diabetic rats. 6. These results suggest that functional changes in endothelium but not in guanylate cyclase activity in the aorta may occur in diabetes, and thus, spontaneous and ACh-induced formation of cyclic GMP may be decreased. This decrease in production of cyclic GMP may be responsible for the decreased response of the aorta to the relaxant effect of ACh.

Acetylcholine↗
PubMed1989

Endothelium-dependent vasodilator effects of platelet activating factor on rat resistance vessels.

1. To elucidate the mechanisms of the powerful and long-lasting hypotension produced by platelet activating factor (PAF), its effects on perfusion pressure in the perfused mesenteric arterial bed of the rat were examined. 2. Infusion of PAF (10(-11) to 3 x 10(-10) M; EC50 = 4.0 x 10(-11) M; 95%CL = 1.6 x 10(-11) - 9.4 x 10(-11) M) and acetylcholine (ACh) (10(-10) to 10(-6) M; EC50 = 3.0 +/- 0.1 x 10(-9) M) produced marked concentration-dependent vasodilatations which were significantly inhibited by treatment with detergents (0.1% Triton X-100 for 30 s or 0.3% CHAPS for 90 s). 3. Pretreatment with CV-6209, a PAF antagonist, inhibited PAF- but not ACh-induced vasodilation. 4. Treatment with indomethacin (10(-6) M) had no effect on PAF- or ACh-induced vasodilatation. 5. These results demonstrate that extremely low concentrations of PAF produce vasodilatation of resistance vessels through the release of endothelium-derived relaxing factor (EDRF). This may account for the strong hypotension produced by PAF in vivo.

Acetylcholine↗
PubMed1989

Platelet-activating factor: lack of direct action on guinea pig myocardium and possible transmitter release from cardiac sympathetic nerve endings at high concentrations.

Microelectrode and mechanical studies were performed with isolated guinea pig myocardium (right ventricular free walls and papillary muscles) to examine the effects of platelet-activating factor (PAF) and lysophosphatidylcholine (LPC). Low concentrations of PAF (10(-8) to 10(-6) M, a range equivalent to the blood concentrations that produce marked hypotension in vivo) had no effects on action potential configuration and contractile force. High concentrations (10(-5) to 10(-4)M) of PAF and LPC per se elicited slow response action potentials with concomitant contraction (restored contraction) in the myocardium depolarized with elevated K+ (25 mM); they also augmented slow responses and restored contractions produced by a low concentration of isoproterenol (10(-8) M). Although these results suggested there was an increase in slow Ca current, the slow responses and restored contractions thus produced were greatly suppressed or abolished by the addition of a beta-adrenoceptor blocking agent, sotalol (10(-5) M), and by pretreatment with reserpine (5 mg/kg i.p., 24 h prior). In accordance with our previous conclusions, the present results suggest that direct cardiac action is not involved in the mechanisms of hypotension produced by PAF. It was also shown that high concentrations of PAF and LPC may act nonspecifically as amphiphilic compounds to induce transmitter release from sympathetic nerve endings, which may in turn augment the Ca current channels in the myocardial cell membrane.

Action Potentials↗
PubMed1989

Effects of opioid peptides administered in conscious rats on the changes in blood adrenaline levels caused by immobilization stress.

Effects of several opioid peptides administered in the lateral cerebroventricle on the changes in blood adrenaline (AD) levels were examined at 10, 20 and 30 min after the start of immobilization in conscious rats. beta-Endorphin, (D-Ala2)-Met-enkephalinamide, morphiceptin and (D-Ala2, D-Leu5)-enkephalinamide produced significantly lower elevations of AD than the control, and the effect was enhanced by naloxone. The effect of dynorphin, however, was almost the same as that of the control.

Animals↗
PubMed1989

Subacute toxicity of (-)15-deoxyspergualin in BALB/c mice. I. Hematological study.

(-)15-Deoxyspergualin (DSP), a bacterial metabolite obtained from Bacillus laterosporus, was shown to effectively suppress autoantibody production in mice and alloimmune reaction in mice and rats. Its potential toxicity and safety margin in BALB/c mice were studied by administering the drug, 0.5-5.0 mg/kg body weight, s.c., 6 days/week for 3 months. The animals were weighted every two weeks, and their blood was drawn for hematological and liver function studies. Control animals showed a gradual increase in body weight from 17.8 +/- 1.1 g (SD) to 20.2 +/- 3.2 g during the 3 months of treatment. The body weight of 0.5 mg- and 2.5 mg-DSP group was not significantly different from that of the control group. In contrast, 5.0 mg-DSP group of animals showed significant decrease in their weight compared with the control after 5 weeks of treatment (P less than 0.01). They were then sacrificed. WBC in 0.5 mg-, 2.5 mg- and 5.0 mg-DSP groups were significantly lower compared with the control after 3 months of treatment. On the other hand, only 5.0 mg-DSP group showed significantly lower level in their RBC, Hb and Hct values (P less than 0.05). In contrast, platelet counts in 2.5 mg- and 5.0 mg-DSP group significantly increased. No manifest effect due to DSP on differential count of leukocytes was observed, although on day 92, a significant difference was shown in the stab cells of the 0.5 mg-DSP group and in the eosinophils in the 2.5 mg-DSP.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1989

Subacute toxicity of (-)15-deoxyspergualin in BALB/c mice. II. Histopathological study.

Following the preceding report on hematological aspects in subacute toxicity of (-)15-deoxyspergualin (DSP), the present report dealt with the histopathological changes produced by DSP, 0.5-5.0 mg/kg, given to BALB/c mice for three months. At sacrifice, various internal organs such as heart, lungs, liver, spleen and kidneys, were taken, and their wet weights immediately measured. HE- or PAS-stained sections were histopathologically studied under light microscope. Additionally, frozen sections of the spleen were prepared to evaluate the effect of DSP on the lymphocyte surface markers like thy 1 and B220 by avidin-biotin complex (ABC) technique. Although the mean weights of lungs, liver, spleen and kidneys in the 0.5 mg- and 2.5 mg-DSP groups were not significantly different from those in the control animals, the weights of the heart, lungs, liver and spleen in the 5 mg-DSP group were significantly lower. Histopathological studies by light microscopy revealed no abnormalities in the heart, lungs, liver or kidneys taken from the mice given 0.5-5.0 mg/kg DSP. In contrast, significant changes were observed in the spleen and bone marrow of the 5.0 mg group of mice. Likewise, in the intestine of the 0.5-5.0 mg groups dose-dependent lesions, such as degeneration or disappearance of the mucosal epithelium, infiltration by inflammatory cells, and pseudo-membrane formation, was observed. By ABC technique, preferential decrease of B cells was seen in the splenic corpuscles of the DSP-treated mice. Histopathological changes due to DSP predominantly seen in the lymphoid and/or hematopoietic organs may be directly related to the immunosuppressive potency inherent to this drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Involvement of endothelial cells in relaxation and contraction responses of the aorta to isoproterenol in naive and streptozotocin-induced diabetic rats.

Experiments were designed to investigate the importance of the endothelium in the relaxation of isolated rat aorta caused by a beta adrenoceptor agonist. Mechanical removal of the endothelium attenuated the relaxation induced by isoproterenol (ISO) and did not affect the relaxation produced by forskolin and by sodium nitroprusside. High concentrations of ISO produced an increase in the resting tension of aortic strips with and without endothelium in a concentration-dependent manner. Mechanical removal of the endothelium or treatment with methylene blue enhanced the maximal contraction induced by ISO. Phentolamine antagonized the contractile responses induced by ISO. In the case of streptozotocin-induced diabetic rats, both aortic strips with and without endothelium generated concentration-response curves for ISO-induced relaxation that were shifted to the right. The relaxant responses to forskolin and sodium nitroprusside were not significantly different between vessels from diabetic and age-matched control rats. In both aortic strips with and without endothelium, the maximal contraction in response to high concentrations of ISO was significantly enhanced in strips from diabetic rats. These results suggest that ISO-induced relaxation of aortic strips with endothelium is mediated by beta adrenoceptors on both the endothelium and the smooth muscle, and high concentrations of ISO produce an increase in the resting tension through alpha adrenoceptors. It is further suggested that the decreased relaxant response of the aorta to ISO in diabetes may be due to decreased density or affinity of beta adrenoceptors on the smooth muscle.

Animals↗
PubMed1989

[Recovery kinetics of hematopoiesis after peripheral blood stem cell autotransplantation].

Hematopoietic recovery kinetics was evaluated in five children with therapy-refractory cancers who received peripheral blood stem cell autotransplantation (PBSCT) following marrow-ablative chemotherapy. Four children received graft containing more than 1.5 X 10(4) CFU-GM/kg and days required to achieve granulocyte counts of greater than 0.5 X 10(9)/l were 6, 10, 13, and 18, respectively. One patient received 0.9 X 10(4) CFU-GM/kg, but, recovery of granulopoiesis was retarded (greater than 30 days). The days required to achieve platelet count of greater than 50 X 10(9)/l were 12, 15, 16, 195, and greater than 240, respectively. Transient decrease of blood cell counts developed 3 to 5 weeks after transplantation and thereafter, the recovery of hematopoiesis became stable. With the use of a large number of progenitors, PBSCT seems to be safe and effective new type of stem cell rescue operation as an alternative to bone marrow transplantation.

Acute Disease↗
PubMed1989

[Effect of recombinant human erythropoietin administration on cardiovascular system in patient with chronic renal failure: an analysis of the blood pressure upward].

To investigate the mechanism of blood pressure upward after recombinant human erythropoietin (EPO) administration in patient with chronic renal failure (CRF), hemodynamic changes following on the improvement of anemia was evaluated by the echocardiography. Fourteen (5 males, 9 females) normotensive patients with less than 23% of hematocrit (HT) were administered 1,500 approximately 3,000 units of EPO three times a week. Four patients with systolic (greater than 160 mmHg) or diastolic (greater than 90 mmHg) hypertension after EPO administration was named group H, the remaining patients was named group N. Blood pressure, heart rates and parameters of echocardiography examined after the improvement of anemia were compared to those examined before EPO administration, respectively. Patients had an increase in Ht from 20.0 +/- 1.6% to 33.0 +/- 1.9% (p less than 0.01). LVDd, LVEDV, CO and flow velocity in group N were significantly decreased after EPO administration; while those in group H did not show the significant changes. IVSth and LVPWth in each group were significantly increased after EPO administration. These data showes that decrease in CO maintains the patients normotensive after EPO administration.

Adult↗
PubMed1989

[Successful right pneumonectomy in pulmonary aspergilloma].

Right extrapleural pneumonectomy was performed on a 50-year-old male with aspergilloma suffering from severe hemoptysis. The post operative course was uneventful and he was discharged on the 30th day following operation. Aspergilloma is a potentially life threatening disease with large hemoptysis. So surgery is the only choice for treatment. We discussed the preoperative and postoperative problems including selection of the operative techniques for pulmonary aspergilloma.

Aspergillosis↗
PubMed1988

Similarities between the relaxations induced by vasoactive intestinal peptide and by stimulation of the non-adrenergic non-cholinergic neurons in the rat stomach.

The characteristics of the non-adrenergic, non-cholinergic inhibitory response of the rat stomach fundus to transmural nerve stimulation were compared with the relaxation induced by vasoactive intestinal polypeptide (VIP). Treatment with alpha-chymotrypsin (5 U/ml) or VIP antiserum (1:200) significantly reduced the relaxation induced by transmural nerve stimulation at 30 Hz, indicating that the possible transmitter in the non-adrenergic, non-cholinergic nerves is a peptide and may be VIP or a closely related peptide. VIP was able to relax, fully and dose-dependently, the stomach fundus that had previously been constricted by treatment with 10(-6) M serotonin, and the IC50 value for VIP was 2.4 X 10(-9) M. VIP elevated levels of cyclic AMP in a dose-dependent manner and the EC50 value was 2.8 X 10(-9) M in the presence of 10(-6) M atropine and 10(-6) M guanethidine. The stomach fundus was relaxed by transmural nerve stimulation (30 Hz, 50 mA) and transmural nerve stimulation also caused production of cyclic AMP in the rat stomach in the presence of atropine and guanethidine. The basal level of cyclic AMP in the stomach was 8.7 +/- 0.26 pmole/mg protein. When transmural nerve stimulation was applied for 5 min, the contraction of the stomach, induced by 10(-6) M serotonin, was inhibited by 54% in the presence of atropine and guanethidine and the level of cyclic AMP was increased to 13.0 +/- 0.73 pmol/mg protein. Apamin inhibited the transmural nerve stimulation-induced relaxation and shifted the dose-response curve for VIP to the right.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Lupus nephropathy in New Zealand F1 hybrid mice treated by (-)15-deoxyspergualin.

The effect of (-)15-deoxyspergualin (15-dsp), a new immunosuppressant which was originally separated from the culture filtrate of a strain of Bacillus laterosporus, was evaluated in this study. Various doses of 15-dsp were subcutaneously administered to New Zealand black/white F1 hybrid mice (B/WF1) four times a week starting at 14 weeks of age, just prior to the onset of nephropathy. The life span of the treated animals, studied at 0.6 to 6.0 mg/kg body weights, compared with the control mice was significantly prolonged by 15-dsp treatment (percent survival of the treated mice at 50 to 70 weeks of age was significantly higher than that of the control mice, except that of the 0.6 mg group at 60 wks of age, P less than 0.05 by Fisher's exact test). In the 6.0 mg group of mice, complete suppression of spontaneously progressive splenomegaly with decreased total spleen cells was observed at 24 through 36 weeks of age compared with the same-aged control group of mice (P less than 0.01). Absolute numbers of L3T4+ splenocytes determined by flow cytometry, as well as L3T4+/Lyt2+ ratio, were decreased, while in vitro interleukin 2 production by splenocytes induced with staphylococcal enterotoxin A was significantly enhanced. Serum IgG anti-ds DNA antibody levels, measured by radioimmunoassay in the treated mice, were significantly lower at 24 through 36 weeks of age than those in the control mice (P less than 0.01), and the incidence of significant proteinuria (greater than or equal to 100 mg/dl) in the 15-dsp group was lower at both 32 and 36 weeks of age (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗