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Biomedical subjects

M Imakita

Publications and source records attributed to M Imakita.

At least 19 recordsLinked to original sources
PubMed1998

Effects of the endothelin receptor antagonist TAK-044 on hepatocyte element alterations in the ischemic-reperfused liver in Beagle dogs.

BACKGROUND/AIMS: This study was designed to investigate elemental alterations of subcellular organelles (cytoplasm, nucleus, mitochondria) after ischemia of the liver, and the effects of the pre-ischemic administration of an endothelin ETA/ETB receptor antagonist (TAK-044) on subcellular elements. METHODS: We determined serial changes in subcellular elements by X-ray microanalysis using liver biopsy specimens, and we compared the liver functions of a control and a TAK-044-treated group of Beagle dogs, before and after 70% partial ischemia (60 min). TAK-044 was given intravenously at a dose of 3 mg/kg before ischemia. RESULTS: In the control, the Ca concentration in the cytoplasm showed a slight increase after ischemia and a marked increase immediately after reperfusion. It returned to approximately pre-ischemic levels at 6 h after reperfusion. In contrast, in the TAK-044 group, the increase was significantly suppressed. The changes in Na and Cl, which increased in parallel with Ca, were also suppressed in the TAK-044 group. The alterations in K were opposite to those Ca. These changes were also suppressed to a significant degree in the TAK-044 group. Elemental alterations in the nucleus and mitochondria were similar to those in the cytoplasm in both the control and TAK-044 groups. The changes in the liver functions and the electron microscopic findings supported the differences in serial changes in subcellular elements between the two groups. CONCLUSIONS: TAK-044 exhibited a hepatoprotective effect on ischemia-reperfusion injury from the aspect of subcellular elemental dynamics and liver functional and morphologic changes.

Animals↗
PubMed1998

Caffeine inhibits paresthesia induced by herpes simplex virus through action on primary sensory neurons in rats.

Herpetic infection causes paresthesia, including hypoalgesia, in humans and hypoalgesia in rats. This study was conducted to examine the effect of caffeine, which inhibits replication of herpes simplex virus type-1 (HSV) and affects several neuronal functions, on HSV-induced paresthesia in rats. HSV-induced hypoalgesia was suppressed by repeated treatment of unilateral hindpaw with 10% caffeine gel regardless of when the treatment was started. Repeated treatment with acyclovir, an anti-HSV agent, suppressed HSV-induced hypoalgesia only when started before inoculation; acyclovir did not produce therapeutic effects on the HSV-induced sensory abnormality. Many dorsal root ganglion neurons were positive for HSV antigen following HSV inoculation of the hindpaw. Repeated treatment with caffeine and acyclovir markedly decreased HSV antigen-positive neurons in the dorsal root ganglia when started before, but not 2 or 4 days after, infection. These results suggest that topical caffeine inhibited HSV-induced paresthesia through direct action on sensory neurons, and that not only antiviral activity but also direct alteration of neural functions are involved in the caffeine sensory actions.

Acyclovir↗
PubMed1998

Immune response to varicella-zoster virus glycoproteins in guinea pigs infected with Oka varicella vaccine.

A varicella skin test antigen has been developed based on the induction of delayed-type hypersensitivity to varicella-zoster virus (VZV), and has been used to evaluate the immune status to VZV. The authors have purified gB, gE:gI and gH:gL and examined their cutaneous reactivity in guinea pigs infected with Oka varicella vaccine. The cutaneous reaction to each glycoprotein was observed and the maturation process of cutaneous reaction was examined in infected guinea pigs. Cutaneous reaction to gH:gL, a major target of virus-neutralizing antibody, appeared first on day 3 among three glycoprotein complexes and the reaction to gE:gI, the most abundant glycoprotein, became strongest three weeks after infection. The earliest recognition of gH:gL may contribute to minimizing the spread of viral infection. Thus, the skin test may be a suitable marker to assess the cell-mediated immunity in varicella, including vaccine recipients and zoster, in relation to the immune status of glycoproteins.

Animals↗
PubMed1998

Two cases of mesothelial/monocytic incidental cardiac excrescences of the heart.

Two cases of mesothelial/monocytic incidental cardiac excrescences in a 66-year-old female and an 80-year-old male are presented. Lesions had solid and tubular pattern formations which were composed of two predominant cell types of histiocytoid cells and cuboidal cells arranged in strips. The histiocytoid cells were round and had well-defined nuclei with prominent nuclear grooves. They had a low nuclear to cytoplasmic ratio. There were no atypical mitoses. Immunohistochemically, these cells were positive for leukocyte common antigen (LCA) and CD68 (KP-1) but negative for keratin. The cuboidal cells were present in strips, had haphazardly arranged surface microvilli and had small round non-cleaved nuclei. These cells were positive for keratin but negative for LCA, CD68, p53, proliferative cell nuclear antigen, alpha-smooth muscle actin, Factor VIII, epithelial membranous antigen and vimentin. These lesions are probably reactive because of their heterogeneous components; an expected feature for an essentially artifactual lesion that is related to cardiac surgery and invasive catheterization. Immunohistochemical studies are useful for avoiding misdiagnosis of neoplasms.

Aged↗
PubMed1998

Morphometric and histologic assessment of remodeling associated with restenosis after percutaneous transluminal coronary angioplasty.

The role of remodeling in restenosis of coronary arteries on which percutaneous transluminal coronary angioplasty (PTCA) had been performed was investigated. At autopsy, presence (n = 6) or absence of restenosis (n = 5) based on the cross-sectional area of stenosis was determined in 11 coronary lesions. Remodeling was defined as a ratio of the artery area at the PTCA site to that at the reference site of <1.0. According to this definition, remodeling had occurred in all of the lesions in the restenosis group, and in only 1 lesion in the group with no restenosis which had the least residual plaque (p < 0.05). Dense caps of collagen fibers in the adventitia in the vicinity of the disrupted internal elastic laminae were present in all of the remodeling lesions. We suggest that remodeling, which results in adventitial scarring, is one of the major causative factors of restenosis.

Aged↗
PubMed1998

A huge coronary aneurysm resulting from a coronary artery-to-left ventricle fistula.

A huge coronary aneurysm resulting from a coronary artery-to-left ventricle fistula is a rare condition. A 57-year-old male had severe recurrent angina attacks. The cause of angina pectoris was a right coronary artery-to-left ventricle fistula with a huge coronary aneurysm. The histological examination of surgically excised specimens revealed that two vertical smooth muscle layers of media of the aneurysm might be associated with dysplasia. Mucoid degeneration was also shown in the intima and around the vasa-vasorum. Abnormal hemodynamics related to the fistula might have induced these vessel wall changes resulting in the huge coronary aneurysm.

Angina Pectoris↗
PubMed1998

Comparison of percentage area of myocardial fibrosis and disarray in patients with classical form and dilated phase of hypertrophic cardiomyopathy.

This study compared the percentage area of myocardial fibrosis and disarray between hypertrophic cardiomyopathy (HCM) and DHCM (progression to dilatation of the left ventricle in patients with HCM, i.e., dilated phase HCM), and investigated whether DHCM is included in the natural course of HCM. Twenty-six autopsied hearts were studied, 14 from patients with HCM, and 12 from patients with DHCM, classified by age/decade group. The section at the level of the binding site of papillary muscle was used for the morphometrical examination. In the overall evaluation of both ventricles, all 4 HCM age groups showed percentage area of myocardial fibrosis < 10%, and the value gradually increased with age. In contrast, the percentage area of the DHCM cases was over 20%, and these cases showed diffuse massive fibrosis that did not increase with age. The percentage area of myocardial disarray was over 90% in 3 cases with DHCM. The percentage areas of myocardial fibrosis and disarray of the DHCM hearts were extremely high compared with the HCM hearts, indicating that DHCM is not included in natural course of HCM. Other abnormalities including contractile proteins may be important role in the widespread myocardial disarray leading to massive fibrosis in the pathogenesis of DHCM.

Adolescent↗
PubMed1997

Hepatoprotective effect of a nonselective endothelin receptor antagonist (TAK-044) in the transplanted liver.

This study was designed to investigate whether or not a novel nonselective endothelin A/B (ETA/ETB) receptor antagonist (TAK-044) provides hepatoprotection during porcine liver transplantation. The grafts were stored in chilled Euro-Collins solution and recirculated following reflush with lactated Ringer's with (TAK group) or without (control group) TAK-044 (10 mg/kg). Intracellular (cytoplasma, mitochondria, and nucleus) calcium (Ca) concentrations were measured in the hepatic biopsy materials obtained serially at varying time point from donor laparotomy to recipient closure using an electron probe X-ray microanalyzer. Liver function tests also were determined. The cold and warm ischemia times of the grafts were comparable between the two groups. The peak endothelin-1 T-1) concentration after recirculation was significantly higher in the TAK group than in the control group (129 +/- 30 pg/ml vs 26 +/- 6.5 pg/ml). However, release of liver enzymes, increases in total bile acid, and deterioration of indocyanine green retention rate were significantly suppressed in the TAK group. In the control group, the intracellular Ca concentrations, especially in the mitochondrial fraction, were elevated markedly following recirculation of the hepatic arterial flow. In the TAK group, this effect was suppressed. Thus, the supplementary use of the nonselective ETA/ETB receptor antagonist TAK-044 via a rinse route may alleviate an early postreperfusion microcirculatory disturbance of the liver grafts without adverse effects by the increased ET-1 on the systemic circulation.

Animals↗
PubMed1997

Topical cooling-assisted hepatic segmentectomy for cirrhotic liver with hepatocellular carcinoma.

BACKGROUND: A safe limit for normothermic consecutive portal triad occlusion in hepatectomy for the cirrhotic liver was believed to be around 30 minutes. Possibly, the occlusion time can be prolonged by cooling the ischemic liver in vivo. We describe the technique of segmentectomy assisted by topical cooling and its usefulness in prolonging the hepatic inflow occlusion time for cirrhotic livers without causing further ischemic injury. STUDY DESIGN: Fifty patients with hepatocellular carcinoma and chronic hepatic disease who underwent right-sided segmentectomy under hemihepatic inflow occlusion were divided into two groups: normothermic (n = 27), and hypothermic with hemihepatic topical cooling using ice slush (n = 23). Segmentectomies were carried out in the same way in both groups, guided by initial enbloc ligation of the corresponding portal pedicles. RESULTS: The mean right hepatic inflow occlusion time was significantly longer in the hypothermic group than in the normothermic group (53 +/- 22 minutes compared with 17 +/- 9.3 minutes). Despite the significant difference in occlusion time, no differences were found in the recovery of hepatic functions and the incidence of postoperative complications between the groups. Intraoperative blood loss was significantly less in the hypothermic group. CONCLUSIONS: The hepatic right-sided partial inflow occlusion time can safely be prolonged to 60 to 90 minutes in the presence of cirrhosis without causing another injury from ischemia and intermittent reperfusion.

Aged↗
PubMed1996

Cascade of fever production in mice infected with influenza virus.

The cascade of fever production in influenza was studied. To analyse fever production in a murine model, we selected DBA/2 mice that have the highest susceptibility in fibrile responses among seven mouse strains. Intranasal influenza infection- and interferon (IFN)-induced fever production was studied in this mouse model. Fever was induced prominently on day 2 after influenza infection and IFN activity was also increased in serum. Only the level of interleukin (IL)-1 alpha, an endogenous pyrogen, rose markedly in serum among cytokines (IL-1 alpha, IL-2, IFN-gamma, and tumor necrosis factor-alpha) examined. Fever was induced 14 hr after intraperitoneal IFN-alpha treatment and IL-1 alpha level rose significantly in the serum of the IFN-alpha-treated mice as compared with that of untreated mice. Fever production was significantly suppressed by treatment with anti-IFN-alpha/beta or anti-IL-1 alpha antibody in infected mice and the former significantly suppressed responsive IL-1 alpha production, indicating that elevated IFN activity induced IL-1 alpha production and subsequently fever production in infected mice. The activity of cyclooxygenase (COX) that produces prostaglandin (PG)E2 was significantly augmented in the brain of infected mice on day 2 after infection. Fever production was suppressed by the inhibition of COX activity with aspirin, although IL-1 alpha level was maintained at the elevated level. Therefore, influenza infection in mice turned on the following cascade for fever induction: IFN production, IL-1 alpha production, elevated COX activity, and PGE2 production. We elucidated the relationship among IFN activity, IL-1 alpha production and COX activity and demonstrated the cascade of fever production in influenza infection.

Animals↗
PubMed1996

Prophylactic treatment of cytomegalovirus infection with traditional herbs.

Hot water extracts of four traditional herbs, Geum japonicum, Syzygium aromaticum, Terminalia chebula and Rhus javanica, which have been shown to have anti-herpes simplex virus (HSV) activity in vivo, were examined for anti-cytomegalovirus (CMV) activity in vitro and in vivo in this study. They inhibited replication of human CMV and murine CMV (MCMV) in vitro. These anti-CMV activities in vivo were examined in an MCMV infection model using immunosuppressed mice. Mice were subcutaneously treated with various doses of cyclosporine, and immunosuppression and MCMV infection were monitored by suppression of antibody production and virus yield in the lung, respectively. Each herbal extract was orally administered to mice treated with 50 mg/kg of cyclosporine from a day before intraperitoneal infection, and the efficacy of herbs was evaluated by the reduction in the virus yield in the lung. Among them Geum japonicum, Syzygium aromaticum, and Terminalia chebula significantly suppressed MCMV yields in lungs of treated mice compared with water treatment. Efficacy of oral treatment with 750 mg/kg per day of Geum japonicum extract was similar to that of the intraperitoneal administration of 2 mg/kg per day of ganciclovir in increasing the body weight of infected mice and reducing the virus yield in the lungs. These herbs may be beneficial for the prophylaxis of CMV diseases in immunocompromised patients.

Animals↗
PubMed1996

Small cell carcinoma of the uterine cervix with syndrome of inappropriate antidiuretic hormone secretion.

In a 59-year-old woman suffering from the syndrome of inappropriate antidiuretic hormone secretion, a small cell carcinoma of the uterine cervix was detected. The tumor was immunoreactive for antidiuretic hormone as well as for neuron specific enolase, chromogranin A, and Leu-7, but not vimentin. Electron microscopic examination of the tumor revealed neurosecretory granules. To our knowledge, this is only the second report of the syndrome of inappropriate antidiuretic hormone secretion with small cell carcinoma of the uterine cervix and the first one confirmed immunohistopathologically.

CD57 Antigens↗
PubMed1996

[Histopathological study of valvular deposits of amyloid protein in cardiac amyloidosis].

Cardiac amyloidosis is associated with amyloid deposits in cardiac valves which also show the thickening of leaflets and cusps. This study examined amyloid deposits on cardiac valves to investigate the possible involvement in echocardiographic valvular abnormalities in 17 patients with systemic amyloidosis (12 males and 5 females aged 44 to 82, mean 66.4 years) in the autopsy files of the National Cardiovascular Center between 1980 and 1993. All four cardiac valves were examined histologically using hematoxylin-eosin and Congo red stains with polarization. All cusps and leaflets were divided into six segments and all segments of each cusp and leaflet were scored for the proportional area of amyloid deposit (from 0 to 3). The immunohistochemical types of amyloid proteins were immunoglobulin light chain-related (AL) amyloidosis in 16 cases, and amyloid A-related (AA) amyloidosis in one case. Twelve of 16 cases with AL amyloidosis were subclassified as AL lambda type and 4 were subclassified as AL kappa type. In the atrioventricular valve leaflets, the atrial side of basal portion showed the most remarkable amyloid deposits among the six segments. In the semilunar valves, amyloid deposits were mild in the tip and middle portions. Among the patients with AL amyloidosis, those with AL lambda type amyloid appeared to have greater deposits than those with AL kappa type amyloid. Mitral valves appearing abnormal by echocardiography had greater amyloid deposits. However, considering other factors affecting valvular function, the relationship between the localization or the degree of amyloid deposition and endocardiographic valvular abnormalities was unclear.

Adult↗
PubMed1995

Efficacy of kakkon-to, a traditional herb medicine, in herpes simplex virus type 1 infection in mice.

Kakkon-to is one of the representative traditional herb medicines (Kampo formulae) and has been used historically for the treatment of infectious diseases in China and Japan. The efficacy of this preparation was characterised using a cutaneous herpes simplex virus type 1 (HSV-1) infection in mice as a model for human viral infection. Kakkon-to at a dose corresponding to human use reduced significantly the mortality of HSV-1-infected mice and localised skin lesions. Delayed type hypersensitivity (DTH) response to HSV-1 antigen was significantly stronger in treated mice than in untreated mice. However, no histopathological difference was noted in the skin lesions between treated and untreated mice except for the size of the lesions. Kakkon-to did not inhibit the growth of HSV-1 in vitro. Natural killer cell activity, natural cytotoxic killer cell activity, and the population of T-cell subsets in spleen cells of infected mice were not affected by the drug. Kakkon-to did not augment interferon induction and anti-HSV-1 antibody production, nor increased cytokine levels such as interleukin-1 alpha, interleukin-2, interferon-gamma, and tumour necrosis factor-alpha in sera of infected mice. Thus, Kakkon-to induced strong DTH to HSV-1 in infected mice, which may have caused localisation of skin lesions and reduction in the mortality of treated mice.

Animals↗