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Biomedical subjects

M Kodama

Publications and source records attributed to M Kodama.

At least 235 records · Page 13Linked to original sources

Failure of copper incorporation into ceruloplasmin in the Golgi apparatus of LEC rat hepatocytes.

Copper incorporation into ceruloplasmin during ceruloplasmin synthesis was studied by comparing LEC and control rats. Major 132 and 136 kDa ceruloplasmins were found in microsomes and the Golgi apparatus, respectively, isolated from liver homogenates of LEC and control rats. Copper analysis showed that no copper was detected in the ceruloplasmin in the microsomes of either rat. Copper was present in ceruloplasmin in the Golgi apparatus and serum of controls, while it was not detected in ceruloplasmin in the Golgi apparatus and serum of the LEC rat. These results indicate that copper is incorporated into ceruloplasmin in the Golgi apparatus of normal hepatocytes. LEC rats fail to incorporate copper into ceruloplasmin in the Golgi apparatus.

Animals↗

Effects of 15-deoxyspergualin on experimental autoimmune giant cell myocarditis of the rat.

BACKGROUND: The benefits of immunosuppressive therapy for human myocarditis are controversial. The effects of a new immunosuppressant agent, 15-deoxyspergualin (DSG), on rats with experimental autoimmune myocarditis (EAM), an animal model of human giant cell myocarditis, were examined. METHODS AND RESULTS: Lewis rats were immunized with cardiac myosin in Freund's complete adjuvant on day 0. In the first experiment, the effective doses of DSG required to prevent EAM were investigated. Rats were placed into one of five groups: the control group (A) was administered saline from days 1 to 10; group B, 0.3 mg/kg per day of DSG; group C, 1.0 mg/kg per day of DSG; group D, 3.0 mg/kg per day of DSG, and group E, 10.0 mg/kg per day of DSG. Rats were killed on day 28. The heart weight/body weight ratios of the rats of groups D and E were significantly lower than that of the control group. Macroscopic and microscopic scores for myocarditis decreased in groups D and E. In the next experiment, the effects of delayed administration of DSG in preventing autoimmune myocarditis were studied. Two groups of rats received 3.0 and 10.0 mg/kg per day of DSG from days 6 to 15, respectively. Two other groups of rats received the same doses of DSG from days 11 to 20. No preventive effect of delayed DSG treatment was observed. The effects of long-term, delayed initiation therapy then were evaluated. Rats were administered 10.0 mg/kg per day of DSG from days 6 to 25. The heart weight/body weight ratio and macroscopic and microscopic scores of the rats so treated significantly decreased compared with the controls. CONCLUSIONS: It was demonstrated that DSG can prevent the development of cardiac myosin-induced autoimmune myocarditis.

Animals↗

Asymptomatic hyperglycaemia is associated with increased intimal plus medial thickness of the carotid artery.

Atherosclerotic changes have not been demonstrated directly in asymptomatic hyperglycaemic non-diabetic subjects, although high mortality due to coronary heart disease has been reported. We measured arterial wall thickness non-invasively, in order to directly demonstrate atherosclerosis of the carotid arteries of hyperglycaemic non-diabetic subjects and to evaluate its risk factors. The thicknesses of the intimal plus medial complex (IMT) of the carotid arteries of 112 asymptomatic hyperglycaemic non-diabetic subjects (aged 22-81, 95 males and 17 females) were compared with those of 55 healthy male subjects and 211 non-insulin-dependent NIDDM male diabetic patients. The subjects were subgrouped into impaired glucose-tolerant (IGT) subjects who had a 2-h glycaemic level of more than 7.8 mmol/l, and non-IGT subjects whose 2-h glycaemic levels were within 6.7-7.7 mmol/l. Non-IGT and IGT subjects showed significantly greater IMTs than age-matched healthy males and showed no significant differences compared to age-matched NIDDM patients. Multivariate analysis demonstrated that the risk factors for IMT of non-IGT and IGT subjects were age and systolic blood pressure. According to data on the accumulation of atherogenic risks (hypertension, dyslipidaemia, and smoking), IMT increased linearly in non-IGT and IGT subjects. However, non-IGT and IGT subjects without hyperlipidaemia, hypertension, or smoking risk still had significantly greater IMT than age-matched normal males (1.019 +/- 0.063 vs 0.770 +/- 0.111 mm, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Dysphagia caused by an anterior cervical osteophyte: case report.

Cervical spondylosis and ankylosing hyperostosis of the cervical vertebrae are commonly asymptomatic. Dysphagia caused by cervical osteophyte formation is rare. We report a case of spondylotic dysphagia with striking radiographic findings. A massive anterior cervical hyperostosis was resected via the anterior cervical approach with excellent relief of dysphagia.

Cervical Vertebrae↗

Experimental rat model representing both acute and chronic heart failure related to autoimmune myocarditis.

The most important clinical manifestation of myocarditis is congestive heart failure. The precise mechanisms of heart failure during myocarditis have not been elucidated because no animal model that would permit in vivo study of hemodynamics in severe active myocarditis has been available. We monitored hemodynamics and left ventricular function in a rat model of experimental autoimmune myocarditis to determine if this model could be useful for the study of in vivo hemodynamics in severe active myocarditis. Lewis rats were immunized with human cardiac myosin suspended in complete Freund's adjuvant. Baseline hemodynamics were measured using an ultraminiature catheter pressure transducer via the right internal carotid artery, 4 weeks after immunization in one group of rats (acute phase) and 3 months after immunization in another group (chronic phase). Untreated rats served as the control group. Hemodynamic measurements were also obtained after infusion of dobutamine in the acute-phase and chronic-phase groups. The heart weight-to-body weight ratios were significantly higher in both the acute-phase group and the chronic-phase group compared with normal control rats. The baseline left ventricular systolic pressure was significantly lower in the chronic phase group than in the control group. Peak dP/dt and peak -dP/dt were significantly lower in both the acute-phase group and the chronic-phase group compared with the control group. Dobutamine significantly increased left ventricular systolic pressure, peak dP/dt, and peak -dP/dt in the chronic-phase group but caused only minor changes in hemodynamic variables in the acute-phase group. In vivo measurements of hemodynamic variables indicated the presence of left ventricular dysfunction in rats with experimental autoimmune myocarditis. This animal model may be useful for the study of both acute heart failure related to acute myocarditis and chronic heart failure due to diffuse myocardial fibrosis.

Acute Disease↗

Successful management of infantile hepatic hilar hemangioendothelioma with obstructive jaundice and consumption coagulopathy.

A 4-month-old boy with benign hemangioma of the porta hepatis is described. Obstructive jaundice and consumption coagulopathy developed, which were treated by percutaneous transhepatic drainage (PTHD), without resection of the tumor or bypass surgery. Because of tumor regression, the patient has remained free of symptoms even after the PTHD tube was removed. Because juvenile hemangioma is a benign tumor and occasional spontaneous regression is known to occur (as in our case and other reports), it is suggested that complete resection or bypass surgery is not necessary for juvenile hemangioendothelioma, even with obstructive jaundice, if bile drainage is adequately maintained.

Cholestasis↗

Guanidine neurotoxins are released with the digestive fluid of crabs (Crustacea, Brachyura).

During agonistic interactions intertidal crabs, when exposed to air, produce a foam made of digestive secretions, sea water and air bubbles. They also may release their digestive secretions in water when disturbed. Crabs belonging to the families Majidae, Xanthidae and Portunidae from Atlantic and Pacific areas, not related with human poisoning, possess substances in their digestive secretion which are neurotoxic to mice, block action potentials in nerve preparations, and are reversible on washing. After purification in Bio-gel P-2 chromatography and HPLC analysis, the spontaneously regurgitated secretion, the digestive secretion collected by stomach cannulation of crabs, and the water aquarium replete of intertidal crabs kept overnight show the presence of guanidine neurotoxins.

Animals↗

A simple and rapid method for preliminary evaluation of in vivo efficacy of anti-HIV compounds in mice.

In vivo efficacy of anti-HIV compounds is affected by various factors such as bioavailability, metabolism, clearance, and toxicity. Here we report a simple and rapid method that might be useful for preliminary evaluation of in vivo efficacy of anti-HIV compounds. MT-4 cells carrying proviral HTLV-1 were infected with HIV-1 in vitro and injected into the peritoneal cavity of SCID mice or BALB/c mice. Inoculated cells survive for 1-2 days, and support one to two cycles of viral replication which can be monitored by RT activity or p24 content in the supernatants of peritoneal wash fluids. Test compounds were administered either orally or subcutaneously. AZT, DDC and DDI, the nucleoside-type RT inhibitors currently in clinical use, all showed potent anti-HIV-1 activities in this mouse/MT-4 assay. HEPT (E-EBUdM), a non-nucleoside RT inhibitor, also showed potent anti-HIV-1 activity in vivo, whereas TIBO (R82913), another non-nucleoside RT inhibitor, was less active. In protease inhibitors KNI-272 and Ro 31-8959 showed good in vivo activities, while KNI-144, a compound closely related to KNI-272, showed poor in vivo activity. This mouse/MT-4 assay, although having a number of shortcomings as an animal model for HIV-1 infection, may be of some practical utility for preliminary evaluation of in vivo efficacy of potential anti-HIV compounds.

Animals↗

The localization of DMPO spin adducts of OH in endothelial cells exposed to hydrogen peroxide.

Examination by electron spin resonance (ESR) spectroscopy revealed the localization of 5,5-dimethyl-l-pyrroline-N-oxide (DMPO) spin adducts of hydroxyl radicals (.OH) produced by bovine endothelial cells exposed to hydrogen peroxide. Addition of 10 mM chromium oxalate, a line-broadening agent, to the reaction mixture virtually abolished the signal of DMPO-OH spin adducts. Moreover, the spin adducts were recovered in the filtrated fraction of the cell suspension. We, therefore, concluded that the location of DMPO-OH due to .OH radicals produced by endothelial cells was extracellular. Contrastingly, the site of formation of DMPO-OH was confirmed to be intracellular by the effect of Desferal, an iron chelator, and the effect of poly(ethylene glycol), an extracellular scavenger of OH radicals, as previously reported. The DMPO-OH adducts in the cell suspension mixture were degraded by a cyanide sensitive pathway and they were apparently more unstable than in the extracellular fraction. The initial amount of DMPO-OH adducts formed in endothelial cells could potentially be monitored by the DMPO-OH signals in the extracellular reaction mixture better than those in the cell suspension mixture.

Animals↗

An ultrastructural study on experimental autoimmune myocarditis with special reference to effector cells.

The previously described animal model of autoimmune myocarditis induced by immunization of Lewis rats with cardiac myosin was investigated pathologically, ultrastructurally and immunohistologically. Cardiac dendritic cells and infiltrating macrophages were dominantly encamped at the front of the myocarditis. The macrophages accompanied by neutrophils infested cardiocytes, forming rosette figures as a sign of active cardiocytolysis. The dendritic cells reached into intact muscle at a short distance from the inflammation. T cells, the most important candidate for effector cells in this animal model, were generally found at a distance from active muscle necrosis.

Animals↗

Targeting of chrolamphenicol acetyltransferase to human immunodeficiency virus particles via Vpr and Vpx.

Vpr and Vpx are the auxiliary proteins of human immunodeficiency viruses (HIVs) selectively incorporated into mature viral particles. We showed that the bacterial chloramphenicol acetyltransferase (CAT) fused to the N-terminus of HIV-1 Vpr, HIV-2 Vpr, or HIV-2 Vpx was incorporated into mature virions in a type-selective manner. By using chimeric proteins between HIV-1 Vpr and HIV-2 Vpx, we found that the N-terminal side of these proteins was mainly important for type-selective virion incorporation. The C-terminal arginine-rich region of HIV-1 Vpr was also found to transport CAT fusion proteins into virions but without any type selectivity. Furthermore, the corresponding regions of HIV-2 Vpr and HIV-2 Vpx had no such activity. This region of HIV-1 Vpr may interact nonspecifically with viral genomic RNA. Collectively, Vpr and Vpx may provide a means to introduce foreign proteins and other molecules into HIV virions for therapeutic purposes.

Amino Acid Sequence↗

Localization of urokinase-type plasminogen activator, plasminogen activator inhibitor-1, 2 and plasminogen in colon cancer.

We examined the localization of urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitors (PAI-1 and PAI-2) and plasminogen (plg) in 26 cases of colon cancer by immunohistochemical staining. The u-PA antigen was detected in the cytoplasm of cancer cells (18/26) and stromal cells adjacent to cancer tissues (9/26). The localization of u-PA mRNA examined by in situ hybridization was consistent with that of u-PA antigen. The PAI-1 antigen was detected in fibroblasts and endothelial cells (22/26), while PAI-2 antigen was found in cancer cells (20/26). The plg antigen was seen in the extracellular matrix of the cancer stroma. The u-PA expression in cancer cells was significantly more frequently detected in cases with lymph node metastasis than in cases without metastasis. In either PAI-1- or PAI-2-expressing cases, lymph node metastasis seemed to be restrained. These findings indicate that cancer cells themselves produce u-PA, and suggest that u-PA converts plg into plasmin, which dissolves the extracellular matrix surrounding cancer cells, resulting in cancer invasion and metastasis. PAI-1 and PAI-2 may have inhibitory actions on cancer invasion and metastasis mediated by u-PA.

Colonic Neoplasms↗

High cell-density culture system of hepatocytes entrapped in a three-dimensional hollow fiber module with collagen gel.

A compact three-dimensional (3D) module is needed for hepatocyte culture in order to develop an effective hybrid artificial liver system that can retain hepatocellular structure and differentiated functions. We treated the 3D module with collagen gel to entrap rat hepatocytes. This method yielded a high hepatocellular density (2 x 10(7) cells/ml) over a period of 14 days and maintained the secretion of albumin and ureogenesis at the same level as the control monolayer method. The ammonia removal remained at 43% of the Day 0 value over 8 days of perfusion. Our data show that this approach may be useful for liver support therapy in an extracorporeal circuit.

Albumins↗

Relationship between apparent total body clearance of cyclosporin A and its erythrocyte-to-plasma distribution ratio in renal transplant patients.

To establish an optimal method for determining a cyclosporin A (CyA) regimen based on physiological changes that occur during immunosuppressive therapy, the relationship between apparent CyA body clearance (CL/f) and the CyA erythrocyte-to-plasma distribution ratio (CyA-EP) was examined using clinical time courses obtained during routine monitoring. The CyA-EP, which was calculated by a multiple regression formula using routine data, was increased during renal dysfunction involving the normal recovery phase after transplantation, during nephrotoxicity, during acute tubular necrosis, and during acute renal rejection. CyA total body clearance (CLt), calculated by multiplying CL/f and converted bioavailability, fc (which is equal to 0.009 x LD, where LD represents the CyA level in blood per dose ratio), showed hyperbolic decay with increasing CyA-EP (the mean CLt was defined as follows: CLt = 0.937/CyA-EP), whereas fc showed exponential decay with increasing CyA-EP (the mean fc was defined as follows: fc = 0.593 x exp(-0.155 x CyA-EP)). These findings suggest that total CyA body clearance and its bioavailability were suppressed during the renal dysfunction phase. Hence, the mean CL/f as a function of the CyA-EP was given by the following equation: CL/f = 1.390 x exp(0.204 x CyA-EP)/CyA-EP. Since the CyA-EP reflects a patient's disease state and alterations in the CyA pharmacokinetic profile, these model formulae should provide an adequate method for determining a CyA dosage regimen for several disease states after renal transplantation.

Adult↗

Naturally occurring 5-lipoxygenase inhibitors. VI. Structures of ardisiaquinones D, E, and F from Ardisia sieboldii.

New 1,4-benzoquinone derivatives, ardisiaquinones D(2), E(4), and F(5) along with the known ardisiaquinones A(1) and B(3) have been isolated from the leaves of Ardisia sieboldii (Myrsinaceae) and shown to be 5-lipoxygenase inhibitors. Their structures have been elucidated by spectroscopic analysis and chemical degradation. The degree of inhibition of 5-lipoxygenase activity by the ardisiaquinones and some derivatives of ardisiaquinone A is reported.

Animals↗