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Biomedical subjects

T Wakabayashi

Publications and source records attributed to T Wakabayashi.

At least 19 recordsLinked to original sources

Small-angle synchrotron x-ray scattering reveals distinct shape changes of the myosin head during hydrolysis of ATP.

In the energy transduction of muscle contraction, it is important to know the nature and extent of conformational changes of the head portion of the myosin molecules. In the presence of magnesium adenosine triphosphate (MgATP), fairly large conformational changes of the myosin head [subfragment-1 (S1)] in solution were observed by small-angle x-ray scattering with the use of synchrotron radiation as an intense and stable x-ray source. The presence of MgATP reduced the radius of gyration of the molecule by about 3 angstrom units and the maximum chord length by about 10 angstroms, showing that the shape of S1 becomes more compact or round during hydrolysis of MgATP. Comparison with various nucleotide-bound S1 complexes that correspond to the known intermediate states during ATP hydrolysis indicates that the shape of S1 in a key intermediate state, S1-bound adenosine diphosphate (ADP) and phosphate [S1**.ADP.P(i)], differs significantly from the shape in the other intermediate states of the S1 adenosine triphosphatase cycle as well as that of nucleotide-free S1.

Adenosine Triphosphate

Spontaneous rupture of hepatocellular carcinoma: an approach with delayed hepatectomy.

Two cirrhotic patients with ruptured hepatocellular carcinoma (HCC), presenting with hemoperitoneum, were successfully treated by elective hepatectomy. Both of these patients, a 67-year-old female and a 76-year-old male, had first been taken to other primary hospitals by ambulance due to hypovolemic shock. They were then found to have a mass of approximately 5 cm in the cirrhotic liver. In the initial management, however, neither any direct hemostasis by surgery nor indirect measures such as transcatheter hepatic arterial embolization were performed in either case. Instead, conservative treatment consisting mainly of fresh blood and plasma transfusions were continued for more than a month until the liver function stabilized. In both hepatectomies, the use of a microwave tissue coagulator resulted in minimal intra-operative blood loss and an appreciably excellent post-operative course. These cases point to the effectiveness of a "wait and see" policy for selected patients with ruptured HCC.

Aged

Characterization of human gliomas by a monoclonal antibody both on tissue culture and paraffin-embedded sections.

A monoclonal antibody designated OITIC3-11 was produced against GFAP positive human glioblastoma multiforme tumour cells. The specificity of the monoclonal antibody was tested on different types of human brain tumours and on normal adult brain both on tissue cultures and paraffin-embedded sections. The OITIC3-11 monoclonal antibody reacted with 16 of 18 malignant and 1 of 6 benign gliomas but did not react with meningioma, pituitary adenoma, metastatic brain tumours and normal adult brain tissue.

Animals

Disseminated Pneumocystis carinii infection in a hemophiliac patient with acquired immunodeficiency syndrome.

A case of disseminated Pneumocystis carinii (PC) infection in a 28-year-old Japanese male hemophiliac with acquired immunodeficiency syndrome (AIDS) is reported. The patient had displayed a high fever and diffuse faint interstitial infiltrates on chest X-ray films without dyspnea three months before his death. At that time, no PC was detected after four consecutive induced sputum tests. Serum anti-cytomegalovirus (CMV) IgM was positive by EIA. No treatment for PC and CMV was given at the patient's request. Autopsy findings disclosed disseminated PC infection consisting of granulomas with caseation-like necrosis and frothy exudate in the lungs and disseminated organized calcification in the blood vessels of extrapulmonary organs. PC cysts and/or trophozoites were detected in these lesions.

Acquired Immunodeficiency Syndrome

Effects of alkyl alcohols and related chemicals on rat liver structure and function. III. Physiochemical properties of ethanol-, propanol- and butanol- treated rat liver mitochondrial membranes.

The physicochemical properties of mitochondria in liver tissue obtained from rats given 32% ethanol, 32% propanol or 6.9% butanol in drinking water for up to 3 months were investigated using differential scanning calorimetry and fluorescence polarization measurements. The results obtained were as follows: 1) Phospholipids extracted from mitochondria showed increases in the relative amounts of phosphatidylcholine, phosphatidylinositol and phosphatidylserine, and a decrease in the relative amount of phosphatidylethanolamine. An increase in the unsaturated/saturated fatty acid ratio of phospholipids was also observed. 2) Elevation of the thermotropic lipid phase transition temperature with a decrease in the enthalpy value (delta H) was revealed by differential scanning calorimetry. 3) The elevation of the lipid phase transition temperature was detected also by fluorescence polarization measurements using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a probe. Elevation of mitochondrial membrane fluidity was found in some of the experimental animals, but most showed no changes in comparison with the control. A possible role of membrane fusion in the mechanism of formation of ethanol-, propanol- and butanol-induced hepatic megamitochondria is discussed on the basis of these results.

1-Propanol

Behavioral study on the gracile axonal dystrophy (GAD) mutant mouse.

We investigated motor function and pain sensation in the gracile axonal dystrophy (GAD) mutant mouse, using the tail-flick test and the rotarod test. GAD (gad/gad) and normal sib mice (gad/+ or +/+) were used between 5 and 11 weeks of age, during which time the behavioral signs of GAD mice shifted from sensory ataxia (about 4 to 8 weeks of age) to paresis (after about 9 weeks of age). In the tail-flick test, significant shortening of latency was observed at 6 and 8 weeks of age in female GAD mice, in comparison with normal female mice. This may be related to dysfunction or degeneration of axons in the fasiculus gracilis, whose collaterals are thought to control the transmission of nociceptive information. In the rotarod test, a cumulative chi 2 test showed significant reduction in the performance times of GAD mice beginning at 5 and 6 weeks of age in males and females, respectively, indicating that the rotarod test can detect the development of motor incoordination as early as these ages. The performance times of GAD mice dropped sharply from 9 weeks of age onwards, and this is believed to reflect the progression of paresis. The rotarod test therefore appears to be a good method of quantifying behavioral changes in GAD mice and to be applicable both to objective selection of GAD mice before 8 weeks of age and to evaluation of drugs to treat ataxia or paresis.

Age Factors

Tumor-specific binding of radiolabeled G-22 monoclonal antibody in glioma patients.

Iodine-131-labeled G-22 monoclonal antibody F(ab')2 fragment reaching specifically with a glioma-associated surface glycoprotein was administered to 12 glioma patients to investigate its use in radioimaging of intracranial gliomas. No immediate or delayed side effects were attributable to antibody injection. Nine patients received the radiolabeled complex intravenously. The images of low-grade gliomas were generally poor and disappeared within 4 days. High-contrast images were obtained beyond the 7th day in high-grade gliomas except one case in the pineal region. Three patients received intraventricular or intratumoral administration. Clear images of all tumors were demonstrated from the 2nd until later than the 7th day. One patient with cerebrospinal fluid (CSF) dissemination of brainstem glioma demonstrated negative CSF cytology after intraventricular administration.

Antibodies, Monoclonal

Effectiveness of interferon-beta, ACNU, and radiation therapy in pediatric patients with brainstem glioma.

Sixteen pediatric patients with brainstem glioma were treated with a combination of interferon-beta, 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitroso ure a hydrochloride (ACNU), and radiation therapy (IAR therapy). All patients received 1-1.5 million IU/day of interferon-beta intravenously for 1 week of each 6-week cycle. In addition, ACNU (2-3 mg/kg) was given on the 2nd day of each cycle. Conventional focal irradiation (1.5-2 Gy/day for 5 days to a total dosage of 40-60 Gy) was administered beginning on day 3. Patients underwent at least two 6-week cycles. Adverse effects included nausea, vomiting, and myelosuppression, but were mild and transient. Response to treatment was evaluated by the reduction in tumor size measured on postcontrast computed tomographic scans and magnetic resonance images. Responses occurred in 10 of 11 patients with the intrinsic type of brainstem glioma, including three complete and seven partial responses. Two of five patients with exophytic type gliomas partially responded. The median survival was 15.7 months, a remarkable improvement over the natural course of this disease. These results indicate that IAR therapy is a useful primary treatment for pediatric patients with brainstem gliomas.

Adolescent

Clinical effect of intra-arterial tumor necrosis factor-alpha for malignant glioma.

Recombinant human tumor necrosis factor-alpha was administered intra-arterially to treat 20 cases of malignant gliomas, mostly progressive or recurrent. The optimum dosage was determined to be 1 x 10(5) U/sq m/day. Among the 10 evaluable patients treated at this dosage, two responded (one completely and one partially), resulting in a 20% response rate. Side effects were mild and easily controllable. Improvement of neurological symptoms was noted in 47% of the patients a few days after treatment, even when computerized tomography showed no tumor regression. This might have been due to the pleiotypic biological activity of tumor necrosis factor-alpha. Neuroradiographic observations revealed narrowing of the tumor-feeding artery, a decrease in tumor staining ability, and necrosis in the central part of a tumor. The authors suggest that intra-arterial administration of tumor necrosis factor-alpha may be an effective treatment for malignant glioma, including recurrent cases.

Adolescent

[Endoscopic ultrasonographic study of gastric ulcer treated with proton pump inhibitor].

We examined 70 cases of gastric ulcer by endoscopic ultrasonography. Of these, 18 cases were treated with proton pump inhibitor (PPI), another cases were treated with histamine H2 receptor antagonist or mucosal protective drugs. The Endoscopic cumulative healing rate at the eighth week was 71.4% in all gastric ulcers. On the other hand, all of gastric ulcers treated with PPI were healed within eight weeks endoscopically. Gastric ulcers which were revealed ultrasonographically to be refractory with were healed by PPI therapy. The length of the ulcer echo in gastric ulcers treated with PPI was shorter than that in gastric ulcer treated by other drugs. In spite of endoscopic scar findings, a wide ulcer echo was observed in some cases.

Adenosine Triphosphatases

[A case of multiple myeloma with intracerebral metastasis].

Compared to leukemia, malignant lymphoma and other hematogenous tumors, multiple myeloma rarely metastasizes to the central nervous system. Intracerebral metastasis without involvement of the cranium itself is rarer. We report a case of Ig-G k-type multiple myeloma with metastasis to the left frontal lobe extending to the right basal ganglia without involvement of the cranium. A 71-year-old male complained of exertional dyspnea and lumbago. His laboratory data revealed hyperproteinemia and an abnormal increase in Ig-G (6117mg/dl) in his serum. Serum protein immunoelectrophoresis revealed an IgG k-type band, and Bence-Jones protein was detected in his urine. MMPP, VMCP, VIPP and MP chemotherapy was given, and serum IgG level decreased to a normal range. 21 months after his first admission, incontinence, disorientation, gait disturbance and apathy developed. CT-scan showed an isodense lesion with massive edema in the left frontal lobe and right basal ganglia. On MRI, a Gd-DTPA enhancing lesion was detected extending from the left frontal to the opposite frontal lobe through the splenium. No abnormal skull punched out lesions were noted. Left frontal lobectomy was performed. Histopathology revealed plasmablastic myeloma cells with clear nucleole and eccentric nucleus in the cerebrum. He was diagnosed as having intracerebral metastasis of multiple myeloma without involvement of the cranium. Unfortunately, he died of pancytopenia and pneumonia. Our case suggests the possibility of metastasis via blood into the cerebrum.

Aged

Convulsions in senescence-accelerated mice (SAM-R/1/Eis).

Senescence-accelerated mice (SAM) are one of the animal models used for studying senescence, which consist of several substrains such as SAM-R/1, R/2, P/1, P/2. SAM-R/1/Eis maintained in Eisai Tsukuba Research Laboratories, Ibaraki, Japan, was originally introduced as a substrain of a normal control SAM-R/1 from Kyoto University, Japan. We have noted signs of convulsions in SAM-R/1/Eis mice during routine animal care, particularly while changing cages. We identified the clinical signs and determined the concentrations of glucose and immunoreactive insulin in plasma of SAM-R/1/Eis mice. There were no differences in the male:female ratios of mice showing prodrome only, grand mal, or no-signs. The ages at which prodrome and grand mal were first noted peaked between 20 and 25 weeks. Concentrations of glucose and immunoreactive insulin in plasma did not indicate the mice were in insulin hypoglycemia, which is one cause of convulsions. AKR strain mice, some of which originated with the SAM strain are known to become convulsive by repeated "throwing" stimulations. Conversely, in SAM-R/1/Eis, throwing stimuli are not needed to cause convulsive signs. Thus it is likely that in SAM-R/1/Eis mice the signs are triggered by repeating mild environmental changes, such as changing cages. The results of this study show that SAM-R/1/Eis is neither a normal control strain, nor an original SAM-R/1 strain. But it is possible that SAM-R/1/Eis is another useful animal model for studying spontaneous convulsion.

Aging

S-antigen localization in developing rds mouse retina.

The morphology of the photoreceptor cell and localization of the cytoplasmic soluble protein, S-antigen, in the retina of the developing retinal degeneration slow (rds) mutant mouse (2-505 postnatal days) were studied by improved immunocytochemical and freeze-substitution methods. Anti-S-antigen antibody labeling was observed first in the postnatal 10-day retina under light microscope. Labeling signals increased progressively to a maximum level in 20 days, and then decreased gradually to an undetectable level by 505 postnatal days. By electron microscopic immunocytochemical methods, S-antigen was detected first in the photoreceptor cells at 3 postnatal days, and increased with development. It was located in the entire cytoplasm of the photoreceptor cell including the rudimentary outer segment, but degenerated and disappeared by 505 postnatal days. S-antigen was also present in the membranous vesicles budding off from the photoreceptor membrane to the subretinal space. The rds photoreceptor cell seems to lose other soluble proteins together with these vesicles. From these results and other published data, we speculate that the degeneration of the photoreceptor cells may be the secondary effects of the loss of a large amount of soluble and membrane proteins following the malfunction of membrane. Recent reports show the rds mouse must have a gene defect in the membrane component such as peripherin or the 39 kDa protein.

Animals

[Comparative study of extracorporeal shock wave lithotripsy (ESWL) between spark gap system and piezoelectric system].

We have analyzed the results of the treatment given on 170 cases of cholecystolithiasis, using two different systems of ESWL: Spark Gap System (hereinafter SGS) and Piezoelectric System (hereinafter PES). 1) In the total cases, there were no significant differences in the fragmentation rate between the two systems. PES was, however, superior to SGS in terms of the complete stone free rate. On the other hand, SGS was superior to PES in terms of the average fragmentation rate. 2) We have classified cholecystolithiasis into 4 groups, combining CT and US. PES showed superiority in the ESWL Group 1 (seeming Pure Cholesterol Stone) and Group 2 (seemingly Mixed Stone) in terms of stone free rate. SGS showed superiority in ESWL Group 3 (seemingly Combination Stone) and Group 4 (seemingly Pigment Stone) in terms of fragmentation effect. 3) We have gained good results from both of the system according to Munich Criteria Modified. 4) Concerning the failures of fragmentation and insufficient stone free, further study shall be required to determine whether fragmentation should be repeated, the case should be handled as "beyond adaptability", or the two-system-combined therapy should be applied.

Adult

Isolation and some biochemical properties of porcine pancreas mitochondria.

Morphologically and functionally intact mitochondria were isolated from the porcine pancreas using a conventional, differential centrifugation method. The homogenate of the porcine pancreas made in a medium containing 0.25 M sucrose, 10 mM Tris-Cl, pH 7.4, 0.5% bovine serum albumin and 1 mM EDTA, in the presence or in the absence of dibucaine and trypsin inhibitor, was centrifuged for 10 min at 700xg. The supernatant was centrifuged for 10 min at 7000xg, and the pellet was washed three times. Trypsin activity of mitochondria isolated in the absence of dibucaine and trypsin inhibitor was as low as that of mitochondria isolated in the presence of dibucaine and trypsin inhibitor, and a major part of the activity remained inactivated. Phospholipase A2 activity of the former mitochondria was as low as that of the latter, and remained unchanged up to 8-10 hr at 4 degrees C. The presence of bovine serum albumin and EDTA in the respiration medium was absolutely required to obtain good respiratory controls of those mitochondria. These data suggest that well-coupled mitochondria can be obtained from the pancreas by a conventional isolation procedure without activating the major part of trypsin.

Animals

Nephritogenicity of the lprcg gene on the MRL background.

The novel lymphoproliferative and autoimmune lprcg gene, originally discovered in the CBA/K1Jms (CBA) strain of mice, was transferred onto the MRL/MpJ (MRL) strain background, and the resultant partially congenic MRL-lprcg/lprcg carrying 93% or more MRL genomes on average were examined for immune-complex glomerulonephritis and serological aberrations. Ordinary histological studies revealed that MRL-lprcg/lprcg mice developed glomerulonephritis histologically indistinguishable from that in MRL-lpr/lpr but at a lower frequency than in MRL-lpr/lpr mice. Glomerular immune complex deposition was almost the same in MRL-lprcg/lprcg and MRL-lpr/lpr mice. The levels of serum Ig, circulating immune complexes and autoantibodies in MRL-lprcg/lprcg were comparable to or even higher than those in MRL-lpr/lpr mice. Comparison of the serological abnormalities between MRL-lprcg/lprcg with glomerulonephritis and CBA-lprcg/lprcg without it evidenced the enhanced class switch from IgM to IgG responses in both class-specific autoantibody responses and serum Ig levels in MRL-lprcg/lprcg as in MRL-lpr/lpr mice. These results taken together indicate that the lprcg gene functions in much the same manner as lpr in induction of glomerulonephritis and serological abnormalities on the MRL background as expected from the allelism between the two mutant genes.

Animals

Effects of meals on peripheral blood flow reduction by cold exposure in rabbit ears.

Although insulin is known to have various actions on the cardiovascular system, its effects on the microvessels in vivo have not been fully elucidated. This study was aimed to examine the effects of the increased endogenous insulin release after meals on the reflex vasoconstriction induced by cold exposure in the rabbit ears using a laser Doppler flowmeter. A reflex blood flow reduction by cold exposure was tested 3-4 hours after meals in the rabbits with or without pretreatment with a somatostatin analogue (Sandostatin, 100 micrograms/body). The degrees of the blood flow reduction were decreased after the diet intake compared to the responses in the fasting state. The blood flow reduction after diet intake in the non-treated group was significantly attenuated compared to the treated group (88.4 +/- 13.0% in the non-treated group vs. 47.5 +/- 13.4% in the treated group at 1 minute of cold exposure; p less than 0.05, and 87.6 +/- 20.2% vs. 40.2 +/- 24.8%, respectively, at 5 minutes of cold exposure; p less than 0.05). The somatostatin-treated rabbits showed a significant suppression of the increase in the serum insulin levels after meals compared to the non-treated control rabbits (17.8 +/- 10.2 microU/ml in the treated group vs. 78.6 +/- 38.3 microU/ml in the non-treated group, p less than 0.05). In the somatostatin-treated rabbits, the exogenously applied insulin caused a decreased response of blood flow to cold exposure. These findings suggest that in the postprandial state the endogenous insulin release may regulate the reactivity of the microvessels to the sympathetic stimuli.

Animals