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Biomedical subjects

K Tsuruta

Publications and source records attributed to K Tsuruta.

At least 55 records · Page 3Linked to original sources

Genetic changes and histopathological grades in human hepatocellular carcinomas.

Loss of heterozygosity (LOH) on chromosomes 1p, 4q, 5q, 8p, 13q, 16q, 17p, and 22q, and mutation of the p53 gene were simultaneously analyzed in 63 hepatocellular carcinomas (HCCs) with distinct histopathological grades, 80% of the tumors being from patients who had been exposed to hepatitis B virus (HBV) or hepatitis C virus (HCV). The frequencies of LOH on 8 chromosomes were 0-25% in 10 well differentiated HCCs, LOH being observed on 4q, 5q and 17p, 21-53% in 26 moderately differentiated HCCs, LOH on 8p and 17p being high, and 29-75% in 27 poorly differentiated HCCs, LOH on 17p, 4q and 8p being the most frequent. p53 gene mutation was detected in moderately and poorly differentiated HCCs at 15% and 52%, respectively, but not at all in well differentiated HCCs. Of the mutations detected, 42% were transition mutation and only 5% were CpG transition, in contrast to the high frequencies of these types of mutations in colon tumors (78% and 54%, respectively). LOH on every chromosome and p53 mutation were more frequent in more advanced tumors, and accumulation of genetic changes increased with increase of the histopathological grade. Frequency of genetic changes in HCCs from HBV-positive patients was comparable to that from HCV-positive patients. The present results suggest that accumulation of genetic changes in multiple tumor suppressor genes, especially LOH on 17p, 4q and 8p, and mutation in p53 gene, are involved in the progression of liver cancer, and LOH on 17p and 4q precedes other genetic changes. Differences in the direction of p53 mutation between HCC and colon carcinoma suggest that liver carcinogens are distinct from colon carcinogens. Furthermore, mechanisms affecting the frequency of LOH in HCCs in HBV-infected patients may be similar to those in HCV-infected patients.

Base Sequence↗

[Successful documentation by coronary angiography of spontaneous simultaneous multivessel coronary spasm in a variant angina patient: a case report].

A 59-year old female who complained of chest discomfort was admitted to our hospital. Electrocardiogram (ECG) on admission and treadmill exercise test showed negative for ischemia. She underwent coronary arteriography. Initial angiography showed there was no significant coronary arterial stenosis. However, when we were preparing the spasm provocation test, she complained of the same kind of chest discomfort as she had felt before. We found that ST segment was elevated in both the anterior and inferior leads on the ECG. Coronary arteriography showed that severe spasm occurred in both the left anterior descending artery (Seg. 6) and the right coronary artery (Seg. 1). Heart rate decreased and electromechanical dissociation occurred. She temporarily lost consciousness. After cardiopulmonary resuscitation, she recovered and the elevation of ST segment returned on the ECG. This is the first case report which has documented spontaneous simultaneous multivessel coronary spasm by coronary arteriography.

Angina Pectoris, Variant↗

Frequent loss of heterozygosity for loci on chromosome 8p in hepatocellular carcinoma, colorectal cancer, and lung cancer.

Frequent loss of heterozygosity at chromosomal loci in a specific tumor type may indicate the presence of a tumor suppressor gene. We have examined loss of heterozygosity on chromosome 8p in paired tumor and constitutional DNA from 346 patients representing seven different types of human cancer. Frequent allelic losses were observed in hepatocellular carcinoma (22 of 46 cases, 47.8%), in colorectal cancer (12 of 26, 46.2%), and in non-small cell lung cancer (14 of 35, 40.0%), in contrast to low frequencies detected in breast cancer (5 of 56, 8.9%) and renal cell carcinoma (2 of 27, 7.4%). Ovarian cancer and gastric cancer showed intermediate frequencies of 33.3% and 22.2%. Subsequent analysis of 120 hepatocellular carcinomas and 94 colorectal cancers with five polymorphic markers along the short arm of chromosome 8 defined commonly deleted regions within the same chromosomal interval, 8p23. 1-8p21.3, suggesting that one or more tumor suppressor genes for both cancers may be present in that region.

Alleles↗

Lymphoplasmacytic sclerosing pancreatitis with cholangitis: a variant of primary sclerosing cholangitis extensively involving pancreas.

Pancreatic involvement in primary sclerosing cholangitis (PSC) is an extremely rare condition, and its pathologic features are poorly documented. We report two cases of an unusual lymphoplasmacytic sclerosing inflammatory disease involving the total pancreas, common bile duct, gallbladder, and, in one patient, the lip. Two elderly men presented with waxing and waning obstructive jaundice, and exhibited radiologic and ultrasonographic findings highly suggestive of pancreatic carcinoma. Gross appearance of the pancreas showed firm and mass-like enlargement with regional lymph node swelling. Histologic findings were characterized by diffuse lymphoplasmacytic infiltration with marked interstitial fibrosis and acinar atrophy, obliterated phlebitis of the pancreatic veins, and involvement of the portal vein. Similar inflammatory processes involved the bile duct and the gallbladder. Lymphoplasmacytic sclerosing pancreatitis with cholangitis is thought to be a more appropriate term for this condition, of which a similar lesion has been previously noted in a single case of "PSC involving pancreas". Differences in age, radiologic appearance, and the negative history of ulcerative colitis exist, but the two cases in this study could be considered as a variant of PSC extensively involving pancreas, which can readily be mistaken for pancreatic carcinoma.

Aged↗

[Coronary reperfusion using an extracorporeal circulating system performed in cases with abruptly obliterated coronary arteries: a new method].

For the cases with the abruptly obliterated coronary artery during angioplasty or angiography, emergency bypass surgery is mandatory. However, a "bail-out" perfusion catheter with multiple side-holes, which maintains antegrade coronary flow, is not efficient in preventing the myocardium from developing ischemia, because blood flow is interfered due to pressure-dependent perfusion mechanism in the shock state. We developed a new perfusion catheter coupled with an extracorporeal circulating system and a perfusion pump. Its effectiveness and safety were tested experimentally in canine hearts. The system is composed of a perfusion catheter (125 cm in length) with 4 side-holes within 1.5 cm of the catheter tip, and a rolar pump. Maximum flow volumes were 123 ml/min, 84 ml/min, and 52 ml/min for 4.5F, 4.3F, and 4F perfusion catheters, respectively. The left anterior descending coronary artery (LAD) was ligated after the perfusion catheter was advanced into the proximal LAD under fluoroscopic control. To avoid formation of pericatheter intracoronary thrombi, 50 U/kg/hr heparin was continuously injected during a 5-hour ligation. In the nonperfusion group (n = 4), the ST segments elevated in all dogs; 2 died of ventricular fibrillation within 30 min, and one was confirmed to have myocardial necrosis by NBT staining. In the perfusion group (n = 4), neither ECG changes nor hemodynamic deterioration was observed. Intracoronary thrombi were not observed in any surviving dogs. Coronary perfusion using our new device was performed in 2 patients: one patient, a 73-year-old man with 99% stenosis in the very proximal portion of his LAD, had massive intimal dissection after PTCA, and angiography revealed total occlusion of his proximal LAD and LCX. Coronary perfusion was immediately initiated by advancing the perfusion catheter into his LAD. After that the patient recovered from shock. Emergency bypass surgery was successfully performed after 120 min coronary perfusion with the support of IABP and inotropics. The other patient, a 58-year-old man with effort angina, had intimal dissection in the proximal portion of his right coronary artery, which was supplying collaterals to the mid LAD and LCX. Successful bypass surgery was performed 320 min after the coronary perfusion without IABP and inotropics. In conclusion, coronary reperfusion with an extracorporeal circulating system proved to have a greater effect than did passive perfusion in such cases with cardiogenic shock.

Aged↗

A new family with Joseph disease in Japan. Homovanillic acid, magnetic resonance, and sleep apnea studies.

Four male patients and one female patient of a new family with Joseph disease are reported. Their disease was characterized by autosomal dominant inheritance, bulging eyes, rigidity and spasticity of the lower extremities, dystonia, and bradykinesia. Cerebrospinal fluid homovanillic acid level was markedly reduced. Levodopa improved dystonia. Magnetic resonance imaging revealed mild atrophy of the frontal lobe and the cerebellum and marked atrophy of the lenticular nucleus and the brain stem. Polysomnographic studies revealed non-rapid eye movement stage central type sleep apnea syndrome. This is the first report using magnetic resonance imaging and sleep apnea studies of Joseph disease.

Adult↗

An autopsy case of mitochondrial encephalomyopathy: biochemical and electron microscopic studies of the brain.

A 29-year-old single woman had recurrent stroke-like episodes. She developed loss of consciousness, myoclonic seizures, and lactic acidosis. She died at the age of 30. A muscle biopsy study revealed mitochondrial myopathy, and the postmortem biochemical analysis demonstrated decreased cytochrome c oxidase activity in the skeletal muscles by 20% of normal control. The brain had multiple ischemic lesions in the cerebral cortex without major vascular occlusions. We present this case as an autopsy case of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) with a partial deficiency of cytochrome c oxidase. The analytical electron microscopic study of the calcified small vessels in the globus pallidus revealed increased calcium, phosphorus and iron. No accumulation of chromium, nickel or zinc was noted in this case, which was different from the previously reported cases of basal ganglia calcification.

Adult↗

Pulmonary and placental 15-hydroxyprostaglandin dehydrogenase in rat during pregnancy.

15-Hydroxyprostaglandin dehydrogenase (PGDH) in rat lung and placenta during pregnancy was examined using a photometric assay. Pulmonary PGDH activity varied slightly during pregnancy, being significantly higher on days 10 and 19 of gestation than on day 22. Placental PGDH activity changed strikingly according to the day of pregnancy. Activity was relatively high on day 10 of gestation, fell to a low level on day 15, then increased to a maximum on day 22. A rapid fall in pulmonary PGDH activity and a remarkable increase of placental PGDH activity occurred on the day just before parturition. The results suggest that pulmonary and placental PGDH activity may cooperatively contribute to the continuity of pregnancy, and the process of parturition.

Animals↗

New inhibitor(s) of 15-hydroxyprostaglandin dehydrogenase in human milk.

New inhibitor or inhibitors of nicotinamide-adenine dinucleotide-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) activity were found in breast milk but not in powdered milk. Milk samples were obtained manually from 23 puerperae who had delivered at 38 to 41 weeks. The inhibition pattern was competitive and noncompetitive. The percentage of inhibition of PGDH activity kept at 4.0 degrees C increased to a maximum at 12 hours after milk sampling and decreased thereafter. The percentage of inhibition of each milk sample decreased gradually with the duration postpartum. In addition, the inhibitor or inhibitors showed a smaller molecular weight than 1000 daltons and were partially resistant to heat and trypsin. Moreover, they were easily soluble in petroleum ether at various pH values, although the adsorption to C18 cartridge was inadequate. These new factor or factors may increase the benefits of breast feeding.

Animals↗

Selective and persistent deposition and gradual drainage of iodized oil, Lipiodol in the hepatocellular carcinoma after injection into the feeding hepatic artery.

The selective and long-term deposition of iodized oil in the hepatocellular carcinoma (HCC) and its gradual drainage were clinicopathologically analyzed in 13 cases. All patients were Japanese and had an intrahepatic arterial injection of Lipiodol (LIP) mixed with Mitomycin C. The comparison among the follow-up computerized tomography (CT) findings, the observation of the soft x-ray radiogram, and histopathologic studies of the surgical or autopsy materials revealed that the selective deposition of LIP in HCC lasted for a long term, particularly in cases treated by LIP combined with transcatheter arterial embolization (TAE). Also revealed was an extremely gradual decrease of LIP from the HCC. It was thus postulated that, mainly, the accumulated macrophages surrounding LIP around the necrotic cancer tissue and, partially, the intrahepatic lymphatic system itself contributed to this drainage. Further, in histologic sections with lipid staining, x-ray microanalysis proved that the lipid droplets in the cancer tissue included highly concentrated iodine, as a deposition of LIP.

Carcinoma, Hepatocellular↗

Regulation of placental 15-hydroxyprostaglandin dehydrogenase activity by obstetric drugs.

The in vitro effects of obstetric drugs on 15-hydroxyprostaglandin dehydrogenase activity were investigated. Enzyme activity was inhibited by indomethacin, methylergometrine maleate, Solcoseryl, conjugated estrogen and progesterone, and was activated only by isoxsuprine-HCL. Methylergometrine maleate and isoxsuprine-HCl, which have opposite functions on uterine muscle, also exerted contrary effects on enzyme activity. Inhibitory and stimulatory effects of these drugs suggested that they could directly regulate uterine activity and also indirectly influence the uterus due to their effects on prostaglandin catabolism in vivo.

Actihaemyl↗

Purification of an NAD+-dependent 15-hydroxyprostaglandin dehydrogenase from the human placenta.

We purified 15-hydroxyprostaglandin dehydrogenase (PGDH) from the human placenta by gel filtration high performance liquid chromatography (GFHPLC) with spectrophotometric assay for the chromophore of 15-keto PG. Purification steps were as follows; homogenization and centrifugation at 10,000g, for 30 min, ammonium sulfate precipitation, DEAE-cellulose (DE-52), Sephadex G-100 gel filtration, NAD-affinity chromatography (AGNAD type 1), and GFHPLC. The specific activity was increased from 1.5 X 10(-2) unit/mg in the initial supernatant to 1272 X 10(-2) after GFHPLC. PGDH showed a single band on SDS-polyacrylamide gel electrophoresis and the molecular weight determined by GFHPLC and electrophoresis was approximately 50,000 daltons. After 4 months of storage, PGDH in a buffer containing 50% glycerol at -20 degrees C retained 80% of its activity. Michaelis constant for PGE2 was 0.4 microM at pH 7.0 with NAD as a cofactor. These properties of PGDH were compared with the results reported in other literature.

Chromatography, Gel↗

Delta-guanidinovaleric acid as an endogenous and specific GABA-receptor antagonist: electroencephalographic study.

Sporadic spike discharges recorded on EEGs from epidural electrodes appeared 5-10 min after topical application of 0.3 nmol delta-guanidinovaleric acid (DGVA) on the pia mater of the sensorimotor cortex, on the same side as the application. Spike discharges induced by DGVA were completely suppressed within 10 min of supplementary application of GABA (50 nmol), (3R)-(-)-4-amino-3-hydroxybutanoic acid (L-GABOB) (5 nmols) or muscimol (5 nmols) on the pia mater, but the discharges were not affected by supplementing with 500 nmol of alpha-amino-DGVA, i.e., arginine (Arg). Whereas spike discharges were not induced by DGVA together with L-GABOB or muscimol, DGVA applied together with Arg induced spike discharges. Neither phenobarbital (PB) (20 mg/kg, i.m.), diazepam (DZ) (10 mg/kg, i.p.), sodium valproate (200 mg/kg, i.p.) nor diphenylhydantoin (20 mg/kg, i.p.) showed any suppressive effects on spike discharges induced by DGVA. DGVA induced spike discharges 20 min after pre-injection of PB or DZ. These electroencephalographic findings suggest that DGVA, which has one more carbon in its chain than N-amidino-GABA, might act directly on the GABA-receptor to induce spike discharges and might be a specific GABA-receptor antagonist.

Animals↗

[NAD+-dependent 15-hydroxyprostaglandin dehydrogenase from the human term placenta].

A NAD+-dependent 15-hydroxyprostaglandin dehydrogenase was purified from human term placenta using monoclonal antibody-coupled Sepharose affinity chromatography. The monoclonal antibodies were prepared against the molecule which was purified according to the method of Jarabak et al. About 4,800-fold purification was achieved with a 3% yield. The highest specific activity was 1,890 mU/mg. The molecular weight of the enzyme determined by gel filtration was 49,000. Polyacrylamide gel electrophoresis of the purified enzyme revealed the presence of two protein bands which were thought to be derived from the same enzyme molecule. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed two main bands of which the molecular weights were 28,000 to 30,000 and 52,000 to 56,000. Electrophoretic analyses suggest a labile oligomeric structure that may relate to the instability of the enzyme activity, which contradicts the monomer theory reported by Jarabak et al.

Chromatography, Affinity↗

Labile oligomeric structure of human placental 15-hydroxyprostaglandin dehydrogenase.

NAD-dependent 15-hydroxyprostaglandin dehydrogenase has been isolated from human term placenta. About 9,000-fold enrichment was achieved with a yield of 7.6%. Electrophoretic analyses suggested that glycerol stabilized an active structure of the enzyme, and sodium dodecyl sulfate might dissociate it. The instability of the enzyme activity may relate to its labile oligomeric structure which is easily dissociated into subunits.

Electrophoresis, Polyacrylamide Gel↗