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Biomedical subjects

M Kurihara

Publications and source records attributed to M Kurihara.

At least 181 records · Page 10Linked to original sources

Specific binding sites for 125I-endothelin-1 in the porcine and human spinal cord.

Specific binding sites for 125I-endothelin-1 (125I-ET-1) in the spinal cord were investigated using quantitative receptor autoradiographic and chemical cross-linking methods. The binding sites were highly concentrated in porcine and human spinal cord areas corresponding anatomically to the dorsal horn (Rexed's laminae I-III), an area around the central canal (lamina X) and the principal part of the intermediolateral nucleus (IMLp). The localization of the binding sites differed from those of 125I-omega-conotoxin GVIA (125I-CgTx) and 125I-Bolton-Hunter substance P (125I-BH-SP), with the exception that the IMLp shared 125I-ET-1 with 125I-CgTx and 125I-BH-SP binding sites. Specific 125I-ET-1 binding sites in the areas examined were characteristically single and of high affinity. There were no differences between the potencies of unlabeled ET family peptides, ET-1, ET-2, ET-3 and sarafotoxin S6b at inhibiting 125I-ET-1 binding to the areas. Chemical cross-linking studies showed that 125I-ET-1 and 125I-ET-3 mainly bound to a protein with molecular mass of 43 kDa in the porcine and human thoracic spinal cord membranes. The present finding shows the neuronal significance of this newly discovered peptide in the spinal cord.

Aged↗

Isolation and primary structure of a novel pheromonotropic neuropeptide structurally related to leucopyrokinin from the armyworm larvae, Pseudaletia separata.

A novel pheromonotropic neuropeptide has been isolated from a head extract of the armyworm larvae, Pseudaletia separata, by a seven step purification procedure using an in vivo assay with decapitated female moths of Bombyx mori. Amino acid sequence analysis and comparison with synthetic peptides established the primary structure of the peptide, termed Pseudaletia pheromonotropin (Pss PT), as H-Lys-Leu-Ser-Tyr-Asp-Asp-Lys-Val-Phe-Glu-Asn-Val-Glu-Phe-Thr-Pro-Arg-Le u-NH2. Pss PT is structurally related to leucopyrokinin, an insect myotropic neuropeptide, and possesses the C-terminal pentapeptide, Phe-Thr-Pro-Arg-Leu-NH2, responsible for the biological activity.

Amino Acid Sequence↗

Severe type Hunter's syndrome. Polysomnographic and neuropathological study.

The clinico-pathological and polysomnographical findings of an adult male patient with severe type of Hunter's syndrome are presented. He died of respiratory failure aged 19, which was much older than the average in this disease. Mucopolysaccharidosis was suspected at the age of one year, and diagnosed by leucocyte enzyme assay at 4 years of age. Mental and physical activity gradually deteriorated until his death. He often showed central type sleep apnea during the sleep stage 2, in addition to common obstructive apnea in Hunter's syndrome. The autopsy showed marked fibrous thickening of the endocardium and valves, enlargement of the liver and spleen, dilatation of the lateral ventricles and diffuse atrophy of the brain. Histologically, diffuse cytoplasmic vacuolations were found in fibroblast-like cells in the thickened endocardium and vascular walls, in Kupffer cells, and in many neurons of the central and peripheral nervous systems. Most neuronal inclusions were considered to be a ganglioside, and in other cells to be a mucopolysaccharide, by their ultrastructure. Massive accumulation of ganglioside in the neurons in the respiratory center might be reflected on central type sleep apnea.

Adult↗

Squamous cell carcinoma of unknown origin in middle mediastinum.

We report a rare case of squamous cell carcinoma located in the middle mediastinum as a solitary mass. Histologically, lymphatic tissues remained together with nests of squamous cell carcinoma which were occupying the greater part of the mass. Examinations of the whole body failed to detect a primary site of the squamous cell carcinoma. It is considered that the carcinoma cells reflect metastasis from a primary-unknown carcinoma (most likely TO lung squamous cell carcinoma) or that they originated from benign epithelial inclusions in a mediastinal lymph node.

Carcinoma, Squamous Cell↗

[A clinical course and autopsy results of an 8-year-old severely handicapped girl with marked periventricular leukomalacia].

We reported a clinical course and autopsy results of an 8-year-old severely handicapped girl with marked periventricular leukomalacia. She was well until 3 days prior to first admission in local hospital. Two days prior to admission, she began to vomit. Twelve hours later, she was noted to be lethargic and developed malaise with frequent vomiting. At physical examination on admission, she had frequent fits and her posture was decerebrate rigidity. Consciousness disturbance continued for two weeks. Thereafter, she became severely handicapped with spastic quadriplegia, mental retardation and intractable epilepsy. She was transferred to our hospital one month later. We cared her totally and carefully with our rehabilitation staff, but during her course several rare happening occurred; she suffered from subdural hemorrhage due to hypocupremia and received an operation for the release of contracture of her hips. She died of acute cardio-respiratory failure at 8 years and 5 months of age. Her autopsy findings were characteristic of the damage to an immature brain during development; cactus formation of cerebellar cortex and periventricular leukomalacia.

Acute Disease↗

[Mycobacterium fortuitum pulmonary infection in a healthy 17-year-old man].

A 17-year-old man was admitted with a 5-month history of intermittent dyspnea on exertion, 10 kg weight loss, cough, sputa and fever. He did not smoke, had no apparent underlying pulmonary disease, and was not immunocompromised. Mycobacterium fortuitum was cultured from sputa at admission. Chest radiograph showed many thin-walled cavities and infiltration in the bilateral middle and upper fields. Chest CT detected multiple cystic lesions that were not revealed in conventional X-ray. It was suggested that the formation of the cystic lesions was one of the predisposing factor of Mycobacterium fortuitum pulmonary infection in this patient. The pneumonic change improved after six-month treatment using isoniazid, rifampicin and streptomycin, despite in vitro resistance of the bacilli to all of these drugs.

Adolescent↗

[An autopsy case of acute encephalopathy associated with hypertrophy of the inferior olives].

We presented an autopsy case of a severely handicapped girl with sequelae of acute encephalopathy at 10 months old. The autopsy findings were diffuse leukomalacia in cerebral medulla, loss of nerve cells and marked gliosis in thalamus, leukomalacia with fibrous gliosis in central tegmental tracts, and marked fibrous gliosis of the cerebellar hemisphere. Purkinje cells were spared much more than granular cells. Hypertrophy of the nerve cells in the inferior olives were seen and the bundles of its efferent nerve fibers were thin. This case is worth reporting that she has suffered from brain damage about 8 years before, and the inferior olives are hypertrophic yet.

Acute Disease↗

[Endoscopic treatment of early colorectal cancer].

Early cancer of the colon and rectum is currently treated by endoscopic or surgical resection. We studied the indications for endoscopic treatment of early colorectal cancers (80 lesions) in relation to the size and macroscopic findings. The endoscopic treatment consists of polypectomy for a pedunculated or a sessile polyp and strip biopsy for a plaque-like or a depressive lesion. Microscopic or most small cancers were completely treated endoscopically. From macroscopic findings of the early cancers, type Ip (less than 2cm and 2cm in diameter) was completely treated by polypectomy, type I s and type II a (less than 1cm and 1cm in diameter) by polypectomy or strip biopsy, and type II c (less than 0.5cm and 0.5cm in diameter) by strip biopsy.

Colonic Neoplasms↗

[Effect of glycerol and mannitol on the distribution of brain tissue water determined by differential calorimetric scanning analysis].

To further clarify their mechanisms as "dehydrators", the effect of glycerol and mannitol on the distribution of tissue water was studied by using differential scanning calorimetry. In normal rat brain, glycerol, 30 minutes after infusion, reduced, by a certain amount, the free water contents. However, mannitol had no effect on the amount of tissue water. In the focal ischemic model, produced by Tamura's method, glycerol reduced the free water contents in the perifocal brain tissue. As for the contralateral brain tissue, mannitol not glycerol, reduced the total water contents. Above findings suggest that the effect of glycerol is mainly to decrease free water fraction in the non ischemic brain tissue, while mannitol shows its effect through the decrease it produces in the extra-brain water fraction.

Animals↗

[A phase II clinical study of cis-diammine glycolato platinum, 254-S, for gastrointestinal cancers. 254-S Gastrointestinal Cancer Study Group].

A phase II clinical study of 254-S, a new anticancer platinum complex for gastrointestinal cancers, was conducted by the 254-S Gastrointestinal Cancer Study Group consisting of 16 institutions. 254-S was administered at 100 mg/m2 by intravenous drip infusion. This administration was repeated at 4-week intervals. The cases in which 254-S could be administered at least two times were regarded as complete cases evaluable for tumor response; of 75 cases registered, 53 were complete cases (29 cases with esophageal cancer, 12 with stomach cancer and 12 with colon cancer). As a result, 15 partial responses (PR) were obtained in the 29 patients with esophageal cancer and 1 PR from the 12 patients with stomach cancer, for a 51.7% and 8.3% response rate, respectively. 5 PR (55.6%) were obtained in 9 esophageal cancer patients with prior chemotherapy, including 2 PR in 4 patients previously treated with cisplatin. Major toxic effects observed were hematotoxicity including thrombocytopenia (59.0%), leukopenia (68.9%) and anemia (57.4%) and gastrointestinal toxicity such as nausea and vomiting (63.9%) and anorexia (41.0%); since grade 3 or 4 thrombocytopenia was observed with an incidence of 27.9%, careful monitoring seems to be required during the treatment with this product. Abnormal parameter changes on renal function included elevations of BUN (18.0%) and serum creatinine (9.8%). Based on these results, it was concluded that 254-S is a useful anticancer agent for the treatment of esophageal cancer.

Antineoplastic Agents↗

Neurones with epileptiform discharge in the central nervous system and chronic pain. Experimental and clinical investigations.

Epileptiform discharge was recorded from neurons in the thalamic nuclei of chronic pain patients during stereotactic surgery. Hyperactive neurons showed regular firing of 3-5 trains of epileptic-like group discharges with a frequency of 4 to 5 Hz. As described by Lombard et al. (1979), we operated on the dorsal root unilaterally, sectioning C5 to Thl in male Wistar rats. One to three months after the operation, hyperactive neurons were examined in the contra-lateral thalamic nuclei (VP, zona incerta), and lemniscus medialis. The firing patterns and distribution of hyperactive neurons in these animals was very similar to those of humans. The hyperactive neuron was unaffected by electrical stimulation of the nucleus raphe dorsalis (NRD) and locus ceruleus (LC). Administration of phenytoin and diazepam reduced the firing. However, no effect was seen with valproic acid. During spreading depression of the sensorimotor cortex, a remarkable reduction was seen on the firing of thalamic hyperactive neurons. This suggested that hyperactive neurons of the thalamic nuclei received facilitory effects from the sensorimotor cortex with little influence from adrenergic or serotoenergic systems.

Animals↗

A cooperative randomized study on tegafur plus mitomycin C versus combined tegafur and uracil plus mitomycin C in the treatment of advanced gastric cancer.

A randomized controlled trial involving 13 institutions in Japan was conducted in order to compare the efficacy of tegafur plus mitomycin C (MMC) (Regimen A) and UFT (a combination of uracil and tegafur at a molar ratio of 4 to 1) plus MMC (Regimen B) for patients with advanced gastric cancer, who had not received any prior cancer chemotherapy. Regimen A (tegafur + MMC) consisted of 5 mg of MMC/m2/week given intravenously, and 500 mg of tegafur/m2/day given orally. Regimen B consisted of the same schedule of MMC and 375 mg of UFT/m2/day given orally. One hundred and eighty-six patients with primary gastric cancer were entered; 183 were eligible and 3 were ineligible for the study. A total of 169 were evaluable for efficacy of the treatment, including 90 patients with Regimen A and 79 with Regimen B. A response rate of 7.8% (7/90 cases) for Regimen A and one of 25.3% (20/79 cases) for Regimen B were obtained, indicating a significantly higher response rate for Regimen B according to the Criteria for Evaluating Efficacy of Chemotherapy/Radiation Therapy in the Treatment of Gastric Cancer (P = 0.004). Regarding side effects, no marked differences in either severity or incidence were observed between the two groups. The group assigned to Regimen B showed a significant survival advantage after adjustment for major prognostic factors using a proportional hazards model (P = 0.0398). Moreover, a close correlation of antitumor effect and survival duration was found when the above criteria were used.

Administration, Oral↗

Autoradiography of atrial natriuretic peptide (ANP) receptors in the rat brain.

Quantitative autoradiography was used to localize and characterize atrial natriuretic peptide (ANP) receptors in the rat brain and to study their regulation. Peptide receptors are selectively located to circumventricular organs outside the blood brain barrier, such as the subfornical organ, and to brain areas involved in fluid and cardiovascular regulation. Dehydration, either by water deprivation of normal rats, or chronic dehydration present in homozygous Brattleboro rats lacking vasopressin, results in large increases in ANP binding in receptor number in the subfornical organ. In the deoxycorticosterone acetate (DOCA)-salt hypertensive model, only salt treatment, but not DOCA alone or the combination of DOCA-salt, increased the ANP receptor number in the subfornical organ and the choroid plexus. Both young and adult genetically hypertensive rats have a greatly decreased ANP receptor number in the subfornical organ and the choroid plexus. Selective displacement with an inactive analog lacking the disulfide bond (ANP 111-126) suggests that genetically hypertensive rats may lack C (clearance) atrial natriuretic peptide receptors. Our results implicate brain atrial natriuretic peptide receptors in the central response to alterations in fluid regulation and blood pressure.

Animals↗

Specific 125I-endothelin-1 binding sites in the central nervous system.

The quantitative receptor autoradiographic method we used revealed that specific 125I-endothelin-1 (125I-ET-1) binding sites are highly concentrated in the choroid plexus (ChP), subfornical organ (SFO), lacunosum molecular layer of the hippocampus (LMol) and granular layer of the cerebellum (GC) of the rat brain. High densities of the binding sites were also observed in the laminae I-III and intermediolateral nucleus of the porcine spinal cord. 125I-ET-1 bound to the rat ChP and LMol with a high-affinity and to the SFO and GC with a low-affinity. The possibility that ET-1 acts as a neuropeptide within the central nervous system by interacting with specific receptors would have to be considered.

Animals↗

Human monocyte antigens in a random sample from Japan.

We studied a random sample of Japanese and compared both Japanese and German monocyte antigen frequencies and performed a segregation analysis in Japanese families. In Japanese, the following gene frequencies were established: 0.1033 for HMA-A1; 0.0299 for HMA-A3; 0.0033 for HMA-A6; 0.1521 for HMA-B2. Data on the gene frequency in Germans were presented by Rose. In this comparison, the frequency for HMA-B2 in Japanese is more than two times higher; for antigen HMA-A6, the Japanese is a fifth of the German quantity. The antigen HMA-B4 was not found in Japanese. The results we obtained from family analysis confirmed an unambiguous autosomal, codominant inheritance of the examined HMA antigens.

Gene Frequency↗

[Phase I clinical study of zinostatin stimalamer (YM 881) by intravenous injection].

A phase I clinical study by intravenous injection of zinostatin stimalamer (YM 881), a protein anti-cancer drug, was conducted in 50 patients with malignant tumors. The initial dose was 0.5 mg/m2 (n) in the single dose test, and 0.2 mg/m2/day in the repeated dose test for 5 successive days. Doses were increased up to 12n according to the modified Fibonacci's method in both the single and repeated dose tests. The dose limiting factor was thrombopenia in both the single and repeated dose tests. The maximum tolerated dose was 6.0 mg/m2 (12n) in the single dose test, and the subtoxic dose was 2.4 mg/m2/day in the five day repeated dose study. These results indicate that dose of 1.0 to 1.4 mg/m2/day (5 n to 7 n) are appropriate for the phase II repeated dose study.

Adult↗

[Early phase II study of YM 881 (zinostatin stimalamer) by intravenous injection. Research group for intravenous YM 881].

An early phase II multicentered study of YM 881 (zinostatin stimalamer) was conducted in 36 patients to investigate response and the safety of the drug in malignant tumors. The response could be evaluated in 18 patients, one with brain tumor, 2 with lung cancer, one with breast cancer, one with liver cancer, one with pancreatic cancer, 6 with gastric cancer, and 6 with colon cancer. PR was found in the patient with brain tumor. Major subjective unwanted effects were gastrointestinal symptoms. Objective evidence of hematological changes (thrombocytopenia, decreased hematocrit, and lymphocytopenia) was also obtained.

Adult↗

[Phase II clinical trial of anticancer drugs].

For the evaluation of the therapeutic efficacy of anticancer drugs, we should perform the clinical trials step by step under the protocol with well designed and considered the ethical aspects. In the phase II study, it should determine whether a drug has antitumor activity. In our country, many investigators used the criteria of the Japan society for cancer therapy and also used the criteria made by every society of medical department. It should have a formal registration mechanism for entry. And all patients including the ineligible and incomplete cases (withdrawal and dropouts) should be reported. This is particularly important in the assessment of response rate, because response rate is directly influenced by the numbers of ineligible and incomplete cases. The efficacy is effected by the various prognostic factor and it is necessary to arrange the patients with uniform prognostic factor. The adequate sample size also should be required enough to establish the efficacy of the antitumor activity.

Antineoplastic Agents↗