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Biomedical subjects

T Ohta

Publications and source records attributed to T Ohta.

At least 811 records · Page 45Linked to original sources

Changes in monoamine levels in mouse brain elicited by forced-swimming stress, and the protective effect of a new monoamine oxidase inhibitor, RS-8359.

As a stress model, a forced swimming test was applied to mice; and a typical behavioral change, an immobile posture, was recognized. This affected the brain monoamine levels significantly. The norepinephrine concentration was reduced, while that of its product was increased; and in the case of dopamine, both the amount of the amine and its product were increased. Stress increased the levels of serotonin and its product in the brain. The effects of RS-8359, (+/-)-4-(4-cyanophenyl)amino-6,7-dihydro-7-hydroxy-5H-cyclopenta[d ]- pyrimidine, a new inhibitor of type A monoamine oxidase, on the behavioral and biochemical changes caused by forced swimming were also investigated. RS-8359 significantly improved the immobile posture elicited by the forced swimming test. It reduced the increased turnover of norepinephrine and serotonin systems caused by swimming. These results suggest that the effect of RS-8359 on behavioral and biochemical changes by stress may be mainly due to its effects on norepinephrine and serotonin systems, presumably by the inhibition of type A monoamine oxidase.

Animals↗

Cosmid clones from microdissected human chromosomal region 15q11-q13.

A human chromosomal region, 15q11-q13, was microdissected, its DNA was amplified with the primer-linker PCR method, and the PCR products were cloned into a plasmid vector to construct a microclone library. Of 193 microclones analyzed with Southern blot hybridization on hybrid cell panels, 26 (13.5%) were either single-copy (unique) or low-repetitive fragments. By screening of a cosmid library of human genomic DNA using the 26 microclones as probes, 47 positive cosmids were obtained and underwent regional mapping with chromosome fluorescence in situ hybridization (FISH). Sixteen cosmids gave FISH signals at 15p-cen, 5 at 15q11-q13, 6 at 15q22-q26, 3 at other chromosomes, and 17 no signal. These 27 cosmids mapped to chromosome 15 are useful additions to the inventory of DNA markers of this chromosome including the much interested Prader-Willi/Angelman syndrome region.

Base Sequence↗

Isolation and mapping of microsatellites from a library microdissected from the Werner syndrome region, 8p11.2-p22.

We have constructed a new genetic linkage map of the Werner syndrome (WRN) region, using microsatellites from a library which was developed by a chromosome microdissection and enzymatic amplification method. These microsatellites were used to genotype members of CEPH families using a simplified detection system of polymerase chain reaction (PCR) products. Two-point analysis was used to assign 4 microsatellite markers relative to each marker and other markers reported in the CEPH public data base. We confirmed that these 4 markers are located to the WRN region, 8p11.2-p22. Such microsatellites microdissected from the definite chromosome region may be useful for positional cloning.

Base Sequence↗

Follow up study on children with dyslipidaemia detected by mass screening at 18 months of age: effect of 12 months dietary treatment.

The present study was done to evaluate the effect of short-term dietary therapy on 148 dyslipidaemic children (24 familial hypercholesterolaemia, 105 non-familial hypercholesterolaemia and 19 hypertriglyceridaemia), detected by mass screening in children at 18 months of age. In the model diet used for treatment, 15% of the total calories were obtained from protein, 27% from fat and 57% from carbohydrate. Cholesterol intake was set at < 200 mg/day and the ratio of polyunsaturated to saturated fatty acid (P/S ratio) was 1.2. When compared to the composition of the diet ingested by the dyslipidaemic children, only the P/S ratio changed from 0.7 to 1.2. During 12 months treatment, levels of total cholesterol, low density lipoproteins cholesterol and apoB decreased by 10%-15% in children with familial and non-familial hypercholesterolaemia. There was no significant change in the levels of high density lipoproteins. In 19 children with hypertriglyceridaemia, the intake of carbohydrate was limited to 55% of the total calories consumed and after 12 months of treatment, triglyceride levels reverted to normal. Throughout the study period, approximately 70% of the children on this dietary therapy were seen in our clinics every 3-6 months and physical development was within normal ranges. These results, taken together, indicate that dietary therapy can be effective for correcting dyslipidaemia, even in young children.

Analysis of Variance↗

A case of serous cystadenoma of the pancreas with focal malignant changes.

We present a serous cystadenoma of the pancreas with focal malignant changes, and describe its characteristic histological features. On gross examination, a tumor was present on the anterior surface of the body of the pancreas and measured approx 25 x 25 x 20 mm. Microscopically, most tumor cells showed the typical histological features of serous cystadenoma, characterized by a microcystic architecture and glycogen-rich cells with a uniform and bland appearance. However, in some areas, a tendency to papillary structures with fibrovascular cores was noted. These papillary lesions were composed mainly of nonmucinous, glycogen-poor epithelial cells, the nuclei of which showed a mild atypia. In addition, vascular and perivascular invasion was focally observed. However, there was no clinical evidence of local or distant metastasis. From these findings, we diagnosed this lesion as a serous cystadenoma of the pancreas with focal malignant changes rather than a serous cystadenocarcinoma of the pancreas.

Blood Vessels↗

The pattern of lymph node involvement in carcinoma of the head of the pancreas. A histologic study of the surgical findings in patients undergoing extensive nodal dissections.

To clarify the pattern of lymph node metastasis in carcinoma of the pancreas, lymph node involvement was examined in forty-two patients who underwent extensive nodal dissections, including the paraaortic lymph nodes. The correlation between the spread of the tumor and lymph node involvement was evaluated: The most common site of involved lymph nodes was the retropancreatic region. The prevalence of nodal metastases was 78.6%. Metastases to the paraaortic region were present in seven patients, among whom metastases in the paraaortic region were most common in the median region from the celiac artery to the inferior mesenteric artery and in the space between the aorta and the vena cava. The risk of lymph node metastases tended to increase with tumor size, except in the paraaortic region, where the correlation between the frequency of metastasis and tumor size was poor. The probability of lymph node metastases increased with the degree of lymphatic invasion (ly) and the growth pattern of the tumor (INF) and was high in patients with invasion into the retropancreatic tissue and in tumors with scirrhous histology. These results indicate that even in small cancers, lymph nodes of the paraaortic region frequently harbor metastases and should be dissected en block during radical resections of pancreatic cancer.

Humans↗

Expression of argyrophilic nucleolar organizer regions in ductal adenocarcinoma of the pancreas and its relationship to prognosis.

The aim of the present study was to investigate the relationship between Ag-NOR count levels and survival in 33 patients undergoing resection for ductal adenocarcinoma of the pancreas at Kanazawa University Hospital from 1985 to 1991. To determine the biologic behavior of invasive ductal adenocarcinoma of the pancreas, 33 tumors were classified into two groups according to the median value of Ag-NOR counts: Group 1, Ag-NOR count > or = 3.25 (higher Ag-NOR count group); Group 2, Ag-NOR count < 3.25 (lower Ag-NOR count group). As a result, we found that tumors with a higher Ag-NOR count were more likely to have liver or peritoneal metastasis than those with a lower Ag-NOR count, although the differences were not statistically significant. Tumors with lower Ag-NOR count levels were associated with favorable prognoses 2 and 3 yr after surgery, whereas those with higher Ag-NOR count levels were related to poor prognosis. Our results indicate that a Ag-NOR count level is a reliable prognostic parameter in resected pancreatic ductal adenocarcinoma.

Adult↗

Mutagenicity of blue rayon extracts of human bile in the Ames test.

The mutagenicity of human bile was examined in the Ames Salmonella/microsome assay. Bile samples were obtained from the gallbladders resected from patients with cholelithiasis, choledocholithiasis, gallbladder cancer, extrahepatic bile duct cancer and other diseases. For extraction of mutagenic components, the bile samples were treated with blue rayon and the adsorbed materials were assayed with Salmonella typhimurium TA98 in the presence of S9 mix. Twenty-four bile samples were tested and positive mutagenic activity was found in 14 samples. A 200-microliter bile equivalent material gave 6.3 times as many revertant colonies as the solvent control. With several samples that had undergone two cycles of blue rayon extraction, clear dose-response relationships in mutagenicity were demonstrated.

Adult↗

Antimutagenic effects of N-methyl-valyl-amiclenomycin (BA-2) isolated from the metabolites of Streptomyces sp.

A novel antimutagenic factor, BA-2, active against UV-induced mutagenesis in Escherichia coli WP2 was isolated from the metabolites of Streptomyces sp. strain AJ9455. BA-2 also suppressed mutations induced by 4-nitroquinoline N-oxide (4-NQO) and furylfuramide (AF-2) in E. coli WP2s (uvrA) without any decrease of cellular viability. BA-2 strongly inhibited the UV induction of SOS repair functions when it was monitored by beta-galactosidase activity expressed from the sulA::lacZ fusion gene of strain PQ37. It is assumed that the antimutagenic effect of BA-2 on mutagenesis induced by UV, 4-NQO or AF-2 was the result of inhibition of induction of the inducible error-prone SOS repair. The structure of BA-2 was considered to be N-methyl-valyl-amiclenomycin, and the structural unit of 4-amino-2,5-cyclohexadiene must be essential for the antimutagenic activity, since deamination by heating results in the loss of antimutagenic activity of BA-2.

Aminobutyrates↗

o-Vanillin enhances chromosome aberrations induced by alkylating agents in cultured Chinese hamster cells.

The enhancing effects of o-vanillin (2-hydroxy-3-methoxybenzaldehyde) on structural chromosome aberrations induced by alkylating agents were studied in cultured Chinese hamster cells. o-Vanillin was not a clastogen by itself. When cells were treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the presence of 400 micrograms/ml of o-vanillin for 2 h, the frequency of aberrant cells with chromosome aberrations was increased 2.8-fold compared with cells treated with MNNG alone. The total number of breakage-type and exchange-type aberrations was increased 18.5- and 8.3-fold, respectively. The enhancing effects were also observed for chromosome aberrations induced by N-methyl-N-nitrosourea and N-ethyl-N-nitrosourea. On the other hand, those induced by N-butyl-N-nitrosourea were only slightly enhanced. The frequency of chromosome aberrations induced by mitomycin C or bleomycin was not changed by o-vanillin treatment. It was considered that DNA repair of methylated damage may be inhibited by o-vanillin.

Alkylating Agents↗

Mutation enhancing effect of o-vanillin in the lacZ gene of Escherichia coli: characterization of mutational spectrum.

The enhancing effect of o-vanillin (2-hydroxy-3-methoxybenz-aldehyde) on mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was characterized with mutational specificity. The mutational spectrum of MNNG-induced mutations in the presence of o-vanillin was compared with that in the absence of o-vanillin by means of a series of mutant lacZ genes in E. coli that can detect each of the six types of base substitutions and five kinds of frameshift events. In the absence of o-vanillin, the mutational spectrum induced by MNNG consisted mainly of G.C-->A.T transitions and, to a lesser extent, -1(G.C) frameshift mutations. By adding o-vanillin at 75 micrograms/plate, a marked enhancement was observed in two transitions, G.C-->A.T and A.T-->G.C, and in two frameshift mutations, +1(G.C) and -1(G.C). Only a small change was observed in the -2(C.G-G.C) fraction. Regarding the MNNG-induced frameshifts at the A.T base pair, the +1(A.T) frameshift was much more enhanced by o-vanillin than the -1(A.T) frameshift.

Benzaldehydes↗

Gastric vasodilator and motor responses to splanchnic stimulation and tachykinins in the dog.

1. Gastric blood flow and motor responses to greater splanchnic nerve stimulation and intra-arterial injection of tachykinins were studied in anaesthetized dogs. 2. Splanchnic nerve stimulation (40 V, 10 Hz) with pulse durations of 0.05 and 1 msec caused a gastric relaxation and contraction, respectively. Both types of stimulation produced a decrease followed by an increase in blood flow. The responses to stimulation with a pulse duration of 0.05 msec were inhibited by hexamethonium. 3. After treatment with hexamethonium, stimulation with 1 msec caused frequency-dependent gastric contraction and vasodilation. Both responses had two components, sensitive and resistant to atropine. 4. Intra-arterial injection of substance P (SP), neurokinin A (NKA), neurokinin B (NKB), physalaemin (PHY) or eledoisin (ELE) elicited dose-dependent gastric contraction and vasodilation. The order of potency for contraction was SP = PHY = ELE = NKA >> NKB and that for vasodilation was SP = PHY > ELE > NKA > NKB. 5. Atropine partly inhibited the tachykinin-induced gastric contraction but not gastric vasodilation. Spantide partly inhibited the atropine-resistant vasodilation but not contraction in response to splanchnic nerve stimulation and SP. 6. It is concluded that splanchnic nerve stimulation produced cholinergic and SPergic vasodilation after ganglionic blockade in the dog stomach.

Animals↗

Pancreatitis and anomalous union of the pancreaticobiliary ductal system in childhood.

From January 1978 to December 1989, 48 patients were diagnosed as having anomalous union of the pancreaticobiliary ductal system (AUPBD) at the Second Department of Surgery, Kanazawa University Hospital and its affiliated hospitals. Among these 48 patients, 13 (28.1%) were children under 13 years of age. Four of these patients had acute pancreatitis. The clinical, radiological, and surgical features of these patients are presented. The chief presenting complaint was epigastric pain in all cases; three patients had recurrent episodes of epigastric pain and had been diagnosed as having autotoxicosis. AUPBD was clearly demonstrated in all patients, three by endoscopic retrograde cholangiopancreatography (ERCP) and one by operative cholangiography. At operation, macroscopic evidence of pancreatitis was recognized in all cases. In one case, roentogenolucent pancreaticolithiases were seen on ERCP. We consider AUPBD as an important cause of pancreatitis in children and advocate ERCP in children who are suspected having biliary tract or pancreatic disease. The diagnosis of AUPBD should be considered when children with abdominal pain and elevated serum or urinary amylase levels are evaluated.

Abnormalities, Multiple↗

Successful reconstruction of a high-pressure injection injury of the hand using a first web flap of the foot.

High-pressure injection injury to the hand often results in loss of tissue and hand function. The successful reconstruction of a hand following high-pressure injection injury is reported. A free neurovascular flap was transferred from the first web space of the foot to cover a skin defect in the first web space area of the hand. The digital nerves of the thumb and index finger were repaired using sural nerve grafts.

Adolescent↗

Role of the endothelium on extraluminal and intraluminal vasoactive mechanisms in the perfused rabbit basilar artery.

In order to investigate the role of the endothelium in the regulation of cerebrovascular tone, we studied selective intraluminal and extraluminal vasoactive mechanisms of acetylcholine, potassium and serotonin. We also examined the effects of removal of the endothelium on these vasoactive responses. With 0.75 g of tension, isolated rabbit basilar arteries were fixed in a perfusion system with the ability to isolate the intraluminal and extraluminal surfaces, and perfused at 8 ml-1 min-1 under a pressure of 8 mmHg. To remove the endothelium, we applied several concentrations of saponin. The endothelium was completely removed by 0.05 mg-1 ml-1 saponin, confirmed histologically. Extraluminal and intraluminal acetylcholine induced endothelium-dependent relaxations. Intraluminal potassium induced greater contraction than extraluminal potassium in both saponin denuded (p < 0.01) and intact preparations (p < 0.05, n = 8). Intraluminal and extraluminal serotonin induced symmetric contractions, and for both sides the response was enhanced by removal of the endothelium (p < 0.05, n = 6). Our results suggest that inhibitory (relaxant) contribution of the endothelium to contractile responses varies depending on the vasoactive agent. The fact that the effects of some extraluminal agents were enhanced when the endothelium was denuded, may be of some importance in potentiating the mechanism of vasospasm following subarachnoid haemorrhage.

Acetylcholine↗

Haemodynamic study of arteriovenous malformations using a hydraulic model.

Despite the accumulation of intraoperative data on arteriovenous malformations (AVMs), details of the haemodynamics have not yet been elucidated. A hydraulic model was constructed from silicone and glass tubes to simulate a high-flow AVM. During stepwise obliteration of the nidus, haemodynamic changes were continuously measured in residual parts of the AVM and in the surrounding brain. The flow in the residual AVM decreased nonlinearly with the advance of obliteration. The feeder pressure increased markedly from 37 mmHg to 94 mmHg, while the drainer pressure decreased gradually. The flow volume in the surrounding brain increased markedly from 40 ml/min to 100 ml/min at an occlusion ratio of 60%, where the pressure gradient across the nidus reached 60 mmHg. In the presence of autoregulation, further obliteration showed no change in the flow volume with the increased pressure gradient to 93.7 mmHg. Under dysautoregulatory conditions the flow volume increased to 122 ml/min, although the pressure gradient was 8.3 mmHg lower than that under autoregulatory conditions. Simulation study is useful in understanding haemodynamic changes during the treatment of AVMs.

Arteriovenous Malformations↗

Analysis of mutational specificity induced by heterocyclic amines in the lacZ gene of Escherichia coli.

Mutational spectra induced by different heterocyclic amines were characterized and compared with those obtained from diethylnitrosamine and N-methyl-N-nitrosourea. Mutation classes were identified by means of a series of mutant lacZ genes in F' episomes in Escherichia coli engineered to detect specifically each of two transitions, four transversions and five kinds of frameshift events. More than 99.5% of the mutations induced by heterocyclic amines were frameshift mutations. -2(C.G-G.C) frameshifts were favored over other types, such as +1(G.C), -1(G.C), +1(A.T) and -1(A.T), except when 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) was administered. -1(G.C) and +1(G.C) frameshifts predominate following Trp-P-1 treatment. A small number of G.C-->T.A transversions were induced by the treatment with 2-amino-3,4-dimethylimidazo[4,5-f]quinoline as well as with several other heterocyclic amines examined. Since G.C-->T.A transversions, but not frameshift mutations, are reported to play a role in heterocyclic amine-induced activation of the c-Ha-ras protooncogene or inactivation of the p53 tumor suppressor gene, the low level of base substitutions, particularly G.C-->T.A transversions, may represent a partial explanation for the relatively modest carcinogenic activity of heterocyclic amines, despite their extraordinarily strong mutagenicity in the Salmonella mutation assay.

Amines↗