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Biomedical subjects

S Ohta

Publications and source records attributed to S Ohta.

At least 901 records · Page 50Linked to original sources

Hypoosmotic swelling test with a medium of distilled water.

The functional competence of the human sperm membrane is assessed by studying the swelling reaction of sperm when suspended in a medium of distilled water (water test). Eighty-seven patients with idiopathic infertility were investigated by the water test and the results were compared with various semen parameters. High correlations with the percentage of b-g type swollen sperm in the water test were observed for sperm concentration (r = .53, p < .05) and percent motility (r = .62, p < .01). The sperm swelling values obtained by the water test correlated well with those obtained by the hypoosmotic swelling test (HOST). Correlation coefficients in b-g and g swelling pattern were 0.89 and 0.71, respectively. The percentage of g-type swelling obtained by the water test was significantly larger than that obtained by the HOST (p < .05), although the two hypoosmotic procedures gave similar percentages of b-g swelling pattern. The percentage of g swelling pattern obtained by the water test correlated well with percent motility (r = .70, p < .001). These findings suggest that the water test is more useful for assessing the integrity of the sperm membrane than the HOST. The relationship between this test and subsequent fertility, as well as to other sperm function tests, needs further investigation.

Adult↗

Effect of pentoxifylline on sperm motion.

The ability of pentoxifylline to stimulate sperm motility characteristics was assessed. The effect of pentoxifylline was immediate and lasted for 240 min. The percent motility was increased 1.5-fold when compared with the control at 120, 180, and 240 min after pentoxifylline treatment. Significant increases in velocity and amplitude of lateral head displacement by the agent were observed at 120 min after the start of incubation. Conversely, linearity was reduced by pentoxifylline. Beat-cross frequency did not show any significant change by the agent at any time point. Sperm swelling was not influenced by pentoxifylline throughout the experiment. It would appear that pentoxifylline stimulates sperm motion in vitro with no change of the sperm membrane.

Humans↗

Varicocelectomy: changes in Resazurin Reduction test.

The Resazurin Reduction Test was performed on semen specimens from 27 patients with varicocele before and after varicocelectomy. The increases in both sperm concentration and motility were slight 3 months after surgery, but sperm concentration significantly improved 6 months after surgery (P < 0.01). The positive rate in the Resazurin Test significantly increased 3 and 6 months after surgery (each, P < 0.05) and the resazurin grade also increased at these times (each, P < 0.01). Of 13 patients with improved seminal findings, 7 had negative reactions during the preoperative Resazurin Test and 3 of these 7 patients continued to have negative reactions, while the other 4 had positive reaction after surgery. Of 14 patients with no improvement of semen characteristics, 6 continued to have negative reactions after surgery, but 4 with negative reactions before treatment showed positive reactions postoperatively. The Resazurin Test seems to assess fertility potential accurately after varicocelectomy.

Adult↗

Changes in seminal plasma transferrin concentration following administration of clomiphene citrate.

This study was designed to investigate the functional changes in Sertoli cells following clomiphene citrate administration to patients with idiopathic infertility. The agent was administered to 44 oligozoospermic patients. Patients with improvement in sperm concentration after treatment (improvement group) showed significantly lower pretreatment follicle-stimulating hormone (FSH) levels in serum. Serum FSH and testosterone levels significantly increased in the improvement group after treatment (both p < 0.05). Seminal transferrin concentration significantly increased in the improvement group after treatment (p < 0.05), although there was no significant difference between pretreatment seminal transferrin concentration in the improvement group and that in patients with no improvement in sperm concentration. Seminal plasma transferrin concentration in patients in whom pretreatment luteinizing hormone level in serum was below 10 mIU/mL, and in those in whom the ratio of post- to pretreatment values was 1.5 or more, tended to increase after treatment. This group also contained a few more patients with improvement in sperm concentration than the other groups. The patients showing low pretreatment FSH levels and a high ratio of post- to pretreatment values demonstrated a significant increase in seminal plasma transferrin concentration after treatment (p < 0.01), and this group contained more patients with improvement than the other groups. It would appear that Sertoli cell stimulation may induce an increase in sperm concentration after clomiphene citrate administration, and the elevated transferrin secretion seems to be associated with the increase of serum FSH level after treatment.

Adult↗

Overview of clinical studies of childhood acute lymphoblastic leukemia for more than ten years by the Japanese Children's Cancer and Leukemia Study Group.

Since 1981, the Children's Cancer and Leukemia Study Group (CCLSG) has developed a series of protocols for treatment of acute lymphoblastic leukemia (ALL) in childhood. In the first randomized controlled study of the 811 protocol (1981-1983) a comparison of conventional daily 6-mercaptopurine and methotrexate with a pulsed regimen of the two drugs was performed. The superiority of the pulsed regimen was shown. In the next 841 protocol (1984-1987) a comparison of two drugs and three drugs during induction therapy was conducted. The three-drug regimen resulted in a significantly higher event-free survival (EFS) rate. In the 874 protocol (1987-1990) two regimens with or without cranial irradiation were randomly compared, and there was no significant difference between the two regimens for the standard-risk group. To further improve the EFS rate a risk group-directed protocol 911 was conducted starting in January 1991. Life-table analysis of serial CCLSG protocols revealed that the outcome of overall ALL has gradually improved with an increase of the EFS rate; 41.4% +/- 3.6% at 14 years for the 811 protocol, 51.3% +/- 3.5% at 11 years for the 841 protocol, 56.7% +/- 3.1% at 8 years for the 874 protocol, and 78.2% +/- 3.1% at 4 years for the more recent 911 protocol.

Antineoplastic Combined Chemotherapy Protocols↗

Cdc6 expression as a marker of proliferative activity in brain tumors.

Antibodies against human proteins that regulate DNA replication such as Cdc6 and Mcm5 became available as a new marker of proliferation. We performed immunohistochemical analysis with MIB-1 and antibody against Cdc6 on 35 brain tumors, including tumors of neuroepithelial tissue, vestibular schwannomas, meningiomas, and pituitary adenomas. Median reactivity for MIB-1 was 8.8%, and that for Cdc6 was 55%. Reactivity in most brain tumors was significantly higher for Cdc6 than for MIB-1, but reactivity of Cdc6 was independent of tumor grade. Detection of Cdc6 expression might be useful for the estimation of proliferative activity in brain tumors.

Antigens, Nuclear↗

Vinca alkaloids induce granulocyte-macrophage colony stimulating factor in human peripheral blood mononuclear cells.

Several anti-cancer drugs are known to have proliferation-related effects on various cells, such as an activation of some transcription factors and an induction of some cytokines. We examined the effect of anti-cancer drugs on granulocyte-macrophage colony stimulating factor (GM-CSF) induction in human peripheral blood mononuclear cells (PBMC). Increase of GM-CSF protein and mRNA were observed in PBMC after exposure to vindesine sulfate (VDS). Induction of GM-CSF protein was dose-dependent and detectable at VDS concentrations of 0.1 microgram/ml. This effect was also observed in response to treatment with other microtuble-depolymerizing agents, vincristine sulfate and vinorelbine ditartrate, but not with cisplatin, etoposide, or paclitaxel. In order to elucidate the mechanism of this phenomenon, we examined the effects of cyclohexamide and actinomycin D on the expression of GM-CSF mRNA. Both of these drugs completely inhibited GM-CSF mRNA expression after VDS exposure, implying that VDS induces de novo GM-CSF synthesis in an indirect manner. As a candidate for the initial signaling, we next examined the role of the IL-1 beta autocrine or paracrine pathways in GM-CSF induction by VDS. IL-1 beta protein and mRNA expression were induced after VDS exposure more rapidly (from 4 hours) than expression of GM-CSF (protein from 12 hours and mRNA from 8 hours). Addition of anti-IL-1 beta antibody partially inhibited induction of GM-CSF by VDS. These results suggest that GM-CSF induction by VDS is partially mediated through the initial generation of IL-1 beta in PBMC.

Antineoplastic Agents, Phytogenic↗

A simultaneous resection of a concomitant abdominal aortic aneurysm and hepatocellular carcinoma: two cases.

We report two cases of simultaneous surgical treatment in patients with a concomitant abdominal aortic aneurysm (AAA) and hepatocellular carcinoma (HCC). The first patient underwent abdominal echography and was observed to have an abnormal hepatic mass. A consecutive computed tomographic (CT) scan showed an AAA, measuring 8 cm in size. The hepatic mass, which reached 5 cm in size, existed in the S5 and was strongly suspected to be HCC. The second patient was observed to have AAA by CT scan three years ago and also shown to have a hepatic mass, which reached 3 cm in size, in the S8. Both patients underwent a simultaneous resection. At first, a resection and reconstruction of the aneurysm was performed, followed by an extended right lobectomy and anterior segmentectomy of the liver. The postoperative course was uneventful and they were discharged on the 29th and 22nd postoperative day. To our knowledge, this is the first report of patients who underwent a successful simultaneous resection of an AAA and HCC.

Aged↗

Establishment and characterization of malignant rhabdoid tumor of the kidney.

Malignant rhabdoid tumor of the kidney (MRTK) is a highly aggressive tumor which occurs in childhood and which is histologically characterized by the existence of eosinophilic intracytoplasmic inclusions. We established and characterized a cell line from this tumor with histological, immunohistochemical and cytogenetical analysis. Histologically, the tumor cells demonstrate typical eosinophilic inclusions, while immunohistochemically the cells demonstrate common mesenchymal and epithelial differentiation. Although the conventional karyotyping of this tumor lacked the abnormalities of 22q chromosome, Southern blot analysis and microsatellite analysis verified abnormalities of the BCR gene and of the hSNF5/INI1 gene. Despite the variety of locations, these common genetic abnormalities appear to contribute to distinguish rhabdoid tumor from such other small round cell tumors as primitive neuroectodermal tumor, rhabdomyosarcoma, poorly differentiated synovial sarcoma and desmoplastic small round cell tumor.

Animals↗

Prostate-specific antigen density adjusted for the transition zone for staging clinically localized prostate cancer in Japanese patients with intermediate serum prostate-specific antigen levels.

The prostate-specific antigen (PSA) density of the transition zone (PSATZ) in 45 prostate cancer patients who received radical prostatectomy with a PSA value of 4.1-10 ng/ml was determined to see whether PSATZ was useful in the prediction of extracapsular invasion of prostate cancer. The value of PSATZ for the detection of extracapsular invasion was compared with that of PSA and PSA density (PSAD). Thirty-one patients (68.9%) had pathologically organ confined cancer while 14 (31.1%) had extracapsular disease. Patients with organ confined tumor had significantly lower PSAD and PSATZ than those with non-organ confined tumor. PSATZ was superior to PSA when analyzed by receiver operating characteristics curves. In those patients with a cut-off value of 1.0 ng/ml per ml of transition zone volume, the PSATZ had a sensitivity of 43% and a specificity of 90% for prediction of extracapsular extension. The present study demonstrated that PSATZ was superior to PSA as a predictor of extracapsular invasion in intermediate PSA levels. Measurement of PSATZ may be of additional value to indicate the need for radical prostatectomy.

Adenocarcinoma↗

Efficacy of endoscopic hemoclipping for GI bleeding in relation to severity of shock.

BACKGROUND/AIMS: To examine the efficacy of prospectively performing endoscopic hemoclipping in patients with severe gastrointestinal bleeding by assessing in relation to the severity of the case. METHODOLOGY: Endoscopic hemoclipping was performed in 44 patients in shock caused by severe gastrointestinal bleeding. The level of severity was categorized using two factors. One factor was the presence or absence of severe shock, and the other was the presence or absence of active bleeding at endoscopy. Age, blood transfusion volume, APACHE III score, coagulopathy, initial hemostatic, rebleeding and mortality rate were recorded in relation to those four subsets. If rebleeding occurred, the systolic blood pressure, heart rate and serum hemoglobin concentration were compared between the initial time of bleeding and rebleeding. RESULTS: Initial hemostasis was successfully achieved in all cases. The severe shock group required significantly more blood transfusions. The most severe subset had the highest APACHE III score, and coagulopathy. Rebleeding occurred in seven cases in the severe shock group only. In the rebleeding group, the systolic body pressure was lower, heart rate was higher, and serum hemoglobin concentration was lower than the non-rebleeding group. Four patients, all in subset 1, died, but no patient died due to gastrointestinal bleeding. CONCLUSIONS: The endoscopic hemoclipping method is very effective for severe gastrointestinal bleeding in shock. The severity of shock was a more important risk factor than the presence of active bleeding. Our category of severity is simple, it reflects the patients' clinical condition accurately, and is very useful for patients with gastrointestinal bleeding.

APACHE↗

Metabolism and penetration through blood-brain barrier of parkinsonism-related compounds. 1,2,3,4-Tetrahydroisoquinoline and 1-methyl-1,2,3,4-tetrahydroisoquinoline.

14C-Labeled 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) were synthesized, and their metabolism and tissue distribution were studied. Both compounds showed similar metabolic patterns. In 24 hr after po administration (50 mg/kg) to rats, 76% of TIQ and 72% of 1MeTIQ were excreted unchanged, and 2.7 and 8.7% were excreted as the 4-hydroxyl derivatives, 4-hydroxy-TIQ and 4-hydroxy-1MeTIQ, respectively. Small amounts of N-methylated metabolites, 2-methyl-TIQ (0.4%) and 2-methyl-1MeTIQ (0.7%) were detected. Isoquinoline (2.5%) also was found as a metabolite of TIQ and 1-methyl-3,4-dihydroisoquinoline (1.0%) was found as a metabolite of 1MeTIQ. The concentration of labeled compounds in the brain was about 4.5-fold higher than the blood concentration at 4 hr after dosing, and over 90% was unchanged TIQ or 1MeTIQ. These data indicated that TIQ and 1MeTIQ easily passed through the blood-brain barrier and were concentrated in the brain. Thus, it appears that TIQ and 1MeTIQ as endogenous or exogenous amines may accumulate in the brain and may be related to the onset of Parkinson's disease.

Animals↗

Application of chemical cytochrome P-450 model systems to studies on drug metabolism. IV. Mechanism of piperidine metabolism pathways via an iminium intermediate.

Oxidations of the piperidine ring by chemical model and liver microsomal systems were investigated with a simple piperidine derivative, N-benzylpiperidine (BP) (3), as the substrate in order to probe the generality and the mechanism of the biotransformation of the piperidine ring. The piperidine ring of BP (3) as well as that of phencyclidine (1) was suggested to be oxidized to a ketone at the beta-position in the meso-tetraphenylporphinatoiron(III) chloride system, and the reaction was expected to occur in the liver microsomal system. The beta-oxo formation was observed directly in the liver microsomal system, and found to be dependent on cytochrome P-450. Then it was suggested that the piperidine-beta-oxo formation was a general oxidation pathway of the piperidine biotransformation. Hydrogen abstraction in the reaction was not a rate-determining step. Therefore, we presumed a possible mechanism of beta-oxo formation via BP-iminium (21). From the comparative study on the reactivities of dipropylbenzylamine (DPB) (18) and BP (3), and the stabilities of iminium (Im+) species of BP (3) and DPB (18), it was suggested that BP-Im+ (21) was relatively stable and was the most likely precursor of BP-beta-oxo (6). BP-Im+ (21) and its free base, enamine (29), afforded large amounts of BP-beta-oxo as well as BP-alpha-oxo (9) in the chemical model and the microsomal systems. This evidence supported the iminium-enamine mechanism expressed as scheme III.

Animals↗

Detection of infectious bronchitis virus antigen from experimentally infected chickens by indirect immunofluorescent assay with monoclonal antibody.

Infectious bronchitis virus (IBV) was detected by indirect immunofluorescent assay with a monoclonal antibody (MAb-IFA). The monoclonal antibody was specific for the nucleocapsid protein of IBV strain M41. The MAb-IFA clearly detected IBV with high specificity in infected chicken kidney cells. The assay furthermore detected IBV in tracheal smears and sliced tracheas from experimentally infected chickens. The positive reaction was found to be longer than that in the virus recovery test. These results indicate that MAb-IFA is a useful method for the detection of IBV from chickens suspected to have infectious bronchitis.

Animals↗

Small cell carcinoma of the prostate: CT and MRI findings.

We report two cases of small cell carcinoma of the prostate and describe the CT and MRI findings, which were primarily based on the rapid growth and high metastatic potential of the tumor. CT and MRI are extremely useful for demonstration of metastatic lesions. Histological confirmation is needed if the findings of CT or MRI are unusual for ordinary adenocarcinoma of the prostate.

Aged↗

Effect of taxol on vinblastine sulfate-induced crystallization of tubulin.

In human lung adenocarcinoma cells exposed to vinblastine (VLB) and stained with fast green, large tubulin crystals were seen in the cytoplasm. In contrast cells exposed to taxol had prominent bundles of stabilized microtubules. Pre- or co-incubation of cells with taxol before exposure to VLB prevented formation of the crystals. However, VLB did not prevent formation of stabilized microtubules by taxol if added at the same time. Under a fluorescent microscope, VLB induced crystals stained with secondary antibodies against anti-alpha- and anti-beta- tubulin antibodies. Neither of the drugs altered binding of the antibodies to these crystals.

Adenocarcinoma↗

Inter-individual differences of 4-[4-(4-methylphenyl)-phenylmethoxy-1-piperidinyl]butyric acid disposition in rats: possible involvement of genetic polymorphism.

Inter-individual differences of drug plasma concentration were recognized in outbred rats after an oral or intravenous administration of (+)-4-[4-(4-methylphenyl)phenylmethoxy-1-piperidinyl]butyric acid hydrochloride ((+)-MPPB). Rats could be divided into two phenotypes, the rapid metabolizing (RM) group and the slow metabolizing (SM) group. The hepatic clearance of RM-phenotyped Sprague-Dawley rats was about 10 times larger than that of the SM group. Outbred male and female Sprague-Dawley rats and male Wistar rats were mixtures of the RM and SM groups. On the other hand, all inbred male Lewis rats were RM, and all inbred male F344 and ACI rats were SM. This study was undertaken to investigate the inter-individual differences of (-)-MPPB and the metabolic pathways of (+)- and (-)-MPPB. When (-)-MPPB was orally administered to male Sprague-Dawley rats, similar inter-individual differences of plasma concentration were recognized. RM-phenotyped Sprague-Dawley rat liver microsomes metabolized (+)-MPPB to 4-hydroxymethylphenyl-MPPB (M1), and (-)-MPPB to M1 and 4'-hydroxyphenyl-MPPB (M2). The formation of these metabolites was less with SM-phenotyped than with RM-phenotyped Sprague-Dawley rat liver microsomes. The kinetic parameters of M1 formation from (+)-MPPB by RM-phenotyped rat liver microsomes were characteristic of a two-enzyme system with a 100-fold difference in their affinities (KM values). On the other hand, SM-phenotyped rats have only the low-affinity enzyme system. An inhibition study demonstrated that both enzymes were cytochrome P450.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗