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Biomedical subjects

T Ohno

Publications and source records attributed to T Ohno.

At least 397 records · Page 22Linked to original sources

[Surgical treatment of mycotic coronary artery aneurysm associated with infective endocarditis: a case report].

53-year-old male was introduced our hospital for treatment of his infective endocarditis and congestive heart failure. Further evaluation revealed massive destruction of the mitral valve and aneurysm of the right coronary artery. We carried out an operation of aneurysmectomy and CABG with RGEA for coronary artery, and MVR using 29 mm SJM valve. Postoperative course was excellent. Graftgram showed good patency and perfusion of RGEA. Pathological findings were 1) macrophage infiltration into thrombi, 2) disappearance of elastic fibers of the media. 3) least atherosclerosis of the intima. We concluded that it was a mycotic coronary artery aneurysm. There have been no report of surgical treatment of such a mycotic coronary artery aneurysm upon our investigation.

Aneurysm, Infected↗

Relationship between the therapeutic effects or side-effects and the serum disopyramide or mono-N-dealkylated disopyramide concentration after repeated oral administration of disopyramide to arrhythmic patients.

After we had developed a method to determine simultaneously the blood concentrations of disopyramide (DP) and its metabolite mono-N-dealkylated disopyramide (MND) by high-performance liquid chromatography, DP was administered repeatedly to arrhythmic patients in order to examine the relationship between the serum DP or MND concentration and the therapeutic effects or side-effects. To 79 arrhythmic patients (57 patients with ventricular premature contraction, 13 with supraventricular arrhythmia and 9 with atrial fibrillation), DP was administered repeatedly at an initial oral dose of 200 to 400 mg/day. Of the 61 patients which were possible to evaluate after reaching a steady state, 32 were evaluated as effective and 29 as non-effective, the effective rate being 52.5%; the mean blood DP concentration (+/- S.D.) was 2.14 +/- 0.65 and 1.74 +/- 0.62 micrograms/ml, respectively, with a significant difference between the two groups (p +/- 0.05). At the final dose, 40 patients were evaluated as effective and 18 as non-effective, the effective rate being 69.0%; the mean blood DP concentration was 2.03 +/- 0.67 and 2.09 +/- 0.68 micrograms/ml, respectively, with no significant difference between the two groups. Among 42 patients with premature contraction, 26 were evaluated as effective and 16 as non-effective, the effective rate being 62%; the mean blood DP concentration was 2.01 +/- 0.62 and 2.20 +/- 0.70 micrograms/ml respectively, with no significant difference between the two groups. The incidence of side-effects was 17.7%, and there were no significant differences in blood DP or MND concentrations between the groups with and without side-effects. A blood DP concentration more than 2 micrograms/ml may be required to achieve the therapeutic effect of DP administered repeatedly.

Adult↗

Gonadotropin-releasing hormone receptor in gynecologic tumors. Frequent expression in adenocarcinoma histologic types.

BACKGROUND: Gonadotropin-releasing hormone (Gn-RH) analogs have been used in the therapy of the endocrine-dependent cancers. The authors attempted to determine the frequency with which Gn-RH receptor (Gn-RHR) is present in gynecological cancers. METHODS: Experiments were performed on gynecologic tumors that had been surgically removed and their cloned cell lines. Gn-RHR was characterized by [3H]Gn-RH binding to plasma membrane preparations. Gn-RHR messenger ribonucleic acid was determined by reverse transcription-polymerase chain reaction using oligonucleotide primers synthesized according to the published human Gn-RHR sequence. RESULTS: High affinity binding sites with nanomolar range of Kd and Gn-RHR mRNA were detected in a high proportion (over 90%) of the specimens from endometrium (6 of 6) and endometrial carcinomas (16 of 17), myometrium (6 of 6) and myomas (4 of 5), epithelial carcinoma (21 of 23), and stromal tumors (3 of 3) of the ovary. There was no substantial Gn-RHR in cervical carcinomas or germ cell-derived tumors of the ovary. Cloned cell lines gave identical results to those obtained in their respective mother tumors. CONCLUSIONS: We detected Gn-RHR in a wide range of the carcinomas and tissues originating from the endometrium and ovary, but not in the uterine cervix or germ cell-derived tumors. The expression of Gn-RH receptor raises the possibility that Gn-RH may play a direct regulatory role in the growth of these carcinomas, and provides a possible point of attack for therapeutic approaches using Gn-RH analogs in these malignancies.

Adenocarcinoma↗

Complete obstruction of the inferior vena cava due to chronic relapsing pancreatitis: a case report.

A woman aged 62 with long history of chronic relapsing pancreatitis presented with swelling and ulcer in the lower limbs and occasional gastrointestinal bleeding. The radiological imaging showed complete obstruction of Inferior Vena Cava (IVC) at the level of the pancreas and well developed collateral vessels. Portal vein and splenic vein were also obstructed and superior mesenteric venous blood drained into the liver via coronary vein. She was originally found to have pancreas head tumor, which was not resectable. A palliative operation was performed, but histological examination of pancreatic specimen suggested only chronic inflammation and no evidence of malignancy. She was diagnosed as tumor-forming type chronic pancreatitis. Although SPV or SMV-PV obstruction has been recognized as a complication of chronic pancreatitis, IVC obstruction can occur by the same mechanism. This is the only case but one ever reported. Not only splenoportography but IVC-graphy will contribute to more precise understanding of patient's condition with chronic pancreatitis.

Chronic Disease↗

Gene therapy for vascular smooth muscle cell proliferation after arterial injury.

Accumulation of vascular smooth muscle cells as a consequence of arterial injury is a major feature of vascular proliferative disorders. Molecular approaches to the inhibition of smooth muscle cell proliferation in these settings could potentially limit intimal expansion. This problem was approached by introducing adenoviral vectors encoding the herpesvirus thymidine kinase (tk) into porcine arteries that had been injured by a balloon on a catheter. These smooth muscle cells were shown to be infectable with adenoviral vectors, and introduction of the tk gene rendered them sensitive to the nucleoside analog ganciclovir. When this vector was introduced into porcine arteries immediately after a balloon injury, intimal hyperplasia decreased after a course of ganciclovir treatment. No major local or systemic toxicities were observed. These data suggest that transient expression of an enzyme that catalyzes the formation of a cytotoxic drug locally may limit smooth muscle cell proliferation in response to balloon injury.

Adenoviridae↗

Identification of unlawful food dyes by thin-layer chromatography-fast atom bombardment mass spectrometry.

A thin-layer chromatographic-fast atom bombardment mass spectrometric (TLC-FAB-MS) method incorporating an analyte condensation technique was established for the identification of the 27 food dyes consisting the twelve dyes permitted for use in foods and the fifteen unlawful dyes in Japan. The use of magic bullet [1,4-dithiothreitol-1,4-dithioerythritol (3:1)] as a matrix allowed the measurement of the FAB mass spectra of the food dyes except for Food Blue No. 2 (Indigo Carmine). The separation was performed on a C18-modified silica gel TLC plate using the following two solvent systems: methanol-acetonitrile-5% aqueous sodium sulphate solution (3:3:10) and methyl ethyl ketone-methanol-5% aqueous sodium sulphate solution (1:1:1). The condensation technique for concentration of a diffuse sample spot on the TLC plate improved the detection limit 4-20-fold with good reproducibility. The method was successfully applied to the identification of unlawful dyes in imported foods.

Chromatography, Thin Layer↗

Demonstration by DNA fingerprint analysis of genomic instability in mouse BALB 3T3 cells during cell transformation.

We employed DNA fingerprint analysis to monitor DNA rearrangements in BALB 3T3 cells transformed spontaneously or by treatment with 3-methylcholanthrene (MCA) and UV-C. The effect of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in combination with MCA was also examined. Twenty-three spontaneously transformed cells, 28 induced transformed cells (18 by 1 microgram/ml MCA, six by 5 micrograms/ml MCA, and four by UV-C), and 31 non-transformed subclones were isolated from parental BALB 3T3 A31-1-1 cells. The DNAs were digested with HinfI and subjected to DNA fingerprint analysis with three multi-locus minisatellite probes, Per-6, Core, and Ins. Per-6 was the most effective probe for detecting DNA rearrangements. Rearranged bands detected by the Per-6 probe were observed in 9/31 (29%) of non-transformed subclones, 14/23 (61%) of spontaneously transformed cells, 16/18 (89%) of cells transformed by 1 microgram/ml of MCA, 6/6 (100%) of cells transformed by 5 micrograms/ml MCA, and 4/4 (100%) of UV-C-transformed cells. Higher numbers of DNA rearrangements (> or = 3) occurred most frequently in the induced transformed cells. TPA enhanced the frequency of DNA rearrangements in cells transformed by MCA. These data indicate that (1) genomic DNA in BALB 3T3 cells is unstable and susceptible to rearrangement, (2) its instability is elevated during cell transformation, and (3) MCA and UV-C induce DNA rearrangements, and TPA enhances the effect of the former, probably via the recombination process. DNA fingerprint analysis is valuable for monitoring genomic instability during cell transformation.

3T3 Cells↗

Malignant histiocytosis associated with autoimmune thrombocytopenia.

We describe a patient with malignant histiocytosis whose serum contained an autoantibody against platelet protein. The patient was admitted because of nasal bleeding and high-grade fever. The clinical course was fulminantly progressive and terminated with cerebral hemorrhage. Bone marrow aspirate showed the proliferation of large atypical cells, some of which exhibited phagocytic activity. At postmortem examination, there was diffuse infiltration of these atypical cells in the liver, spleen, kidney, and bone marrow. Morphological, cytochemical, immunohistochemical, and genotypic characteristics suggested that the proliferating cells were derived from the monocyte-macrophage system. Western blot analysis revealed the presence of autoantibody against an approximately 88 kd molecule of platelet proteins. Although the relationship of cause and effect remains to be clarified, this autoantibody appeared to have stimulated thrombophagocytosis of the neoplastic cells.

Autoimmune Diseases↗

Phase I study of E1077, a novel parenteral cephem antibiotic.

The safety and pharmacokinetics of E1077, a new injectable cephem antibiotic, were evaluated in healthy male adult volunteers. In the single-dose studies, 100, 250, 500, 1,000, and 2,000 mg of E1077 were administered by intravenous infusion at a constant rate for 60 minutes, then 1,000 mg of the drug by intravenous infusion at a constant rate for 5 minutes. The Cmax were 6.4, 15.7 +/- 12.0, 34.7 +/- 4.6, 63.2 +/- 4.6, 142.7 +/- 5.6, and 131.6 +/- 36.0 (means +/- SD) micrograms/mL, respectively, and the Cmax and AUC increased linearly with the dose. Plasma concentration-time curves were well described by a two-compartment open model. The plasma elimination half life of the drug was 1.88 +/- 0.15 hours. The mean urinary recovery within the first 24 hours was 94.1 +/- 5.1% of the dose. In the multiple-dose study, 2,000 mg of E1077 was intravenously administered at a constant rate over 60 minutes every 12 hours for 4.5 days (a total of nine times). The Cmax after the first and ninth doses were 134.0 +/- 17.4 and 135.5 +/- 15.5 micrograms/mL, respectively, and trough levels in day 1 and day 5 (at 12 hours after the first and ninth administration, respectively) were 2.2 +/- 0.8 and 1.9 +/- 0.4 micrograms/mL, respectively. No accumulation of the drug in plasma was observed. There were no significant differences in plasma levels or in the urinary recoveries between the single- and multiple-dose regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pharmacokinetics and pharmacodynamics of intravenous OPC-18790 in humans: a novel nonglycosidic inotropic agent.

OPC-18790, a nonglycosidic intropic agent, is now under clinical development for treatment of congestive heart failure. Two separate studies (one placebo-controlled) were conducted to evaluate its pharmacokinetics and pharmacodynamics after intravenous administration to a total of 36 healthy male subjects. The drug was administered both rapidly as a .05-, .1-, .2-, or .4-mg/kg intravenous dose, and as a 1-hour infusion of .5, 1.0, 2.5, 5.0, 10.0, or 15.0 micrograms/kg/minute. Echocardiograms (ECHO) were evaluated before and immediately and 4 hours after the rapid administrations. Blood pressure (BP), heart rate (HR), and QTc in the electrocardiogram also were monitored in the rapid administration study. OPC-18790 was generally well tolerated by all subjects. Maximum peak plasma concentration and area under the curve increased linearly with dose in both studies. The t1/2, total body clearance of drug from plasma (CL), and the dose fraction excreted unchanged in the urine (fe) were comparable and dose-independent at the doses tested in both studies. The overall mean values of t1/2 alpha, t1/2 beta, CL, and fe were .08 +/- .01 hours, 3.64 +/- .22 hours, .46 +/- .01 L/kg, and 43.5 +/- 1.0%, respectively. Echocardiograms showed that, immediately after rapid administration of up to .4 mg/kg, OPC-18790 increased left cardiac function dose-proportionally (P < .05 to .01): the ejection fraction by 21.1% and fractional shortening by 26.5% compared with the predose values, blood pressure, heart rate, and QTc did not differ between subjects given OPC-18790 and these receiving placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

New genotype of hepatitis C virus in South Africa.

Partial nucleotide sequences in the core region of the hepatitis C viral genome were determined by reverse transcription followed by polymerase chain reaction, in a patient with chronic hepatitis from South Africa. These nucleotide sequences showed a low degree of homology with known types of HCV: the degree of homology between the nucleotide sequences of these clones with HC-J1, J4, J6, J7, Tr, and Eb-1 were 86.1-87.3%, 87.3-87.9%, 83.0-83.9%, 81.1-82.0%, 81.0-82.2%, and 82.8-83.4%, respectively, and that the deduced amino acid sequence homologies between these clones and HC-J1, J4, H6, J7, Tr, and Eb-1 were 90.7-91.6%, 89.7-91.6%, 91.6-93.5%, 90.7-91.6%, 81.5-82.4%, and 89.2-90.2%, respectively. The nucleotide sequence homologies of these clones with HC-J1, J4, J6, J7, Tr, and Eb-1 were very low, compared to those between the same genotype. Further comparison using molecular evolutionary methods suggested that this sequences should be classified in a new genotype.

Amino Acid Sequence↗

Nucleotide sequence of the core region of hepatitis C virus in Pakistan and Bangladesh and the geographic characterisation of hepatitis C virus in south Asia.

A large number of complete and partial hepatitis C virus (HCV) sequences have been reported and classified into several genotypes, although none have been reported from South Asia. We have determined and evaluated partial sequences in the core region of HCV obtained from patients with chronic hepatitis in Pakistan and Bangladesh. Nucleotide sequences from these viruses show significant homology with the Japanese HCV-TR isolate (91.7%-97.9%) and low homology with other Japanese, American, and UK isolates including HCV-1, HC-J4, HC-J6, HC-J8, and E-b1 (79.3%-86.2%). The homologies of their deduced amino acids sequence with HCV-1, HC-J4, HC-J6, HC-J8, E-b1, and HCV-TR were 84.3%-89.8%, 85.0-87.9%, 84.1%-86.9%, 84.3%-87.0%, 90.2%-93.1%, and 89.8%-93.5%, respectively. These results suggest that our clones might be classified into the same genotype as HCV-TR. Further analysis using molecular evolutionary methods strongly supported the classification of these sequences with the HCV-TR genotype. Moreover, we could not detect any isolates which were closely related to our clones or HCV-TR in countries outside the South Asian area. These data further support the association of HCV genotypes with distinct geographic regions.

Amino Acid Sequence↗

Presence of gonadotropin-releasing hormone receptor and its messenger ribonucleic acid in endometrial carcinoma and endometrium.

In support of a possible clinical use of gonadotropin-releasing hormone (Gn-RH) analogs in the treatment of the endometrial carcinoma, this study was undertaken to establish the presence and characteristics of Gn-RH receptor on endometrial cancer. Materials were human endometrial carcinomas surgically removed and endometrial carcinoma cell lines. Gn-RH receptor was characterized by [3H]Gn-RH binding to plasma membrane preparations. Gn-RH receptor messenger ribonucleic acid (mRNA) was determined by reverse transcription-polymerase chain reaction (PCR) using oligonucleotide primers synthesized according to the published human Gn-RH receptor sequence. Specific Gn-RH binding sites were shown to be present in 16 of 18 well-differentiated and 4 of 7 poorly differentiated adenocarcinoma specimens (Kd = 5.89 +/- 3.59 nM, Bmax = 1.80 +/- 0.95 pmol/mg protein) and cell lines RL95-2 and HHUA with Kd of 2.38 +/- 0.86 nM. The high-affinity binding sites were also detected in six proliferative-phase endometrium (Kd = 4.24 +/- 2.32 nM, Bmax = 2.73 +/- 1.12 pmol/mg protein). Gn-RH receptor mRNA was detected in all endometrial carcinoma and endometrial specimens and cell lines where the specific binding sites were detected, but not in adenomyosis or myometrial samples. The expression of Gn-RH receptor provides a possible point of attack for therapeutic approaches using Gn-RH analogs in this malignancy.

Adenocarcinoma↗

Long-term serum/plasma-free culture of human cytotoxic T lymphocytes induced from peripheral blood mononuclear cells.

Tumor-specific human cytotoxic T lymphocytes (CTL) were induced by co-culturing peripheral blood mononuclear cells with X-ray-irradiated human lung squamous carcinoma cells, SQ-5, in the medium supplemented with interleukin(IL)-1, IL-2, IL-4 and IL-6, and 5% autologous plasma for 3 or 5 days. The CTL grew in serum/plasma-free medium containing these four interleukins and 0.5% bovine serum albumin for over a month and maintained killing activity of target cells within 48 h at an effector/target ratio of 1.25. Their growth was essentially dependent on the target SQ-5 cells, which were renewed every 5 days. Under these conditions, IL-4 and IL-6 could be omitted. When anti-CD3 monoclonal antibody was added to the serum/plasma-free medium supplemented with IL-1 and IL-2, the target tumor cells were not required to maintain the specific killing activity of the CTL. A large number of CTL (10(11)) were obtained in 35 days.

Carcinoma, Squamous Cell↗

The role of insulin in coronary atherosclerosis.

In 197 patients with coronary artery disease (CAD) who underwent coronary angiography, 75 g oral glucose tolerance test (OGTT) was performed, measuring plasma glucose(PG) and plasma insulin (IRI) at 4 time points (0, 30, 60 and 120 min). Subjects were separated into two groups by their insulinogenic index (I.I. = delta IRI/delta PG from 0 up to 30 min), 99 cases with good insulin response (I.I. > or = 0.4) and 98 cases with poor insulin response (I.I. < 0.4). Only two subjects were diabetic in good insulin response, while 37 were diabetic in poor insulin response. The severity of coronary atherosclerosis was expressed as a coronary index (CI), calculated according to Balcon's method. Fasting PG and the sum of PG were significantly higher in the latter group, while the sum of IRI was significantly lower. CI was not significantly different, however. In the group with good insulin response, the severity of CAD was significantly correlated to fasting IRI (n = 99, r = -0.387, P < 0.02), but, there was no such relationship in the other group. We conclude that hyperinsulinemia might be a risk factor for ischemic heart disease, but in diabetics it is difficult to link the relationship between fasting IRI and CI.

Adult↗