Biomedical subjects

H Ohtani

Publications and source records attributed to H Ohtani.

At least 163 records · Page 9Linked to original sources

PubMed1997

The insulin-like growth factor II receptor gene is mutated in genetically unstable cancers of the endometrium, stomach, and colorectum.

Disruption of the DNA mismatch repair system, characterized by microsatellite instability (MI), plays an important role in the course of human carcinogenesis. Repetitive sequences constitute targets for mutation in MI+ cells, and frequent mutations have indeed been reported in such regions within the transforming growth factor beta receptor II (RII) gene in genetically unstable colorectal and gastric cancers. However, other genes that are targets for mutations in MI+ cells during the course of carcinogenesis have proven elusive. Because the insulin-like growth factor II receptor (IGFIIR) gene contains several repetitive sequences within its coding region, we examined mutations of this gene in MI+ cancers occurring at various primary sites. We found frameshift mutations in the poly(G)8 tract of IGFIIR in eight tumors, all of which were MI+: 4 of 26 (15%) MI+ endometrial cancers, 3 of 12 (25%) MI+ gastric cancers, and 1 of 18 (6%) MI+ colorectal cancers. In contrast, no mutation was found in 51 pancreatic cancers, 7 of which (14%) were MI+. These results implicate abnormal IGFIIR-mediated growth control in carcinogenesis involving the endometrium, stomach, and colorectum but not the pancreas.

Breast Neoplasms↗

PubMed1997

Determination of erythromycin concentrations in rat plasma and liver by high-performance liquid chromatography with amperometric detection.

A simple method for the quantitative determination of erythromycin (EM) concentrations in rat plasma and liver by high-performance liquid chromatography with amperometric detection was developed. EM was extracted from 200 microl of plasma or liver homogenate sample under sodium hydroxide alkaline conditions with tert.-butyl methyl ether. Oleandomycin was used as an internal standard. The recovery rate of EM was up to 100%. The detector cell potential for the oxidation of EM was +1100 mV. The calibration curves were linear over the concentration ranges 0.1-20.0 microg/ml for plasma and 0.5-100.0 microg/g for liver. The method was applied to the determination of the plasma and liver concentrations of EM in rats after intravenous administration (50 mg/kg dose). The method presented here has proved to be of great use for the investigation of the pharmacokinetic characteristics of EM in small animals such as rats.

Animals↗

PubMed1997

Simple technique for pancreatogastrostomy and the histological findings of pancreatogastric anastomosis.

The leakage of pancreatic juice is the most serious complication after pancreatoduodenectomy. In an attempt to lessen the incidence of this complication, we have developed a simple technique for the anastomosis of pancreatogastrostomy. Since March 14, 1995, we have already performed surgical procedures on 8 cases of pancreatogastrostomy using this technique and as yet have never experienced fatal complications. We report the autopsy findings of pancreatogastric anastomosis histologically. The specimen taken from the anastomosis reveals good mucosal continuity. This result suggests the importance of reliable sutures between the pancreatic parenchyma and the full thickness of the gastric wall for the anastomosis of pancreatogastrostomy.

Adenocarcinoma↗

PubMed1997

Pleomorphic adenoma of the breast: report of a case.

We present herein the case of a 74-year-old woman found to have a pleomorphic adenoma, or so-called mixed tumor, of the breast. The patient presented with a hard mass, 3 cm in diameter, located just beneath the left areola. Physical examination suggested a diagnosis of breast carcinoma; however, the findings of both ultrasonography and mammography indicated a benign neoplasm. Aspiration biopsy cytology was evaluated as class III and the diagnosis of pleomorphic adenoma was finally confirmed by examination of an excisional biopsy specimen. As it is a rare benign tumor, pleomorphic adenoma of the breast has been mistaken for a malignant tumor clinically, mammographically, cytologically, and even by frozen section. Thus, an awareness of this disease in the breast will help to prevent misdiagnosis and overaggressive surgery.

Adenoma, Pleomorphic↗

PubMed1997

Fluorescence replication banding of frog chromosomes.

To identify individual chromosomes of a frog karyotype by their fluorescence banding patterns, chromosomes were stained with actinomycin D and 4,6-diamidino-2-phenylindole (DAPI) after incorporation of BrdU during the late S-phase. The chromosomes of three Rana species which were selected for this study (R. ridibunda, R. lessonae and R. japonica) showed well-defined late replication bands. The fluorescence patterns obtained were the reverse of those produced by a 4Na-EDTA Giemsa-staining technique. Fluorescence patterns of the two water frog species (R. ridibunda and R. lessonae) were similar to each other, except for the different fluorescence of the centromeric heterochromatin, which gave extremely bright signals in R. ridibunda but no signal in R. lessonae. Experiments also showed differences between the fluorescence patterns of R. lessonae chromosome 13 in the Italian and Luxembourgian populations. These results show that the fluorescence replication banding using actinomycin D and DAPI is very effective in identifying individual frog chromosomes and detecting their structural changes.

Animals↗

PubMed1997

Evidence for two successive pericentric inversions in sex lampbrush chromosomes of Rana rugosa (Anura: Ranidae).

The objective of this study was to clarify the course of inversions by which a ZW sex chromosome dimorphism has become established in Rana rugosa. Fortunately, R. rugosa preserves three different forms of sex chromosomes in the several isolated populations. In both males and females, the homomorphic sex chromosomes from Hiroshima were closely similar to Z, while those from Isehara were slightly different from the Z. Females from Hirosaki demonstrated heteromorphic sex chromosomes. In this study, the configuration and pairing behavior of sex lampbrush chromosomes were examined in the female offspring produced from a cross between a female from Hiroshima and a male from Isehara, as well as the female offspring of a female from Hirosaki and the male from Isehara. For the sex lampbrush chromosomes from Hiroshima and Isehara, chiasmata were exclusively formed between the distal regions of the long arms of one sex chromosome and the terminal regions of the short arms of the other. As a result, landmarks arranged in reverse order were observed in the achiasmatic regions of these chromosomes. For the sex lampbrush chromosomes from Isehara and Hirosaki, on the other hand, chiasma formation was mainly confined to the lower half of the chromosomes corresponding to the long arms, and the landmarks in the achiasmatic regions of these chromosomes were disposed in the opposite direction to each other. These results seem to indicate that in the primitive sex chromosomes of the Hiroshima type two pericentric inversions occurred, leading to the differentiation of the W chromosomes. This is the first report to substantiate the process of sex chromosome differentiation experimentally.

Animals↗

PubMed1997

Pentaerythritol tetranicotinate (niceritrol) decreases plasma lipoprotein(a) levels.

We determined the most effective dosage of pentaerythritol tetranicotinate (niceritrol) to reduce plasma lipoprotein(a) [Lp(a)] levels in 44 Japanese patients (16 men and 28 women; mean age, 59.2 +/- 10.8 years) with hyperlipidemia types IIa, IIb, and IV. Patients received oral niceritrol at a dosage of 750 mg (3 tablets)/d for 8 weeks, followed by 1,500 mg (6 tablets)/d for 8 weeks. Administration of niceritrol 750 mg/d for 8 weeks decreased total and low-density lipoprotein (LDL) cholesterol in patients with type IIa hyperlipidemia and decreased triglycerides in patients with type IV hyperlipidemia, but did not affect Lp(a). However, niceritrol 1,500 mg/d for 8 weeks decreased Lp(a) in patients with initial Lp(a) levels greater than 30 mg/dL in addition to decreasing total and LDL cholesterol and triglycerides. These results suggest that the effective dosage of niceritrol to reduce the serum Lp(a) concentration in Japanese hyperlipidemic patients with a high Lp(a) level (> or = 30 mg/dL) is greater than 1,500 mg/d.

Aged↗

PubMed1997

Reduction of plasma cholesterol levels and induction of hepatic LDL receptor by cerivastatin sodium (CAS 143201-11-0, BAY w 6228), a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, in dogs.

The effects of cerivastatin sodium (BAY w 6228), a new type of inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on plasma cholesterol concentrations and the induction of hepatic LDL receptors were investigated with beagle dogs and Hep G2 cells. Oral administration of cerivastatin (0.01, 0.03, and 0.1 mg/kg per day) for 3 weeks reduced plasma total and very low-density lipoprotein plus low-density lipoprotein (VLDL + LDL) cholesterol concentrations and increased hepatic LDL receptor binding activity in dogs. Scatchard plot analysis revealed a 1.9-fold increase in the maximum binding capacity of hepatic LDL receptors in cerivastatin-treated animals. Similar results were obtained by administration of pravastatin (1.0 and 5.0 mg/kg/day) for 3 weeks. Binding activity of the LDL receptor, as well as receptor mRNA and protein concentrations, were increased in a dose-dependent manner (0.01-1.0 microM) by exposure of Hep G2 cells to cerivastatin. The results suggest that cerivastatin reduces plasma cholesterol concentrations by increasing hepatic LDL receptor expression. The mechanism of lowering cholesterol concentration by cerivastatin was the same as with the other previously examined HMG-CoA reductase inhibitors, but the effects with cerivastatin were apparent at doses much lower than the effective doses of the other drugs. Cerivastatin, therefore, shows potential for clinical use as a potent and efficacious plasma cholesterol-lowering drug.

Animals↗

PubMed1997

IgG subclasses in patients with membranoproliferative glomerulonephritis, membranous nephropathy, and lupus nephritis.

Primary glomerulopathy can be classified into seven essential patterns based on histopathological studies. The pathogenesis of membranoproliferative glomerulonephritis (MPGN), and membranous nephropathy (MN), which show glomerular IgG deposition and induce mainly nephrotic syndrome, is not known. To clarify the role of IgG subclass in glomerulonephritis, we compared serum concentrations of IgG subclasses, the ratio of serum IgG subclasses to total IgG (%IgG subclass), and glomerular deposition of IgG subclasses between 7 MPGN patients, 21 MN patients, and 9 lupus nephritis (LN) patients. Serum IgG subclasses and %IgG in all groups were almost within normal range based on the values in Japanese healthy adults. In the MPGN and MN groups, the IgG1 concentration was significant lower than that of the LN group (P < 0.001, P < 0.0001, respectively). The IgG2 concentration in the MPGN group decreased significantly compared with that in the LN group (P < 0.05). The %IgG2 of the LN group decreased significantly compared with that of the MN group (P < 0.05). The %IgG3 of the MPGN group was significantly higher that that of the MN group (P < 0.05). The glomerular immunofluorescent intensity of IgG1 and IgG2 were significantly stronger in the LN group than in the MPGN and MN groups (IgG1, P < 0.001, P < 0.01, respectively; IgG2, P < 0.0001, P < 0.0001, respectively). IgG3 in the MPGN and LN groups deposited significantly compared with that in the MN group (P < 0.0001, P < 0.01, respectively). The intensity of IgG4 in the MN group showed a significant difference compared with that in the MPGN and LN groups (P < 0.0001, P < 0.01, respectively). IgG3 is an important factor in the pathogenesis of primary MPGN, while IgG4 relates to glomerular IgG deposition in MN.

Adolescent↗

PubMed1997

Levels of interleukin-6, CRP and alpha 2 macroglobulin in cerebrospinal fluid (CSF) and serum as indicator of blood-CSF barrier damage.

We measured the levels of interleukin-6 (IL-6), albumin, C-reactive protein (CRP) and alpha 2 macroglobulin (alpha 2M), all of which have different spectrums of molecular weight, in the cerebrospinal fluid (CSF) and serum in 121 patients to evaluate damage to the blood-cerebrospinal fluid barrier (BCB) in meningitis. There was an extraordinary high level of IL-6 in the CSF when patients had bacterial or viral meningitis, but the level returned to a normal range within a week in almost all of these cases. There were no significant differences in CSF albumin levels among the different disease groups. The CRP level in CSF is considered to correlate with the serum level, and CSF CRP was higher in bacterial meningitis than in viral meningitis, however, CRP in CSF was increased in some of the infectious diseases without meningitis. The alpha 2M in CSF, which tends to be at extraordinarily high levels when there is damage to the BCB, correlated highly with CSF cell counts. CSF IL-6 seemed to be a useful indicator to identify the acute active phase of meningitis. CRP and alpha 2M in CSF are considered to be useful to differentiate bacterial meningitis, bacterial infection without meningitis and viral meningitis. Extraordinarily high levels of alpha 2M, which has a high molecular weight, in CSF is indicative of BCB damage.

Adult↗

PubMed1997

Comparison of assay methods for benzodiazepines in urine. A receptor assay, two immunoassays, and gas chromatography-mass spectrometry.

We analyzed 127 urine samples for benzodiazepines by a radioreceptor assay and two immunoassays (cloned enzyme donor immunoassay [CEDIA, Boehringer Mannheim, Indianapolis, Ind] and agglutination immunoassay [ONLINE, Roche Diagnostic Systems, Branchburg, NJ]). Sixty samples that were positive by at least one of these assays were submitted to gas chromatography-mass spectrometry, which detected benzodiazepines such as oxazepam, nordiazepam, and lorazepam in 44 samples. Diagnostic sensitivity and specificity of the receptor assay were almost equal or superior to those of the two immunoassays, although discrepant results were obtained in some samples. The discrepancies resulted from differences in the cross-reactivity of these assays. For example, the receptor assay could detect lorazepam, while the two immunoassays could not, and CEDIA was interfered with by a metabolite of sertraline while the others were not. This is the first report showing the utility of a receptor assay for screening benzodiazepines in urine.

Agglutination Tests↗

PubMed1997

Mouth and genital ulcers with inflamed cartilage (MAGIC syndrome): a case report and literature review.

A 39-year-old woman had relapsing polychondritis and Behçet's disease, which was described as mouth and genital ulcers with inflamed cartilage syndrome (MAGIC). Serologic human leukocyte antigen analysis showed A24 (9), A31 (19), B56 (22), B62 (15), Cw6, DR4, DR9. Human leukocyte antigen allele analysis revealed DRB1* 0406/0901, DQA1* 0301/0301, DQB1* 0302/0303, DPB1* 0201/0501 through determining the genotype using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Treatment with methotrexate (5 mg/week) and pentoxifylline (300 mg/d) was effective to control oral ulcers, erythema nodosum, and arthritis.

Adult↗

PubMed1997

Expression of adhesion molecules in nonallergic chronic sinusitis.

Endothelial and epithelial adhesion molecules are important in the recruitment of leukocytes to inflammatory sites. To determine the relationship between recruited leukocytes and adhesion molecules in the paranasal sinus mucosa of nonallergic chronic sinusitis, we surgically obtained mucosa from 16 patients and identified the expression of intercellular adhesion molecules (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin by immunohistochemistry. Neutrophils were significantly dominant in the nasal discharge as compared with eosinophils. The degree of neutrophil infiltration in the paranasal sinus mucosa was prominent in both intraepithelial and subepithelial areas as compared with the lamina propria. In each tissue site, the degree of infiltration of neutrophils was similar to that of eosinophils. These findings suggest that the tissue neutrophils actively and rapidly migrated into the lumen. All the adhesion molecules except VCAM-1 were expressed in the vascular endothelial cells. On the other hand, the surface epithelial cells showed the expression of only ICAM-1. The expression of ICAM-1 on the endothelial cells correlated with the degree of neutrophil infiltration in the mucosa The eosinophil infiltration was not dependent on any adhesion molecules examined here. It was concluded that ICAM-1 expression in the mucosa may be involved in neutrophil recruitment and may contribute to the establishment of the inflammatory cell distribution in the paranasal sinus of nonallergic chronic sinusitis.

Adolescent↗

PubMed1997

Stromal expression of MMP-9 and urokinase receptor is inversely associated with liver metastasis and with infiltrating growth in human colorectal cancer: a novel approach from immune/inflammatory aspect.

MMP-9 (gelatinase B) and urokinase-type plasminogen activator receptor (u-PAR), which are involved in cancer cell invasion and metastasis, are reported to be predominantly expressed by immune/inflammatory cells in human colorectal cancers. To investigate their significance in cancer progression, we morphometrically analyzed the tissue expression of MMP-9 and u-PAR among different stages of colorectal cancer. The numbers of MMP-9- and u-PAR-positive cells along the invasive margin were significantly smaller in cases with liver metastasis than in cases without liver metastasis, and were also smaller in cases with an infiltrating margin than in cases with an expanding margin. Both variables were larger in colon cancer cases with conspicuous lymphocytic infiltration. These results indicated that the degree of tissue expression of MMP-9 and u-PAR by host cells is inversely associated with liver metastasis and an infiltrating growth pattern in human colorectal cancers. Essentially the same results were obtained for the number of macrophages distributed along the invasive margin. We also found that the expression pattern of MMP-9 was similar to that of MMP-8 (polymorphonuclear leukocyte collagenase). These data are consistent with clinicopathologic studies of host cells. Therefore, our data suggest a dual role of MMP-9 and u-PAR expression in colon cancer tissue; i.e., not only are these proteinases cancer-promoting factors, but also they are related to the host defensive mechanism when they are expressed by host cells.

Antigens, CD↗

PubMed1997

Mucosa-associated lymphoid tissue lymphoma coexisting with epithelioid granulomas in the stomach of a patient with systemic sarcoidosis.

Malignant lymphoma arising in the stomach of a 23-year-old Japanese man with systemic sarcoidosis is presented. The patient was followed because of systemic sarcoidosis involving the lungs, eyes, and lymph nodes. Biopsy specimens from the stomach were repeated because of recurrent epigastralgia and multiple ulcerations. Some of the specimens revealed epithelioid granulomas with no caseous necrosis, which confirmed gastric involvement of sarcoidosis. Three years after the initial diagnosis, biopsy specimens taken from the stomach were diagnosed as malignant lymphoma of the large cell type. The resected stomach revealed multicentric mucosa-associated type malignant lymphoma of low-grade B cell type, with foci of high-grade transformation coexisting with numerous epithelioid granulomas with no caseous necrosis. Epithelioid granulomas were observed in all the respected lymph nodes, liver, and appendix, which had been obtained at operation, whereas malignant lymphoma was limited to the stomach. Helicobacter pylori (H. pylori) infection was also observed in the stomach. Consequently, the present report is a rare case of coexistence of malignant lymphoma and involvement of sarcoidosis in the stomach. Both H. pylori infection and active sarcoid nodules may play a role in the development of malignant lymphoma, although the exact mechanism remains unclear.

Adult↗

PubMed1997

A comparative pharmacokinetic-pharmacodynamic study of the electrocardiographic effects of epinastine and terfenadine in rats.

The effects of epinastine hydrochloride and terfenadine on electrocardiographic (ECG) parameters in rats were investigated from a pharmacokinetic and pharmacodynamic perspective. Epinastine hydrochloride (1 or 3 mg kg-1 h-1) or terfenadine (5, 10 or 15 mg kg-1 h-1) was intravenously infused into rats anaesthetized with urethane and alpha-chloralose. The changes in the QT interval derived from limb lead II and the chest lead, heart rate and PR interval were analysed. The time-course of the plasma drug-concentration of each drug was also investigated. Terfenadine prolonged the QT interval in an infusion-rate-dependent manner, its EC50 value was 792-1039 ng mL-1. An obvious QT prolongation was, moreover, observed even at a plasma terfenadine concentration of 100-200 ng mL-1, which is clinically quite high, but might be achieved under a definite condition such as a restrained terfenadine metabolism. Terfenadine also induced PR prolongation and bradycardia in an infusion-rate dependent manner. Epinastine slightly increased the heart rate, but did not affect any of the other ECG parameters even at a plasma concentration of 400 ng mL-1, which is more than 10 times the maximum concentration attained after an ordinary dosage regimen in man. We conclude that epinastine might have an advantage over terfenadine in avoiding adverse electrocardiographic reactions.

Animals↗

PubMed1997

Eosinophils as a source of matrix metalloproteinase-9 in asthmatic airway inflammation.

Bronchial asthma is characterized by eosinophil infiltration and tissue remodeling. Matrix metalloproteinases (MMPs) are thought to play critical roles by degradating interstitial matrices in a wide range of lung diseases associated with reorganization of the airway architecture. To investigate whether MMPs are involved in the pathologic processes of bronchial asthma, we examined MMP expression in asthmatic subjects. In situ hybridization revealed abundant expression of MMP-9 (gelatinase B) mRNA in biopsy specimens from asthmatic subjects (n = 5), with an average positive cell distribution of 117.8 +/- 41.1 (mean +/- SEM)/mm2. In contrast, sparse expression of the mRNA (10.8 +/- 4.8 /mm2) was observed in specimens from normal subjects (n = 4). The vast majority of cells expressing the mRNA were eosinophils in asthmatic tissues (92.2 +/- 1.2%). MMP-9 protein, which was confined to the submucosal cells in the normal subjects, was not abundantly expressed in inflammatory cells, but there was positive reactivity for MMP-9 protein in the extracellular matrix. Immunoelectron microscopic analysis showed sparse immunolocalization of MMP-9 in the perinuclear spaces of eosinophils, but not in the granules. These findings suggest the overexpression of MMP-9 by eosinophils in bronchial tissues of asthmatic individuals, and the participation of MMPs in the pathologic changes in asthmatic airways.

Adult↗

PubMed1997

Molecular cloning of cDNA for the zeta isoform of the 14-3-3 protein: homologous sequences in the 3'-untranslated region of frog and human zeta isoforms.

14-3-3 proteins constitute a family of well-conserved eukaryotic proteins that possess diverse biochemical activities such as regulation of gene transcription, cell proliferation and activation of protein kinase C. At least 7 subtypes (alpha to theta) of 14-3-3 protein are known, but the zeta subtype of this protein has been cloned only in mammals. We cloned the zeta subtype of 14-3-3 protein (14-3-3 zeta) from the frog, Rana rugosa. The sequence encoded 245 amino acids that share 92% identity with rat and bovine 14-3-3 zeta s, and 92% with human phospholipase A2 (PLA2; 14-3-3 zeta). Northern blot analysis revealed a single band of about 1.8 kb in tadpoles at stage 25. The 14-3-3 zeta mRNA level was high in the brain, lung, spleen and kidney, and low in the heart and testis, as opposed to the mRNA level, which was only faintly detected in the liver, pancreas, ovary and muscle. Furthermore, high similarity in the 3'-untranslated region (3'-UTR) was observed between frog and human 14-3-3 zeta cDNA. The results suggest that 14-3-3 zeta is highly conserved throughout eukaryotic evolution, and that the homologous sequence in the 3'-UTR of 14-3-3 zeta cDNA may be conserved in frogs and humans.

14-3-3 Proteins↗