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Biomedical subjects

H Imanishi

Publications and source records attributed to H Imanishi.

At least 19 recordsLinked to original sources
PubMed2001

Development of orally active nonpeptidic inhibitors of human neutrophil elastase.

5-Amino-2-phenylpyrimidin-6-ones, some of their desamino derivatives, and miscellaneous derivatives were synthesized and biologically evaluated on both in vitro activity and oral activity in an acute hemorrhagic assay. These compounds contained an alpha-keto-1,3,4-oxadiazole moiety to bind covalently to the Ser-195 hydroxy group of human neutrophil elastase (HNE). Among those tested, compounds 11a-c,e,i-l(F), 11d,e,k(H), 21d,e,k(F), and 21d,e(H) showed a good oral profile. RS-Mixture 3(H) was selected for clinical evaluation based on its oral potency, duration of action, enzyme selectivity, safety profile, and ease of synthesis. Structure-activity relationships (SARs) are discussed.

Administration, Oral↗
PubMed2001

Idiopathic hemochromatosis with the mutation of Ala176Val heterozygous for HFE gene.

Most patients with hereditary hemochromatosis are homozygous for C282Y in the HFE gene in populations of Celtic origin, but the genetic cause of this disease is unknown in Japan because of its rarity. A 48-year-old Japanese patient was recently diagnosed with idiopathic hemochromatosis. Analysis of the entire coding region of the patient's HFE by RT-PCR showed a heterozygous nucleotide substitution at nucleotide 527 from C to T, which resulted in A176V amino acid substitution. Another mutation at nucleotide 942 from T to C was observed, but this was a nonsense mutation. C282Y and another mutation, H63D, were not found in the patient. The mutation may have a possible role on the cause of hemochromatosis in this Japanese case.

Alanine↗
PubMed2000

Investigation of TTV by in situ hybridization in patients with chronic hepatitis.

To clarify whether TT virus (TTV) was present in liver tissues, 12 liver tissue samples from patients with chronic hepatitis positive for TTV in their serum and 11 samples from serum-negative patients were obtained by needle biopsies and investigated using in situ hybridization. Positive staining was observed in nine (75%) of 12 cases positive for TTV (serum-positive group) and three (27.3%) of 11 cases negative for TTV (serum-negative group) (P=0.061). Three kinds of staining patterns were observed: nuclear, cytoplasmic and both. In 58.3% (7/12) of the patients positive for TTV staining, the stained areas were found in both the nucleus and cytoplasm. Only cytoplasmic staining was observed in three cases from the serum-positive group. Only nuclear staining was observed in two cases from the serum-negative group. No significant differences were found in the clinical background between the in situ hybridization-positive and -negative groups, and between the serum-positive and -negative groups. The present study shows that TTV exists in the liver tissue, especially in hepatocytes, of chronic hepatitis patients and that the localization of TTV in the cell is different from case to case, although why this is so remains to be clarified.

Journal Article↗
PubMed1997

The tumor-derived fetal-intestinal alkaline phosphatase cDNA is identical in sequence to the adult intestinal alkaline phosphatase isozyme gene.

The alkaline phosphatase (AP) of Caco-2 cells, a cell line derived from a human adenocarcinoma of the colon, is quite similar to fetal intestinal AP in its enzymatic properties. The nucleotide sequence of a cDNA encoding AP produced in Caco-2 cells was examined. The sequence was identical to one of the three sequences of adult intestinal AP reported previously. We further investigated the entire nucleotide sequence of cDNA of intestinal-type AP produced in cancer cell lines such as HuH-7 cells, FL-amnion cells, and HuG-1 cells. The sequence of these cell APs was identical to that of Caco-2 cell AP. These results indicate that cancer cells producing intestinal-type AP have the same nucleotide sequence as that of adult intestinal AP, and suggest that the differences in electrophoretic mobilities of these cell APs compared with adult intestinal AP may be due to post-translational modifications.

Adult↗
PubMed1997

Tumor necrosis factor alpha alters the cytotoxic effect of hydrogen peroxide in cultured hepatocytes.

We examined whether tumor necrosis factor-alpha (TNF) affects the cytotoxic capacity of reactive oxygen species on rat hepatocytes in culture. Both TNF and reactive oxygen species are involved in many inflammatory events including hepatic ischemia/reperfusion injury and endotoxic shock. Synchronous treatment of hepatocytes with both TNF and H2O2 demonstrated that TNF (2000 ng/ml) enhanced the cytotoxic effect of H2O2 (500 microM). By contrast, pretreatment with TNF (2000 ng/ml) for 24 h followed by exposure to H2O2 (1000 microM) reduced the reactive oxygen-induced cytotoxicity. We conclude that TNF increases the effects of reactive oxygen-induced cytotoxicity when exposed synchronously, whereas TNF pretreatment induces a cytoprotective effect to reactive oxygen species, presumably by up-regulation of the reduced form of glutathione levels in hepatocytes.

Analysis of Variance↗
PubMed1997

Reduced gastric surface mucus layer in experimental portal hypertension.

The pathogenesis of portal hypertensive gastropathy has not yet been thoroughly elucidated. Changes in the gastric surface mucus layer in prehepatic portal hypertensive and cirrhotic rat models were studied by observing frozen sections fixed with formaldehyde vapor and stained with hematoxylin and eosin. We produced prehepatic portal hypertensive rats by partial ligation of the portal vein, and cirrhotic rats by prolonged administration of carbon tetrachloride (CCl4) and phenobarbital sodium. The thickness of the corporal and antral gastric surface mucus was significantly reduced in prehepatic portal hypertensive and cirrhotic rats compared with the values obtained in control rats for portal hypertension (subjected to sham operation) and control rats for cirrhosis (treated with phenobarbital but not CCl4). These results indicate that the hemodynamic changes associated with portal hypertension reduce the thickness of the gastric surface mucus layer and may be one of the causes of the gastropathy associated with portal hypertension.

Animals↗
PubMed1997

Familial hypocholinesterasemia found in a family and a new confirmed mutation.

A 45-year-old man was hospitalized because of acute hepatitis. His serum cholinesterase (ChE) was below 10 IU/l (normal range: 105-240 IU/l) during the disease course and after his recovery. The patient was suspected of having familial hypocholinesterasemia. His family members were healthy except that his father had hypertension and gall stones. Analysis of ChE gene in the propositus and his family revealed three point mutations at nucleotides 298 (CCA to TCA), 1,410 (CGT to CGG) and 1,615 (GCA to ACA). The first mutation caused an amino acid change at codon 100 from proline to serine, which was a new mutation not previously reported, but the second one was a silent mutation. The third mutation resulted in an amino acid alteration from alanine to threonine at codon 539 in exon 4 of the ChE gene. The mode of transmission of these mutations is described.

Adult↗
PubMed1996

Alzheimer-type pathology in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).

A 53-year-old Japanese woman with a point mutation in mitochondrial DNA (tRNALeu(UUR), nt3243) consistent with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and Alzheimer-type brain pathology is reported. This woman had suffered myopathy and psychosis without any clinical evidence of, stroke-like episodes during the last 10 years of her life, and had died after an accident. At autopsy 30 h post mortem, a part of the brain was snap frozen for biochemical and histochemical studies, and the remaining part was processed for a routine examination and electron microscopy. In the brain there were no ischemic lesions. Instead, primitive/diffuse senile plaques were found throughout the brain, predominantly in the frontal and temporal lobes, while Alzheimer neurofibrillary tangles were found only in the parahippocampal gyrus. These plaques were positive for beta-protein and mostly negative for tau protein, ubiquitin, neurofilaments, alpha-choline acetyltransferase, and acetylcholinesterase. Mutations in codon 331 of the ND2 gene as well as codons 693, 713 and 717 of the beta-amyloid precursor protein gene, known to be responsible for some cases of familial Alzheimer disease, were not found. Furthermore, coincidental Down syndrome was ruled out by chromosome analysis. The results suggest a possible correlation between this mitochondrial DNA abnormality and Alzheimer-type pathology.

Alzheimer Disease↗
PubMed1996

Management of new hepatic nodules detected by intraoperative ultrasonography during hepatic resection for hepatocellular carcinoma.

BACKGROUND: During hepatic resection for hepatocellular carcinomas (HCCs) it is not uncommon that intraoperative ultrasonography detects "new nodules" that were not found by preoperative examinations. Because the operative procedure may have to be changed if the new nodule is another HCC lesion, differential diagnosis of such nodule is critical. This study examines ultrasonographic findings and clinical features of new nodules and discusses how to cope with such nodules in the operating room. METHODS: Fifty-one new nodules detected in 92 liver resections were analyzed. Intraoperative ultrasonography was performed by using 5.0 or 7.5 MHz probes after mobilization of the liver. Histologic diagnosis of the new nodules was made by means of enucleation, resection with the primary lesions, thick-needle biopsy, or additional partial resection of the liver. RESULTS: New nodules were detected in 27 (29.3%) of 92 resected cases. Internal echoic pattern of the nodules were type I, hypoechoic (29 nodules); type II, hyperechoic (19); and type III, mosaic (3). Ten HCC nodules (17.9%) were included, and chance of being malignant for each type was 24.1%, 0%, and 100%, respectively. Of the seven patients with malignant new nodules, three underwent additional systematic resection and all were alive without recurrence 49, 13, and 11 months after the operation. Others were treated by use of enucleation (two cases), intraoperative ethanol injection (one case), and intraarterial chemotherapy (one case). CONCLUSIONS: Although most of the new nodules lacked specific findings for HCC, hypoechoic nodules, 24.1% of which were HCCs, should not be overlooked. Histologic confirmation of the new nodules is necessary especially when the number of lesions detected before operation is multiple or the interval between lipiodol computed tomography and the operation is longer than 2 months. Once the diagnosis of HCC has been made for the new nodule, systematic additional resection to remove the new lesion is recommended.

Adult↗
PubMed1996

A fetal intestinal-type alkaline phosphatase produced in Caco-2 cells.

Enzymic, immunological and lectin-binding properties of alkaline phosphatase (AP) produced in Caco-2 cells, a human colon carcinoma cell line, were investigated. The enzyme was very similar to fetal intestinal (meconium) AP in the enzymic and immunological properties, but different from fetal intestinal AP in lectin-binding properties; expression of the galactose moiety was altered in AP of Caco-2 cells, compared to that of fetal intestinal AP. These results indicate that AP of Caco-2 cells can be used in place of fetal intestinal AP when the enzymic properties of an AP of unknown origin are investigated, but cannot be used instead of fetal intestinal AP in the structural study of AP.

Alkaline Phosphatase↗
PubMed1995

Impaired phorbol ester-induced hepatocyte proliferation in cirrhosis.

Cirrhotic livers are considered to regenerate less actively than normal livers after hepatic resection. Little is known about the mechanisms responsible for impaired capacity of regeneration in cirrhotic liver. In the present study, we investigated the effect of phorbol ester on hepatocyte proliferation in healthy and cirrhotic hepatocytes, using one of the phorbol esters, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which has a direct effect on activation of protein kinase C (PKC). Cirrhosis was established by the administration of carbon tetrachloride and phenobarbital to rats. Healthy and cirrhotic hepatocytes were isolated from Wistar male rats by a two-step collagenase perfusion technique. DNA synthesis was estimated by [3H]thymidine incorporation into DNA and by autoradiographic nuclear labeling index. [3H]Thymidine incorporation was measured 24 hr after hepatocytes were stimulated by appropriate reagents. TPA (50 nM) stimulated [3H]thymidine incorporation in healthy hepatocytes (control vs TPA, 991 +/- 247 vs 2569 +/- 766 mean +/- SEM cpm/microgram DNA; P < 0.05), whereas TPA (50 nM) failed to stimulate in cirrhotic hepatocytes (control vs TPA, 1144 +/- 184 vs 1304 +/- 187 cpm/microgram DNA; NS). Staurosporine, a specific PKC inhibitor, suppressed [3H]thymidine incorporation in TPA-stimulated healthy hepatocytes (806 +/- 263 cpm/microgram DNA; P < 0.05); however, it had no effect on cirrhotic hepatocytes (1295 +/- 180 cpm/microgram DNA; NS). An autoradiographic nuclear labeling index exhibited the same results with [3H]thymidine incorporation. We conclude that TPA stimulates hepatocyte proliferation in healthy rat hepatocytes but has no effect on cirrhotic hepatocytes.

Alkaloids↗
PubMed1994

Vasopressin stimulates DNA synthesis in cultured rat hepatocytes.

Liver regeneration following partial hepatectomy is significantly impaired in rats with hereditary vasopressin (AVP) deficiency. This suggested that AVP might have a direct effect on cultured rat hepatocytes. Hepatocytes from male Sprague-Dawley rats were isolated using a two-step collagenase perfusion technique and plated at a density of 10(5)/16-mm Primaria plate. After a suitable attachment period, hepatocytes were incubated with minimal essential media, AVP, AVP plus a specific AVP antagonist, or oxytocin. Hepatocyte proliferation was measured by [3H]thymidine incorporation ([3H]Thy) into hepatocyte DNA. AVP (10 nM) increased [3H]Thy significantly (and this effect was blocked by an AVP-specific antagonist (50 nM). Oxytocin had no effect on hepatocyte DNA synthesis. To further investigate the influence of AVP on hepatocyte proliferation, the effect of AVP on transforming growth factor-alpha (TGF-alpha)-stimulated hepatocyte proliferation was also studied. This combination was chosen based on the ability of AVP to inhibit the biologic effects of EGF (a TGF-alpha analog). There was significant attenuation of TGF-alpha (50 nM)-stimulated [3H]Thy in the presence of AVP (10 nM). In summary: (1) AVP stimulates proliferation of cultured rat hepatocytes. (2) The effect of AVP can be significantly abolished by a specific AVP antagonist. (3) The proliferative response of AVP is specific. (4) AVP significantly attenuates TGF-alpha-stimulated hepatocyte hepatic DNA synthesis. Further studies should elucidate the mechanisms for the effects of AVP on hepatic proliferation alone or in combination with other factors.

Animals↗
PubMed1993

Dental findings of the elderly with or without senile dementia at a special nursing home.

Survey of dental health condition was performed at a special nursing home for the elderly with senile dementia (28 subjects, 83.3 +/- 6.8 year-old; SD group) or without senile dementia (68 subjects, 84.6 +/- 7.2 year-old; NSD group). There was no difference in number of teeth survived between SD and NSD groups. However, the elderly in SD group had more unfunctionable and/or unrestorable teeth (C4) and less sound and filled teeth (SFT) than those in NSD group. Number of teeth of the elderly in 85- to 89-year-old group was smaller than those of not only younger but older age groups, irrespective of senile dementia. Lower canines showed the highest survival rate among all kinds of teeth in SD as well as in NSD group.

Aged↗
PubMed1992

Establishment of an enzyme immunoassay using monoclonal antibody (HG1-219) and its application for the diagnosis of hepatocellular carcinoma.

A monoclonal antibody (MoAb HG1-219) against a human gastric cancer cell line (HuG-1) and its shedding antigen (HG1-219 Ag) was generated and a solid-phase sandwich enzyme immunoassay (EIA-219) was developed. The mean serum HG1-219 Ag concentration in normal individuals was 30.5 +/- 14.5 U/ml measured by EIA-219. When the mean +3 SD of the antigen concentration in normal individuals was used as a cut-off level, 4.3% (2/47) of patients with chronic hepatitis, 9.1% (4/44) of cirrhotic patients and 37.5% (18/48) of patients with hepatocellular carcinoma (HCC) had HG1-219 Ag above the cut-off value. The positive rates of a-fetoprotein (AFP) (> 400 ng/ml) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC were 26.7% (12/45) and 33.3% (12/36), respectively. There was no significant correlation between HG1-219 Ag and AFP or PIVKA-II in patients with HCC. The combination assay of EIA-219, AFP and PIVKA-II for HCC gave the positive rate of 75% (27/36). The effect of periodic acid on the HG1-219 Ag and the inhibition of EIA-219 by CA 19-9 suggest that the epitope of HG1-219 Ag is a suger chain similar to CA 19-9.

Animals↗