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Biomedical subjects

M Furutani

Publications and source records attributed to M Furutani.

At least 55 records · Page 3Linked to original sources
PubMed1997

Decreased expression and rare somatic mutation of the CIP1/WAF1 gene in human hepatocellular carcinoma.

CIP1/WAF1, a critical downstream effector of tumor suppressor p53, encodes a cyclin-dependent kinase inhibitor. By Northern blot analysis, the CIP1/WAF1 mRNA level in the tumor was significantly lower than that in the corresponding normal liver from 19 Japanese patients with hepatocellular carcinoma (P < 0.05). In the tumor from only one out of 19 patients (5%), somatic mutations of the CIP1/WAF1 as well as that of p53 gene were identified by RT-PCR/SSCP analysis. These results suggest that the decreased CIP1/WAF1 expression is involved in the carcinogenesis or the progression of hepatocellular carcinoma.

Adult↗
PubMed1997

Calcium-evoked insulin release from insulinoma cells is mediated via calcium-sensing receptor.

BACKGROUND: We have previously reported that high extracellular calcium ([Ca2+]o) levels elicited rapid increases in the cytosolic free calcium ([Ca2+]i) and insulin release from human insulinoma cells. In this study we further investigated the mechanism for stimulus-secretion coupling of insulinoma cells exposed to high levels of [Ca2+]o. METHODS: Insulinoma tissues were surgically obtained for primary culture. The changes of [Ca2+]i level in response to various agents were monitored by fluorometry. Total RNA was extracted from tissues and subjected to reverse transcription-polymerase chain reaction (RT-PCR) with calcium-sensing receptor (CaR)-specific primers. PCR products were subcloned and sequenced. RESULTS: When [Ca2+]o level was elevated, [Ca2+]i in insulinoma cells was immediately increased. Application of neomycin abolished the increase in [Ca2+]i level, although extracellular nifedipine and lanthanum chloride did not affect it. The depletion of intracellular calcium stores with thapsigargin or carbachol eliminated the increase in [Ca2+]i level. RT-PCR analysis identified the 682 bp product, of which the sequence was identical to the corresponding regions of human parathyroid CaR. CONCLUSIONS: Intracellular Ca2+ release might be important in insulin release from insulinoma cells after exposing to high level of [Ca2+]o. CaR could be involved in this mechanism.

Adult↗
PubMed1997

Benefits of trazodone and mianserin for patients with late-life chronic schizophrenia and tardive dyskinesia: an add-on, double-blind, placebo-controlled study.

The objective of the present study was to evaluate the efficacy of mianserin and trazodone as antidepressants with serotonin 2 antagonist properties on negative symptoms and tardive dyskinesia in elderly patients with chronic schizophrenia. In this double-blind, placebo-controlled study the dose of each drug was increased gradually, from 20 mg/day mianserin to 60 mg/day, and from 50 mg/day trazodone to 200 mg/day. Symptoms were assessed using the Brief Psychiatric Rating Scale, the Scale for Assessment of Negative Symptoms and the Abnormal Involuntary Movement Scale every week for 5 weeks. A total of 38 patients (23 men and 15 women) completed the trial. Mianserin (n = 13) and trazodone (n = 12) did not alter the Brief Psychiatric Rating Scale positive symptom factor over the 5 weeks. In the mianserin group, the Scale for Assessment of Negative Symptoms total score decreased significantly after 5 weeks. Scores of 'affective flattening and blunting' and 'alogia' scores on the Scale for assessment of Negative Symptoms decreased significantly in both treatment groups. In the trazodone group, the decrease in the Abnormal Involuntary Movement Scale total score was statistically significant at weeks 2 and 3. Results indicate that serotonergic antidepressants, when used in conjunction with neuroleptics, are safe and effective for treating negative symptoms in elderly patients with chronic schizophrenia. Results also indicated a possible beneficial effect of trazodone in treating tardive dyskinesia.

Age Factors↗
PubMed1997

[Surgical treatment and result for metastatic pulmonary tumor: comparison between sarcoma and carcinoma].

Purpose of this study is to estimate the effectiveness of surgical treatment for metastatic pulmonary tumor by comparing sarcoma with carcinoma. There ware 43 cases and 64 operations of metastatic pulmonary tumor from 1981 to 1995 in Tottori university hospital. When we compared the background factors between sarcoma and carcinoma, there were significant differences in age, numbers of metastatic tumor and times of operation. Patients of sarcoma were much younger and had more number of metastatic tumor and more times of operation than those of carcinoma. Long term results after operation were 50.8% at 5 years and 44.4% at 10 years survival rate in all cases. The 5 year survival rate of sarcoma (38.1%) had a tendency of worse result than that of carcinoma (57.3%). Important factors that influence the post operative long term result were more numbers of pulmonary metastasis and more times of operation in sarcoma. On the other hand, because cases of carcinoma included many low grade malignancies in the group of multiple metastasis, the postoperative result of multiple metastasis became relatively better in our study.

Adolescent↗
PubMed1997

[Four cases of subpleural intrapulmonary lymph node].

We presented four cases of subpleural intrapulmonary lymph node showing the indeterminate pulmonary nodule. Case 1 was a 54-year-old male who had a subpleural nodule, 7 mm in diameter in the right S8 segment on chest CT. This nodule showed difficulty to differentiate from small peripheral lung carcinoma. Case 2 was a 72-year-old male who was diagnosed adenocarcinoma of lung. Chest CT showed multiple pulmonary nodules, about 5 mm in diameter except main tumor in the right middle and lower lobes. These nodules showed difficulty to differentiate from intrapulmonary metastasis. Case 3 was a 70-year-old female who was diagnosed lung metastasis of sigmoid colon cancer. Chest CT showed a subpleural nodule, 3 mm in diameter except main tumor in the right S9 segment. This nodule also showed difficulty to differentiate from lung metastasis. Case 4 was a 40-year-old female who had a subpleural nodule, 10 mm in diameter in the right S9 segment. This nodule also showed difficulty to differentiate from small peripheral lung carcinoma. We diagnosed subpleural intrapulmonary lymph nodes, in case 1, 2 and 3, by open thoracotomy and in case 4, thoracoscopic surgery. It should be always kept in mind that subpleural pulmonary nodules in especially middle and lower lobes of lung might be intrapulmonary lymph nodes. Thoracoscopic surgery would be a very useful procedure for diagnosis and therapy of subpleural intrapulmonary lymph nodes.

Adult↗
PubMed1996

Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene expression in liver tumor.

Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. However, the relationship between the vascularity of HCC and the expression of angiogenic factors has not been investigated. In addition, no detailed studies have examined the possible involvement of angiogenic factors in the grade of malignancy of HCC. The aim of this study was to determine which angiogenic factors regulate tumor angiogenesis and contribute to the invasive ability of liver tumors, especially of HCC. Northern blot analysis was used to examine the transcriptional expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF), and acidic FGF in resected surgical specimens (20 HCC and 9 metastatic liver tumors). Correlations between messenger RNA (mRNA) expression and arteriographic findings, as well as histopathological findings, were evaluated. Immunohistochemistry was performed to identify the localization of cells expressing VEGF in HCC. Higher levels of VEGF mRNA were observed in 12 of 20 HCC and 2 of 9 metastatic liver tumors than in corresponding nontumorous tissues. The degree of VEGF mRNA expression was significantly correlated with the intensity of tumor staining in angiograms (P<.01). On immunohistochemical observation, VEGF protein was intensely detected in HCC cells. Furthermore, basic FGF mRNA was detected in 9 of 20 HCC and was related to the capsular infiltration of cancer cells (P<.05). In contrast, no significant difference was observed in the very low levels of acidic FGF mRNA found in the tumorous and nontumorous portions of the liver. In conclusion, these results suggest that VEGF contributes to angiogenesis of liver tumors, whereas basic FGF may be involved in the invasion of HCC into the surrounding tissues.

Aged↗
PubMed1996

Chemical mediators released by primary-cultured human hepatic macrophages in patients with and without cirrhosis: a study in tumor-bearing patients.

To elucidate the possible role of chemical mediators in modulating the host-defense activity of patients with cirrhosis, primary-cultured human hepatic macrophages (HHMphi) were obtained from cirrhotic and noncirrhotic patients who received liver resections because of the presence of malignant liver tumors. The cirrhotic and noncirrhotic groups consisted of patients with similar malignancies: noncirrhotic patients had normal liver function and normal liver histology for nontumorous portions. The cultured HHMphi were analyzed for their ability to release chemical mediators with specific activities in the host defense system. Dose-dependent increases in superoxide release, interleukin-1 (IL-1) release, and, within a relatively narrow range, prostaglandin-E2 (PGE2) release were observed in opsonized zymosan (oz)-stimulated HHMphi derived from both cirrhotic and noncirrhotic patients. The release of O2- and PGE2 from HHMphi derived from cirrhotic patients was significantly less than HHMphi derived from noncirrhotic patients, whereas the release of IL-1 was significantly greater. Although, because of the limited sample availability, only tumor-bearing patients were studied, the mediator-releasing ability of HHMphi derived from cirrhotic patients was significantly different from the ability of HHMphi derived from noncirrhotic patients with similar malignancies. This phenomenon may be related to altered host defenses in patients with cirrhosis.

Adjuvants, Immunologic↗
PubMed1996

Overexpression of matrix metalloproteinase 9 gene in hepatocellular carcinoma with invasive potential.

The prognosis for hepatocellular carcinoma (HCC) depends mainly on the clinicopathological characteristic regarding invasion and metastasis. In addition, another distinguishing feature of HCC is the high incidence of concomitant liver cirrhosis, in which the extracellular matrix proliferates markedly. Therefore, the present study was designed to investigate the molecules responsible for the invasion potential of HCC by focusing on matrix metalloproteinase (MMP) in particular, MMP-2 and MMP-9 and the corresponding tissue inhibitor of metalloproteinase (TIMP-2 and TIMP-1), because these enzymes participate in the degradation of the extracellular matrix including the basement membrane. Tumorous and adjacent nontumorous liver samples were obtained from 23 HCC patients who underwent a partial hepatectomy. In 16 of the 23 HCC samples, transcripts for MMP-9 were detected in the tumorous tissues, and 15 of 16 of these samples showed stronger expression in the tumorous tissues than in the nontumorous tissues. On the other hand, MMP-2 messenger RNA (mRNA) was detected in 18 of the 23 cases. Eight of these 18 cases showed more intense expression in the tumorous tissues than in the nontumorous tissues, whereas the expression levels were lower in the tumorous tissues than in the nontumorous tissues in 7 of 18 samples. With respect to the correlation between the clinicopathological features and mRNAs expression, it was found that the expression of MMP-9 mRNA in HCC with capsular infiltration was significantly higher than in HCC without capsular infiltration. HCC with capsular infiltration also tended to have a higher ratio of MMP-9 mRNA expression to TIMP-1 mRNA expression. In addition, the expression of MMP-2 mRNA in nontumorous cirrhotic tissues was significantly higher than in nontumorous tissues from patients with chronic hepatitis. Immunohistochemical examinations revealed that MMP-9 immunoreactivity was the most intense in the HCC cells, particularly in those cells in the marginal areas of the tumorous tissues. In conclusion, the present study shows that MMP-9 is closely participated in capsular infiltration in HCC.

Adult↗
PubMed1996

kan-1 (bile acid CoA:amino acid N-acyltransferase) messenger RNA as a novel predictive indicator for prognosis of hepatocellular carcinoma patients after partial hepatectomy.

We identified kan-1 complementary DNA (cDNA), the sequence of which is identical to bile acid CoA:amino acid N-acyltransferase (BAT), a liver enzyme that catalyzes the conjugation of bile acids with glycine or taurine. Kan-1(BAT) messenger RNA (mRNA) levels of the resected specimens obtained from 37 hepatocellular carcinoma (HCC) patients were studied in an attempt to evaluate prognostic significance in HCC patients after partial hepatectomy. Using Northern blot hybridization, kan-1(BAT) mRNA levels were quantified in tumorous and nontumorous tissues, and the ratio of the former to the latter was defined as the kan-1(BAT) ratio. Twelve patients had a kan-1(BAT) ratio < 0.5 (low kan-1[BAT] ratio), and 25 patients had a ratio >0.5 (high kan-1[BAT] ratio). The patients with a low kan-1(BAT) ratio demonstrated poorer survival than the patients with a high kan-1(BAT) ratio (P = .0013). The overall estimated hazard ratio for death in patients with a low kan-1(BAT) ratio was 68.05 according to a multivariate model (P = .0005). Thus, the kan-1(BAT) ratio may serve as a new molecular prognostic marker in HCC patients, following hepatic resection.

Acyltransferases↗
PubMed1995

Reduced expression of kan-1 (encoding putative bile acid-CoA-amino acid N-acyltransferase) mRNA in livers of rats after partial hepatectomy and during sepsis.

We isolated a cDNA clone, kan-1, from a rat liver cDNA library using a reverse transcriptase PCR cloning method. The kan-1 cDNA encoded a polypeptide of 420 amino acids, and was 70 and 69% identical in nucleotide and amino acid sequences respectively with human liver bile acid-CoA-amino acid N-acyltransferase (BAT). Thus Kan-1 is probably a rat homologue of human BAT (rBAT). Kan-1/rBAT mRNA was mainly expressed in the livers of adult rats and rats immediately after, but not before, birth. It was expressed in the hepatocytes, the sinusoidal endothelial cells and the Kupffer cells of the liver. An anti-Kan-1/rBAT polyclonal antibody detected a protein of molecular mass 46 kDa in the liver. After partial hepatectomy, the levels of Kan-1/rBAT mRNA decreased at 6 and 12 h in the regenerating liver. In a sepsis model, hepatic expression of Kan-1/rBAT mRNA decreased at 6 and 12 h after caecal ligation and puncture. The kinetics of Kan-1/rBAT mRNA expression suggests that it may play a role in acute-phase reactions.

Acyltransferases↗
PubMed1995

Enhanced expression of multiple protein tyrosine phosphatases in the regenerating mouse liver: isolation of PTP-RL10, a novel cytoplasmic-type phosphatase with sequence homology to cytoskeletal protein 4.1.

To elucidate the role that protein tyrosine phosphatase (PTPs) may play in liver regeneration, PTPs expressed in the mouse liver after partial hepatectomy (PH) were investigated by a PCR-based cloning method. Sequencing of 115 cDNA clones identified 10 different sequences including MPTP (T cell PTP), PTP-1B, PTP-P19, mR-PTP mu, R-PTP alpha, PTP NE-3 (PTP-P1), R-PTP-kappa and the murine homologue of human LAR. The remaining two sequences, PTP-RL9 and PTP-RL10, encoded novel PTPs. PTP-RL10 cDNA contained an open reading frame of 1176 amino acids with no apparent membrane-spanning region. The amino-terminal region had sequence homology to those of human erythrocyte protein 4.1 and ezrin, cytoskeletal proteins. In the regenerating liver, the levels of five PTP gene mRNAs (MPTP, PTP-P19, R-PTP alpha, LAR homologue, and PTP-RL9) increased within 6 h, decreased to the normal level by 24 h, and increased again at 48 to 72 h after PH. The levels of PTP-1B and R-PTP-kappa mRNAs peaked within 6 h, decreased gradually, and returned to the normal level by 168 h after PH. In contrast, the levels of two PTP mRNAs (mR-PTP mu and PTP-RL10) peaked at 48 to 72 h, and returned to the normal level by 168 h after PH. No expression of PTP NE-3 was detected in the liver by Northern blotting. The differential expression of multiple PTPs during the pre-replicative and post-replicative stages of liver regeneration suggests that PTPs are involved in the regulation of growth and differentiation of liver cells.

Amino Acid Sequence↗
PubMed1995

Expression of cytokine genes during liver regeneration after partial hepatectomy in rats.

In the present study to demonstrate the relationship between cytokines and liver regeneration we investigated by Northern blot hybridization the cytokine gene induction in the regenerating liver and several other organs (spleen, lung, and kidney) in the rat after partial hepatectomy (PH). We also examined whether Kupffer cells and the spleen are involved in the induction of cytokine mRNA in the regenerating liver. Both IL-1 alpha and beta mRNA increased transiently 1/2 to 1 hr after PH in nonparenchymal cells (NPC) of the regenerating liver; they reached a maximum before the peak of hepatocyte DNA synthesis. PH also induced a slight, but significant, gene expression of IL-1 in lung and kidney in the early postoperative period. TNF-alpha mRNA increased gradually in the spleen, but not the liver, of partially hepatectomized rats at 3 to 12 hr and then reached a peak at 24 hr after PH. IL-6 transcripts were not detected in the regenerating liver, spleen, lung, or kidney during liver regeneration. In contrast, no cytokine gene expression was induced in any of these four organs during the first 3 days after sham operation or unilateral nephrectomy. When Kupffer cell activity was suppressed by gadolinium chloride pretreatment, or when splenectomy was performed 24 hr before PH, the constitutive IL-1 alpha and beta mRNA expressions in NPC of the normal rat liver were completely suppressed. In conclusion, the present study demonstrates, for the first time, the specific kinetics of cytokine gene expression in the liver, spleen, lung, and kidney after PH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Participation of hepatic macrophages and plasma factors in endotoxin-induced liver injury.

The present study was designed to investigate the mechanism responsible for endotoxin-induced liver injury, based on the working hypothesis that hepatic macrophages activated by endotoxin play a key role in the development of this injury. At both the protein and the transcription levels, the intravenous administration of endotoxin was shown to have increased the capacity of hepatic macrophages to produce chemical mediators. To inhibit the function of hepatic macrophages, gadolinium chloride (GdCl3), a specific inhibitor of resident hepatic macrophages, was preadministered to rats before endotoxin injection. GdCl3 reduced the elevated glutamic oxaloacetic transamiase and lactate dehydrogenase serum levels produced by endotoxin treatment, suppressed the increased mRNA expression of tumor necrosis factor (TNF-alpha) produced in liver nonparenchymal cells by endotoxin, and then improved the survival rate of lipopolysaccharide-injected rats. These results indicated that hepatic macrophages played a crucial role in liver injury and that TNF-alpha was the most likely factor implicated in the development of endotoxin-induced liver injury. Furthermore, we found that liver injury did not progress during perfusion of endotoxin-pretreated extirpated liver with lactate Ringer's solution, whereas liver perfused with plasma developed remarkable hepatic impairment, which was inhibited almost completely by GdCl3-pretreatment; moreover, addition of heparin to the perfusate also prevented this deterioration. Thus, the present study showed that the activation of hepatic macrophages and factors in the plasma were two essential elements in the occurrence and development of endotoxin-induced liver injury.

Animals↗
PubMed1995

Bronchoalveolar mast cells in summer-type hypersensitivity pneumonitis: increase in numbers and ultrastructural evidence of degranulation.

To investigate the role of mast cells in the development of summer-type hypersensitivity pneumonitis (SHP), which is the most common type of hypersensitivity pneumonitis in Japan, bronchoalveolar lavage fluid (BALF) cells from 13 patients with this disease was studied by light and electron microscopy. The proportion and number of BALF mast cells recovered from SHP patients were significantly greater than those from patients with sarcoidosis and from control subjects. The BALF mast cells from the SHP patients showed various ultrastructural changes such as the transformation of granules, cytoplasmic vacuolation, and an increase of lipid droplets. These findings appeared to reflect activation and degranulation of bronchoalveolar mast cells, suggesting that mast cells play a role as inflammatory cells in the development of SHP.

Adult↗
PubMed1994

Pathogenic role of Kupffer cell activation in the reperfusion injury of cold-preserved liver.

The present study was designed to investigate the possible participation of Kupffer cells in the development of reperfusion injury of the cold-stored liver graft. In the cold preservation of Kupffer cells with Euro-Collins solution, the proportion of asialo-GM1-positive cells was significantly increased at 12 and 24 hr of storage, and the TNF alpha-producing activity in these cells was approximately fivefold greater than control. Northern blot analysis demonstrated that TNF alpha mRNA was remarkably elevated in the reperfusion of the cold-preserved liver, although that of the prereperfused graft was only slightly induced. The reperfusion experiments of the cold-stored liver graft showed that addition of anti-TNF alpha antibody to the perfusate suppressed the elevation of the effluent levels of GOT and LDH significantly, and that pretreatment with a Kupffer cell inhibitor, gadolinium chloride, inhibited the increase of these enzymes in the effluents almost completely. Histological study revealed deposition of a fibrinlike substance in the sinusoid and the central veins extensively in the reperfused liver graft, whereas no apparent deposition was observed in the gadolinium-pretreated liver. Thus, the present study showed that Kupffer cells were primed by cold preservation with Euro-Collins solution, and then activated when the reperfusion was done. It seems likely that the Kupffer cell activation induced by cold preservation/reperfusion plays a major role in reperfusion injury with sinusoidal microcirculatory disturbance, and that TNF alpha is responsible for the impairment of the reperfused liver graft.

Alanine Transaminase↗
PubMed1994

Mandibular involvement in patients with multiple myeloma.

A survey of changes in the jaw bones of 38 patients with multiple myeloma revealed five cases with mandibular involvement. One case showed a pathological fracture of the mandibular angle, and in another case, a radiolucent area was found in the body of the mandible. These two clinical findings led to the diagnosis of multiple myeloma. The other three cases had no symptoms related to the oral region. All five cases also showed typical "punched-out" lesions in the skull. It is suggested that a skeletal radiologic survey including the jaw should be performed in patients with multiple myeloma.

Adult↗
PubMed1994

Ultrastructural observation of Pneumocystis carinii in bronchoalveolar lavage fluid from non-AIDS patients with P carinii pneumonia.

To investigate the morphology of Pneumocystis carinii in vivo, we studied the ultrastructure of P carinii in bronchoalveolar lavage fluid (BALF) obtained from four non-AIDS patients with P carinii pneumonia (PCP), and observed the morphologic changes after treatment in one patient. Every form recognized in the normal life cycle of P carinii, ie, thick-walled cysts, crescent-shaped cysts, and trophozoites, was detected in the pretreatment BALF specimens. In the posttreatment BALF, P carinii revealed marked ultrastructural changes such as the elongation of thick-walled cysts, the degeneration of intracystic bodies, and the disappearance of trophozoites. Massive debris derived from P carinii was still found in the BALF even after the treatment. Examination of P carinii in BALF, including ultrastructural observations, might help us to evaluate the disease status and the effect of treatment in patients with PCP.

Aged↗