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Biomedical subjects

H Suwa

Publications and source records attributed to H Suwa.

At least 37 records · Page 2Linked to original sources
PubMed1998

Overexpression of the rhoC gene correlates with progression of ductal adenocarcinoma of the pancreas.

It has been reported that the rho genes, which consist of a ras-related small GTPase protein family, regulate cytoskeletal structures and have the potential to transform cultured cells. To investigate the biological relevance of the rho genes in pancreatic carcinogenesis, we examined expressions of the rhoA, B and C genes by polymerase chain reaction after reverse transcription (RT-PCR) in 33 cases of ductal adenocarcinoma of the pancreas. In addition, mutations of the K-ras, rhoA, B and C genes were studied in the same series of tumour tissues to correlate with rho gene expressions. The expression levels of the rhoC gene were significantly higher in tumours than in non-malignant portions (P < 0.001). Metastatic lesions overexpressed the rhoC gene compared with primary tumours (P < 0.05). Carcinoma tissues with perineural invasion and lymph node metastasis exhibited significantly higher expressions of the rhoC gene than tumours without these manifestations (P < 0.001 and P < 0.05 respectively). Overexpression of the rhoC gene significantly correlated with poorer prognosis of patients with pancreatic adenocarcinoma (P < 0.05). In contrast, the expression levels of the rhoA and B genes showed no significant relationship with clinicopathological findings. Mutation was not found either in the rhoA, B or C gene sequences examined. K-ras gene mutation, detected in 27 out of 33 (81.8%) cases, did not affect the expression levels in any of the rho genes. These suggest that elevated expression of the rhoC gene may be involved in the progression of pancreatic carcinoma independent of K-ras gene activation.

Adult↗
PubMed1998

An immunohistochemical study of bcl-2 and p53 protein expression in pancreatic carcinomas.

BACKGROUND: Only a few articles have examined the relationship between bcl-2 expression and clinical findings or bcl-2 expression and p53 expression in pancreatic carcinomas. METHODS: We investigated bcl-2 protein and p53 protein expression by means of immunohistochemical methods. RESULTS: The immunostaining for bcl-2 was positive in 16 (20%) of 81 cases of pancreatic carcinoma. There were no significant correlations between bcl-2 expression and the age, gender, region of sampling, or clinical stage of the patients. Bcl-2 protein was detected more frequently in histologically high-grade pancreatic carcinomas (grade III, 31%; grade II, 14%; grade I, 0%); however, there was no significant difference in prognosis between patients with and without bcl-2 protein expression. Immunostaining for the p53 protein was positive in 45 (56%) of 81 cases of pancreatic carcinoma. There was no significant correlation between bcl-2 protein expression and p53 protein expression. CONCLUSION: Bcl-2 was often detected in histologically high-grade pancreatic carcinomas, although there was no significant correlation between bcl-2 expression and the prognosis.

Adenocarcinoma↗
PubMed1998

BE-31405, a new antifungal antibiotic produced by Penicillium minioluteum. I. Description of producing organism, fermentation, isolation, physico-chemical and biological properties.

A new antifungal antibiotic, BE-31405, was isolated from the culture broth of a fungal strain, Penicillium minioluteum F31405. BE-31405 was isolated by adsorption on high porous polymer resin (Diaion HP-20), followed by solvent extraction, precipitation and crystallization. BE-31405 showed potent growth inhibitory activity against pathogenic fungal strains such as Candida albicans, Candida glabrata and Cryptococcus neoformans, but did not show cytotoxic activity against mammalian cells such as P388 mouse leukemia. The mechanism studies indicated that BE-31405 inhibited the protein synthesis of C. albicans but not of mammalian cells.

Animals↗
PubMed1998

Quantitative analysis of carcinoembryonic antigen messenger RNA in peripheral venous blood and portal blood of patients with pancreatic ductal adenocarcinoma.

One major therapeutic failure of pancreatic adenocarcinoma treatment is metastasis to the liver. To screen patients with high risk for such hematogenous dissemination, we previously developed a very sensitive system to detect carcinoembryonic antigen (CEA) in blood. For a more practical application, we improved this system by making it quantitative and capable of analyzing both preoperative peripheral blood and intraoperative portal blood for the presence of CEA mRNA. CEA mRNA was not detected in the peripheral venous blood of any of the three patients examined, but it was identified in the portal blood without fail. In addition, the quantities of CEA mRNA identified in the portal blood before and after pancreatectomy were different. This study suggests that analysis of the portal blood seems to be important for the precise evaluation of hematogenous dissemination and of the pathophysiology of pancreatic ductal adenocarcinoma.

Adenocarcinoma↗
PubMed1997

Mouse homolog of poliovirus receptor-related gene 2 product, mPRR2, mediates homophilic cell aggregation.

Poliovirus receptor (PVR) is a cell surface glycoprotein that belongs to the immunoglobulin superfamily. Although MPH was initially reported as the mouse homolog of human PVR, recent data strongly suggest that MPH is the mouse homolog of human PRR2, a PVR-related gene 2 product, and not that of human PVR. Thus MPH is renamed mPRR2 in this study. Physiological functions of the PVR-related gene products have not been elucidated, although PVR has been well characterized as the poliovirus receptor. In this study, a possible function of mPRR2 (MPH), which is not a functional receptor for poliovirus, was investigated. Mouse L cells expressing mPRR2 were prepared. Those mouse cells showed a higher activity of cell aggregation than the parental mouse L cells. Enhancement of cell aggregation was also observed for insect Sf9 cells infected with recombinant baculovirus carrying mPRR2 cDNA. On the other hand, L cells expressing human PVR or monkey PVR (AGM alpha1 or AGM alpha2) did not show increased cell aggregation. The cell aggregation activity of L cells expressing mPRR2 was inhibited by the addition of anti-mPRR2 monoclonal antibodies or a soluble mPRR2 molecule produced by the baculovirus expression system. An immunofluorescence study revealed that mPRR2 protein was localized to the cell-cell contact sites between cells expressing mPRR2. A similar localization of mPRR2 was observed for intrinsic mPRR2 molecules of the mouse neuroblastoma cell line NS20Y. The contact site-specific localization of mPRR2 was not observed on the border between mPRR2-expressing and nonexpressing HeLa cells. Furthermore, mPRR2 proteins directly bound to each other in vitro. mPRR2 was detected on various types of cultured cells of mouse origin and in various mouse tissues. These results suggest that mPRR2 is an intercellular adhesion molecule with a homophilic binding manner.

Animals↗
PubMed1997

Depressive symptoms in acute schizophrenic inpatients.

Prospective and longitudinal assessment of depressive, positive, and negative symptoms were performed on 86 newly admitted schizophrenic patients. The improvement of depressive symptoms was significantly correlated with the improvement in positive symptoms, but did not correlate with the improvement in negative symptoms. However, depressive symptoms were heterogeneous. Principal components analysis was used to subdivide depressive symptoms into five factors. The improvement of the depression-anxiety factor was significantly associated with improvement of positive symptoms. On the other hand, improvement of negative symptoms was significantly related to that of the reduced activity factor. The change in hypochondriasis had a significant positive correlation with the change in positive symptoms and had a significant negative correlation with the change in negative symptoms. Changes in the other factors of depressive symptoms did not appear to be associated with changes in positive or negative symptoms. The present findings suggest that the various depressive symptoms associated with acute schizophrenia may have different pathophysiological origins.

Adult↗
PubMed1997

Selective inhibition of vascular cell adhesion molecule-1 expression by verapamil in human vascular endothelial cells.

Up-regulated expression of adhesion molecules on vascular endothelial cells (ECs) is an initial event in leukocyte adhesion to ECs, which is a crucial step in the process of inflammatory or immune reaction leading to organ transplant rejection. Verapamil and other calcium channel blockers have been reported to improve transplantation outcome and seem to possess immunosuppressive functions. Therefore, we tested the effect of verapamil on adhesion molecule expression of ECs and adherence of leukocytes to ECs. Verapamil was added to replicate human umbilical vein EC cultures, before adding cytokines. Protein and mRNA expression of E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 were measured by cell-ELISA and by Northern blot analysis after stimulation of ECs. Adherence of leukocytes to ECs was analyzed after stimulation of ECs by tumor necrosis factor-alpha, with pretreatment of verapamil. Verapamil selectively inhibited cytokine-induced protein and mRNA levels of VCAM-1, and suppressed cell adherence between tumor necrosis factor-alpha-stimulated ECs and mononuclear leukocytes or Molt-4 cells. These results suggest that verapamil may suppress immune response partly via inhibition of VCAM-1 expression on ECs and a certain subset of lymphocytes adherent to ECs.

Calcium Channel Blockers↗
PubMed1997

Immunohistochemical expression of nm23 gene product, nucleotide diphosphate kinase, in pancreatic neoplasms.

CONCLUSION: Our findings suggest that contrary to the proposed role for the nm23 protein as a tumor metastasis suppressor, in pancreatic tumors, the nm23 protein does not play an important role as a suppressor against tumor metastasis. BACKGROUND: The nm23 gene product, nucleotide diphosphate kinase, is believed to suppress tumor metastasis. Although a number of studies on many kinds of tumors have examined the relationship between nm23 expression and metastatic potential, the antimetastatic activity of nm23 remains controversial. The expression of the nm23 protein has not been examined in pancreatic tumors, except for a few reports on pancreatic duct cell carcinomas. METHODS: We have investigated nm23 expression in pancreatic duct cell carcinomas, islet cell tumors, and ampullary carcinomas by immunohistochemical methods. RESULTS: In 73 cases of pancreatic duct cell carcinomas, the nm23 expression was increased when compared with the adjacent normal pancreatic ducts; diffuse immunostaining was detected in 21 (29%) cases, focally positive immunostaining in 47 (64%) cases, and negative immunostaining in 5 cases (7%). All five negative samples were obtained from distant metastatic regions. However, there was no significant difference in the nm23 expression between primary tumors and regional lymph node metastases. Furthermore, there was no significant correlation between nm23 expression and the prognosis of the 55 resected cases. In the 15 cases of ampullary carcinomas, all 15 tumors were positive for nm23 protein (6 diffuse and 9 focal), and the staining intensity was stronger than in normal pancreatic ducts. There was no significant difference in the nm23 expression in the primary regions between patients with and without lymph node metastasis (2 diffuse and 5 focal out of 7 patients with lymph node metastasis, and 4 diffuse and 4 focal out of 8 patients without lymph node metastasis). All 12 islet cell tumors showed strong and diffuse staining for the nm23 protein.

Adenoma, Islet Cell↗
PubMed1997

Cytokeratin 19 fragment in serum and tissues of patients with pancreatic diseases.

CONCLUSION: The present study has shown that increased serum levels of cytokeratin 19 fragment reflect increases in the size of the pancreatic carcinomas, although the sensitivity for detecting small pancreatic carcinomas was low. BACKGROUND: Cytokeratin is a member of the intermediate family of filaments in epithelial cells. The cytokeratin 19 fragment is an acidic cytokeratin, which is found in various epithelial tissues. Recently, the serum fragment of cytokeratin 19 has been measured and found to be a good marker for squamous cell carcinoma. Cytokeratin 19 is known to be expressed in normal pancreatic tissues and pancreatic carcinomas. However, serum cytokeratin 19 levels in pancreatic diseases have not been precisely detailed. METHODS: In this study, we evaluated serum cytokeratin 19 levels and the immunohistochemical expression of cytokeratin 19 in various pancreatic diseases. RESULTS: Serum cytokeratin 19 levels were high (> 2 ng/mL) in 51 of 99 (52%) cases of pancreatic duct cell carcinoma, but were low in all 24 cases of chronic pancreatitis and in 7 cases of islet cell tumors. The sensitivity of the cytokeratin 19 assay increased with increased size of the pancreatic carcinomas, but was not influenced by the presence of obstructive jaundice. Immunohistochemical studies using a monoclonal anticytokeratin 19 antibody showed that staining for cytokeratin was positive in all 38 of the pancreatic carcinomas examined and in 2 of 6 islet tumors.

Biomarkers, Tumor↗
PubMed1997

Clinical significance of serum p53 antigen in patients with pancreatic carcinomas.

BACKGROUND: Alterations in the p53 gene are often found in pancreatic cancer, and accumulation of the p53 protein has been noted in tumour cells. AIMS: To investigate whether serum p53 protein concentrations could be used as markers for p53 gene mutations in neoplasms of the pancreas. METHODS: Serum p53 protein concentrations were determined by an enzyme linked immunosorbent assay (ELISA) in 104 cases of pancreatic adenocarcinoma, and 61 matched formalin fixed tissue sections were also stained by an anti-p53 DO-7 monoclonal antibody. RESULTS: The mean serum concentration of p53 protein in the adenocarcinoma patients was 0.27 (SEM 0.02) ng/ml, and was significantly higher than in 35 healthy blood donors (0.15 (0.02) ng/ml, SD = 0.11) or in 15 cases of chronic pancreatitis (0.15 (0.02) ng/ml). Adopting an arbitrary cut off value for the serum p53 protein concentration of 0.37 ng/ml, which corresponded to a value 2 SD above the mean value from the healthy blood donors, positive serum p53 protein concentrations were found in 23 out of 104 (22.1%) patients with adenocarcinomas examined, 16 out of 47 (34.0%) patients with carcinomas with distant metastases, but only seven of 57 patients (12.3%) with carcinomas without metastases (p < 0.05). In 11 patients with pancreatic adenocarcinomas, the mean serum p53 protein concentration after tumour resection was 0.21 (0.05) ng/ml, and had decreased compared with the preoperative concentrations (0.25 (0.05) ng/ml) (P < 0.05). There were no significant associations between the serum concentrations of p53 protein and serum concentrations of markers such as CA19-9 or CEA; however, serum concentrations of p53 protein demonstrated a potential role as an additional tumour marker. Immunohistochemical studies disclosed that the p53 protein was expressed in 28 out of 61 pancreatic adenocarcinomas (45.9%). Serum p53 protein concentrations in the positively immunostained cases were significantly higher than in the negatively immunostained cases (0.35 (0.05) ng/ml v 0.15 (0.01) ng/ml; p < 0.005). Furthermore, positive immunostaining for p53 protein was found in eight out of 10 (80%) serum positive p53 protein cases with adenocarcinomas. CONCLUSION: An increase in serum p53 protein concentrations appears during the progression of pancreatic adenocarcinoma and correlates with the accumulation of p53 protein as a result of a mutation of the p53 gene. An analysis of p53 antigen concentrations can detect p53 gene alterations, which could be useful for the selection of treatment regimens.

Adenocarcinoma↗
PubMed1997

Excitatory and inhibitory inputs from saccular afferents to single vestibular neurons in the cat.

Connections from saccular afferents to vestibular neurons were studied by means of intracellular recordings of excitatory (E) and inhibitory (I) postsynaptic potentials (PSPs) in vestibular neurons after focal stimulation of the saccular macula in decerebrated cats. Focal stimulation was given to the saccular macula in two ways, in which the polarity of stimulus current via a pair of electrodes was changed. In group A, one of the electrodes was inserted into the ventral and the other into the dorsal edge of the saccular macula. The focal stimulation was across the striola so that the reversal of morphological polarization in hair cells was bridged by the pulse stimulus. In 22/36 vestibular neurons tested, the stimulation of the saccular macula evoked monosynaptic (</=1.2 ms) EPSPs, including EPSP-IPSP sequences, with one polarity of stimulation, and disynaptic (>/=1.5 ms) IPSPs when the polarity of the stimulus current was changed. In 14/36 neurons, the response pattern was the same regardless of the stimulus polarity; EPSPs (12/36) or IPSPs (2/36). In group B, a pair of electrodes was inserted into the dorsal edge of the saccular macula, so that the striola was not bridged by the current stimulus. In all of the vestibular neurons tested, the response pattern was always the same regardless of the polarity: mono- (22/31) and disynaptic (3/31) EPSPs or disynaptic IPSPs (6/31). In addition, the saccular nerve was stimulated after removing the macula in some cats (group C). The stimulation of the saccular nerve evoked EPSPs in 62 vestibular neurons (including EPSP-IPSP sequences in 31 neurons) and IPSPs in 19 vestibular neurons. Convergence between the saccular nerve and other vestibular nerves was studied by the intracellular recording of PSPs. Fifty-six percent (18/32) of the saccular-activated neurons had excitatory and/or inhibitory potentials evoked after stimulation of the utricular nerve and the horizontal and anterior semicircular canal nerves, and 44% (19/43) of the neurons received inputs from the posterior semicircular canal nerve. The results support the hypothesis that saccular afferents from one population of hair cells activate vestibular neurons monosynaptically and that afferents from another population of hair cells located on the opposite side of the striola appear to project to the same vestibular neurons disynaptically via inhibitory interneurons. Neural circuits from saccular afferents to vestibular neurons, which we term cross-striolar inhibition, thus may provide a mechanism for increasing the sensitivity to vertical linear acceleration. The circuit described is provided not only with high sensitivity but also with input noise-resistant characteristics.

Afferent Pathways↗
PubMed1997

Interhemispheric chronic subdural hematoma--case report.

A 74-year-old male presented with right hemiparesis greater in the lower than the upper extremity. He had no apparent head trauma. He had been treated with anticoagulants for cerebral and myocardiac infarction. Computed tomography (CT) and magnetic resonance imaging demonstrated an unusual combination of subdural hematomas in the interhemispheric space on the left, and the left temporoparietal and right frontotemporooccipital regions. The left convexity hematoma was irrigated through a single burr hole. Postoperatively, the size of the left convexity hematoma was diminished and the left interhemispheric subdural hematoma disappeared. However, his consciousness deteriorated, and a second irrigation of the recurrent left convexity hematoma was performed 7 days after the first surgery. CT obtained 3 days after the second operation showed a right interhemispheric subdural hematoma, which diminished spontaneously. The convexity hematoma on the left reaccumulated, and was treated by shunting. His neurological status did not improve, and he died from myocardial infarction 39 days later. Irrigation of convexity hematoma may be effective to treat an associated ipsilateral interhemispheric subdural hematoma.

Aged↗
PubMed1997

Utricular input to cat extraocular motoneurons.

Intracellular recordings from 200 identified extraocular motoneurons in the bilateral III, IV and VI cranial nuclei were studied to determine the connectivities between the utricular nerve and the extraocular motoneurons in cats. Stimulating electrodes were placed within the left utricular nerve, while other branches of the vestibular nerve were removed. Monosynaptic and disynaptic connections between the utricular nerve and the ipsilateral abducens motoneurons and interneurons were recorded as described previously. Stimulation of the utricular nerve evoked longer latency depolarizing and hyperpolarizing potentials in contra- and ipsilateral medial rectus motoneurons, respectively. Depolarizing and hyperpolarizing potentials with longer latencies were also recorded in the ipsilateral inferior oblique and contralateral trochlear motoneurons. The short and longer latency circuits between the utricular nerve and extraocular motoneurons may play a role in stabilizing the retinal image during head tilt and horizontal linear acceleration.

Abducens Nerve↗
PubMed1996

Evaluation of cholecystokinin, gastrin, CCK-A receptor, and CCK-B/gastrin receptor gene expressions in gastric cancer.

The brain-gut hormones, cholecystokinin (CCK) and gastrin, regulate the growth of gastrointestinal mucosa and tumor cells. In this study, reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate messenger RNA expression for CCK, gastrin, CCK-A receptor, and CCK-B/gastrin receptor in surgical specimens of gastric cancers and in normal antrum and body mucosa of the stomach. The CCK mRNA expression was detectable in 4/14 (29%) samples of gastric cancer and in 3/12 (25%) samples of antral mucosa. However, the gastrin mRNA expression was not detectable in any gastric cancer samples, although it was detectable in all the samples of antral mucosa. The CCK-A receptor mRNA expression was detectable in 5/14 (36%) samples of gastric cancer and in 7/12 (58%) body mucosa. Three cases out of 14 (21%) of gastric cancer expressed both CCK gene and CCK-A receptor gene. The CCK-B receptor mRNA expression was detectable in only 1/14 (7%) samples of gastric cancer, although it was detectable in 10/12 (83%) body mucosa of the stomach. These findings may suggest a greater role for CCK and CCK-A receptor than for gastrin and CCK-B receptor in gastric cancers.

Cholecystokinin↗
PubMed1996

Immunohistochemical study of metallothionein in pancreatic carcinomas.

Metallothioneins are a family of intracellular metalloproteins that have been thought to be involved in anticancer drug resistance. However, the role of metallothioneins in pancreatic cancer has not been investigated in detail. The immunohistochemical localization of metallothionein was examined in normal human adult pancreas tissue and in 75 pancreatic duct cell carcinomas, using monoclonal anti-metallothionein antibody. Furthermore, in vitro studies on the sensitivity of pancreatic cancer to cisplatin were performed in 10 cases of pancreatic carcinoma. Metallothionein staining was weakly positive in the acinar and islet cells and intralobular ducts but was negative in the large pancreatic ducts. In pancreatic carcinomas, metallothionein staining was diffusely positive in 6 (8%), focally positive in 25 (33%) and negative in 44 (59%) of the 75 pancreatic carcinomas. The expression of metallothioneins in pancreatic tumors was related to metastasis, poor prognosis and poor histological grading (poorer glandular differentiation and nuclear anaplasia). The in vitro study of tumor sensitivity to cisplatin showed no significant correlation between metallothionein expression and resistance to cisplatin. Metallothionein-positive pancreatic carcinoma will be potentially highly malignant or acquire an enhanced ability to produce metallothioneins as the malignant potential increases. The expression of metallothionein could be a prognostic indicator in pancreatic carcinomas.

Adult↗
PubMed1996

Exocrine pancreatic function in the early period after pancreatoduodenectomy and effects of preoperative pancreatic duct obstruction.

Exocrine pancreatic function in the early period after pancreatoduodenectomy was investigated. The effects of preoperative pancreatic duct obstruction on exocrine pancreatic function were also investigated. The volume of pancreatic juice and its amylase activity were investigated in 39 patients who underwent pancreatoduodenectomy (including pylorus-preserving pancreatoduodenectomy). The N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) test was performed on 23 of 39 patients about 40 days after pancreatoduodenectomy. The exocrine pancreatic function was inhibited three to eight days after pancreatoduodenectomy (amylase activity: 23,700 +/- 4300 IU/day), and recovered on days 9-15 (48,000 +/- 8400 IU/day) in patients with a normal main pancreatic duct. In patients with pancreatic duct obstruction, the exocrine pancreatic function was almost eliminated (amylase activity: 440 +/- 260 IU/day) and BT-PABA test results were low (45 +/- 17%). In patients with narrowed pancreatic duct, amylase secretion was significantly inhibited even in patients with a normal number of acinar cells. There was a good positive correlation (Spearman's rank correlation coefficient, rs = 0.715, P < 0.01) between amylase secretion and BT-PABA test. Amylase secretion more than 10,000 IU/day is essential for a normal BT-PABA test and normal digestive function. The inhibited digestive function in patients with pancreatic duct obstruction may be due to the decreased number of acinar cells and the inhibition of exocrine pancreatic function.

4-Aminobenzoic Acid↗
PubMed1996

Immunohistochemical localization of P-glycoprotein and expression of the multidrug resistance-1 gene in human pancreatic cancer: relevance to indicator of better prognosis.

We investigated immunohistochemical localization of P-glycoprotein (P-gp) on paraffin-embedded sections from 103 cases of previously untreated pancreatic tumors and also analyzed multidrug resistance-1 (MDR1) gene expression by polymerase chain reaction after reverse transcription in 35 cases. High positive staining for P-gp was observed in 72.8% of pancreatic tumors and in 73.2% of ductal adenocarcinoma. In ductal adenocarcinoma, immunoreactivity of P-gp was inversely correlated with biological aggressiveness of tumors determined by histologic grading (P<0.01), tumor size (P < 0.01), retroperitoneal invasion (P < 0.01) and portal invasion (P < 0.05). Expression of the MDR1 gene was detected in all the pancreatic tumors examined and was significantly higher than that in normal pancreas (P < 0.05). The levels of MDR1 mRNA showed a moderate correlation with those of P-gp (r=0.62, P<0.0001). Higher expression levels of MDR1/P-gp significantly correlated with better prognosis of patients with ductal carcinoma (P < 0.05). Among patients with ductal carcinoma, the high staining group for P-gp revealed a 3.5-fold better prognosis compared with the low staining group (HR=3.47, 95% CI=1.62, 7.45; P=0.0016). In conclusion, MDR1 gene/P-gp expression in pancreatic cancer without chemotherapy inversely correlates with biological aggressiveness and is an independent indicator of favorable prognosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗