Biomedical subjects

Y Matsuzaki

Publications and source records attributed to Y Matsuzaki.

At least 19 recordsLinked to original sources

PubMed2001

Side chain hydroxylations in bile acid biosynthesis catalyzed by CYP3A are markedly up-regulated in Cyp27-/- mice but not in cerebrotendinous xanthomatosis.

The accumulation of various 25-hydroxylated C(27)-bile alcohols in blood and their excretion in urine are characteristic features of cerebrotendinous xanthomatosis (CTX) a recessively inherited inborn error of bile acid synthesis caused by mutations in the mitochondrial sterol 27-hydroxylase (CYP27) gene. These bile alcohols may be intermediates in the alternative cholic acid side chain cleavage pathway. The present study was undertaken to identify enzymes and reactions responsible for the formation of these bile alcohols and to explain why Cyp27(-/-) mice do not show CTX-related abnormalities. Microsomal activities of 5beta-cholestane-3alpha,7alpha,12alpha-triol 25- and 26-hydroxylases, 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol 23R-, 24S-, and 27-hydroxylases and testosterone 6beta-hydroxylase, a marker enzyme for CYP3A, in Cyp27(-/-) mice livers were markedly up-regulated (5.5-, 3.5-, 6.5-, 7.5-, 2.9-, and 5.4-fold, respectively). In contrast, these enzyme activities were not increased in CTX. The activities of 5beta-cholestane-3alpha,7alpha,12alpha-triol 25- and 26-hydroxylases and 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol 23R-, 24R-, 24S-, and 27-hydroxylases were strongly correlated with the activities of testosterone 6beta-hydroxylase in control human liver microsomes from eight unrelated donors. Troleandomycin, a specific inhibitor of CYP3A, markedly suppressed these microsomal side chain hydroxylations in both mouse and human livers in a dose-dependent manner. In addition, experiments using recombinant overexpressed human CYP3A4 confirmed that these microsomal side chain hydroxylations were catalyzed by a single enzyme, CYP3A4. The results demonstrate that microsomal 25- and 26-hydroxylations of 5beta-cholestane-3alpha,7alpha,12alpha-triol and microsomal 23R-, 24R-, 24S-, and 27-hydroxylations of 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol are mainly catalyzed by CYP3A in both mice and humans. Unlike Cyp27(-/-) mice, CYP3A activity was not up-regulated despite marked accumulation of 5beta-cholestane-3alpha,7alpha,12alpha-triol in CTX.

Animals↗

PubMed2001

Role of individual oligosaccharide chains in antigenic properties, intracellular transport, and biological activities of influenza C virus hemagglutinin-esterase protein.

The hemagglutinin-esterase (HE) glycoprotein of influenza C virus is composed of three domains: a stem domain active in membrane fusion (F), an acetylesterase domain (E), and a receptor-binding domain (R). The protein contains eight N-linked glycosylation sites, four (positions 26, 395, 552, and 603) in the F domain, three (positions 61, 131, and 144) in the E domain, and one (position 189) in the R domain. Here, we investigated the role of the individual oligosaccharide chains in antigenic properties, intracellular transport, and biological activities of the HE protein by eliminating each of the glycosylation sites by site-specific mutagenesis. Comparison of electrophoretic mobility between the wild-type and the mutant proteins showed that while seven of the glycosylation sites are used, one (position 131) is not. Analysis of reactivity of the mutants with anti-HE monoclonal antibodies demonstrated that glycosylation at position 144 is essential for the formation of conformation-dependent epitopes. It was also evident that glycosylation at the two sites in the F domain (positions 26 and 603), in addition to that in the E domain (position 144), is required for the HE molecule to be transported from the endoplasmic reticulum and that mutant HEs lacking one of these three sites failed to undergo the trimer assembly. Removal of an oligosaccharide chain at position 144 or 189 resulted in a decrease in the esterase activity. By contrast, two mutants lacking an oligosaccharide chain at position 26 or 603, which were defective not only in cell surface expression but in trimerization, possessed full-enzyme activity, suggesting that the HE monomers present within the cell have acetylesterase activity. Fusion activity of cells expressing each of mutant HEs was found to be comparable with the ability of the protein to be transported to the cell surface, suggesting that there is no specific oligosaccharide chain that plays a critical role in promoting membrane fusion.

Acetylesterase↗

PubMed2001

Expression of nm23-H1 gene product in esophageal squamous cell carcinoma and its association with vessel invasion and survival.

BACKGROUND: We assessed the nm23-H1 gene product expression and its relationship with lymphatic and blood vessel invasion in patients with esophageal squamous cell carcinoma. METHODS: Formalin-fixed and paraffin-embedded tissue sections from 45 patients who were treated surgically were used in this study. Pathologists graded lymphatic and blood vessel invasion in each of the tissue samples. Expression of nm23-Hl gene product was determined using a specific monoclonal antibody. RESULTS: Expression of nm23-H1 gene product was present in 17 (37.8%) cases. We found an inverse correlation between nm23-H1 gene product expression and lymphatic vessel invasion, whereas no correlation between nm23-H1 gene product expression and blood vessel invasion. Overall survival rate was not different between nm23-H1 gene product positive and negative patients (p = 0.21). However, reduced expression of nm23-H1 gene product was associated with shorter overall survival in patients with involved lymph nodes (p < 0.05), but not in patients without involved lymph nodes (p = 0.87). CONCLUSIONS: In patients with esophageal squamous cell carcinoma, there appears to be an inverse relationship between nm23-H1 gene product expression and lymphatic vessel invasion. Furthermore, nm23-H1 gene product expression might be a prognostic marker in patients with involved lymph nodes. Our data does not demonstrate any correlation between nm23-H1 gene product expression and blood vessel invasion.

Biomarkers, Tumor↗

PubMed2001

WFS1 (Wolfram syndrome 1) gene product: predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain.

Wolfram (DIDMOAD) syndrome is an autosomal recessive neurodegenerative disorder accompanied by insulin-dependent diabetes mellitus and progressive optic atrophy. Recent positional cloning led to identification of the WFS1 (Wolfram syndrome 1) gene, a member of a novel gene family of unknown function. In this study, we generated a specific antibody against the C-terminus of the WFS1 protein and investigated its subcellular localization in cultured cells. We also studied its distribution in the rat brain. Biochemical studies indicated the WFS1 protein to be an integral, endoglycosidase H-sensitive membrane glycoprotein that localizes primarily in the endoplasmic reticulum (ER). Consistent with this, immunofluorescence cell staining of overexpressed WFS1 showed a characteristic reticular pattern over the cytoplasm and overlapped with the ER marker staining. No co-localization of WFS1 with mitochondria argues against an earlier clinical hypothesis that Wolfram syndrome is a mitochondria-mediated disorder. In the rat brain, at both the protein and mRNA level, WFS1 was found to be present predominantly in selected neurons in the hippocampus CA1, amygdaloid areas, olfactory tubercle and superficial layer of the allocortex. These expression sites, i.e. components of the limbic system or structures closely associated with this system, may be involved in the psychiatric, behavioral and emotional abnormalities characteristic of this syndrome. ER localization of WFS1 suggests that this protein plays an as yet undefined role in membrane trafficking, protein processing and/or regulation of ER calcium homeostasis. These studies represent a first step toward the characterization of WFS1 protein, which presumably functions to maintain certain populations of neuronal and endocrine cells.

Animals↗

PubMed2001

Effect of bile acids on the uptake of irinotecan and its active metabolite, SN-38, by intestinal cells.

The intestinal transport of irinotecan (CPT-11) and its active metabolite, SN-38, has been previously reported (K. Kobayashi et al., Int. J. Cancer, 83 (1999) 491-496). In the present study, the effect of the two major primary bile acids, cholic acid (CA) and taurocholic acid (TCA), on the uptake of CPT-11 and SN-38 by hamster intestinal epithelial cells was investigated. These two bile acids at concentrations up to 200 microM did not directly alter the cellular uptake of CPT-11 and SN-38. However, under physiologically acidic intestinal pH conditions, micelle formation induced by 20 mM TCA significantly reduced the cellular uptake of CPT-11 and SN-38 by 60% and 80%, respectively.

Animals↗

PubMed2001

Expression of nm23-H1 gene product in mediastinal lymph nodes from lung cancer patients.

OBJECTIVE: Although numerous studies have shown that nm23-H1 gene product expression is inversely related to metastatic potential in some cancers, the expression in lymph nodes has not been studied in detail. An analysis of nm23-H1 gene product expression in mediastinal lymph nodes from lung cancer patients is reported. METHODS: One hundred and thirty-four, randomly selected lymph nodes (63 with positive pathological lymph node status) from 39 surgically treated lung cancer patients were examined. Expression of nm23-H1 gene product was determined using specific monoclonal antibodies. Metastatic cancer cells were highlighted using anti-cytokeratin antibody. RESULTS: Expression of nm23-H1 gene product in patients with less and more than 50% nodes-positive was 12/23 (52.2%) and 15/16 (93.8%) cases, respectively. Immunohistochemical studies with cytokeratin revealed micrometastasis in 6/39 (15.4%) patients and 9/71 (12.7%) nodes previously reported as cancer negative. Expression of nm23-H1 gene product in micrometastasis and metastasis-positive nodes was 5/9 (55.6%) and 55/63 (87.3%), respectively. We also found nm23-H1 gene product expression in germinal center cells. However, we found no relationship between expression of nm23-H1 gene product in germinal center cells and extent of metastasis. CONCLUSIONS: Our study demonstrates a positive relationship between expression of nm23-H1 gene product and extent of metastasis in mediastinal lymph nodes from lung cancer patients. Our data for normal germinal center cells suggests that nm23-H1 gene product expression does not play a specific biological role in suppressing tumor metastasis in lung cancer.

Adenocarcinoma↗

PubMed2001

Association of mast cells with tumor angiogenesis in esophageal squamous cell carcinoma.

The association of mast cells with tumor angiogenesis was investigated in patients with esophageal squamous cell carcinoma. Surgical specimens from 48 patients with esophageal squamous cell carcinoma were studied. Mast cells in tumor sections were stained with Alcian blue and safranin O. The number of mast cells was counted under light microscopy and the average count recorded. To highlight the microvessels, endothelial cells were stained with anti-human factor VIII antibody. Microvessel density was also counted. We found a significant correlation between mast cell count and microvessel density in patients with esophageal squamous cell carcinoma. Double staining of the microvessels revealed highly angiogenic areas densely populated with mast cells. There appears to be a direct correlation between the number of mast cells and tumor angiogenesis in patients with esophageal squamous cell carcinoma.

Adult↗

PubMed2001

Etiologic significance of defects in cholesterol, phospholipid, and bile acid metabolism in the liver of patients with intrahepatic calculi.

Intrahepatic calculi, highly prevalent in the Far East, including Japan, are characterized clinically by chronic proliferative cholangitis with frequent stone recurrences. Intrahepatic calculi consist of 2 groups, i.e., brown pigment stones, including a high cholesterol content, and cholesterol stones, with the former predominating. To gain insights into the pathogenesis of intrahepatic calculi, cholesterol and bile acid biosynthesis, as well as alterations in intracellular transport and/or canalicular secretion of phospholipid and bile acid were investigated in liver of patients with intrahepatic calculi. Enzyme activities of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase were increased (12.8 +/- 1.9 pmol/min/mg protein, mean +/- SEM vs. 5.5 +/- 0.4 in controls; P < .01) and cholesterol 7 alpha-hydroxylase activities were decreased (1.3 +/- 0.4 vs. 4.9 +/- 0.6; P < .01) in liver specimens of patients with brown pigment stones. In addition, messenger RNA (mRNA) levels of multidrug resistance P-glycoprotein 3 (MDR3 Pgp) and phosphatidylcholine transfer protein (PCTP) were markedly low in the liver specimens compared with the levels in specimens of control subjects, gallbladder stone patients, and patients with obstructive cholestasis. The protein levels and the immunohistochemical staining were decreased for MDR3 Pgp and PCTP in the liver. Consistently, the concentrations of phospholipid were markedly reduced in the hepatic bile from both affected and unaffected hepatic segments. In patients with intrahepatic calculi, biliary cholesterol supersaturation and the formation of cholesterol-rich brown pigment as well as cholesterol stones may be attributed to decreased hepatic transport and biliary secretion of phospholipids, in the setting of increased cholesterogenesis and decreased bile acid synthesis.

Adult↗

PubMed2001

A case of esophageal sarcomatoid carcinoma with molecular evidence of a monoclonal origin.

A case of polypoid tumor of the esophagus consisting of a sarcomatous tumor partly covered with superficial squamous cell carcinoma is described. The sarcomatous component consisted of anaplastic spindle and pleomorphic tumor cells that mimicked malignant fibrous histiocytoma (MFH). Both the sarcomatous and carcinomatous components were positive for p53 immunohistochemically. Further molecular analysis revealed that the two components had the same somatic mutation in the p53 gene. These results suggest a monoclonal origin of this biphasic tumor.

Aged↗

PubMed2001

Ultrasonography of gastric volvulus: "peanut sign".

We report a case of chronic gastric volvulus in which ultrasonography (US) was useful. An 81-year-old woman was hospitalized due to vomiting, and upper gastroduodenoscopy revealed that the stomach was spirally twisted and constricted. An upper gastrointestinal barium study demonstrated an organoaxial-mesenteroaxial combined type gastric volvulus. US showed constriction between the dilated upper stomach body and the lower stomach body similar to a "peanut". Thereafter, the patient's vomiting stopped and follow-up US demonstrated that the constriction of the stomach was loosened. Therefore, we believe that this characteristic US sign paralleled the symptoms of the patient.

Aged↗

PubMed2001

Differences in hepatic levels of intermediates in bile acid biosynthesis between Cyp27(-/-) mice and CTX.

Cerebrotendinous xanthomatosis (CTX) is a rare, recessively inherited lipid storage disease characterized by a markedly reduced production of chenodeoxycholic acid and an increased formation of 25-hydroxylated bile alcohols and cholestanol. Patients with this disease are known to have mutations in the sterol 27-hydroxylase (Cyp27) gene. However, one study showed that mice with a disrupted Cyp27 gene did not have any CTX-related clinical or biochemical abnormalities. To explore the reason, hepatic cholesterol, cholestanol, and 12 intermediates in bile acid biosynthetic pathways were quantified in 10 Cyp27(-/-) and 7 Cyp27(+/+) mice, two CTX patients (untreated and treated with chenodeoxycholic acid), and four human control subjects by high resolution gas chromatography-mass spectrometry. Mitochondrial 27-hydroxycholesterol and 5beta-cholestane-3alpha,7alpha,12alpha,27-tetrol were virtually absent in both Cyp27(-/-) mice and CTX patients. In Cyp27(-/-) mice, microsomal concentrations of intermediates in the early bile acid biosynthetic pathway (7alpha-hydroxycholesterol, 7alpha-hydroxy-4-cholesten-3-one, 7alpha,12alpha-dihydroxy-4-cholesten-3-one, and 5beta-cholestane-3alpha,7alpha,12alpha-triol), 25-hydroxylated bile alcohols (5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol, 5beta-cholestane-3alpha,7alpha,12alpha,23R,25-pentol, and 5beta-cholestane-3alpha,7alpha,12alpha,24R, 25-pentol), and cholestanol were all significantly elevated compared with those in Cyp27(+/+) mice, although the levels were lower than those in untreated CTX patients. The intermediate levels in early bile acid biosynthesis were more elevated in male (16;-86% of CTX) than in female Cyp27(-/-) mice (7-30% of CTX). In contrast, 25-hydroxylated bile alcohol concentrations were not significantly different between male and female Cyp27(-/-) mice and were considerably lower (less than 14%) than those in CTX patients.These results suggest that 1) in Cyp27(-/-) mice, especially in females, classic bile acid biosynthesis via 7alpha-hydroxycholesterol is not stimulated as much as in CTX patients; and 2) formed 25-hydroxylated bile alcohols are more efficiently metabolized in Cyp27(-/-) mice than in CTX patients.

Adult↗

PubMed2001

[Anti-bleeding effect of nafamostat mesilate for the surgery of thoracic ascending aorta].

UNLABELLED: During extracorporeal cardiopulmonary bypass (ECB), the activated coagulation and fibrinogenolysis system causes bleeding and postoperative multiple organ failures. We studied the effect of an anti-bleeding agent, nafamostat mesilate (NM) during the surgery of thoracic ascending aorta to decrease a side effect of bleeding. From March 1980 to January 1998, for thoracic ascending aorta operations in our department (true aneurysm, 16-, psudoaneurysm, 2-, and dissection, 11 cases, in 29 cases, respectively), age from 16 to 79 (mean 62.9 +/- 9.5 year of age), we classified the objects in two groups, NM group (intraoperative infusion with NM of 60 mg/hr and with heparin 300 IU/kg) and C group (only with heparin treated, 500 IU/kg). We investigated the preoperative factors (age and aneurysmal diameter), the intraoperative factors (ACT, hematcrit, platelet, aorta clamping time, operative time, ECB time, bleeding volume, and blood transfusion), and the postoperative factors (bleeding and blood transfusion) after the administration of NM. RESULTS: There was no significance for the protection effect of NM infusion on the preoperative and the postoperative factors. However, intraoperative bleeding and blood transfusion volume in NM group were significantly lesser than those in group C. CONCLUSIONS: It might be useful for NM infusion during the surgery of thoracic ascending aorta due to the decrease of volume of intraoperative bleeding and blood transfusion amount with the remarkable anti-bleeding effect.

Adolescent↗

PubMed2000

Aquaporin 4: lack of mRNA expression in the rat regenerating muscle fiber under denervation.

The recently identified water channel aquaporin 4 is a major component of the orthogonal arrays observed with freeze-fracture electron microscopy. We examined the expression of aquaporin 4 mRNA and protein in rat regenerating muscle under innervated and denervated conditions. We found decreased sarcolemmal immunostaining of aquaporin 4 in denervated regenerating muscle as opposed to innervated muscle. Quantitative reverse transcription-polymerase chain reaction revealed that aquaporin 4 mRNA was expressed in the innervated regenerating muscle; whereas it was not expressed in denervated muscle. Thus, lack of aquaporin 4 protein may be due to lack of aquaporin 4 mRNA in the denervated regenerating muscle. We conclude that the nerve supply influences expression of aquaporin 4 at the mRNA level in regenerating muscle.

Animals↗

PubMed2000

Surgical management of ductus arteriosus aneurysm in adults.

Aneurysm of the ductus arteriosus is rare, especially in adults, and preoperative diagnosis is very difficult, requiring intraoperative diagnosis. A 71-year-old man was preoperatively diagnosed with ductus arteriosus aneurysm by computed tomographic scanning, magnetic resonance imaging, and aortography, which demonstrated a saccular aneurysm of the distal aortic arch. Under partial extracorporeal circulation, the aneurysm was replaced by an artificial vascular graft. The location and morphology of the aneurysm confirmed the preoperative diagnosis. The postoperative course was uneventful. Surgery for this condition is safe and is recommended the same as for common thoracic aortic aneurysm.

Aged↗

PubMed2000

A rapidly growing benign intrathoracic neurofibroma after lung lobectomy.

A 67-year-old male underwent a right upper lung lobectomy for lung cancer in January 1993. Follow-up chest X-rays revealed a progressive and rapidly growing intrathoracic mass in the right thorax. The mass, however, did not resemble a tumor recurrence, and the patient complained only of shortness of breath. Computerized tomography and magnetic resonance imaging confirmed the presence of the intrathoracic mass and its associated compression of the residual lung. A right thoracotomy was performed in January 1998, and a mass found arising from the sympathetic nerve trunk was resected. Microscopic examination revealed stellate or spindle-shaped cells in myxoid stroma with sparsely distributed collagen fibers. Immunohistochemically, the cells were positive for neuron-specific enolase, and the tumor was identified as neurofibroma. The patient did not suffer from von Recklinghausen's disease, and there was no family history of the disease. After resection of the neurofibroma, the compressed lung was able to re-expand, and the patient's shortness of breath disappeared. At one year postoperative, the patient remains well, and there is no evidence of recurrence.

Aged↗

PubMed2000

Successful treatment of a bronchial inflammatory pseudotumor by bronchoplasty in an 8-year-old boy: report of a case.

We report herein the rare case of an 8-year-old boy in whom an inflammatory pseudotumor of the upper lobe bronchus of the right lung was successfully treated by bronchoplasty. A bronchoscopy was initially performed to investigate the cause of pulmonary atelectasis in the right upper lobe, which revealed a tumor in the right main bronchus. Thus, a thoracotomy followed by bronchotomy of the right main bronchus was carried out. The tumor was seen to have polypoid protrusion into the right main bronchus at the orifice of the upper lobe. A bronchoplasty with a wedge resection of the right main bronchus and right upper lobectomy was carried out, effectively preserving right pulmonary function. Histological examination confirmed the diagnosis of an inflammatory pseudotumor. The patient had an uneventful postoperative course and has been free of recurrence for 3 years since his operation.

Biopsy, Needle↗

PubMed2000

Effect of mast cells on tumor angiogenesis in lung cancer.

BACKGROUND: We conducted a retrospective study to clarify the effect of mast cells on tumor angiogenesis in lung cancer patients. METHODS: Formalin-fixed and paraffin-embedded tumor sections were used in this study. Parenchymal mast cells were stained with Alcian blue and safranin O. The number of mast cells per ten fields at a magnification of 200x was counted under light microscopy, and the average count was determined. To highlight the microvessels, endothelial cells were stained with anti-human factor VIII antibody. After the microvessel count was determined, the microvessels were further stained with Alcian blue and safranin O to show areas of mast cell infiltration. Expression of vascular endothelial growth factor was assessed using a polyclonal antibody. RESULTS: We found a significant correlation between mast cell count and microvessel density. This correlation was also observed in patients with adenocarcinoma (p < 0.001) as well as in patients with squamous cell carcinoma (p < 0.01). Double staining of the microvessels showed highly angiogenic areas densely populated with mast cells. Although we detected a slight trend toward a correlation between vascular endothelial growth factor expression and microvessel density, it was not statistically significant. We found no association between vascular endothelial growth factor expression and mast cell count. CONCLUSIONS: There appears to be a direct correlation between the number of mast cells and tumor angiogenesis in patients with lung cancer, and this relationship appears to be independent of vascular endothelial growth factor expression.

Adult↗

PubMed2000

Nafamostat mesilate treatment during open heart operation in immune thrombocytopenic purpura.

A 58-year old woman with idiopathic thrombocytopenic purpura underwent mitral and aortic valve replacements and tricuspid annuloplasty. Preoperative therapeutic interventions including prednisone and immunoglobulin were successful in elevating the platelet count to 93,000/ mm2. Furthermore, we used nafamostat mesilate for coagulopathy prophylaxis during cardiopulmonary bypass. Postoperative bleeding was average and clinical course was uneventful. The perioperative management for patients with idiopathic thrombocytopenic purpura requiring cardiac operation is reviewed.

Anticoagulants↗