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S Furuya

Publications and source records attributed to S Furuya.

At least 37 records · Page 2Linked to original sources

Role of neutrophils in sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats.

BACKGROUND AND AIMS: The authors have shown previously that sinusoidal endothelial cell injury developed concomitantly with the accumulation of neutrophils in the hepatic sinusoidal space in cholestatic rats after extensive hepatectomy. The aim of the present study was to investigate the role of neutrophils in the development of this kind of endothelial cell injury. METHODS: Rats underwent 78% partial hepatectomy after 2 weeks of cholestasis, and subsequent external biliary drainage for 5 days. To decrease the number of neutrophils, antirat neutrophil serum was administered intraperitoneally. Some serum parameters and histological specimens were examined 48 h after partial hepatectomy. RESULTS: Anti-neutrophil serum significantly reduced the number of accumulated neutrophils in the hepatic sinusoids. Although the purine nucleoside phosphorylase: alanine aminotransferase ratio, a marker of non-parenchymal cell injury, was increased in cholestatic-hepatectomized rats, this abnormality was significantly attenuated by the treatment with antineutrophil serum. Electron microscopically, focal detachment of cytoplasms of sinusoidal endothelial cells was observed occasionally in cholestatic-hepatectomized rats, but was not found in the antirat neutrophil serum-treated rats. CONCLUSION: These results indicate that accumulated neutrophils might be important effector cells in the pathogenesis of sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats, even after appropriate external biliary drainage.

Alanine Transaminase↗

Expression of vascular endothelial growth factor and its receptors correlates closely with formation of the plexiform lesion in human pulmonary hypertension.

The pulmonary vasculature exhibits various morphological changes in patients with pulmonary hypertension (PH). Among them, the plexiform lesion is one of the most characteristic vascular lesions, although nothing is known about the molecular mechanisms of its formation. In the present study, the expression of vascular endothelial growth factor (VEGF), an endothelial cell-specific angiogenic mitogen, and its receptors, fms-like tyrosine kinase (Flt-1) and kinase insert domain-containing receptor (KDR), in the lungs of five cases with PH, were examined. By in situ hybridization, VEGF expression was found in modified smooth muscle cells inside the plexiform lesions as well as in medial smooth muscle cells of the arteries adjacent to the lesions. The expression of Flt-1 mRNA was observed in endothelial cells of the arteries adjacent to the plexiform lesions, while KDR mRNA was expressed in the endothelial cells inside the plexiform lesions. VEGF was immunolocalized to the endothelial cells expressing its receptors as well as the modified smooth muscle cells producing VEGF. These results demonstrate that VEGF and its receptors are upregulated with a close correlation to the plexiform lesions, and suggest that VEGF expressed by smooth muscle cells may activate the endothelial cells to form the plexiform lesions.

Adolescent↗

Inhibition of acidic sphingomyelinase by xanthone compounds isolated from Garcinia speciosa.

Sphingomyelinase is considered to be involved in the regulation of apoptosis and cell growth. In the course of our screening for acidic sphingomyelinase inhibitors we isolated three xanthone compounds, alpha-mangostin, cowanin, and cowanol, from the bark of Garcinia speciosa. These compounds competitively inhibited bovine brain-derived acidic sphingomyelinase with IC(50) values of 14.1, 19.2, and 10.9 microM, respectively and inhibited the acidic sphingomyelinase more effectively than the neutral sphingomyelinase of bovine brain. alpha-Mangostin inhibited the acidic sphingomyelinase in the most selective manner. alpha-Mangostin was chemically modified and its structure-activity relationships are discussed.

4-Chloro-7-nitrobenzofurazan↗

Hepatic resection for colorectal metastases: analysis of prognostic factors.

PURPOSE: Hepatic resection affords the best hope of survival for patients with colorectal carcinoma metastatic to the liver. However, recurrences are observed in about 60 percent of patients after curative hepatic resection. The purpose of this study was to examine the prognostic factors of patients undergoing curative hepatic resection for colorectal metastases. METHODS: Between April 1984 and September 1997, 168 patients underwent curative hepatic resection for colorectal metastases. The clinicopathologic factors studied for prognostic value were gender, age, primary site, nodal status of primary tumor, time of metastases, preoperative serum level of carcinoembryonic antigen, hepatic tumor size and distribution, number of metastases, type of hepatic resection, resection margin, presence of micrometastases in resected specimen and microscopic fibrous pseudocapsule between the hepatic tumor and surrounding hepatic parenchyma, nodal status of hepatoduodenal ligament, adjuvant regional chemotherapy, and perioperative transfusion. RESULTS: The overall survival was 42 percent at three years and 26 percent at five years, including a 3.5 percent 60-day surgical mortality rate. Thirty-one percent of patients had micrometastases located at a median distance of 3 mm from the metastatic tumor edge. Presence of microscopic fibrous pseudocapsule was observed in 28 percent of patients. Univariate and multivariate analyses showed that significant prognostic factors for survival were nodal status of primary tumor, number of metastases, resection margin, microscopic fibrous pseudocapsule, and adjuvant regional chemotherapy. CONCLUSIONS: We conclude that 1) hepatic resection is effective in select patients with colorectal metastases; 2) adequate resection margin and adjuvant regional chemotherapy can improve outcome; and 3) microscopic fibrous pseudocapsule may offer additional postoperative information as an independent prognostic factor.

Adult↗

Aggressive surgical resection for hepatic metastases involving the inferior vena cava.

BACKGROUND: The implications of aggressive surgical approaches for hepatic metastases involving the inferior vena cava (IVC) have not been clarified yet. The aim of this study is to assess the preliminary results of aggressive surgical resection for hepatic metastases involving the IVC. METHODS: Sixteen patients with hepatic metastases involving the IVC underwent surgical resections with the repair and reconstruction of the IVC: patch repair in 2 and ringed Goretex in 1, primary closure in 13 patients. Hepatic metastases were from colorectal cancer in 14, stomach cancer in 1, and uterine cancer in 1 patient. RESULTS: Vascular control utilized for resecting the IVC were total hepatic vascular exclusion in 8, hypothermic isolated hepatic perfusion in 3, and side clamp in 5 patients. The combined IVC resection with hepatectomy in 16 patients brought about 25% and 6% surgical morbidity and mortality rates, respectively. Survival rates following surgical resections were 64%, 33%, 33%, 22%, 22% for 14 patients of colorectal metastases involving the IVC as compared with 82%, 58%, 41%, 37%, 27% at 1, 2, 3, 4, 5 years, respectively, for 154 patients of colorectal metastases not involving the IVC. CONCLUSION: Hepatic metastases involving the IVC could be safely resected without an increase in surgical risk. Aggressive surgical approaches might bring about a favorable outcome in select patients with colorectal hepatic metastases involving the IVC.

Adult↗

Effective hepatic artery chemoembolization for advanced hepatocellular carcinoma with extensive tumour thrombus through the hepatic vein.

BACKGROUND AND AIMS: Advanced hepatocellular carcinoma (HCC) with extensive tumour growth through the hepatic vein still has an extremely poor prognosis, even after cancer chemotherapy and/or transarterial embolization. Although aggressive surgical treatments using extracorporeal circulation and liver transplantation have been performed by some authors, the reported results were still unsatisfactory. In this study, we report the favourable result of hepatic artery chemoembolization and subsequent surgical resection in three patients with advanced HCC with extensive tumour thrombus through the hepatic vein. METHODS AND RESULTS: Three irresectable patients with HCC with extensive tumour thrombus through the hepatic vein underwent hepatic artery chemoembolization with aclarubicin, mitomycin C, lipiodol and/or Gelfoam. After the reduction of tumour extent with hepatic artery chemoembolization, two of the three patients underwent surgical resection. These two patients are still alive at 59 and 21 postoperative months, respectively. In the other case, the extent of the tumour and functional reserve of the liver prevented us from performing surgical resection, but the patient is doing well 62 months after the initial treatment. CONCLUSIONS: Hepatic artery chemoembolization with aclarubicin, mitomycin C, lipiodol and/or Gelfoam might be an effective treatment for irresectable advanced HCC with extensive tumour thrombus into the inferior vena cava or the right atrium through the hepatic vein. Radical surgical resection might be applicable for selected patients without high surgical risk after reducing tumour extent by hepatic artery chemoembolization.

Aclarubicin↗

Hematospermia: an investigation of the bleeding site and underlying lesions.

BACKGROUND: The site of hemorrhage and causative lesions in patients with hematospermia were evaluated using the puncture technique for seminal vesicles and/or müllerian duct cysts under ultrasound guidance. METHODS: Twenty-one patients aged 26-75 years (mean, 49.8 years) underwent transperineal needle aspiration of the seminal vesicles and/or müllerian duct cysts guided by transrectal ultrasonography (TRUS). RESULTS: Dark reddish seminal vesicle fluid was aspirated and the site of bleeding was considered to be the seminal vesicles in 11 patients (52%) (group A). In group A, abnormalities of the seminal vesicles were noted in nine patients (82%). These consisted of dilated seminal vesicles in seven (bilateral in four, unilateral in three), a seminal vesicle cyst in one and seminal vesicle amyloidosis in one. A müllerian duct cyst was confirmed to be the bleeding site in two patients (10%; group B). The bleeding site was estimated to be organs rather than the seminal vesicles in four patients (group C), in all of whom ectopic prostatic tissue was observed in the prostatic urethra. In groups B and C, seminal vesicle abnormalities were not detected by TRUS. In the remaining four patients (group D), failure to aspirate seminal vesicle fluid means that it is unclear whether hemorrhage was from the seminal vesicle or from another source. In group D, ectopic prostatic tissue was demonstrated in the prostatic urethra of three patients and unilateral seminal vesicle dilation was detected by TRUS in one patient. CONCLUSION: Puncture of the seminal vesicles and/or mullerian duct cysts under ultrasonic guidance as well as cystourethroscopy is a useful and minimally invasive examination for determination of the bleeding site responsible for hematospermia.

Adult↗

Sympathetic activation and contribution of genetic factors in hypertension with neurovascular compression of the rostral ventrolateral medulla.

OBJECTIVE: The rostral ventrolateral medulla is an important center for the regulation of sympathetic and cardiovascular activities. Reportedly, neurovascular compression of the rostral ventrolateral medulla may be causally related to essential hypertension. We aimed to determine the mechanism behind elevated blood pressure in hypertensive patients with compression of the rostral ventrolateral medulla and to investigate whether genetic factors contribute to the etiology of hypertension with compression. DESIGN AND METHODS: The study included 56 patients with essential hypertension and 25 normotensive individuals. With the use of magnetic resonance imaging, the essential hypertension group was subdivided into hypertension with compression and without compression groups. We compared plasma levels of hormones that raise blood pressure and family histories of hypertension between the two hypertension groups and the normotension group. RESULTS: Plasma norepinephrine levels, but not plasma renin activity, aldosterone, epinephrine, or vasopressin levels, were significantly higher in the hypertension with compression group (389+/-53 pg/ml) than in the hypertension without compression group (217+/-38, P<0.05) or in the normotension group (225+/-30, P<0.05). The percentage of individuals who had two hypertensive parents was significantly higher in the hypertension with compression group (39.4%) than in the hypertension without compression group (13.0%, P<0.05) or in the normotension group (8.0%, P<0.01). CONCLUSIONS: These results indicate that neurovascular compression of the rostral ventrolateral medulla might be, at least in part, causally related to essential hypertension by increasing sympathetic nerve activity. They also suggest that genetic factors might contribute to the etiology of hypertension with neurovascular compression.

Alleles↗

Clinical application of magnetoencephalography in a patient with corticobasal degeneration.

Previous neuroimaging studies in corticobasal degeneration (CBD), such as MRI and positron emission tomography, showed lateralized cortical atrophy and a decrease in cortical oxygen metabolism, respectively. The advantage of magnetoencephalography in the research of the auditory system is that activity of both hemispheres can be detected separately. Auditory-evoked magnetic fields (AEFs) were then applied to a patient with corticobasal degeneration. The strength of N100m equivalent current dipoles (ECD) in left hemisphere was extremely smaller (20 nAm) than that in right hemisphere (48 nAm). This results implies that CBD patient might have a decrease in the number of neurons in the primary auditory cortex. This study suggests that AEF measurement is one of the most powerful tools for detecting latent impairment of auditory function in patients with corticobasal degeneration.

Aged↗

Decreases in blood pressure and sympathetic nerve activity by microvascular decompression of the rostral ventrolateral medulla in essential hypertension.

BACKGROUND: Neurovascular compression of the rostral ventrolateral medulla, a major center regulating sympathetic nerve activity, may be causally related to essential hypertension. Microvascular decompression of the rostral ventrolateral medulla decreases elevated blood pressure. CASE DESCRIPTION: A 47-year-old male essential hypertension patient with hemifacial nerve spasms exhibited neurovascular compression of the rostral ventrolateral medulla and facial nerve. Microvascular decompression of the rostral ventrolateral medulla successfully reduced blood pressure and plasma and urine norepinephrine levels, low-frequency to high-frequency ratio obtained by power spectral analysis, and muscle sympathetic nerve activity. CONCLUSIONS: This case suggests not only that reduction in blood pressure by microvascular decompression of the rostral ventrolateral medulla may be mediated by a decrease in sympathetic nerve activity but also that neurovascular compression of this area may be a cause of blood pressure elevation via increased sympathetic nerve activity.

Blood Pressure↗

Occurrence of an unusual phospholipid, phosphatidyl-L-threonine, in cultured hippocampal neurons. Exogenous L-serine is required for the synthesis of neuronal phosphatidyl-L-serine and sphingolipids.

We have recently reported that L-serine released from astroglial cells supports the survival and neuritogenesis of hippocampal neurons under a serum- and glia-free culture condition (Mitoma, J., Furuya, S., and Hirabayashi, Y. (1998) Neurosci. Res. 30, 195-199). In this study, we show that exogenous L-serine is required for the synthesis of phosphatidyl-L-serine (PS) and sphingolipids in hippocampal neurons. When hippocampal neurons were maintained under an astroglial cell-free condition, the levels of sphingolipids and phosphatidyl-L-serine in the neurons were greatly reduced in the absence of external L-serine or glycine. Instead, a novel phospholipid appeared just ahead of PS on TLC. This novel lipid was determined to be phosphatidyl-L-threonine by TLC blotting/negative secondary ion mass spectrometry and amino acid analysis. Biochemical studies on rat brain microsomes have indicated that phosphatidyl-L-threonine is synthesized by the base exchange enzyme that is involved in PS synthesis with much lower affinity, that is, approximately (1)/(150) of L-serine. Addition of L-serine or glycine to the culture medium restored the synthesis of PS and sphingolipids in the neurons. These observations show that hippocampal neurons require exogenous L-serine for the synthesis of PS and sphingolipids in the absence of astroglial cells and suggested that astroglial cells contribute to neuronal lipid synthesis through the supply of L-serine.

Animals↗

Molecular characterization of Xenopus embryo heparan sulfate. Differential structural requirements for the specific binding to basic fibroblast growth factor and follistatin.

Enzymatic elimination of heparan sulfate (HS) causes abnormal mesodermal and neural formation in Xenopus embryos, and HS plays an indispensable role in establishing the embryogenesis and tissue morphogenesis during early Xenopus development (Furuya, S., Sera, M., Tohno-oka, R., Sugahara, K., Shiokawa, K., and Hirabayashi, Y. (1995) Dev. Growth Differ. 37, 337-346). In this study, HS was purified from Xenopus embryos to investigate its disaccharide composition and binding ability to basic fibroblast growth factor (bFGF) and follistatin (FS), the latter being provided in two isoforms with core sequences of 315 and 288 amino acids (designated FS-315 and FS-288) originating from alternative mRNA splicing. Disaccharide composition analysis of the purified Xenopus HS showed the preponderance of a disulfated disaccharide unit with uronic acid 2-O-sulfate and glucosamine 2-N-sulfate, which has been implicated in the interactions with bFGF. Specific binding of the HS to bFGF and FS-288, the COOH-terminal truncated form, was observed in the filter binding assay, whereas HS did not bind to FS-315, indicating that the acidic Glu-rich domain of FS-315 precluded the binding. The binding of the HS to bFGF or FS-288 was markedly inhibited by heparin (HP) and various HS preparations, but not by chondroitin sulfate, supporting the binding specificity of HS. The binding specificity was further investigated using FS-288 and bovine intestinal [3H]HS. Competitive inhibition assays of the HS binding to FS-288 using size-defined HP oligosaccharides revealed that the minimum size required for significant inhibition was a dodecasaccharide, which is larger than the pentasaccharide required for bFGF binding. The binding affinity of FS to HS increased in the presence of activin, a growth/differentiation factor, which could be inactivated by direct binding to FS. These results, taken together, indicate that the structural requirement for binding of HS to bFGF and FS is different. HS may undergo dynamic changes in its structure during early Xenopus embryogenesis in response to the temporal and spatial expression of various growth/differentiation factors.

Activins↗

Bipotential roles of ceramide in the growth of hippocampal neurons: promotion of cell survival and dendritic outgrowth in dose- and developmental stage-dependent manners.

Ceramide is now regarded as a lipid messenger molecule involved in a variety of cellular processes, including growth, differentiation, and cell death. Previously, we demonstrated that ceramide is required for cell survival and dendritic growth of cerebellar Purkinje neurons (Furuya et al.: J Neurochem 65: 1551-1561, 1995). Here, we show that ceramide plays growth-supportive roles in hippocampal neurons at immature stages of development. Application of cell-permeable N-hexanoyl-D-erythro-sphingosine (C6-ceramide) at a concentration of 3 microM promoted cell survival and dendritic outgrowth of the immature neurons. A structurally related compound, N-hexanoyl-D-erythro-dihydrosphingosine (C6-dihydroceramide), was ineffective, showing a requirement of 4-5 double bonds in the sphingosine moiety for activity. Incorporation of 5-bromo-2'-deoxyuridine into neurons was not altered by the treatment with C6-ceramide, indicating that C6-ceramide did not facilitate neuronal proliferation but protected hippocampal neurons against basal cell death. The survival-promoting activity of C6-ceramide, however, appeared to be biphasic; C6-ceramide at a concentration of 10 microM caused retraction of the dendrites and detachment of the neurons from the culture plate followed by cell death. In contrast to the immature neurons, the treatment of mature hippocampal neurons with C6-ceramide did not support cell survival but caused nonnecrotic cell death, even at a concentration of 3 microM. These results suggest strongly that ceramide regulates the fate of hippocampal neurons, depending on its concentration and on the developmental stage.

Animals↗

Expression of substance P receptor in the substantia nigra.

Since the substantia nigra receives abundant substance P innervations but lacks clear evidences about a presence of substance P receptors, expressions for mRNA and protein of substance P receptors were investigated in the rat to resolve this mismatch. Expression levels of substance P receptors mRNA in the substantia nigra pars compacta and reticulata were 37.7 and 24.1% of those in the striatum, respectively, by reverse transcription-polymerase chain reaction (RT-PCR). Substance P receptors mRNA was found in dopamine neurons of the substantia nigra pars compacta by single cell RT-PCR. Ca. 90% of dopamine neurons in the substantia nigra pars compacta were immunoreactive to anti-substance P receptor antibody in the colchicine treated rats. These are the first direct evidence for the existence of substance P receptors in dopamine neurons of the substantia nigra pars compacta.

Animals↗

Gene expression of noncollagenous bone matrix proteins in the limb joints and intervertebral disks of the twy mouse.

The twy (tiptoe walking Yoshimura) mouse is an autosomal recessive mutant manifesting multiple osteochondral lesions characterized by pathologic calcium deposition. To elucidate the pathophysiology of the limb joint lesions and the intervertebral disk lesions of the twy mouse, we assessed the mRNA expression of noncollagenous bone matrix proteins such as osteocalcin, osteonectin, osteopontin, and matrix Gla protein (MGP) by in situ hybridization, but only expression of MGP was observed in association with the pathologic calcium deposits in twy mice. Mild degeneration and abnormal growth of the cartilage in contact with the joint capsule was observed at 5 weeks in the articular cartilage of the ankle joint of the twy mouse, and MGP gene expression was observed at the same time. Simultaneous growth of synovial membrane cells and relatively undifferentiated articular cartilage cells in the knee joint, and of cartilage-like cells near the insertion of the cruciate ligament was observed in the twy mouse, and MGP gene expression was found to be present at the same time. Hypertrophy of abnormally proliferated chondrocyte-like cells, which are different from fibrocartilaginous cells of the annulus fibrosus, was observed in the intervertebral disks of the twy mouse at 3 weeks of age, and MGP gene expression was noted at the same time. These findings suggest that abnormal expression of MGP plays a major role in the pathologic calcification of the twy mouse.

Animals↗

Intravenous injection of guanylin induces mucus secretion from goblet cells in rat duodenal crypts.

Guanylin, structurally related to the heat-stable enterotoxin of E. coli, is a 15-amino-acid peptide isolated from rat small intestine. We investigated the morphological effects of an intravenous injection of rat and human guanylin upon the rat intestine. Various doses of rat guanylin were injected intravenously in anesthetized rats. After 5, 10 and 30 min, rats were killed by intracardiac perfusion with aldehyde fixative, and specimens of the intestine were then prepared for light and electron microscopy. Intravenously injected rat guanylin rapidly induced mucus secretion from crypt goblet cells in the duodenum. About half of the crypt goblet cells secreted mucous granules by compound exocytosis within 5 min. The villus goblet cells, in contrast, were not sensitive to guanylin. Goblet cells in the jejunum were less responsive than those in the duodenum. This secretory response was rare in the ileum and colon. Human guanylin produced similar results. The mucus secretion induced by guanylin was inhibited by a prior-injection of atropine, but not hexamethonium. Moreover, guanylin induced intense edema in the mucosa and submucosa of the small intestine 5 min after the injection, which disappeared after 30 min. A prior-injection of atropine did not block the appearance of edema. In conclusion, the intravenous injection of guanylin induces two phenomena related to water movement: (1) compound exocytosis of mucous granules from crypt goblet cells in the rat duodenum and jejunum; (2) perineural, inter-epithelial and intra-epithelial edema in the rat small intestine.

Animals↗