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Biomedical subjects

S Kondo

Publications and source records attributed to S Kondo.

At least 433 records · Page 24Linked to original sources

Selective deoxygenation and O-methylation of benanomicin A: synthesis of 9-deoxy-, 9-O-methyl- and 14-O-methylbenanomicin A.

The selective modifications of phenolic hydroxy groups in the chromophore of benanomicin A are described. Hydride reduction of 9-O-tosylate with sodium borohydride/nickel chloride led to 9-deoxybenanomicin A. Methylation of 1-O-diphenylmethylbenanomicin A diphenylmethyl ester with sodium hydride/iodomethane gave 9-O-methyl derivative and with Hünig's base/diazotrimethylsilylmethane afforded the 14-O-methyl derivative. These compounds showed the diminished activity against fungi.

Anthracyclines↗

[Cerebral perfusion and oxygen metabolism in Parkinson's disease: positron emission tomographic study using oxygen-15-labeled CO2 and O2].

In many previous studies, positron emission tomography (PET) has been used to evaluate cerebral perfusion and oxygen metabolism in Parkinson's disease. In this article, these previous reports are reviewed together with our recent findings. Hypoperfusion and hypometabolism in parkinsonian brains reported previously seemed to be derived chiefly from psychiatric manifestations, including intellectual decline and depression. In our study on 34 patients with asymmetric symptoms, the blood flow and oxygen metabolism were significantly higher in the caudate head and putamen, contralateral to the predominant patient's symptoms, than in the opposite nuclei. The asymmetry in the perfusion and metabolism is clearer in the early stage of the disease or in patients without DOPA therapy. These findings suggest that the striatal dysfunction is caused by uninhibited activities, supersensitivities, or compensatory hyperactivities of the striatum.

Brain↗

[Intrapulmonary laceration revealed by computed tomography in a patient with pneumomediastinum].

An 18-year-old man had bronchial asthma and a pneumomediastinum. A computed tomographic scan of the chest revealed the pneumomediastinum, intrapulmonary laceration of the S1b, and a small amount of air in the perivascular space from V1a to V1. Increased pressure in intrapulmonary airways may have resulted in ruptured S1b alveoli and air leakage into the interstitium between the surrounding secondary lobules. The air may have moved along the perivascular space (pulmonary vein) toward the hilum, and eventually into the mediastinum. We know of no previous report of pneumomediastinum in which images of intrapulmonary lesions are presented. In this case computed tomography revealed the mechanism by which the pneumomediastinum probably developed.

Adolescent↗

Presurgical identification of extradural nerve root anomalies by coronal fat-suppressed magnetic resonance imaging: a report of six cases and a review of the literature.

In an attempt to depict the anatomy of the nerve roots, we obtained magnetic resonance (MR) images of the lumbar spine in the coronal plane with the frequency-selective fat-suppression technique. With this technique, extradural anomalies were identified in 20 (6.7%) of 300 patients. We report the appearance on coronal MR images of six surgically confirmed extradural anomalous nerve roots together with the myelography findings. These include type Ia, type Ib, and type 3 anomalies. These are readily recognized and allow detailed evaluation of the type of nerve root anomaly.

Adult↗

Preoperative transcatheter arterial embolization for giant cavernous hemangioma of the liver with consumption coagulopathy.

We describe a 40-yr-old woman with a giant hepatic hemangioma and consumption coagulopathy who underwent transcatheter arterial embolization (TAE) prior to liver resection. Post-contrast computed tomography showed a large mass in the right hepatic lobe with a peripheral, nodular enhancement pattern that enlarged on delayed-phase images. There was a low fibrinogen concentration and decreased platelet count. The patient received i.v. nafamostat mesilate and underwent selective embolization of the arteries feeding the hemangioma; consequently, the plasma fibrinogen concentration increased to 1.6-fold before surgery. Right hepatic lobectomy with partial resection of the caudate lobe was performed. The intraoperative blood loss was only 1380 g. This patient illustrates the usefulness of preoperative TAE for hepatic hemangioma with consumption coagulopathy; TAE appears to improve coagulopathy and increase the safety of surgery.

Adult↗

Cyclosporin inhibits intercellular adhesion molecule-1 expression and reduces mast cell numbers in the asebia mouse model of chronic skin inflammation.

The asebia mouse represents a spontaneous mutation in BALB/c mice leading to hyperplasia of the epidermis and chronic inflammatory dermal changes including enhanced cellularity, oedema and elevated mast cell numbers. We demonstrated that asebia mice have constitutively elevated intercellular adhesion molecule-1 (ICAM-1) mRNA expression, which is not detectable in the wild type, and that dermal mast cell numbers were 3.1-fold higher than the wild type (P < 0.001). We utilized this model to explore the anti-inflammatory effects of cyclosporin A (CsA). After 3 weeks subcutaneous injection with 5 or 10 mg/kg CsA the expression of ICAM-1 mRNA was determined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and was found to be decreased 2.7-fold (P < 0.001) and three-fold (P < 0.001) relative to controls for 5 and 10 mg/kg treatments, respectively. Dermal mast cell counts were dose-dependently decreased by CsA. Mast cells, visualized by toluidine blue staining, decreased 4.5-fold with 10 mg/kg CsA (P < 0.001) bringing them down to numbers typical of the wild type. CsA also appeared to stabilize mast cell histamine content. Histological examination of haematoxylin-eosin-stained sections revealed that CsA treatment restored the wild-type skin phenotype decreasing epidermal hyperplasia, dermal cellularity and oedema. Thus, CsA exhibits a wide range of anti-inflammatory effects including reduction of ICAM-1 expression and mast cell numbers, and may be useful in the treatment of mast cell-mediated dermatoses.

Animals↗

Carcinoma of the common bile duct with superficial spread to the intrahepatic segmental bile ducts: a case report.

A 54-year-old woman presented with jaundice. Percutaneous transhepatic biliary drainage, cholangiography via a percutaneous transhepatic biliary, drainage catheter, and percutaneous transhepatic cholangioscopy were performed to alleviate the jaundice and to evaluate her biliary system. A diffuse-type tumor was detected in the common bile duct. The tumor had spread superficially up to the right anterior segmental duct and the left hepatic duct and involved the caudate branches. Curative surgery, which included a right anterior segmentectomy, total caudate lobectomy, and pylorus-preserving pancreatoduodenectomy, was performed. The histopathologic diagnosis was moderately differentiated tubular adenocarcinoma originating at the common bile duct. The extent of the superficial spread of the tumor corresponded to our preoperative determination. Her postoperative recovery was uneventful. In this case report, we discuss the accurate preoperative diagnosis and rational surgical treatment of bile duct carcinoma with superficial spread.

Adenocarcinoma↗

Hypnotic activities of N3-benzyl and xylyl substituted arabinofuranosyluracil.

N3-Substituted derivatives of arabinofuranosyluracil (1), methyl (2), ethyl (3), propyl (4), butyl (5), allyl (6), benzyl (7), o-, m-, p-xylyls (8, 9, 10) and alpha-phenethyl (11) derivatives, were synthesized and their CNS depressant effects were evaluated by intracerebroventricular (i.c.v.) injection in mice by using hypnotic activity and pentobarbital-induced sleep prolongation as indices. At a dose of 2.0 mumol/mouse, the values of mean sleeping time induced by 7, 8, 9, and 10 were 144, 154, 117, and 33 min, respectively. Although the alkyl (2-6) derivatives did not cause any hypnotic activity, some derivatives tested (5, 7-10) significantly prolonged the pentobarbital-induced sleeping time.

Animals↗

Over-expression of bcl-xL gene in human gastric adenomas and carcinomas.

The present study was designed to clarify whether bcl-xL is involved in the development of carcinoma in the stomach. Levels of bcl-xL and bcl-2 mRNA were determined by a reverse-transcription/polymerase-chain reaction in endoscopic gastric biopsy specimens from 10 control subjects, 11 patients with adenomas and 14 patients with carcinomas. In 6 of 11 adenomas, 5 of 8 early carcinomas and 3 of 6 advanced carcinomas, the bcl-xL gene was over-expressed. In carcinomas, over-expression of the bcl-xL gene was observed in 6 of 9 intestinal-type carcinomas and 2 of 5 diffuse-type carcinomas. No correlation was observed between bcl-xL and bcl-2 gene expression. In cases in which the bcl-xL gene was over-expressed, an apparent increase in the protein level of Bcl-xL was observed by immunoblot analysis and intense Bcl-x immunoreactivity was detected immunohistochemically within the tumor cells. In conclusion, we showed that bcl-xL is over-expressed in gastric carcinomas at both the RNA and protein levels, suggesting that over-expression of bcl-xL may play a role in gastric carcinogenesis.

Adenoma↗

2-Arachidonoylglycerol, a putative endogenous cannabinoid receptor ligand, induces rapid, transient elevation of intracellular free Ca2+ in neuroblastoma x glioma hybrid NG108-15 cells.

Low concentrations of 2-arachidonoylglycerol were found to induce rapid, transient elevation of intracellular free Ca2+ in NG108-15 cells (EC50 was 150 nM). Free arachidonic acid, 2-palmitoylglycerol, 2-oleoylglycerol, 2-linoleoylglycerol and 2-docosahexaenoylglycerol were inactive. Anandamide acted as a partial agonist. Importantly, desensitization was observed upon sequential challenge with 2-arachidonoylglycerol. Furthermore, cross-desensitization was observed between 2-arachidonoylglycerol and WIN 55212-2, a cannabinoid receptor agonist. Pretreatment of the cells with SR141716A, a cannabinoid receptor antagonist, abolished the activities of both 2-arachidonoylglycerol and WIN 55212-2. These results strongly suggest that 2-arachidonoylglycerol and WIN 55212-2 bind to a common cannabinoid receptor to elicit cellular responses and that 2-arachidonoylglycerol has some physiological role in nervous tissues.

Arachidonic Acids↗

Contribution of the CD28 molecule to allergic and irritant-induced skin reactions in CD28 -/- mice.

The CD28 molecule is thought to be essential for the costimulatory signals and is required for mitogenic activation of T cells. The aim of this study was to evaluate the contribution of CD28 in contact hypersensitivity using CD28 gene-targeted (CD28 -/-) mutant mice. Contact hypersensitivity to dinitrofluorobenzene and oxazolone was significantly decreased in CD28 -/- mice compared with that in normal (C57BL/6) mice. Significant increases in IL-2 mRNA were detected in the skin after dinitrofluorobenzene challenge in normal mice, while this response was blunted in CD28 -/- mice. In addition, responses to irritant chemicals (croton oil and phenol) were also impaired in CD28 -/- mice. IL-2, IFN-gamma, and TNF-alpha mRNA levels were lower in CD28 -/- mouse skin treated with phenol. T cells from CD28 -/- mice did not bind to epidermal cells derived from normal mice, while cocultivation of T cells with epidermal cells from normal mice demonstrated a significant binding. These results indicate that the CD28 molecule is required not only for optimal induction of allergic contact dermatitis, but also for the development of irritant-induced skin inflammation. The expression of B7-1 and B7-2 molecules on epidermal cells was induced by an allergen treatment in normal and CD28 -/- mice, whereas only B7-2 was induced after irritant treatment. Lack of CD28 signaling may influence cutaneous inflammation by modulating skin cytokine profiles, possibly due to the decreased contact of T cells with other cell populations expressing ligands for CD28. In addition, the results of this study suggest that allergic contact dermatitis and irritant dermatitis have overlapping pathophysiologic mechanisms, but subtle differences exist.

Animals↗

Regulation of extracellular matrix by mechanical stress in rat glomerular mesangial cells.

Increases in intraglomerular pressure are known to predispose to the development of glomerular sclerosis, which is characterized by accumulation of extracellular matrix within the glomerulus. Glomerular mesangial cells are exposed to pulsatile capillary pressures and are a potential target for mechanical stress. In the present studies, we subjected cultured rat mesangial cells to continuous cycles of stretching and relaxation (stretch/relaxation) and examined alterations in extracellular matrix gene expression. After 48 h of stretch/relaxation, immunofluorescent localization of matrix accumulation indicated increases in types I, III, and IV collagens, fibronectin, and laminin, with the greatest increases seen at the periphery of the culture dish, at the point of the greatest deformation. Northern blot analysis of total RNA revealed time-dependent induction of alpha1(I) collagen, alpha1(III) collagen, alpha1(IV) collagen, fibronectin, and laminin by stretch/relaxation, with maximal increases occurring between 12 and 24 h. Transient transfection of reporter gene constructs of the 5' flanking region of alpha1(I) collagen gene indicated that stimulation of gene transcription was involved in the increased expression of matrix mRNA. Gelatinolytic activity in conditioned media was decreased at 24 and 48 h of stretch/relaxation, in association with a significant decrease in levels of mRNA for matrix metalloproteinase-2 (68-72 kD type IV collagenase) occurring within 6 h of stretch/relaxation. In contrast, expression of tissue inhibitor of metalloproteinase-2 was increased within 12 h of stretch/relaxation. Stretch/relaxation increased immunoreactive TGF-beta at 48 but not 12 h. TGF-beta1 mRNA levels remained unchanged during the initial 12 h of stretch/relaxation, but were significantly elevated at 48 h, and no differences in TGF-beta bioactivity could be detected in conditioned media for up to 12 h of stretch/relaxation. These findings demonstrate that in glomerular mesangial cells, repeated cycles of stretching and relaxation lead to matrix accumulation by stimulating production of extracellular matrix and decreasing activity of degradative enzymes. The observed induction of TGF-beta1 suggests a role in matrix accumulation occurring in response to continued mechanical deformation.

Animals↗

The transforming activities of MDM2 in cultured neonatal rat astrocytes.

Although the molecular events regulating the pathogenesis of malignant astrocytomas remains unclear, the inactivation of tumor suppressor genes may be a key factor. The inactivation of p53 by mutation or deletion, however, is not the only obligatory step in astrocytoma genesis. The MDM2 protein has been shown to bind to and downmodulate p53 function, and to have oncogenic capacity. The MDM2 gene is also amplified and overexpressed in a subset of malignant astrocytomas without p53 mutation. Here we show that overexpression of MDM2 promoted the DNA synthesis of cultured neonatal rat astrocytes (RNB cells), abrogated the transcriptional activity of wild-type p53, conferred invasive activity, and subsequently induced the transformation from astrocytes to high-grade astrocytomas. Intriguingly, MDM2 enhanced the expression of angiogenic mitogens; basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) in RNB cells. These results indicate that MDM2 may play an important role in the progression of astrocytomas, by not only conferring invasive activity but also stimulating the expression of angiogenic growth factors.

Animals↗

Localization of Alzheimer-associated presenilin 1 in transfected COS-7 cells.

Presenilin 1 (PS 1) is the recently identified gene, located on chromosome 14, of which missense mutations can cause early-onset familial Alzheimer's disease. To understand the normal biological function of presenilin 1, we examined the sub-cellular localization by using a monoclonal anti-presenilin 1 antibody. Immuno-electronmicroscopic and biochemical analysis indicated that presenilin 1 is localized on cellular membrane (plasma, endoplasmic reticulum, and perinuclear) in COS-7 cells overexpressing presenilin 1. Interestingly, the PS 1 immunoreactivity in the plasma membrane was concentrated in the regions with cell-cell contact. This observation suggests a possible role of PS 1 on the cell membrane as a cell adhesion molecule.

Alzheimer Disease↗

WAF1/CIP1 increases the susceptibility of p53 non-functional malignant glioma cells to cisplatin-induced apoptosis.

Induction of apoptosis in tumor cells is an important determinant in the outcome of therapy. Molecular details of the apoptosis pathway, however, are still poorly defined. The recently discovered WAF1/CIP1 gene is a potent inhibitor of cyclin-dependent kinases and a mediator of tumor-suppressor p53-dependent apoptosis by DNA damage. In addition, WAF1/CIP1 expression is shown to be triggered through the p53-independent pathway. The relationship between WAF1/CIP1 and p53-independent apoptosis by DNA damage, however, remains unclear. In this study, we show that WAF1/CIP1 was induced in p53-dependent apoptosis of U87-MG glioma cells by cis-diamminedichloroplatinum (cisplatin), and overexpression of WAF1/CIP1 induced apoptosis in U87-MG cells without cisplatin treatment. In contrast, the p53-independent apoptosis of GB-1 glioma cells by cisplatin did not express WAF1/CIP1. Overexpression of WAF1/CIP1 inhibited DNA synthesis in GB-1 cells, but did not induce apoptosis. Interestingly, WAF1/CIP1 increased the susceptibility of GB-1 cells to cisplatin-induced apoptosis. These results suggest that overexpression of WAF1/CIP1 may have potential for the treatment of tumors with non-functional p53.

Antineoplastic Agents↗