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Biomedical subjects

Toshio Nishikawa

Publications and source records attributed to Toshio Nishikawa.

At least 19 recordsLinked to original sources
PubMed2006

Syntheses of naturally occurring terphenyls and related compounds.

Naturally occurring terphenyls and related compounds such as terferol and its corresponding quinone and phlebiarubrone were synthesized from 2,5-diphenyl-1,4-benzoquinone. According to the proposed biosynthetic pathway, chemical conversion of phlebiarubrone to ustalic acid, a toxic compound isolated from the poisonous mushroom, Tricholoma ustale, was examined to find a low-yield conversion to the ustalic acid dimethyl ester.

Agaricales↗
PubMed2006

Synthesis of beta-analogues of C-mannosyltryptophan, a novel C-glycosylamino acid found in proteins.

alpha-C-Mannosyltryptophan (alpha-C-Man-Trp) has been found to be a novel post-translational modification of tryptophan found from some biologically important glycoproteins. In order to analyze the biological functions of alpha-C-Man-Trp, we have developed an efficient synthetic strategy for alpha-C-Man-Trp and its glucose and galactose analogues, starting from alpha-C-glycosidation of the corresponding hexapyranoside derivatives with tinacetylene. According to the synthetic routes, we describe here syntheses of beta-anomers of C-Man-Trp, and its glucose and galactose analogues from the corresponding beta-C-glycosylacetylenes. During this study, we have developed a highly stereocontrolled synthesis of beta-C-mannosylacetylene that is required for the synthesis of beta-C-Man-Trp, while the precedented method gave an anomeric mixture of the C-mannosylacetylene. The synthetic C-Man-Trp and its analogues were analyzed by HPLC.

Carbohydrate Conformation↗
PubMed2006

Colonic interposition and supercharge for esophageal reconstruction.

AIMS: We evaluated the techniques of colonic interposition and supercharge for esophageal reconstruction and discussed the main considerations related to these procedures. PATIENTS AND METHODS: In this study, we performed 51 esophageal reconstructions using colonic interposition. Twenty-eight of the 51 patients had synchronous or allochronic gastric malignancy. We selected colonic interposition for high anastomosis in 11 patients and also for esophageal bypass in 3 patients. This procedure was also selected to preserve gastric function in 5 patients. We recently performed the supercharge technique for colonic interposition in 41 patients. RESULTS: Despite the long duration and multistep nature of the operation procedure, no perioperative complications were noted. The patients returned to a good quality of life. The incidence of postoperative weight loss did not differ significantly between the colonic reconstruction group and the gastric reconstruction group. In terms of heartburn and dumping syndrome, the outcome was markedly better in the colonic reconstruction group (no cases of heartburn or dumping syndrome) than that in the gastric reconstruction group. CONCLUSION: For reconstruction of the esophagus, the colonic interposition and supercharge technique is advantageous and contributes to the patient's quality of life.

Adult↗
PubMed2006

Accuracy of PET for diagnosis of solid pulmonary lesions with 18F-FDG uptake below the standardized uptake value of 2.5.

UNLABELLED: Benign and malignant pulmonary lesions usually are differentiated by 18F-FDG PET with a semiquantitative 18F-FDG standardized uptake value (SUV) of 2.5. However, the frequency of malignancies with an SUV of <2.5 is significant, and pulmonary nodules with low 18F-FDG uptake often present diagnostic challenges. METHODS: Among 360 consecutive patients who underwent 18F-FDG PET to evaluate pulmonary nodules found on CT, we retrospectively analyzed 43 who had solid pulmonary lesions (excluding lesions with ground-glass opacity, infiltration, or benign calcification) with an SUV of <2.5. The uptake of 18F-FDG was graded by a visual method (absent, faint, moderate, or intense) and 2 semiquantitative methods (SUV and contrast ratio [CR]). Final classification was based on histopathologic findings or at least 6 mo of clinical follow-up. RESULTS: We found 16 malignant (diameter, 8-32 mm) and 27 benign (7-36 mm) lesions. When faint visual uptake was the cutoff for positive 18F-FDG PET results, the receiver-operating-characteristic (ROC) analysis correctly identified all 16 malignancies and yielded false-positive results for 10 of 27 benign lesions. Sensitivity was 100%, specificity was 63%, and the positive and negative predictive values were 62% and 100%, respectively. When an SUV of 1.59 was the cutoff for positive 18F-FDG PET results, the ROC analysis revealed 81% sensitivity, 85% specificity, and positive and negative predictive values of 77% and 89%, respectively. At a cutoff for positive 18F-FDG PET results of a CR of 0.29, the ROC analysis revealed 75% sensitivity, 82% specificity, and positive and negative predictive values of 71% and 85%, respectively. The areas under the curve in ROC analyses did not differ significantly among the 3 analyses (visual, 0.84; SUV, 0.81; and CR, 0.82). Analyses of intra- and interobserver variabilities indicated that visual and SUV analyses were quite reproducible, whereas CR analysis was poorly reproducible. CONCLUSION: These results suggested that for solid pulmonary lesions with low 18F-FDG uptake, semiquantitative approaches do not improve the accuracy of 18F-FDG PET over that obtained with visual analysis. Pulmonary lesions with visually absent uptake indicate that the probability of malignancies is very low. In contrast, the probability of malignancy in any visually evident lesion is about 60%.

Adult↗
PubMed2005

Sister Joseph umbilical nodule coexisting with endometriosis from endometrial carcinoma.

A 58-year-old woman was diagnosed with endometrial carcinoma. Total hysterectomy, bilateral salpingo-oophorectomy and paraaortic and a pelvic lymph node dissection were performed. The cytology of peritoneal fluid was negative. There was no peritoneal dissemination except umbilical nodule. A peritoneal 2.0x1.5 cm umbilical nodule was also resected. The nodule was identified as a metastasis from endometrial cancer with endometriosis. The pelvic lymph nodes also showed metastatic lesion with endometriosis. Our case showed that endometriosis coexisted with umbilical and pelvic lymph nodal metastatic lesions from endometrial cancer. This fact suggests that the mode of metastasis to the umbilicus via lymph flow from endometrial cancer is the same as that for endometriosis.

Adenocarcinoma↗
PubMed2005

Fulminant myocarditis demonstrating uncommon morphology--a report of two autopsy cases.

Two autopsy cases of fulminant myocarditis demonstrating uncommon morphology were studied. Subjects included two male patients: a 42-year-old (case 1) and a 39-year-old (case 2). Both cases had fever, chest or epigastric pain, electrocardiographic abnormalities, prominent elevation of serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, lactic dehydrogenase and creatine phosphokinase. They were treated with intra-aortic balloon pumping and percutaneous cardiopulmonary support, and they died at 3 days and 4 days after admission (total course of 10 days and 9 days), respectively. Case 1 showed focal necrosis, severe myocardial dystrophic calcification positive for Kossa stain, inflammatory edema, lymphocyte and macrophage infiltration and extravasation of erythrocytes. Case 2 showed acute inflammation and severe myocardial necrosis with neutrophilic abscess, lymphocyte and macrophage infiltration, cell debris and purulent exudate. Calcified, degenerative and necrotic cardiac myocytes and macrophages were reacted with anti-Enterovirus antibody (clone 5-D8/1), which recognizes an epitope on the VP1 peptide of most Coxsackievirus, echovirus, poliovirus and enterovirus strains. Therefore, the present two cases may be compatible with fulminant enterovirus-associated myocarditis. Using reverse transcriptase-semi-nested polymerase chain reaction, picornaviral RNA was detected in the amplified products extracted from the paraffin-embedded myocardial sample of case 1 but not in case 2.

Adult↗
PubMed2005

Stereocontrolled syntheses of alpha-C-mannosyltryptophan and its analogues.

The total synthesis of alpha-C-mannosyltryptophan (C-Man-Trp), a naturally occurring C-glycosylamino acid, was achieved from a commercially available alpha-methyl-D-mannoside in 10 steps including the following key steps: the C-glycosidation of a mannose derivative with a stannylacetylene, Castro indole synthesis, and Sc(ClO4)3-promoted coupling with L-serine-derived aziridine carboxylate. The glucose- and galactose-analogues of C-Man-Trp were also synthesized in a similar manner. Conformational analyses of the synthesized C-glycosyltryptophan and its synthetic intermediate are briefly discussed.

Aziridines↗
PubMed2005

Diagnostic utility of tenascin-C for evaluation of the activity of human acute myocarditis.

Tenascin-C (TN-C) is an extracellular matrix protein that is expressed transiently in close association with tissue remodelling in various body sites. In the heart, TN-C is only present during early stages of development, is not expressed in the normal adult, but reappears in pathological states. The purpose of this study was to analyse the expression of TN-C in myocardial tissue from myocarditis patients, and to evaluate the diagnostic value of immunostaining for TN-C in the assessment of inflammatory activity in biopsy specimens. A total of 113 biopsy specimens obtained from 32 patients with a clinical diagnosis of acute myocarditis were examined by immunohistochemistry and in situ hybridization for TN-C. The immunostaining was semi-quantified and compared with histological diagnosis according to the Dallas criteria. Furthermore, serial biopsies from 22 patients were taken during convalescence, and sequential changes in TN-C levels were analysed. Expression of TN-C was specifically detected in endomyocardial biopsy specimens from patients with active-stage inflammation, and disappeared in healed stages. The degree of expression of TN-C correlated with the severity of histological lesions. These data suggest that TN-C reflects disease activity in cases of human myocarditis. Immunostaining for TN-C could enhance the sensitivity and accuracy of diagnosis using biopsy specimens.

Acute Disease↗
PubMed2005

Probability of axillary lymph node metastasis when sentinel lymph node biopsy is negative in women with clinically node negative breast cancer: a Bayesian approach.

BACKGROUND: Although sentinel lymph node biopsy(SLNB)is highly accurate in predicting axillary nodal status in patients with breast cancer, it has been shown that the procedure is associated with a few false negative results. The risk of leaving metastatic nodes behind in the axillary basin when SLNB is negative should be estimated for an individual patient if SLNB is performed to avoid conventional axillary lymph node dissection(ALND). METHODS: A retrospective analysis of 512 women with T1-3N0M0 breast cancer was conducted to derive a prevalence of nodal metastasis by T category as a pre-test(i.e., before SLNB)probability and to examine potential confounders on the relationship between T category and axillary nodal involvement. Probability of nodal metastasis when SLNB was negative was estimated by means of Bayes' theorem which incorporated the pre-test probability and sensitivity and specificity of SLNB. RESULTS: Axillary nodal metastasis was observed in 6.1% of T1a-b, 25.1% of T1c, 28.7% of T2, 35.0% of T3 tumors. Point estimates for the probability of nodal involvement when SLNB was negative ranged from 0.3-1.3% for T1a-b, 1.6-6.3% for T1c, 2.0-7.5% for T2, and 2.6-9.7% for T3 tumors with representative sensitivities of 80%, 85%, 90% and 95%, respectively. The risk may be higher when the tumor involves the upper outer quadrant of the breast, while it may be lower for an underweight woman. CONCLUSIONS: The probability of axillary lymph node metastasis when SLNB is negative can be estimated using a Bayesian approach. Presenting the probability to the patient may guide the decision of surgery without conventional ALND.

Adult↗
PubMed2004

Alpha-C-mannosyltryptophan is not recognized by conventional mannose-binding lectins.

Alpha-C-mannosyltryptophan (C-Man-Trp) is a novel, naturally occurring C-linked carbohydrate-protein linkage first found in 1994 from human ribonuclease 2. Since then, a number of C-Man-Trp residue have been found from several important proteins such as interleukin 12 beta, components of complement system, thrombospondin-1, and erythropoietin receptor, however, the biological functions have remained unknown even though its biosynthetic pathway has been revealed. In order to find a clue as to the biological functions, we examined the affinity of C-Man-Trp with conventional mannose lectin such as concanavarin A (Con A) and mannose-binding lectin (MBL). The affinity of C-Man-Trp with Con A, a typical mannose-binding lectin from plant was examined using a Con A-Sepharose column. Unlike p-nitrophenyl-alpha-O-Man, C-Man-Trp was not retained on the column. MBL-C, a major mannose-binding lectin purified from mouse serum, did not bind with N-biotinylated C-Man-Trp, judging from ELISA based assay. These results imply that C-Man-Trp may be recognized with the other specific proteins associated with its unknown biological functions.

Blotting, Western↗
PubMed2004

Stereocontrolled synthesis of 8,11-dideoxytetrodotoxin, an unnatural analogue of puffer fish toxin.

8,11-Dideoxytetrodotoxin, an unnatural tetrodotoxin analogue, was synthesized in a highly stereoselective manner from a common intermediate from our synthetic studies on tetrodotoxin. The key features in the synthesis were as follows: neighboring group participation of a trichloroacetamide to allow regioselective and stereoselective hydroxylation, protection of a delta-hydroxylactone as an ortho ester, and guanidine installation through the use of Boc-protected isothiourea. Global deprotection of the fully protected intermediate under acidic conditions gave 8,11-dideoxytetrodotoxin, which exhibited very weak biological activities.

Animals↗
PubMed2004

Swimming exercise in infancy has beneficial effect on the hearts in cardiomyopathic Syrian hamsters.

The phenotypic expression of cardiomyopathy is greatly influenced by extrinsic factors other than intrinsic genetic defects, such as environmental stress. Exercise is assumed to be an important extrinsic factor, since sudden death is sometimes seen during exercise in young patients with hypertrophic cardiomyopathy (HCM). However, the long-term effects of mild exercise on phenotypic expression in cardiomyopathy remain unclear. To evaluate the effects of exercise performed during infancy or adolescence in cardiomyopathic patients, cardiomyopathic Syrian hamsters (BIO14.6) were subjected to swimming. BIO14.6 and age-matched congenic normal hamsters (CN) as controls were divided into three groups: sedentary (Sed), and trained during infancy (Inf) and during adolescence (Ado). Histological and biochemical analysis of 41-week-old hamsters revealed that (1) the relative level of beta-myosin heavy chain mRNA was significantly lower in the Inf group than in the Sed and Ado groups of BIO14.6. The level in the Inf group of BIO14.6 was compatible with that in the age-matched Sed group of the CN strain; (2) in BIO14.6, degenerative mitochondrial change in the cardiomyocytes was not seen in the Inf group while it was common in the Sed and Ado groups; (3) calcineurin phosphatase activity in the swimming group in 10-week-old CN was significantly higher than that of the age-matched sedentary group, and was as much as that of the swimming and sedentary groups in 10- and 41-week-old BIO14.6.

Age Factors↗
PubMed2004

Aldosterone antagonist facilitates the cardioprotective effects of angiotensin receptor blockers in hypertensive rats.

BACKGROUND: There is increasing evidence to support the importance of blocking aldosterone to prevent target-organ damage in hypertension. We recently demonstrated an aldosterone breakthrough phenomenon during administration of an angiotensin type 1 receptor blocker (ARB). OBJECTIVE: To elucidate the pathophysiological significance of residual aldosterone by investigating the influence of the aldosterone antagonist on the cardioprotective effects of the ARB in hypertensive rats. METHODS: Injection vehicle alone, ARB (1.0 mg/kg per day candesartan by mouth), aldosterone antagonist (10 mg/kg per day spironolactone, subcutaneously), or combined treatment were administered to male stroke-prone spontaneously hypertensive rats for 24 weeks from the age of 4 weeks. Blood pressure, plasma angiotensin II and aldosterone concentrations, left ventricular weight, expression of type I and type III collagen mRNA, and histological findings were determined. RESULTS: In the ARB-treated group, aldosterone concentrations remained unchanged (1.10 +/- 0.20 nmol/l, compared with 1.17 +/- 0.46 nmol/l in the control group), whereas systolic blood pressure (178 +/- 9 mmHg), left ventricular weight (0.372 +/- 0.035 g/100 g body weight), expression of collagen mRNA, and cardiac interstitial and perivascular fibrosis all decreased significantly compared with the control group (systolic blood pressure: 222 +/- 10 mmHg, P < 0.05; left ventricular weight: 0.483 +/- 0.021 g/100 g body weight, P < 0.05). Although blood pressure (217 +/- 9 mmHg) and left ventricular weight (0.467 +/- 0.027 g/100 g body weight) remained unchanged in the group receiving spironolactone, the expression of both types of collagen mRNA and cardiac interstitial and perivascular fibrosis showed a significant decrease compared with the vehicle-treated group. In the rats receiving combined treatment with the ARB and spironolactone, left ventricular weight (0.352 +/- 0.005 g/100 g body weight, P < 0.05), expression of collagen mRNA, and cardiac interstitial and perivascular fibrosis all showed a further improvement compared with both the ARB and spironolactone groups. CONCLUSIONS: These results demonstrate that residual aldosterone has a significant impact on target-organ damage in hypertension, even during chronic administration of an ARB. The addition of an aldosterone antagonist has an advantage in facilitating the cardioprotective effects of ARBs.

Aldosterone↗
PubMed2003

First asymmetric total synthesis of tetrodotoxin.

Tetrodotoxin, a toxic principle of puffer fish poisoning, is one of the most famous marine natural products because of the complex structure having many functional groups and its potent biological activity leading to death. Since the structure elucidation in 1964, this toxin has been recognized as a formidable target molecule for total synthesis. We have recently achieved the first asymmetric total synthesis from 2-acetoxy-tri-O-acetyl-d-glucal as a chiral starting material. The highly hydroxylated cyclohexane ring was constructed by Claisen rearrangement and regioselective hydroxylations of an acetone moiety and an intramolecular directed aldol condensation of the precursor having methyl ketone with dihydroxyacetone, which was synthesized through Sonogashira coupling. Installation of nitrogen functionality was unsuccessful through an attempted Overman rearrangement. We, therefore, employed a new intramolecular conjugate addition strategy between the carbamate and unsaturated ester groups. The alpha-hydroxyl lactone moiety was synthesized through an intramolecular epoxide opening by the Z-enolate of aldehyde, which was followed by oxidation-reduction of the resulting cyclic vinyl ether. The lactone was then converted to a protected ortho ester, and then gunanidinylation was followed by cleavage of the 1,2-glycol to give the fully protected tetrodotoxin. Selection of the protective groups has finally led us to accomplish the total synthesis of tetrodotoxin in an enantiomerically pure form. All the stereogenic centers were controlled with high selectivity, and the hydroxyl groups were differently protected to discriminate for the future analogue synthesis of a bioorganic program. The synthetic tetrodotoxin was purified by ion exchange chromatography and characterized to be identical with the natural compound.

Cyclohexanes↗