pp60c-src activation in gastric carcinoma: a preliminary study.
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Biomedical subjects
Publications and source records attributed to K Taniguchi.
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FK584[(-)-N-tert-butyl-4,4-diphenyl-2-cyclopentenylamine hydrochloride, (-)-4-HCl], a potential candidate for the treatment of overactive detrusor, was synthesized in a 4-step approach starting with Sharpless oxidation of cyclopentenol 6 (kinetic resolution). This epoxidation is a rare case in that the empirical rule does not work. Regio- and stereoselective introduction of tert-butylamine to the obtained epoxycyclopentanol 5 and subsequent conversion of the resulting diol to an olefin completed the synthesis. The absolute configuration of FK584 was determined to be S by X-ray crystallographic analysis of the salt of S-(+)-mandelic acid.
Blood viscosity (etaB) is low in athletes, but the effect of exercise training on etaB during endurance exercise at an anaerobic threshold (AT) intensity in non-athletes is not well known, although it is known that exercise training sometimes induces the hyperviscosity syndrome. Fourteen subjects were recruited and divided into 2 groups: those who trained at an AT intensity for 30 min/day, 3 times weekly for 1 year (Group T, n=8), and sedentary subjects (Group C, n=6). The test protocol consisted of a single 30-min treadmill exercise at each individual's AT intensity, which was determined in advance. The etaB, plasma viscosity (etaP), and hematocrit were measured just before and at the end of the treadmill exercise. The subjects were not allowed to drink any water before exercise. In the Group C subjects, the hematocrit and etaP increased significantly and the etaB tended to increase. However, in the Group T subjects, the hematocrit and etaP did not increase and the etaB decreased significantly. These data indicate that long-term exercise training attenuates the increase in blood viscosity during exercise.
To identify and quantify the amount of viable hibernating myocardium in patients with chronic coronary artery disease, resting 201Tl single photon emission computed tomography (SPECT) was compared with 99mTc-methoxy-isobutyl isonitrile (MIBI) SPECT after nitrate infusion (nitrate-99mTc-MIBI) and 201Tl SPECT after 201Tl with glucose-insulin-potassium infusion (201Tl-GIK) in 25 patients. Twenty-one patients also underwent completely left ventriculography beforehand and 5+/-4 months afterwards. SPECT images were divided into 9 segments and scored visually from 0 (normal uptake) to 3 (absent). The defect score was calculated as the summation of the total scores (TDS) in each patient. The TDS of nitrate-99mTc-MIBI images (6.3+/-4.3) and 201Tl-GIK images (5.8+/-4.2) were significantly lower than the 7.4+/-4.3 of resting 201Tl images (p<0.01). Based on the improvement of wall motion after coronary revascularization, the sensitivity of 201Tl-GIK imaging (85%) was significantly higher (p<0.05), and that of nitrate-99mTc-MIBI imaging (79%) also tended to be higher (p=0.08), than that of 201Tl imaging (62%) in detecting viable myocardium. The specificity of the 3 methods was almost the same. The nitrate-99mTc-MIBI and 201Tl-GIK methods were more useful than the resting 201Tl method for evaluating viable hibernating myocardium. Furthermore, the 201Tl-GIK method may provide a more accurate estimate of the amount of viable myocardium than the nitrate-99mTc-MIBI method.
The discordant cases of seronegative, but culture and proviral HIV-2 DNA positive were found in Mumbai, India. This was corroborated by the successful isolation of HIV-2-RNA in culture medium, HIV-2 cDNA sequence determination and the detection of the antigen. The sequence of the isolated HIV-2 genomic RNA does not seem to be altered to the extent that the change will alter antibody binding. Furthermore, antibody from the same individual (even at 8 months from initial sampling) from whom HIV-2 was isolated did not react with the antigen of this strain. Those evidences imply that extremely low or non-production of the antibody may be due to suboptimal immune stimulation due to extremely slow HIV-2 replication. This low virus-load may be responsible for the negative antibody results in the HIV-2 carriers.
Xenopus laevis has three distinctive olfactory neuroepithelia. We examined the axonal projection from each of these epithelia to the olfactory bulb by Di-I labeling, and confirmed that the Xenopus primary olfactory pathways involve the dorsal pathway from the olfactory epithelium to the dorsal region of the main olfactory bulb, the ventral pathway from the middle chamber epithelium to the ventral region of the main olfactory bulb, and the vomeronasal pathway from the vomeronasal epithelium to the accessory olfactory bulb. We next examined expression patterns of glycoconjugates in the three olfactory pathways by lectin-histochemistry using 21 biotinylated lectins. Fourteen out of 21 lectins stained the Xenopus primary olfactory system. RCA-I stained the three olfactory pathways uniformly. PHA-E stained only the dorsal pathway. LEL, STL, PNA, ECL and UEA-I stained the dorsal pathway more intensely than the ventral pathway, and among them, only UEA-I stained the vomeronasal pathway. In contrast, s-WGA, DBA, SBA, BSL-I VVA, SJA and PHA-L showed intense stainings in the ventral pathway and moderate stainings in the vomeronasal pathway, but faint or weak stainings in the dorsal pathway. These observations suggest that the ventral pathway expresses glycoconjugates shared commonly with either the dorsal or the vomeronasal pathway. In addition, from the binding patterns of the lectins with a binding specificity for N-acetylgalactosamine, glycoconjugates containing this saccharide seem to play an important role for the organization of the olfactory pathways.
The histological disorders related to the focal disappearance of the epiphyseal growth plate were examined histochemically in the proximal tibia of rats administered a high dose of vitamin A. Animals were given 100,000 IU/100 g body weight/day of vitamin A for 5 days from 4 weeks after birth (VA rats) or given deionized water as control and sacrificed on Day 12 and 19 of the experiment. Tibiae were examined by immunohistochemistry for type I, II and X collagens, lectin-histochemistry for Helix pomatia and backscattered electron imaging. On Day 12, the abnormally developed calcified cartilage matrix was detected within the epiphyseal growth plate in VA rats. The uncalcified cartilage matrix contained type I collagen but lacked type II collagen. In addition, the eroded regions accompanied with numerous osteoclasts and osteoblasts were detected in the epiphyseal growth plate. On day 19, eroded regions penetrated the epiphyseal growth plate to result in its focal disappearances with the eroded surfaces entirely covered with bone tissue in VA rats. These findings suggested that the cartilage matrix of the epiphyseal growth plate was abnormally calcified and showed the phenotypes like bone matrix. The eroded regions of the epiphyseal growth plate seemed to be caused by the invasion of osteoclasts into the altered cartilage matrix and might develop to the focal disappearances by the modeling or remodeling due to action of osteoclasts and osteoblasts.
Recently a novel biochemical method that uses an immunoassay to quantitate serum smooth muscle myosin heavy chain (SMMHC) levels was developed for diagnosis of aortic dissection.) The purpose of this study was to determine whether SMMHC released from the coronary arterial wall can be used to predict restenosis after percutaneous transluminal coronary angioplasty (PTCA). Fifty-two consecutive patients undergoing successful PTCA for single vessel disease were examined (40 men, 12 women, 63 +/- 8 years). Intracoronary blood samples were obtained distal to the lesion, and from the femoral artery after PTCA. In 10 patients, blood samples were taken immediately after the final balloon inflation, and 10 and 20 minutes after PTCA. SMMHC levels were measured by ELISA using SMMHC-specific monoclonal antibodies. Follow-up coronary angiography was performed 3 months after PTCA. Intracoronary serum SMMHC levels were significantly higher than those obtained from the femoral artery (10.6 +/- 1.5 vs 2.1 +/- 0.1 ng / ml, p < or = 0.001). Of 40 patients without apparent dissection, the 23 patients who did not develop restenosis in the follow-up study were found to have had higher levels of intracoronary SMMHC levels immediately after PTCA compared to the 17 patients with restenosis (15.2 +/- 2.9 vs 7.1 +/- 1.2 ng /ml, p < or = 0.05). We suggest that elevated intracoronary SMMHC levels after PTCA may reflect the extent of injury to the arterial wall. Intracoronary SMMHC may be a possible biochemical marker for the prediction of restenosis.
The VP7 and VP4 genes of two human group A rotavirus strains Mc323 and Mc345 with unique serologic and genomic properties, and isolated in Chiang Mai, Thailand, in 1989 [Urasawa et al. (1992) Journal of Infectious Diseases 166:227-234] were further characterized. The nucleotide and deduced amino acid sequences of the VP7 genes allowed the classification of both strains as serotype G9. The VP4 genes of both strains are 2,359 nucleotides in length and encode a protein of 775 amino acids like in most human rotaviruses. A comparison of the VP4 amino acid sequence of strain Mc323 with those of strain Mc345 and 24 human and animal rotaviruses representing 20 distinct VP4 genotypes reported to date showed that VP4 of Mc323 and Mc345 belong to genotype 19 previously reported for porcine rotavirus [Burke et al. (1994) Journal of General Virology 75:2205-2212]. To investigate the serological type (P serotype) of these VP4s, six reassortant viruses each containing a distinct VP4 gene characteristic of human rotaviruses and the VP7 gene of porcine rotavirus strain Gottfried (G4) were prepared, and antisera to these reassortants produced in rabbits. In neutralization tests, the P serotype of Mc323 was clearly differentiated from the five major P serotypes reported previously for human rotaviruses, suggesting that Mc323 and Mc345 represent a new human rotavirus P serotype tentatively called P11.
A 69-year-old man was examined at our hospital because of a sense of upper abdominal fullness. He was diagnosed as having stage IVb (H2P0N4T4) gastric cancer and treated with neoadjuvant chemotherapy. One course of the regimen consisted of 10 mg CDDP (day 1-5), 10 mg MMC (day 1), 250 mg 5-FU (day 1-20) and 50 mg ETP (day 6, 7). The patient underwent the regimen three times in succession. After the chemotherapy, his hepatic metastases showed necrotic changes and the swelling of the para-aortic lymph nodes disappeared on a CT scan. A histological examination revealed that the cancer cells had completely vanished both at the site of the hepatic tumor and the para-aortic lymph nodes. This combination chemotherapy, named PMFE therapy, is considered effective without serious side effects for gastric cancer in patients with non-curative factors.
The significance of exercise-induced ST segment depression in patients with left circumflex artery involvement was investigated by comparing exercise electrocardiography with exercise thallium-201 single photon emission computed tomography(Tl-SPECT) and the wall motion estimated by left ventriculography. Tl-SPECT and exercise electrocardiography were simultaneously performed in 51 patients with left circumflex artery involvement(angina pectoris 30, myocardial infarction 21). In patients with myocardial infarction, exercise-induced ST depression was frequently found in the V2, V3 and V4 leads. In patients with angina pectoris, ST depression was frequently found in the II, III, aVF, V5 and V6 leads. There was no obvious difference in the leads of ST depression in patients with myocardial infarction with ischemia and without ischemia on Tl-SPECT images. In patients with myocardial infarction, the lateral wall motion of the infarcted area evaluated by left ventriculography was more significantly impaired in the patients with ST depression than without ST depression(p < 0.01). Exercise-induced ST depression in the precordial leads possibly reflects wall motion abnormality rather than ischemia in the lateral infarcted myocardium.
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OBJECTIVES: This study evaluated whether dobutamine gated blood pool scintigraphy can predict improvement of cardiac sympathetic nerve activity and cardiac function. METHODS: Sixteen patients(10 men and 6 women, mean age 59 +/- 13 years) with dilated cardiomyopathy underwent dobutamine gated blood pool scintigraphy to measure left ventricular ejection fraction (LVEF) using tracer at 0, 5, 10 and 15 micrograms/kg/min before treatment. Patients were divided into good responders (LVEF increase > or = 15%) 8 patients(GR Group) and poor responders(LVEF increase < 15%) 8 patients (PR Group) after treatment with beta-blocker or amiodarone with a background treatment of digitalis, diuretics and angiotensin converting enzyme inhibitor. I-123 metaiodobenzylguanidine(MIBG) imaging to evaluate cardiac sympathetic nerve activity and echocardiography were performed before and at one year after treatment. MIBG imaging was obtained 4 hours after tracer injection, and the heart/mediastinum count ratio(H/M ratio) calculated from the anterior planar image and the total defect score(TDS) from the single photon emission computed tomography image. LVEF and left ventricular endo-diastolic dimension (LVDd) were measured by echocardiography and New York Heart Association(NYHA) functional class was evaluated. RESULTS: The GR Group showed TDS decreased from 28 +/- 6 to 17 +/- 12(p < 0.05), H/M ratio increased from 1.79 +/- 0.26 to 2.07 +/- 0.32(p < 0.05), LVEF increased from 29 +/- 8% to 48 +/- 10%(p < 0.01), and LVDd decreased from 65 +/- 4 mm to 58 +/- 5 mm(p < 0.05). In contrast, the PR Group showed no significant changes in TDS, H/M ratio, LVEF and LVDd. NYHA functional class improved in both groups. The improvement was better in the GR Group than in the PR Group. CONCLUSIONS: Dobutamine gated blood pool scintigraphy is useful to predict the improvement of the cardiac sympathetic nerve activity and cardiac function, and symptoms after treatment in patients with dilated cardiomyopathy.
The expression of topoisomerase II alpha (Topo II alpha) was investigated in six human glioma cell lines as a function of doubling time, cell cycle distribution, and sensitivity to an antineoplastic agent, etoposide (ETP). The Topo II alpha level was determined by immunohistochemical and flow cytometric studies using monoclonal antibody, 8D2, specific for Topo II alpha. In all cell lines, the Topo II alpha level correlated directly with sensitivity to ETP, but not with doubling time or percentage of cells in any phase of the cell cycle. These findings suggest that the cytocidal activity of ETP may be mediated by qualitative and quantitative changes in Topo II alpha in human glioma cells. We speculate that better knowledge of Topo II alpha expression in surgical specimens may lead to more individualized use of ETP in patients with malignant glioma.
OBJECTIVES: Several anatomical distances of Koch's triangle including the ablation site were measured and correlated with clinical features and slow pathway potentials in patients with atrioventricular nodal reentrant tachycardia to improve the avoidance of complete atrioventricular block. METHODS: Sixty consecutive patients (24 males and 36 females, mean age 47 +/- 12 years) with successfully eliminated atrioventricular nodal reentrat tachycardia were studied. The distances between the His-bundle area and the base of the coronary sinus ostium (Dis HBE-CS) and the distances between the successful ablation site and the base of the CS ostium (Dis SP-CS) were measured in both right anterior oblique and left anterior oblique views, and used to define the dimensions of Koch's triangle. The relationship between the slow pathway potentials at the successful ablation site and anatomical distances was estimated. RESULTS: The Dis HBE-CS in the right anterior oblique view was negatively correlated with patient age (r = -0.759, p < 0.001) and body mass index. In contrast, the Dis HBE-CS in the left anterior oblique view had only weak correlations with patient age and body mass index. The mechanism of the short Dis HBE-CS in the right anterior oblique view in elderly obese patients tended to change the shape of the tricuspid annulus from a circle to an ellipse, compressed by the ascending aorta and diaphragma. The Dis SP-CS in the right anterior oblique view associated with the low frequency potential (Haissaguerre's slow pathway potential) was longer than that associated with the high frequency potential (Jackman's slow pathway potential). CONCLUSIONS: Elderly obese patients had shorter distances between the proximal His-bundle area and the base of the coronary sinus ostium in the right anterior oblique view. In contrast, the Dis HBE-CS in the left anterior oblique view was not so narrow. Therefore, slow pathway ablation can be performed safely without complicated complete atrioventricular block, using both the slow pathway potential guided approach and the anatomical guided approach, especially in the left anterior oblique view.
S100A4 is known to be involved in cancer cell motility by virtue of its ability to activate nonmuscle myosin. E-cadherin has an important role in the homophilic cell-cell adhesion and is called an invasion suppressor gene. In the current study, we investigate the histological type and metastatic potential of gastric cancer from the aspect of the interrelationship of E-cadherin and S100A4 expression. Expression of E-cadherin and S100A4 in gastric cancer cell lines, primary gastric cancers, and their normal counterparts were analyzed by reverse transcription-PCR, Western blot, and immunohistochemical methods. S100A4 protein and E-cadherin were expressed in five of eight gastric cancer cell lines, and inverse expression of the two proteins are found in four cell lines. In the clinical specimens, E-cadherin mRNA expression in differentiated adenocarcinomas (88%, 14 of 16) was significantly more frequent than that in poorly differentiated adenocarcinomas (50%, 22 of 44; P = 0.015). Western blot analysis demonstrates that S100A4 protein expression in poorly differentiated adenocarcinomas was 1.6-fold higher than in well differentiated adenocarcinoma. Immunohistochemically, S100A4 expression was detected in 51 (55%) of 92 primary gastric cancers. Reduced expression of E-cadherin in primary tumors was found in 66 (72%) of 92 tumors. S100A4 expression in the poorly differentiated adenocarcinomas had a strong relation to positive lymph node involvement or peritoneal dissemination. Reduced E-cadherin expression showed a strong relationship with positive serosal involvement and infiltrating type. Tumors classified as a group with reduced E-cadherin and high expression of S100A4 reveal positive peritoneal dissemination, serosal involvement, and infiltrating type in the growth pattern. Furthermore, these tumors showed a strong correlation with the poorly differentiated adenocarcinoma. In contrast, tumors with preserved E-cadherin and low expression of S100A4 have a close relation to the well differentiated adenocarcinoma and a favorable prognosis. By the Cox proportional hazard model, S100A4 and E-cadherin tissue status was judged as an independent prognostic factor. S100A4 and E-cadherin tissue status may be a powerful aid in evaluating metastatic potential or the prognosis of patients with gastric cancer.
OBJECTIVE: After developing criteria for epidemic periods for 16 infectious diseases, we investigated temporal (annual and monthly) and geographical (regional) variation in epidemics. METHODS: Data from an infectious disease surveillance system for the years 1993 to 1997 were used for the analysis. The weekly number of patients per monitoring station was calculated from the data and used in developing criteria for an epidemic period. Based on these latter, we calculated the average number of epidemics occurring at each public health center in a year, an average length of the epidemic period, and the average number of patients per monitoring station reported during an epidemic period. These figures were used to explore temporal (annual, monthly) and geographical (regional) variation. RESULTS: With most diseases, the average number of epidemics occurring at a public health center was 0.3-0.5 per year and the average length of an epidemic period was 6-12 weeks. The average number of patients per monitoring station reported during an epidemic period differed according to the diseases. These indices showed that there were few annual differences, but great monthly differences, in most diseases. The average number of epidemics occurring in a public health center showed regional differences with some diseases. CONCLUSION: Temporal and geographical variation in epidemics for 16 infectious diseases was established by developing criteria for an epidemic period.
To evaluate salvaged myocardium of acute myocardial infarction (AMI), we performed rest 99mTc-tetrofosmin (TF) SPECT with rest Tl and Tc-pyrophosphate (PYP) dual SPECT within 10 days after admission in 19 patients with initial AMI, who all were reperfused successfully and without restenosis. TF SPECT was obtained at 15 minutes (E) after tracer injection, 4 hours later (D), and 5 months later (FU). We calculated the regional uptake score (RUS) of infarcted area estimated by Tc-PYP uptake and defined RUS(FU) of TF(FU) as salvaged myocardium, and then regarded RUS/RUS(FU) x 100 (%) as subacute predicted value of salvaged myocardium. Furthermore, we regarded the improvement of wall motion estimated by QGS method as the guidepost of myocardial viability. The subacute predicted value of TF(E) was 85 +/- 25%, which was significantly higher than 61 +/- 28% of Tl and 36 +/- 24% of TF(D) (p < 0.01). Sensitivity and specificity of myocardial viability based on the improvement of wall motion SPECT image were 78% and 73% for Tl, 90% and 87% for TF(E) and 52% and 87% for TF(D). TF myocardial early imaging in subacute period was useful to detect salvaged myocardium.