Monoataxia of upper extremity in motor cortical infarction.
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Biomedical subjects
Publications and source records attributed to K Noda.
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Canine cerebral arterial strips denuded of endothelium responded to nicotine and transmural electrical stimulation with relaxations, which were abolished by NG-nitro-L-arginine and methylene blue. Magnitudes of relaxation did not differ in the arteries contracted with prostaglandin F2alpha and sumatriptan, an effective therapeutic of migraine. Sumatriptan concentration-dependently contracted the arteries responding to 2 Hz stimulation with persistent relaxations, and the concentration of this 5-HT1B/1D/1F receptor agonist to overcome the relaxation averaged 1.06 x 10(-7) M. Acetylcholine inhibited the response to nerve stimulation due possibly to its action on prejunctional nitroxidergic nerves; the inhibition did not differ in the arteries contracted with prostaglandin F2alpha and K+. It appears that sumatriptan does not interfere with the release of nitric oxide from nerves but counteracts the neurogenic relaxation by functional antagonistic action on smooth muscle. Prejunctional inhibition by muscarinic receptor activation is unlikely associated with opening of neuronal K+ channels.
In order to elucidate the clinical significance of the erbB family, epidermal growth factor receptor (EGF-R), c-erbB-2, c-erbB-3 and c-erbB-4 in hepatocellular carcinoma (HCC), we investigated the expression of these proteins by means of immunohistochemistry for HCC as well as adjacent noncancerous lesions. EGF-R was expressed in 68% of the HCC examined and showed correlation with the proliferating activity, stage, intrahepatic metastasis and carcinoma differentiation. c-erbB-2 was expressed in only 21% of the cases and showed no relationships with the clinicopathological parameters. c-erbB-3 protein was observed in 84% of the HCC and 38.1% of the noncancerous lesions. Its expression in HCC was equal to or greater than noncancerous lesions in 90.5% of the cases, and was related to the stage, portal invasion, cell proliferating activity, tumour size, intrahepatic metastasis and carcinoma differentiation. c-erbB-4 protein was expressed in 61.0% of HCC and in as much as 86.1% of the noncancerous lesions. Unlike the expression of c-erbB-3, that of c-erbB-4 in HCC was less than that of the adjacent noncancerous lesions in 51.2% of the cases. No statistical significance could be established between this protein expression in HCC and clinicopathological features. EGF-R and c-erbB-3 affected disease-free survival, but were not recognized as independent prognostic factors by multivariate analysis. The present study suggests that, of the four receptors, EGF-R and c-erbB-3 play important roles in the progression of HCC.
Previous reports have suggested that changes in oligosaccharide structures, especially beta1-6 branching in N-glycans, which are biosynthesized by UDP-N-acetylglucosamine:alpha mannoside beta1,6 N-acetylglucosaminyltransferase (GnT-V), are linked to tumor metastasis and invasion. In the present study, we investigated GnT-V expression in human hepatocellular carcinoma (HCC) tissues. High expression of GnT-V mRNA was observed in both HCC and the surrounding tissues but not in normal liver. Immunohistochemical study using a newly established monoclonal antibody against GnT-V revealed that positive staining of GnT-V was observed in 75% of HCC tissues and 60% of surrounding tissues and that liver cirrhosis showed much stronger staining of GnT-V than chronic hepatitis without liver cirrhosis (p = 0.0035). In contrast, all of 12 cases of atypical adenomatous hyperplasia diffusely expressed GnT-V. beta1-6 branching in N-glycans, products of GnT-V, was increased in HCC tissues with high expression of GnT-V, as judged by lectin blotting. Levels of GnT-V expression in HCC tissues were positively correlated with a low Ki-67 labeling index (p = 0.0009), small size (p < 0.0001), poor differentiation (p < 0.0001) and absence of portal invasion (p = 0.018). Furthermore, HCC cases with low or no expression of GnT-V were more likely to show recurrence than cases with high expression (p = 0.0373). These findings strongly suggest that GnT-V expression is concerned mainly with an early phase of hepatocarcinogenesis.
The enzyme GnT-III (beta 1,4-N-acetylglucosaminyltransferase III) catalyzes the addition of a bisecting N-acetylglucosamine (GlcNAc) residue on glycoproteins. Our previous study described that the transfection of GnT-lll into mouse melanoma cells results in the enhanced expression of E-cadherin, which in turn leads to the suppression of lung metastasis. It has recently been proposed that the phosphorylation of a tyrosine residue of beta-catenin is associated with cell migration. The present study reports on the importance of bisecting GlcNAc residues by GnT-lll on tyrosine phosphorylation of beta-catenin using three types of cancer cell lines. An addition of bisecting GlcNAc residues to E-cadherin leads to an alteration in cell morphology and the localization of beta-catenin after epidermal growth factor stimulation. These changes are the result of a down-regulation in the tyrosine phosphorylation of beta-catenin. In addition, tyrosine phosphorylation of beta-catenin by transfection of constitutively active c-src was suppressed in GnT-III transfectants as well as in the case of epidermal growth factor stimulation. Treatment with tunicamycin abolished any differences in beta-catenin phosphorylation for the mock vis à vis the GnT-lll transfectants. Thus, the addition of a specific N-glycan structure, the bisecting GlcNAc to E-cadherin-beta-catenin complex, down-regulates the intracellular signaling pathway, suggesting its implication in cell motility and the suppression of cancer metastasis.
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The effect of interleukin-4 (IL-4) on the induction of intestinal mast cells and cytokine profiles during Strongyloides ratti infection was studied using IL-4 knockout (IL-4 KO) mice. The antigen-specific proliferative response of mesenteric lymph node cells was not impaired in IL-4 KO mice. The number of intestinal mast cells induced in IL-4 KO mice during S. ratti infection was 2- to 3-fold lower than that observed in WT mice. Intestinal mastocytosis had disappeared in IL-4 KO mice by day 21 postinfection, when significant mastocytosis continued to be observed in WT mice. In mesenteric lymphnode of IL-4 KO, IL-3 production decreased and mice IFN-gamma production significantly increased as compared with those of WT mice. The numbers of eggs excreted per gram of feces (EPG) by IL-4 KO mice were greater than those excreted by WT mice on day 6 postinfection, but no difference was observed in the subsequent period. In conclusion, intestinal mast cells are induced during S. ratti infection in the absence of IL-4, and IL-4 is not essential for protection against intestinal adult worms of S. ratti.
BACKGROUND: It has been reported that the combination of gemcitabine (LY188011; GEM) and cisplatin (CDDP) in a 4-week schedule showed a high response rate for patients with non-small-cell lung cancer (NSCLC), but GEM could not be administered on day 15 because of increased myelosuppression in many patients. The present study was performed to evaluate the efficacy and safety of GEM and CDDP in a 3-week schedule. METHODS: Patients with unresectable NSCLC without prior chemotherapy were enrolled. We administered 1000 mg/m2 of GEM on days 1 and 8, and 80 mg/m2 of CDDP on day 1. The feasibility of the combination therapy was confirmed in 8 patients, and then 20 more patients were enrolled, to evaluate the efficacy and safety of this combination therapy for all 28 patients. RESULTS: The response rate was 42.9% (12/28) and the median survival time was 12.6 months. Neutropenia, leukopenia, anemia, thrombocytopenia or lymphocytopenia of grade 3 or higher were observed as hematological toxicity, and anorexia, nausea, fatigue, or vomiting of grade 3 were the nonhematological toxicities, but most of these toxicities were of grade 2 or less. For GEM and CDDP, 89% and 91% of the scheduled doses, respectively, were administered. CONCLUSION: This is the first study of the combination of GEM and CDDP with a 3-week schedule in Japan, and the results showed a low level of myelosuppression, high dose intensity, and high response rate, similar to the results reported in other countries. Accordingly, the combination of GEM and CDDP with a 3-week schedule may be a promising regimen for the treatment of NSCLC in Japan.
BACKGROUND: Little is known about the anatomic limitations of in situ right internal thoracic artery (RITA) grafting to the circumflex artery. METHODS: To evaluate the technical aspects and outcome of revascularization of the proximal and distal major branches of the circumflex artery (obtuse marginal [OM] branch and posterolateral [PL] branch), a total of 145 patients who possessed a graftable branch of the circumflex artery were enrolled into the prospective project. There were 73 patients who had the PL branch as a primary target and 72 patients with OM branches, which were allocated by a blinded observer who reviewed the preoperative angiography. RESULTS: Changes of primary target vessels were required in 9 patients (6.2%), yielding an overall success rate of RITA grafting of 93.8%. The success rates of RITA grafting to the OM branch and the PL branch were 95.8% (69/72; CI 88.3% to 99.1%) and 91.7% (67/73; CI 83.0% to 96.9%), respectively. The univariate analysis identified grafting under hypothermic ventricular fibrillation as predictors of inability to use in situ RITA grafting for revascularization of the circumflex artery. RITA grafting to the PL branch is not identified as a predictor. Postoperative angiography in 136 patients revealed only one occlusion (0.75%) of the RITA graft anastomosed to the marginal artery. There were no significant differences in patency rates between left and right ITA grafts. CONCLUSIONS: This prospective study showed that in situ RITA was, in most cases, able to reach most branches of the major circumflex artery and demonstrated an excellent patency rate.
Mechanisms underlying celiprolol-induced vasodilatation were analyzed in isolated porcine coronary arteries. Celiprolol induced dose-related relaxation of the artery rings with endothelium, an effect which was suppressed by N(G)-nitro-L-arginine methylester (L-NAME), nitric oxide (NO) scavenger, guanylate cyclase inhibitor, endothelium denudation, and removal of Ca(2+). L-NAME contracted, and superoxide dismutase relaxed, the arteries only when the endothelium was preserved. Neither superoxide dismutase nor beta-adrenoceptor antagonists changed celiprolol-induced relaxations. Celiprolol increased the cyclic GMP content in the tissue. The release of NO from endothelium, estimated by the extracellular production of cyclic GMP in arteries incubated in medium containing guanylate cyclase and GTP, was augmented by celiprolol, and L-NAME abolished this action of celiprolol. It is concluded that celiprolol elicits relaxation by acting on sites other than beta-adrenoceptors in the endothelium and by releasing NO, which activates soluble guanylate cyclase in smooth muscle and produces cyclic GMP. Scavenging of superoxide anions from the endothelium does not seem to account for the induced relaxation.
BACKGROUND/AIMS: The aim of this study was to investigate whether c-Src is involved in carcinogenesis and progression of human hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma. METHODS: We designed an immunohistochemical study using Clone 28, an antibody that specifically recognizes the activated form of c-Src. RESULTS: Hepatocytes in normal liver, chronic hepatitis with or without cirrhosis, atypical adenomatous hyperplasia, as well as bile ductular cells, and infiltrating mononuclear cells were all negative for immunohistochemical staining for the activated c-Src. Among 87 cases of HCC tested, 40 (46%) were positively stained for the activated c-Src, and this positive staining was inversely correlated with the Ki-67 labeling index (LI) (P = 0.0031), intrahepatic metastasis (P = 0.0099), TNM stage (P = 0.0062), alpha-fetoprotein (P = 0.0103) and epidermal growth factor-receptor expression (P = 0.0153). Positive staining for the activated c-Src was more frequently observed in well- or moderately-differentiated carcinoma (P = 0.0256). In multivariate analysis, the activated c-Src expression was independently related to the Ki-67 LI (P = 0.0197). In contrast to positive staining in HCC, cholangiocarcinoma were classified as negative in all 19 cases examined. CONCLUSIONS: These results strongly suggest the involvement of activated c-Src in early stages of HCC, and suggest that cholangiocarcinoma might employ different signaling mechanisms.
It is important to clarify the distribution of infected triatomine bugs in the endemic area of Chagas' disease for proper control. In the present study, we tried to detect T. cruzi kinetoplast DNA by PCR from dried triatomine feces collected from the house wall of an endemic area to assess the distribution of infected bugs more easily. The primers (P35/P36) were chosen to amplify the conserved region within the minirepeats of T. cruzi kinetoplast minicircle DNA. The kinetoplast DNA of T. cruzi could be actually detected in the dried feces collected from the wall of a brick-built house in Santa Cruz, Bolivia. Next, we examined the stability of T. cruzi kinetoplast DNA in the feces exposed to artificial environments. T. cruzi DNA was also detected by PCR in the feces left for 26 weeks at 25 degrees C and in those left for 4 weeks at 40 degrees C. The present study indicates that examination of dried feces on the wall can be an effective tool for surveillance of the natural infection of triatomine bugs that live in houses.
AlphaB-crystallin is known as a small heat shock protein with a cytoprotective function. This study was undertaken to investigate the relationship between alphaB-crystallin and changes seen in Alzheimer's disease. The distribution and immunohistochemical characteristics of alphaB-crystallin positive neurones in the cerebral cortices of 4 patients with Alzheimer's disease were examined. AlphaB-crystallin positive neurones were mainly distributed in the limbic and paralimbic regions, namely parahippocampal gyrus, fusiform gyrus, cingulate cortex, middle and superior frontal gyrus, and insular cortex, which corresponded to commonly affected regions in Alzheimer's disease. Moreover, such neurones were present predominantly in the III or V layer of the cerebral cortex. The number of alphaB-crystallin positive neurones increased in parallel with the neuronal loss. Logistic regression analysis revealed a significant relation between the density of alphaB-crystallin positive neurones and that of extracellular neurofibrillary tangles (NFTs), with a correlation coefficient (r) of 0.57 and P < 0.0001 in 14 regions of the cerebral cortex. In contrast, the relation was not statistically significant between the density of alphaB-crystallin positive neurones and that of classical senile plaques, diffuse plaques or intracellular NFTs. Modified Gallyas-Braak (GB) staining on alphaB-crystallin positive neurone demonstrated several patterns of the structures: faint GB positive structures in the swollen perikaryon with straight neurites, fine granules compressed and contorted into fuzzy bundles, intensely GB positive filamentous structures together with fine granules and very intensely GB positive ring-like NFTs in a swollen perikaryon with curved neurites. In positive neurones, the density of ring-like NFTs correlated with that of atrophic perikaryon, or bent neurites and a decrease in the immunoreactivity of alphaB-crystallin. These data suggest that a close relationship exists between the appearance of alphaB-crystallin in neurones, extracellular NFTs, and neurofibrillary formation in alphaB-crystallin positive neurones in Alzheimer brain.
In March 1982, a 60-old woman presented with an International Federation of Gynecology and Obstetrics grade 1, stage Ib endometrial adenoacanthoma, histological subtype of endometrial carcinoma. The patient underwent radical hysterectomy and was followed up for 10 years, without disease. In August 1998, an abnormal shadow in the right lung was suggested on a chest X-ray film at her routine health check-up and she came to our hospital for further evaluation. A thin-section computed tomographic scan of the chest suggested a malignant lung tumor, but the diagnosis remained tentative. Open biopsy was recommended, but the patient refused and was followed up on an outpatient basis. In November 1999, a thin-section computed tomographic scan of the chest revealed a slightly enlarged tumor and laboratory examination showed a high serum progastrin-releasing peptide concentration of 90.7 pg/ml. We performed partial resection of right upper lobe with video-assisted thoracic surgery. Pathological examination confirmed the lung tumor had metastasized from endometrial adenoacanthoma. Immunohistochemical stainings of estrogen receptor and progesterone receptor were positive both in the primary and lung tumor, only in the component of adenocarcinoma. After surgery, the serum progastrin-releasing peptide concentration remained unchanged. The patient is currently alive and free of disease.
The Purple leaf (Pl) locus of rice (Oryza sativa L.) affects regulation of anthocyanin biosynthesis in various plant tissues. The tissue-specific patterns of anthocyanin pigmentation, together with the syntenic relationship, indicate that the rice Pl locus may play a role in the anthocyanin pathway similar to the maize R/B loci. We isolated two cDNAs showing significant identity to the basic helix-loop-helix (bHLH) proteins found in the maize R gene family. OSB1 appeared to be allelic to the previously isolated R homologue, Ra1, but showed a striking difference at the C-terminus because of a 2-bp deletion. Characterization of the corresponding genomic region revealed that the sequence identical to a 5'-portion of OSB2 existed approximately 10-kb downstream of the OSB1 coding region. OSB2 lacks a conserved C-terminal domain. Restriction fragment length polymorphism analyses using an F(2) population indicate that both genes co-segregate with the purple leaf phenotype. A transient complementation assay showed that the anthocyanin pathway is inducible by OSB1 or OSB2. These results suggest that the Pl(w) allele may be complex and composed of at least two genes encoding bHLH proteins.
To clarify the clinicopathologic, molecular, and immunohistochemical characteristics of uterine isthmic endometrial cancer (UIE), we examined 13 cases of UIE and compared them with 33 cases of endometrial cancer of the uterine corpus (UCE) with respect to clinicopathologic factors, the expression of p53, the estrogen receptor (ER) and the progesterone receptor (PR) status, DNA ploidy, and microsatellite instability (MSI). Five (38.4%) of the UIE patients had stage I, two (15.4%) had stage II, and six (46.2%) had stage III disease (FIGO 1988). Myometrial invasion was confirmed in 92.3% of the UIE patients, and these patients had a higher (p < 0.05) frequency of > 50% myometrial invasion (46.2%) than the patients with UCE (15.2%). Moreover, the UIE patients had a higher frequency of positive peritoneal cytology (p < 0.05) and pelvic lymph node metastases (p < 0.05). No UIE tumors exhibited MSI, and the tumors in these patients had a higher expression of p53 (p < 0.01), a lower expression of ER (p < 0.05) and PR (p < 0.05), and a higher frequency of DNA aneuploidy (p < 0.01) than the UCE tumors. These findings suggest that the UIE is clearly different from UCE in the clinicopathologic, immunohistochemical features, and microsatellite status.
A synchrotron light source dedicated to medical applications has been designed at National Institute of Radiological Sciences. The storage ring, with circumference of 80 m, is designed for acceleration of 2.3 GeV and a stored current of 420 mA. It is equipped with two multipole wigglers to produce sufficient photon flux in a hard x-ray region required for medical applications. The purposes of the synchrotron light source are clinical performance of medical diagnoses clinically and research and development relating with medical applications. One of the most interesting applications for us is dual-energy x-ray computed tomography (CT). It gives the information about electron density of human tissue. The information plays an important role in advancing heavy-ion radiotherapy of cancers. Electron density can be derived from attenuation coefficients measured by different energy x rays. In this paper, a practical method of the dual-energy x-ray CT with synchrotron radiation is proposed with the theoretical consideration. The primitive experiment using monochromatic x rays emitted from radioisotopes proved the procedure of analysis mentioned here effective to derive electron densities from linear attenuation coefficients for two x rays of a different energy. The beamline dedicated to dual-energy x-ray CT is also proposed. It has a multipole wiggler as a light source and it mainly consists of a dual crystal monochromator and a rotating filter for attenuating photon flux of x rays and two-dimensional detector.