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Showing papers by "Kanazawa Medical University published in 1998"


Journal Article
TL;DR: A correlation was observed between FDG uptake and the degree of cell differentiation in adenocarcinoma of the lung and FDG PET may show negative results for BAC.
Abstract: The goals of our study were to establish PET accuracy wfth 18F-fluorodeoxyglucose (FDG) in finding localized formations of bronchioloalveolar lung carcinoma (BAC) and to investigate the correlation between FDG uptake and the degree of cell differentiation in adeno carcinoma of the lung. Materials: Twenty-nine patients with 30 adenocarcinomas of the lung (7 bronchioloalveolar lung carcinomas, 9 well differentiated, 2 well-moderately differentiated, 11 moderately differentiated and 1 poorly differentiated) were studied., All patients underwent thoracotomies within 4 wk after the FDG PET study. For qualitative and, sis, the degree of FDG activity in the tumors was visually scored using a five-point grading system: 0 = same to background activity, 1 = less than mediastinal blood-pool activity, 2 = same to mediastinal blood-pool activity, 3 = slightly greater than mediastinal blood-pool activity and 4 = substantially greater than mediastinal blood-pool activity. Foci of activity with Grades 2–4 were considered tumors. For semiquantitative analysis, standardized uptake values (SUV) were calculated. Results: In 7 BACs, 4 lesions (57%)showed negative results on FDG PET, while in 23 non-BACs, only 1 lesion (4%), which was a well-differentiated adenocarcinoma showed a negative result. BACs9 mean visual score (1.43 ± 1.27) was significantly lower than that of non-BACs (3.17 ± 1.03)(p = 0.001). The BACs9 mean SUV (1.36 ± 0.821) was significantly lower than that of well-differentiatedadenocarcinomas (2.92 ± 1.28)(p = 0.014); the mean SUV of well-differentiated adenocarcinomas was significantly lower than that of moderately differentiated adenocarcinomas (4.63 ± 1.86)(p = 0.031). No significant differences were apparent in average size among these three histologIC types. Conclusion: A correlatlon was observed between FDG uptake and the degree of cell diferentiation in adenocarcinoma of the lung. FDG PET may show negative results for BAC.

353 citations


Journal Article
TL;DR: The overexpression of AIM-1 in colorectal tumor cell lines is thought to have a causal relationship with multinuclearity and increased ploidy, and defects of pathways essential for mitotic regulation are important during human cancer development.
Abstract: Aurora- and Ipl1-like midbody-associated protein (AIM-1) is a serine/threonine kinase that is structurally related to Drosophila aurora and Saccharomyces cerevisiae Ipl1, both of which are required for chromosome segregation. A kinase-negative form of AIM-1 inhibits the formation of cleavage furrow without affecting nuclear division, indicating that the gene controls entry into cytokinesis during M phase in mammalian cells. A human gene that encodes the protein AIM-1 was overexpressed in colorectal and other tumor cell lines. The regulation of AIM-1 expression was cell cycle dependent in normal and tumor cells, and the maximum accumulation was observed at G 2 -M. Exogenous overexpression of wild-type AIM-1 produced multinuclearity in human cells, suggesting that the excess amount of AIM-1 had a dominant-negative effect on the overexpressing cells. In long-term culture of AIM-1-overexpressing cells, multiple nuclei in a cell were occasionally fused, and then an increased ploidy and aneuploidy were induced. Thus, the overexpression of AIM-1 in colorectal tumor cell lines is thought to have a causal relationship with multinuclearity and increased ploidy. Cytokinesis error caused by AIM-1 overexpression is a major factor in the predisposition of tumor cells to the perturbation of chromosomal integrity that is commonly observed in human neoplasia. Thus, defects of pathways essential for mitotic regulation are important during human cancer development.

337 citations


Journal ArticleDOI
TL;DR: Both 53BP1 and 53BP2 enhanced p53-mediated transcriptional activation and induced the expression of a p53 -dependent protein, suggesting that these proteins might function in signal transduction pathways to promote p53 activity.

215 citations


Journal ArticleDOI
01 Sep 1998-Diabetes
TL;DR: The Cox proportional-hazards model adjusted for age, sex, circadian BP pattern, duration of diabetes, therapy for diabetes, various diabetic complications, and hypertension demonstrated thatcircadian BP pattern and age exhibited significant, high adjusted relative risks for fatal events, and that diabetic nephropathy, postural hypotension, and pulmonary hypotension as well as circadian BP patterns exhibitedsignificant, highadjusted relative risks with respect to the occurrence of various nonfatal vascular events.
Abstract: To assess the significance of reversed circadian blood pressure (BP) rhythms as a predictive factor of vascular events in NIDDM, vital status after an average 4-year follow-up was determined in 325 NIDDM subjects in whom the circadian BP profile had been monitored between 1988 and 1996. Circadian BP rhythm was analyzed by the COSINOR (a compound word for cosine and vector) method, as previously described. After exclusion of 37 dropped-out subjects, 288 were recruited to the further analysis, of which 201 had a normal circadian BP rhythm (group N) and the remaining 87 had a reversed one (group R). There was no difference in sex, HbA1c, the prevalence of smokers, serum lipids, or serum electrolytes between groups N and R at baseline, whereas age, the prevalence of hypertension, serum creatinine, and diabetic complications were more pronounced in group R than in group N. During the follow-up period (which averaged 52 months in group N and 36 months in group R), fatal and nonfatal vascular (cerebrovascular, cardiovascular, peripheral vascular arteries, and retinal artery) events occurred in 20 subjects in group N and 56 in group R. Unadjusted survival times and event-free times were estimated by the Kaplan-Meier product-limit method, and there was a significant difference in both unadjusted survival and event-free survival rates between groups N and R (P < 0.001 each; log-rank test). The Cox proportional-hazards model adjusted for age, sex, circadian BP pattern, duration of diabetes, therapy for diabetes, various diabetic complications, and hypertension demonstrated that circadian BP pattern and age exhibited significant, high adjusted relative risks for fatal events, and that diabetic nephropathy, postural hypotension, and hypertension as well as circadian BP pattern exhibited significant, high adjusted relative risks with respect to the occurrence of various nonfatal vascular events. These results suggest that reversed circadian BP rhythm is associated with occurrences of both fatal and nonfatal vascular events in NIDDM subjects.

196 citations


Journal Article
TL;DR: The results suggested that ROS from leukocytes including O2- plays an important role for continuous and excessive production of chemotactic factors, leading to chronic inflammation and hyperplasia, which are inhibitable by ACA.
Abstract: Double applications of phorbol esters trigger excessive reactive oxygen species (ROS) production in mouse skin. Previously reported data suggest that the two applications induce distinguishable biochemical events, namely, priming and activation. The former is characterized as a recruitment of inflammatory cells, such as neutrophils, by chemotactic factors to inflammatory regions and edema formation. The latter is responsible for ROS generation. Thus, inhibitory effects of 1'-acetoxychavicol acetate (ACA), previously reported to be a superoxide generation inhibitor in vitro, on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative stress and inflammatory responses in mouse skin model were examined using a double application of ACA. We demonstrated that two pretreatments and pretreatment with ACA (810 nmol) in the activation phase suppressed double TPA application-induced H2O2 formation in mouse skin. ACA exhibited no inhibitory effects on edema formation and the enhancement of myeloperoxidase activity during the first TPA treatment, whereas the anti-inflammatory agent genistein administered at the same dose inhibited both biomarkers. No inhibitory potential of ACA for TPA-induced H2O2 formation in the priming phase was confirmed. On the other hand, in the in vitro study, ACA inhibited ROS generation in differentiated HL-60 cells more strongly than did 1'-hydroxychavicol, which showed no inhibition by pretreatment in the activation phase. In addition, allopurinol did not inhibit double TPA application-induced H2O2 formation in mouse skin. These findings suggest that the NADPH oxidase system of neutrophils rather than the epithelial xanthine oxidase system is dominant for the O2--generating potential in double TPA-treated mouse skin. ACA significantly inhibited mouse epidermis thiobarbituric acid-reacting substance formation, known as an overall oxidative damage biomarker. Moreover, histological studies demonstrated that ACA inhibited double TPA treatment-induced morphological changes reflecting inflammatory response, such as edema formation, leukocyte infiltration, hyperplasia, and cell proliferation. Furthermore, pretreatment with ACA but not 1'-hydroxychavicol in the activation phase inhibits double TPA application-induced increases in both number of leukocytes and proliferating cell nuclear antigen index. These results suggested that ROS from leukocytes including O2- plays an important role for continuous and excessive production of chemotactic factors, leading to chronic inflammation and hyperplasia, which are inhibitable by ACA. Thus, we concluded that O2- generation inhibitors are agents that effectively inhibit oxidative stress and inflammatory responses in mouse skin.

168 citations


Journal ArticleDOI
TL;DR: The present data suggest that the naphthoquinones, juglone and plumbagin, could be promising chemopreventive agents for human intestinal neoplasia.

161 citations


Journal ArticleDOI
TL;DR: The mutual phylogenetic relationships of these strains were demonstrated using internal transcribed spacer 1 (ITS1) region ribosomal DNA sequences from 37 stock strains and clinical isolates provisionally termed Trichophyton mentagrophytes complex in Japan and were applicable to the phylogenetic analysis of closely related strains.
Abstract: Using internal transcribed spacer 1 (ITS1) region ribosomal DNA sequences from 37 stock strains and clinical isolates provisionally termed Trichophyton mentagrophytes complex in Japan, we demonstrated the mutual phylogenetic relationships of these strains. Members of this complex were classified into 3 ITS1-homologous groups and 13 ITS1-identical groups by their sequences. ITS1-homologous group I consists of Arthroderma vanbreuseghemii, T. mentagrophytes human isolates, and several strains of T. mentagrophytes animal isolates. Five strains of Arthroderma simii form a cluster comprising ITS1-homologous group II. The Americano-European and African races of Arthroderma benhamiae, T. mentagrophytes var. erinacei, and one strain of a T. mentagrophytes animal isolate constitute ITS1-homologous group III. According to the phylogenetic tree constructed with Trichophyton rubrum as an outgroup, ITS1-homologous groups I and II comprised a monophyletic cluster and ITS1-homologous group III constituted another cluster which was rather distant from the others in the complex. This system was applicable to the phylogenetic analysis of closely related strains. Using this technique, human and animal isolates of T. mentagrophytes were also clearly distinguishable from each other.

147 citations


Journal ArticleDOI
TL;DR: The results suggest that mechanical stretch could evoke hypertrophic responses in cardiac myocytes that lack the AT1 signaling pathway possibly through tyrosine kinase activation.

135 citations


Journal Article
TL;DR: The findings suggest that the inhibitory effects of auraptene on AOM-induced colon tumorigenesis at the initiation level might be associated, in part, with increased activity of Phase II enzymes, and those at the postinitiation stage might be related to suppression of cell proliferation and lipid peroxidation in the colonic mucosa.
Abstract: In our previous short-term experiment, Citrus auraptene inhibited the development of azoxymethane (AOM)-induced aberrant crypt foci, which are precursor lesions for colorectal carcinoma. In the present study, the possible inhibitory effect of dietary administration of auraptene was investigated using an animal colon carcinogenesis model with a colon carcinogen AOM. Male F344 rats were given s.c. injections of AOM (15 mg/kg body weight) once a week for 3 weeks to induce colon neoplasms. They also received diets containing 100 or 500 ppm auraptene for 4 weeks in groups of "initiation" feeding, starting 1 week before the first dosing of AOM. The diets containing auraptene were also given to rats for 38 weeks in groups of "postinitiation" feeding. At the termination of the study (38 weeks), dietary administration of auraptene caused dose-dependent inhibition in AOM-induced large bowel carcinogenesis. Auraptene feeding during the initiation phase reduced the incidence of colon adenocarcinoma by 49% at 100 ppm (P = 0.099) and 65% at 500 ppm (P = 0.0075). Auraptene administration during the postinitiation phase inhibited the incidence of colon adenocarcinoma by 58% at 100 ppm (P = 0.021) and 65% at 500 ppm (P = 0.0075). Also, the multiplicity of colon carcinoma was significantly reduced by initiation feeding at a dose level of 500 ppm (P < 0.01) and postinitiation feeding at a level of 100 and 500 ppm (P < 0.05 and P < 0.01, respectively). Feeding of auraptene suppressed the expression of cell proliferation biomarkers (ornithine decarboxylase activity and polyamine content) in the colonic mucosa and reduced the production of aldehydic lipid peroxidation [malondialdehyde and 4-hydroxy-2(E)-nonenal]. In addition, auraptene increased the activities of Phase II drug-metabolizing enzymes (glutathione S-transferase and quinone reductase) in the liver and colon. These findings suggest that the inhibitory effects of auraptene on AOM-induced colon tumorigenesis at the initiation level might be associated, in part, with increased activity of Phase II enzymes, and those at the postinitiation stage might be related to suppression of cell proliferation and lipid peroxidation in the colonic mucosa.

134 citations


Journal ArticleDOI
TL;DR: Although dose-dependent effect was not found, citrus auraptene is effective in inhibiting the development of oral neoplasms induced by 4-NQO, and inhibition occurring during the post-initiation might be related to suppression of increased cell proliferation caused by 5-nitroquinoline 1-oxide in the oral mucosa.
Abstract: The modifying effects of citrus auraptene given during the initiation and post-initiation phases of oral carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. At 6 weeks of age, animals were divided into experimental and control groups, and fed the diets containing 100 ppm or 500 ppm auraptene. At 7 weeks of age, all animals except those treated with auraptene alone and control groups were given 4-NQO (20 ppm) in the drinking water for 8 weeks to induce tongue carcinoma. Starting 7 days before the 4-NQO exposure, groups of animals were fed the diets containing auraptene (100 and 500 ppm) for 10 weeks and then switched to the basal diet. Starting 1 week after the cessation of 4-NQO exposure, the groups given 4-NQO and a basal diet were switched to the diets mixed with auraptene (100 and 500 ppm), and maintained on these diets for 22 weeks. The other groups consisted of rats fed auraptene alone (500 ppm) or untreated rats. All rats were necropsied at the termination of the study (week 32). The incidences of tongue lesions (neoplasms and preneoplasms), polyamine levels in the tongue tissue and cell proliferation activity estimated by 5-bromodeoxyuridine (BrdU)-labelling index were compared among the groups. In addition, the activities of gluthathione S-transferase (GST) and quinone reductase (QR) in liver and tongue of rats gavaged various doses of auraptene (0, 200, 400 and 800 mg/kg body wt) for 5 days were assayed. Feeding of auraptene at both doses during the initiation phase caused a significant reduction in the frequency of tongue carcinoma (100 ppm auraptene, 91% reduction, P < 0.001; 500 ppm auraptene, 63% reduction, P < 0.05). When fed auraptene after 4-NQO exposure, the frequency of tongue carcinoma was also decreased (100 ppm auraptene, 100% reduction, P < 0.001; 500 ppm auraptene, 74% reduction, P < 0.01). The incidences of tongue severe dysplasia in these groups were significantly smaller than those in carcinogen controls (P < 0.05). There were no pathological alterations in rats treated with 500 ppm auraptene alone or those in an untreated control group. Dietary administration of auraptene significantly decreased BrdU-labelling index and polyamine concentrations in the oral mucosa (P < 0.05). In addition, auraptene administration significantly increased the activities of GST and QR in the liver and tongue. Although dose-dependent effect was not found, citrus auraptene is effective in inhibiting the development of oral neoplasms induced by 4-NQO. Thus, suppression by the initiation-feeding of auraptene might relate to elevation in the phase II enzymes GST and QR of the liver and tongue, and inhibition occurring during the post-initiation might be related to suppression of increased cell proliferation caused by 4-NQO in the oral mucosa.

92 citations


Journal ArticleDOI
TL;DR: The findings suggest that the Fas protein is reduced or not present on the cell surface in the primary lung tumors and is sequestered within A549 tumorigenic lung cells, and these alterations directly affect the cells resistance to Fas-mediated apoptosis.
Abstract: The Fas receptor and ligand initiate an apoptotic pathway. Alterations in this pathway within tumor cells can result in escape from apoptosis and immune surveillance. We evaluated Fas protein expression in 42 primary pulmonary adenocarcinomas, and Fas expression and function in the lung adenocarcinoma cell lines A549 and A427. Immunohistochemical analysis demonstrated Fas protein expression in 47.6% of the tumors; however, Fas-positive tumors demonstrated cytoplasmic staining without cell surface expression. Northern blot analysis indicated that levels of Fas mRNA were similar in Fas protein-positive tumors to levels in normal lung tissue, but were reduced in Fas protein-negative tumors. Soluble form Fas was not detected in the majority of these tumors either by RT-PCR or Western blot analysis. Cell surface Fas protein expression was minimal in A549 and A427 cell lines as determined by flow cytometry. Both cell lines demonstrated Fas mRNA expression by Northern blot analysis and abundant protein expression by Western blot analysis. Transfection of the Fas cDNA derived from A549 cells induced surface Fas protein in COS cells; however, stable transfection of a native Fas cDNA into A549 cells failed to induce surface Fas protein expression. Parental A549 cells and A549 cells transfected with a Fas expression vector were resistant to Fas-mediated apoptosis. Transgenic expression of a FLAG-tagged Fas cDNA in A549 cells, with visualization of the Fas-FLAG protein using confocal microscopy, demonstrated that the Fas-FLAG protein was retained within cytoplasmic portions of the cell and was not translocated to the cell surface. These findings suggest that the Fas protein is reduced or not present on the cell surface in the primary lung tumors and is sequestered within A549 tumorigenic lung cells, and these alterations directly affect the cells resistance to Fas-mediated apoptosis.

Journal ArticleDOI
TL;DR: It is concluded that the free radical-producing mitochondrial NADH-quinone oxidoreductase is a novel oxidation-reduction system participating in PQ toxicity, in good agreement with previous results showing that PQ selectively damaged Mt in vivo and in vitro, resulting in cell death.

Journal Article
TL;DR: MR sialography has the potential to produce diagnostic findings in the parotid gland ducts of patients with Sjögren syndrome and the results suggest that this method will augment and possibly replace X-ray sIALography.
Abstract: PURPOSE The purpose of this study was to evaluate the effectiveness of MR sialography of the parotid gland ducts in the diagnosis and staging of Sjogren syndrome. METHODS MR imaging was performed on a 1.5-T unit with a neck phased-array coil. MR sialographic source images were obtained using a heavily T2-weighted fast spin-echo sequence with spectral fat suppression. All images were analyzed on the basis of maximum intensity projection reconstruction. Five healthy control subjects and 51 patients with definite Sjogren syndrome (43 with primary disease and eight with secondary disease) were examined with MR sialography. A labial gland biopsy was performed in all patients and histopathologic grading was done by means of focal scores. The findings of MR sialography were compared with the results of labial gland biopsy to determine the effectiveness of the technique in the diagnosis and staging of Sjogren syndrome. RESULTS In all five control subjects, the main duct and the primary branching ducts of the parotid glands were clearly visible on MR sialographic images. In patients with Sjogren syndrome, a punctate, globular, cavitary, or destructive appearance was well seen within the parotid glands. Findings obtained at MR sialography correlated well with the results of labial gland biopsy. CONCLUSION MR sialography has the potential to produce diagnostic findings in the parotid gland ducts of patients with Sjogren syndrome. Our results suggest that this method will augment and possibly replace X-ray sialography.

Journal Article
TL;DR: Both techniques have clinical value for the noninvasive detection of primary lung cancer that is 2 cm or greater in diameter, however, if a PET camera is available, FDG PET is considered the method of choice for the evaluation of patients with suspected primary lung cancers that is less than 2 cm in diameter.
Abstract: UNLABELLED We compared the diagnostic value of [18F]2-fluoro-2-deoxy-D-glucose (FDG) PET imaging and 201Tl SPECT imaging in the detection of primary lung cancer and mediastinal lymph node metastases. METHODS Thirty-three patients with histologically-proven primary lung cancer were examined with both FDG PET and TI SPECT (early and delayed scans) within a week of each study. For semiquantitative analysis, the tumor-to-nontumor activity ratio (T-to-N ratio) was calculated. RESULTS Although both techniques delineated focal lesions with an increase in tracer accumulation in 28 patients, PET identified three additional patients in whom Tl SPECT images did not visualize any lesions on both early and delayed scans. In the detection of lung cancer of less than 2 cm in size, FDG PET provided higher sensitivity (six of seven, 85.7%) than did Tl SPECT early scan (one of seven, 14.3%) and delayed scan (four of seven, 57.1%). Neither technique visualized any lesions in two patients who had bronchioloalveolar carcinoma. The T-to-N ratio was significantly higher with FDG PET (10.39 +/- 6.63) than it was with Tl SPECT (early scan, 2.37 +/- 0.86; delayed scan, 3.01 +/- 1.01) (p < 0.0001), whereas there was significant positive correlation between the FDG T-to-N ratio and the thallium T-to-N ratio (p < 0.01). Twenty-two patients had thoracotomies. Regarding the staging of mediastinal nodes, FDG PET detected mediastinal lymph node metastasis that was negative on Tl SPECT, whereas both techniques excluded tumor involvement in enlarged node at CT. CONCLUSION Both techniques have clinical value for the noninvasive detection of primary lung cancer that is 2 cm or greater in diameter. However, if a PET camera is available, FDG PET is considered the method of choice for the evaluation of patients with suspected primary lung cancer that is less than 2 cm in diameter.

Journal ArticleDOI
TL;DR: Serum levels of soluble vascular cell adhesion molecule-1 and soluble E-selectin in patients with systemic sclerosis suggest that endothelial activation is involved in the development of this disease.
Abstract: SUMMARY Objective. To determine the serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) in patients with systemic sclerosis (SSc). Methods. Serum samples from 80 patients with SSc and 20 healthy control subjects were examined by a sensitive enzymelinked immunosorbent assay. Results. The serum levels of sVCAM-1 and sE-selectin were significantly higher in the patients with SSc than in the healthy controls. The serum levels of sVCAM-1 were correlated with the presence of pulmonary fibrosis, joint involvement and elevated erythrocyte sedimentation rate levels. The serum levels of sE-selectin were correlated with the presence of pulmonary fibrosis. Conclusion. These results suggest that endothelial activation is involved in the development of this disease. Scleroderma, or systemic sclerosis (SSc), is a general- activated endothelium [7, 15, 16 ]. Unlike that of other ized connective tissue disease which is characterized by endothelial adhesion molecules such as VCAM-1, microvascular obliteration and increased deposition of E-selectin expression appears to be restricted to endocollagen, resulting in fibrotic lesions [1, 2]. It had been thelial cells. The inflammatory cytokines TNF-a, IL-1, suggested that a vascular alteration might be the interferon gamma (IFN-c) and LPS are known to act triggering factor in its pathogenesis [3]. Many investig- as inducers and enhancers of E-selectin [17]. ators have suggested that the adhesive interactions of Recently, soluble forms of these molecules have been leucocytes with the endothelial cells and with the identified [17, 18]. High levels of soluble VCAM-1 extracellular matrix have a central role in the function (sVCAM-1) and soluble E-selectin (sE-selectin) have of the immune system [4]. These interactions are been detected in a variety of inflammatory and neocrucial in all diseases with immune dysregulation, plastic conditions [18‐22]. including SSc [5]. In the present study, we measured the serum levels In recent years, a number of the molecules which of sVCAM-1 and sE-selectin in patients with SSc, and mediate leucocyte‐endothelial adhesion have been investigated whether these levels were correlated with identified; these include vascular cell adhesion the clinical or serological features of this disease. molecule-1 ( VCAM-1) [6 ] and E-selectin [7]. VCAM-1 is a 105‐110 kDa single-chain glycoprotein

Journal ArticleDOI
TL;DR: Findings indicate that the 111/NT molecule possesses the receptor-recognition site structurally different from Okra/NT, probably causing a decreased specific toxicity.
Abstract: The neurotoxin of strain 111 (111/NT) associated with type B infant botulism showed antigenic and biological properties different from that (Okra/NT) produced by a food-borne botulism-related strain, Okra The specific toxicity of 111/NT was found to be about 10 times lower than that of Okra/NT The monoclonal antibodies recognizing the light chain cross-reacted with both neurotoxins, whereas most of the antibodies recognizing the carboxyl-terminal half of the heavy chain of Okra/NT did not react to 111/NT Binding experiments with rat brain synaptosomes revealed that 125I-labeled 111/NT bound to a single binding site with a dissociation constant (Kd) of 25 nM; the value was rather lower than that (042 nM) of 125I-Okra/NT for the high-affinity binding site In the lipid vesicles reconstituted with ganglioside GT1b, 125I-Okra/NT interacted with the amino-terminal domain of synaptotagmin 1 (Stg1N) or synaptotagmin 2 (Stg2N), fused with the maltose-binding protein, in the same manner as the respective full-length synaptotagmins, and the Kd values accorded with those of the low- and high-affinity binding sites in synaptosomes However, 125I-111/NT only exhibited a low capacity for binding to the lipid vesicles containing Stg2N, but not Stg1N, in the presence of ganglioside GT1b Moreover, synaptobrevin-2, an intracellular target protein, was digested to the same extent by the light chains of both neurotoxins in a concentration-dependent manner These findings indicate that the 111/NT molecule possesses the receptor-recognition site structurally different from Okra/NT, probably causing a decreased specific toxicity

Journal ArticleDOI
TL;DR: It is proposed that a unilateral lesion of the nucleus intercalatus is sufficient to cause primary position upbeat nystagmus (ppUBN) and that the nuclei of this structure are a part of the vertical position‐to‐velocity neural integrator in the human ocular–motor system.
Abstract: We report on a patient who developed primary position upbeat nystagmus (ppUBN) due to a unilateral medial medullary infarction. On oculography, the slow phases of the nystagmus sometimes had an exponentially decreasing velocity waveform, indicating that the nystagmus was due to impairment of the vertical position-to-velocity neural integrator. On magnetic resonance imaging, the lesion was caudal to the vestibular nuclei and to the most rostral of the perihypoglossal nuclei, the nucleus intercalatus, a structure that was also involved in a previously reported case of ppUBN due to a unilateral medullary lesion. On the basis of these imaging and oculographic observations, we propose that a unilateral lesion of the nucleus intercalatus is sufficient to cause ppUBN and that the nucleus intercalatus is a part of the vertical position-to-velocity neural integrator in the human ocular-motor system.

Journal ArticleDOI
TL;DR: Rec recombinant viruses between these strains of the two subgroups are used to demonstrate that the DA L coding region of DA strain is important for virus growth in J774-1 cells, and indicates that L* protein may play a critical role in the DA-induced restricted demyelinating infection by allowing growth in macrophages, a major site for virus persistence.
Abstract: Strain GDVII and other members of the GDVII subgroup of Theiler’s murine encephalomyelitis virus (TMEV) are highly virulent and cause acute polioencephalomyelitis in mice. Neither viral persistence nor demyelination is demonstrated in the few surviving mice. On the other hand, strain DA and other members of the TO subgroup of TMEV are less virulent and establish a persistent infection in the spinal cord, which results in a demyelinating disease. We previously reported that GDVII does not actively replicate in a murine macrophage-like cell line, J774-1, whereas DA strain productively infects these cells (M. Obuchi, Y. Ohara, T. Takegami, T. Murayama, H. Takada, and H. Iizuka, J. Virol. 71:729–733, 1997). In the present study, we used recombinant viruses between these strains of the two subgroups to demonstrate that the DA L coding region of DA strain is important for virus growth in J774-1 cells. Additional experiments with a mutant virus indicate that L* protein, which is synthesized out of frame with the polyprotein from an additional alternative initiation codon in the L coding region of TO subgroup strains, is a key determinant responsible for the cell-type-specific restriction of virus growth. L* protein may play a critical role in the DA-induced restricted demyelinating infection by allowing growth in macrophages, a major site for virus persistence.

Journal ArticleDOI
TL;DR: Microstructural study revealed that all 3 cases of median raphe cysts had similar findings to those of the common urethral mucosa and contain features that to the authors' knowledge have not been previously reported.

Journal ArticleDOI
TL;DR: In this article, the distal part of the uterine artery was embolized with polyvinyl alcohol particles via catheterization of the right femoral artery, which resulted in considerable pain that required morphine analgesic medication and epidural analgesia.
Abstract: Background Therapeutic embolization of the uterine arteries has been successfully used to manage profuse gynecological hemorrhage. In the present study we aimed to investigate whether embolization of uterine arteries may serve as a safe and effective alternative treatment in cases of menorrhagia in fertile and perimenopausal women. As a first step, we have evaluated the methodology, patient reactions and effects on the uterine vasculature. Methods The distal part of the uterine artery was embolized with polyvinyl alcohol particles via catheterization of the right femoral artery. Total abdominal hysterectomy was performed the next day. Results Bilateral embolization in two patients resulted in considerable pain that required morphine analgesic medication and epidural analgesia. One patient was embolized unilaterally and experienced only slight discomfort with no need for analgesic medication at all, indicating that unilateral embolization is a well-tolerated method. After embolization, angiography showed stagnant flow in embolized vessels without contrast filling of distal branches. Angiography of the specimen showed normal vascular architecture in non-treated vessels. In treated vessels the main arterial trunks were patent but all smaller branches were occluded. Histology showed that most of the particles lodged in small arteries and that arterioles never showed injected material. Conclusion The study indicates that the procedure involves an efficient occlusion of uterine vessels and that unilateral embolization of uterine arteries is well tolerated.

Journal ArticleDOI
TL;DR: The factor analysis using principal factoring with an oblique rotation resulted in three factor structures that had different implications from the MBI: Emotional Ex exhaustion/Depersonalization, Personal Accomplishment, and Physical Exhaustion.
Abstract: This article presents an evaluation of the factor structures of the Japanese version of the Maslach Burnout Inventory (MBI). The MBI is a widely used psychometric instrument for measuring ‘burnout’ developed by Maslach and her co-workers. The MBI consists of four subscales: Emotional Exhaustion, Personal Accomplishment, Depersonalization, and Involvement. The MBI was translated into Japanese along with a back-translation and was administered to a sample of 267 nurses.Various psychometric analyses showed that the Japanese version of the MBI has high reliability for the 22 items scored for the frequency dimension. The factor analysis using principal factoring with an oblique rotation resulted in three factor structures that had different implications from the MBI: Emotional Exhaustion/Depersonalization, Personal Accomplishment, and Physical Exhaustion. The correlationship between the MBI and the General Health Questionnaire (GHQ), measures of depression, showed that burnout was a unique phenomenon.

Journal ArticleDOI
TL;DR: It is concluded that the protein villin is highly expressed in Barrett's adenocarcinomas and is well maintained in these and other esophageal tumors.
Abstract: Villin is a cytoskeletal protein that is involved in the formation of brush-border microvilli in normal small intestine and colon epithelium. This protein is present in Barrett's metaplasia but is reported not to be expressed in Barrett's adenocarcinoma. In this study, we analyzed villin protein expression in Barrett's metaplasia and in both Barrett's adenocarcinomas and tumors of the gastric cardia. Immunohistochemical analysis was used to evaluate the expression and cellular localization of the villin protein in 21 cases of Barrett's metaplasia, 30 cases of Barrett's adenocarcinoma, 16 cases of gastric cardia adenocarcinoma, and eight cases of adenocarcinoma of the distal esophagus. Southern, northern, and western blot analyses were used to evaluate the potential mechanisms for regulation of villin protein expression. Villin protein expression was observed in 21 of 21 cases (100%) of intestinal-type Barrett's metaplasia and in 28 of 30 cases (93%) of Barrett's adenocarcinoma and was thus highly expressed in these tumors. Northern blot analysis demonstrated villin mRNA (3.5 and 2.7 kb) in both villin-positive Barrett's metaplasia and adenocarcinomas. Western blot analysis with the antibody used for immunohistochemical analysis confirmed the presence of a single villin protein band of 95 kDa. Abundant villin expression also was present in both adenocarcinoma of the gastric cardia (13 of 16 cases; 81%) and distal esophageal adenocarcinomas of unknown origin (six of eight cases; 75%). The intestinal brush-border enzyme sucrase isomaltase was found to be present in only 22 of 46 cases (48%) of the adenocarcinomas that expressed villin. We concluded that the protein villin is highly expressed in Barrett's adenocarcinomas and is well maintained in these and other esophageal tumors. Mol. Carcinog. 22:182–189, 1998. © 1998 Wiley-Liss, Inc.

Journal ArticleDOI
TL;DR: This study suggests that patients with a sagittal diameter in the cervical spinal canal of less than 12 mm have a high risk of cervical myelopathy.
Abstract: The sagittal diameter of the cervical spinal canal on roentgenograms in normal adult Japanese aged 15 years or over, 505 males and 492 females, was investigated to define the normal distribution and lower limit. Lateral roentgenograms of cervical spinal canals were taken at a constant focus-film distance of 1.5 m. The mean ± SD magnification coefficient was 1.17 ± 0.02. The mean ± SD sagittal diameters of the cervical spinal canals at each vertebral level were: C-1, 21.0 ± 2.2 mm; C-2, 18.0 ± 1.7 mm; C-3, 15.8 ± 1.5 mm; C-4, 15.2 ± 1.5 mm; C-5, 15.3 ± 1.5 mm; C-6, 15.7 ± 1.5 mm; and C-7, 15.9 ± 1.4 mm. The lowest mean — 2 SD values were: C-1, 16.6 mm; C-2, 14.6 mm; C-3: 12.8 mm; C-4, 12.2 mm; C-5, 12.3 mm; C-6, 12.7 mm; and C-7, 13.1 mm. The smallest diameter was at the C-4 level, but there was no significant difference between values at the C-4 and C-5 levels. Males had significantly larger diameters than females (mean difference 0.8 mm) (p < 0.01). Younger subjects had greater diameters than older subjects. The incidence of spondylotic changes was 40.1% in subjects aged 50-59 years, 57.7% in those aged 60-69 years, and 76.6% in those aged 70-79 years. Males had a higher incidence than females. Ossification of the posterior longitudinal ligament was observed in 2.1% of all subjects. This study suggests that patients with a sagittal diameter in the cervical spinal canal of less than 12 mm have a high risk of cervical myelopathy.

Journal ArticleDOI
TL;DR: CMV can induce IL‐8, which can augment CMV replication directly and indirectly by counteracting antiviral activity of IFN, particularly that of α‐type against picornaviruses such as encephalomyocarditis virus and poliovirus.
Abstract: The observations that several types of viruses induced interleukin (IL)-8 production prompted us to investigate the interrelationship between IL-8 and cytomegalovirus (CMV) infection. CMV infection caused IL-8 production in a human monocytic cell line, THP-1, in dose- and time-dependent manners. Moreover, CMV induced IL-8 gene expression by concurrently activating transcription factors, NF-kappaB and AP-1. Furthermore, CMV infection of human fibroblast cell lines increased gene expression of a specific receptor for IL-8, CXCR1. IL-8 in turn enhanced CMV replication in a human embryonic fibroblast, MRC-5, in dose- and time-dependent manners. Augmented replication eventually culminated in the increased production of infectious CMV virions. Moreover, IL-8 can attenuate the antiviral activity of interferon (IFN), particularly that of alpha-type against picornaviruses such as encephalomyocarditis virus and poliovirus. The inhibitory effects were associated with reduced 2',5'-A oligoadenylate synthetase activity. These results would imply that CMV can induce IL-8, which can augment CMV replication directly and indirectly by counteracting antiviral activity of IFN.

Journal ArticleDOI
Takeshi Matsui1, Takahide Ota1, Y. Ueda1, M. Tanino1, S. Odashima1 
TL;DR: H SC-3 and HSC-3-M3 cell lines which have the same origin but different lymphatic metastatic capacities could be a useful model system for studying mechanisms involved in lymph node metastasis of human oral SCC.

Journal ArticleDOI
15 May 1998-Cancer
TL;DR: Five patients with B‐cell lymphoma complicated by HPS were studied for elevated serum cytokines, the association of EBV, and CD25 expression of lymphoma cells, suggesting that both EBV and proliferating T/NK‐lymphoma cells play significant roles in the development of HPS.
Abstract: BACKGROUND The recent recognition of the association of Epstein-Barr virus (EBV) with T-cell/natural killer cell (T/NK-cell) lymphoma has documented that particular types of EBV-containing T/NK-cell lymphoma are frequently complicated by hemophagocytic syndrome (HPS). This observation suggests that both EBV and proliferating T/NK-lymphoma cells play significant roles in the development of HPS. Cytokines released from neoplastic T cells are presumed to account for the activation of macrophages, which is followed by a complex cascade of cytokine production, resulting in full-blown HPS. Five patients with B-cell lymphoma complicated by HPS were studied for elevated serum cytokines, the association of EBV, and CD25 expression of lymphoma cells; the aim of this study was to verify whether the mechanisms of HPS development hypothesized for T/NK-cell lymphoma also operate in B-cell lymphoma. METHODS Sera were analyzed for the presence of inflammatory and immunoregulatory cytokines. Flow cytometry, immunohistology (IH), in situ hybridization (ISH), polymerase chain reaction (PCR), and Southern blot analysis were performed using bone marrow aspirates, biopsy specimens, and autopsy specimens. RESULTS Immunophenotypic and Southern blot studies verified that the lymphoma cells of all five patients were of B-cell lineage. Bone marrow aspirates demonstrated histiocytosis with extensive hemophagocytic activity. Marked elevation of serum cytokines and expression of CD25 were observed in all five patients. However, the results of PCR, ISH using EBER1 probe, and IH for latent membrane protein indicated that these lymphoma cells were free of EBV infection. CONCLUSIONS In patients with B-cell lymphoma, EBV infection is not necessarily required for the initiation of HPS. In this article, the pathogenesis of HPS assumed to be operative in B-cell lymphoma is discussed with reference to T/NK-cell lymphoma complicated by HPS. Cancer 1998;82:1963-72. © 1998 American Cancer Society.

Journal ArticleDOI
TL;DR: The results suggest that S. schenckiiisolates in North and South America mainly belong to Group A, which is based on the phylogeny of 20 mtDNA types constructed by estimating sequence divergences of mtDNA.
Abstract: Mitochondrial DNA (mtDNA) types based on restriction fragment length polymorphism (RFLP) patterns with HaeIII were investigated in clinical isolates of Sporothrix schenckii in North and South America. In addition to 14 mtDNA types (Types 1–14) so far reported, six new mtDNA types, Types 15–20 were found in this study. Type 3 was divided into two subtypes, Subtype 3A and Subtype 3B based on RFLP with Msp1. Type 14 was also divided into three subtypes, Subtype 14A, Subtype 14B and Subtype 14C based on RFLP with Hha1. Nineteen isolates in the United States consisted of 1 isolate of Type 1, 12 of Type 2, 2 of Type 4, 3 of Type 14 (1 of Subtype 14B and 2 of Subtype 14C) and 1 of Type 15. Twenty nine isolates in Venezuela consisted of 13 of Type 3 (Subtype 3B), 6 of Type 4, 1 of Type 18, 3 of Type 19 and 6 of Type 20. Thirteen isolates in Argentina consisted of 2 of Type 3 (Subtype 3A), 4 of Type 4, 4 of Type 16 and 3 of Type 17. One isolate in Brazil was Type 3 (Subtype 3A). Based on the phylogeny of 20 mtDNA types (Types 1–20) constructed by estimating sequence divergences of mtDNA, mtDNA types were clustered into two groups: Group A (Types 1–3, Type 11 and Types 14–19) and Group B (Types 4–10, Types 12–13 and Type 20). These results suggest that S. schenckiiisolates in North and South America mainly belong to Group A.

Journal ArticleDOI
TL;DR: Initial lens changes in cases with AD which may be occult cataractous findings were often detectable and significant numbers of patients with AD who have not yet shown manifest lens changes were found among the subjects.
Abstract: In order to know the initial lens changes that accompany atopic dermatitis (AD), 99 patients diagnosed dermatologically to have AD without any or with slight external ocular infl

Journal ArticleDOI
TL;DR: The pharyngeal cross-sectional area, defined as the region from the fauces to the glottis, posturally changed with successive decreases in the sitting, left lateral decubitus and supine positions, and did not correlate with either age or body size.
Abstract: Obstructive sleep apnea syndrome is ascribed to pharyngeal dysfunction, but there are only a few reports about the normal morphological values in this anatomical region. We measured the pharyngeal cross-sectional area and the compliance (collapsibility), using the acoustic reflection technique with air breathing, in 181 healthy subjects (age 21-69 years). We assessed their sex-related differences, and the effects of age, body size and body postures on these parameters. The pharyngeal cross-sectional area, defined as the region from the fauces to the glottis, posturally changed with successive decreases in the sitting, left lateral decubitus and supine positions. The area was significantly greater in male than in female subjects in the sitting position (p < 0.01), but no difference was present in the recumbent positions. The pharyngeal cross-sectional area did not correlate with either age or body size. The specific pharyngeal compliance was greater in the males than in the females (p < 0.01) and increased with age only in the male subjects.

Journal ArticleDOI
TL;DR: Fungi, including pathogenic species, were sensitive to FNQ with MICs similar to those of amphotericin B, and FNQ showed significantly lower MICs against methamphetamine-resistant Staphylococcus aureus than against methicillin-sensitive S. aUREus.
Abstract: Analogs of furanonaphthoquinone (FNQ) from Tecoma ipe Mart had MICs ranging from 1.56 to 25 μg/ml against gram-positive bacteria. FNQ showed significantly lower MICs against methicillin-resistant Staphylococcus aureus than against methicillin-sensitive S. aureus. FNQ inhibited Helicobacter pylori with an MIC of 0.1 μg/ml. Fungi, including pathogenic species, were sensitive to FNQ with MICs similar to those of amphotericin B.