[From the first to the 50th annual meeting of the Japanese Society for Virology and my concern for a bio-terrorism using a smallpox virus as a weapon].
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Biological Warfare↗
Biomedical subjects
S Kato
Publications and source records attributed to S Kato.
Diltiazem, a calcium antagonist, inhibits matrix metalloproteinase-1 (tissue collagenase) production and collagenolytic activity in human vascular smooth muscle cells.
Calcium antagonists (CAs) are widely prescribed for patients with cardiovascular diseases. CAs have been reported to inhibit smooth muscle cell (SMC) proliferation in addition to their effects on vascular tone. To determine whether CAs potentially affect vascular remodeling, we measured the expression of matrix-degrading enzymes in growth factor-stimulated SMC. Human cultured SMC were stimulated with 10 ng/ml of platelet-derived growth factor (PDGF)-BB with or without a calcium antagonist, diltiazem. In the cell counting assay, diltiazem (10-5 M) alone had no effect on the proliferation of quiescent SMC, however 10-6-10-5 M of diltiazem dose-dependently inhibited PDGF-stimulated SMC proliferation. The inhibitory effects of diltiazem on SMC proliferation were further confirmed by a 5-bromo-2'-deoxyuridine (BrdU) incorporation assay and flow cytometry. In Western blotting, matrix metalloproteinase (MMP)-1 (tissue collagenase) but not MMP-2 (72-kDa gelatinase) expression was upregulated by PDGF and phorbol ester (TPA), which were reduced by diltiazem in a dose-dependent manner. The downregulation of MMP-1 expression was consistent with the reduction of collagenolytic activity measured by a FITC-conjugated type I collagen breakdown assay. PDGF-stimulated c-Jun/AP-1 expression, a major transcriptional factor for MMP-1, was not affected by diltiazem. In contrast, intracellular calcium ions measured with a fluorometric assay of Fluo-3AM-loaded cells revealed that the PDGF-stimulated increase in the intracellular calcium content was dose-dependently reduced by diltiazem. Our data suggest that diltiazem inhibits not only proliferation but also MMP-1 expression and collagenolytic activity in PDGF-stimulated SMC. The administration of CAs potentially influences the process of vascular remodeling, and this possibility should be further verified in vivo.
Blotting, Western↗
Expression of G1 cell cycle markers and the effect of adenovirus-mediated overexpression of p21Waf-1 in squamous cell carcinoma of the esophagus.
To determine the crucial abnormality in the cell cycle regulatory proteins in human squamous cell carcinoma of the esophagus, we examined the cell growth ratio (CGR) and basal expression levels of G1 cyclins (cyclin D1, cyclin E), cyclin-dependent kinase (cdk) 2, cdk4, proliferating cell nuclear antigen (PCNA), and p21Waf-1 using 9 cell lines (KE3, KE4, TE8, TE9, TE10, TE11, YES1, YES2, and YES6). Western blotting revealed an inverse linear correlation between the basal levels of p21Waf-1 expression and CGR. The protein levels of G1 cyclins, cdks, and PCNA did not coordinately reflect the CGR. There was no relationship between p21Waf-1 expression levels and mutation of the p53 gene. Next, when the cells were stimulated with serum 48 h after the starvation, stimulated levels of the above G1 cell cycle markers were variously observed among cell lines irrespective of CGR. Serum stimulation markedly induced phosphorylated Rb in TE9 (a high CGR cell line, CGR>2.0), but not in KE4 (a low CGR cell line, CGR<1.5). Furthermore, adenovirus-mediated expression of exogenous p21Waf-1 effectively reduced cell growth in KE3 and TE9 (high CGR cell lines), but not in KE4 and TE11 (low CGR cell lines). p21Waf-1-mediated growth suppression was associated with the induction of involucrin, a marker of squamous cell differentiation. Our data suggested that the basal level, but not the stimulated level, of p21Waf-1 expression play a pivotal role in abnormal growth in human squamous cell carcinoma of the esophagus.
Adenoviridae↗
[Epidemiology and clinical role of childhood Helicobacter pylori infection].
Colonization of Helicobacter pylori depends on virulence factors of the organism, host factors and environmental factors. The prevalence of H. pylori differs between developing and Western developed countries, suggesting that the socioeconomic status influences the acquisition of the infection. The prevalence of Japanese children has been almost equal to that of Western countries. Although a main mode of transmission remains unclear, childhood is critical for acquisition of the infection. H. pylori causes gastritis (especially nodular gastritis) and duodenal ulcers in children but rarely gastric ulcers. No pediatric cases with H. pylori-associated gastric cancer have been reported. However, precancerous lesions including mucosal atrophy can develop in the infected children. Further studies in children are needed on strategy for H. pylori infection including prophylaxis of gastric cancer.
Child↗
"Internet delusion" in a patient with a schizoaffective disorder.
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Bipolar Disorder↗
Evaluation of the AMPLICOR CMV, COBAS AMPLICOR CMV monitor and antigenemia assay for cytomegalovirus disease.
The AMPLICOR CMV (qualitative DNA assay by PCR), COBAS AMPLICOR CMV Monitor (quantitative DNA assay by PCR), and antigenemia assay were tested for their ability to diagnose cytomegalovirus (CMV) infection in 115 immunocompromised patients. The AMPLICOR qualitative assay and the antigenemia assay were positive for all nine patients with a clinical diagnosis of CMV disease. The AMPLICOR quantitative assay was negative for one of the nine patients. In 106 patients without CMV disease, the AMPLICOR qualitative test was positive in 22, the quantitative test was positive in 23, and the antigenemia test was positive in 55 patients. The AMPLICOR qualitative and quantitative assays had specificities of 79% and 78% in patients without CMV disease, while that of the antigenemia assay was 48%. Diagnostic efficiencies were 79% for the AMPLICOR qualitative assay, 69% for the AMPLICOR quantitative assay, and 48% for the antigenemia assay. All three tests yielded positive results before, or at the same time as, the onset of CMV disease in most cases, which suggests they can be used to predict disease before the onset of symptoms. During antiviral treatment, test results tended to decrease quantitatively and finally became negative; negative results were followed by remission of symptoms. This suggests that the AMPLICOR quantitative assay and the antigenemia assay could be useful for monitoring therapeutic efficacy. The AMPLICOR qualitative and quantitative assays, as well as the antigenemia assay were considered effective for all of the following: diagnosing CMV disease, predicting the onset of disease, and evaluating the effectiveness of antiviral chemotherapy. The antigenemia assay was at times difficult to perform in the case of severely neutropenic patients, whereas the AMPLICOR assays could be used in such cases.
Antigens, Viral↗
[Unusual changes detected by iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid myocardial single photon emission computed tomography in the process of acute myocardial infarction: a case report].
Iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid myocardial single photon emission computed tomography(iodine-123 BMIPP myocardial SPECT) is useful for the diagnosis and evaluation of ischemic myocardial disease or cardiomyopathy. Changes in fatty acid metabolism in the post-myocardial ischemic state were evaluated using iodine-123 BMIPP myocardial SPECT. A 77-year-old woman was hospitalized for treatment of acute myocardial infarction. Emergency coronary angiography showed severe stenosis with delayed filling of contrast medium in the middle portion of the left anterior descending artery, so primary percutaneous transluminal coronary angioplasty was performed successfully. On the second day, iodine-123 BMIPP uptake was decreased slightly on the early imaging in the apico-anterior region, and increased slightly on the delayed imaging. On the seventh day, iodine-123 BMIPP uptake was decreased moderately or markedly in the apico-anterior region on the early imaging, and decreased markedly on the delayed imaging. Iodine-123 BMIPP myocardial SPECT subsequently became almost normalized. These unusual dynamic changes In iodine-123 BMIPP myocardial SPECT imaging may reflect metabolic changes of fatty acids in the ischemic state, the size of the triacylglycerol pool, and the degree of turnover in the triacylglycerol pool.
Aged↗
[Psychopathological study of twin schizophrenia from the viewpoint of twin interaction].
Schizophrenia research requires both genetical and environmental approaches. Some researchers have studied the environmental aspects of schizophrenia by comparing schizophrenic twins with non-schizophrenic ones in discordant pairs. But few studies have taken notice of the interaction between twins. This article focused on the unique relationship between twins, "inter-twin community", which might be considered one of the most important environmental factors. This study included 14 pairs of twins, 28 people including 17 schizophrenic patients. These inter-twin communities were divided into "close type" and "distant type" according to the closeness between the twins prior to the onset of schizophrenia. The close type, in which there was a high degree of closeness, included 8 pairs of twins, 16 people, 11 of whom were patients. The distant type, in which there was a low degree of closeness, included 5 pairs, 10 people, 5 of whom were patients. An additional sub-class of the close type was the "close-competitive type". This sub-type had a high degree of closeness and a high degree of competition, and included 1 pair, both of whom were patients. Eight out of the 11 patients in the close type (72.7%) had an excellent prognosis. In this type of inter-twin community the relationships gave patients a strong and stable protective environment. In the close-competitive type, the twins supported each other while one twin was having difficulty, but fought with each other when they recovered and eventually one twin relapsed, resulting in an alternating pattern of schizophrenic episodes. The twins were unable to separate from each other and they both had a poor prognosis; thus their relationship both provided the patients with a degree of protection and had a marked harmful effect. In the distant type, 4 of the 5(80%) patients had an poor prognosis. In this type, when one twin became ill, the other twin did not support them, and the relationship provided little protective effect, resulting in poor outcomes. The findings in this study support the idea that the nature of the inter-twin community has a strong influence on the course of schizophrenia in twins. Additionally, since all the female pairs belonged to the close type, and the male pairs tended to be the distant type, there are probable gender differences in the types of inter-twin communities. Finally, in making therapeutic plans for twin schizophrenics, it is very important to consider their relationship in terms of the inter-twin communities.
Adult↗
[Some questions to Dr. Takigawa's article (Part II)].
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Conditioning, Operant↗
[Intubation with a double lumen tube in patients with difficult airway using endoscopy mask, and tracheal tube guide].
A 71-year-old-man with pneumothorax was scheduled for a video-assisted-thoracic-surgery. He had received subtotal resection of the mandible and was anticipated to have difficult airway. Anesthesia was induced by fentanyl, midazolam, and maintained by 0.4% isoflurane in pure oxygen. The patient was ventilated using Endoscopy Mask, having a port for fiberscopy. A fiberoptic bronchoscope and an endotracheal tube can be passed through the port without significant air leakage during positive pressure ventilation. First, a single lumen orotracheal tube was passed through the port, and Endoscopy Mask was removed. Then, a Tracheal Tube Guide was inserted through the single lumen tube. After the tube had been removed, a double lumen tube was advanced into the trachea guided by the Tracheal Tube Guide. During this procedure oxygen saturation was maintained at 100%.
Aged↗
[Availability of NMP22 (nuclear matrix protein 22) for the diagnosis of urothelial cancer].
We evaluated the availability of NMP22 for the diagnosis of urothelial cancer. Of 154 patients with gross hematuria or microscopic hematuria, 14 patients with bladder cancer and 4 patients with upper urothelial cancer were detected. Of 73 patients continued to be followed for urothelial cancers, 11 patients with bladder cancer were detected. NMP22 was not available when a large number of RBC was present in urine. Also, NMP22 was significantly higher in patients with urothelial cancers. Interpretation of the ROC curve indicated an optimal cutoff value of 9.2 u/ml. Using 9.2 u/ml as a cutoff, the sensitivity and specificity were, respectively 87.0% and 64.0% in patients with hematuria, and 81.8% and 78.7% in patients with a history of TCC. This indicated that when NMP22 was used for the diagnosis of urothelial cancers, 12.0 u/ml, the value recommended as a cutoff in Japan, might be too high to differentiate patients with urothelial cancers.
Biomarkers, Tumor↗
Bisphenol a glucuronide, a major metabolite in rat bile after liver perfusion.
The environmental estrogen bisphenol A, orally introduced into the body, passes through the liver and modulates the endocrine system to elicit irreversible changes in the functioning of reproduction. To elucidate the actual and dynamic metabolism of bisphenol A in the liver before its arrival at target organs, this study evaluated the metabolism and disposition of the compound within the passage through the liver in Sprague-Dawley rats. On perfusion of 7.5 micromol of bisphenol A into the liver via the portal vein, approximately 91% of the infused bisphenol A was absorbed by the liver tissue, and about 65% of the absorbed bisphenol A was glucuronidated within 60 min. Roughly 65% of the bisphenol A glucuronide that formed in the liver was excreted into the bile and about 35% into the hepatic vein. On perfusion of 0.01, 0.05, and 0.1 mM bisphenol A solution into the liver, free bisphenol A was excreted only into the vein at 5.6, 9.3, and 14.6%, respectively, of the total bisphenol A. These results suggest that most bisphenol A absorbed by the intestine is probably glucuronidated exclusively in the liver and the conjugate is excreted mainly into the bile.
Animals↗
Rapid detection and typing of oculopathogenic strain of subgenus D adenoviruses by fiber-based PCR and restriction enzyme analysis.
PURPOSE: To develop a new detection and typing method of oculopathogenic strains of subgenus D adenoviruses directly from conjunctival scrapings by a combination of polymerase chain reaction (PCR) and restriction enzyme analysis (REA). METHODS: A new PCR method using primer pairs of AF2/AR2, which are specific for the fiber genes, were developed to amplify 1150-bp products from nine oculopathogenic prototypes of subgenus D adenoviruses. Amplicons were cleaved with three restriction enzymes: DdeI, HinfI, and RsaI. Clinical specimens of 102 conjunctival scrapings were also evaluated by this PCR method. Restriction patterns of prototypes were used for the typing of clinical samples. Detection limit was determined by the PCR amplification of a known amount of purified adenovirus serotype 8 DNA. RESULTS: A novel PCR method based on the fiber genes allowed the amplification of nine oculopathogenic serotypes of subgenus D (Ad8, Ad9, Ad15, Ad17, Ad19, Ad22, Ad28, Ad37, and Ad39). As little as 38.4 fg of adenovirus type 8 could be detected by this method. Positive results were obtained from 48 of 102 samples (47%) by both hexon- and fiber-based PCR, whereas only 29 of 102 (28.4%) yielded positive results by culture isolation/neutralization test (NT). All positive specimens (29 samples) of culture isolation and PCR-RFLP methods showed positive results by our new fiber-based PCR method, and no positive products were detected from other subgenus of adenovirus or nonadenoviral DNA. CONCLUSIONS: A newly developed fiber-based PCR-REA method for the detection and typing of adenoviruses is faster than any former PCR methods. This all-in-1-day detection and typing method will be quite useful to the rapid diagnosis of subgenus D adenovirus infection.
Adenovirus Infections, Human↗
Isolation of copper-binding proteins from activated sludge culture.
Six copper-binding microbial proteins were isolated from activated sludge cultures grown on media containing copper at various concentrations. Molecular weights among isolated proteins were ranged from 1.3k to 1 74k dalton. Isolated proteins were compared for their copper binding capabilities. Proteins isolated from cultures grown in the presence of copper in the growth media exhibited higher copper binding capabilities than those isolated from the culture grown in the absence of copper. The highest metal uptake of 61.23 (mol copper/mol protein) was observed by a protein isolated from a culture grown with copper at a concentration of 0.25 mM. This isolated protein (CBP2) had a molecular weight of 24k dalton. Other protein exhibited copper binding capability of 4.8-32.5 (mol copper/mol protein).
Carrier Proteins↗
Acute lethal injury of lung and liver in mice transplanted with ex vivo-expanded CTLs.
Clinical application of cytotoxic T lymphocytes (CTL) induced in vitro is extensively used for the treatment of viral infection and malignant diseases. We produced anti H-2d CTL in vitro from C57BL/6 (B6) splenocytes presensitized with (B6 x DBA/2) F1 (BDF1) splenocytes to establish a model system of CTL therapy. The specificity and cytotoxic activity were high enough (E/T ratio 1:1 = 38.8%) to induce graft versus host reaction. Though the total number of B6 splenocytes decreased by 0.27 during the 4 days of culture, the number of CD8+ lymphocytes increased 1.3-fold. When more than 5 x 10(6) cells of H-2d-reactive CTL were transplanted into BDF1 mice, mice died within 2 days postinduction. This lethal effect was not seen in the mice induced with ConA-stimulated T cells. Histological examination of the lungs and liver revealed massive infiltration of neutrophils in alveoli and the necrosis of hepatocytes. Therefore, this protocol was shown to be effective to produce alloantigen-specific CTLs and applicable to in vitro manipulation such as retrovirus-mediated gene transfer.
Animals↗
Variations in 5-fluorouracil concentrations of colorectal tissues as compared with dihydropyrimidine dehydrogenase (DPD) enzyme activities and DPD messenger RNA levels.
Dihydropyrimidine dehydrogenase (DPD) is the initial key enzyme in 5-fluorouracil (5-FU) catabolism. We measured DPD activities represented as DPD protein levels (units/mg protein) and the associated mRNA levels in tumorous and normal tissues from 40 colorectal cancer patients, and we studied the relation to 5-FU concentrations in the same samples after treatment with doxifluridine, a prodrug of 5-FU. DPD mRNA levels were also measured in biopsy samples before treatment for comparison with those in surgical samples. 5-FU concentrations in tumors were higher than those in normal tissues (P < 0.05) and were inversely associated with DPD protein levels (r = -0.463; P < 0.05). DPD activities in tumorous and normal tissues showed a significant correlation (r = 0.527; P < 0.01). DPD protein levels correlated with their mRNA levels detected by semiquantitative reverse transcription-PCR in tumor tissues (r = 0.740; P < 0.01). DPD mRNA levels in tumor biopsy specimens correlated with those in surgical specimens (r = 0.366; P < 0.05). These results suggest DPD activities in tumors to be predictive of 5-FU levels in colorectal cancer tissues and are reflected by DPD mRNA levels as measured by reverse transcription-PCR.
Antimetabolites, Antineoplastic↗
[Experimental gene therapy using p21/WAF1 gene in esophageal squamous cell carcinoma--adenovirus infection and gene gun technology].
p21/WAF1 (p21) inhibits the activity of the cyclin/cdk complex and controls the G1 to S cell phase transition. In the present study, we used a recombinant adenoviral approach and gene gun technology to introduce p21 into esophageal cancer cells in order to assess the effect of p21 on cell growth. Infection with the p21 adenovirus (AdV) using gene gun technology resulted in inhibition of TE9 and KE3 cell growth. The levels of involucrin, which is a marker of squamous epithelium differentiation, markedly increased at 48 h and 72 h after p21 AdV infection in TE9 cells. These results indicate that p21 plays an important role in esophageal cancer cell proliferation. Overexpression of the p21 gene can inhibit cell growth and induce differentiation in esophageal cancer cells. p21 gene therapy may prove beneficial in the treatment of esophageal cancer.
Adenoviridae↗
[A clinical perspective, a frontiers of PPAR function].
In developed societies, chronic diseases such as diabetes, obesity, atherosclerosis and cancer are responsible for most deaths. These ailments have complex causes involving genetic, environmental and nutritional factors. There is evidence that a group of closely related nuclear receptors, called peroxisome proliferator-activated receptors(PPARs), may be involved in these diseases. This, together with the fact that PPAR activity can be modulated by drugs such as thiazolidinediones and fibrates, has instigated a huge research effort in to PPARs. Here we present the latest developments in the PPAR field, with particular emphasis on the physiological function of PPARs during various nutritional states, and the possible role of PPARs in several chronic disease.
Animals↗