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Biomedical subjects

H Watanabe

Publications and source records attributed to H Watanabe.

At least 487 records · Page 27Linked to original sources

Stromal sialyl Le(a) expression is correlated with vascular invasion of human gallbladder adenocarcinoma.

Sialyl Le(a) antigen (CA19-9), a member of a family of high molecular weight glycoproteins, was originally described as a gastrointestinal- and pancreatic-specific tumor marker. Recent studies have demonstrated that sialyl Lea is a ligand for E-selectin and may play an important role in tumor metastasis. However, expression patterns of sialyl Le(a) have not yet been established in human gallbladder carcinomas. In this study, we examined sialyl Le(a) expression in human gallbladder adenocarcinoma and its clinicopathological significance. Sialyl Le(a) immunoreactivity was detected not only in cancer cells (cytoplasmic type; 68.5%, 37/54) but also in cancer stroma (stromal type; 46.3%, 24/54). According to TNM classification, stromal sialyl Le(a) expression was detected in 60. 0% (24/40) and 7.1% (1/14) of the T2-4 and T1 cancers, respectively (p<0.01). Stromal sialyl Le(a)-positive gallbladder cancers frequently showed lymphatic invasion, venous invasion and lymph node metastasis (62.9%, 62.5% and 70.0%, respectively) (p<0.01). These observations suggested that sialyl Le(a) expression plays important roles in vascular invasion and metastasis of human gallbladder adenocarcinomas.

Adenocarcinoma↗

[A temporal feature of memory for plans].

How do we remember future plans? In this study, three experiments were conducted to examine this issue. Thirty to forty different undergraduate or graduate students participated as subjects in each experiment. In Experiment 1, subjects were asked to memorize plans for a day, assuming that they were of tomorrow in the 'future' condition and that they were of yesterday in the 'past' condition. The result showed that plans for the morning and the evening were recalled better than plans for the daytime (the U-shape effect), only in the future condition. In Experiment 2, plans were presented without time, so that subjects could not use any specific schema associated with time. In this condition, the U-shape effect disappeared. In Experiment 3, subjects were required to memorize plans for two days, tomorrow and the day after tomorrow. The result showed the U-shape effect for each day, not for two consecutive days. These results lead to the conclusion that some 'temporal information' about a day may affect the memory for future plans.

Adult↗

Effect of Saireitoh on rabbit smooth muscle cell proliferation and experimental atherosclerosis.

Saireitoh is a traditional Chinese medicine that is often given to patients with nephrotic syndrome or glomerulonephritis. Studies have reported that Saireitoh stimulates intrinsic steroid secretion in rats and suppresses the proliferation of fibroblasts in vitro. We examined the effects of Saireitoh on vascular smooth muscle cell proliferation and migration in vitro and experimental atherosclerosis in vivo. Saireitoh rabbit serum obtained from New Zealand White rabbits which were given a diet containing 2% Saireitoh for 3 days significantly inhibited [3H]-thymidine incorporation by smooth muscle cells, which were isolated from thoracic aorta explants of rabbits. The addition of 10% Saireitoh rabbit serum to a culture medium containing smooth muscle cells inhibited DNA synthesis by 50% as compared with a control culture to which 10% normal rabbit serum was added. We also found that the number of smooth muscle cells in the culture containing Saireitoh rabbit serum was decreased. When PDGF was used as a chemoattractant, we demonstrated that Saireitoh rabbit serum slightly inhibits the migration of smooth muscle cells. In in vivo experiments, Saireitoh did not suppress the development of atherosclerosis but tended to reduce the damage. We concluded that although Saireitoh inhibited the proliferation of smooth muscle cells, the effect of prevention on the development of atherosclerosis is weak in the in vivo condition.

Animals↗

A case of small polypoid esophageal carcinoma with multidirectional differentiation, including neuroendocrine, squamous, ciliated glandular, and sarcomatous components.

A small composite esophageal carcinoma measuring 1.5 x 1.4 x 1.0 cm is described. The tumor had a polypoid elevation with a superficial extension. Histologic examination revealed invasion of the submucosal layer and multidirectional differentiation, including neuroendocrine, squamous, ciliated glandular, and sarcomatous components. The neuroendocrine component was strongly positive for chromogranin and formed the bulk of the polypoid tumor. The squamous cell carcinoma exhibited a superficial extension. The adenocarcinoma was located in a small region of the tumor and contained ciliated glandular cells. The spindle cell sarcomatous component, which was positive for alpha-smooth muscle actin and negative for cytokeratin, exhibited no specific mesenchymal differentiation. Each component was found in 60%, 10%, 5%, and 25% of the tumor, respectively. Cases of small composite esophageal carcinoma containing various carcinomatous and sarcomatous components are extremely rare.

Actins↗

Synthesis of pironetin and related analogs: studies on structure-activity relationships as tubulin assembly inhibitors.

Pironetin (1) and demethylpironetin (2) are potent inhibitors of tubulin assembly. They arrested the mammalian cell cycle in M-phase and showed antitumor activity against a murine tumor cell line, P388 leukemia, transplanted in mice. To investigate the chemical and biological properties of 1, we synthesized several derivatives and investigated the structure-activity relationships. All synthesized derivatives decreased biological activities, such as inhibition of cell cycle progression, and disruption of the microtubule network in situ. The most drastic decrease was observed in 6, 8 and 10. These results suggested that alpha,beta-unsaturated lactone, chirality at the 7-position bearing a hydroxyl group and the terminal portion of the alkyl chain are important for microtubule inhibitory activity of pironetins.

Animals↗

[Evidence based chemotherapy for lung cancer].

There is often little foundation for decisions in experience-based or impression-based medicine. Therapy, however, should be based on the highest level of available evidence. In many clinical cancer practices, "uncertainty" exists. When no evidence is available, it is important that we perform clinical trials to generate new evidence. Organizing multi-institutional clinical trials in Japan is an urgent necessity. Limited disease SCLC Concurrent radiotherapy in combination with cisplatin and etoposide is considered to be a standard treatment in limited disease SCLC. Extensive disease SCLC Chemotherapy regiments such as PE or CAV/PE are standard therapy for ED SCLC. There is no current evidence for alternating chemotherapy, dose intensive chemotherapy, high dose chemotherapy, late intensification chemotherapy or maintenance chemotherapy in extensive disease SCLC. New drugs in combination with cisplatin have been reported to show promising antitumor activity in extensive disease SCLC. The impact of CPT-11 + CDDP on survival may be discussed at the 2000 ASCO meeting. Surgically unresectable stage III NSCLC In a recent meta-analysis, cisplatin-based chemotherapy plus radiotherapy was compared with radiotherapy alone in prolonging survival. Cisplatin-based chemotherapy with or followed by radiation was proven to enhance survival. However, the optimal sequencing of chemotherapy and radiation has not been definitively established. Chemoradiotherapy with new drugs (paclitaxel, docetaxel, vinorelbine, gemicitabine, CPT-11) has been evaluated for activity and efficacy. Metastatic stage IV NSCLC Compared with the best supportive care alone, cisplatin-based chemotherapy yields an absolute improvement in survival. New drugs in combination with cisplatin or carboplatin have been reported to show promising antitumor activity. There is no combination therapy including a new anti-cancer agent which can be recommended as a "gold standard". There is no current evidence that either confirms or refutes non-platinum-based combination chemotherapy. Second line chemotherapy Second line chemotherapy (docetaxel 75 mg/m2) improves survival in patients previously treated with platinum-based chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Biosynthesis of Vicia graminea lectin- and Vicia unijuga lectin-binding glycoproteins in human tumor and nontumor cells and an estimation of its epitope structure.

We investigated biosynthesis of Vicia graminea lectin (VGA)- and Vicia unijuga lectin (VUA)-binding (Vgu) glycoproteins, which are human malignant tumor-associated antigens, in cultured human tumor and non-tumor cells by pulse-labeling experiments with [35S]-methionine, followed by immunoprecipitation using immobilized VUA, SDS-PAGE and autofluorography. It was shown that Vgu glycoproteins synthesized by tumor cells were 15-30 times greater than those of non-tumor cells. It was also shown that about 40-70% of Vgu glycoproteins synthesized by non-tumor cells were secreted from the cells while more than 80% of the antigen synthesized by tumor cells was not secreted, and that Vgu glycoproteins consisted of multiple molecular species with the same epitope. To estimate the epitope structure of Vgu glycoproteins, in preliminary experiments we prepared sialoglycoproteins and/or sialoglycopeptides from purified human glycophorin A. Human glycophorins A(M) and A(N) (GPs-A(M) and A(N)) were treated with Clostridium perfringens neuraminidase to remove all sialic acid residues linked to carbohydrate chains, with Newcastle disease virus (NDV) to remove alpha2-3 linked sialic acid residues, and by Edman's degradation to eliminate N-terminal amino acid of GP-As. Partial or complete desialylation reactions resulted in disappearance of the reactivity of GP-A(M) and GP-A(N) with corresponding antisera and in appearance of reactivities with VUA and VGA. Elimination of N-terminal amino acid of GP-As also resulted in appearance of reactivities with VUA. These results show that sialoglycoproteins with similar serological properties of Vgu glycoprotein could be prepared from GP-As, and suggest that the epitope structure of Vgu glycoprotein may be related to the MN blood type-epitope structure and its sialic acid residues at N-terminal moiety of GP-As.

Amnion↗

Salmonella typhimurium DT104 from livestock in Japan.

We examined the distribution of multidrug-resistant Salmonella enterica serotype Typhimurium definitive phage type 104 (DT104) among Japanese livestock from 1973 to 1998. The 144 S. Typhimurium field isolates were tested for susceptibility to ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, tetracycline, kanamycin, trimethoprim, nalidixic acid, and norfloxacin. Thirty-six of 68 strains which exhibited resistance to five or more antimicrobials (ACSSuT+) were identified as DT104. Results of plasmid profiling showed that all DT104 strains retain a 90-kb virulence plasmid, while 20 of 36 strains possessed a few additional small plasmids ranging from 2 to 4 kb. These results showed that DT104 strains have existed in Japanese livestock since 1990, and that this phage type may be an important pathogen for cattle in Japan.

Animals↗

International comparability of the pathological diagnosis for early cancer of the digestive tract: Munich meeting.

Large differences have been found between Western and Japanese pathologists' diagnosis of adenoma/dysplasia versus early carcinoma for gastric, esophageal. and colorectal epithelial neoplastic lesions. In this study we examined whether differences in experience in gastrointestinal pathology can to some extent explain these differences in diagnostic practice. Three Japanese, one British, and two German pathologists with much experience and one North American pathologist with less experience in routine diagnostic work reviewed 52 microscopic slides: 16 gastric, 24 esophageal, and 12 colorectal biopsy and resection specimens obtained from patients with lesions ranging from early carcinoma to adenoma, dysplasia, and regenerative epithelium. The extent of agreement between the diagnoses of the four individual Western pathologists and the most common Japanese diagnoses was assessed by kappa statistics. For the 16 gastric lesions, a diagnosis of suspected or definite carcinoma was made by the Japanese pathologists in 69%-75% of the slides, by three experienced Western pathologists in 56%-63% (high kappa values: 0.61, 0.64, 0.65), and by the less experienced Western pathologist in only 31% of the slides (low kappa value: 0.10). For the 24 specimens of esophageal squamous lesions, carcinoma in situ and suspected or definite carcinoma were diagnosed by the Japanese in 96%-100% and by the Western pathologists in 63%-88% of the slides (low kappa values: 0.17, 0.25, 0.25, 0.27). For the 12 colorectal lesions, the Japanese diagnosed suspected or definite carcinoma in 58%-83%, whereas all Western pathologists followed the World Health Organization definition of colorectal carcinoma and diagnosed suspected or definite carcinoma in only 0-42% of the slides (kappa values: 0.04, 0.10,0.12, 0.49). In conclusion, there were few differences in diagnoses between experienced Western and Japanese pathologists for gastric lesions but considerable differences for esophageal and colorectal lesions. The differences in the diagnosis of adenoma/dysplasia versus early carcinoma between Western and Japanese pathologists found in previous studies may in large part be attributable to differences in experience with regard to gastric neoplasia and to differences in interpretation and nomenclature with regard to esophageal and colorectal neoplasia.

Biopsy↗

Colony-stimulating factor-1 (CSF-1) rescues osteoblast attachment, survival and sorting of beta-actin mRNA in the toothless (tl-osteopetrotic) mutation in the rat.

We have shown that in the osteopetrotic rat mutation toothless (tl) osteoblasts are absent from older bone surfaces in mutants and that mutant osteoblasts in vivo lack the prominent stress fiber bundles polarized along bone surfaces in osteoblasts from normal littermates. Our recent data demonstrate that in normal osteoblasts in vitro beta- and gamma-actin mRNAs have different, characteristic intracellular distributions and that tl (mutant) osteoblasts fail to differentially sort these mRNAs. Because bone resorption and formation are highly interdependent and injections of CSF-1, a growth factor, increase bone resorption and growth in tl rats, we examined the effects of CSF-1 treatment on osteoblast survival and ultrastructure in vivo and ability to sort actin mRNAs in vitro. Neonatal CSF-1 treatment of mutants restores osteoblasts on older bone surfaces, normalizes the intracellular distribution of stress fibers in osteoblasts in vivo and promotes normal sorting of beta-actin mRNA in mutant osteoblasts in vitro without normalizing gamma-actin distribution. These data suggest the beta- and gamma-actin mRNAs in osteoblasts are sorted by different mechanisms and that the differential sorting of beta-actin mRNA is related to the characteristic polarization of stress fibers in osteoblasts and their survival on bone surfaces. This experimental system can be used to explore the relationships and regulation of these aspects of cell and tissue biology.

Actins↗

[Diagnosis--radiologic imaging].

One of the most important recent advances in imaging technology for the diagnosis of lung cancer is CT consisting of high-resolution and helical volumetric techniques. CT has made a detailed morphological analysis correlated with histopathology as well as the detection of small peripheral lung cancers possible. MRI still remains as a complementary role to CT, but MR angiography using fast gradient-echo technique has achieved a great progress. FDG-PET is the most encouraging development in nuclear medicine and is vigorously evaluated for its cost-effective clinical value in differentiating benign and malignant nodules as well as in staging of lung cancer. In chest radiography, the development of computer-aided diagnosis is underway and seems promising.

Humans↗

Steroid-induced short term diabetes in chick embryo: reversible effects of insulin on metabolic changes and cataract formation.

PURPOSE: To determine the reversible effect of insulin on glucocorticoid (GC)-induced cataract formation in relation to systemic metabolic changes in the developing chick embryo. METHODS: Hydrocortisone sodium succinate (HC; 0.25 micromoles) was administered to 15-day-old embryos followed by administration of long-acting recombinant human insulin, 4 and 28 hours later. At the indicated time after HC administration, the incidence of cataractous lenses and any changes in the components of the lenses, liver, and blood were determined. RESULTS: At 48 hours after HC administration, the following observations were made: opacification of lenses; an elevation of glucose and lipids in the blood and lenses; an increase in lipid peroxide (LPO) in the blood, liver, and lenses; a decrease in glutathione (GSH) in the lens and liver (at 24 hours after HC administration); and a depletion of adenosine triphosphate (ATP) in the liver. These changes in response to HC administration were reversed by a double application of insulin. CONCLUSIONS: Insulin antagonizes GC-induced gluconeogenesis, stimulates glycolysis, and ultimately leads to recovery of decreased activity in the citric acid cycle. The restoration of ATP by the recovered citric acid cycle may facilitate de novo synthesis of GSH, which in turn may diminish GC-induced elevation of LPO in the liver. Thus, the metabolic changes in response to HC-accelerated gluconeogenesis in the liver, which can be reversed by insulin, are likely to produce oxidative stress that leads to cataract formation. GC-induced metabolic changes in the liver, which are antagonized by insulin, may relate to production of one of the risk factors for cataract formation.

Adenosine Triphosphate↗

[Clinical features and etiology of community-acquired pneumonia at a general hospital between 1994 and 1997].

To characterize the clinical features and etiology of recently encountered cases of community-acquired pneumonia (CAP), we carried out a hospital-based retrospective study of 120 episodes of CAP (115 patients) at Tagami Hospital, Nagasaki City between 1994 and 1997. We identified the causative pathogens in 55 episodes (50 patients) by sputum Gram stain and quantitative culture, for a determination rate of 45.8%. Streptococcus pneumoniae (17 episodes) and Haemophilus influenzae (15 episodes) were the primary causative organisms. It is noteworthy that two major nosocomial pathogens, Pseudomonas aeruginosa (P. aeruginosa; 5 episodes) and Methicillin-resistant Staphylococcus aureus (MRSA; 2 episodes), were also identified as causative agents of CAP. These two pathogens were isolated from patients with severe underlying diseases and patients who had been repeatedly hospitalized. The incidence of CAP due to P. aeruginosa and MRSA is increasing because patients with respiratory colonization by these nosocomial pathogens are often followed up on an outpatient basis.

Adolescent↗

[CNS cryptococcosis with idiopathic CD4+ T lymphocytopenia].

A 33-year-old Japanese man, with a history of recurrent skin cryptococcosis, was admitted complaining of fever and severe headache for 3 weeks. He had no known risk factors for human immunodeficiency virus (HIV) infection. Cerebrospinal fluid examination revealed an elevated opening pressure of 32 cm H2O, cell counts of 884/mm3, a total protein value of 184 mg/dl, a glucose level of 16 mg/dl, and demonstrated a positive India ink stain for fungus. Cultures grew Cryptococcus neoformans. Hematological studies showed a persistently low CD4+ cell count (30/mm3) and a low CD4/CD8 ratio of 0.1. He has been repeatedly seronegative (ELISA and Western blot) for HIV-1 and HIV-2. He responded to fluconazole, and was given itraconazole as secondary prophylaxis because of persistent low CD4 counts. To our knowledge this is the first patient with idiopathic CD4+ T lymphocytopenia associated with CNS cryptococcosis in Japan. CD4 counts should be part of the initial work up for patients with CNS cryptococcosis.

Adult↗