Biomedical subjects
Publications and source records attributed to T Sano.
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We examined whether a 70% pancreatectomy changes the morphofunctionality of pancreatic A cells in a model rat (Otsuka Long-Evans Tokushima Fatty [OLETF]) with non-insulin-dependent diabetes mellitus. Male OLETF rats aged 6 weeks were assigned to two groups: partial pancreatectomy (Px) and sham pancreatectomy (sham). The Px group was divided into three subgroups based on treatment received after surgery, which included treatment with nicotinamide, phlorhizin, or saline. As a control, their diabetes-resistant counterparts, Long-Evans Tokushima Otsuka (LETO) rats, were similarly treated and grouped. Six weeks after surgery, plasma glucagon responses to arginine- and insulin-induced hypoglycemia were examined. In addition, the glucagon content and morphological features of pancreatic A cells in Px-remnant and remnant-equivalent pancreata were investigated 7 weeks after surgery. A sustained nonfasting hyperglycemia was evident in Px OLETF rats, which was ameliorated by administration of nicotinamide. The glucagon content and A-cell mass were not decreased significantly in the remnant pancreas of saline- and phlorhizin-treated Px animals of either strain but increased in nicotinamide-treated animals compared with those in the remnant equivalent of the respective sham rats. The areas under the response curves of plasma glucagon (zigma IRG) during an arginine infusion test and 90 minutes of insulin-induced hypoglycemia were 1,010.7 +/- 72.9, 1,083.1 +/- 95.3, 1,029.6 +/- 65.0, and 1,779.8 +/- 226.9 pmol.L-1.min-1 versus 1,997.0 +/- 283.1,2,217.0 +/- 395.0, 1,479.6 +/- 78.0, and 3,466.4 +/- 174.0 pmol.L-1.min-1 in phlorhizin-, nicotinamide-, and saline-treated Px OLETF and sham OLETF rats, respectively. A similar trend was observed for differences in the response of pancreatic A cells to both stimuli among various groups of LETO rats. There was no significant difference in sigma IRGs during both tests between OLETF and LETO rats with similar treatments, except during an insulin tolerance test (ITT) in saline-treated Px rats. The magnitude of the plasma glucagon response to both stimuli in the test animals was roughly parallel to the glucagon content in the pancreas. These findings suggest that differences in the proliferation and responsiveness of pancreatic A cells between OLETF and LETO rats after a 70% pancreatectomy are not nearly as significant as compared with B cells.
Exercise training has been shown to be effective in preventing the development of non-insulin-dependent diabetes mellitus (NIDDM) in a model rat (Otsuka-Long-Evans-Tokushima Fatty [OLETF]). For determination of how long a preventive effect of exercise training against the development of NIDDM lasts in this model, six male OLETF rats each were assigned to training (1) for a whole experimental period, from 7 to 28 weeks of age (E-E); (2) for the first half of the period, from 7 to 15 weeks of age (E-S); and (3) for the second half of the period, from 16 to 28 weeks of age (S-E). In addition, eight male OLETF rats were given no exercise during the experimental period (S-S). At 28 weeks of age, E-E, E-S, S-E, and S-S rats, weighed averages of 514, 542, 557, and 669 g and had abdominal fat deposits of 13.9, 21.3, 38.2, and 76.0 g, respectively. At 28 weeks of age, the cumulative incidence of NIDDM in S-S was 100%, while none of the trained rats were diabetic. The glucose infusion rate (GIR) during a hyperinsulinemic euglycemic clamp test, an index of insulin sensitivity, in the E-E group was significantly greater than that in the S-S group. The values in the E-S and S-E groups were slightly, but not significantly, less than that in the E-E group. Morphologic studies on the pancreas of E-E rats and S-E rats showed minimal changes of islets, whereas sections of islets from E-S rats appeared slightly enlarged and fibrotic, although significantly less than those of islets of S-S rats. These results demonstrate that the preventive effect of excercise training against the development of NIDDM lasts for at least 3 months after the cessation of exercise in this model.
Condylar or subcondylar fractures are severe traumatic lesions of the temporomandibular joint (TMJ) but the damage to the intracapsular soft tissues is not fully defined. In this study, twelve joints in ten patients with condylar and subcondylar fractures of the TMJ between two and twelve days after injury, were examined by magnetic resonance imaging to evaluate the damage to the intracapsular soft tissues in the acute phase. The joint capsule and the retrodiscal tissue were both swollen and showed increased signal intensity. Tears were recognized in the capsule of the eight joints and in the retrodiscal tissue of six joints. All discs were displaced in an anteromedial direction along with the fractured condylar fragments, but tear (rupture) was not recognized. In all cases, high signal intensity was seen in the joint spaces, and haemarthrosis was recognized in six joints during open reduction surgery.
Oscillapeptin G, a tyrosinase inhibitor, was isolated from the freshwater toxic cyanobacterium Oscillatoria agardhii. The structure was determined to be 1 by chemical degradation and 2D NMR analyses.
Natural tetrameric streptavidin has two subunit interfaces; one is a strong interface between subunits in a tightly associated dimer, and the other is a weak interface between a pair of such dimers (dimer-dimer interface). To test whether strengthening the weak dimer-dimer interface could provide streptavidin with additional structural stability, covalent crosslinks were introduced between adjacent subunits through the dimer-dimer interface. Specific crosslinking sites were designed by site-directed mutations of His-127 residues that are in close proximity in natural streptavidin. The first and second streptavidin constructs have a disulfide bond and an irreversible covalent bond, respectively, between two Cys-127 residues across the dimer-dimer interface. The third variant is a hybrid tetramer consisting of two different streptavidin species, one having lysine and the other aspartic acid at position 127, which are covalently crosslinked. All streptavidin constructs with intersubunit crosslinks showed higher biotin-binding ability than natural core streptavidin after heat treatment. All of these crosslinked streptavidins retained bound biotin more stably than natural core streptavidin in guanidine hydrochloride at very acidic pH. These results suggest that the introduction of covalent bonds across the dimer-dimer interface enhances the overall stability of streptavidin.
OBJECTIVE: Previous studies of Pit-1 expression in human pituitary tumours have produced conflicting results. We have studied expression of Pit-1 mRNA in human pituitary adenomas, as well as in normal human and rat pituitaries, and results were compared with clinical, histological, and immunohistochemical features. In addition, expression of GH, PRL, and TSH-beta mRNA was also studied and compared with Pit-1 gene expression. MATERIAL AND METHODS: The adenomas consisted of 13 GH cell adenomas, 7 PRL cell adenomas, 3 TSH cell adenomas, 4 ACTH cell adenomas, and 10 clinically non-functioning adenomas. Expression of the Pit-1, its isoforms, and each hormone, was studied using the reverse transcription polymerase chain reaction. RESULTS: Pit-1 mRNA was expressed not only in normal human and rat pituitaries, but also in all GH, PRL and TSH cell adenomas. There was no correlation between Pit-1 transcripts and biological behaviour or histological findings in these three types of adenoma, suggesting that Pit-1 is generally required for the determination of cell phenotype but is insufficient for the regulation of hormonal activity and tumour growth in these pituitary adenomas. In addition, Pit-1 was also expressed in some ACTH cell (2/4) and non-functioning adenomas (7/10). Although there were no GH, PRL or TSH-beta transcripts in Pit-1 mRNA-negative ACTH cell and non-functioning adenomas, PRL mRNA was detected in all Pit-1 mRNA-positive ACTH cell adenomas and GH, PRL and/or TSH-beta mRNA were found in four of seven Pit-1 mRNA-positive non-functioning adenomas. In contrast, Pit-1 mRNA was expressed without any GH, PRL, or TSH-beta transcripts in only three non-functioning adenomas. These data suggest that expression of Pit-1 mRNA in these two types of adenomas can be mainly attributed to the presence of GH, PRL and/or TSH-beta mRNA expressing cells and that true Pit-1 transcripts found in non-functioning adenomas may be a rare event. Moreover, there were two cases which expressed Pit-1 alpha mRNA, but failed to show other Pit-1 isoform mRNA. There were, however, no clinical or histological differences between these two adenomas showing only Pit-1 alpha mRNA and the others expressing both Pit-1 alpha mRNA and other Pit-1 isoform mRNA. CONCLUSIONS: Pit-1 mRNA was expressed not only in GH, PRL and TSH cell adenomas but also in other types of adenoma. However, it is suggested that expression of Pit-1 mRNA in most ACTH cell and non-functioning adenomas can be attributed to GH, PRL and/or TSH-beta mRNA expressing cells. Further studies are necessary to elucidate the role of Pit-1 transcripts in the three non-functioning adenomas without GH, PRL and/or TSH-beta mRNA expression.
OBJECTIVE: Sixty-one of 83 patients with acromegaly treated between 1969 and 1993 were analysed retrospectively to clarify which early postoperative factors were significant predictors of a successful long-term outcome and which preoperative factors significantly influenced the early postoperative results. PATIENTS: Of the 61 patients, 30 were operated on before 1987 and 31 afterwards. A successful long-term surgical outcome was defined as a long-term mean basal GH level < 6 mU/l (comparable to < 3 micrograms/l), a normal IGF-I level, and normal GH dynamics. RESULTS: Overall, 59% of patients (37% before 1987 and 81% after) had an early postoperative mean basal GH level < 6 mU/l, and 56% (29% before 1987 and 77% after) met all three of the specified criteria for a successful long-term surgical outcome. Statistical analysis confirmed that GH dynamics and postoperative mean basal GH level < 6 mU/l were significant predictors of the long-term surgical outcome, whereas the postoperative IGF-I level alone was not. On the other hand, abnormal preoperative GH dynamics were normalized in all patients with a postoperative mean basal level < 6 mU/l. In addition, there were no patients showing an unsuccessful long-term outcome in those associated with both the early postoperative mean basal GH level < 6 mU/l and normalization of the IGF-I level. Therefore, measurement of the early postoperative mean basal GH level and the IGF-I level may be an economical and simple guide to predict the long-term surgical outcome. Moreover, multivariate analysis indicated that cavernous sinus invasion was an independent significant factor influencing the early postoperative outcome. CONCLUSIONS: Successful long-term surgical outcome may be predicted if early postoperative mean basal GH level is reduced to < 6 mU/l (< 3 micrograms/l) and IGF-I level becomes normal. This study also confirms that early diagnosis and treatment by an experienced endocrinologist and neurosurgeon can improve the operative results in patients with acromegaly.
Solitary fibrous tumor is a rare spindle cell neoplasm of adults that usually arises in the pleura, recently reported in other locations. The authors describe three cases of solitary fibrous tumors in adults that occurred as circumscribed masses in the somatic soft tissue, including the arm, back, and abdomen. Histologically, they were characterized by a proliferation of spindle cells separated by thick bands of collagen and prominent vascularity often showing a hemangiopericytoma-like pattern. The spindle cells, having low mitotic figures and little nuclear atypicality, exhibited a variety of growth patterns, including storiform, fascicular and herringbone, and nuclear palisading. Vimentin and CD34 immunoreactivities were observed in many spindle cells of all tumors. They had ultrastructural features of fibroblast and myofibroblast in two cases examined. Solitary fibrous tumors seem to represent distinct mesenchymal neoplasms that require us to identify their unusual location other than the pleura and be familiar with their histologic appearances for arriving at the correct diagnosis.
Among 4608 patients with gastric carcinoma treated during a 20-year period from 1971 to 1990, 328 (7.1%) were less than 40 years of age. The clinicopathologic features and treatment results in this young group were compared with those for older gastric carcinoma patients (40-79 years of age, control group). In the young group, the male/female ratio and the prevalence of tumors in the lower third of the stomach were both lower than in the control group, and undifferentiated-type adenocarcinomas with diffusely infiltrative growth predominated. The TNM stage distribution and the proportion of curative resections were similar in the two groups. The overall cumulative 5-year survival rates were also similar, although that of patients who underwent curative resection was higher in the young group, due probably to the low rate of death from other causes. There was no difference in the recurrence rates after curative resection between the two groups. Contrary to widely held belief, the prognosis of young patients with gastric carcinoma is not poorer than that of older patients if the disease is diagnosed at a reasonably early stage.
We present a case of very late and unusual recurrence of gastric cancer. Nine years following total gastrectomy for gastric carcinoma, a 57-year-old man presented with disseminated intravascular coagulation associated with bone marrow recurrence. The primary tumor was a signet ring cell carcinoma invading the subserosal layer with lymph node metastasis. The patient was treated with sequential administration of methotrexate and 5-fluorouracil and went into remission. After treatment, he survived 10 months. Autopsy revealed diffuse bone marrow infiltration and distant lymph node metastasis with signet ring carcinoma cells.
In 1993, mumps with a high incidence of aseptic meningitis became prevalent in Akita prefecture, Japan. Three mumps virus isolates obtained from the nonvaccine-associated cases lacked the BamHI restriction cleavage site of the P gene, like the Urabe strain (Yamada, A. et al, Vaccine 8: 553-557). However, four additional nucleotide substitutions were found in the determined region of 157 bp. Fourteen of 19 cases from which mumps virus showing the Urabe-like RFLP profile was detected were complicated with symptomatic meningitis, whereas there were only four cases of meningitis among 23 individuals infected with the wild type showing no Urabe-like RFLP profile (non-"Urabe-like" wild-type). The incidence of meningitis was over 70% among patients infected with the "Urabe-like" wild-type virus. The "Urabe-like" wild-type. disappeared after February 1994 in the epidemic area and was replaced by the non-"Urabe-like" wild-type. Patients infected with the "Urabe-like" wild-type lived in a closed colony, in which there were two instances of transmission between siblings. Thus this outbreak was transient and narrowly localized.
We have used fluorescence-labeled primers and an auto-sequencer to detect telomerase activity quickly and easily. The current procedure is superior to the original telomeric repeat amplification protocol in several respects: 1) the result is obtained in real time during electrophoresis, 2) semi-quantitative results are possible without using a photo-capture system, and 3) no radioisotope is needed.
Myofibroblasts have ultrastructural and functional characteristics intermediate between fibroblasts and smooth muscle cells. Previous studies indicated that most myofibroblasts express actin and vimentin but not desmin immunophenotypes. Two benign intramuscular myofibroblastic tumors which displayed a desmin-positive and actin-negative immunophenotype are reported. The tumors occurred on the back of a 45 year old man who had neurofibromatosis 1 and the thigh of a 37 year old man without neurofibromatosis. Both tumors were encapsulated and composed of short intersecting bundles of spindle cells in a collagenous background. Although the tumors were cellular, nuclear pleomorphism was minimal and mitotic figures were rare. Characteristically, most tumor cells were immunoreactive strongly for desmin and vimentin but gave negative staining for muscle-specific actin, alpha-smooth muscle actin, alpha-sarcomeric actin, myosin, S-100 protein, cytokeratins, and CD34. On electron microscopy, the tumor cells were characterized by short spindle-indented nuclei, abundant cytoplasmic intermediate filaments, prominent plasmalemmal pinocytosis and frequent cell coverage by basal lamina. Aggregation of thin myofilaments with focal condensations was identified occasionally. Although the tumors showed distinct morphological and immunohistochemical features enabling delimitation from other soft tissue lesions, they may overlap histologically with myofibroblastoma of the breast, lymph node and soft tissue, low grade malignant nerve sheath tumor, leiomyosarcoma, cellular schwannoma, inflammatory fibrosarcoma and nodular fasciitis.
The role of taurocholate, one of the major conjugated bile acids present in portal blood, in excretion of bilirubin from liver parenchyma to biliary and vascular compartments was studied in isolated perfused rat liver. Contents of bilirubin and carbon monoxide (CO) in the bile or venous effluents were determined by enzyme-linked immunosorbent microassay with the use of antibilirubin monoclonal antibody 24G7 and myoglobin-assisted spectrophotometry, respectively. In the presence of taurocholate, bilirubin excreted into the biliary compartment constituted greater than 90% of the total bilirubin excreted from the liver (0.26 nmol.min-1.g liver-1), corresponding to 60% of the outflow of CO into the venous effluents. In its absence, however, the total amount of bilirubin excreted into extrahepatic compartments was reduced to 27% of CO flux, and more than 90% of the excreted bilirubin was in the venous effluent. Thus a choleretic bile acid such as taurocholate is necessary for directional transport of bilirubin into bile in the perfused liver preparation.
Airway epithelial cells are known to produce a granulocyte/macrophage colony-stimulating factor (GM-CSF), which induces eosinophilic inflammation in bronchial asthma. Interleukin-4 (IL-4), IL-10, and IL-13 produced by Th2 cells are involved in the pathogenesis of bronchial asthma. To assess their contributions to airway inflammation, we examined their effects on GM-CSF production by bronchial epithelial cells. Human bronchial epithelial cells were obtained under bronchoscopy from 21 patients with various respiratory diseases and incubated with or without IL-4, IL-10, or IL-13. Then the GM-CSF concentrations in the cell-free supernatants were measured by enzyme-linked immunosorbent assay. Results showed that IL-4 and IL-13 stimulated GM-CSF production by the epithelial cells dose-dependently, whereas IL-10 did not. The eosinophil survival-stimulating activity in the culture supernatants was closely correlated with GM-CSF concentration and was neutralized by anti-GM-CSF antibody. Thus, IL-4 and IL-13 may contribute to airway inflammation by upregulating GM-CSF production by bronchial epithelial cells.
Idiopathic eosinophilic pneumonia (IEP) is characterized by the accumulation of eosinophils in the alveolar spaces and the interstitium of the lung, frequently accompanied by peripheral eosinophilia. To clarify the roles of adhesion molecules of eosinophils in the pathogenesis of eosinophilic pneumonia, we analysed their expression by eosinophil and T-lymphocyte populations in peripheral blood and bronchoalveolar lavage fluid (BALF) obtained from 11 patients with eosinophilic pneumonia, using flow cytometric methods. Cell differentials in BALF showed increased numbers of eosinophils, the increase correlating with the number of activated T-lymphocytes in BALF. The expressions of CD11a (lymphocyte function-associated antigen-1 (LFA-1)), CD11b (Mac-1), CD18, CD49d (very late activation antigen-4 (VLA-4)), and CD62L (L-selectin) by eosinophils in BALF were all lower than those of eosinophils in peripheral blood. In contrast, CD54 (intercellular adhesion molecule-1 (ICAM-1)) was expressed by eosinophils in BALF, but not by those in peripheral blood. These results indicate that intercellular adhesion molecule-1 expression by eosinophils in bronchoalveolar lavage fluid but not in peripheral blood may be induced by locally activated T-cells or macrophages and may be important in the pathogenesis of idiopathic eosinophilic pneumonia.