Biomedical subjects
Publications and source records attributed to C Yoshida.
We examined the effect of an electric field strength gradient on DNA sequencing efficiency using capillary array electrophoresis. Several types of gradients were applied to DNA sequencing and tested in terms of read length and accuracy. Our original method improved the accuracy of DNA sequencing for longer fragments at high temperature.
BACKGROUND: A central question in vertebrate transcriptional regulation is how cis-regulatory modules, including enhancers, silencers and promoters, communicate with each other over long distances to mandate proper gene expression. In order to address this question we analysed protein/DNA interactions in the human beta-globin locus control region (LCR). One of the many proteins that are potentially implicated in LCR function is Bach1. Bach1 possesses a basic leucine zipper (bZip) domain, as well as a BTB/POZ domain that has been shown to be involved in the regulation of chromatin structure. Bach1 forms heterodimers with small Maf proteins through its leucine zipper and binds to Maf recognition elements (MARE). RESULTS: Using atomic force microscopy we visualized large looped DNA structures between MAREs located in different regulatory elements within the human beta-globin LCR that were mediated by Bach1/MafK heterodimers. The formation of these DNA loops required the Bach1 BTB/POZ protein interaction domain. Furthermore, in transfection studies we found that Bach1 repressed the enhancer activity of the LCR in a BTB/POZ domain-dependent manner. CONCLUSION: Our results suggest that Bach1 and other BTB/POZ transcription factors may represent a class of nuclear architectural proteins that mediate long range interactions between cis-regulatory elements in order to regulate gene expression.
Diabetic cataracts are thought to be caused by hyperglycemia associated with disturbed glucose metabolism. Diabetes mellitus often involves abnormal lipid metabolism in addition to abnormal glucose metabolism. To date, however, very few studies have counted hyperlipidemia as a risk factor for diabetic cataracts. The present study was undertaken to determine whether this abnormal lipid metabolism is a risk factor for diabetic cataracts in rats. Cataracts were caused by streptozotocin (STZ) administration in the ordinary diet or cholesterol rich diet fed rats. When rats with STZ (65 mg/kg)-induced diabetes mellitus were fed an ordinary diet, cataracts became evident at 9 weeks in 26.7% of animals, and increased to an incidence of 53.3% after 10 weeks of STZ treatment. However, in rats with STZ-induced diabetes mellitus that were fed a cholesterol rich diet to induce severe hyperlipidemia and low high density lipoprotein (HDL) cholesterol, cataracts were observed one week earlier, after 8 weeks of treatment, in 40.0% of animals, with an increase to a 53.3% incidence and an 86.7% incidence after 9 and 10 weeks of STZ treatment, respectively. Plasma glucose levels did not differ between the groups. These results suggest that hyperlipidemia and low HDL cholesterol are associated with an earlier onset and an elevated incidence of diabetic cataracts. We then investigated the relationship between plasma lipids and cataracts by STZ (45-85 mg/kg) administration. The results showed that the onset of cataracts correlated positively with plasma total cholesterol, triglyceride, non-HDL cholesterol and glucose levels, and negatively with HDL cholesterol levels. The results of this study suggest that hyperlipidemia and low HDL cholesterol levels may be risk factors for the onset of diabetic cataracts and that diabetic cataracts may be accelerated by hyperlipidemia and low HDL cholesterol in rats.
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Mesenteric tumor emboli have been rarely reported in the literature. Tumors associated with this phenomenon include aortic angiosarcomas, pulmonary neoplasms, Hodgkin's lymphoma, and renal cell carcinoma. In most cases, presentation is dramatic and death is rapid. We present a case of mesenteric tumor emboli from an aortic source that had a more subtle presentation with recurrent abdominal pain and leukocytosis.
Prostaglandin E2 (PGE2) was converted into prostaglandin B2 (PGB2) by alkaline treatment and quantitated by a novel and specific competitive enzyme immunoassay using an anti-PGB2 antibody and a biotin-PGB2 conjugate as a tracer. This assay was relatively specific for PGE1 and PGE2 (n-6 type); the reactivity for PGE3 (n-3 type) was below 2% of that for n-6 type, and was applicable to the quantitation of PGE2 synthesized in lipopolysaccharide-stimulated peritoneal macrophages from mice fed either a high linoleate or a high alpha-linolenate diet.
Monoesters with the ester groups at C-2 of pyrroloquinoline quinone (PQQ) and C-9 of imidazopyrroloquinoline (IPQ) were synthesized, and radical scavenging activities of coenzyme PQQ, IPQ compounds synthesized from PQQ and various amino acids, and monoesters of PQQ and IPQ were studied in vitro and in vivo. PQQ and PQQ monoesters had strong radical scavenging activity using ESR in in vitro experiments. The IC50 value for superoxide (O2-) was from 1 to 6 x 10(-8) M and that for the hydroxy radical (.OH) was from 4 to 6 x 10(-5) M. IPQ compounds and IPQ monoesters also showed radical scavenging activity. These compounds prevented injury during in vivo experiments, such as hydrocortisone-induced cataracts, endotoxin shock and CCl4-induced liver injury (isolated hepatocytes and rats). Especially, the monoesters of PQQ and IPQ prevented liver injury in rats equally by oral or intraperitoneal administration. These results suggest that PQQ functions as a radical scavenging factor in addition to being a cofactor of quinoprotein enzymes, and monoesters with the ester groups at C-2 of PQQ and C-9 of IPQ are developed as treatment or preventive medicine for disease caused by radical compounds on the basis of strong radical scavenging activities, absorbability into cells, toxicity, safety and chemical stability.
Multifocal tumors within the same parotid gland are very rare. We treated 13 patients with multiple tumorous lesions within the unilateral parotid gland. We evaluated the multiple nodules by CT-sialography or magnetic resonance imaging (MRI). These imagings showed clearly two or more distinct nodular-appearing lesions. Recurrent pleomorphic adenoma (6 patients) was predominant, followed by Whartin's tumor (3 patients). The other lesions were two differential parenchymal tumors (polymorphous low grade adenoma/adenoma) within the same gland, a malignant lymphoma, a squamous cell carcinoma metastatic to the gland, and a tuberculous lesion. On palpitation, 9 of the patients had an unilateral tumor, one a palpable parotid mass in the gland, and the other four had two or more tumors in the unilateral gland. The patients with intra-parotid lymph node and metastatic lesions had extra-parotid cervical adenopathy. The clinical features and the differential diagnosis of the unilateral multiple tumorous lesions of the parotid gland are discussed.
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Diabetic cataracts are thought to be caused by hyperglycemia associated with disturbed glucose metabolism. Diabetes mellitus often involves abnormal lipid metabolism in addition to abnormal glucose metabolism. To date, however, very few studies have counted hyperlipidemia as a risk factor for diabetic cataracts. The present study was undertaken to determine whether this actually is a risk factor for diabetic cataracts and to confirm that the onset of cataracts associated with diabetes mellitus can be suppressed by correction of hyperlipidemia. When rats with streptozotocin (STZ)-induced diabetes mellitus were fed an ordinary diet, cataracts became evident at 9 weeks in 26.7% of animals, and increased to an incidence of 73.3% after 10 weeks of STZ treatment. However, in rats with STZ-induced diabetes mellitus that were fed a cholesterol rich diet to induce severe hyperlipidemia, cataracts were observed one week earlier, after 8 weeks of treatment, in 36.0% of animals, with an increase to a 52.0% incidence and a 76.0% incidence after 9 and 10 weeks of STZ treatment, respectively. Hyperlipidemia was therefore associated with an earlier onset and an elevated incidence of diabetic cataracts. When the lipoprotein lipase (LPL) activator NO-1886 was administered to diabetic rats which had developed severe hyperlipidemia, they showed a decrease in plasma total cholesterol, triglyceride and non-high density lipoprotein (non-HDL)-cholesterol levels and an increase in high density lipoprotein (HDL)-cholesterol level, and the onset of diabetic cataracts was markedly suppressed. The results of this study suggest that hyperlipidemia and low HDL-cholesterol levels may be risk factors for the onset of diabetic cataracts, and that this onset can be suppressed if measures are taken to alleviate these risk factors. The LPL activator NO-1886 may be useful in preventing the onset of diabetic cataracts.
A case of internal herniation into a broad ligament pouch 5 months after obturator herniorrhaphy is reported. We believe this to be the first reported postoperative case of internal herniation into such a defect in the broad ligament following obturator herniation repair. Computed tomography was useful in the preoperative diagnosis.
In order to elucidate the analgesic mechanism of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-on e (T-614), its effects on the kinin-forming system were examined both in vivo and in vitro. T-614, at doses more than 10 mg/kg p.o., exhibited a significant inhibitory effect on the increased levels of bradykinin released into the pouch fluid of kaolin-induced inflammation in rats. In the kaolin-induced writhing response in mice, which is shown to be mainly dependent on the action of bradykinin, T-614 reduced not only the writhing frequency but also the peritoneal levels of bradykinin in a dose-dependent manner. Whereas, in the zymosan-induced writhing response in which prostaglandin I2 (PGI2) is shown to be an important mediator, it did not exert an obvious inhibition on either writhing responses or peritoneal PGI2 levels at a highest dose of 100 mg/kg. T-614 did not inhibit the activities of serine proteases, such as trypsin, thrombin, kallikrein and plasmin. Furthermore, it did not affect the kinin-forming enzymes of rat plasma in vitro. The above results suggest that the analgesic effects of T-614 may be partly mediated by the inhibition of bradykinin release in the local inflamed tissue.
In vitro effects of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-on e (T-614), a novel antiinflammatory compound, on the production of interleukin-1 (IL-1) and/or interleukin-6 (IL-6) by human monocytes and the THP-1 cells of a human monocytic cell line, were examined. T-614 inhibited the release of immunoreactive IL-1 beta from these cells stimulated with lipopolysaccharides (LPS) in a dose-dependent manner (0.3-30 micrograms/ml). The release of IL-6 from THP-1 cells, as determined by the assays for its hepatocyte-stimulating activities and immunoreactivities, was inhibited by T-614 with the IC50 values of 2.0 and 6.6 micrograms/ml, respectively. Northern blotting analysis using LPS-stimulated THP-1 cells indicated that the inhibitory effect of T-614 on IL-1 beta production is caused by the suppression of IL-1 beta mRNA expression. The inhibition of cytokine production by T-614 may provide an important insight into the additional mechanisms contributing to its antiinflammatory activities.
The in vitro and in vivo effects of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-on e (T-614, CAS 123663-49-0), a new antiinflammatory agent, on arachidonic acid metabolism were investigated in comparison with those of reference drugs. Although the inhibitory effect of T-614 on the synthesis of prostaglandins by rabbit renal microsomes was very weak (IC50 of 58 micrograms/ml), T-614 effectively inhibited the prostaglandin E2 (PGE2) generation by mouse fibroblasts stimulated with bradykinin with an IC50 value of 0.47 micrograms/ml. The suppressive effect of T-614 on the PGE2 generation in fibroblasts was also found when cells were stimulated with Ca ionophore A23187, but not when induced with arachidonic acid. T-614 suppressed the A23187-induced PGE2 generation by rat macrophages, but not the leukotriene B4 production. In addition, 5-lipoxygenase activities in guinea-pig peritoneal exudated cells were not inhibited. In in vivo experiments, at doses of more than 1 mg/kg, T-614 reduced the PGE2 contents in inflammatory exudate of rat carrageenin-sponge type inflammation, but it was almost inactive in inhibiting gastric prostaglandins production up to 100 mg/kg. T-614 also did not affect the urinary PGE2 excretion in rats, and slightly inhibited the thromboxane synthesis in rat blood. Furthermore, the convulsion-induced increase of PGE2 in mouse brain was inhibited by T-614. These data suggest that T-614 inhibits the production of cyclooxgenase-mediated products with apparently different mode from classical non-steroidal antiinflammatory drugs, and may partly explain the discrepancy in pharmacological properties between this compound and other drugs.
The antiinflammatory, analgesic and antipyretic activities of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-on e (T-614, CAS 123663-49-0) were investigated in various animal models and compared with those of nimesulide, indomethacin and ibuprofen. The antiinflammatory potency of T-614 on carrageenin-induced paw edema, paper disk granuloma and established adjuvant arthritis was greater than that of ibuprofen, but slightly lower than those of nimesulide and indomethacin. In acute inflammatory models, unlike indomethacin, T-614 suppressed the edemas provoked by dextran and bromelain in rats, but its inhibitory action on ultraviolet erythema in guinea-pigs was weak. Although the analgesic activity of T-614 was hardly demonstrated in writhing tests in mice, its potency against the inflammatory pain such as Randall-Selitto test, adjuvant-induced hyperalgesia and antigen-induced arthritic pain in rats was superior to that of ibuprofen. Moreover, it had a potent analgesic effect on urate-induced synovitis in dogs. T-614 exerted a prompt and strong antipyretic effect in both yeast-induced febrile rats and lipopolysaccharide-induced febrile rabbits. T-614 had virtually no gastrointestinal ulcerogenic action and did not affect water and sodium excretion in rats. T-614 is a novel antiinflammatory compound with different pharmacological properties from that of the reference drugs.
We report discovery of the lymphatic routes in the gastric cardia and adjacent diaphragm after producing a blockage in the descending lymphatic route in dogs. CH40 black carbon hydrate was injected into the cardia portion during operation followed by total gastric and diaphragm combined resection to investigate lymphatic routes. In the 12 dogs with a blockage, and an ascending route to the lower mediastinum was recognized in 4 cases, and lateral routes from the hiatus of the esophagus to the diaphragm in a further 3 of the 12 cases. The lateral route was considered to be a collateral lymphatic route of neo-lymphatic vessel. Further, we found that phrenic lymphatic flows went in multiple directions, whereas the lymphatic flow at the phrenic lumbar vertebrae went mainly in the direction of the esophageal opening or aortic opening, although there was some expansion to the mediastinal side or celiac side. Consequently, it was assumed that metastasis to the lateral direction besides the ascending route might occur in cases with cancer in the cardiac portion infiltrating to the hiatus of the esophagus.
Operative ultrasonography was performed during operations to improve the accuracy of diagnosing the extent of the spread of carcinoma of the stomach in the following areas: tumor invasion in the gastric wall (31 patients), para-aortic lymph node metastasis (30 patients) and hepatic metastasis (30 patients). The over-all diagnostic accuracy rates of operative ultrasonography were 81 per cent for determining the depth of tumor invasion, 80 per cent for carcinoma of the mucosa, 70 per cent for carcinoma of the submucosa, 83 per cent for carcinoma of the proper muscle, 80 per cent for carcinoma of the subserosa and 100 per cent for carcinoma of the extraserosa. The over-all accuracy of operative ultrasonography in diagnosing para-aortic lymph node metastasis was 93 per cent. In comparison with the results of preoperative studies, the accuracy (sensitivity) of operative ultrasonography was significantly superior in diagnosing metastasis to the lymph nodes. In three of 30 operations, preoperatively unrecognized and nonpalpable (occult) hepatic metastases were identified by operative ultrasonography. Operative ultrasonography provides more accurate information regarding the spread of carcinoma of the stomach, and thus may be helpful in deciding upon the type of surgical procedure or in avoiding unnecessary tissue dissection.
From 1979 to 1988, a total of 1083 patients with gastric cancer underwent resection at Kurume University Hospital. Among these cancers, 183 (16.8%) were located in the upper third of the stomach. Of these, 56 (5.2%) were adenocarcinomas in the esophagogastric (E-G) junction. Cancer in this area was designated as cardia cancer when the focus of the cancer was macroscopically located within 2 cm of the E-G junction line and the tumor was less than 8 cm in diameter. The incidence of early gastric cancer in the cardia was only 13%, while the incidence for stage III advanced cancer was high at 46%, and the positive lymph node metastasis rate was 59%. Thirty-nine (70%) were cured by resection with a 5-year-survival rate of 64%, while for non-curative resection, this was only 10%. Twenty-two cases of either advanced cardia or advanced CE cancer underwent combined resection of the diaphragm. The rate of invisible metastasis to the diaphragm was 20% in our experimental study. The two year-survival rate for a combined resection of the diaphragm was 64%, while the rate for those who did not undergo a required combined resection was 42%.