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Biomedical subjects

T Seki

Publications and source records attributed to T Seki.

At least 379 records · Page 21Linked to original sources

Cell-mediated immune-pancytopenia complicating primary Sjögren's syndrome.

A 64-year-old woman with mild bilateral parotid gland swelling and bilateral lower extremity purpura was admitted for evaluation of xerostomia and pancytopenia. The patient had an increased erythrocyte sedimentation rate, pancytopenia, and positive tests for antibodies to nuclear antigen, SS-A, and SS-B. Impaired cell-mediated immunity was also present. Bone marrow aspiration showed a hypoplastic marrow with an increased percentage of lymphocytes. A positive Schirmer's test and keratoconjunctivitis were also noted. A diagnosis of primary Sjögren's syndrome was made by sialography and histological salivary gland findings. Therapy with prednisolone improved the pancytopenia. Addition of the patient's peripheral blood mononuclear cells to cultures of bone marrow mononuclear cells derived from a healthy volunteer dose dependently inhibited colony formation, including mixed hemopoietic colonies. On the other hand, addition of the patient's serum failed to inhibit colony formation by normal bone marrow mononuclear cells. These results suggested that one of the causes of pancytopenia in primary Sjögren's syndrome might be mediated by the inhibition of mononuclear cells to the hemopoietic progenitors.

Blood Physiological Phenomena↗

Prodrugs of 2',3'-didehydro-3'-deoxythymidine.

Six ester prodrugs of 2',3'-didehydro-3'-deoxythymidine (D4T) were synthesized, and their physicochemical properties were evaluated. Marked differences were observed. All of the prodrugs were chemically stable within the pH range 2-7. Hydrolysis of these esters was observed in all cases for four rat enzyme systems (plasma, liver, duodenum, and kidney), with D4T being regenerated. D4T or the prodrug was administered orally to rats, and the plasma concentrations of D4T and a corresponding prodrug were measured. The half-life of D4T after intravenous administration was 35.9 min. The half-life calculated from the terminal phase and the maximum concentration in plasma following oral administration of D4T were 35.9 min and 48.4 microM, respectively. After oral prodrug administration (with water or olive oil as a solvent), though none of the prodrugs was detected in plasma except for 5'-hemisuccinyl D4T and 5'-hemiglutaryl D4T with olive oil as a solvent, retention time of plasma D4T concentration was extended and the elevated D4T concentration in plasma decreased.

Administration, Oral↗

Biliary endoprosthesis in bile duct obstruction secondary to hepatocellular carcinoma.

The effect of biliary endoprosthesis was evaluated in 13 patients with major bile duct obstruction secondary to invasion by hepatocellular carcinoma. In 12 patients major portal vein branches were also invaded by the tumors. After several days' instillation of nasobiliary or percutaneous drainage tubes to flush the bile ducts, biliary endoprosthesis was performed either endoscopically (N = 9) or percutaneously (N = 4). Significant decrease (less than 50% of initial values) of alkaline phosphatase and bilirubin levels was observed in eight and two patients on day 20, respectively. Twelve patients died of hepatic failure at 27-132 days (mean 60 days). One patient without portal vein involvement is currently alive at 300 days. Biliary endoprosthesis has a limited role in the palliation of bile duct obstruction secondary to hepatocellular carcinoma, and the prognosis may be influenced mainly by the underlying hepatic function.

Adult↗

Comparison of the clinical and immunogenetic features between patients with autoimmune hepatitis and patients with type C chronic active hepatitis.

We clarified the clinical and immunogenetical differences between patients with autoimmune hepatitis (AI-CAH), and patients with type C chronic active hepatitis (C-CAH) and type B chronic active hepatitis (B-CAH) who were positive for autoantibodies and hyperglobulinemia. While histories of blood transfusion, intravenous drug abuse and tattoo were seen frequently in patients with type C-CAH, they were rare in patients with AI-CAH. The severe subjective symptoms including anorexia, lethargy, icterus, high fever and extrahepatic manifestations, and severe abnormality of biochemical data were seen in AI-CAH predominantly. Ongoing or past infection of HCV was seen in only 14% of patients with AI-CAH. HLA-DR4 was the most frequently associated with AI-CAH (89%) and 6 DR4-negative patients were positive for DR2. HLA-DNA typing showed that there was no significant difference in the frequency of DR4-associated Dw-alleles between the patients and controls who were positive for DR4. These findings suggest that the basic amino acid at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), may contribute to the susceptibility to autoimmune hepatitis of Japanese. Thus, we conclude that AI-CAH is a genetically restricted, disease, and different from C-CAH which is a viral infectious disease.

Adult↗

Lower extremity ischemia secondary to internal thoracic-coronary artery bypass grafting.

Vascular complications associated with the use of the internal thoracic artery as a conduit for coronary artery bypass are infrequent. However, acute limb-threatening ischemia can occur after the use of the internal thoracic artery for myocardial revascularization when this vessel forms an important collateral to an obstructed aortoiliac artery system. Although this is a rare complication, the consequences are devastating. Due to the risk of peripheral vascular insufficiency, we now perform simultaneous revascularization of the myocardium and the lower extremity when an internal thoracic artery that appears to be a major collateral to the ipsilateral aortoiliac system is used.

Acute Disease↗

Light-induced binding of proteins to rhabdomeric membranes in the retina of crayfish (Procambarus clarkii).

Light-induced protein interaction as part of the process of visual transduction in arthropods with rhabdomeric photoreceptors was investigated biochemically by using crayfish retina. Two kinds of retinal buffer soluble proteins (one of 40 kDa and the other of 46 kDa) were found to bind to the irradiated rhabdomeric membranes both in vitro and in vivo. The proteins bound to the membranes in the presence of metarhodopsin. An antibody against mouse arrestin (S-antigen) cross-reacted with the 40 kDa protein. These results suggest that the binding of the proteins to the membranes is caused by the formation of metarhodopsin, and that the 40 kDa protein has a similar structure to arrestin.

Animals↗

Distribution and possible roles of the highly polysialylated neural cell adhesion molecule (NCAM-H) in the developing and adult central nervous system.

The neural cell adhesion molecule (NCAM) is a cell surface glycoprotein which is thought to mediate cell adhesion and recognition. During developmental stages, NCAM is highly polysialylated (NCAM-H) by a unique alpha-2,8-linked polysialic acid chain (PSA), and this PSA portion of NCAM-H has been found to be closely associated with various developmental processes of the nervous system. Further, recent immunohistochemical investigations have revealed that even in the adult nervous system, a persistent PSA expression has been found confined to several regions: the olfactory bulb, the piriform cortex, the hippocampal dentate gyrus, the hypothalamus, some nuclei of the medulla and the dorsal horn of the spinal cord, which are related directly or indirectly to sensory systems. Moreover, in the dentate gyrus and olfactory bulb the expression is connected with adult neurogenesis that may add new neuronal circuits to the adult neural tissue. Therefore, the possible role of NCAM-H in the central nervous system may be associated not only with neural development, but also with adult functions, such as the processing system of sensory information and neuronal plasticity.

Animals↗

Expression of highly polysialylated neural cell adhesion molecule in calcitonin-producing cells.

Calcitonin-producing cells are endocrine derivatives of the neural crest and have several neuron-like properties. Expression of the neural cell adhesion molecule in calcitonin-producing cells was examined using two types of antibodies to neural cell adhesion molecule: monoclonal antibody 12E3 recognizes the polysialic acid portion of highly polysialylated neural cell adhesion molecule, and monoclonal antibody AF11 and polyclonal antiserum react with the polypeptide portion common to three major isoforms of neural cell adhesion molecule. An immunohistochemical study revealed that highly polysialylated neural cell adhesion molecule was expressed both in fetal rat thyroidal calcitonin-producing cells and in a calcitonin-producing cell line, rMTC 6-23, established from explantable neoplasm of rat calcitonin-producing cells. The neural cell adhesion molecule in the rMTC 6-23 cells was further characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analysis. Two anti-neural cell adhesion molecule monoclonal antibodies, 12E3 and AF11, revealed a broad positive band around 200,000-250,000 mol. wt in solubilized proteins. When the polysialic acids were eliminated by neuraminidase treatment, the immunoreactivity to monoclonal antibody 12E3 was completely abolished, and core polypeptide corresponding to neural cell adhesion molecule with a molecular weight of 120,000 was detected by monoclonal antibody AF11. These results suggest that cells of the calcitonin-producing cell line express on their surfaces highly polysialylated 120,000 mol. wt form of neural cell adhesion molecule polypeptide.

Animals↗

Clinical experience of incidentally discovered adrenal tumor with particular reference to cortical function.

We reviewed 14 male and 9 female patients with adrenal tumor discovered incidentally by imaging studies in an attempt to assess adrenal function, mainly cortical function. Pathological diagnosis consisted of cortical adenoma in 12 patients, cortical nodular hyperplasia in 2, medullary hyperplasia in 1, cavernous hemangioma in 1, metastatic tumor in 4 and cyst in 2. Another adrenal cyst was diagnosed by percutaneous puncture. In all patients peripheral levels of plasma cortisol and aldosterone were normal. Plasma catecholamine levels were also normal except for 1 patient with medullary hyperplasia who had equivocal elevation. Among the patients with cortical adenoma and hyperplasia, however, 5 of 10 (50%) had excessive excretion of 24-hour urinary 17-hydroxycorticosteroids, 4 of 13 (31%) had a loss of plasma cortisol circadian rhythm and 7 of 14 (50%) had insufficient suppression on the dexamethasone test. Furthermore all patients had an increased ipsilateral uptake that was not suppressed after dexamethasone on 131iodine-adosterol scintigraphy, while a diminished contralateral uptake was noted in 5 of 15 (33%). Postoperatively, hypertension decreased to normal in 2 of 3 patients and impaired glucose tolerance was improved in 1 of 2. Two patients with cortical adenoma who exhibited a loss of plasma cortisol circadian rhythm experienced postoperative adrenal insufficiency. These data indicate that a considerable number of incidentally discovered adrenal tumors are not nonfunctioning particularly in reference to glucocorticoid secretion, and adrenalectomy seems to be beneficial in some of those patients with hypertension or impaired glucose tolerance.

17-Hydroxycorticosteroids↗

Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer.

We performed an experimental study on slow releasing anticancer drug implantation treatment as a new therapy for hepatocellular carcinoma. Hydroxyapatite (HAP) was chosen for the carrier material and doxorubicin hydrochloride (DOX) for anticancer agent. DOX-HAP was produced by adsorbing DOX to porous HAP particles of 1375 +/- 125 microns diameter using the freeze drying method. In vitro experiments showed slow release of the drug resulting in the steady release of DOX from HAP for 1 month duration. In healthy white rabbits with DOX-HAP implantation in the liver, serum DOX was not detectable, and DOX release rate was stable at the implanted region after 7, 14, and 21 days. When DOX-HAP (DOX; 100 mg kg-1) was administered to mice with sarcoma 180, an improved survival rate was observed without acute toxicity. We also found that VX2 liver tumour growth on white rabbit was inhibited by implantation of DOX-HAP, without acute toxicity. We hope that DOX-HAP implantation therapy will open up new avenues for the treatment of hepatoma.

Animals↗

Zollinger-Ellison syndrome and pheochromocytoma. Report of a case.

A 49-year-old woman was diagnosed in 1985 as having pheochromocytoma because of hypertension with high levels of plasma catecholamine concentration and 24-hour urine excretion of vanillyl-mandelic acid and metanephrine together with a right adrenal mass. The excised tumor cells had fine granular basophilic cytoplasm with argyrophilic granules by Grimelius' method. Four years later, she was diagnosed as having a duodenal bulb ulcer. Serum gastrin showed an abnormally high level of 1900 pg/ml. Abdominal echogram and computed tomography revealed a hypoechoic lesion in the pancreas and intrahepatic multiple tumors. A needle biopsy specimen of the liver tumor was compatible with the histology of metastatic islet cell tumor. A diagnosis of Zollinger-Ellison syndrome was made due to malignant gastrinoma with multiple liver metastases. The patient had no family history of endocrinological or neoplastic disorders. The present case indicates the possibility that pheochromocytoma and gastrinoma, that is, endocrine tumors characteristic of multiple endocrine neoplasia (MEN) I and MEN II, may be coincident even in a person without MEN. A continued awareness of previously rare or undescribed manifestations is important in patients with islet cell tumors or pheochromocytoma.

Adrenal Gland Neoplasms↗

Continuous 5-fluorouracil infusion causing acute gastric mucosal lesions.

A 59-year-old woman with advanced gastric cancer was treated with continuous 5-fluorouracil infusion for thirty-five days. Endoscopy of the upper gastrointestinal tract was performed due to continuing nausea seven days after the cessation of 5-fluorouracil infusion and revealed multiple erosions in the antrum which were absent before chemotherapy. Continuous 5-fluorouracil infusion was probably the cause of acute gastric mucosal lesions and should be included in the differential diagnosis of dyspepsia in 5-FU-treated patients.

Adenocarcinoma↗

Signaling pathways for sphingosylphosphorylcholine-mediated mitogenesis in Swiss 3T3 fibroblasts.

Sphingosylphosphorylcholine (SPC), or lysophingomyelin, a wide-spectrum growth promoting agent for a variety of cell types (Desai, N. N., and S. Spiegel. 1991. Biochem. Biophys. Res. Comm. 181: 361-366), stimulates cellular proliferation of quiescent Swiss 3T3 fibroblasts to a greater extent than other known growth factors or than the structurally related molecules, sphingosine and sphingosine-1-phosphate. SPC potentiated the mitogenic effect of an activator of protein kinase C, 12-O-tetradecanoylphorbol 13-acetate, and did not compete with phorbol esters for binding to protein kinase C in intact Swiss 3T3 fibroblasts. However, downregulation of protein kinase C, by prolonged treatment with phorbol ester, reduced, but did not eliminate, the ability of SPC to stimulate DNA synthesis, indicating that SPC may act via both protein kinase C-dependent and -independent signaling pathways. SPC induced a rapid rise in intracellular free calcium ([Ca2+]i) in viable 3T3 fibroblasts determined with a digital imaging system. Although the increases in [Ca2+]i were observed even in the absence of calcium in the external medium, no increase in the levels of inositol phosphates could be detected in response to mitogenic concentrations of SPC. Furthermore, in contrast to sphingosine or sphingosine-1-phosphate, the mitogenic effect of SPC was not accompanied by increases in phosphatidic acid levels or changes in cAMP levels. SPC, but not sphingosine or sphingosine-1-phosphate, stimulates the release of arachidonic acid. Therefore, the ability of SPC to act an extremely potent mitogen may be due to activation of signaling pathway(s) distinct from those used by sphingosine or sphingosine-1-phosphate.

3T3 Cells↗

Increased plasma endothelin-1 concentration in Kawasaki disease.

We compared the variation in plasma endothelin-1 (ET-1) levels by the sandwich-enzyme RIA method during each of the clinical stages of Kawasaki disease, a systemic vasculitis occurring in children (30 cases, ages 4-62 months) and examined whether ET-1 could be a clinical parameter for predicting coronary artery dilatation. The results revealed that the ET-1 level in the acute stage was higher than that in the recovery stage, the chronic stage, or in healthy controls (3.46 +/- 1.22 versus 2.20 +/- 0.56, 1.55 +/- 0.52, and 1.57 +/- 0.45 pg/ml, respectively; p < 0.01). Furthermore, in the acute stage the ET-1 level in the group with coronary artery dilatation (positive group, five cases) increased more than that in the negative group (25 cases) (5.13 +/- 1.64 versus 3.09 +/- 0.70 pg/ml, respectively; p < 0.01). When the ET-1 value was more than 4.5 pg/ml in the acute stage, our prediction for coronary artery dilatation demonstrated a high value in indices of both sensitivity (100%) and specificity (96.1%). Thus, plasma concentration of ET-1 was increased in the acute stage of Kawasaki disease and was very high in patients with coronary artery dilatation. The plasma ET-1 level was considered to be an important factor in predicting the dilatational lesions of the coronary artery in the acute stage of Kawasaki disease.

Child, Preschool↗