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T Nishihara

Publications and source records attributed to T Nishihara.

332 records · Page 19Linked to original sources

Ultrastructural immunocytochemical analysis of lymphocytes infiltrating bile duct epithelia in primary biliary cirrhosis.

Subpopulations of lymphocytes in portal areas, especially infiltrating bile duct epithelia were analyzed by light and electron microscopy using indirect peroxidase-labeled antibody method and monoclonal antibodies against pan-T (Leu 1), cytotoxic/suppressor T (Leu 2a), helper/inducer T (Leu 3a) and natural killer/K (Leu 7) and suppressor T (Leu 15) cells in liver biopsy specimens from four patients with primary biliary cirrhosis. Bile ducts with chronic nonsuppurative destructive cholangitis were observed in two patients. Leu 1+ and Leu 2+ cells were frequently seen in intimate contact with epithelial ductal cells. The majority of intraepithelial cells possessing Leu 2a antigen did not react with anti-Leu 15 antibody. Leu 3a+ or Leu 7+ cells seldom infiltrated ductal epithelia. These findings indicate that the majority of intraepithelial lymphocytes in bile ducts most likely represent Leu 2a+15- cytotoxic T cells. By immunoelectron microscopy, Leu 1+ or Leu 2a+ lymphocytes often breached the basement membrane of bile ducts and were present within dilated intercellular spaces between biliary epithelial cells. Furthermore, they often formed sharp or broad contacts with the epithelial cells, and occasionally pseudopods projecting from the surfaces of Leu 2a+ cells extended into the epithelial cells. Most of Leu 2a+ lymphocytes contained little cytoplasm with few granules and a small Golgi apparatus. Such findings suggest that cytotoxic T cells may contribute to the pathogenesis of chronic nonsuppurative destructive cholangitis in primary biliary cirrhosis.

Adult↗

Successful treatment of a 93-year-old patient with hypoplastic acute monocytic leukemia using macrophage colony-stimulating factor.

A 93-year-old patient with hypoplastic acute monocytic leukemia (AMoL) achieved a complete remission after macrophage colony-stimulating factor (M-CSF) therapy. Initially, the patient was treated with a low dose of cytarabine, but this treatment proved ineffective. M-CSF was administered for 14 days by drip intravenous infusion, 800 x 10(4) units per day. After a gradual decrease in the number of leukemic cells, a rapid increase in neutrophils was observed in the peripheral blood, and a bone marrow examination 22 days after discontinuation of M-CSF medication revealed a complete remission. These findings suggest that M-CSF may be useful in treating some elderly patients who have hypoplastic AMoL.

Aged↗

Bone morphogenetic protein 2 suppresses the transformed phenotype and restores actin microfilaments of human lung carcinoma A549 cells.

Bone morphogenetic protein 2 (BMP2) is a member of the transforming growth factor beta (TGFbeta) superfamily. Here we report a biological function of BMP2. Treatment of human lung carcinoma cell line, A549 cells with BMP2 resulted in inhibition of A549 cell growth in anchorage-dependent and independent growth conditions. Furthermore, BMP2 induced microfilament organization restoration in A549 cells. These changes were also observed in TGFbeta1-treated A549 cells. BMP2 and TGFbeta1 additionally suppressed the transformed phenotypes and restored actin microfilaments in A549 cells. In contrast, activin A, another member of the TGF superfamily did not induce these phenomena. It was also noted that the development of the microfilaments is almost proportional to the extent of the inhibition of cell growth in our system.

Actin Cytoskeleton↗

Radioimmunotherapy of orthotopically transplanted pancreatic cancer with 131I-labeled chimeric monoclonal antibody Nd2.

Recombinant mouse/human chimeric antibody Nd2 was previously reported to have the same specificity and reactivity against pancreatic cancer as murine Nd2 without HAMA production which induced serious problems in clinical application. We established orthotopic SW1990 transplanted mice to represent the progression of pancreatic cancer. We examined anti-tumor effect of 131I-labeled chimeric Nd2 in an orthotopic transplant model. 131I-labeled chimeric Nd2 inhibited the growth of orthotopically transplanted tumors and extended the survival time of the mice. These results suggest that 131I-labeled chimeric Nd2 has high clinical applicability in the therapy of pancreatic cancer.

Animals↗

[A case of mononeuropathy multiplex associated with anti-GM1 and -SGLPG antibodies in a patient with ongoing Hashimoto disease].

We reported a case of mononeuropathy multiplex associated with anti-GM1 and -SGLPG antibodies in a patient with ongoing Hashimoto disease. A 56-year-old woman was admitted with asymmetrical patchy sensory and motor disturbance in the extremities. Muscle atrophy and weakness in the left palm and bilateral tibialis anterior muscles were also noted. Deep tendon reflexes were normal in all the extremities. Superficial and deep sensations were reduced in the hands and feet bilaterally, and the distribution of sensory loss was irregular. Her serum was positive for antinuclear antibody, rheumatoid factor, anti-RNP antibody, and anti-SS-A antibody. Serial electrophysiological studies suggested that the predominant process was axonal degeneration of the sensorimotor nerves. On sural nerve biopsy, there were no findings of vasculitis but severe axonal degeneration was observed. Thin-layer chromatography with immunostaining revealed anti-GM1 and -SGLPG antibodies. Treatment with corticosteroids was successful. In this case, the anti-GM1 antibody may have played a role in the pathogenesis of mononeuropathy multiplex associated with autoimmune disease.

Autoantibodies↗

Physiologically based pharmacokinetics of a new penem, SUN5555, for evaluation of in vivo efficacy.

SUN5555, (5R,6S)-6-[(R)-1-hydroxyethyl]-7-oxo-3-[(R)-2- tetrahydrofuryl]-4-thia-1-azabicyclo-[3.2.0]-hept-2-ene-carboxylic acid, is a newly developed and orally effective penem with a broad antibacterial spectrum. SUN5555 was degraded in rat tissue homogenates and serum, and its degradations in the kidney and lung homogenates were significantly inhibited by cilastatin, an inhibitor of dehydropeptidase I. The pulmonary extraction was evaluated to be 0.033 by comparing the AUCs resulting from iv and intra-arterial administration of 10 mg/kg. From the arterial-to-venous concentration differences under steady state conditions in rats, extraction ratios of SUN5555 across the kidney, hind leg, gut, and liver were determined to be 0.333, 0.104, 0.071 and 0.053, respectively, whereas no appreciable extraction across the brain was observed. Therefore, organ clearances of SUN5555 are limited by the product of plasma unbound fraction and organ intrinsic clearances in various tissues. Using a physiologically based pharmacokinetic model, unbound concentrations of SUN5555 in the tissue interstitial fluids, which are the measure of in vivo antibacterial efficacy, were estimated to be almost identical with, or higher than, those in plasma in rats. Similarly, serum concentration-time profiles of SUN5555 after iv administration in other animal species were predicted and found to be in good agreement with the observed data in dogs. A preliminary prediction of the pharmacokinetics of SUN5555 in a human subject was also attempted by animal scale-up technique.

Animals↗