Analysis of rejection mechanisms in small bowel allotransplantation.
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Biomedical subjects
Publications and source records attributed to K Kishimoto.
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The leucine-to-alanine mutation at residue 201 of D-amino acid aminotransferase provides a unique enzyme which gradually loses its activity while catalyzing the normal transamination; the co-enzyme form is converted from pyridoxal 5'-phosphate to pyridoxamine 5'-phosphate upon the inactivation [Kishimoto,K., Yoshimura,T., Esaki,N., Sugio,S., Manning,J.M. and Soda,K. (1995) J. Biochem., 117, 691-696]. Crystal structures of both co-enzyme forms of the mutant enzyme have been determined at 2.0 A resolution: they are virtually identical, and are quite similar to that of the wild-type enzyme. Significant differences in both forms of the mutant are localized only on the bound co-enzyme, the side chains of Lys145 and Tyr31, and a water molecule sitting on the putative substrate binding site. Detailed comparisons of the structures of the mutant, together with that of the pyridoxamine-5'-phosphate form of the wild-type enzyme, imply that Leu201 would play a crucial role in the transamination reaction by keeping the pyridoxyl ring in the proper location without disturbing its oscillating motion, although the residue seems to not be especially important for the structural integrity of the enzyme.
The effects of a recently synthesized anti-platelet aggregation drug (E-5510) on platelet deposition in a knitted Dacron aortic graft underwent preliminary evaluation by In-111 oxime labeled platelet imaging. Seven patients undergoing aortofemoral bypass using this graft for occlusive disease were randomized into two groups: those receiving E-5510 and those receiving no medication. This agent was administered for 17 days postoperatively, and on the 14th day In-111 platelets were injected and images were acquired at 24, 48, and 72 hours. Platelet deposits in the grafts were assessed by the ratios of graft radioactivity to that of the adjacent native iliac arteries. Platelet deposition at the sites of anastomosis and deposition along the entire graft were normalized by initial deposition at 24 hours, and had significantly decreased at 72 hours in the three treated patients, while the normalized deposition increased progressively over time in the remaining four nonmedicated patients. E-5510 seems to have the potential to inhibit excessive platelet deposition on recently implanted grafts.
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We present a case of immunoblastic lymphadenopathy-like T cell lymphoma (IBL-T) who subsequently developed a massive proliferation of plasma cells. At diagnosis of IBL-T, the patient had polyclonal hypergammaglobulinemia and subsequently, while on chemotherapy, developed paraproteinemia with biclonal peaks and the IBL-T lesion was replaced with a massive proliferation of CD38-positive plasma cells. The evolution was not likely to be attributed to a new neoplastic proliferation of B cells. It appeared that two B cell clones possibly had a growth advantage among the polyclonal B cells due to a depletion of suppressor T cells or to a disturbance in the immune system.
D-glutamate, an indispensable component of peptidoglycans of bacteria, is provided by glutamate racemase in E. coli cells. Compensation for D-glutamate auxotrophy of E. coli WM335 cells lacking the glutamate racemase gene, murI, with the D-amino acid aminotransferase gene suggests that presence of a threshold concentration for the D-glutamate required by E. coli cells, as well as a regulation system for murI expression.
We studied 86 patients with bladder cancer who were 80 years old and over. All were studied at the time of their first presentation for treatment in our hospital. About 40% of then were somewhat limited in performing usual daily activities before the first treatment, and they could not come to the hospital by themselves. Tumors in patients were larger, of higher grade and more invasive than those in younger patients. Transurethral resection of the bladder tumor (TUR-Bt) was done in 94% of patients with a superficial tumor and in 56% of those an invasive tumor. The recurrence rates after TUR-Bt for superficial tumor were 48%, 64% and 89% in 1 year, 3 years and 5 years, respectively. Recurrence rates were significantly different in younger patients. Overall cancer related survival rates were 86%, 60%, and 56% in 1 year, 3 years and 5 years, respectively. The outcome were significantly worse in patients over 80 years old than in those under 79 years old. To improve the outcome of treatment for bladder cancer in patients over 80 years old, cooperation among doctors, patients and families was important.
A 39-year-old man with schizophrenia and suicide attempt was diagnosed with stage IIb testicular tumor. He was initially admitted to the psychiatry ward and underwent high orchiectomy. After schizophrenia became stable by administration of antipsychopathic drugs, he was transferred to the ordinary urology ward and treated with 3 courses of chemotherapy (bleomycin, etoposide, cisplatin) and retroperitoneal lymph noded dissection. The mental status of the patient remained under good control throughout the course of treatment. He has been free of recurrence for 8 months postoperatively. We discussed general medical issues concerning the treatment of malignant diseases in patients with psychosis.
Fifty-nine primary breast cancers were analyzed by flow cytometric cellular DNa-RNA contents stained by acridine orange simultaneous DNA-RNA double staining. Forty-three cases (72.9%) out of 59 had abnormal stemlines (DNA aneuploidy), and 16 normal ones (DNA diploidy). RNA indices widely ranged from 1.41 to 9.02 (2.99). There was no correlation between DNA indices and RNA indices. The patients with DNA diploidy had a better prognosis than those with DNA aneuploidy, but the differences were not significant. The patients with a high RNA index of more than 4.0 had a significantly poorer prognosis than those with an index of less than 4.0. Those results suggest that RNA contents, and DNA contents are independent prognostic factors, and especially RNA contents may be a good prognostic factor in long-term survival in breast cancer.
The effect of systemic and local allergic responses on the mucociliary system of the Eustachian tube was investigated. Egg albumin was administered to guinea pigs via the jugular vein to evoke systemic anaphylaxis in animals previously sensitized with egg albumin. Ciliary activity in the Eustachian tube of sensitized animals was significantly higher than that of control animals. However, the mucociliary clearance time of the Eustachian tube in sensitized animals was significantly longer than in control animals. Local allergic response induced by intratympanic instillation of (BPO)61-BGG induced cilioexcitation and prolonged mucociliary clearance in the guinea pigs sensitized with BPO-BGG. A partial loss of the inner layer of the mucus blanket of the Eustachian tube was observed under electron microscopy. In conclusion, the systemic as well as the local allergic response accelerates ciliary activity but may affect the mucus blanket and induce mucociliary dysfunction in the Eustachian tube, resulting in a predisposition to middle ear diseases.
The detection of specific IgE is a critical prerequisite for both the definitive diagnosis and the therapeutic strategy of allergic rhinitis and other allergic disorders. The aim of the present study was thus to evaluate the clinical significance of the solid phase capture system (CAP) and the lumiward immunoassay system (LMD) in the diagnosis of allergic rhinitis due to Dermatophagoides farinae (D. farinae) and Japanese cedar (Cryptomeria japonica) pollens. The specificity of both the CAP and the LMD in the detection of D. farinae-specific IgE and Japanese cedar pollen-specific IgE was 100%. The sensitivity to detect D. farinae-specific IgE was 95.76% in the skin test, 86.53% in the CAP and 88.53% in the LMD, respectively. The combination of the nasal provocation test and the CAP substituted for the skin test resulted in correct diagnoses for 98.25% of the patients, and the combination of the nasal provocation test and the LMD substituted for the skin test resulted in correct diagnoses for 98.00% of the patients. Therefore, the diagnostic significance of the LMD for perennial allergic rhinitis is likely to be equal to that of the CAP. The sensitivity to detect Japanese cedar pollen-specific IgE was 94.50% in the skin test, 84.47% in the CAP, and 96.76% in the LMD, respectively. The sensitivity of the CAP in the detection of Japanese cedar pollen-specific IgE was inferior to that of the skin test, but the sensitivity of the LMD in the detection of pollen-specific IgE was somewhat superior to that of the skin test. In addition, the combination of the nasal provocation test and the CAP substituted for the skin test resulted in correct diagnoses for 98.38% of the patients, whereas the combination of the nasal provocation test and the LMD substituted for the skin test resulted in correct diagnoses for 100% of the patients. Therefore, the diagnostic significance of the LMD for seasonal allergic rhinitis due to Japanese cedar pollens is probably larger than that of the CAP. In conclusion, the LMD may be a better "gold standard" for the detection of Japanese cedar pollen-specific IgE than the skin test, and the combination of the nasal provocation test and the LMD is a better diagnostic tool for the detection of Japanese cedar pollen-induced seasonal allergic rhinitis than the combination of the nasal provocation test and the skin test or the CAP.
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D-Amino acid aminotransferase is the only aminotransferase that catalyzes the transamination of D-amino acids. We studied the role of the binding site for the alpha-carboxyl group of substrates, which is presumably crucial for the unique stereospecificity of the enzyme. The site-directed mutagenesis of Arg98, which is the putative carboxyl-binding site, as judged on the basis of X-ray crystallographic studies [Sugio, S., Petsko, G.A., Manning, J.M., Soda, K., and Ringe, D. (1995) Biochemistry 34, 9661-9669], by replacement with methionine and lysine, resulted in decreases in the kmax values and increases in the Kd values for both amino donors and amino acceptors. The introduction of another mutation, that of Tyr88, which is located near Arg98 in the spacial structure, by replacement with arginine, in addition to the above Arg98 mutation, resulted in increases in the kmax values but little change in the Kd values. These results suggest that Arg98 constitutes the carboxyl-binding site for the substrate, efficient catalysis by the enzyme being facilitated upon binding. The mutant enzymes are also relieved from inhibition by high concentrations of alpha-ketoglutarate, which is an inherent character of the wild-type enzyme. Therefore, Arg98 is also responsible for the inhibition by alpha-ketoglutarate.
We reported a 59-year-old woman who received a diagnosis of psoriasis vulgaris at the age of 35 and had been under medical treatment. She was admitted to our department on August 16, 1993 because of lymphadenopathy, arthralgia and neuralgia. We observed cervical and axillar lymphadenopathy 1-3 cm in diameter, anemia and leukothrombocytosis. Elevated levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and immunoglobulin G (IgG), but not M-protein were observed by immunological analysis of the serum. Bone marrow aspiration biopsy revealed hypercellularity with myeloid hyperplasia and slight increase in plasma cells. Elevated levels of serum interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) were detected; IL-6 was 62.1 pg/ml and G-CSF was 66 pg/ml, but IL-1 alpha, IL-1 beta and TNF-alpha were within the normal range. Idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hyperimmunoglobulinemia was diagnosed by lymph-node biopsy and the patient received following treatment with prednisolone and hydroxyurea. Leukocytes, platelets and skin eruptions increased again when the steroid dose was tapered, so we changed treatments to MP (melphalan, prednisolone) therapy. In addition, various neurological abnormalities such as convulsions, loss of consciousness and peripheral polyneuritis were observed. Despite treatment her condition deteriorated and she finally died. Very few reports show these neurological abnormalities in IPL or Castleman's disease therefore we think this is a very rare case.
The physiological features of the mildiomycin production by Streptoverticillium rimofaciens were examined in iron-sufficient and -deficient media. Activities of NADP-linked glutamate dehydrogenase (GDH) and aspartate aminotransferase (AAT) were markedly enhanced by the addition of 10 micrograms/ml of ferrous ion into culture. Ammonium nitrogen assimilation increased with the increase in mildiomycin production. These indicate that ferrous ion contributes the supply of amino acids as a precursor of mildiomycin production. In the iron-sufficient medium, glutamate, aspartate, serine and arginine in cells were 2 to 10-fold to those in the iron-deficient medium. The major amino acid excreted from cells was arginine in the iron-sufficient culture, while in the iron-deficient culture, valine. Change in the amino acid profile by addition of ferrous ion was useful for mildiomycin biosynthesis, in which ferrous ion played a leading role in amino acid metabolism.
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The physiological features of the mildiomycin production by Streptoverticillium rimofaciens were examined in iron-sufficient and -deficient media. Activities of NADP-linked glutamate dehydrogenase (GDH) and aspartate aminotransferase (AAT) were markedly enhanced by the addition of 10 micrograms/ml of ferrous ion into culture. Ammonium nitrogen assimilation increased with the increase in mildiomycin production. These indicate that ferrous ion contributes the supply of amino acids as a precursor of mildiomycin production. In the iron-sufficient medium, glutamate, aspartate, serine and arginine in cells were 2 to 10-fold to those in the iron-deficient medium. The major amino acid excreted from cells was arginine in the iron-sufficient culture, while in the iron-deficient culture, valine. Change in the amino acid profile by addition of ferrous ion was useful for mildiomycin biosynthesis, in which ferrous ion played a leading role in amino acid metabolism.