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Biomedical subjects

Y Nojima

Publications and source records attributed to Y Nojima.

At least 37 records · Page 2Linked to original sources

Improvement of extrathymic T cell type of large granular lymphocyte (LGL) leukemia by cyclosporin A: the serum level of Fas ligand is a marker of LGL leukemia activity.

We report a case of gammadelta T-cell-type large granular lymphocyte (LGL) leukemia (CD3 +,CD8 +, CD57 +,TCR gammadelta+), which was accompanied by pure red cell aplasia, neutropenia and thrombocytosis. Southern blotting analysis of the T-cell receptor beta gene showed the germline configuration, but clonal TCR J gamma rearrangements were identified. These granular lymphocytes demonstrated non-major histocompatibility complex-restricted cytotoxicitity. The serum-soluble FasL (sFasL) concentration of this patient was very high, whereas the serum levels of tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), interleukin-1 beta (IL-1beta), interleukin-2 (IL-2) and thrombopoietin were normal. After treatment with cyclosporin A, anemia and thrombocytosis were improved, and LGL and the elevated sFasL concentration decreased. These observations suggested that FasL may have played a role in the establishment of the clinical symptoms of this patient and could be useful as an indicator of disease activity.

CD3 Complex↗

Treatment of adult Still's disease with dexamethasone, an alternative to prednisolone.

We successfully treated three cases of adult Still's disease (ASD) with dexamethasone. High dose prednisolone, which was initially used to treat these patients, failed to remit the disease in all cases. Although they were resistant to prednisolone, all these patients had remarkable improvements in clinical and laboratory findings after switching to an equivalent dose of dexamethasone. We propose using dexamethasone as an alternative for treating ASD before adding immunosuppressants or disease modifying anti-rheumatic drugs (DMARD), when prednisolone therapy does not suppress disease activity sufficiently.

Adolescent↗

Adult Still's disease as a paraneoplastic manifestation of breast cancer.

We treated a patient who developed symptoms and findings indistinguishable from those of adult Still's disease as a manifestation of metastatic breast cancer 7 years after treatment for a stage 1 tumor. Although clinical features fulfilled diagnostic criteria for adult Still's disease, examination of a bone marrow biopsy specimen indicated that the apparent adult Still's disease was a paraneoplastic manifestation associated with diffuse marrow infiltration by breast cancer. The fever and polyarthralgia resolved with administration of prednisolone, and antiestrogen therapy with tamoxifen citrate was also started.

Breast Neoplasms↗

Impaired collagen gel contraction with cultured skin fibroblasts from patients with systemic sclerosis.

We investigated the capacity of skin fibroblasts, derived from 9 patients with systemic sclerosis (SSc), to contract collagen lattices in a three-dimensional culture system. In comparison with control fibroblasts (N = 8), more than 30% of SSc fibroblasts exhibited markedly impaired ability to contract collagen lattices. The expression of alpha2beta1 integrins and integrin-mediated signals were not significantly different between normal and SSc fibroblasts. Although the underlying mechanisms remain to be determined, our present data provide evidence that certain aspects of interaction with collagen are impaired in SSc fibroblasts.

Adolescent↗

Extracorporeal membrane oxygenation for the management of respiratory failure due to ANCA-associated vasculitis.

We present here two patients whose near fatal respiratory distress was caused by pulmonary hemorrhage, and who were treated successfully by extracorporeal membrane oxygenation (ECMO). The underlying disease was anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis. They were initially treated with methylprednisolone pulse therapy along with cyclophosphamide. However, their respiratory failure progressed with a low PaO2/FiO2 ratio (< 100 mmHg) despite mechanical ventilation, and ECMO was initiated. After several days, the pulmonary hemorrhage subsided, and the patients were weaned successfully from ECMO. We suggest that ECMO may be used to manage life-threatening pulmonary hemorrhage in patients suffering from ANCA-associated systemic vasculitis.

Adult↗

Factor VII R110C: a novel missense mutation (Arg110Cys) in the second epidermal growth factor-like domain causing factor VII deficiency in members of a Japanese family.

This report describes the findings of a genetic analysis of the factor VII (FVII) gene in a Japanese, male patient with FVII deficiency. The proband showed FVII activity level of 25% and FVII antigen level of 28% of the normal value, but he had no severe bleeding episodes. We identified the mutation by direct sequencing of polymerase chain reaction products representing all exons except 1b and their flanking intronic regions of his FVII gene. We detected a single point mutation, a C-->T substitution at nucleotide position 7863 in exon 5, which results in an amino acid replacement of Arg (CGC) to Cys (TGC) at codon 110 in the second epidermal growth factor-like domain. Homozygosity was confirmed in the propositus by loss of a site for the restriction endonuclease Eco47III. Furthermore, his parents, who had moderately reduced levels of factor VII activity and antigen, carried this mutation site as a heterozygote. Although the Arg11O residue is located distal to the tissue factor (TF) in the soluble TF-FVIIa crystal structure, we infer that the replacement of the positively charged and larger Arg residue with a neutral Cys residue may be likely to impair proper folding, resulting in destabilization of the protein structure.

Adult↗

Clinical pharmacokinetics and effects of an oral sustained-release preparation of disopyramide prescribed for patients undergoing maintenance hemodialysis.

AIMS: We evaluated the clinical pharmacokinetics of a sustained-release preparation of disopyramide phosphate (DSR) and its effects on supraventricular arrhythmias in hemodialysis patients. METHODS: Eight hemodialysis patients with either paroxysmal supraventricular tachycardia (PSVT) or PSVT plus paroxysmal atrial fibrillation (Paf) were given 150 mg of DSR 2 h before each hemodialysis. The frequency of PSVT, the duration of Paf before and 2 weeks after starting DSR and the blood concentration of the drug were evaluated. RESULTS: There was no significant difference between serum levels of DSR before and after hemodialysis. The frequency of PSVT and the duration of Paf were significantly reduced by the therapy. Side effects and electrocardiographic abnormalities did not appear during the period. CONCLUSION: We conclude that hemodialysis does not remove DSR, and that a single dose of 150 mg of DSR given 2 h before hemodialysis is safe and sufficient to reduce the incidence of supraventricular arrhythmias.

Administration, Oral↗

Therapeutic effects of ulinastatin on experimental crescentic glomerulonephritis in rats.

Ulinastatin is a potent protease inhibitor purified from the human urine that has been used clinically to treat acute pancreatitis and circulatory shock. In the current study, we evaluated the therapeutic effects of Ulinastatin in a rat model of crescentic glomerulonephritis (CrGN) and investigated its putative mechanisms. Wistar-Kyoto rats were injected with nephrotoxic serum and received daily intraperitoneal injection of Ulinastatin. Ulinastatin treatment significantly reduced proteinuria and glomerular crescentic formation. Moreover, glomerular infiltration of neutrophils and ED1+ cells (monocytes/macrophages) was significantly suppressed by Ulinastatin. In contrast, the glomerular deposition of heterologous (rabbit) and autologous (rat) antibodies was not changed. Neither serum complement activation nor the anti-rabbit immune response was affected by Ulinastatin administration. Our results suggest that Ulinastatin has preventive effects on rat experimental CrGN, mediated at least in part by inhibiting intraglomerular infiltration of inflammatory cells.

Animals↗

[Protective efficacy of BCG Tokyo 172 in the guinea pig model of pulmonary tuberculosis].

BCG Tokyo 172 strain was examined for its protective efficacy against pulmonary tuberculosis in a guinea pig model. Guinea pigs were vaccinated with an intradermal injection of 10(3) CFU of BCG Tokyo 172 strain. BCG Copenhagen 1331 was employed as a control strain. Eight weeks after the vaccination, the animals were infected with about 10 CFU of M. tuberculosis H37Rv by a respiratory route in an aerosol chamber. Five weeks after infection, the animals were euthanized and their spleens, lungs and livers were obtained for enumeration of M. tuberculosis H37Rv and histopathological examinations. The mean log10 CFU of M. tuberculosis H37Rv recovered from right lower lung lobes of guinea pigs vaccinated with BCG Tokyo 172 (frozen), BCG Tokyo 172 (freeze-dried), BCG Copenhagen 1331 (freeze-dried) and placebo were 4.72, 4.23, 4.35 and 5.76, respectively. The mean log10 CFU of the bacteria recovered from spleens were 2.11, 1.51, 1.37 and 5.90, respectively. There was a significant difference in bacterial recovery from both lung and spleen between the vaccinated and the non-vaccinated groups. No significant difference was seen among the groups vaccinated with different strains of BCG in any organ. The lungs exhibited just small granulomatous nodules and the spleens showed no granulomatous nodules in the BCG-vaccinated guinea pigs. On the other hand, the lungs and spleens from non-vaccinated guinea pigs showed much larger granulomatous nodules with central necrosis. These histopathological difference between the vaccinated and the non-vaccinated guinea pigs was consistent with the difference of bacterial growth between them. The results of this study have clearly indicated that BCG Tokyo 172 strain possesses a significant protective efficacy against M. tuberculosis as well as BCG Copenhagen 1331 strain. These results have also shown that the respiratory infection model in guinea pigs is very useful to evaluate efficacy of vaccines against pulmonary tuberculosis.

Animals↗

[A case of transient cortical blindness complicated by Henoch-Schönlein purpura with bronchiectasis].

A 19-year-old woman had been treated for bronchiectasis since she was born. In October 1995, she was diagnosed as Henoch-Schönlein purpura (HSP) and HSP nephritis with the findings as follows; palpable petechial rash of legs, abdominal pain, arthralgias, and proteinuria. The administration of oral prednisolone was started, the clinical symptoms except for proteinuria was disappeared. However, nephrotic syndrome was continued despite the therapy of intravenous methylprednisolone pulse, various immunosuppressive drugs and warfarin. In February 1998, she was admitted to our hospital because of pneumonia. Several days later, her pneumonia improved on treatment with antibiotics, but she suddenly developed transient cortical blindness and acute renal failure. A provisional diagnosis of hypertensive encephalopathy and cerebral edema related to vasculitis was made, and she was treated with nifedipine, Glycelo, and high dose immunoglobulin. After the treatment, her vision and renal function had improved. She is a rare case associated with transient cortical blindness, bronchiectasis, and HSP.

Adult↗

Hypercalcemia induced by metastatic bone cancer in a patient with chronic renal failure.

We present a diagnostically challenging case of hypercalcemia in a 50-year-old Japanese woman with chronic renal failure due to chronic interstitial nephritis. She had a history of a radical mastectomy for breast cancer at the age of 30. Despite her chronic renal failure, serum levels of calcium and alkaline phosphatase were abnormally high, and levels of intact parathyroid hormone and of parathyroid hormone-related protein were undetectable on repeated assays. Bone scintigram revealed multiple hot lesions in the ribs, which were suggestive of bone metastases of breast cancer. After treatment with tamoxifen citrate was initiated, her serum calcium levels returned to the normal range and hot lesions were no longer evident on bone scintigraphy in 14 months. Thus, our patient's hypercalcemia was considered to be related to bone metastases of breast cancer. Physicians should be aware of existence of malignancy in the patient with chronic renal failure and hypercalcemia.

Alkaline Phosphatase↗

[Goodpasture's syndrome].

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Anti-Glomerular Basement Membrane Disease↗

Four cases of anti-myeloperoxidase antibody-related rapidly progressive glomerulonephritis during the course of idiopathic pulmonary fibrosis.

We report here 4 cases of rapidly progressive glomerulonephritis (RPGN) which developed during the management of idiopathic pulmonary fibrosis. In each patient, pulmonary disease preceded the onset of nephritis by 1 to 6 years. All patients had a high titer of serum autoantibodies against myeloperoxidase (MPO-ANCA) when the diagnosis of RPGN was made. Although the association of pulmonary fibrosis with ANCA-related glomerulonephritis has been occasionally described in the past literature, the sequence of pulmonary and renal injury has not been well defined. The present report demonstrates that idiopathic pulmonary fibrosis exists as a preceding condition in some patients with MPO-ANCA-related nephritis.

Aged↗

Decreased dipeptidyl peptidase IV enzyme activity of plasma soluble CD26 and its inverse correlation with HIV-1 RNA in HIV-1 infected individuals.

Human plasma contains soluble CD26/dipeptidyl peptidase IV (sCD26/DPPIV) although its physiological significance remains unclear. To determine whether the plasma sCD26 levels have clinical relevance in HIV-1 infected individuals, the concentration and DPPIV enzyme activity of plasma sCD26 were measured. While there is no significant difference between the plasma levels of sCD26 in 90 HIV-1 infected individuals and in 79 uninfected controls, specific DPPIV enzyme activity of sCD26 was significantly decreased HIV-1 infected individuals (P < 0.0001). Specific DPPIV enzyme activity was correlated with the levels of CD4+ T cells (r = 0.247; P < 0.02), CD8+ T cells (r = 0.236; P < 0.03), and adenosine deaminase (r = 0.227; P < 0.05) and had an inverse correlation with HIV-1 RNA (Spearman's r = 0.474; P = 0.0012). Furthermore, recombinant sCD26 enhanced the in vitro PPD-induced response of lymphocytes from HIV-1 infected individuals with decreased specific DPPIV enzyme activity. These results suggest that the specific DPPIV enzyme activity of plasma sCD26 may contribute to the immunopathogenesis of HIV infection.

Adenosine Deaminase↗

A case of cimetidine-induced acute tubulointerstitial nephritis associated with antineutrophil cytoplasmic antibody.

We present a case of acute tubulointerstitial nephritis (ATIN) that developed in a 63-year-old man who had been taking cimetidine for treatment of a gastric ulcer. The constellation of clinical, laboratory, and histopathologic findings suggested drug-induced ATIN. Of interest, the patient had antineutrophil cytoplasmic antibody (ANCA) in his sera, reactive with myeloperoxidase, elastase, and lactoferrin. Prominent renal histological features included marked plasmacyte infiltration into the renal interstitium. Withdrawal of cimetidine resulted in complete resolution of renal findings, and the titers of ANCA concomitantly declined. Thus, cimetidine may have played a causative role in the development of ANCA-associated ATIN.

Anti-Ulcer Agents↗

Fyn and Lck tyrosine kinases regulate tyrosine phosphorylation of p105CasL, a member of the p130Cas docking protein family, in T-cell receptor-mediated signalling.

We have previously shown that engagement of the T-cell receptor (TCR)/CD3 complex with anti-CD3 antibody induces tyrosine phosphorylation of p105CasL (CasL), a member of the p130Cas docking protein family. In the present work, we attempted to determine which protein tyrosine kinases (PTKs) regulate TCR-mediated phosphorylation of CasL. We show here that an association between CasL and two types of Src family PTKs, Fyn and Lck, is induced by anti-CD3 cross-linking of human H9 T cells. In contrast, ZAP-70, another PTK that also plays a critical role in the TCR signalling, failed to bind CasL, even after anti-CD3 stimulation. In vitro kinase assays revealed that Fyn and Lck, but not ZAP-70, were capable of phosphorylating CasL. Moreover, we found that CasL was constitutively hyperphosphorylated in vivo in splenocytes of MRL-MP-lpr/lpr mice, in which overproduction and excessive activation of Fyn and Lck have previously been shown to occur. Constitutive in vivo binding of CasL to both kinases was also demonstrated in lpr splenocytes. These results strongly suggest that CasL is a substrate for Fyn and Lck PTKs in TCR signal transduction.

Adaptor Proteins, Signal Transducing↗