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Biomedical subjects

A Nakajima

Publications and source records attributed to A Nakajima.

At least 145 records · Page 8Linked to original sources
PubMed1996

[Adverse effects of low-dose methotrexate therapy in rheumatoid arthritis].

To analyze the possible adverse effects of low dose methotrexate (MTX) therapy, 276 patients with rheumatoid arthritis (RA) were examined retrospectively. One hundred and seven patients (39%) experienced 113 adverse events : 57 showed liver dysfunction, 24 gastrointestinal complaints, 13 cutaneous symptoms, 6 respiratory symptoms, and 6 malignancies. Interestingly, 3 patients developed a dry cough without infiltration nor interstitial shadow on chest X-ray. The cough was rapidly resolved by discontinuation of MTX, but it recurred in 1 patient when MTX was re-administered. This finding might suggest a close association between MTX administration and the occurrence of dry cough. Of the 6 patients with malignancies diagnosed during MTX therapy, 2 showed malignant lymphoma, 2 lung cancer, 1 breast cancer and 1 colon cancer. MTX might have an oncogenic potential in RA because the coincidence rate, especially with respect to lymphoma, was significantly higher than estimated in a normal population.

Adult↗
PubMed1995

Preferential dependence of autoantibody production in murine lupus on CD86 costimulatory molecule.

Blockade of the interactions between CD28/CTLA-4 and their ligands, CD80 (B7, B7.1)/CD86 (B70, B7.2), seems an attractive means to induce antigen-specific peripheral tolerance in organ transplantation and autoimmune disease. Recently, diversities between CD80 and CD86 in expression, regulation, and function have been reported in certain cell populations and murine experimental disease models. To investigate the possible differential role of CD80 and CD86 in the development of lupus, we treated lupus-prone NZB/W F1 mice with specific monoclonal antibodies (mAb) against CD80, CD86, or both. The treatment with a combination of anti-CD80 and CD86 mAb before the onset of lupus completely prevented autoantibody production and nephritis, and prolonged survival. Interestingly, we found that anti-CD86 mAb alone, but not anti-CD80 mAb, efficiently inhibited autoantibody production. Subclass study on IgG anti-double-stranded (ds) DNA antibody revealed that the treatment with anti-CD86 mAb almost completely inhibited both IgG1 and IgG2b, but not IgG2a production. The incomplete reduction of IgG2a anti-dsDNA antibody by anti-CD86 mAb was compensated by the addition of anti-CD80 mAb. A significant reduction of mRNA for interleukin (IL)-2, interferon-gamma, IL-4 and IL-6 was observed in mice treated with a combination of anti-CD80 and CD86 mAb or anti-CD86 mAb alone. Treatment with both mAb after the onset of lupus resulted in a significantly prolonged survival with reduction of autoantibody production. These results suggest that CD86 plays a more critical role in autoantibody production, and CD86, but not CD80, contributes to Th2-mediated Ig production. However, the blockade of both CD80 and CD86 are required for preventing the development and progression of lupus.

Animals↗
PubMed1995

HLA-linked susceptibility and resistance genes in Crohn's disease.

BACKGROUND & AIMS: Previous studies have shown a positive association of HLA-DR4-DQ4 with Crohn's disease in the Japanese population, but the association between Crohn's disease and HLA genes has yet to be fully elucidated. The aim of this study was to determine the Crohn's disease/HLA association using a DNA typing method. METHODS: A total of 90 unrelated patients with Crohn's disease and 336 healthy controls were typed for HLA class II genes including DP using DNA typing with the polymerase chain reaction-sequence-specific oligonucleotide probes method. RESULTS: Allelic analysis showed that DRB1*0405, DRB1*0410, DQA1*03, DQB1*0401, and DQB1*0402 are positively associated and DRB1*1501, DRB1*1302, and DQB1*0602 negatively associated with Crohn's disease. DP genes showed no significant association with Crohn's disease. Haplotype analysis showed positive associations with DRB1*0405-DQA1*03-DQB1*0401, DRB1*0410-DQA1*03-DQB1* 0402, and DRB1*0802-DQA1*03-BQB1-0402 haplotypes and negative associations with DRB1*1501-DQA1*0102-DQB1*0602 and DRB1*1302-DQA1*0102-DQB1*0604 haplotypes. CONCLUSIONS: In Crohn's disease in the Japanese population, the HLA-linked disease susceptibility gene is primarily associated with DQB1*04, in which leucine at the 56th position is a unique amino acid, and the disease resistance allele is suggested to be DQA1*0102.

Base Sequence↗
PubMed1995

Clinical and histopathologic features of corneal dystrophies in Japan.

PURPOSE: To examine retrospectively the frequency of various corneal dystrophies among Japanese patients who underwent keratoplasty or keratectomy at the authors' institution over a 34-year period, and to compare the histopathologic features of these disorders in the Japanese population with those reported in the Western literature. METHODS: Corneal specimens obtained during keratectomy or keratoplasty (lamellar and penetrating) performed at the authors' institution from 1959 through 1992 were reviewed. Immunohistochemical studies were performed using monoclonal antibodies to keratan sulfate and gelsolin, as well as two lectins (concanavalin A and wheat germ agglutinin). RESULTS: Of 1259 corneal specimens, 159 (12.6%) specimens from a total of 80 patients showed corneal dystrophy. Virtually all were non-Fuchs dystrophies; only one case of primary Fuchs dystrophy was identified histologically. Granular dystrophy and gelatinous drop-like dystrophy were the most common dystrophies identified in the specimens, largely because of multiple specimens from individual patients with recurrent disease. These two disorders accounted for 86 of the 159 specimens. In terms of numbers of patients, lattice dystrophy was the most common (26 patients, 32.5%), followed by macular dystrophy (16 patients, 20%), gelatinous drop-like dystrophy (15 patients, 18.8%), granular dystrophy (14 patients, 17.5%), and Avellino dystrophy (3 patients, 3.75%). Dystrophies represented by only one or two patients included congenital hereditary endothelial dystrophy, primary spheroidal keratopathy, posterior polymorphous dystrophy, Schnyder crystalline dystrophy, and Fuchs dystrophy. CONCLUSIONS: This histopathologic study showed a very low incidence of Fuchs dystrophy in the authors' Japanese patient population, compared with the incidences seen in studies of populations in Western countries. Of the non-Fuchs dystrophies, lattice dystrophy was the most common among the patients, although there were large numbers of specimens with granular dystrophy and gelatinous drop-like dystrophy due to their recurrent character. The causes of clinical and histopathologic differences and similarities among the Japanese patients and the patients described in the Western literature are likely related to genetic factors, but a complete understanding of their specific mechanisms awaits future molecular biologic and genetic elucidation.

Antibodies, Monoclonal↗
PubMed1995

A novel adrenaline derivative, AZ002, and its hypoglycemic action in yellow KK mice.

AZ002 (L-threo-(3,4-dihydroxy phenyl)-N-methyl serine methyl ester) is a newly synthesized adrenaline derivative. AZ002 caused relaxation of rat jejunum (beta 3-receptors) (ED50 = 18 microM), but did not affect the atrial rate (beta 1) or tracheal relaxation (beta 2) at a concentration of 0.3 mM. The pA2 values for propranolol in inhibiting the isoproterenol- and AZ002-stimulated relaxation of rat jejunum were 6.27 and 6.33, respectively. Thus, AZ002 is a selective agonist for beta 3-adrenoceptor. AZ002 stimulated lipolysis (ED50 = 10 microM) and glucose uptake (ED50 = 1 microM) in rat adipocytes. In both cases, stimulation was antagonized by high concentrations of the beta-adrenoceptor antagonist propranolol, but not by the alpha-adrenoceptor antagonist phentolamine. The effect of AZ002 on glucose uptake was synergistic with that of insulin. AZ002 was also assessed in vivo by using genetically obese mice (KK/Ay strain) with hyperglycemia. Administration of AZ002 in the diet for a week decreased blood glucose and non-esterified fatty acids.

Animals↗
PubMed1995

Atrophic nerve fibers in regions of reduced MIBG uptake in doxorubicin cardiomyopathy.

A myocardial MIBG-SPECT examination was conducted 2 wk after doxorubicin chemotherapy on a 52-yr-old woman without cardiac symptoms. Despite normal 201TI scintigraphy, reduced MIBG uptake was detected in the apical anterior, inferior and lateral segments of the left ventricle. The patient died of congestive heart failure due to doxorubicin-induced cardiomyopathy 10 mo later. At necropsy, the left ventricle was markedly dilated and the apical anterior, inferior and lateral walls were thin, stiff and whitish. Nerve fibers in the apical inferior wall were atrophic and markedly fibrotic where MIBG uptake was most reduced. Nerve fibers in the septum were normal where MIBG uptake had remained normal. The histologic findings correspond with the findings on the MIBG image. MIBG imaging may detect cardiac sympathetic denervation in doxorubicin-induced cardiomyopathy before cardiac symptoms are manifest and cardiac function deteriorates.

3-Iodobenzylguanidine↗
PubMed1995

[Efficacy of treatment with frequent and low-dose epirubicin in two cases of pulmonary metastases after surgery of liver cancer].

Case 1 was a 55-year-old male with multiple pulmonary metastases after two operations to excise hepatocellular carcinoma. Treatment consisted of initial administration of 5'-DFUR (po), followed by frequent administration of low-dose epirubicin (20 mg/body once every 2 weeks iv). This resulted in disappearance of the pulmonary metastases and a striking decrease in the AFP level. Case 2 was a 68-year-old male with multiple pulmonary metastases after surgery for hepatocellular carcinoma. Treatment with 5-FU (iv; once a week) and epirubicin (20 mg/body once every 2 weeks iv) resulted in disappearance of the pulmonary metastases and a marked decrease in the AFP level. It was concluded that administration of epirubicin in frequent, low doses is a useful method for the treatment of pulmonary metastasis after surgery for liver cancer, and it can be safely performed even on an outpatient basis.

Aged↗
PubMed1995

Clinical features of Japanese Leber's hereditary optic neuropathy with 11778 mutation of mitochondrial DNA.

The G to A transition of nucleotide position (nt) 11778 of mitochondrial DNA (mtDNA) has been frequently observed in Japanese Leber's hereditary optic neuropathy (LHON) cases. Therefore, we performed a multi-institutional study in Japan of LHON cases with this 11778 mutation of the mtDNA. Genetic and clinical data on 108 cases (90 affected and 18 carriers) in 79 unrelated families were obtained from 64 Japanese institutions. Detection of the nt11778 mutation was performed using restriction enzymes (74 cases) or dot blot with allele specific oligonucleotide (34 cases). Heteroplasmy was observed in 13 of the 90 affected cases and in 8 of the 18 carrier cases. Forty-five families had family history of LHON (44 maternal inheritance, 1 undetermined), and in 28 families (35.9%) there were isolated cases. The male-to-female ratio in the affected was 82:7 (92.1% male). The age at onset of visual loss ranged from 7 to 59 years (average: 23.4 years). All cases had bilateral involvement except one case with a blind eye resulting from ocular infection during childhood. Onset interval between the two eyes ranged from simultaneous to 17 months (average: 2.5 months), in 91.3% of cases being under 6 months. Visual acuity was 0.1 or worse in 152 (85.9%) of 177 eyes, only 6 eyes showing over 0.5. Progression of visual loss ranged from 0 to 48 months (average: 6.2 months). Central visual field abnormality was observed in 162 eyes (96.4%) of 168 eyes. Nonsuspect fundus in the ophthalmoscopic examination constituted 22.8% of eyes. Systemic corticosteroid was given to 45 (52.9%) of 85 cases and visual acuity was improved in only 2 cases (4.4%). Arrhythmia, neurological and muscular abnormality were observed as rare general complications. The present survey indicates that the male-to-female ratio is higher than the previous Japanese LHON statistics and that the visual outcome is better than in American LHON cases with the 11778 mutation.

Adolescent↗
PubMed1995

Identification of efonidipine hydrochloride metabolites in rats.

The metabolism of efonidipine hydrochloride (CAS 111011-76-8, NZ-105), a new dihydropyridine calcium antagonist, was studied after oral or intraperitoneal dosing in rats. Six metabolites were isolated from urine and bile and their structures were confirmed by spectral and chromatographic comparison with the authentic compounds. The main metabolic pathway of efonidipine hydrochloride involved N-debenzylation, N-dephenylation, oxidative deamination, ester hydrolysis and oxidation of the 1,4-dihydropyridine ring to the corresponding pyridine.

Administration, Oral↗
PubMed1995

[A case of Sjögren's syndrome and systemic lupus erythematosus complicated with necrotizing angiitis of the gallbladder].

A 71 year-old man with Sjogren's syndrome and systemic lupus erythematosus was admitted to our hospital because of abdominal pain and fever. Laboratory investigation showed an ESR of 76 mm/hr, elevation of CRP and marked leukocytosis. Abdominal ultrasound and CT scan showed enlargement of the gallbladder and intravesicular sludge without stones. With a clinical diagnosis of acute cholecystitis and pan-peritonitis, the surgical procedures including cholecystectomy were performed. Histological examination of the gallbladder showed a presence of necrotizing angiitis of small arteries. The postoperative course was uneventful with daily administration of 10 mg of prednisolone.

Acute Disease↗
PubMed1995

Clinical characteristics of hepatitis C virus-associated retinopathy.

The morbidity rate for retinopathy of unknown origin was significantly higher (P < 0.001) in the chronic hepatitis C group, 27 (31.8%) of 85 cases, than in the control group, 6 (6.0%) of 100 cases. Among hepatitis C virus (HCV)-associated retinopathy patients, 6 cases (22.2%) were aware of ocular subjective symptoms, retinopathy recurred in 8 (29.6%) cases, binocular retinopathy occurred in 14 (51.9%) cases, and retinopathy related to liver dysfunction, in 13 (81.3%) of 16 tested cases. HCV-associated retinopathy involved hemorrhage at the posterior pole retina in 21 (77.8%), cotton-wool patches in 9 (33.3%), and hemorrhage at the peripheral retina in 7 (25.9%) cases. Sequelae occurred in only one case. Retinopathy worsened or recurred in all 7 cases treated with interferon. The risk factors for HCV-associated retinopathy were mild thrombocytopenia (P < 0.001), long-term hepatitis illness (P < 0.005), advanced age (P < 0.02), concurrence with liver cirrhosis (P < 0.02), history of systemic hypertension (P < 0.05), and female gender (P < 0.05).

Adult↗
PubMed1994

[DNA ploidy and proliferating cell nuclear antigen positivity rate as predictive indication of effectiveness of preoperative radiation].

We compared histological effects following radiotherapy in relation to the DNA ploidy pattern and the proliferating cell nuclear antigen (PCNA) positivity rate in 37 patients with rectal cancer who underwent preoperative radiation therapy. Twelve of 23 cases in which the PCNA positivity rate before irradiation was more than 25% showed the effectiveness of radiotherapy (52.2%), against 2 of 6 cases with a rate of less than 25%. Cases in which the rate was more than 25% tended to show more effectiveness. Seventeen of 23 cases in which the PCNA positivity rate was more than 25% showed a decrease in PCNA positivity rate (73.9%). The rate in 6 cases showed no change, and no cases had an increase. In particular, in 12 cases in which the PCNA positivity rate was more than 55%, half showed effectiveness, and the PCNA rate decreased 20% on average. The PCNA positivity rate tended to decrease as a result of irradiation, and especially in diploid cases there were significant differences in the rate before and after irradiation. We suggest that cases in which the PCNA positivity rate is more than 55% with diploid DNA pattern would show most effect. The effects of irradiation could be predicted with biopsy materials and by measuring the DNA ploidy pattern and the PCNA positivity rate.

Adenocarcinoma↗