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Biomedical subjects

A Nakajima

Publications and source records attributed to A Nakajima.

At least 19 recordsLinked to original sources

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

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

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

[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

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

Protective effect of a selective endothelin receptor antagonist, BQ-123, in ischemic acute renal failure in rats.

To elucidate the pathophysiological role of endogenous endothelin (ET), we examined the effects of the newly synthesized ETA receptor-selective antagonist, BQ-123, on ischemic acute renal failure induced by bilateral clamping of renal artery and vein followed by reperfusion in rats. BQ-123, when given by i.v. infusion of 0.5 mg/kg per min for 2.5 h during the pre- and post-ischemic period, was found to prevent the decrease in creatinine clearance and increases in blood urea nitrogen, plasma creatinine and the fractional excretion of sodium. Morphological observation also showed an effect of BQ-123, i.e. prevention of proximal tubular (S3 segment) necrosis. At 2 h after the start of reperfusion, the ET-1 content in the kidney increased to its maximal level. At this time, the Ca2+ content in the mitochondrial fraction of the renal cortex increased, with a concomitant increase in blood urea nitrogen. However, these increases were limited by treatment with BQ-123. Thus, BQ-123 was effective to both prevent mitochondrial Ca2+ accumulation in the early phase of ischemic acute renal failure and protect proximal tubular cells from post-ischemic degeneration. We conclude that ET may be at least partially involved in the pathogenesis of tubular cell injury in this acute renal failure model.

Acute Kidney Injury

Diode laser iridotomy in rabbit and human eyes.

We investigated the use of an infrared diode laser to perform iridotomies in 20 eyes of ten rabbits and 40 eyes of 24 patients with primary angle-closure glaucoma. We used a two-stage method with initial circular stretch burns and subsequent penetrating multiple burns. The iris was perforated in one session and remained patent through ten months in rabbits, and seven to nine months in humans. Transitory clinical complications included intraocular pressure increase of more than 10 mm Hg (20%, eight of 40 eyes), corneal endothelial changes (5%, two of 40 eyes), clouding of lens surface (60%, 24 of 40 eyes), localized cataract (5%, two of 40 eyes), and pupillary distortion (70%, 28 of 40 eyes). No retinal damage was observed. Diode laser can be used for peripheral iridotomy.

Acute Disease

Vibrio cholerae non-O1 isolated from ayu fish (Plecoglossus altivelis) in Japan.

A fish pathogen, Vibrio cholerae non-O1, was isolated from diseased ayu fish (Plecoglossus altivelis) collected from rivers in eight prefectural districts of Japan. This organism was found to have biochemical characteristics similar to those of V. cholerae non-O1, except that our isolates were negative for ornithine decarboxylase. Antiserum against an ayu isolate did not agglutinate with the majority of environmental V. cholerae non-O1 isolates, but a major O antigen was common among the ayu isolates. All strains were hemolytic to sheep erythrocytes, and oral administration of culture supernatants induced fluid accumulation in suckling mice. However, the crude toxin was not lethal to adult mice, and no cholera toxin-like enterotoxins were detected.

Agglutination Tests

The use of bovine anti-PMSG serum in beef cattle after PMSG-superovulation.

Thirteen beef cows were superovulated using 4,000 i.u. of pregnant mare serum gonadotrophin (PMSG) on days 9 to 14 of the estrous cycle, followed by two injections of 500 micrograms prostaglandin F2 alpha analogue (PGF2 alpha) 48 and 55 hrs later. Seven of them were injected intramuscularly with bovine anti-PMSG serum 12 hrs after the first signs of estrus. The remaining 6 cows were served as controls and received no antiserum. Peripheral blood concentrations of progesterone (P) and estradiol-17 beta (E2) were compared in relation to the superovulatory responses. The injection of anti-PMSG serum did not significantly affect the numbers of the corpora lutea (CL), the anovulatory follicles and the transferable embryos at 7 to 8 days after superovulatory estrus, but increased the ratio of embryos classified as excellent or good quality. Although the plasma P concentration showed no significant differences between the anti-PMSG-treated and control cows, the plasma E2 concentration displayed a characteristic difference, suppressing the second E2 peak in the anti-PMSG-treated cows. It is concluded that the use of bovine anti-PMSG serum for PMSG/PGF2 alpha-treated cows at 12 hrs after the beginning of the estrus improves the quality of embryos recovered, probably due to inhibition of high estrogenic environment following ovulation.

Animals

Functional evaluation by gait analysis of various ankle-foot assemblies used by below-knee amputees.

Twelve different prosthetic feet were tested by 10 male subjects with right below-knee amputations. Level walking with each prosthetic foot was investigated using a pair of force plates. Five parameters were selected to compare the functional characteristics of the feet: 1) step length, 2) walking velocity on the sound side in relation to the prosthetic side, 3) depth of valley in the pattern of the vertical component of the floor reaction force, 4) efficiency of the deceleration and acceleration by the prosthetic foot, and 5) irregular patterns in the wave form of the fore and aft components of the floor reaction force. Each of the above parameters was rated numerically. The total score of the objective evaluation attained by analysing the five parameters showed some coincidence to the results of subjective evaluation. However, a good correlation existed between the objective negative score and the subjective negative rating (p < 0.05). Non-axial feet developed recently, such as the SAFE II and Seattle Light feet achieved higher scores in the older age group, while single-axis feet, such as the LAPOC and Otto Bock feet achieved higher scores in the younger age group (p < 0.05).

Adult

The prevention of blindness--past, present and future.

Prevention of blindness is the most important aim of ophthalmology. Prevention of blindness is related to many factors. It is related to many factors, such as science and technology, economy and social behavior. There are worldwide activities by WHO, NGOs and other functions to promote the prevention of blindness in the world. More than 90% of blind population lives in developing world. Cataract is the top causes of blindness which is curable. Onchocerciasis is an endemic disease in west Africa and central America. Onchocerca Control Project (OCP) was formed in 1974 under WHO for the control of oncocerciasis by the funds of developed countries. The control of vector (simulium) as well as new drug are giving the the project the prospect of success in eradicating the disease, thus preventing the blindness by diseases. The situation on blindness by trachoma, childhood blindness, glaucoma, diabetes will be discussed. The progress of molecular genetics of eye disease may open the gate for prevention of blindness by these disease in future.

Blindness

[The prevention of blindness--past, present and future].

Prevention of blindness is the most important aim of ophthalmology. Prevention of blindness is related to many factors. It is related to many factors, such as science and technology, economy and social behavior. There are worldwide activities by WHO, NGOs and other functions to promote the prevention of blindness in the world. More than 90% of blind population lives in developing world. Cataract is the top causes of blindness which is curable. Onchocerciasis is an endemic disease in west Africa and central America. Onchocerca Control Project (OCP) was formed in 1974 under WHO for the control of onchocerciasis by the funds of developed countries. The control of vector (simulium) as well as new drug are giving the the project the prospect of success in eradicating the disease, thus preventing the blindness by diseases. The situation on blindness by trachoma, childhood blindness, glaucoma, diabetes will be discussed. The progress of molecular genetics of eye disease may open the gate for prevention of blindness by these disease in future.

Blindness

[Magnetic resonance imaging: evaluation of the Blalock-Taussig shunts and anatomy of the pulmonary artery].

The morphology and circulation of the pulmonary arteries and shunt vessels were evaluated by magnetic resonance imaging (MRI) in 8 patients with cyanotic heart disease after a Blalock-Taussig shunt operation. Their ages ranged from one month to 17 years. MRI permitted assessment of the size and patency of the Blalock-Taussig shunts, as well as the size and morphology of the pulmonary arteries in all patients. Measurements of the vessel diameters on MRI correlated well with the angiographic measurements (main pulmonary artery, r = 0.98; right pulmonary artery, r = 0.98; left pulmonary artery, r = 0.98; and Blalock-Taussig shunt, r = 0.97). MRI successfully imaged 3 of 4 shunt obstructions and 3 of 4 pulmonary stenoses with high resolution. In assessing peripheral pulmonary stenosis or obstruction, MRI was superior to echocardiography, the latter being unable to image peripheral pulmonary arteries satisfactorily. We concluded that MRI is an excellent noninvasive method for serially evaluating the anatomy and function of Blalock-Taussig shunts and pulmonary arteries, which is particularly useful for children with cyanotic congenital heart disease.

Adolescent

[A clinical study of postinfarction angina (PIA): the significance of electrocardiographic ST segment changes during anginal attacks].

We studied the clinical significance of electrocardiographic ST segment changes during PIA attacks. Of 478 AMI patients admitted to the CCU of our hospital within 48 hours after onset, we evaluated 73 (15.3%) with PIA. According to electrocardiographic ST segment changes during PIA attacks, the patients were divided into three groups, namely ST elevation at the same infarction site (same site elevation group), ST depression at the same site (same site depression group), and ST depression at other sites (other site depression group), and their pathological condition was studied. There were 33 patients (45.2%) in the same site elevation group, 19 (26.0%) in the same site depression group, and 21 (28.8%) in the other site depression group. The predominant infarction areas were anteroseptal and inferior wall in the same site elevation group, NTMI in the same site depression group, and inferior wall in the other site depression group. PIA usually occurred within 4 days after the onset of infarction in the same site elevation group, and within 5-7 days in the other site depression group, but no uniform trend was observed in the same site depression group. With respect to the number of vessels showing disease, cases of single-vessel disease tended to predominate in the same site elevation group, while cases of three-vessel disease tended to predominate in the same site depression group and the other site depression group. Stenosis rates in the vessels responsible for infarction were high in the same site elevation group in the acute period. Prognoses were poorest in the same site depression group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris

[The empirical risk of retinitis pigmentosa in Japan].

The empirical risk of hereditary retinitis pigmentosa (RP), was studied based on a survey of the data from 378 families with RP who were seen in Juntendo University hospital from 1980 to 1988. If the cases have had affected sibling, the empirical risk is 19% for the other siblings, and 29% if they have parental consanguinity. Moreover the risk for male siblings is about 1.7 times higher than for female siblings. The prevalence in the general population of carriers with autosomal recessive hereditary RP was calculated to be about 0.8 to 1.7 in 100 persons. If a hereditary RP case marries a normal and unrelated partner, the risk is 0.4-0.9% for their child. If a case has many affected relatives (parents, grandparents, uncles or aunt etc), the risk is 24% for a son, and 30% for a daughter. Some normal persons among autosomal dominant families with incomplete penetrance are suspected to be carriers. The rate of penetration of the autosomal dominant gene was estimated to be 0.54. Therefore, the risk is 8.6% for the children of such persons. If the carriers are among X-linked families, the risk is 36% for their son. The risk is 1% or more for children of sporadic cases.

Adolescent