Biomedical subjects

A Nakajima

Publications and source records attributed to A Nakajima.

At least 127 records · Page 7Linked to original sources

PubMed1997

Cervical spondylosis in paraplegic patients and analysis of the wheelchair driving action: a preliminary communication.

We investigated cervical spondylotic changes in paraplegic patients by examining the radiographs of their cervical spine. The incidence of cervical spondylosis in these patients was significantly higher than was found in normal control subjects of a matching age. We attributed this finding to the mechanical stress on the cervical spine during wheelchair driving. We then performed a biomechanical analysis using electromyography and goniometer. Paraplegic patients frequently flexed and extended their cervical spine shown by the goniometer, whilst the normal control subjects walked almost without moving their cervical spine. However, the integrated electron myography (IEMG) of the paraplegic patients was not synchronously increased with the integration of goniometer (IGOM) and the IEMG of the normal controls was significantly larger than that found in paraplegic patients on increasing their speed. This was thought to be necessary for steadying the head whilst walking or running.

Adult↗

PubMed1997

Critical role of Fas/Fas ligand interaction in CD28-independent pathway of allogeneic murine hepatocyte rejection.

Cytolytic induction of T cells requires both the T-cell receptor (TCR)-mediated antigenic stimulation and the CD28-mediated co-stimulatory signal. Blockade of the interactions between CD28 and its ligands, CD80 and CD86, prolongs the survival of allografts in some transplantation models. However, we found that allogeneic hepatocytes were completely rejected within 7 days after intrasplenic transplantation, even when treated with monoclonal antibodies (mAbs) against CD80 and CD86 (anti-CD80/86). Recent studies have shown that there are two main mechanisms of T-cell-mediated cytotoxicity, perforin-based and Fas-based ones. It has been shown that the liver is highly sensitive to induction of apoptosis by an agonistic anti-Fas mAb. We then investigated the role of the Fas/Fas ligand (FasL) system in the CD28-independent allogeneic hepatocyte rejection. With the anti-CD80/86 mAb treatment, hepatocytes from C57BL/6 lpr/lpr (B6 lpr) mice, which express little Fas antigen, could survive for 7 days after intrasplenic transplantation, and hepatocytes from C57BL/6 (B6) mice could also survive for 7 days in the spleen of C3H/ He gld/gld (C3H gld) mice, which express no functional FasL. CD28-independent induction of cytotoxicity against allogeneic hepatocytes was not observed when the effector cells were derived from C3H gld mice. These results indicated that the Fas/FasL system plays a critical role in the CD28-independent pathway of allogeneic hepatocyte rejection.

Animals↗

PubMed1997

Requirement of CD28-CD86 co-stimulation in the interaction between antigen-primed T helper type 2 and B cells.

The interaction between CD28 and its ligands, CD80 and CD86, is crucial for an optimal activation of antigen-specific T cells. However, the requirement of CD80 or CD86 co-stimulation in Th2 cell differentiation and activation is controversial. Freshly isolated murine CD4+ and CD8+ T cells were incubated with P815 transfectants expressing a similar level of either CD80 or CD86 in the presence of anti-CD3 mAb. Both CD80 and CD86 co-stimulated the proliferation of CD4+ and CD8+ T cells at comparable time-kinetics and magnitude, but CD86 alone was able to co-stimulate IL-4 and especially IL-10 production in CD4+ T cells. In typical Th2-dependent immune responses elicited by Nippostrongylus brasillensis infection, the anti-CD86 mAb treatment but not the anti-CD80 mAb treatment efficiently inhibited antigen-specific IgE and IgG1 production, which was accompanied with the reduced IL-4 production. Our results suggest that CD86 co-stimulation plays a dominant role not only in the primary activation of Th2 cells but also in the secondary interaction between antigen-primed Th2 cells and B cells.

Animals↗

PubMed1997

Fatty acid compositions of colostrum, cord blood, maternal blood and major infant formulas in Japan.

Lipid profiles in colostrum, cord blood, maternal blood and major infant formulas in Japan were analyzed. In the first part of the study, colostrum obtained from 36 normal delivery women and six kinds of infant formulas provided by three major milk companies were analyzed for their fatty acid composition using capillary gas-lipid chromatography. Although enriched with docosahexaenoic acid (DHA), the percent composition of DHA in the six infant formulas (0.15-0.21%) was significantly lower than that in the colostrum (1.1 +/- 0.54). Arachidonic acid (AA) and eicosapentaenoic acid (EPA) were present in the colostrum but not detectable in the infant formulas. It is recommended that although the exact amount of specific fatty acids needed in the infant diet was not completely known, to be as close as possible to natural breast milk, the level of DHA, EPA and AA should be raised in the infant formulas. In the second part of the study, 19 pairs of maternal and cord blood were analyzed for their lipid profile. All samples were from normal vaginal delivery. The measurement of cholesterol, triglycerides, phospholipids and free fatty acids was performed with commercially available enzymatic methods on an automated discrete random access analyzer. Total fatty acid was determined as described in the first part of the study. The results were analyzed with Spearman's rank correlation coefficient. No correlation could be found between maternal and fetal concentrations of cholesterol, triglycerides, phospholipids or total fatty acids. Correlation could be found in non-esterified fatty acids, in palmitic acids, and oleic acid levels. It was concluded that the lipid transport and metabolism in the fetal-placenta unit is complex and further delicate investigation is required.

Adult↗

PubMed1997

Effects of sulindac on sporadic colorectal adenomatous polyps.

BACKGROUND: Although sulindac is known to cause regression of colorectal adenomatous polyps in familial adenomatous polyposis, less is known about the effect of sulindac on sporadic adenomas. The precise mechanisms of these effects also remain to be determined. AIMS: Sulindac was given to patients with sporadic colorectal adenomatous polyps to evaluate its effects on them, and histological analysis was performed to elucidate the mechanism of the polyp regression, as well the kind of adenomatous polys that are susceptible to the agent. SUBJECTS: 20 adenomatous polyps in 15 patients were studied. METHODS: Sulindac (300 mg daily) was given for four months, followed by colonoscopy with removal of the residual polyps. Polyp size, degree of atypia, inflammatory cell infiltration in the polyps, and immunostaining for mutant p53 product were evaluated before and after treatment. RESULTS: 13 of the 20 polyps shrank or disappeared. Patient sex, polyp location, size, degree of atypia, or p53 mutation did not affect the response, but polyps in older patients were more sensitive to sulindac. The degree of atypia or inflammatory cell infiltration was not affected by the treatment. A polyp containing a focal cancer was unresponsive. CONCLUSIONS: Sulindac can cause regression of sporadic colorectal adenomatous polyps.

Adenomatous Polyps↗

PubMed1997

The base specificities of tomato ribonuclease (RNase LE) and its Asp44 mutant enzyme expressed from yeast cells.

RNase LE from cultured tomato cells is a member of the RNase T2 family. It is, however, distinguishable from RNase Rh from Rhizopus niveus, a typical RNase of the RNase T2 family, by its CD spectrum in the 200-250 nm region. In order to reinvestigate the base specificity of RNase LE and to study the role of Asn44 in RNase LE, which is considered to correspond to the base recognition site Asp51 of RNase Rh, RNase LE, and its Asp mutant at the 44th position were expressed from yeast cells with the same expression system as RNase Rh [K. Ohgi, et al., J. Biochem., 109, 776-785 (1991)]. RNase LE with four extra amino acid residues at the 2nd amino acid residue of mature RNase LE and its Asp44 mutant were secreted from yeast cells to give a yield of 10 mg/liter and 0.5 mg/liter culture broth, respectively. The expressed RNase LE (RNase RNAP LE) had the same characteristics as native RNase LE in the CD spectrum and specific activity. This is the first example of the expression of plant RNase from microbes and in sufficient amount to perform further enzymological research. The base specificity of RNase LE was guanylic acid preferential and that of N44D was changed to a more adenylic acid preference as compared to that of RNase LE. These experiments showed that Asn44 of RNase LE is crucial for base recognition as the case of Asp51 in RNASE Rh, and also suggested that the base recognition mechanism of RNase LE is very similar to that of RNase Rh.

Amino Acid Sequence↗

PubMed1997

[Costimulatory molecules in autoimmunity: role of CD28/CTLA4-CD80/CD86].

Optimal T cell activation requires at least two signals. One is provided by the interaction between antigen-specific T cell receptor and antigen-MHC complexes. The other is provided by costimulatory signals. One best characterized costimulation is mediated by CD28/CTLA4-CD80/CD86 (CD28/B7). In the past decade, costimulatory signal mediated by CD28 has been shown to be critical to augment T cell proliferative response and effector function such as cytokine production. Recent intensive analysis of the CD28/B7 pathway have revealed unexpected means in which this pathway may be involved in the maintenance and breakdown of self-tolerance. In vivo studies using antagonists or transgenes of this pathway reveals that inappropriate expression of CD80, ligand for CD28/CTLA4, could induce autoimmunity and blockade of CD28/B7 pathway could ameliolate several autoimmune disease models. Furthermore, CD80 and CD86 plays differential roles for the development of autoimmune disease since helper T cell development is differentially affected by the blockade of either. CD80 or CD86 in certain conditions. More recent studies demonstrated the crucial role of CTLA4 in negatively regulating T cell activation and autoreactivity. Taken together, this pathway play pivotal roles for autoimmunity, and manipulation of this pathway raises the possibility for controlling autoimmune diseases.

Abatacept↗

PubMed1997

[Manipulation of costimulatory pathways in autoimmune disease].

The past year has seen significant advances in our understanding of the role of costimulatory pathways in antigen-specific T cell activation and maintenance of self-tolerance. It has been suggested that the absence of costimulators on normal tissue cells could serve to induce self-tolerance and that inappropriate expression of costimulators on antigen-presenting cells (APC) could activate self-reactive T cells, resulting in autoimmunity. CD28 on T cells and CD80 and CD86 on APC are key molecules in the maintenance and breakdown of anergy. CTLA-4Ig fusion protein, that binds to both CD80 and CD86 with high affinity and thereby prevents interaction of CD80/CD86 with CD28/CTLA-4, prevents or ameliorates several autoimmune disease in experimental animal models, supporting an importance of this pathway in the development of autoimmune diseases. However, the studies using specific monoclonal antibodies against CD80 and CD86 have shown different outcomes in individual autoimmune models. This suggests that the actual regulatory mechanisms of this pathway in autoimmunity is much more complex, because of the existence of two receptors (CD28 and CTLA-4) and two ligands (CD80 and CD86) and the opposite function of CD28 and CTLA-4 in T cell activation. Further investigation on physiological function of this pathway in vivo may help for developing rational therapeutic approaches manipulating this pathway.

Abatacept↗

PubMed1997

[Effects of low dose methotrexate therapy in rheumatoid arthritis: a comparison of three different dosage regimens].

The effectiveness of methotrexate (MTX) in treatment of rheumatoid arthritis (RA) was evaluated by following the course of 232 cases. The number of cases in which MTX treatment was assessed as effective amounted to 149 (64.2%), and among these the number of cases in which the effect was excellent amounted to 59 (25.4%). As for the time required to achieve the therapeutic effect, effectiveness was evident within one month in most cases and the more prominent was the result, the shorter was the time required to achieve the effect. In analysis of it's effectiveness, no relationship to the patient's background such as morbidity period, the extent of inflammation, or the period of administration of anti-rheumatic drugs was observed and this drug seems promising for treatment of severe inflammation in cases of RA with prolonged course enabling application to a wide range of patients. Also, therapeutic effectiveness was observed in a group of elderly patients, who were more than 65 years old. However, in such cases, MTX should be administered carefully because of its reported strong adverse effects. Its effectiveness and adverse effects have been shown to be dose-dependent. Therefore, as the optimum dosage of MTX, it is recommended to administer a dose of 5.0 mg/week initially for an evaluation period of two months and in those cases in which no effect is observed, the dose is then increased to 7.5 mg/week.

Adult↗

PubMed1997

[A case of microscopic polyangitis accompanied by hearing loss as the initial sign of the disease].

Here we report a case of microscopic polyangitis (MPA) with anti-neutrophil cytoplasmic antibodies against myeloperoxidase (MPO-ANCA) accompanied by perceptive dominant hearing loss as the initial sign of the disease. A 52-year-old woman was admitted to Tokyo Metropolitan Ohtsuka Hospital in April 1996 because of bilateral progressive hearing loss. On admission, she had presented bilateral perceptive hearing loss, fever, myalgia, and weight loss. Laboratory data showed accelerated erythrocyte sedimentation rate, proteinuria, microscopic hematuria, leukocytosis, hypoproteinemia, and elevated creatinine level. Serum level of MPO-ANCA was elevated. Chest X-ray and computed tomography showed mild pleural effusion and interstitial shadow in bilateral lung fields. The biopsy findings detected that focal glomerulonephritis, and necrotizing angitis of small artery in kidney. The diagnosis of MPA was made with clinical course, laboratory findings, radiographic findings, and biopsy finding. Treatment was initiated with 45 mg of prednisolone, followed by marked improvement of hearing loss and decreased titer of serum MPO-ANCA. There are only seven reports showing hearing loss as the initial sign of the disease occurred in polyarteritis nodosa and MPA. The present case suggests the possibility that hearing loss may be the symptom of MPO-ANCA associated vasculitis.

Anti-Inflammatory Agents↗

PubMed1996

Specific clonal T cell accumulation in intestinal lesions of Crohn's disease.

The initial cellular events that take place at the outset of autoimmune diseases and that may be the most important in terms of understanding their pathogenesis are poorly understood, especially in humans. This is mainly due to the difficulties in the identification of primary lesions and the accessibility to such material. In this respect, it is noteworthy that the appearance of small reddish erosions, known as aphthoid lesions, is known to be an early event in Crohn's disease. In the present study, accumulation of lesion-specific clonal TCR bands in the intestinal lesions of Crohn's disease patients was demonstrated by means of a highly sensitive method based on single strand conformational polymorphism. Such clonal accumulation was demonstrated in both aphthoid and discrete ulcer lesions. There were several TCR BV bands that were present in both aphthoid lesions and discrete ulcer lesions, but some were specific to the aphthoid lesions. In addition, the same aphthoid lesion-specific/dominant T cell clones were found to be expanded in separate aphthoid lesions of a single patient, and were absent from intervening, non-inflamed mucosa. Some of these bands may represent T cell clones activated primarily at the onset of disease.

Adolescent↗

PubMed1996

Chronic intestinal pseudoobstruction associated with autoantibodies against proliferating cell nuclear antigen.

Autoantibodies against proliferating cell nuclear antigen (PCNA) have been detected almost exclusively in sera from patients with systemic lupus erythematosus (SLE). Because of the extremely low prevalence of anti-PCNA, however, it has been difficult to establish its disease specificity and clinical associations. We present 2 cases in which patients with anti-PCNA developed severe gastrointestinal dysfunction that led to chronic intestinal pseudoobstruction. Neither patient had manifestations suggestive of SLE. Although sclerodermatous skin changes were minimal or absent in these patients, physical and radiographic findings indicated that systemic sclerosis was a likely cause of the gastrointestinal dysfunction. The similarity of the clinical features in these patients implies that the unusual detection of this unique autoantibody may not be a coincidence.

Autoantibodies↗

PubMed1996

Divergent effects of methotrexate on the clonal growth of T and B lymphocytes and synovial adherent cells from patients with rheumatoid arthritis.

OBJECTIVE: To define the mechanisms whereby methotrexate (MTX) manifests its effects in patients with rheumatoid arthritis. METHODS: T and B cells from peripheral blood and rheumatoid synovial tissues, synovial adherent cells, and the human fibrosarcoma cell line HT1080 and its mutant (defective in an enzyme in the nucleotide salvage pathway) were tested for clonal growth when cultured with MTX. Normal human fibroblasts and those with a deficiency in a salvage pathway were cultured with MTX in the presence or absence of purine and pyrimidine bases. RESULTS: Clonal growth of T and B cells, but not synovial cells, was inhibited by clinically relevant concentrations of MTX. Slowly proliferating fibroblast lines were resistant to MTX, whereas their rapidly proliferating counterparts were not. However, mutant fibroblast lines deficient in a salvage pathway were sensitive to MTX despite slow proliferation. Similarly, while skin fibroblasts were resistant to MTX, germline mutant fibroblasts deficient in a salvage pathway were sensitive to small concentrations of MTX. CONCLUSION: T and B lymphocytes, but not synovial cells, may be the target of MTX in vivo. Resistance to MTX may be associated with slow proliferation and the ability to synthesise nucleotides via salvage pathways. MTX can inhibit proliferation of even slowly growing cells by restricting the supply of nucleotides obtained via a salvage pathway, by removal of purine and pyrimidine bases, or by inducing a deficiency in a salvage pathway. It may be possible to manipulate the therapeutic effect of MTX by adjusting the amounts of purines and pyrimidines available to the cells in vivo.

Antirheumatic Agents↗

PubMed1996

[Usefulness of newly developed subcutaneous one point lifting method in gynecological laparoscopic operation].

We first introduced the abdominal wall lifting method in gynecological laparoscopic operations in 1994. Now we have developed a new one-point lifting technique (Tokyo Medical College method) that enables gynecological laparoscopic operations to be performed more safely, easily and economically. 1. The TMC method provides a sufficiently spacious operative field in the same way as artificial pneumoperitoneum and can overcome the negative influence of obesity on the operative field. 2. Because the abdominal wall is lifted up by means of a single stainless steel wire passed under the skin in this method, the limitations of previous methods are completely overcome. Furthermore setting up for this method is very easy and can be completed in a short time. 3. Because the aperture for the Surgigrip made in the abdominal wall is short and has a large internal diameter, we can manipulate operative instruments freely. Especially suturing and ligation can be carried out simply and accurately. 4. We were able to continue irrigation and suction without deterioration of the operative field and to easily remove resected tissue from the abdominal cavity. 5. The frequency of intracorporeal suture and ligation in this method increased significantly compared with the pneumoperitoneum method in cases of ovarian diseases. As a result, most operative procedures in ovarian diseases became cystectomies, preserving the healthy part of the ovary. This also reduced operative cost by avoiding expensive autosuture equipment. 6. There were no complications such as subcutaneous bleeding with this method. There was no significant difference between this method and pneumoperitoneum in terms of postoperative pain. The TMC method is a new laparoscopic operative technique that allows procedures to be performed under conditions close to laparotomy procedures and solves most of the problems of the pneumoperitoneum method.

Abdominal Muscles↗

PubMed1996

[Development of quality of life questionnaire for patients with colorectal cancer in surgical area--a study of reliability and validity of Tokyo Yamabuki Forum Version].

We developed a new questionnaire in the surgical area based on a core quality of life (QOL) questionnaire for patients with gastrointestinal cancer. In this study, we investigated the validity and reliability of a QOL questionnaire (Tokyo Yamabuki Forum Version) for patients with colorectal cancer. The questionnaire was composed of 17 items including 5 scales (basic sensory scale, psychological scale, physiological scale, defection-related scale and active scale) and a face scale as an global scale. The time needed to answer questionnaires was expected to be around 7 minutes and the questionnaires should basically be answered by the patients themselves everyday in the hospital. The study was performed in 10 hospitals in the Tokyo area, and 394 samples collected from 21 patients with rectal and colonic cancers were analyzed. A number of respondents failed to answer the question "Do you feel your foods tasty?", so we judged this item inappropriate and deleted it from the analysis. Fifteen items, including 5 scales showed satisfactory internal consistency and construct validity in correlation and factor analyses. Performance status showed a low correlation between each item, each scale and the global scale, while SDS and STAI showed an inordinately negative correlation with the fundamental and physical scales. Especially, SDS revealed an extremely close correlation with the active scale, and STAI showed an excessive correlation with the psychological scale. In the time course of QOL under chemotherapy, reductions (aggravations) were observed in both the total score of 15 items and global scale within one week postoperatively, but after that recovered to preoperative levels at 2 weeks postoperatively. A tendency to QOL improvement was observed 2 weeks after starting chemotherapy or chemoimmunotherapy. QOL of 13 patients was measured over 3 months, and the longest term was 8 months. The results suggested that this QOL questionnaire has sufficient reliability and validity to be usable for patients with colorectal cancer in the surgical area and that this model is applicable for long-term QOL surveys and frequent measurement.

Adult↗

PubMed1996

[Two cases of malignant lymphoma with initial symptoms like orbital cellulitis and complicated by hemophagocytosis].

We reported 2 patients with malignant lymphoma complicated by hemophagocytic syndrome. Their clinical signs at onset were those of orbital cellulitis. Lymphoma complicated with hemophagocytosis is called lymphoma-associated hemophagocytosis syndrome (LAHS) and its prognosis is reported to be very poor. So far as we know, this is the first report in the ophthalmological field. In our patients, we suspected that the lesions occurred from the orbit or skin of this area. The first patient was a 22-year-old man and the second patient a 16-year-old girl. The diagnosis was very difficult at the onset of disease. Within 6 months after the first opthalmological examination, both died. When orbital cellulitis is suspected and antibiotic therapy is ineffective, we should suspect hemophagocytic syndrome (HPS) and should examine serum ferritin which is a good markers of HPS. Early biopsy and consultation with a hematologist are very important.

Adolescent↗

PubMed1996

Three histologically different tiny gastric cancers developing adjacent to each other, resected endoscopically in a single mucosal piece.

In this report, we describe a case with triple tiny cancers of the stomach developing adjacent to each other and resected endoscopically in a single mucosal piece. The three cancers differed from each other histologically. The surrounding mucosa was atrophic pyloric gland mucosa with moderate to severe intestinal metaplasia. Both histological and serological examinations were negative for Helicobacter pylori. Each of the three cancer lesions was positive for mutant p53 product immunohistochemically. None of the cancers were positive for Epstein-Barr virus sequence in an in situ hybridization analysis. These lesions suggest that certain local conditions in the gastric mucosa can result in carcinogenesis of different histological types of gastric cancers.

Adenocarcinoma↗

PubMed1996

[Suppression of experimental autoimmune uveitis by energy restriction].

The effects of energy restriction on experimental autoimmune uveitis (EAU) were investigated. Seven-week-old, male Lewis rats were divided into three groups. Experiment A) A control group was fed ad libitum, a second group was given 50% calorie restricted food from the day of immunization, and a third group was given 50% calorie restricted food from 2 weeks before immunization. Experiment B) A control group was fed ad libitum, a second group was given 25% calorie restricted food from 4 weeks before immunization, and a third group was given 50% calorie restricted food 4 weeks before immunization. All rats were immunized with interphotoreceptor retinoid-binding protein (IRBP). In experiment A), in the group given 50% calorie restricted food from 2 weeks before immunization, and in experiment B), in the group given 50% calorie restricted food from 4 weeks before immunization, the onset of EAU was significantly delayed, the clinical symptoms were lessened, and delayed hypersensitivity against IRBP was suppressed. Clinically and histologically, the severity was also low. In the group given 50% calorie restricted food from 4 weeks before immunization, the titer of anti-IRBP antibody was also significantly lower than in the control group.

Animals↗