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Biomedical subjects

J Abe

Publications and source records attributed to J Abe.

At least 19 recordsLinked to original sources
PubMed1995

Antitumor effect induced by granulocyte/macrophage-colony-stimulating factor gene-modified tumor vaccination: comparison of adenovirus- and retrovirus-mediated genetic transduction.

Irradiated tumor cells genetically modified to secrete granulocyte/macrophage-colony-stimulating factor (GM-CSF tumor vaccine) are potent stimulators of systemic antitumor immunity. For the preparation of a GM-CSF gene-modified tumor vaccine, it is important to achieve efficient genetic transduction of tumor cells, leading to an appropriate expression of the induced gene. In this report, with a view to developing a protocol for an effective cancer vaccination therapy, we examined the vaccination efficacies of tumor cells secreting GM-CSF by either adenovirus- or retrovirus-mediated genetic transduction. By using an adenoviral vector, Adex1CAmGMCSF, a highly efficient gene delivery and a high-level expression of the GM-CSF gene were achieved. Unexpectedly, animal vaccination studies showed that the GM-CSF tumor vaccine transduced with the Adex1CAmGMCSF recombinant adenovirus (adenoviral GM-CSF tumor vaccine) was less efficacious than that transduced with the MFGmGMCSF recombinant retrovirus (retroviral GM-CSF tumor vaccine). The GM-CSF serum concentration attained by the adenoviral GM-CSF tumor vaccine was much higher than that obtained by the retroviral GM-CSF tumor vaccine. Our findings indicate that an optimal level of GM-CSF production is important for the tumor vaccine to elicit an adequate response in the host antitumor immunity.

Adenoviridae↗
PubMed1995

1,25-Dihydroxyvitamin D3 upregulates the phosphatidylinositol signaling pathway in human keratinocytes by increasing phospholipase C levels.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) induces the differentiation of normal human keratinocytes, in part by increasing their basal intracellular calcium levels (Cai) over a period of hours. Agonists such as ATP acting through membrane receptors cause an immediate but transient increase in Cai accompanied by an increase in inositol trisphosphate (IP3). Treatment of keratinocytes for 24 h with 1 nM 1,25(OH)2D3 resulted in a two- to four-fold potentiation of the Cai response of these cells to ATP. This potentiation was inhibitable with cycloheximide, unaccompanied by a change in total intracellular calcium pools, but associated with an increase in basal IP3 levels and ATP-stimulated IP3 production. Treatment with 1,25(OH)2D3 raised the protein and mRNA levels of phospholipase C isoenzymes, particularly phospholipase C-beta 1 in a dose-dependent manner. These studies indicate that 1,25(OH)2D3 modulates the keratinocyte signal transduction pathway by induction of phospholipase isoenzymes, a previously undescribed action for this hormone.

Adenosine Triphosphate↗
PubMed1994

Adoptive immunotherapy with murine tumor-specific T lymphocytes engineered to secrete interleukin 2.

Adoptive immunogene therapy of cancer is not widely studied, although it has been proposed as a promising strategy for cancer gene therapy. One of the major obstacles to this approach is the difficulty in introducing cytokine genes efficiently into T lymphocytes. In this report, we developed an adoptive immunotherapy model with murine tumor-specific cytotoxic T lymphocytes. By using an adenoviral vector, we achieved up to 100% gene transduction of murine T lymphocytes. Treatment of mice with the cytotoxic T lymphocytes genetically modified to produce interleukin 2 resulted in reduction of tumor metastasis and longer survival from intracerebral tumor death, providing a hopeful strategy for treatments of human cancers.

Adenoviridae↗
PubMed1992

Barley malt-alpha-amylase. Purification, action pattern, and subsite mapping of isozyme 1 and two members of the isozyme 2 subfamily using p-nitrophenylated maltooligosaccharide substrates.

Isoforms AMY1, AMY2-1 and AMY2-2 of barley alpha-amylase were purified from malt. AMY2-1 and AMY2-2 are both susceptible to barley alpha-amylase/subtilisin inhibitor. The action of these isoforms is compared using substrates ranging from p-nitrophenylmaltoside through p-nitrophenylmaltoheptaoside. The kcat/Km values are calculated from the substrate consumption. The relative cleavage frequency of different substrate bonds is given by the product distribution. AMY2-1 is 3-8-fold more active than AMY1 toward p-nitrophenylmaltotrioside through p-nitrophenylmaltopentaoside. AMY2-2 is 10-50% more active than AMY2-1. The individual subsite affinities are obtained from these data. The resulting subsite maps of the isoforms are quite similar. They comprise four and six glucosyl-binding subsites towards the reducing and the non-reducing end, respectively. Towards the non-reducing end, the sixth and second subsites have a high affinity, the third has very low or even lack of affinity and the first (catalytic subsite) has a large negative affinity. The affinity declines from moderate to low for subsites 1 through 4 toward the reducing end. AMY1 has clearly a more negative affinity at the catalytic subsite, but larger affinities at both the fourth subsites, compared to AMY2. AMY2-1 has lower affinity than AMY2-2 at subsites adjacent to the catalytic site, and otherwise mostly higher affinities than AMY2-2. Theoretical kcat/Km values show excellent agreement with experimental values.

Electrophoresis, Polyacrylamide Gel↗
PubMed1992

Selective expansion of T cells expressing T-cell receptor variable regions V beta 2 and V beta 8 in Kawasaki disease.

Kawasaki disease (KD) is an acute vasculitis complicated by the development of coronary artery abnormalities. The etiology of KD is unknown. Based on the observation that KD is associated with marked activation of T cells and monocyte/macrophages, we hypothesized that KD may be caused by a superantigen [e.g., a bacterial toxin that stimulates T cells expressing particular T-cell receptor beta chain variable (V beta) gene segments]. Peripheral blood T cells from patients in the acute and convalescent phases of KD and from various control groups were analyzed for T-cell receptor V beta gene expression by using a quantitative PCR technique and cytofluorographic analysis with available anti-V beta monoclonal antibodies. Patients with acute KD demonstrated significantly elevated levels of circulating V beta 2+ and V beta 8.1+ T cells compared to the other control groups. none of the other 20 V beta populations analyzed by quantitative PCR were found to be significantly elevated. Using flow cytometry, we confirmed a significant elevation of T cells reactive with anti-V beta 8.1 and the lack of change in several other V beta subsets--i.e. V beta 5.1, -5.2, -6.7, and -12. During the convalescence phase of KD, there was a reduction in the abnormal levels of V beta 2+ and V beta 8.1+ T cells. These observations suggest that KD may be caused by a superantigen and may provide insight into the nature of the etiologic agent.

Gene Expression↗
PubMed1992

Decreased interferon gamma and increased interleukin-4 production in atopic dermatitis promotes IgE synthesis.

The mechanism(s) responsible for increased IgE synthesis in atopic dermatitis (AD) are unknown, but they may be related to either decreased interferon gamma (IFN-gamma) and/or increased interleukin (IL)-4 production. In this study we examined peripheral blood mononuclear cells (PBMCs) from 21 patients with AD, six patients with psoriasis, and 22 nonatopic healthy controls for IFN-gamma and IL-4 production after stimulation with concanavalin A (Con A). The Con A-induced proliferative response of AD PBMCs was similar to the response of healthy controls (p = 0.9). After mitogen stimulation, however, AD culture supernatants contained significantly less IFN-gamma (p = 0.001) but increased IL-4 (p = 0.001) compared with supernatants from nonatopic controls. In contrast, PBMCs from patients with psoriasis produced normal levels of IFN-gamma and IL-4 in vitro. Since IL-4 is known to decrease IFN-gamma synthesis, we examined the effect of neutralizing anti-IL-4 on IFN-gamma production. Anti-IL-4 significantly increased IFN-gamma production in patients with AD (p = 0.008) and nonatopic controls (p = 0.02) but did not normalize IFN-gamma production by AD PBMCs. Supernatants from AD PBMCs, but not supernatants from nonatopic PBMCs, induced IgE synthesis in PBMCs from nonatopic donors (p = 0.02). When an anti-IFN-gamma receptor antibody, which blocks cellular binding of IFN-gamma, was added to supernatants from nonatopic controls their capacity to induce IgE synthesis was significantly greater (p = 0.03). These results demonstrate an imbalance of IL-4 and IFN-gamma production, which may contribute to increased IgE synthesis in AD.

Dermatitis, Atopic↗
PubMed1992

An autopsy case of Kawasaki disease with reference to occurrence of acute coronary thrombosis in the convalescent stage.

A one-year, four month-old boy who had suffered from Kawasaki disease died suddenly during convalescence despite intensive gamma-globulin treatment. Autopsy revealed a) sausage-like aneurysms of the left and right coronary arteries and fresh thrombosis in the right coronary aneurysm, b) fresh transmural myocardial necrosis in the whole wall of the left ventricle and the anterior part of the wall of the right ventricle, and c) swelling of the cervical lymph nodes and thymus (60 g). Histologically, fibrocellular thickening of the intima and destruction of the media and internal elastic lamina were conspicuous in the area of the aneurysm, but those of the intima and media in the areas adjacent to the aneurysm were mild. Abrupt narrowing of the lumen at the border between the aneurysm and periphery of the right coronary artery was detected, and this may have been responsible for formation of the thrombus in the right coronary aneurysm. In the systemic arteries, perivascular fibrosis was very noticeable despite less severe injury to the intima and media. These findings suggest that severe inflammation of the periarterial regions was present in the acute phase. The lymph system still showed inflammation, supporting the infectious or toxic nature of Kawasaki disease.

Acute Disease↗
PubMed1992

Neuronal hyaline inclusions observed in an autopsy case of Behçet's disease.

An autopsy case of Behçet's disease is reported. The patient, a 59-year-old Japanese woman, died of intestinal bleeding after a 34-year clinical course of Behçet's disease. She also suffered from recurrent oral aphthous ulcers, erythema nodosum-like cutaneous lesions and genital ulcerated lesions. Autopsy revealed marked atherosclerosis of the aorta and multiple deep ulcerations in the terminal ileum with no significant vascular lesions. Lewy bodies and globular hyaline inclusions in the neurons of the central nervous system were noted, although there were no clinical symptoms of Parkinson's disease throughout the clinical course. These findings appear to suggest that the patient was probably in the preclinical or early stage of Parkinson's disease. However, the presence of Lewy bodies in the 6th decade without any accompanying symptoms is very rare. This case seems to draw attention to the presence of these neuronal inclusions in Behçet's disease.

Autopsy↗
PubMed1992

Analysis of HLA-DQA1 in Japanese patients with type 1 diabetes mellitus, using DNA-PCR-RFLP typing.

DNA-polymerase chain reaction(PCR)-RFLP(restriction fragment length polymorphism) typing of the DQA1 gene was performed on 39 patients with type 1 diabetes and 30 controls. Analysis of the frequency of the subtypes of DQA1 alleles, using the DNA-PCR-RFLP typing technique, showed that the DQA1*0301 subtype was most strongly associated with the disease (97.4% vs 56.7%, R.R. = 19.8, pc less than 0.00005). These results indicated that DQA1*0301 may determine the disease susceptibility in the Japanese. In addition, we analyzed the frequency of the subtypes of DQA1 genes in the ten patients carrying the DRW8-DQW8 haplotype, and found that at least eight of them (80%) were classified as having DQA1*0301. The DRW8-DQW8-DQA1*0301 may be one of the susceptible haplotypes among the Japanese.

Diabetes Mellitus, Type 1↗
PubMed1992

Acute transverse myelitis in a 15-month-old girl: report of a case with MRI findings.

A 15-month-old girl demonstrated progressive weakness in all limbs. Magnetic resonance imaging (MRI) on admission revealed (1) diffuse and symmetric cervical cord swelling, (2) diffuse decrease and increase in signal intensity within the affected cord on T1- and T2-weighted images, respectively, (3) preserved anatomic structure of gray and white matter of the cord, and (4) lack of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhancing effect. She showed rapid clinical improvement in response to steroid therapy, and repeat MRI showed marked reduction in the degree of cord swelling and abnormal signal intensity. Based on the above clinical and MRI findings, the diagnosis of acute transverse myelitis was made. Although various pathologic conditions also could produce similar cord swelling and abnormal signal intensity on MRI, the third and fourth findings mentioned above suggested that the lesion was inflammatory rather than neoplastic. Our case indicates that MRI may be informative in differentiating acute transverse myelitis from other intramedullary disorders.

Acute Disease↗
PubMed1992

Characterization of human thymic lymphocytes forming rosettes with stromal cells.

The interaction of thymic lymphocytes and stromal cells is believed to be important for T cell development in thymus. In this study, thymic rosettes (TR), which are cell-cell complexes of thymic lymphocytes and stromal cells, were isolated from human thymic tissue, and were characterized. Treating human thymus with collagenase in mild condition, human TR were successfully isolated. Subsequently, TR were purified by the 1G sedimentation method. Human TR consisted of a stromal cell in center surrounded by lymphocytes. The stromal cells were positive for CD14, CD11b, and HLA-DR but negative for thymic epithelial cell specific mAb, UH-1, suggesting that they are macrophage/dendritic cells. The lymphocytes which formed TR (TRL) were mainly double positive (CD4+CD8+) and CD1+ cells, and few of them expressed bright CD3, indicating that TRL are in the intermediate maturation stage. TRL expressed activation markers (Ta1 and HLA-DR) in a significantly higher percentage of cells than did unselected thymocytes. Blocking test revealed that CD11a and CD2 are involved in the binding of TRL and the stromal cells as adhesion molecules.

Antigens, Surface↗
PubMed1992

[The significance of C4 locus II deletion in IgA nephropathy and Henoch-Schonlein nephritis and it's correlation with other HLA genes].

IgA nephropathy and HSP nephritis share some similar immunological abnormalities, for example, high IgA serum concentration, existence of IgA-IC, alternative pathway activation, monocyte and B-cell activation and the same histological findings of renal biopsy. The genetic factors may play an important role in both diseases. The increased frequency of homozygous null C4 phenotypes was reported in Caucasians. But the regional variation of C4 null alleles were recognized distinctly, and the significance of C4 isotype deficiency remained unclear. We studied the relationship between IgA nephropathy and Class II and Class III HLA antigens in Japanese by not only C4 protein phenotypes but also gene analysis (TaqI, Nla IV and EcoO 109). The frequency of C4 protein isotype deficiency was the same with control groups, but significantly increased C4 gene deletion was observed in both diseases. Neither DR4 nor DQB4/8/9 related to C4 gene deletion, but the total C4 serum concentration was lower in gene deletion groups. We could not detect any deviation between C4A and C4B locus deletion by Nla IV and EcoO 109 analysis. Considering the changing process of C4A to C4B, there is a possibility that the mechanism of deletion process itself causes the elevated sensitivity to the diseases.

Chromosome Deletion↗
PubMed1992

[Anesthetic experience of two patients with holoprosencephaly].

We experienced anesthetic management of two 6-month-old female patients with holoprosencephaly (HP). HP is characterized by hypoplasia of prosencephalon, facial anomalies (hypotelorism, flat nose, and/or small prolabium), abnormality of autonomic nervous system functions (hypernatremia and/or poikilothermia), and clonic convulsion. First case was a lobar type and the second case was an alobar type according to DeMyer's classification. In both cases repair of bilateral cleft lip was performed. Anesthesia was slowly induced with N2O-O2-halothane and maintained with fentanyl in N2O-O2. Body temperature (BT) was adjusted with a warming blanket while monitoring rectal temperature. In the first case clonic convulsion and bradycardias occurred during the postoperative period, which were treated with IV diazepam and isoproterenol. In the second case BT rose to 39 degrees C during postoperative period; 2 episodes of convulsions were observed; and airway obstruction occurred. They were treated accordingly. The most important points which should be kept in mind in the management of HP patients are the prevention of convulsion, adjustment of BT, maintenance of normal pulse rate and keeping a patient airway.

Anesthesia, Inhalation↗
PubMed1991

Selective stimulation of human T cells with streptococcal erythrogenic toxins A and B.

Streptococcal exotoxins have been implicated in the pathogenesis of a toxic shock-like syndrome and scarlet fever. Previous studies have demonstrated that these toxins are potent stimulators of human T cells and have structural homology to staphylococcal enterotoxins. In the current study, we investigated the mechanism by which streptococcal erythrogenic toxins type A (SPEA) and B (SPEB) activate T cells and compared it with anti-CD3 and the known "superantigen" staphylococcal enterotoxin B. SPEA was found to selectively activate T cells bearing V beta 8, V beta 12, and V beta 14, whereas SPEB selectively activated T cells bearing V beta 2 and V beta 8. Furthermore, fibroblasts transfected with MHC class II molecules were capable of presenting SPEA and SPEB to purified T cells. The T cell response to these toxins, however, was not MHC-restricted. Although the streptococcal exotoxins stimulated both CD4+ and CD8+ T cells, SPEA but not SPEB stimulated the CD4+ T cell subset proportionately more than the CD8+ T cell subset. Our results indicate that SPEA and SPEB, like the staphylococcal enterotoxins, are superantigens and suggest a mechanism by which they may mediate particular systemic syndromes associated with streptococcal infections.

Animals↗
PubMed1991

A clinical study of upper gastrointestinal endoscopy in Japanese children.

A total of 370 children who underwent upper gastrointestinal endoscopy (534 procedures) were retrospectively studied. All procedures were performed successfully. Side effects were demonstrated in only one case (0.2%), which was complicated by perioral cyanosis during the procedure. As to pre-endoscopic medication, it was thought that topical pharyngeal anesthesia alone may well be used for school-age children over 7 years of age, general anesthesia with endotracheal intubation for neonates, and intravenous sedation for infants and younger children. Of 370 patients studied, 70.8% had endoscopic diagnoses. The most common diagnosis was gastritis (136 cases), followed by peptic ulcer (75), duodenitis (29), and esophagitis (20). Several conclusions for indications were drawn from the present study. Pediatric upper gastrointestinal endoscopy is a safe and useful method for diagnostic and therapeutic approach, if adequate pre-endoscopic medication is chosen.

Adolescent↗
PubMed1991

Human leukocyte antigens in childhood idiopathic nephrotic syndrome.

An association of human leukocyte antigens (HLA) with idiopathic nephrotic syndrome (INS) in childhood was studied to characterize the immunogenetic background. We determined the class I antigens using the microlymphocytotoxicity test as well as class II antigens (DRB, DQB, DQA) and class III antigen (complement 4) using DNA restriction fragment length polymorphism (RFLP) in 36 children with INS. In the current study, neither the single allele in HLA class I antigen nor the single gene frequency in the class II region was significantly increased, in contrast to the results in Caucasian INS patients in whom a genetic predisposition to the HLA system, especially to HLA B8, DR3, and DR7, has been frequently reported. Also, in our data, the frequency of deletion of complement 4 gene was not different from that of the controls. These data suggest that there is a difference in immunogenetic background between Caucasian and Japanese INS patients as far as HLA is concerned.

Alleles↗