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Biomedical subjects

J Abe

Publications and source records attributed to J Abe.

At least 127 records · Page 7Linked to original sources

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↗

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↗

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↗

[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↗

[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↗

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↗

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↗

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↗

The noncalcemic analogue of vitamin D, 22-oxacalcitriol, suppresses parathyroid hormone synthesis and secretion.

OCT, a non-calcemic analogue of 1,25(OH)2D3 has been found to have a more potent activity than that of 1,25(OH)2D3 regarding cell differentiation and immunopotentiation activity, and to prolong the average life span of MRL/l mice. Recently, we found that OCT effectively suppressed the secretion and synthesis of PTH without inducing hypercalcemia. In primary cultures of bovine parathyroid cells, OCT was capable of suppressing PTH release in a dose-dependent manner. OCT was also active in vivo, and, like 1,25(OH)2D3, decreased the pre-pro(PTH) mRNA levels. In a group of rats with CRF, daily administration of OCT, 8 ng i.p. for 2 weeks returned PTH levels to normal without changes in serum calcium. Preliminary results in dogs with CRF indicated that after the administration of OCT 5 micrograms i.v., N-terminal PTH decreased by 76% without changes in Ca. In conclusion, OCT may provide a unique contribution to the treatment of secondary hyperparathyroidism.

Animals↗

A novel vitamin D3 analog, 22-oxa-1,25-dihydroxyvitamin D3, inhibits the growth of human breast cancer in vitro and in vivo without causing hypercalcemia.

Although 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has been shown to inhibit the growth of certain malignant cells, its hypercalcemic effect has prevented clinical application. We have recently developed a novel vitamin D3 analog, 22-oxa-1,25-(OH)2D3 (OCT), that is capable of promoting differentiation and inhibiting proliferation without inducing hypercalcemia. The present study was undertaken to determine whether OCT could be applied for the treatment of breast cancer with or without estrogen receptor (ER). OCT inhibited the proliferation of both ER-positive (MCF-7, T-47D, and ZR-75-1) and ER-negative breast cancer cells (MDA-MB-231 and BT-20) in vitro in a time- and dose-dependent manner, as determined by cell number and [3H]thymidine uptake. The antiproliferative effect was observed with a concentration as low as 10(-11) M OCT, and treatment of MCF-7 cells with 10(-8) M OCT for 8 days caused more than a 50% reduction in cell number compared with that of vehicle-treated cells. OCT was approximately 1 order of magnitude more potent than 1,25-(OH)2D3 in inhibiting the proliferation of MCF-7 cells. The in vivo effect of OCT was examined in athymic mice implanted with ER-negative MX-1 tumor, which was established as the xenograft derived from human breast carcinoma. Intratumor administration of OCT three times a week remarkably delayed the growth of MX-1 tumor in a time- and dose-dependent manner. The antitumor effect of 1 microgram/kg BW OCT was greater than that of 500 microgram/kg BW adriamycin, and the relative tumor weights in each group on day 26 were 29.7% and 50.5% of that in the vehicle-treated group, respectively. The effects of OCT and adriamycin were additive, and the relative tumor weight after 26 days of combined treatment was 21.7% of that in the vehicle-treated group. Oral administration of OCT was also effective, and the relative tumor weight in the OCT-treated group (1 microgram/kg BW) was 54.6 +/- 0.1% (mean +/- SEM) of that in the vehicle-treated group. Neither intratumor nor oral administration of OCT raised the serum calcium level in these animals. These results demonstrate that OCT is a potent inhibitor of the proliferation of breast cancer cells with or without ER and that OCT inhibits the growth of breast cancer in vivo without inducing hypercalcemia. We suggest that OCT may provide a new strategy for the treatment of breast carcinoma regardless of ER status.

Animals↗

[Facilitation and recovery of the H-reflex in children].

Facilitation and recovery of the H-reflex were studied in 63 children with cerebral palsy, and the results were compared with those obtained for 60 normal children. H waves were recorded from the gastrocnemius with surface electrodes, after applying paired stimulations to the tibial nerve in the midpopliteal crease. In normal children, both the facilitation and the recovery showed a tendency to decrease with their development, while those for children with cerebral palsy were more marked than normal children in all age groups. The present study indicated that the excitability of spinal alpha motoneurons and the subliminal fringe in the motoneuron pool might change due to the maturation of and the damage to the central nervous system in children. We consider that H-reflex examination provides useful information for the supraspinal control to the spinal mechanism to regulate muscle contraction in children as well as in adults.

Adolescent↗

Alteration of the properties of Aspergillus sp. K-27 glucoamylase on limited proteolysis with subtilisin.

An active derivative (mol. wt. 48,000) of Aspergillus sp. K-27 glucoamylase (mol. wt. 76,000) was obtained by limited proteolysis with subtilisin. The amino acid sequences of native and modified enzymes at the N-termini were Ala-Gly-Gly-Thr-Leu-Asp and Ala-Val-Leu, respectively. The proteolysis greatly decreased the affinity of the enzyme for amylopectin and glycogen, but not for oligosaccharides. It also reduced the ability of the enzyme to degrade raw starch, abolished the ability of the enzyme to adsorb onto starch granules, and eliminated the synergistic action of the enzyme in the hydrolysis of starch granules with alpha-amylase. These findings imply that the enzyme has a specific affinity site for polysaccharide substrates besides the catalytic site, i.e., a starch-binding site, and that the former is removed by proteolysis. The extent of the reduction in the activity for raw starches caused by the modification varied with the starch source, as the modified enzyme digested raw potato starch better than either raw corn or sweet potato starches. A new method for evaluation of the raw starch-digesting activity of glucoamylase is described.

Amino Acid Sequence↗

Cytoskeletal characteristics of myofibroblasts in benign neoplastic and reactive fibroblastic lesions.

The characteristics of the cytoskeleton of myofibroblasts were examined immunohistochemically in 10 extra-abdominal desmoid tumours, 3 palmar and 2 plantar fibromatoses and 5 nodular fasciitis; in the cultured cells of one desmoid tumour, and also ultrastructurally in 3 desmoid tumours. Polyclonal anti-desmin antibody reacted with the cells in 7 extra-abdominal desmoid tumours, 1 palmar fibromatosis, 1 plantar fibromatosis and 3 nodular fasciitis. Monoclonal antidesmin antibody reacted with cells in only 2 desmoid tumours. Desmin-positive spindle cells were scattered throughout these lesions. There were no marked ultrastructural differences between desmin-positive and desmin-negative desmoids. All specimens except one specimen of nodular fasciitis showed immunoreactivity for alpha-smooth muscle actin and vimentin. Muscle actin-positive cells were observed in all specimens. Cultured cells gave positive reactions with polyclonal desmin antibody as well as to vimentin antibodies and two preparations of actin antibodies, whereas the original tumour did not react with desmin antibody. The present studies suggested that the cytoskeleton of some myofibroblasts in both neoplastic and reactive lesions resembles that of smooth muscle cells.

Actins↗

Immunocytochemical demonstration of GAP-like immunoreactive neuronal elements in the human hypothalamus and pituitary.

GnRH-associated peptide (GAP)-like immunonreactive elements located in the human hypothalamus were investigated by PAP immunocytochemistry using specific antiserum against [pro-GnRH (14-69) OH]. Immunoreactive neuronal perikarya were distributed in the MPOA, PVN and infundibular nucleus, with the largest numbers of GAP-like immunoreactive perikarya found in the infundibular nucleus. We also detected the coexistence of GAP-like and GnRH-like immunoreactivities in the same neuronal perikarya in the MPOA by using a double immunolabelling procedure. In addition to the above regions immunoreactive neuronal perikarya were present in the region dorsal to the medial mammillary nucleus. GAP-like immunoreactive fibers were distributed in same areas that immunoreactive perikarya were observed. Many immunoreactive terminals were found adjacent to capillaries in the infundibulum. Immunoreactive dots, presumably terminals, were observed in the posterior pituitary and these were particularly evident along the margin adjacent to the anterior pituitary. The distribution pattern and density of GAP-like immunoreactive neuronal elements are compared with those of other mammalian species. We also compared GAP-like immunoreactive elements with that of GnRH as has been previously observed in the human hypothalamus.

Adult↗

Cytoskeletal properties of alveolar soft part sarcoma.

The immunohistochemical expression of cytoskeletal proteins in alveolar soft part sarcoma (ASPS) was studied by light and electron microscopy. Of the five cases examined by the avidinbiotin-peroxidase complex method, variable numbers of immunoreactive cells for desmin were found in three, for vimentin in two, for muscle-specific actins in three, and for alpha-smooth muscle actin in four. Immunoelectron microscopic study demonstrated that desmin and vimentin were localized on whorled bundles of intermediate filaments in the perinuclear cytoplasm. In addition, a few dispersed intermediate filaments became evident in specimens treated with saponin and fixed with tannic acid. These immunohistochemical results indicate that a few tumor cells of ASPS may express some properties of the cytoskeleton of smooth muscle cells in addition to those of skeletal muscle cells. Considering the discrepancies reported in the actin isoforms demonstrated in myogenic tumors, we conclude that ASPS is probably a peculiar, primitive myogenic tumor that does not show any distinctive features of rhabdomyogenic or leiomyogenic differentiation.

Actins↗

Chronic pancreatitis in muscular cytochrome c oxidase deficiency.

Chronic pancreatitis is described in a 10-year-old boy with mitochondrial myopathy due to cytochrome c oxidase (complex IV) deficiency. There have been few reports of chronic pancreatitis associated with congenital metabolic diseases. Marked pancreatic calcifications and pseudocysts of the pancreatic head and tail were demonstrated by computed tomography of the abdomen and by endoscopic retrograde pancreatography, which were thought to be useful methods for morphological examination of the pancreas. In the patient, no possible etiological factors were identified, including anomalous pancreatobiliary ductal junction or biochemical abnormalities. The association between cytochrome c oxidase deficiency and chronic pancreatitis remains to be established.

Child↗