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Biomedical subjects

M Nagata

Publications and source records attributed to M Nagata.

At least 271 records · Page 15Linked to original sources
PubMed1996

[Surgical effects of trabeculotomy combined with sinusotomy in advanced glaucoma patients controlled in normal intraocular pressure of 15 mmHg or higher].

Trabeculotomy combined with sinusotomy was performed in 30 eyes with advanced open angle glaucoma, whose intraocular pressure (IOP) had been controlled in their high teens with only topical medications. The mean pre- and postoperative IOP levels were 18.2 +/- 1.2 mmHg (mean +/- standard deviation) and 13.2 +/- 1.2 mmHg and the pressure reduction was 4.6 +/- 2.4 mmHg. Average pressure reduction was 28.8 +/- 9.3% and pressure reduction of 30% or more was obtained in 45% of the treated eyes. The pre- and postoperative medication scores were 4.47 +/- 1.50 and 3.07 +/- 1.17, respectively. There was statistically significant difference between the pre- and postoperative medication score. We had no cases in which the IOP reduction was greater than 9 mmHg and postoperative IOP was 9 mmHg or less. A 3-line drop in visual acuity was seen in only one eye. Twenty two of 30 eyes (73%) were controlled at 14 mmHg or less with medications at the last examination. These results show that trabeculotomy combined with sinusotomy in effective, and this procedure can be considered as an alternative choice for surgical treatment in advanced glaucoma.

Aged↗
PubMed1995

Differential effects of granulocyte-macrophage colony-stimulating factor on eosinophil and neutrophil superoxide anion generation.

Eosinophils (EOS) are specifically recruited to sites of allergic inflammation and parasitic infection, while neutrophil (NEUT) influx predominates in bacterial infections. This biologic selectivity suggests that granulocytes may respond differently to inflammatory mediators such as granulocyte-macrophage-CSF (GM-CSF). To establish the mechanisms of the response of granulocytes to GM-CSF, isolated human peripheral blood EOS and NEUT were obtained from allergic rhinitis patients and incubated in vitro with this cytokine. Incubation with GM-CSF (10 or 100 pM) significantly enhanced FMLP-stimulated EOS superoxide anion (O2-) generation, LTC4 release, and adhesion to tissue culture plates. Both GM-CSF-enhanced EOS adhesion and O2- generation were inhibited by an anti-beta 2 (CD18) Ab suggesting that this beta 2 integrin was associated with increased cell function. In contrast, FMLP + cytochalasin B were required to demonstrate GM-CSF enhancement of NEUT O2- and LTB4 generation; GM-CSF had no effect on NEUT adhesion. Furthermore, GM-CSF augmentation of FMLP + cytochalasin B-activated NEUT O2- generation was not affected by anti-beta 2 Ab but was blocked by a 5-lipoxygenase-activating protein antagonist, BAY x 1005. Finally, 0.1 to 10 nM LTB4 mimicked the GM-CSF-priming effect on NEUT O2- generation, thus suggesting that the augmented NEUT respiratory burst was the result of LTB4 production and its effect on the NEUT. These data demonstrate that GM-CSF promotes EOS and NEUT O2- generation to FMLP via distinct mechanisms: enhanced adhesion of EOS vs autocrine-priming by enhanced LTB4 generation of NEUT.

Adult↗
PubMed1995

Administration of monoclonal antibodies against vascular cell adhesion molecule-1/very late antigen-4 abrogates predisposing autoimmune diabetes in NOD mice.

The interaction of vascular cell adhesion molecule-1 and very late antigen-4 (alpha 4 beta 1-integrin) has been recently known to be profoundly involved in the trafficking of lymphocytes from the circulation into the inflammatory tissues. To elucidate the role of these molecules in the development of autoimmune diabetes, the expression of these adhesion molecules on inflamed islets and the effects of administration of monoclonal antibodies to these molecules on insulitis and overt diabetes were evaluated in nonobese diabetic (NOD) mice. Immunohistochemical study revealed the overexpression of vascular cell adhesion molecule-1 on vascular endothelium near or within inflamed islets and alpha 4-integrin on islet-infiltrating mononuclear cells. Either anti-vascular cell adhesion molecule-1 or anti-alpha 4-integrin monoclonal antibody prevented the transfer of diabetes in irradiated NOD mice which received spleen cells from acutely diabetic NOD mice. When both monoclonal antibodies were administrated to NOD mice during 2-30 weeks of age, neither lymphocytic infiltration to islets nor overt diabetes was observed. Furthermore, administration of these antibodies even from 10 weeks of age could inhibit the development of insulitis and diabetes, whereas administration during 2-5 weeks of age could not. Splenocytes obtained from these treated mice showed no significant change of cytokine production and preserved the ability to transfer diabetes into NOD scid/scid mice. This suggests that treatment with antibodies against these adhesion molecules can inhibit insulitis and diabetes without affecting the Th1/Th2 balance or effector T cells. The blockade of vascular cell adhesion molecule-1/very late antigen-4 interaction would be suitable for therapeutical treatment of the predisposing and latent type I (insulin-dependent) diabetic subjects.

Animals↗
PubMed1995

Eosinophil adhesion to vascular cell adhesion molecule-1 activates superoxide anion generation.

Adhesion to the adhesion protein, VCAM-1, on vascular endothelium is proposed to be an important factor in the selective accumulation of eosinophils at sites of allergic inflammation. To determine whether eosinophil adhesion to VCAM-1 is also associated with an alteration of eosinophil function, human peripheral blood eosinophils were isolated from allergic donors and incubated in VCAM-1-coated wells. Spontaneous adherence of isolated eosinophils to VCAM-1-coated wells was greater than cells incubated in FCS-treated control wells (38.0 +/- 1.6% vs 17.1 +/- 1.9%, n = 16, p < 0.0001). In addition, eosinophils incubated in VCAM-1-coated wells spontaneously generated modest but significant amounts of superoxide anion (O2-; 2.0 +/- 1.3 vs 00.5 +/- 0.5 nmol/5 x 10(5) cells, n = 9, p = 0.029). Moreover, when 100 nM FMLP was added to eosinophils in the presence of VCAM-1, significantly greater O2- generation occurred (7.2 +/- 0.9 vs 5.4 +/- 1.0 (FCS control) nmol/5 x 10(5) cells, n = 9, p = 0.009). Adhesion, as well as the spontaneous and enhanced O2- generation to FMLP activation, was blocked by the monoclonal anti-alpha 4 integrin Ab, HP 1/2, implying involvement of an alpha 4 integrin-VCAM-1 interaction. In contrast, the anti-CD18 mAb, L130, inhibited the spontaneous and enhanced O2- generation to FMLP without affecting adhesion, suggesting an involvement of CD18 molecule(s) only in VCAM-1-enhanced respiratory burst. Finally, 1 microM genistein, a tyrosine kinase inhibitor suppressed the VCAM-1-enhancing effect on eosinophil O2- generation and VCAM-1-induced tyrosine phosphorylation, suggesting a role for tyrosine phosphorylation in this eosinophil functional up-regulation. Our observations suggest that eosinophil adhesion to VCAM-1 may be an important step in determining the eventual functional activity of these cells as they migrate from the circulation to the airways and contribute to the allergic inflammatory process.

Adult↗
PubMed1995

Cloning, sequencing and expression of a novel cDNA encoding human vacuolar ATPase (14-kDa subunit).

A cDNA encoding the 14-kDa subunit of vacuolar ATPase was cloned from human fetal brain. The sequence was composed of 680 nucleotides containing an open reading frame of 357 nucleotides. The deduced peptide sequence consisted of 119 amino acid residues with a calculated molecular weight of 13,369 Da and a pI of 5.19. Overall, this amino-acid sequence was respectively 69% and 70% identical to those of Manduca sexta and Drosophila melanogaster 14-kDa subunits, although the two representatives of Class Insecta were remarkably similar to one another (91% identity). Three regions in particular (the N-terminal, amino acids 5-36; the middle, residues 58-68; and the C-terminal, residues 88-118) were highly conserved. Hence, we think that the 14-kDa subunits have evolved from the same ancestral gene, and that the three conserved regions are important for the structure and function of vacuolar ATPase. A single 0.8-kb band was detected in various human tissues by Northern blot analysis. Since the human 14-kDa subunit is expressed ubiquitously, it might be a housekeeping protein. A separate transcript found in the cDNA library lacked a 6-bp segment in the 5' non-coding region (nucleotides -40 to -35) and also carried a 23C to T (8Thr to Ile) point mutation in the coding region; these minor differences likely reflected normal polymorphism.

Amino Acid Sequence↗
PubMed1995

Long-term results of non-filtering surgery for the treatment of primary angle-closure glaucoma.

BACKGROUND: We previously reported the effectiveness of goniosynechialysis and trabeculotomy ab externo for adult-onset glaucoma. In this study, we performed non-filtering surgery on patients with primary angle-closure glaucoma and studied the long-term outcome of this treatment. METHODS: Included in this study were 35 eyes of 25 patients with primary angle-closure glaucoma, each of which had an intraocular pressure greater than 20 mmHg with maximal tolerated antiglaucoma medication, even after laser iridotomy or surgical iridectomy. Of these 35 eyes, 22 underwent trabeculotomy and 13 underwent goniosynechialysis. All patients were followed up for at least 18 months. RESULTS: In 21 (95%) of 22 eyes after trabeculotomy, and in 12 (92%) of 13 eyes after goniosynechialysis, intraocular pressures were well controlled at or below 21 mmHg at the final examination. However, in two of the 21 eyes in which trabeculotomy was a success, and in four of the 12 eyes in which goniosynechialysis was successful, the procedure had to be repeated before adequate control of pressure was achieved. CONCLUSION: Our results show that intraocular pressure in most cases of primary angle-closure glaucoma can be controlled by restructuring of the physiologic aqueous outflow route by means of goniosynechialysis or trabeculotomy, and that filtering surgery is not necessary.

Aged↗
PubMed1995

Acute renal failure associated with Candida albicans infection.

A 16-year-old male with a long history of steroid-responsive nephrotic syndrome developed fever, abdominal pain, thrombocytopenia and acute renal failure. The clinical course and renal histology were similar to, but not typical of, haemolytic uremic syndrome. Positive cultures (throat, oesophagus, stool), an elevation in serum levels of specific antibody and fungal polysaccharide (1,3) beta-D-glucan and response to the antifungal therapy indicated an association between this syndrome and infection with Candida albicans.

Acute Kidney Injury↗
PubMed1995

A novel function of islet-derived CD8+T cells in initiating and developing autoimmune insulin-dependent diabetes mellitus in non-obese diabetic (NOD) mice.

Accumulated studies revealed that CD4+T cells were initially required for diabetes in NOD mice, whereas interaction of CD4+T/CD8+T cells is not fully understood. To address this question, we established islet-derived CD4+T cells and CD8+T cells from NOD mice. One NOD neonate that received CD4+T cells developed diabetes and insulitis with CD8+T cells. Administration of cyclophosphamide to non-diabetic recipients accelerated the development of diabetes, while none of the mice with anti-CD8 antibody did so. Similarly, it was observed that neonates that received islet-derived CD8+T cells developed diabetes and obvious insulitis mainly with CD4+T cells. Administration of anti-CD4 antibody with transfer of CD8+T cells inhibited insulitis. These results imply that CD8+T cells function as an initial element to recruit CD4+T cells to islets as well as a final effector.

Animals↗
PubMed1995

Motor unit firing behavior in slow and fast contractions of the first dorsal interosseous muscle of healthy men.

The motor unit recruitment threshold and firing rate were evaluated during slow and fast contraction of the first dorsal interosseous (FDI) muscle by healthy young men. Using a special quadrifilar electrode myoelectric activity was recorded during voluntary isometric contraction. Motor unit action potentials (MUAPs) were decomposed into individual MUAP trains by the electromyography (EMG) signal decomposition technique. Recruitment thresholds of the motor units decreased with the increase in the speed of contraction, and there was no recruitment reversal despite the increase. In terms of rate coding, the firing rates of the motor units increased as the speed of contraction increased; however, a high threshold motor unit always had a lower firing rate than a low threshold motor unit regardless of the contraction speed. At all contraction speeds, recruitment and rate coding may act through the same mechanism. If excitation of the motoneuron pool occurs rather than excitation of an individual motoneuron, a low threshold motor unit is easier to recruit and fire repetitively than a high threshold one. The motor unit firing behavior during fast contraction basically may be the same as during slow contraction.

Action Potentials↗
PubMed1995

Macrophages in childhood IgA nephropathy.

The role of glomerular macrophages in IgA nephropathy in children was investigated using a new monoclonal antibody (KP1) as a probe. The average number of glomerular macrophages per patient (ANM/P) was closely correlated with the degree of hematuria (P < 0.01) as well as with the degree of leukocyturia (P < 0.01) in the absence of any correlation with proteinuria, serum IgA levels or the interval between the detection of urine abnormalities and renal biopsy. ANM/P was significantly higher in patients diagnosed pathologically as having focal and diffuse proliferative glomerulonephritis than in patients with minor glomerular abnormalities or advanced sclerosis (P < 0.05). Among various types of glomerular morphology in individual patients, macrophages predominantly infiltrated glomeruli with cell-proliferative lesions despite an absence of any increase in glomeruli with minor abnormalities or with sclerosis. Macrophages were mainly localized within the capillary lumen in association with endocapillary proliferative lesions (tuft necrosis), they accumulated in areas of mesangial proliferation, and they were attached to Bowman's capsule in segmental lesions. Macrophages were less evident in sclerosis. Furthermore, ultrastructural analysis revealed macrophages in the paramesangial areas in close proximity to lytic changes in the glomerular basement membrane and effacement of epithelial foot processes. In addition, some cases in repeat biopsy shows prolonged or increased values of ANM/P after several years of interval in association with progression of proliferative lesions. These results suggest that macrophages infiltrate glomeruli during acute glomerular inflammation, and that they are involved in mesangial proliferation or the development of extracapillary lesions in the absence of apparent clinical symptoms. Furthermore, recurrence or prolonged infiltration may promote progression of IgA nephropathy.

Antibodies, Monoclonal↗
PubMed1995

Dystrophic form of inherited epidermolysis bullosa in a dog (Akita Inu).

We report a dog with dystrophic epidermolysis bullosa. This 4-year-old female Akita Inu, a species of Canis familiaris var. japonicus Temminck, had a 3-year-history of ulcers and scars over the pressure areas on the limbs, and dystrophic nails, since the age of 1 year, which corresponds to early adulthood in humans. Electron microscopy of a blister revealed separation beneath the lamina densa, and a reduction in the number of anchoring fibrils. The NC-1 domain of type VII collagen was positively stained with monoclonal antibody LH7.2 at the basement membrane zone. These findings indicate that humans and dogs have a similar response to antibody LH7.2, which may aid the development of an animal model for this disease.

Animals↗
PubMed1995

Preventive effect of dai-saiko-to (da-chai-hu-tang) extract on disrupted hepatic active oxygen metabolism in rats with carbon tetrachloride-induced liver injury.

In order to clarify the preventive action of Dai-Saiko-to (Da-Chai-Hu-Tang) extract (TJ-8) on the progression of acute liver injury in rats intoxicated with carbon tetrachloride (CCl4), we examined the effect of post-oral TJ-8 administration on hepatic active oxygen metabolism following the progression of this liver damage. When TJ-8 (1.0 g/kg body weight) was administered orally to male Wistar rats aged five weeks 2 hrs after i.p. injection of CCl4 (1.0 ml/kg body weight), an apparent liver injury occurred. Significant prevention against the progression of liver injury was found at 24 hrs after injection, judging from the activities of serum transaminases, indexes of liver cell damage. Liver cytosolic superoxide dismutase (SOD) activity decreased 2 and 24 hrs after CCl4 injection, while liver cytosolic catalase and glutathione reductase (GSSG-R) activities decreased 24 hrs after the injection. At 2 and 24 hrs after CCl4 treatment, liver cytosolic Se-containing glutathione peroxidase (GSH-px) activity did not change and liver cytosolic glucose-6-phosphate dehydrogenase (G-6-PDH) activity increased. Post-oral TJ-8 administration significantly ameliorated decreases in liver SOD, catalase, and GSSG-R activities at 24 hrs after CCl4 injection, but did not affect liver Se-GSH-px and increased liver G-6-PDH activities at 24 hrs after the injection. Although increased liver lipid peroxide level and decreased liver reduced glutathione and ascorbic acid levels were observed 2 and 24 hrs after CCl4 injection, post-oral TJ-8 administration significantly prevented these changes found at 24 hrs after injection. These results indicate that post-oral TJ-8 administration can prevent the progression of acute liver injury in CCl4-injected rats by inhibiting enhanced lipid peroxidation and by improving disrupted active oxygen metabolism in the injured liver.

Administration, Oral↗
PubMed1995

Distribution of mRNAs for natriuretic peptides in RV hypertrophy after pulmonary arterial banding.

It has been unclear whether the increases in transcript accumulation for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) during pressure overload are caused by the direct hemodynamic stress imposed on the myocytes or mediated by systemic hormonal factors. We examined the levels and regional distributions of ANP and BNP mRNAs in the hypertrophied right ventricle produced by experimental coarctation of main pulmonary artery (PA) in rats and compared them with those of skeletal alpha-actin mRNA, which is known to be a genetic marker for cardiac hypertrophy. In this experimental model, the left ventricle was free from the influence of pressure overload. By Northern blot analysis, remarkable increases in mRNAs for ANP and BNP, as well as skeletal alpha-actin, were observed in the right ventricle at 1 day after PA banding. Changes of expression of these genes were minimal in the left ventricle. ANP mRNA levels in the right ventricle increased further at days 3 and 7, whereas BNP mRNA remained at its day 1 level through 7 days. Increased expression of ANP, BNP, and skeletal alpha-actin mRNAs occurred exclusively in the right ventricular (RV) free wall and in the junctional region between the RV free wall and the interseptal wall as determined by in situ hybridization. These data suggest that local stimuli caused by hemodynamic overload induce cardiac hypertrophy and its associated increases in ANP and BNP expression in the RV free wall.

Actins↗
PubMed1995

Molecular cloning, characterization, and chromosomal mapping of a novel human gene (GTF3A) that is highly homologous to Xenopus transcription factor IIIA.

We have isolated a novel human cDNA that is highly related to Xenopus transcription factor IIIA (TFIIIA). This clone contains an open reading frame of 1,269 nucleotides encoding 423 amino acids, including nine repeats of the Cys2His2-type of zinc-finger domain. A comparison of its sequence with Xenopus TFIIIA revealed 63% identity in nucleic acids and 58% identity in amino acids over a large portion of the gene and predicted peptide, indicating that the human homologue is likely to function as a transcription factor. The zinc-finger domains of the predicted protein also showed homology with those of human genes such as WT1, transcriptional repressor YY1, and MYC-associated zinc-finger protein (MAZ). Northern analysis showed expression in various tissues examined. The human TFIIIA gene (GTF3A) was localized to chromosome band 13q12.3-->q13.1 by fluorescent in situ hybridization (FISH).

Amino Acid Sequence↗
PubMed1995

Mitosis and the presence of binucleate cells among glomerular podocytes in diseased human kidneys.

Podocytes are highly differentiated cells that appear to be postmitotic. However, it is unclear whether cell division or the proliferation of podocytes takes place in the setting of glomerular injury. In this study, we analyzed the presence of mitotic figures and of binucleate or multinucleate podocytes in diseased human kidneys by light and electron microscopy. Among the 164 cases analyzed, mitotic figures in podocytes were found in only one cell, in a case of focal and segmental glomerulosclerosis, and 6 cases provided evidence of two or more nuclei in a single podocyte. Serial sections by light microscopy confirmed that the nuclei in multinucleate cells were separate and of approximately the same size. Electron-microscopic analysis of the binucleate podocytes revealed hypertrophy and effacement of foot processes. These findings indicate that, in human podocytes, mitosis without cytokinesis (cell division) results in binucleate cells in cases of glomerular injury.

Biopsy↗