Search PubMed⌕ Search

Biomedical subjects

M Iwata

Publications and source records attributed to M Iwata.

At least 289 records · Page 16Linked to original sources
PubMed1995

Synaptic loss in the proximal axon of anterior horn neurons in motor neuron disease.

This report deals with an ultrastructural investigation of the synapses of the proximal axons of normal-appearing anterior horn neurons of 7 patients with amyotrophic lateral sclerosis (ALS) and 4 patients with motor neuron disease who had no upper motor neuron and corticospinal tract involvement (lower motor neuron disease, LMND). Specimens from 12 age-matched individuals who died of non-neurological diseases served as controls. Proximal axons directly emanating from the normal-appearing neurons were examined: 42 axons were from ALS patients, 43 from LMND patients and 87 from controls. Our results show that the number of synapses on axon hillocks, as well as the lengths of the synaptic contact and of the active zone were reduced in both groups of patients (P < 0.0001), but no significant differences were seen between patients and controls with respect to the synaptic parameters of initial axon segments. There was no overall difference between ALS and LMND patients. These findings suggest that the electrophysiological functions pertaining to integration of electrical inputs into the axon and information transduction on the axon may be greatly impaired in the early stages of motor neuron diseases, and that the observed synaptic alterations may be pathological events, likely to be due to anterior horn neuron degeneration.

Aged↗
PubMed1995

Biological characteristics of neuroblastoma with spontaneous tumor reduction: a case report.

The authors examined the biological characteristics of a neuroblastoma with spontaneous tumor reduction. A 6-month-old boy with a pelvic neuroblastoma underwent surgical extirpation of the tumor 1 month after diagnosis. The size of the tumor reduced spontaneously while he was awaiting operation. The low proliferative activity of the tumor cells and the presence of apoptosis in the tumor tissue were shown by an immunohistochemical method using anti-PCNA antibody and a DNA fragmentation analysis, respectively. These results suggest that the spontaneous tumor reduction seen in this patient may well be caused by the overwhelming apoptosis of tumor cells.

Apoptosis↗
PubMed1995

Cross-linking of the TCR-CD3 complex with CD4, CD8 or LFA-1 induces an anti-apoptotic signal in thymocytes: the signal is canceled by FK506.

The immunosuppressant FK506 did not block differentiation of double-negative thymocytes into double-positive (DP) cells, but interfered with differentiation of DP cells into mature single-positive cells in a fetal thymus organ culture system, suggesting that FK506 inhibits positive selection. The drug also reduced the number of DP cells recovered after the culture. As positive selection depends on the inhibition of thymocyte apoptosis at its DP stage by signaling through the TCR-CD3 complex and some of the accessory molecules, including CD4, CD8 and LFA-1, we studied the possibility that FK506 enhanced apoptosis by itself or canceled the inhibition of apoptosis. The results indicated that FK506 was hardly toxic or hardly affected anti-CD3-induced DNA fragmentation in isolated thymocytes in vitro. On the other hand, upon cross-linking TCR-CD3 together with CD4, CD8 or LFA-1, FK506 markedly enhanced DNA fragmentation and cytolysis. The drug, however, hardly or only slightly enhanced these responses upon cross-linking TCR-CD3 together with CD2, CD28, Thy-1 or H-2Kd. Cross-linking of TCR-CD3 together with CD4, CD8 or LFA-1 markedly inhibited glucocorticoid-induced death and the inhibition was canceled by FK506. Furthermore, cross-linking of TCR-CD3 together with LFA-1 potentially induces both an apoptosis-inducing signal and an FK506-sensitive anti-apoptotic signal, and that the latter signal may be related to an essential signal for positive selection.

Animals↗
PubMed1995

Evidence for a short form of alpha 1(IV) as a major polypeptide in bovine lens capsule.

The extracts from bovine lens capsule with acetic acid contained, after reduction, three major collagenous polypeptides with M(r) = 180k, 175k, and 160k, which were specifically immuno-stained with anti-type IV collagen polyclonal antibody. The biochemical properties of 180k and 160k polypeptides were akin and were distinct from that of 175k polypeptide [J. Biochem. (1993) 114,358-362]. In the present study, evidence that the 160k and 180k polypeptides from bovine lens capsule both originated from alpha 1(IV) was obtained on the basis of reactivity with a monoclonal antibody that recognizes alpha 1(IV) chain at the collagenous sequence contained in [KGEPGLPGRGFPGFP]. The epitope-bearing sequence was identified from the following three experiments. Pepsin-solubilized polypeptides from human placenta were purified by affinity chromatography on the antibody-coupled column and sequenced. The restriction map of the clones positively reactive with the monoclonal antibody from human placenta cDNA library was superimposed on that of human alpha 1(IV) cDNA at a specific region. Synthetic peptides corresponding to the sequence were assayed for inhibitory activity against the reaction between epitope-bearing pepsin fragments and the antibody. The 180k and 160k polypeptides showed similar intensities in protein staining as well as in immuno-staining with the monoclonal antibody. In contrast, the 175k polypeptide did not react with the monoclonal antibody, indicating that it is a genetically distinct type IV collagen chain, presumably alpha 2(IV) from its abundance. The 160k, a major type IV collagen polypeptide, is a short form of alpha 1(IV) present as a tissue form in bovine lens capsule.

Amino Acid Sequence↗
PubMed1995

ANCA-associated vasculitis and lupus-like syndrome caused by methimazole.

A 24-year-old woman with Graves' disease treated with methimazole for 4 years, developed recalcitrant ulcers on the lower legs. Histological studies demonstrated vasculitis in deep dermal vessels accompanied by C3 deposition. Laboratory investigation revealed lupus-like abnormalities (leucocytopenia, positive antinuclear and antidouble strand (ds) DNA antibodies, and positive ANCA). The leg ulcers dramatically improved after methimazole was withdrawn. In addition, leucocytopenia and the immunological abnormalities soon faded. Although lupus-like syndrome is well known to be induced by antithyroid drugs, vasculitis is a rare complication. To the best of our knowledge, this is the first report describing ANCA-associated vasculitis caused by methimazole.

Adult↗
PubMed1995

Comprehensive treatment of advanced neuroblastoma involving autologous bone marrow transplant.

Encouraging results are reported with high-dose chemotherapy and total body irradiation followed by autologous bone marrow transplantation in the treatment of advanced neuroblastoma. However, relapse remains a significant problem. We used high-dose chemotherapy, surgery, intraoperative radiation and an autologous bone marrow transplant treated in vitro to remove tumor cells followed by 13-cis-retinoic acid to treat 36 children with advanced neuroblastoma. This comprehensive treatment appears to improve the survival rate of patients with advanced neuroblastoma, including those with N-myc amplification and bony involvement. The disease-free survival rate was 66% (95% confidence interval, 49-84%) at 3 years. All patients who received 13-cis-retinoic acid developed cheilitis, but no bone marrow depression occurred in these patients. Five patients developed hemolytic uremic syndrome (HUS) post-transplant. This may have been related to the procedure used for total body irradiation. Patients who had their kidneys shielded during this procedure did not develop this syndrome. Patients who received local irradiation at the primary site showed no evidence of relapse in this region, indicating that such therapy may help to prevent a relapse. These data suggest a high rate of 3 year disease-free survival with this treatment strategy. The nonrandomized nature of the study and use of multiple modalities precludes analysis of the specific contribution of each.

Adrenal Gland Neoplasms↗
PubMed1995

Evaluation of new medium with chromogenic substrates for members of the family Enterobacteriaceae in urine samples.

A new medium containing 5-bromo-4-chloro-3-indolyl-beta-D-glucuronide cyclohexylammonium salt (Glu agar) for Escherichia coli and a new medium containing 5-bromo-3-indolyl-beta-D-galactoside (Gal agar) for beta-galactosidase-positive members of the family Enterobacteriaceae were compared with MacConkey agar in a diagnostic trial with 3,562 urine specimens. The isolation rates of E. coli and beta-galactosidase-positive Enterobacteriaceae were increased 8.4 and 19.5%, respectively. The sensitivities and specificities of Glu agar and Gal agar were 98.5 and 100% and 99.2 and 99.5%, respectively.

Bacterial Typing Techniques↗
PubMed1995

Protein synthesis inhibition induces cytoresistance in cultured human proximal tubular (HK-2) cells.

After sublethal injury, proximal tubular cells acquire resistance to further attack. This study evaluated whether this could be a possible consequence of decreased protein synthesis, a potential correlate of cell damage. To this end, cultured human proximal tubular cells (HK-2) were subjected to 0-24 h of protein synthesis inhibition (> 98%), either by adding protein synthesis inhibitors [cycloheximide (CH) or verrucarin A] or by inducing sublethal ATP depletion (antimycin A + 2-deoxyglucose). After 24 h of these treatments, significant resistance to Ca2+ ionophore/ATP depletion-induced attack was noted (assessed by vital dye exclusion, compared with normal cells). That < or = 6 h of protein synthesis inhibition caused no cytoresistance implied the importance of evolving protein depletion rather than nonspecific drug effects or protein synthesis inhibition per se. CH plus ATP depletion did not induce additive benefits, suggesting a common mechanism. Cytoresistance was dissociated from the extent of free Ca2+ loading and ATP depletion but was associated with a decrease in membrane deacylation. CH removal promptly restored protein synthesis and cytoresistance was lost; conversely, ATP recovery did not restore protein synthesis and cytoresistance persisted. The emergence of cytoresistance correlated with the disappearance/dephosphorylation of an unidentified 130-kDa tyrosine-phosphorylated protein/protein complex (denoted pp-130). The functional significance of this change was suggested by the fact that tyrosine phosphatase inhibition with orthovanadate maintained pp-130 expression and prevented the cytoresistant state. We conclude that protein synthesis inhibition in HK-2 cells can induce a cytoresistant state. Suppression in phospholipase activity and altered tyrosine phosphorylation events may have functional significance in this regard.

Adenosine Triphosphate↗
PubMed1995

Signaling through CD40 rescues IgE but not IgG or IgA secretion in X-linked immunodeficiency with hyper-IgM.

The ligand for CD40 (CD40L) is a membrane protein on activated T cells that induces B cell proliferation and differentiation. Several mutations of the CD40L gene were reported responsible for defective class switching of B cells in an X-linked immunodeficiency with hyper IgM (X-HIM). We studied four affected males from three families and found three independent mutations including new mutations of CD40L gene. In every X-HIM patient tested, however, anti-CD40 plus IL-10 did not induce class switching from IgM to IgG or IgA, even in the presence of Staphylococcus aureus Cowan I strain (SAC). CD4+ T cell clones, expressing CD40L on their surface, also did not rescue IgG or IgA induction by X-HIM peripheral blood B cells in vitro. But signaling through CD40 induced both B cell proliferation and IgE secretion when IL-4 was added to the culture. Taken together, these results show that in vitro signaling through CD40 rescues IgE but not IgG or IgA secretion by peripheral blood X-HIM B cells and suggest that in vivo CD40 and CD40L interaction might be necessary for IgG and IgA differentiation in X-HIM.

Amino Acid Sequence↗
PubMed1995

Significance of renal kininases in patients with primary aldosteronism.

To elucidate the significance of renal kininases in primary aldosteronism (PA), urinary total kininase, kininase I, II and neutral endopeptidase 24.11 (NEP) were examined and evaluated for the regulation mechanisms of these kininases. Total kininase, kininase I and NEP were significantly higher in PA than in normotensives (NT), whereas no difference was found for kininase II. Moreover, 42% of total kininase consisted of unknown kininase(s), different from kininase I, II or NEP. There were significantly positive correlations between plasma aldosterone concentration and total kininase, kininase I and unknown kininase(s) in PA. After the adrenalectomy, urinary kininases decreased into normal ranges, and unknown kininase(s) were negligible. These findings suggested that: 1) kininase I and NEP are accelerated in PA; 2) unknown kininase(s) differing from kininase I, II or NEP may exist in PA; 3) mineralocorticoids may regulate renal kininases; and 4) accelerated renal kininases may play some role in disorders of the renal water-sodium metabolism and in high blood pressure in PA.

Adrenalectomy↗
PubMed1995

Significance of renal kininases in patients with Cushing's syndrome.

To further clarify the significance of renal kininases in patients with Cushing's syndrome, daily urinary excretions of total kininase, kininase I, Ii and neutral endopeptidase 24.11 (NEP) were examined and evaluated for the relations between plasma cortisol level and these kininases. Urinary total kininase kininase I, II and NEP were significantly higher in patients with Cushing's syndrome than in normotensives. There was a significant positive correlation between plasma cortisol level and total kininase or NEP, and the same tendency was observed between plasma cortisol level and kininase I. After adrenalectomy, urinary kininases decreased to normal levels. These findings suggested that: 1) kininase I, II and NEP are accelerated in Cushing's syndrome; 2) glucocorticoids may regulate renal kininases; and 3) accelerated renal kininases may play some role in disorders of the renal water-sodium metabolism and in high blood pressure in Cushing's syndrome.

Adrenalectomy↗
PubMed1995

The mechanisms of the renal effects of neutral endopeptidase inhibitor in rats.

To further investigate the mechanisms of renal effects of neutral endopeptidase 24.11 (NEP) inhibition, we employed a specific NEP inhibitor, UK 73967 (UK), with or without a specific kinin receptor antagonist, Hoe 140 (Hoe), or nitric oxide (NO) synthase inhibitor, N-monomethyl-L-arginine (L-NMMA), in Sprague-Dawley rats, and evaluated the urinary NEP, kinins, cGMP and plasma atrial natriuretic peptide (ANP). None of the variables changed with vehicle injection. After injection of UK, NEP decreased significantly and urinary kinins, cGMP, urine volume (UV) and urinary sodium excretion (UNaV) increased significantly. Injected Hoe canceled the increase in UV and UNaV induced by UK. Plasma ANP did not show any difference between vehicle and UK groups. With a pretreatment of L-NMMA, injected UK decreased NEP and increased kinins, while urinary cGMP, UV and UNaV did not increase. In conclusion, augmented kinins may play an important role in the renal water-sodium metabolism by NEP inhibition, and NO may contribute to the kinins' action on this mechanism, while ANP may not contribute to it, at least in normotensive rats. Moreover, changes in urinary cGMP do not reflect the changes in plasma ANP, but rather, those in NO under this condition.

Adrenergic beta-Antagonists↗
PubMed1995

The role of kinins and atrial natriuretic peptide on the renal effects of neutral endopeptidase inhibitor in normotensive and hypertensive rats.

To further elucidate the renal effects of NEP inhibition, we employed NEP inhibitor UK 73967 (UK), with or without a kinin receptor antagonist Hoe 140 (Hoe), in Sprague-Dawley normotensive rats and DOCA-salt hypertensive rats. In Sprague-Dawley rats: 1) injected UK significantly decreased NEP, and increased kinins, urine volume (UV) and urinary sodium excretion (UNaV), while none of the variables changed with vehicle treatment; 2) no difference was found in plasma ANP between the vehicle and UK groups; and 3) Hoe canceled the increases of UV and UNaV caused by UK. In DOCA-salt rats: 1) infused UK significantly decreased NEP, and increased UV and UNaV, while UV and UNaV were slightly decreased, and NEP did not change with vehicle treatment; 2) plasma ANP was significantly higher in UK group than in the vehicle group; and 3) Hoe could not abolish the increase of UV and UNaV induced by UK. These data indicate that the contributions of renal kinins and plasma ANP to the diuretic and natriuretic mechanisms of NEP inhibition may differ between Sprague-Dawley normotensive rats and DOCA-salt hypertensive rats.

Adrenergic beta-Antagonists↗
PubMed1995

[A case of localized fibrous mesothelioma arising from visceral pleura of the right lower lobe].

A 56-year-old male who had been followed for chronic hepatitis had cough and hemosputum. Chest X-ray and CT films showed an abnormal mass shadow in the right thorax. On suspicion of intrathoracic tumor, resection was performed. The tumor, which was on the diaphragm without invasion, was pedunculated and arose from the bottom surface of visceral pleura of the right lower lobe. From the microscopic findings and immunohistochemical staining, the tumor was diagnosed as localized fibrous mesothelioma. Some localized fibrous mesothelioma exhibit as malignant tumor. Therefore, complete resection and intensive follow-up should be done.

Humans↗