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Biomedical subjects

N Itoh

Publications and source records attributed to N Itoh.

At least 451 records · Page 25Linked to original sources
PubMed1991

[Combination chemotherapy with methotrexate, vincristine, cisplatinum, cyclophosphamide, adriamycin, and bleomycin (MVP-CAB) for metastatic urothelial cancer].

We studied 31 patients with bidimensionally measurable metastases of urothelial cancer who were treated with a planned regimen (20 mg/m2 methotrexate, 0.6 mg/m2 vincristine, 500 mg/m2 cyclophosphamide, 20 mg/m2 adriamycin, and 30 mg bleomycin on day 1, and 50 mg/m2 cisplatinum on day 2) in cycles given every 3 weeks. CR was achieved in 4 patients (13%) and PR in 17 patients (55%). The response rates according to the disease characteristics were 71% for TCC, 33% for SCC, 67% for renal pelvis tumors, 67% for bladder tumors, 73% for lung metastases, 67% for liver metastases, and 67% for lymph node metastases. The median response duration and the number of cycles of therapy were 32 months/3 cycles for patients with a CR and 6 months/6 cycles for those with a PR. The median duration of survival was 32 months (range: 3-46) in CR, 11 months (range: 1-37) in PR, and 6 months (range: 2-10) in non responders (NC + PD). A significant prolongation of survival was noted in patients with either CR (p less than 0.01) or PR (p less than 0.05). Then main toxic effects were pulmonary fibrosis and myelosuppression. Two patients aged 73 and 81 died of pulmonary fibrosis. However, it was possible to prevent pulmonary fibrosis by not administering bleomycin to patients over 70 years of age, or to patients with pulmonary dysfunction. WBC count nadirs of less than 2,000/m3 were noted in 22 patients (71%). Platelet count nadirs of greater than 5 x 10(4)/mm3 were noted in 7 patients (23%). However, there were no deaths due to myelosuppression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Demonstration of islet cell antibodies in apparently non-insulin dependent diabetic patients; a marker for the later development of insulin dependency.

One hundred and ten diabetic patients who were apparently non-insulin dependent at 1984 were followed up for 5 years from 1984 to 1989. Islet cell antibodies (ICA) of the patients were tested in 1987. Eleven patients were positive for ICA and 99 were negative. There was no significant difference in age, sex, duration of diabetes, and HbA1c levels between ICA-positive and negative groups. Six of 11 (54.5%) patients in ICA-positive group developed insulin-requiring state in the period from 1984 to 1989, while only 5 of 99 (5.1%) patients in ICA negative group became insulin-requiring. Glucagon tolerance test (1 mg i.v.) was performed on 8 patients who developed insulin-requiring state; among them 4 patients were ICA-positive and other 4 patients were ICA negative. The serum C-peptide response to intravenous glucagon injection was markedly decreased in 3 of the 4 ICA-positive patients, and only mildly decreased in all the 4 ICA-negative patients. The markedly decreased C-peptide response indicates that these ICA-positive subjects had developed insulin-dependency. We conclude that the presence of ICA in apparently non-insulin dependent diabetics indicates a high risk for developing insulin-dependency.

Autoantibodies↗
PubMed1991

Influence of subepithelial deposits on permeability of the glomerular capillary wall in serum sickness nephritis in the rat.

Serum sickness nephritis was induced in male Fisher rats by immunization with egg albumin (EA). Correlations of subepithelial deposits (SD) with size and charge barriers of the glomerular filter were investigated using native (NF) and cationized (CF) ferritin as tracer probes. In proteinuric animals large numbers of NF molecules perfused from the abdominal aorta were observed to cross the glomerular basement membrane (GBM) and enter SD. The concentration of NF molecules was higher in GBM segments with SD than in GBM segments without SD, and the concentration of these molecules was higher within SD than in the intervening GBM. In contrast, CF clusters were fewer in number in the lamina rara externa (LRE) of GBM segments with SD than in the GBM segments without SD. CF particles could not be observed within SD, even in the areas of podocyte detachment. It is suggested that permeability in GBM segments with SD increases and that the development of proteinuria in this model can be attributed to alterations in both charge- and size-selective barriers to glomerular filtration.

Animals↗
PubMed1991

Immunological detection of the dystrophin molecule with antibody directed against the synthetic peptide.

We synthesized a peptide designated R8 (amino acid residues 1157-1201) based on the primary structure presumed from the nucleotide sequence of the cDNA clone from the gene for Duchenne muscular dystrophy. Antibody to the synthetic R8 generated by immunization of rabbits was tested on human and mouse skeletal muscle by Western blotting analysis. The antibody reacted with a component of the 400K dystrophin of normal human and mouse skeletal muscles, but not with components of the muscles of Duchenne muscular dystrophy patients and mdx mice. Thus we established that this peptide sequence is in fact missing in the protein product 'dystrophin' encoded by the DMD gene. The antibody may prove useful for the diagnosis of the Duchenne types of muscular dystrophy.

Amino Acid Sequence↗
PubMed1991

The cell-components and cytokines in the subcorneal microabscess of psoriasis.

Munro's microabscess of psoriasis has been generally considered to be composed of polymorphonuclear neutrophils (PMNs). However, the cell-components of the microabscess has not been fully clarified. To identify the presence of mononuclear cells (MNCs) in Munro's microabscess and the subcorneal pustule of pustular psoriasis, we observed psoriatic lesions histologically and immunohistologically. Morphologically a few MNCs were found among PMNs and they seemed to include Langerhans cells (CD1a+), helper/inducer T cells (CD4+, CD5+), and macrophages (CD14+) which expressed HLA-DR. Some of them seemed to produce gamma-interferon (IFN-gamma), interleukin 6 (IL-6) and IL-8. The keratinocytes surrounding the microabscess also had IL-8 and some epidermal cells of the proliferated epidermal papillae also expressed IL-6 and IL-8 in psoriatic lesions. The production of IL-6 and IL-8 is considered to effect both chemotaxis and the proliferation of epidermal cells. The presence of these cytokines also suggests that MNCs exist in Munro's microabscess and that they might contribute to the microabscess formation of psoriatic lesions.

Abscess↗
PubMed1991

Carbonic anhydrase III in serum in muscular dystrophy and other neurological disorders: relationship with creatine kinase.

We measured with a radioimmunoassay the concentrations of carbonic anhydrase III (CA-III, EC 4.2.1.1) in sera from 68 patients with muscular dystrophy, 10 carriers of Duchenne muscular dystrophy (DMD), and 63 patients with other neurological disorders. The values obtained were compared with those for creatine kinase (CK, EC 2.7.3.2). Serum CA-III was strikingly increased in patients with DMD (mean, 274.4 micrograms/L) and congenital (Fukuyama-type) (182.8 micrograms/L) and limb-girdle (203.7 micrograms/L) dystrophies and positively correlated with the activities of CK in patients with DMD. CA-III concentration decreased with the subjects' age and the severity of the disease, similar to the tendency observed between age or severity and the concentration of CK. We found moderately increased CA-III in patients with polymyositis, myotonic dystrophy, amyotrophic lateral sclerosis, spinal progressive muscular atrophy, or Kugelberg-Welander disease and in carriers of DMD.

Adolescent↗
PubMed1991

[The role of gamma-interferon in blister formation of bullous pemphigoid].

Recently it has been reported that cell-mediated immune (CMI) reaction is related to the blister formation as well as the reaction of autoantibody against the basement membrane zone (BMZ-Ab) in bullous pemphigoid (BP). Previously we reported that T-cells infiltrated were producing gamma-interferon (IFN-gamma) and that high levels of IFN-gamma were detected in the blister fluids of BP. In the present study, in order to find the effect of IFN-gamma on the skin, we have done the organ culture of normal skin explants with IFN-gamma. The dermal-epidermal separation (DES) was histologically observed in skin explants which were incubated with high level of IFN-gamma after 24 hours. The DES was found to be located between the basal layer and the site of laminin and type IV collagen. It is considered that IFN-gamma alters the antigenicity and mediates to release some other cytokines in CMI reaction. In addition to these, IFN-gamma seems to directly work on the DES in normal skin. Around the DES of the skin explants, plasminogen activator was accelerated immunohistologically. The results suggest that IFN-gamma mediated by CMI response also plays an important role as well as the autoantibody in the blister formation of BP.

Adult↗
PubMed1991

Ultrastructural studies of hepatocyte cytoskeletons of phalloidin-treated rats by quick-freezing and deep-etching method.

We observed hepatocyte cytoskeletons in phalloidin-treated rats by the quick-freezing and deep-etching method in three dimensions and compared them with the ultrastructural findings on conventional ultrathin sections. The numbers of microvilli in dilated bile canaliculi were decreased in the rats treated with phalloidin for 1 wk. In hepatocytes the cytoplasm around bile canaliculi could be divided into three layers, increased microfilament layer, cell organelle layer of secretory system and increased smooth surface endoplasmic reticulum layer. In the rats treated with phalloidin for 4 wk, microfilaments were extended into the cytoplasm near the nucleus in addition to the increased number of large lysosomes and microtubules. In both groups, three-dimensional structures of microfilaments could be visualized around bile canaliculi and along cell borders by the quick-freezing and deep-etching method. The branching microfilaments with the diameters of 7 to 10 nm were directly attached to other filaments, cell organelles or cytoplasmic sides of cell membranes. Moreover, bundled intermediate filaments were increased around peribiliary microfilaments associated with long-term cholestasis. It is suggested that excessive accumulation of peribiliary microfilaments disturb the secretion of bile components into bile canaliculi. The cytoskeletal reorganizations of intermediate filaments seem to alter the arrangements of various cell organelles.

Actin Cytoskeleton↗
PubMed1991

Expression of murine dihydrofolate reductase complementary DNA in oocytes of Xenopus laevis.

1. Murine dihydrofolate reductase was produced efficiently in a Xenopus laevis oocyte that received microinjection of the dihydrofolate reductase mRNA. 2. Murine dihydrofolate reductase was produced under the direction of the plasmid pAdD26SVpA, which contains adenovirus major late promoter and the simian virus 40 T antigen gene for transcription initiation and murine dehydrofolate reductase complementary DNA fragment. 3. Injection of the plasmid pDHFR26, which contains murine dihydrofolate reductase complementary DNA and normal transcription initiation site segment in the 5' untranslational region, failed to produce proper translational products due to improper transcription.

Animals↗
PubMed1991

[A case of the primary pancreatic lymphoma].

Primary pancreatic lymphoma is extremely rare. A case of the primary pancreatic lymphoma was described. A 74-year-old man was admitted to our hospital on May 26, 1990, because of epigastralgia and 5-kg weight loss. On admission, physical examination revealed mild epigastric tenderness without hepatosplenomegaly and superficial lymphadenopathy. The serum amylase level and trypsin level were normal but serum CA19-9 was slightly elevated. The diagnosis of the pancreatic cancer (body and tail) was strongly suspected on subsequent examination by US, CT, ERP and angiography. Partial pancreatectomy and splenectomy were performed. Pathological examination of the tumor in the pancreas showed diffuse non-Hodgkin's lymphoma and B-cell origin. Peripancreatic fat was involved but peripancreatic lymph nodes and spleen were intact, which strongly suggested that the isolated lymphoma was pancreatic origin.

Aged↗
PubMed1990

Molecular cloning and sequence analysis of cDNA encoding the macrophage lectin specific for galactose and N-acetylgalactosamine.

The primary structure of the macrophage lectin specific for galactose and N-acetylgalactosamine (macrophage asialoglycoprotein-binding protein, M-ASGP-BP) has been deduced from its cDNA sequence. The M-ASGP-BP cDNA encoded a protein consisting of 306 amino acid residues with a molecular mass of 34,242 daltons. The sequence was highly homologous with that of the rat liver asialoglycoprotein receptor (rat hepatic lectin, RHL), particularly that of RHL-1 (the major form of RHL), throughout its whole length, and especially so in its putative membrane-spanning region and carbohydrate recognition domain. There were two N-glycosylation sites in M-ASGP-BP, the location of which were identical to those in RHL-1. However, M-ASGP-BP was characteristic in having a shorter cytoplasmic tail, and an inserted segment of 24 amino acids containing an Arg-Gly-Asp sequence between the membrane-spanning region and carbohydrate recognition domain.

Acetylgalactosamine↗
PubMed1990

The complete amino acid sequence of the shorter form of human basic fibroblast growth factor receptor deduced from its cDNA.

We have isolated a full-length cDNA for human basic fibroblast growth factor (bFGF) receptor-like protein from a human placenta cDNA library. Determination of the nucleotide sequence of the cDNA allows elucidation of the complete amino acid sequence of the receptor (731 amino acids) which has two extracellular immunoglobulin-like domains, a transmembrane domain and an intracellular tyrosine kinase domain. The receptor has remarkable amino acid similarity (98% identity) to the shorter form of murine bFGF receptor reported recently (H.H. Reid et al. (1990) Proc.Natl.Acad.Sci. USA 87, 1596-1600). The receptor described here is expected to be the shorter form of human bFGF receptor.

Amino Acid Sequence↗
PubMed1990

Cysteine proteinase inhibitor in the ascitic fluid of sarcoma 180 tumor-bearing mice is a low molecular weight kininogen. Partial NH2- and COOH-terminal sequences and susceptibility to various glandular kallikreins.

It has been proposed that a cysteine proteinase inhibitor (CPI) found in the ascitic fluid of Sarcoma 180 tumor-bearing mice is a kind of kininogen (Itoh, N., Yokota, S., Takagishi, U., Hatta, A., and Okamaoto, H. (1987) Cancer Res. 47, 5560-5565). The first 40 NH2-terminal residues and 54 residues of the COOH-terminal sequence, including the bradykinin moiety of highly purified ascites CPI, were determined and compared with those of mammalian low molecular weight kininogens (LMWK). The significant identity between these amino acid sequences with those of other mammalian LMWKs suggests that ascites CPI corresponds precisely to mouse LMWK. This kininogen has a light chain composed of 43 amino acid residues, which contains a unique Met-Ala-Arg-bradykinin sequence. Hydroxyproline, which was recently identified in the bradykinin sequence of kininogen from the ascitic fluid of a cancer patient, was not found in the kinin moiety of this mouse kininogen. Among purified glandular kallikreins from human, hog, rat, and mouse, only mouse submaxillary gland kallikrein was able to release bradykinin from this kininogen. Kinetic studies using a newly synthesized fluorogenic substrate, N-t-butoxycarbonyl-Met-Ala-Arg-MCA, revealed that mouse kallikrein hydrolyzes this substrate approximately 80-fold faster than does hog kallikrein, suggesting that the unique Met-Ala-Arg-bradykinin sequence is responsible for the varied susceptibility of mouse kininogen to different kallikreins.

Amino Acid Sequence↗
PubMed1990

[Determination of the normal range of serum LH and FSH levels in normal adult males--comparison with IRMA and RIA].

To determine the normal range of serum LH and FSH levels, blood samples from 53 normal adult males were measured by a double antibody radioimmunoassay system and a new immunoradiometric assay (IRMA) system. It was necessary to evaluate the individual pulsatile secretion and the differences in measured values among laboratories to determine the normal range. Therefore, in 53 normal adult males lacking any evidence of hormonal abnormalities, blood was sampled at 9:00 a.m. daily for 3 days, and these samples were measured in 3 laboratories. The result of the hormone concentration of blood sample was not appropriate as the normal range because of the high amplitude of LH and FSH pulses. Coefficient values (CV) between the mean value of the first two samples and the mean value of all three samples were small. Therefore, the mean value of the first two samples was clinically accurate for use as the normal range. Significant differences in measured values were observed among the 3 laboratories. The normal range, which included individual pulsatile secretion, and the differences in measured values among the laboratories was as followings: LH (RIA): 7.6-13.7 mIU/ml, LH (IRMA): 2.1-4.7 mIU/ml, FSH (RIA): 4.7-9.5 mIU/ml, FSH (IRMA): 3.0-7.4 mIU/ml. The serum LH and FSH levels of 68 untreated male infertility patients tended to rate high with respect to our normal range. It was considered that the normal range determined in this study was useful for clinical management.

Adult↗
PubMed1990

[The inhibitory effects of glycyrrhizin and glycyrrhetinic acid on the metabolism of cortisol and prednisolone--in vivo and in vitro studies].

This experiment was carried out to investigate the inhibitory effects of glycyrrhizin and its aglycon, glycyrrhetinic acid, on the metabolism of cortisol and prednisolone in vivo and in vitro. The effects of glycyrrhetinic acid on the metabolism of cortisol were examined in vitro using rat and bovine liver homogenate. Glycyrrhetinic acid inhibits both hepatic delta 4-5-reductase and 11 beta-hydroxysteroid dehydrogenase in a dose-dependent manner, resulting in the decrease of conversion of cortisol to cortisone, dihydrocortisol and tetrahydrocortisol in rats. The concentrations of glycyrrhetinic acid inducing 50% inhibition of rat liver delta 4-5-reductase and 11 beta-hydroxysteroid dehydrogenase were 2.5 x 10(-6) M and 8.5 x 10(-6) M, respectively. Glycyrrhetinic acid also inhibits bovine liver 11 beta-hydroxysteroid dehydrogenase and 20-hydroxysteroid dehydrogenase in a dose-dependent manner, resulting in the decrease of conversion of cortisol to dihydrocortisol and prednisolone to 20-dihydroprednisolone. The concentrations of this drug inducing 50% inhibition of 11 beta-hydroxysteroid dehydrogenase and 20-hydroxysteroid dehydrogenase were 8.2 x 10(-6) M and 6.5 x 10(-6) M, respectively. This is the first report which demonstrates the marked inhibitory effects of glycyrrhetinic acid on 11 beta-hydroxysteroid dehydrogenase and 20-hydroxysteroid dehydrogenase in vitro. The effects of glycyrrhizin on the rate of metabolism of cortisol as well as prednisolone were studied in 23 patients with or without adrenal insufficiency. Glycyrrhizin had no effect on diurnal rhythm of plasma cortisol in 7 control subjects with normal pituitary adrenal axis, whereas glycyrrhizin significantly increased the half-time (T 1/2) and area under the curve (AUC) for plasma cortisol in 4 patients with adrenocortical insufficiency taking oral cortisol. Glycyrrhizin also increased T 1/2 and AUC for plasma prednisolone in 12 patients taking an oral prednisolone for at least 3 months. These results indicate that the suppression of hepatic delta 4-5-reductase, 11 beta-hydroxysteroid dehydrogenase and 20-hydroxysteroid dehydrogenase by glycyrrhizin and glycyrrhetinic acid may delay the clearance of cortisol and prednisolone and prolong the biological half-life of cortisol or prednisolone.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1990

Anti-skeletal muscle antibodies in the sera from myasthenic patients with thymoma: identification of anti-myosin, actomyosin, actin, and alpha-actinin antibodies by a solid-phase radioimmunoassay and a western blotting analysis.

We recently reported a strong association between the occurrence of anti-skeletal muscle (SM) antibodies and the presence of thymoma in patients with myasthenia gravis (MG). To further examine the immunoreactivity of MG sera against human muscle antigens, we developed a solid-phase radioimmunoassay (RIA) using purified muscle antigens and a Western blotting analysis in MG sera with high titers of anti-SM antibodies. Our results showed that MG patients with thymoma (thymoma group) had markedly high titers of anti-myosin and anti-actomyosin antibodies than those without thymoma (non-thymoma group). Furthermore, a close correlation was found between titers of anti-SM, anti-myosin and anti-actomyosin antibodies. The antibody titers against actin, alpha-actinin and tropomyosin were all low and did not correlate with titers of anti-SM antibodies. But, significant levels of these three antibodies were found in the thymoma group. By a Western blotting analysis, immunoreactivity of sera from the thymoma group appeared to be predominantly directed against myosin, actin and alpha-actinin.

Autoantibodies↗