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N Itoh

Publications and source records attributed to N Itoh.

At least 361 records · Page 20Linked to original sources
PubMed1993

Role of tyrosine-5 in the cytoplasmic tail of the macrophage asialoglycoprotein receptor in the rapid internalization of ligands.

A macrophage asialoglycoprotein binding protein (M-ASGP-BP), which is an endocytic receptor specific for Gal/GalNAc-terminated glycoproteins, was shown to be functionally active as a homooligomer (hexamer or octamer) of a single polypeptide chain of 42 kDa [Ozaki, K., Ii, M., Itoh, N., & Kawasaki, T. (1992) J. Biol. Chem. 267, 9229-9235]. In various endocytic receptors, a four-amino-acid sequence, Tyr-X-Y-Phe, in the cytoplasmic domain has been identified as an internalization signal [Pearse, B.M.F. & Robinson, M.S. (1990) Annu. Rev. Cell Biol. 265, 151-171]. The amino-terminus of the M-ASGP-BP deduced from its cDNA sequence was found to contain the sequence, Tyr5-Glu6-Asn7-Phe8, in its cytoplasmic tail. This was confirmed by the fact that the recombinant M-ASGP-BP isolated from transfected COS-1 cells was found to have the amino-terminal sequence, Thr2-Met3-Ala4-Tyr5-Glu6-Asn7-Phe8. The role of this presumptive internalization signal in the cytoplasmic tail was studied by measuring the endocytic activity of the wild-type and mutant M-ASGP-BPs expressed on COS-1 cells through transfection with the wild-type and mutant cDNAs prepared by oligonucleotide-directed mutagenesis, respectively. On the deletion of Tyr5 or replacement of it with alanine, the internalization of asialoorosomucoid (ASOR) decreased to approximately one-fourth that in the case of the wild-type molecule. On replacement of Tyr5 with phenylalanine, the internalization proceeded at a rate similar to that in the case of the wild-type molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Pharmacokinetics and potential use of gentamicin in budgerigars (Melopsittacus undulatus).

The pharmacokinetics of gentamicin were evaluated in budgerigars. Intramuscular (i.m.) administration of 5 and 10 mg/kg dosages produced serum gentamicin concentrations of 17.3 and 37.0 micrograms/ml respectively, at 0.25 hr following injection, but concentrations declined with a terminal half-life of 0.53 h. Based on these results, a dosage regimen of 5 to 10 mg/kg of gentamicin, intramuscularly, every 8 hours for up to 3 days, was considered to be safe and could be used against many of the common bacterial infections in budgerigars. Serum AST, ALT, LDH, CK, creatinine and uric acid values were determined after i.m. injection of either gentamicin or physiological saline every 8 hours for up to 3 days, and tissue samples of various organs were examined histologically. The most prominent adverse effect found was muscular damage at the injection site. Measurement of AST, ALT and CK activity seemed to be a sensitive method to determine pathological changes at the injection site in the budgerigars.

Animals↗
PubMed1993

Elevation of plasma angiotensinogen in rats with experimentally induced nephrosis.

In order to determine the activity of the renin-angiotensin system in the nephrotic syndrome, the plasma concentration of angiotensinogen was measured in rats with puromycin aminonucleoside (PA)-induced nephrosis using two different methods: a direct radioimmunoassay, which measures both angiotensinogen and des-angiotensin I-angiotensinogen, and an indirect assay, which measures angiotensin I liberated from angiotensinogen by excess renin. The plasma concentration of angiotensinogen as measured by the direct assay increased before the appearance of PA-induced hypoproteinemia or proteinuria and subsequently decreased to normal levels simultaneously with the appearance of proteinuria. The indirect assay of angiotensinogen also demonstrated an increased concentration of plasma angiotensinogen before the development of nephrosis, but the level decreased to below normal after the appearance of proteinuria. Both plasma renin concentration and renin activity also increased simultaneously with the increase in plasma angiotensinogen. The difference between the concentrations of plasma angiotensinogen determined by these methods increased before and during the early phase of PA-induced nephrosis, suggesting the increased consumption of angiotensinogen by renin during this period. Measurement of plasma corticosterone and serum interleukin-6 revealed that these circulating factors were not involved in the elevation of plasma angiotensinogen in rats with PA-induced nephrosis. These results indicate that the renin-angiotensin system is activated before the appearance of PA-induced nephrotic syndrome.

Angiotensinogen↗
PubMed1993

Loss of glomerular anionic sites and the development of albuminuria in rats with streptozotocin-induced diabetes.

Examination was made of changes in the anionic sites of the glomerular basement membrane (GBM) in rats with streptozotocin (STZ)-induced diabetes by the immersion method of polyethyleneimine (PEI). PEI particles in GBM of diabetic rats significantly decreased from the 1st through the 8th week. Urinary albumin excretion in diabetic rats significantly increased at the 2nd but not earlier week. Insulin treatment effectively prevented decrease in PEI particles in STZ-injected rats. In rats with STZ-induced diabetes, initial renal alteration was disturbance of the charge barrier, followed by the development of albuminuria. Continued deterioration of anionic sites and possibly additional disturbance of size barrier were considered responsible for the development of albuminuria. Insulin treatment appears to prevent the loss of anionic sites of GBM.

Albuminuria↗
PubMed1993

Leydig cell tumor: a case report with reference to its endocrinological features.

We reported an adult case of Leydig cell tumor, which demonstrated an increase of serum estradiol (E2) and suppression of serum testosterone (T) before orchiectomy. The direct inhibitory action of the elevated E2 on the enzymes involved in steroidogenesis and the negative feedback action on luteinizing hormone (LH) secretion of the E2 possibly caused the suppression of serum T. A human chorionic gonadotropin test before the operation revealed the elevation of T and E2, although the response was poor compared with that in normal subjects. However, the postoperative test showed no elevation of these hormones. This result may indicate that the Leydig cell tumor preserves a response to LH stimulation.

Chorionic Gonadotropin↗
PubMed1993

Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients.

We examined pancreas biopsy specimens from 18 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients to elucidate the mechanism underlying beta cell destruction. Pancreas islets were seen in all patients and insulitis in eight patients. Infiltrating mononuclear cells consisted of CD4+T, CD8+T, B lymphocytes, and macrophages. Among them, CD8+T lymphocytes were predominant and macrophages followed. The expression of MHC class I antigens was increased in islet and endothelial cells in nine patients. MHC class II expression was increased in endothelial cells of the same patients. The expression of intercellular adhesion molecule-1 was increased in endothelial cells in two of the nine patients with MHC hyperexpression; in one of them, lymphocyte function-associated antigen-3 expression was also increased. Out of the eight patients with insulitis, seven showed MHC class I hyper-expression, whereas 2 of the 10 patients without insulitis showed the phenomenon (P < 0.05). The relation between insulitis and the hyperexpression of adhesion molecules was not evident. In conclusion, we revealed the close relation between CD8+T lymphocyte-predominant insulitis and MHC class I hyperexpression in islet cells. This suggests that infiltrating CD8+T lymphocytes recognize islet autoantigens in association with increased MHC class I molecules and act as major effector cells in autoimmune response against islet cells in IDDM pancreases. The role of adhesion molecules in the pathogenesis of IDDM still remains to be elucidated.

Adolescent↗
PubMed1993

Endotoxin-induced enhancement of angiotensinogen synthesis in the liver: decreased response following repeated endotoxin exposure.

To understand the mechanisms responsible for lipopolysaccharide (LPS)-induced enhancement of angiotensinogen synthesis in the liver, studies were carried out in rats with repeated doses of LPS. The administration of sublethal dose (50 micrograms, i.p.) of LPS to rats resulted in increase in serum levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6), which attained their maximal levels by 1 and 2-4h, respectively. Serum levels of angiotensinogen and alpha 2-macroglobulin, a typical acute-phase protein in the rat, were also increased by a primary LPS challenge, and their maximal levels for the formation of TNF and IL-6 were delayed with peaks at 12 and 48 h, respectively. Repeated i.p. administration of LPS (50 micrograms/d) for 5 consecutive days induced a hyporesponsiveness to its subsequent administration in terms of increasing serum TNF, IL-6 and alpha 2-macroglobulin. In these LPS-tolerant rats, either LPS-induced elevation of angiotensinogen concentration in serum or angiotensinogen mRNA levels in liver was completely eliminated. Angiotensinogen synthesis in rat hepatoma H4 cells was enhanced in vitro by the addition of sera which had been collected 2 or 4 h after a primary injection of LPS, while not by sera collected from LPS-pretreated rats after a secondary LPS exposure. These results indicate that LPS-induced enhancement of angiotensinogen synthesis in the liver is desensitized in rats after repetitive LPS exposure, presumably by the failure of LPS-induced IL-6 production.

Angiotensinogen↗
PubMed1993

Pharmacokinetics and tolerability of chloramphenicol in budgerigars (Melopsittacus undulatus).

Pharmacokinetics and tolerability of chloramphenicol (CP) were evaluated in budgerigars. Following intramuscular administration of CP at 100 and 200 mg/kg of body weight, serum peak concentrations of 35.3 and 90.7 micrograms/ml, respectively, were obtained 0.25 hr following injection, and these values declined with a terminal half-life of 2.5 and 2.7 hr, respectively. Based on these results, an intramuscular dosage regimen of 100 mg/kg of CP 3 times a day or of 200 mg/kg twice daily was recommended as effective against many of the common bacterial infections in budgerigars. Red blood cell count, packed cell volume, hemoglobin, total plasma protein, serum AST, ALT, LDH and CK values were determined after intramuscular injection of either CP or physiological saline 2 or 3 times a day for 5 days. The birds were weighed before and after treatment. Tissue samples from various organs were examined histologically. The most prominent adverse effect was muscular damage at the injection site. A dosage regimen of 200 mg/kg twice daily for 5 days was considered to be safe.

Alanine Transaminase↗
PubMed1993

Adjuvant chemotherapy for invasive urothelial cancer: experience with a methotrexate, vincristine, cisplatin, cyclophosphamide, adriamycin and bleomycin (MVP-CAB) regimen: a preliminary report.

MVP-CAB chemotherapy (methotrexate, vincristine, cisplatin, cyclophosphamide, adriamycin and bleomycin) was administered to 28 patients with high grade, locally-invasive or regional lymph node-involved urothelial cancer as an adjuvant therapy after radical surgery. The median follow-up period of all the evaluated patients was 24 (range, 5-62) months. The median disease-free durations in patients with pT1b+2+3 bladder and upper urothelial cancer were 26 and 22 months, respectively. In contrast, all patients with pT4 disease or lymph node metastases had a recurrence within 24 months of surgery. The median disease-free durations in patients with pure transitional cell carcinoma (grade 3) of the bladder and upper urothelial cancer were 19 and 18 months, respectively. The median disease-free duration in patients with grade 3 pT1b+2+3 pure transitional cell carcinoma was 19 months. In contrast, the median disease-free duration in bladder cancer patients with pT1b+2+3 squamous cell carcinoma components was 35 months. The three-year actuarial survival rates were 79 and 89% for pT1b+2+3 bladder and upper urothelial cancer, respectively, while the three-year actuarial survival rates of patients with pT4 bladder cancer and pT4 upper urothelial cancer were 0 and 100%, respectively. The two-year actuarial survivals in the bladder cancer and upper urothelial cancer patients with lymph node involvement were 0 and 100%, respectively. The three-year actuarial survivals of patients with pure transitional cell carcinoma (grade 3) were 53 and 80% in bladder cancer and upper urothelial cancer patients, respectively. The three-year actuarial survival rate in patients with squamous cell carcinoma or adenocarcinoma components which did not recur was, however, 100%. Although randomized studies comparing MVP-CAB and M-VAC (methotrexate, vinblastin, adriamycin and cisplatin) or other chemotherapeutic regimens will be necessary, we believe our results indicate that MVP-CAB chemotherapy may be useful as an adjuvant therapy for patients with urothelial cancer, including those with squamous cell carcinoma and adenocarcinoma components. More intensive MVP-CAB chemotherapy, i.e., increasing the dose of cisplatin and giving at least five courses, as well as the use of granulocyte colony stimulating factor and a new antiemetic drug (granisetron), will, however, be necessary for patients with pT4 or lymph node-involved disease.

Adenocarcinoma↗
PubMed1993

[Meningoencephalitis associated with polyradiculoneuropathy with increased HSV IgG antibody--report of three cases].

We report three patients presented with meningoencephalitis associated with polyradiculoneuropathy with increased HSV IgG antibody titer. The first patient was a 27-year-old woman with meningoencephalitis who developed status epilepticus. The CSF showed pleocytosis and increase in HSV IgG antibody titer. Herpes encephalitis was suspected, and she was treated with acyclovir. The symptoms of meningoencephalitis improved, but she developed flaccid tetraplegia. The NCV study was compatible with polyradiculoneuropathy. About two months later from the onset, muscle atrophy appeared in her all limbs. The second patient was a 23-year-old woman with meningoencephalitis, which was followed by ascending motor paralysis. The CSF showed pleocytosis and increase in HSV IgG antibody titer. The symptoms of meningoencephalitis improved by administration of acyclovir, but paralysis didn't improve. About two months later from the onset, muscle atrophy of all limbs appeared. The NCV study was compatible with polyradiculoneuropathy. The third patient was a 43-year-old man presenting somnolence, neck stiffness and ascending motor paralysis developing into flaccid tetraplegia. The CSF showed pleocytosis and increase in HSV IgG antibody titer. Somnolence and neck stiffness improved by administration of acyclovir but tetraplegia didn't improve. The NCV study was compatible with polyradiculoneuropathy. Immuno-absorption therapy and administration of prednisolone were performed. Meningoencephalitis associated with increased HSV IgG antibody titer is rare. Auto-allergic process which is initiated by HSV infection may be involved in the pathogenesis of polyradiculoneuropathy in these patients.

Adult↗
PubMed1993

Successful pregnancy in a patient with heart failure secondary to aortic and mitral regurgitation.

In this report, maternal and fetal risks were evaluated in a pregnant patient who had no previously established heart valvular disease. A 41-old-year patient with aortic and mitral regurgitations suffered from progressive congestive heart failure during 20 weeks of gestation. She carried the pregnancy to a successful delivery at 31 weeks. During this time, sudden deterioration in the symptoms occurred, but both the fetal and maternal outcomes were uneventful. This experience of a good outcome may contribute to the future management of pregnancies associated with heart disease.

Adult↗
PubMed1993

Detection and characterization of blocking-type anti-acetylcholine receptor antibodies in sera from patients with myasthenia gravis.

We developed a highly sensitive, convenient assay for measuring blocking-type anti-acetylcholine receptor antibodies, which inhibit the binding of 125I-labeled alpha-bungarotoxin (alpha-BuTx) to the acetylcholine receptor (AChR). This procedure detected inhibitory activities in sera from 76% of patients with myasthenia gravis. Results of an experiment done with synthetic peptide corresponding to the alpha-BuTx binding region in the alpha-subunit of Torpedo AChR suggested that this inhibition is due to nonspecific steric hindrance caused by the binding of antibodies to a region other than the alpha-BuTx site, rather than by direct binding to the latter site. The inhibitory activities of the blocking-type antibodies and the titers of non-blocking-type antibodies were correlated. Moreover, the blocking-type antibodies could dissociate 125I-labeled alpha-BuTx from 125I-labeled alpha-BuTx-human AChR complex, and their dissociation activities showed good correlation with the inhibitory activities.

Amino Acid Sequence↗
PubMed1993

Oxidation of aniline to nitrobenzene by nonheme bromoperoxidase.

Nonheme bromoperoxidase found in Pseudomonas putida catalyzed the bromination of aniline with hydrogen peroxide and bromide ions to give o- and p-bromoanilines. However, in the absence of bromide ions, it oxidized aniline via azobenzene and azoxybenzene finally into nitrobenzene. This is the first report of the biological oxidation of an arylamine to the corresponding nitrocompound at the enzyme level. In addition, nitrobenzene was not formed by a nonheme bromoperoxidase from Corallina pilulifera (marine alga), implying that the alga enzyme has a different reaction mechanism.

Alanine↗
PubMed1992

[Studies on the production rate of estradiol in the testis in male infertility--studies of the predictive values on therapeutic efficacy in patients with oligozoospermia].

It is surmised that studies on the relationship between the endocrinological milieu and therapeutic efficacy in male infertile patients are essential in elucidating the etiology of this disease and devising effective therapeutic methods. The relation between serum gonadotropin level and therapeutic efficacy has already been reported. In the present study, we investigated the basal levels of two sex steroids, i.e., testosterone and estradiol, and the estradiol:testosterone (E2/T) ratio, and also the increases in these parameters after the administration of hCG to human subjects presenting various degrees of testicular dysfunction, e.g., male infertile patients, aged males, Klinefelter's syndrome and hypogonadotropic hypogonadism. Special attention was given to the characteristics of the reserve capacity for secretion of estradiol in male infertile patients. The hCG test was performed on a total 527 subjects, including 65 normal adult males. The reserve capacity for the secretion of estradiol was investigated on the basis of the increasing rate in the serum E2/T ratio. The increasing rate in the serum E2/T ratio was statistically larger in subfertile males, oligozoospermia and azoospermia in comparison with the normal adult males. On the other hand, the aged males did not show any difference from the normal adult males, whereas the results were significantly lower in the male subjects with Klinefelter's syndrome and hypogonadotropic hypogonadism. It was considered that the increase in the serum E2/T ratio is one characteristic of the gonads of male infertile patients. The results of multiple regression analysis showed that the LH level, the pretreatment sperm concentration and the increasing rate in the serum E2/T ratio were important factors determining the increase in the sperm concentration after treatment. Accordingly, for cases of oligozoospermia characterized by an LH level of 13.7mIU/ml or less and a sperm concentration of 5 x 10(6)/ml or more, the relationship between the increasing rate in the serum E2/T ratio and therapeutic efficacy was investigated. It was found that the increasing rate in the serum E2/T ratio was significantly greater in the therapeutically ineffective cases compared with the therapeutically effective cases. On the basis of this finding, it was surmised that the percentage increase in the serum E2/T ratio is one index reflecting testicular function. In addition, for cases of oligozoospermia characterized by an LH level of 13.7mIU/ml or less, a sperm concentration of 5 x 10(6)/ml or more and the increasing rate in the serum E2/T ratio of 4.01 or less, the relationship between the degree of spermatogenesis and therapeutic efficacy was investigated.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

A new member of the insulin receptor family, insulin receptor-related receptor, is expressed preferentially in the kidney.

Shier and Watt isolated human and guinea pig genomic DNA encoding a putative protein, insulin receptor-related receptor (IRR), the primary structure of which is similar to that of other members of the insulin receptor family, the insulin receptor and type-I IGF receptor (J. Biol. Chem. 264, 14605-14608 (1989)). However, the expression of the IRR gene remained unknown. In this paper, we isolated the IRR cDNA from the rat brain and examined the expression of the IRR mRNA in a variety of rat tissues, including the brain, heart, lung, liver, small intestine, kidney, thymus, spleen, muscle, adipose tissue and cartilage by polymerase chain reaction. In contrast to the wide distribution of the insulin receptor and type-I IGF receptor mRNAs, the IRR mRNA is expressed preferentially in the kidney, which indicates that IRR has unique functions as a member of the insulin receptor family.

Amino Acid Sequence↗
PubMed1992

Chromosomal localization and organization of the murine genes encoding the beta subunits (AIC2A and AIC2B) of the interleukin 3, granulocyte/macrophage colony-stimulating factor, and interleukin 5 receptors.

Chromosomal genes for two mouse homologous beta subunits (AIC2A and AIC2B) of the interleukin-3, granulocyte/macrophage colony-stimulating factor, and interleukin-5 receptors were characterized. Both AIC2A and AIC2B genes were present on a 250-kilobase MluI restriction fragment and were mapped on murine chromosome 15 (these loci were provisionally designated as Il3rb-1 (AIC2A) and Il3rb-2 (AIC2B)), closely linked to the c-sis locus. Both genes consist of 14 exons and span about 28 kb each. The major transcription initiation sites of both genes were mapped at 194 bp from the initiation codon. These genes are 95% identical up to 700 bp from the transcription initiation sites. Potential recognition sequences for hemopoietic transcription factors including GATA-1 and PU.1 in addition to a TATA-like sequence are present in the 5'-flanking region. A stretch of 20 bp including the initiation site is homologous to the corresponding region of the erythropoietin receptor and the interleukin-7 receptor genes and to the initiator sequence of the adeno-associated virus P5 promoter, suggesting a possible role in transcription initiation. Comparison of the exon/intron boundaries of AIC2A and AIC2B genes with those of other members of the cytokine receptor superfamily reveals a conserved evolutionary structure. Isolation of various forms of AIC2 cDNAs reveals differential splicing of the transcripts.

Animals↗