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Biomedical subjects

Y Gotoh

Publications and source records attributed to Y Gotoh.

At least 55 records · Page 3Linked to original sources
PubMed1999

Determination of age-related changes in human soluble interleukin 2 receptor in body fluids of normal subjects as a control value against disease states.

A highly sensitive enzyme-linked immunosorbent assay (ELISA) system was developed for human soluble interleukin-2 receptor (sIL-2R) with an ELISA-amplification system (ELAST((R))). The sensitivity of the new method was 20-fold higher than that without the amplification. Thus very low concentrations of sIL-2R in urine can be detected. With this method, serum and urine concentrations of sIL-2R were analyzed for healthy Japanese subjects with age 1-67 years. Mean sIL-2R concentrations in both serum and urine of children were significantly higher than those of adults. However, the concentrations of children showed a progressive decline to those of adults by the age of 15 years. There was no difference in the values between males and females. The results provide a control value of sIL-2R against those in disease states such as nephrotic syndrome. Since the trends in serum and urine were found to be similar, urinary sIL-2R measurement may provide sufficient information, without measuring the blood concentration.

Adolescent↗
PubMed1999

Evaluation of endoscopic variceal ligation in prophylactic therapy for bleeding of oesophageal varices: a prospective, controlled trial compared with endoscopic injection sclerotherapy.

BACKGROUND: To evaluate the efficacy of endoscopic variceal ligation (EVL) in prophylactic therapy for oesophageal varices, we performed a randomized prospective trial to compare the recurrence of oesophageal varices treated by EVL with those treated by endoscopic injection sclerotherapy. METHODS: Fifty patients with liver cirrhosis were divided into two groups at random, after informed consents were obtained, to receive prophylactic therapy for bleeding of oesophageal varices. Group 1 patients underwent sessions of sclerotherapy with 5% ethanolamine oleate used as the sclerosant. Group 2 patients underwent EVL followed by one or two sessions of sclerotherapy. RESULTS: During the 18 month follow-up period, both the recurrence rate in group 2 (56%) and the incidence of bleeding (20%) were significantly higher compared with group 1 (recurrence rate 16%, bleeding 0%). CONCLUSIONS: This result indicates that EVL is not effective for prophylactic therapy for oesophageal varices in liver cirrhosis.

Esophageal and Gastric Varices↗
PubMed1999

Testicular damage after exposure to carbendazim depends on the number of patent efferent ductules.

To study how long-term testicular damage depends on the patency of the efferent ductules (EFDs), rat testes and epididymides were examined after a single exposure to carbendazim (methyl 2-benzimidazole carbamate; MBC). The number of patent EFDs was determined in sections of the caput epididymides at 8, 16, 32 and 70 days post-treatment, and the testes were grouped into the following categories: those with intact EFDs, those with partially patent EFDs, or those with totally occluded EFDs. In each testis, 100 seminiferous tubules were examined for the presence of abnormalities. The mean weight of testes with partially patent EFDs was significantly higher compared with the control, whereas that of testes with totally occluded EFDs was significantly lower. Histologically, most seminiferous tubules of the testes with intact EFDs were normal. The testes with partially patent EFDs contained normal, degenerative and atrophic seminiferous tubules at various frequencies depending on the number of patent EFDs, and it was evident that as the number of patent EFDs increased, the number of normal seminiferous tubules also increased at any interval. In these testes, the number of normal seminiferous tubules increased progressively as the post-treatment interval increased, irrespective of patency of the EFDs. In the testes with totally occluded EFDs, atrophic seminiferous tubules were the most numerous. These results indicate that whether or not the testis is able to survive the long-term deleterious effects of MBC depends largely EFD patency.

Animals↗
PubMed1999

Acute lower respiratory infections in hospitalized children over a 6 year period in Tokyo.

BACKGROUND: Acute lower respiratory infections are major causes of hospitalization in children and are mainly caused by respiratory viruses. In the present study, we investigated the etiologic agents responsible for acute lower respiratory infections from the period November 1986 to October 1992 in order to determine the seasonal pattern and different characteristics of age distribution of respiratory infectious agents, mainly virus infections. METHODS: A total of 1521 patients with lower respiratory infections was hospitalized in Saiseikai Central Hospital, Tokyo, Japan. Nasopharyngeal secretions were obtained for virus isolation and paired sera in the acute and convalescent phases were obtained for serological examination. RESULTS: Etiological agents were identified in 668 of 1521 patients (43.9%) by serological antibody responses, virus isolation and/or detection of virus antigen: 240 (15.8%) with respiratory syncytial (RS) virus; 62 (4.1%) with influenza virus type A; 26 (1.7%) with influenza virus type B; 86 (5.7%) with adenovirus; 81 (5.3%) with parainfluenza virus; 32 (2.1%) with measles virus; 20 (1.3%) with enteroviruses or Herpes virus other than respiratory viruses; 75 (4.9%) with Mycoplasma pneumoniae; 10 (0.7%) with pertussis; and 36 (2.4%) with mixed infections. In the remaining 853 patients (56.1%), etiologic agents were not identified. Respiratory syncytial (RS) virus was a main causative agent of respiratory infections in patients younger than 3 years of age. Influenza virus and M. pneumoniae were two main causative agents in patients with acute respiratory illness over 5 years of age. Parainfluenza virus type 3 was frequently observed in infants from 9 to 12 months of age. A distinct seasonal pattern of viral infections was consistently observed in each year during the study period; RS and influenza viruses were prevalent in winter, parainfluenza virus was prevalent in spring and M. pneumoniae was prevalent in summer and autumn. However, adenovirus infections were observed in all seasons. Serological responses were poor in patients younger than 1 year of age and they were mainly diagnosed by virus isolation or detection of virus antigen. CONCLUSIONS: Virological epidemiology provides useful information in daily clinical practice for the prediction of etiological agents based on patient age and the seasonal distribution of agents. We should examine virus isolation and the detection of virus antigen, along with serological examinations in patients with respiratory infections, especially in infants younger than 1 year of age because of poor serological responses.

Age Distribution↗
PubMed1998

Reactive oxygen species- and dimerization-induced activation of apoptosis signal-regulating kinase 1 in tumor necrosis factor-alpha signal transduction.

Reactive oxygen species (ROS) have been implicated in the induction of apoptosis by tumor necrosis factor-alpha (TNFalpha) and other cytotoxic insults, although the molecule(s) regulated by ROS in TNFalpha signaling have not been identified. Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) superfamily that has been shown to be activated during TNFalpha-induced apoptosis. ASK1 increases apoptosis when overexpressed, but the mechanism of ASK1 activation and the mechanisms of ASK1-induced apoptosis are unclear. We now report that hydrogen peroxide induces the activation of ASK1 in 293 cells. TNFalpha-induced activation of ASK1 was inhibited by antioxidants. Hydrogen peroxide-induced apoptosis was markedly enhanced by the expression of ASK1. These results suggest that TNFalpha-induced activation of ASK1 is mediated by ROS. We also examined how ASK1 activity is regulated by ROS. We found that ASK1 formed dimers or higher order oligomers in 293 cells. TNFalpha or hydrogen peroxide treatment increased the dimeric form of ASK1, and pretreatment with N-acetylcysteine decreased it. Furthermore, synthetic dimerization of an ASK1-gyrase B fusion protein by coumermycin resulted in substantial activation of ASK1, suggesting that dimerization of ASK1 is sufficient for its activation. These results taken together suggest that TNFalpha causes ASK1 activation via ROS-mediated dimerization of ASK1.

Base Sequence↗
PubMed1998

Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1.

Mst1 is a ubiquitously expressed serine-threonine kinase, homologous to the budding yeast Ste20, whose physiological regulation and cellular function are unknown. In this paper we show that Mst1 is specifically cleaved by a caspase 3-like activity during apoptosis induced by either cross-linking CD95/Fas or by staurosporine treatment. CD95/Fas-induced cleavage of Mst1 was blocked by the cysteine protease inhibitor ZVAD-fmk, the more selective caspase inhibitor DEVD-CHO and by the viral serpin CrmA. Caspase-mediated cleavage of Mst1 removes the C-terminal regulatory domain and correlates with an increase in Mst1 activity in vivo, consistent with caspase-mediated cleavage activating Mst1. Overexpression of either wild-type Mst1 or a truncated mutant induces morphological changes characteristic of apoptosis. Furthermore, exogenously expressed Mst1 is cleaved, indicating that Mst1 can activate caspases that result in its cleavage. Kinase-dead Mst1 did not induce morphological alterations and was not cleaved upon overexpression, indicating that Mst1 must be catalytically active in order to mediate these effects. Mst1 activates MKK6, p38 MAPK, MKK7 and SAPK in co-transfection assays, suggesting that Mst1 may activate these pathways. Our findings suggest the existence of a positive feedback loop involving Mst1, and possibly the SAPK and p38 MAPK pathways, which serves to amplify the apoptotic response.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Effect of the chemical modification of the arginyl residue in Bombyx mori silk fibroin on the attachment and growth of fibroblast cells.

We prepared matrices of Bombyx mori silk fibroin (SF) with different degrees of modification of arginyl residues by reaction between 1,2-cyclohexanedione (CHD) and SF. Two kinds of SF, namely native SF (NSF), obtained from the silk gland of silkworm larvae, and regenerated SF (RSF), prepared from cocoons of the same silkworm, were used in this study because their amino acid compositions were slightly different from each other. The attachment and growth of mouse fibroblast (L-929) cells on the matrices of the NSF and RSF, in which half or almost all of the arginyl residues were modified (NSF50, RSF50, NSF100, and RSF100), were studied using a cell culture method. Both NSF50 and NSF100 exhibited higher cell attachment than did the unmodified NSF. While the cell growth on NSF50 was not significantly different from that on NSF and NSF100, the growth on NSF100 was higher than that on NSF. The cells attached to NSF50 and NSF100 were extensively spread out and their filopodia were visible by SEM. The cell attachment and growth on RSF were comparable to those on NSF100. Although RSF50 exhibited almost the same cell attachment as did the unmodified RSF, RSF100 exhibited a lower cell attachment than did the unmodified RSF and RSF50. There were no significant differences in the cell growth among RSF series. The cells attached to RSF50 and RSF100 aggregated to form masses, and their filopodia could not be found. The relationship of cell attachment to the basicity of the substrate is considered because the modification of the positively charged arginyl residue changed the basicity of the substrate and the cell attachment on the substrate.

Amino Acids↗
PubMed1998

Role of TAK1 and TAB1 in BMP signaling in early Xenopus development.

Transforming growth factor-beta (TGF-beta) superfamily members elicit signals through stimulation of serine/threonine kinase receptors. Recent studies of this signaling pathway have identified two types of novel mediating molecules, the Smads and TGF-beta activated kinase 1 (TAK1). Smads were shown to mimic the effects of bone morphogenetic protein (BMP), activin and TGF-beta. TAK1 and TAB1 were identified as a MAPKKK and its activator, respectively, which might be involved in the up-regulation of TGF-beta superfamily-induced gene expression, but their biological role is poorly understood. Here, we have examined the role of TAK1 and TAB1 in the dorsoventral patterning of early Xenopus embryos. Ectopic expression of Xenopus TAK1 (xTAK1) in early embryos induced cell death. Interestingly, however, concomitant overexpression of bcl-2 with the activated form of xTAK1 or both xTAK1 and xTAB1 in dorsal blastomeres not only rescued the cells but also caused the ventralization of the embryos. In addition, a kinase-negative form of xTAK1 (xTAK1KN) which is known to inhibit endogenous signaling could partially rescue phenotypes generated by the expression of a constitutively active BMP-2/4 type IA receptor (BMPR-IA). Moreover, xTAK1KN could block the expression of ventral mesoderm marker genes induced by Smad1 or 5. These results thus suggest that xTAK1 and xTAB1 function in the BMP signal transduction pathway in Xenopus embryos in a cooperative manner.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Chemical transformation of tylosin derivatives into neutral macrolides having a 3'-methoxyl group.

This paper describes the chemical transformation of the basic 16-membered macrolides, tylosin derivatives, into neutral macrolides having a 3'-methoxyl group. 2',4'-Di-O-acetyl-3,23-bis(O-tert-butyldimethylsilyl)mycaminosyltylon olide 9,20-bis(ethylene acetal) N-oxide (1b) was treated with Ac2O-pyridine in CH2Cl2 to afford the 3'-ketone 1c and the 3'-N-acetyl-3'-N-demethyl derivative 1d in 67 and 5% yield; respectively. Reduction of 1c with Zn(BH4)2 gave the 3'-alcohol 1e in 84% yield stereoselectively. O-Methylation of 1e with MeOTf and 2,6-di-tert-butylpyridine gave the 3'-methyl ether 1f in 49% yield in spite of the presence of the adjacent acetoxyl groups. Deprotection of 1f provided the desired neutral macrolide 1g. Similar synthetic routes were also used for transformation of the suitably protected 4'-deoxymycaminosyltylonolide 2b and desmycosin 3c into neutral macrolides having a 3'-methoxyl group. It was found that the mycinose moiety of a neutral macrolide plays an important role in its antimicrobial activity.

Anti-Bacterial Agents↗
PubMed1998

Neurotropic melanoma invading the median nerve.

We report a case of acral lentiginous melanoma of the right thumbnail bed which demonstrated characteristic intraneural invasion and extension along the median nerve. Four years after amputation of the involved thumb, a melanotic tumor recurred on the right thenar. Radiation therapy was given. The tumor invaded the median nerve, however, causing progressive pain and paralysis of the right hand. Despite right arm amputation, the tumor extensively metastasized, and the patient died three years later. Histopathologically, the tumors were characterized by extensive proliferation of spindle-shaped cells forming neuroid fascicles especially prominent in the metastatic region. Tumor cells were positive immunohistochemically with S-100 protein antisera.

Amputation, Surgical↗
PubMed1998

Coordinated expression of Hoxa-11 and Hoxa-13 during limb muscle patterning.

The limb muscle precursor cells migrate from the somites and congregate into the dorsal and ventral muscle masses in the limb bud. Complex muscle patterns are formed by successive splitting of the muscle masses and subsequent growth and differentiation in a region-specific manner. Hox genes, known as key regulator genes of cartilage pattern formation in the limb bud, were found to be expressed in the limb muscle precursor cells. We found that HOXA-11 protein was expressed in the premyoblasts in the limb bud, but not in the somitic cells or migrating premyogenic cells in the trunk at stage 18. By stage 24, HOXA-11 expression began to decrease from the posterior halves of the muscle masses. HOXA-13 was expressed strongly in the myoblasts of the posterior part in the dorsal/ventral muscle masses and weakly in a few myoblasts of the anterior part of the dorsal muscle mass. Transplantation of the lateral plate of the presumptive wing bud to the flank induced migration of premyoblasts from somites to the graft. Under these conditions, HOXA-11 expression was induced in the migrating premyoblasts in the ectopic limb buds. Application of retinoic acid at the anterior margin of the limb bud causes duplication of the autopodal cartilage and transformation of the radius to the ulna, and at the same time induces duplication of the muscle pattern along the anteroposterior axis. Under these conditions, HOXA-13 was also induced in the anterior region of the ventral muscles in the zeugopod. These results suggest that Hoxa-11 and Hoxa-13 expression in the migrating premyoblasts is under the control of the limb mesenchyme and the polarizing signal(s). In addition, these results indicate that these Hox genes are involved in muscle patterning in the limb buds.

Animals↗
PubMed1998

Nucleotide sequence of the gene encoding the precursor protein of pepstatin insensitive acid protease B, scytalidopepsin B, from Scytalidium lignicolum.

A chromosomal DNA of Scytalidium lignicolum was digested with Sau3AI. The digest was self-ligated and amplified by inverse PCR procedure using primers designed based on the nucleotide sequences of up- and down-stream regions of an intron present in the scytalidopepsin B gene. Analysis of the nucleotide sequence of PCR product (700 bp) showed that the enzyme is synthesized as a precursor protein consisting of the prepro- and mature enzyme regions. The deduced amino acid sequence was highly similar to those of aspergillopepsin A and recently reported endothiapepsins B and C, but quite different from those of pepstatin-insensitive bacterial acid proteases and the pepstatin-sensitive aspartic protease family.

Amino Acid Sequence↗
PubMed1998

Permethrin emulsion ingestion: clinical manifestations and clearance of isomers.

BACKGROUND: Oral intoxication with permethrin, an insecticide which prolongs axonal sodium channel depolarization, has not been documented in humans. We treated a 59-year-old man who drank approximately 600 mL of 20% permethrin emulsion in a suicide attempt. METHODS: Sequential blood samples were obtained to determine permethrin isomer levels using high-performance liquid chromatography. RESULTS: Vomiting and diarrhea occurred after ingestion. On admission, loss of consciousness and metabolic acidosis were observed. On regaining consciousness, the patient complained of a burning sensation in the oral cavity. He received fluid therapy after gastric lavage and recovered without severe complications. Apart from initially impaired consciousness, no clinical neurotoxicity such as tremor, hyperexcitation, ataxia, convulsions, or paralysis occurred, though these have been reported in permethrin-intoxicated animals. Serum permethrin concentrations peaked 3-4 hours after ingestion at 868 ng/mL. Clearance of trans permethrin was more rapid than that of cis permethrin. CONCLUSION: The unequal clearance of permethrin isomers paralleled findings in animal experiments. Vomiting and diarrhea probably limited absorption in the present case, resulting in a peak serum concentration and a degree of neurotoxicity far less than those seen in animals.

Administration, Oral↗
PubMed1997

A novel regulatory mechanism in the mitogen-activated protein (MAP) kinase cascade. Role of nuclear export signal of MAP kinase kinase.

Mitogen-activated protein kinase (MAPK) kinase (MAPKK, also known as MEK), a direct activator for MAPK/extracellular signal-regulated kinase, localizes to the cytoplasm excluded from the nucleus during signal transmission. This nuclear exclusion of MAPKK is directed by its nuclear export signal (NES), but its physiological significance has been unknown. We have found that disruption of the NES dramatically potentiates the ability of constitutively active MAPKK to induce morphological changes and malignant transformation of fibroblastic cells. Readdition of the NES sequence reversed the effects induced by the NES disruption. Moreover, we observed that a dramatic increase of activated MAPK in the nucleus was induced by the NES-disrupted MAPKK and that coexpression of MAPK phosphatase-1 (CL-100) or a kinase negative form of MAPK counteracted the phenotypes induced by the NES-disrupted MAPKK, indicating the crucial role of MAPK in the responses. These findings reveal a novel regulatory role of the NES of MAPKK that may be essential for proper signal transductions.

Animals↗
PubMed1997

A novel SAPK/JNK kinase, MKK7, stimulated by TNFalpha and cellular stresses.

Stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), a member of the MAP kinase (MAPK) superfamily, is thought to play a key role in a variety of cellular responses. To date, SEK1/MKK4, one of the MAP kinase kinase (MAPKK) family of molecules, is the only SAPK/JNK kinase that has been cloned. Here we have cloned, identified and characterized a novel member of the mammalian MAPKKs, designated MKK7. MKK7 is most similar to the mediator of morphogenesis, hemipterous (hep), in Drosophila. Immunochemical studies have identified MKK7 as one of the major SAPK/JNK-activating kinases in osmotically shocked cells. While SEK1/MKK4 can activate both the SAPK/JNK and p38 subgroups of the MAPK superfamily, MKK7 is specific for the SAPK/JNK subgroup. MKK7 is activated strongly by tumour necrosis factor alpha (TNFalpha) as well as by environmental stresses, whereas SEK1/MKK4 is not activated by TNFalpha. Column fractionation studies have shown that MKK7 is a major activator for SAPK/JNK in the TNFalpha-stimulated pathway. Moreover, we have found that overexpression of MKK7 enhances transcription from an AP-1-dependent reporter construct. Thus, MKK7 is an evolutionarily conserved MAPKK isoform which is specific for SAPK/JNK, is involved in AP-1-dependent transcription and may be a crucial mediator of TNFalpha signalling.

Amino Acid Sequence↗
PubMed1997

Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery.

Growth factors can promote cell survival by activating the phosphatidylinositide-3'-OH kinase and its downstream target, the serine-threonine kinase Akt. However, the mechanism by which Akt functions to promote survival is not understood. We show that growth factor activation of the PI3'K/Akt signaling pathway culminates in the phosphorylation of the BCL-2 family member BAD, thereby suppressing apoptosis and promoting cell survival. Akt phosphorylates BAD in vitro and in vivo, and blocks the BAD-induced death of primary neurons in a site-specific manner. These findings define a mechanism by which growth factors directly inactivate a critical component of the cell-intrinsic death machinery.

3T3 Cells↗
PubMed1997

Central effects of (5RS, 1'SR)-5-benzyl-3-(3'-morpholino-1'-phenylpropyl)-1,3-oxazolidin-2 -one monofumarate on the function of the bladder and periurethral skeletal muscle in anesthetized rats.

The effects of a newly developed drug for incontinence, (5RS, 1'SR)-5-benzyl-3-(3'-morpholino-1'-phenylpropyl)-1,3-oxazolidin-2- one monofumarate (NC-1800), on bladder and periurethral skeletal muscle functions were tested in urethane-anesthetized rats. When the bladder pressure was low, i.v. administration of NC-1800 at doses of 4 to 16 mg/kg induced dose-dependent increases of vesical pressure associated with increases in pelvic efferent nerve activity. When the bladder was expanded, the same administration of NC-1800 induced dose-dependent inhibitions of both vesical micturition contractions and rhythmic pelvic burst discharges. Hypogastric efferent nerve activity was not affected. The periurethral electromyogram (EMG) activity was excited when the bladder was contracted, and EMG activity was inhibited when the bladder was relaxed by NC-1800. Pelvic ganglionic transmission, neuromuscular transmission of both bladder and urethra, and muscle contractility itself of bladder and urethra were not affected by NC-1800. These results suggest that NC-1800 modulates the functions of the bladder and urethra by influencing pelvic and pudendal nerve activity via the central nervous system.

Anesthesia↗