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Biomedical subjects

K Goto

Publications and source records attributed to K Goto.

At least 325 records · Page 18Linked to original sources
PubMed1997

Pregnancy increases ET-1-induced contraction and changes receptor subtypes in uterine smooth muscle in humans.

The purpose of the present study was to investigate whether pregnancy affects endothelin (ET)-1-induced contraction, the density ofET receptors, and the ratio of receptor subtypes (ET(A) and ET(B)) in uterine smooth muscle in humans. We also investigated which ET receptor subtypes mediate ET-1-induced contraction in the human uterus. In uterine membrane preparations, (125)I-labeled ET-1 ((125)I-ET-1) binding sites (Bmax) in pregnant women did not differ from those in age-matched nonpregnant women (596.2 +/- 107.1 vs. 512.1 +/- 167.7 fmol/mg protein). The dissociation constant (Kd) in pregnant women did not differ from that in nonpregnant women. Competitive displacement experiments with (125)I-ET-1 binding to the membranes using BQ-123 (ET(A) receptor antagonist) showed that the percentage of ET(A) receptors in uterine muscle was significantly higher in pregnant women than in nonpregnant women (P < 0.01). The calculated ratios of ET(A) to ET(B) receptors in pregnant and nonpregnant uteri were 92:8 and 68:32, respectively. Combination treatment with BQ-788 (ET(B) receptor antagonist) completely inhibited the BQ-123-resistant component of (125)I-ET-1 specific binding. ET-1 caused dose-dependent contractions in isolated human uteri from both pregnant and nonpregnant women. The maximum response was markedly greater in pregnant women than in nonpregnant women, whereas pD2 (-log[EC50]) values did not differ between pregnant and nonpregnant uteri. In pregnant human uterus, BQ-123 (10(-6) M) significantly shifted the dose-dependent curve of ET-1 response to the right, whereas BQ-3020 (ET(B) receptor agonist) did not cause contraction. These results suggested that ET-1-induced contraction of the human uterus is mediated through only ET(A) receptors and that ET-1-induced uterine contraction in humans is markedly increased during pregnancy. In addition, the present study suggests that, although (125)I-ET-1 Bmax are not altered during pregnancy, the proportion of ET(A) receptors is increased and that of ET(B) receptors is decreased in the pregnant human uterus.

Adult↗
PubMed1997

Does endothelin-1 participate in the exercise-induced changes of blood flow distribution of muscles in humans?

Endothelin-1 (ET-1) is an endothelium-derived potent vasoconstrictor peptide that potentiates contractions to norepinephrine in human vessels. We previously reported that the circulating plasma concentration of ET-1 is significantly increased after exercise (S. Maeda, T. Miyauchi, K. Goto, and M. Matsuda. J. Appl. Physiol. 77: 1399-1402, 1994). To study the roles of ET-1 during and after exercise, we investigated whether endurance exercise affects the production of ET-1 in the circulation of working muscles and nonworking muscles. Male athletes performed one-leg cycle ergometer exercise of 30-min duration at intensity of 110% of their individual ventilatory threshold. Plasma concentrations of ET-1 in both sides of femoral veins (veins in the working leg and nonworking leg) and in the femoral artery (artery in the nonworking leg) were measured before and after exercise. The plasma ET-1 concentration in the femoral vein in the nonworking leg was significantly increased after exercise, whereas that in femoral vein in the working leg was not changed. The arteriovenous difference in ET-1 concentration was significantly increased after exercise in the circulation of the nonworking leg but not of the working leg, which suggests that the production of ET-1 was increased in the circulation of the nonworking leg by exercise. The present study also demonstrated that the plasma norepinephrine concentrations were elevated by exercise in the femoral veins of both the working and nonworking legs, suggesting that the sympathetic nerve activity was augmented in both legs during exercise. Therefore, the present study demonstrates the possibility that the increase in production of ET-1 in nonworking muscles may cause vasoconstriction and hence decrease blood flow in nonworking muscles through its direct vasoconstrictive action or through an indirect effect of ET-1 to enhance vasoconstrictions to norepinephrine and that these responses may be helpful in increasing blood flow in working muscles. We propose that endogenous ET-1 contributes to the exercise-induced redistribution of blood flow in muscles.

Adolescent↗
PubMed1997

Dose-intensive weekly chemotherapy for treatment of relapsed small-cell lung cancer.

PURPOSE: This study was undertaken to determine the activity and toxicity of dose-intensive weekly chemotherapy (cisplatin, vincristine, doxorubicin, and etoposide [CODE] regimen) for previous treated, recurrent small-cell lung cancer (SCLC). PATIENTS AND METHODS: The 17 patients with relapsed SCLC entered onto the study were to receive intensive weekly chemotherapy with the CODE regimen. All 17 patients had been heavily pretreated with some form of cisplatin-based combination chemotherapy. Six patients had received previous chemotherapy with CODE and one patient with cisplatin and etoposide (PE) as induction therapy. Nine patients had been treated with concurrent or sequential PE plus thoracic irradiation (TRT). The median time off chemotherapy was 6.7 months (range, 3.3 to 72). Patients were treated with 9 weeks of the CODE regimen. Response, survival, and toxicity data were noted. RESULTS: All 17 patients were assessable for response, survival, and toxicity. Fifteen of 17 patients (88.2%) had an objective response, with five complete responses (CRs; 29%) and 10 partial responses (PRs; 58.8%). The median durations of response and survival were 156 days and 245 days, respectively. Myelosuppression was significant, with 76% of patients developing grade 4 leukopenia. No treatment-related death was observed. CONCLUSION: The CODE regimen is highly active in the treatment of relapsed SCLC with an encouraging survival outcome.

Aged↗
PubMed1997

Analysis of the hypervariable region of hepatitis C virus E2/NS1 gene in an infant infected by blood transfusion.

We investigated the sequential change in the hypervariable region 1 (HVR 1) of hepatitis C virus (HCV) E2/NS1 gene in an infant. He was transfused with 160 mL of blood containing the HCV (0.7 Meq/mL) on the 6th d after birth and subsequently developed chronic viremia. At 16 mo, the HVR1 amino acid sequences of HCV observed in the infant's sera were very similar to those from the donor (his maternal grandfather) on the day of transfusion. However, highly variable amino acid sequences of HVR1 were observed throughout infancy. These results demonstrate that an adaptive response of HCV to evade host immunity seems to occur, as in adult cases, even in early infancy when the ability to produce humoral immunoglobulin is thought to be low.

Amino Acid Sequence↗
PubMed1997

[Astrocytes and endothelins: possibilities for tissue-repair in damaged central nervous system].

Endothelins and their receptor of type B (ETBR) that couples with G-protein are widely distributed in the mammalian central nervous system (CNS). ETBR mainly exists on astrocytes, and endothelins exert mitogenic action on astrocytes through stimulation of the receptor. The intracellular signaling of ETBR in astrocytes is converged in the activation of mitogen-activated protein kinase through a protein kinase C-dependent pathway and a pertussis toxin-sensitive G-protein-mediated pathway. We demonstrated that cultured astrocytes. When differentiated and growth-arrested by treatment with dibutyryl cyclic AMP, abundantly expressed ETBR and these cells immediately entered into a proliferative state in response to endothelin-1 at the plasma level. This has the following physiological implication in vivo: plasma-derived endothelin-1 intrudes into parenchyme upon CNS damage, and it initiates astrogliosis through activation of ETBR. We used two models of CNS injury in rats. The first is a brain edema model induced by cold-injury, and the second is a spinal cord injury model, both of which allow plasma to exude into the injured tissues and subsequently trigger sequential proliferative responses of astrocytes after the injury. Anti-endothelin monoclonal antibody and SB209670, an endothelin receptor antagonist, specifically and potently inhibited astrocytic proliferation 24 hr after the injury. It is concluded that endothelin-1 plays a key role for initiation of astrocytic proliferation in the acute phase of CNS damage.

Astrocytes↗
PubMed1997

Comparison of the nuclear DNA stability against freezing-thawing and high temperature treatments between spermatozoa and somatic cells.

Thermostability of sperm genome against freezing-thawing and high temperature treatments was assessed by comparing the degradation patterns of genomic DNAs from epididymal sperms and somatic tissues. Golden hamster liver, kidney, epididymal sperm, and testis were frozen and thawed repeatedly, or incubated in a hot water bath. Genomic DNAs were isolated and then separated by agarose gel electrophoresis. It was revealed that the size of sperm genomic DNA was hardly changed after freezing-thawing treatment, however, the DNA sizes of the other three tissues were gradually reduced with an increasing number of freezing-thawing cycles. In contrast, high temperature treatment appears to damage not only the genomic DNAs of somatic cells but also those of spermatozoa.

Animals↗
PubMed1997

Evidence of alpha-helix slidings during bacteriorhodopsin photocycle-energetics coupling.

The three-dimensional structure of bacteriorhodopsin indicates that the all-trans-cis retinal bending causes alpha-helix slidings during the bacteriorhodopsin photocycle. For the elucidation of alpha-helix slidings taking place during the bacteriorhodopsin photocycle, we calculated ASAs of hydrophobic and hydrophilic atoms translocated by alpha-helix slidings with thermodynamic criteria found previously. Thermodynamic parameters calculated from ASAs (calculated delta Gtransfer and T delta S) were consistent with those (observed delta Gtransfer and T delta S) obtained empirically. These findings indicate that alpha-helix slidings take place during bacteriorhodopsin photocycle-energetics coupling. These mechanisms not only explain various phenomena, including some mutants forming a long-lived intermediate, but also predict various yet-unobserved phenomena, including the generation of heat in early photocycle intermediates.

Amino Acid Sequence↗
PubMed1997

Homology of E2 gene in 8 child-mother pairs infected with hepatitis C virus.

The frequency of genetic homology of hepatitis C virus (HCV) E2 gene in 8 child-mother pairs was investigated. The route of HCV infection of all children suggested mother-to-child infection by their past history. In this study, we analyzed at least 5 complementary DNA (cDNA) clones for each case. In 6 of the 8 (75%) child-mother pairs, for the region between hypervariable region (HVR)-1 and HVR-2, the similarity of the nucleotide sequence of all 5 cDNA clones between each child and the mother was higher than that between the child and the other children, the other mothers and the sequences from GenBank. One of the 8 (13%) child-mother pairs showed a great similarity in parts of all cDNA clones. This was also confirmed by phylogenetic analyses of the sequences of cDNA clones from families and that from GenBank. These results suggested that the homology search of nucleotide sequence of this region was useful to confirm mother-to-child transmission of HCV.

Amino Acid Sequence↗
PubMed1997

The seroprevalence of HTLV-I in patients with ocular diseases, pregnant women and healthy volunteers in the Kanto district, central Japan.

HTLV-I has been shown to be related to the development of inflammatory diseases in various organs such as the eyes, lungs and joints. In south-west Japan where HTLV-I is highly endemic, the term 'HTLV-I associated complex' has been approved. To investigate the seroprevalence of HTLV-I in the Kanto district in central Japan, we have estimated the frequency of seropositivity to HTLV-I in 2,110 patients with various ocular diseases and 2,683 pregnant women, in addition to 5,336 healthy volunteers. Of the healthy volunteers, only 42 (0.79%) were seropositive, and the HTLV-I seroprevalence in pregnant women was also only 16/2,683 (0.60%) which was almost equal to that in female healthy volunteers aged 15-44 years (0.59%). In patients with various ocular diseases, however, there was significantly higher seroprevalence of HTLV-I (2.32%) compared with healthy volunteers in each sex (male: p = 0.0029; female: p = 0.000023). These results suggest that the seroprevalence of HTLV-I in the Kanto district is much lower than in south-west Japan. On the other hand, HTLV-I infection was shown to be correlated to ocular diseases also in the Kanto district. In particular, we found a higher seroprevalence of HTLV-I in patients with inflammatory ocular disease, such as endogenous uveitis, episcleritis, retinitis pigmentosa and degenerative choroiditis. This possibly suggests a causative role of HTLV-I in the development of these inflammatory ocular diseases also where HTLV-I is not endemic.

Adolescent↗
PubMed1997

[A 36-year-old woman with acute onset left hemiplegia and anosognosia].

We report a 36-year-old woman with right hemiplegia, anosognosia, and rapidly deteriorating course. She was well until the end of January, 1995 when she had an onset of fever, sputum, and cough. A 5 x 5 tumor was found in her left lower lobe. She was admitted to the Pulmonary Medicine on May 24, 1995 when she was 36-year-old. General physical examination was unremarkable. Bone scintigraphy revealed increased uptake in the skull, sternum, right scapula, vertebrae, right femur, and in ribs. Cranial CT scan revealed a large mass lesion in the right frontal subcortical region with central low density and peripheral high density areas, and small low density lesions in the right thalamic area and in the right posterior frontal region; ring enhancement was observed in the latter two lesions. On the second day of admission, she noted left-sided weakness which improved by corticosteroid treatment. On June 17, there was a sudden onset of left hemiparesis and a neurologic consultation was asked. Upon neurologic examination, she appeared somnolent but could understand verbal commands. She showed constructional apraxia, neglect of the left hemisphere, and anosognosia. Cranial nerves were unremarkable. Motor-wise, she showed flaccid left hemiplegia. Deep tendon reflexes were exaggerated on the left and the plantar response was extensor bilaterally. Nuchal stiffness was noted. Her cranial CT scan on June 17 revealed enlargement of the right frontal mass lesion. The subsequent course was complicated by DIC and progressive worsening of her consciousness. On June 18, she was comatose and pupillary light reflex was lost. She developed Cheyne-Stokes respiration and expired on that evening. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had a primary adenocarcinoma in the lung with multiple metastases including the brain. The fulminant terminal course was ascribed to hemorrhage within the tumor and subsequent central type of transtentorial herniation. Opinions were divided regarding the cause of hemorrhage; some participants thought hemorrhage was caused by DIC. Post-mortem examination revealed an adenocarcinoma arising at the S6 segment of the left lung with multiple organ metastases. In the brain, a huge hemorrhagic metastasis was found in the right frontal lobe and a non-hemorrhagic metastasis in the right thalamic region. Probably, the size of the metastases influenced the occurrence of hemorrhage. The direct cause of the death was transtentorial herniation.

Adenocarcinoma↗
PubMed1997

p53 mutations in multiple urothelial carcinomas: a molecular analysis of the development of multiple carcinomas.

The purpose of this study is to assess whether the development of synchronous and/or metachronous multifocal urothelial cancers is due to field defect, intraluminal seeding and implantation, or both. We used a series of 42 cases of multiple urothelial cancers. We performed polymerase chain reaction single-strand conformation polymorphism, DNA sequencing, and immunohistochemical studies on p53 gene mutations in 84 multiple urothelial carcinomas (78 urinary bladder carcinomas and 6 ureteric or renal pelvic carcinomas) from 42 patients. p53 Mutations were detected in 42 (50%) of 84 cancerous tumors from 22 (52%) of the 42 patients and were strongly related to the tumor grade but not to the tumor stage. Nine patients had identical mutations with or without additional mutations in the multiple carcinomas, which suggests that the carcinomas had a common origin. Eleven patients, however, had discordant mutations, and two patients had a mutation in one tumor but not in another, a fact that strongly suggests independent origin. Double mutations were observed in 9 (21%) of 42 patients; in these types of mutation, transitions were clearly more frequent than transversions, a difference from previously reported spectra of urothelial carcinomas. The data indicate that multiple urothelial carcinomas seem to be either common or of independent origin. In addition, the different p53 mutational spectra in this series might reflect the presence of other possible mutagens in carcinogenesis of multiple urothelial carcinomas.

Aged↗
PubMed1997

[Recent progress in the research field of nuclear receptors].

In the research field of nuclear receptors, the studies on the protein factors which interact with the steroid hormone receptors and regulate the transcriptional activity, and on the alpha and beta isoforms of glucocorticoid receptor have been in great progress. The include "intermediary Factors" such as RIP140, TIF-1, for the AF-2 which contribute to ligand-dependent transactivation function of the receptors. ARA70 which specifically interacts with androgen receptor was also cloned recently. Informations obtained from steroid hormone receptor knockout-mice experiments can also be available for the estrogen, glucocorticoid, and progesterone receptors. Furthermore, there have been more than sixty orphan receptors identified in these eight years, including HNF, Ad4BP, DAX-1, and nur77/NGFIB, some of which are mutation target genes of human congenital diseases.

Animals↗
PubMed1997

A case of membranous glomerulonephritis associated with gastric cancer.

We describe a patient with gastric cancer and membranous glomerulonephritis (MGN). The patient, a 61-year-old male, was admitted to our Hospital in May, 1996, because of proteinuria and hyperlipidemia persisting for a year. Laboratory examination filled the criteria of nephrotic syndrome and renal biopsy revealed MGN of stage II. Prednisolone therapy (40 mg/day p.o.) was started, followed by a gradual decrease in proteinuria from 4.5 g/day to 0.1 g/day. Endoscopic examination was performed because of stomach-ache revealed advanced gastric cancer of Borrmann 4. Desiring for a conservative therapy, he was discharged and moved to a hospice. In literature review, MGN is the most frequent lesion among various glomerular diseases associated with malignancy, such as the lung, stomach, and colon, particularly at an elderly ages, and sometimes antedates the detection of malignancy, as in the present case. In several cases with MGN, immune-complexes composed of tumor antigens, such as carcino-embryonic antigen, and antibodies have been reported to deposit in basement membrane of glomeruli, causing MGN. In the renal and gastric cancer tissues of the present case, the presence of three novel tumor-associated antigens, Span-1, Thomsen-Friedenreich antigen (T antigen) and F1 alpha antigen, was examined, using a immuno-peroxidase method. Although none of these three antigens were immuno-stained in the renal tissue, clinical course and literature review suggest that MGN in this patient seems to be associated with gastric cancer, which may have produced MGN-causing tumor antigens other than the three antigens. It should be emphasized that malignancy should be carefully and routinely examined in patients with MGN, particularly at elderly ages.

Glomerulonephritis, Membranous↗
PubMed1997

[Facioscapulohumeral muscular dystrophy (FSHD)].

Facioscapulohumeral muscular dystrophy (FSHD; MIM 158900) is one of the major forms of muscular dystrophy, and is inherited in an autosomal dominant fashion. In most patients with FSHD, deletion of 3.3 kb tandemly repeated units within the EcoRI fragment, as detected by p13E-11 (D4F104S1) on chromosome 4q35, is associated with the disease (FSHD1A or 4q35-FSHD). Rare (< 5%) 4q35-unlinked FSHD (FSHD1B) is also known, and therefore genetic heterogeneity exists among FSHD. Recent studies based on the distinction of 4q35 EcoRI fragments from those of 10q26 improved the reliability of molecular diagnosis of the disease (> 95% accuracy). However, gene for FSHD1A has not been identified yet. Identification of the FSHD gene and characterization of the gene product are waited on tiptoe with expectation.

Chromosomes, Human, Pair 4↗
PubMed1997

Serologic survey for HTLV-I in Kanagawa Prefecture.

To investigate the seroprevalence of HTLV-I in Kanagawa Prefecture (central Japan), we tested the sera of 8,264 healthy volunteers and 2,414 pregnant women. Of the 8,264 healthy volunteers, 66 (0.80%) were seropositive. The seroprevalence of HTLV-I in the pregnant women was 14/2,414 (0.58%), and this rate was almost identical to that in the healthy female volunteers 15 to 44 years of age (0.59%). These figures indicate that the seroprevalence of HTLV-I in Kanagawa Prefecture is very low and that sexual contact may not be an important contributory factor.

Adolescent↗