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T Goto

Publications and source records attributed to T Goto.

At least 109 records · Page 6Linked to original sources

p48 subunit of mouse PTF1 binds to RBP-Jkappa/CBF-1, the intracellular mediator of Notch signalling, and is expressed in the neural tube of early stage embryos.

BACKGROUND: Development of the pancreas and the nervous tissues is regulated by common transcription factors. A basic helix-loop-helix protein, p48 of pancreas transcription factor 1 (PTF1), is essential for differentiation of the exocrine acinar cells. RESULTS: We isolated PTF1 p48 from 9.5-day mouse embryos as a binding protein of RBP-Jkappa, a mediator of Notch signalling. p48 bound to RBP-Jkappa more strongly than and in a distinct way from Notch1. In 9.5-12.5 day embryos, p48 was expressed in the dorsal part of the neural tube as well as in the pancreatic buds. Two lines of evidence suggested functions of p48 in neurogenesis: (i) expression of p48 was induced in P19 cells when they committed to neural fate upon retinoic acid treatment, and (ii) p48 over-expressed in Xenopus embryos repressed the development of neuronal precursors. p48 inhibited the MASH1-activated transcription from the E-box, while p48 stimulated transcription from the PTF1 motif synergistically with E47. The p48/E47-activated transcription from the PTF1 motif was stimulated further by RBP-Jkappa and RBP-Jkappa derivatives that mimicked the active RBP-Jkappa/Notch complex. CONCLUSIONS: In developing embryos, p48 is expressed in both the nervous system and the pancreas. p48 inhibits neuronal differentiation. We propose possible mechanisms for this inhibition.

3T3 Cells↗

Developmental fates of the first four blastomeres of the chaetognath Paraspadella gotoi: relationship to protostomes.

Experimental analysis of the development of chaetognaths is virtually lacking. To elucidate developmental fates, single blastomeres of the 2-cell and 4-cell embryos of Paraspadella gotoi were injected with a lineage-tracing dye (Fluoro-Ruby or DiI). The distribution of the labels was observed in the hatchlings. In a previous study, embryos were injected at the 2-cell stage with Fluoro-Ruby and two sets of complementary labeling patterns (DL and VR, and DR and VL) were found. The same results were obtained when DiI was used as a tracer dye. The 4-cell embryo consists of the animal and vegetal cross-furrow cells in a tetrahedral arrangement and one of the vegetal cross-furrow cells typically contains the germ plasm. When single cells were injected at the 4-cell stage, four labeling patterns were observed (D, V, L and R). These four patterns represent subsets of the four patterns observed in the hatchling injected at the 2-cell stage. The V pattern is probably generated from the blastomere containing the germ plasm. It was found that the positions of the blastomeres at the 4-cell stage corresponded to the future body axes, similar to classic spiralians and modified spiralians such as crustaceans. Furthermore, it was confirmed that second cleavage occurs in a leiotropic fashion, which is seen in the second cleavage of the classic spiralians. Chaetognaths may have some similarities to protostomes in their developmental program.

Animals↗

Clinical significance of TT virus in chronic hepatitis C.

BACKGROUND AND AIMS: Much is still unknown about the clinical significance of TT virus (TTV), which has been reported as a candidate for non A-G hepatitis virus. The aim of this study was to clarify the clinical significance of TTV in patients coinfected with TTV and hepatitis C virus (HCV). METHODS: The 95 subjects studied had chronic hepatitis C (CHC), and underwent interferon (IFN) therapy. TT Virus DNA was detected by using polymerase chain reaction. The nucleotide sequences were determined by using a dideoxy chain termination method. A phylogenetic tree was drawn up by using the neighbor-joining method. RESULTS: TT Virus DNA was detected in 37.9% of patients with the use of an open reading frame 1 (ORF1) primer, and in 88.4% of patients by using a 5' untranslated region (5' UTR) primer. Using both sets of primers, no differences were found between TTV-DNA-positive and -negative subjects with CHC in the clinical findings. Serum TTV DNA was eradicated in 30.6% of patients with the ORF1 primer, and in 19.1% of patients with the 5' UTR primer at 6 months after the cessation of IFN therapy. The levels of TTV DNA before IFN therapy were significantly lower in the viral eradication group than in non-eradication group. The changes in alanine aminotransferase (ALT) concentrations were significantly correlated with changes in HCV-RNA in CHC patients with TTV. Moreover, there was no correlation between the changes in TTV DNA and the course of ALT. CONCLUSION: Hepatocellular injury in patients with chronic hepatitis who are coinfected with HCV and TTV appears to primarily be caused by HCV and is less attributable to TTV.

Adult↗

Differences in cell kinetic changes among renal cancer cell lines treated with interferon-alpha.

BACKGROUND: Interferon (IFN)-alpha shows certain clinical effects on the treatment of renal cell carcinoma. The purpose of the present study was to investigate its direct effects and to compare the responses among different human renal cancer cell lines. METHODS: Three cell lines, ACHN, RCC10RGB and OS-RC-2, were incubated with IFN-alpha and evaluated using MTT assay for cell proliferation and two-color flow cytometry for cell-cycle-specific cyclin expressions coupled with DNA ploidy analysis. RESULTS: Interferon-alpha inhibited cell proliferation and caused cell accumulation at S and G2/M phases. However, IFN-alpha induced no significant change in cyclins D1, E, A or B1 expression. Interestingly, cell kinetic changes caused by IFN-alpha were different among cell lines. Cell proliferation was suppressed most in ACHN, then RCC10RGB and least in OS-RC-2. Comparing DNA histograms, ACHN showed distinct increase of G2/M cells associated with elevation of late S cells. RCC10RGB showed a predominant increase of whole S cells accompanied with a slight increase of G2/M. OS-RC-2 showed a modest increase of S cells with a little change of G2/M cells. Chronological observation revealed that S-phase increase and proliferative inhibition appeared on day 1 and day 3, respectively, in ACHN and RCC10RGB, and on day 5 in OS-RC-2. CONCLUSIONS: Interferon-alpha induced substantial cell kinetic interference directly in the tested human renal carcinoma cell lines. The degree of change was different according to the nature of the cell line. It may partly indicate the variety of the efficacy of IFN-alpha treatment against renal cancers.

Carcinoma, Renal Cell↗

Prediction of difficult airway in school-aged patients with microtia.

BACKGROUND: Because the ear and mandible develop from the first and second branchial arches and first branchial cleft, abnormalities of the ear may be a sign that intubation will be difficult. We hypothesized that children with microtia would have a greater incidence of difficult laryngeal visualization with conventional rigid laryngoscopy compared to those with normal facial anatomy. METHODS: We enrolled 93 consecutive school-aged patients with microtia undergoing the first stage of total reconstruction of the auricle. Age-matched patients with normal facial anatomy served as controls. Each patient was examined for the presence or absence of the five dysmorphic features of hemifacial microsomia: orbital asymmetry, mandibular hypoplasia, ear deformity, nerve involvement, soft tissue deficiency (OMENS classification). After a standardized induction of anaesthesia, the laryngeal view during rigid laryngoscopy was graded. RESULTS: The incidence of difficult laryngeal view was 42% in the patients with bilateral microtia, 2% in those with unilateral microtia and 0% in the controls. CONCLUSIONS: There was a strong positive correlation between the number of involved abnormal anatomical components according to the OMENS classification and the degree of difficult visualization of the larynx in patients with both bilateral and unilateral microtia (Spearman rank order correlation coefficient=0.85 and 0.88, respectively).

Adolescent↗

Isolation of novel developmental genes from human germ cell, oocyte and embryo cDNA by differential display.

Due to the difficulties inherent in research on human embryos, almost nothing is known about genes active in human early development. Although the human genome project will provide resources that theoretically provide access to every human gene, those genes specific to human early development may be difficult to define. Also, by definition, genes specific to early development will not be represented in cDNA databases derived from human somatic cells. Yet these unknown human developmental genes are likely to be of key importance for several areas of human health, including assisted reproduction and contraception, embryo stem cell research and tissue transplantation, ageing and cancer. In order to identify and isolate these human developmental genes, we have prepared amplified cDNA from human primordial germ cells, oocytes and embryos, and used differential display to compare patterns of gene expression in these embryonic cells and in the cells of somatic tissues of a 10-week human fetus. This paper reviews the highly sensitive procedures used to create amplified cDNA representing expressed genes in a single cell and the use of differential display to identify developmental genes. Several such genes have been isolated, but their full-length sequences and function are yet to be elucidated. Genes active in human early development are expected to play key roles in the maintenance of the archetypal stem cell state, potential immortality and the invasiveness of trophectoderm and primordial germ cells. They represent candidate genes regulating these functions for targeting in clinical research in human reproduction, stem cell differentiation and cancer.

Animals↗

An improved procedure of electron microscopic in situ hybridization for detecting adenovirus DNA.

Electron microscopic in situ hybridization (EM-ISH) is a useful method in determining the localization of a specific nucleic acid at the ultrastructural level. Since the EM-ISH protocol includes many steps, no standard protocol for EM-ISH is available yet. In this study, we optimized quantitatively the critical conditions with respect to embedding resin, nucleic acid labeling and hybridization reaction time, by using adenovirus-infected cells as the indicator cells. The optimal detection of an adenovirus-specific nucleic acid was obtained by overnight hybridization reaction on sections embedded in Lowicryl K4M resin. Random-primed-labeled probes improved the reactivity. At least 60% of virus particles in paracrystalline arrays was found to contain viral DNA. These arrays in adenovirus-infected cells are useful in evaluating quantitatively the efficiency of protocols of EM-ISH.

Adenoviridae↗

Long-term zinc deficiency decreases taste sensitivity in rats.

The effects of zinc deficiency on taste sensitivity were examined in rats by recording the electrophysiological responses of the chorda tympani (CT) nerve and by use of a preference test. Male 4-wk-old Sprague-Dawley rats were given free access to a diet containing 2.2 (zinc-deficient), 4.1 (low zinc) or 33.7 (zinc-sufficient) mg zinc/kg diet. A fourth group was pair-fed the zinc-sufficient diet (with respect to the zinc-deficient rats). A two-bottle preference test using 0.15 mol/L NaCl and water revealed that NaCl preference was greater in the zinc-deficient and low zinc groups than in the control groups (zinc-sufficient and pair-fed) after 4 d of feeding. In the case of quinine hydrochloride solution (0.01 mmol/L), the preference was greater in zinc-deficient rats than in the other groups after 9 d, and the low zinc rats never showed a preference. Electrophysiological recording indicated that in the zinc-deficient rats, the CT nerve response to 0.20 mol/L NaCl was significantly less than that in the control rats after 21 d of feeding. In the low zinc rats, this response was significantly less than in the control rats after 35 d. The responses to quinine hydrochloride (0.02 mol/L), L-glutamic acid, HCl (0.01 mol/L) and NH(4)Cl (0.25 mol/L) in the zinc-deficient rats were not significantly reduced until d 42. These findings suggest that long-term zinc deficiency decreases taste sensitivity at the level of the CT nerve and that the change in NaCl preference due to zinc deficiency occurs before any change in NaCl taste sensitivity.

Animal Nutritional Physiological Phenomena↗

Expression of a testis-specific member of the olfactory receptor gene family in human primordial germ cells.

Olfactory receptors are G protein-coupled transmembrane receptors. Genes encoding olfactory receptors constitute a large gene family of approximately 1000 total member genes. In mammals, a subset of member genes is specifically expressed in the testis (and not in the olfactory mucosa) and olfactory receptor proteins have been identified in elongated spermatids and mature spermatozoa of dogs. It is postulated that olfactory receptors may recognize signal molecules present in the female genital tract and play a role in chemotaxis of spermatozoa towards the oocyte. In a previous study, we identified 10 cDNA sequences, corresponding to genes specifically expressed in human primordial germ cells (PGC), by differential display. Sequence analysis revealed that one of these sequences appeared to be a member of the olfactory receptor gene family. To investigate this further, we have used degenerate oligonucleotide primers corresponding to conserved amino acid sequences of olfactory receptor proteins to amplify all the olfactory receptor genes expressed in the PGC. Sequence analysis of a total of 30 cloned sequences disclosed that one member gene, which was previously isolated from a human testis cDNA library by others, was also preferentially expressed in our PGC. Our results suggest that specific members of the olfactory receptor gene family may have a function in germ cells in the migratory phase of their life cycle.

Female↗

Minimum alveolar concentration (MAC) of xenon with sevoflurane in humans.

BACKGROUND: Although more than 30 yr ago the minimum alveolar concentration (MAC) of xenon was determined to be 71%, that previous study had technological limitations, and no other studies have confirmed the MAC value of xenon since. The current study was designed to confirm the MAC value of xenon in adult surgical patients using more modern techniques. METHODS: Sixty patients were anesthetized with sevoflurane with or without xenon. They were randomly allocated to one of four groups; patients in group 1 received no xenon, whereas those in groups 2, 3, and 4 received end-tidal concentrations of 20, 40, and 60%, respectively (n = 15 each group). Target end-tidal sevoflurane concentrations were chosen using the "up-and-down" method in each group. After steady state sevoflurane and xenon concentrations were maintained for at least 15 min, each patient was monitored for a somatic response at surgical incision. Somatic response was defined as any purposeful bodily movement. The MAC of sevoflurane and its reduction by xenon was evaluated using the multiple independent variable logistic regression model. RESULTS: The interaction coefficient of the multiple variable logistic regression was not significantly different from zero (P = 0.143). The MAC of xenon calculated as xenon concentration that would reduce MAC of sevoflurane to 0% was 63.1%. CONCLUSIONS: The authors could not determine whether interaction in blocking somatic responses in 50% of patients is additive. The MAC of xenon is in the range of the values that were predicted in a previous study.

Adult↗

The midlatency auditory evoked potentials predict responsiveness to verbal commands in patients emerging from anesthesia with xenon, isoflurane, and sevoflurane but not with nitrous oxide.

BACKGROUND: It has recently been demonstrated that the approximately 40-Hz spectral power of the midlatency auditory evoked potential (MLAEP) correlates well with wakefulness during desflurane or propofol anesthesia. The aim of this study was to characterize how other inhalational anesthetics affects the MLAEP as the patients regain responsiveness to simple verbal command during emergence from anesthesia. METHODS: Sixty patients were randomly assigned to receive xenon, isoflurane, sevoflurane, or nitrous oxide (N2O) supplemented with epidural anesthesia. During emergence, the concentration of an anesthetic was decreased in 0.1-minimum alveolar concentration (MAC) decrements from 0.8 MAC or from 70% in the case of N2O, and each new concentration was maintained for 15 min. Every 5 min during each equilibration period, the MLAEP was recorded and the patients were asked to open their eyes and squeeze and release the investigator's hand. This process was repeated until the first response to either of these commands was observed. RESULTS: Thirteen patients were excluded because of technical reasons. The preanesthetic MLAEP showed a periodic waveform, where the Na-Pa-Nb complex was the most prominent component contributing to the high energy around 29-39 Hz in the power spectrum. Emergence from xenon, isoflurane, and sevoflurane anesthesia produced similar changes in the MLAEP. The spectral power for the frequency 29 Hz or greater was severely suppressed at 0.8 MAC but significantly recovered between the concentration only 0.1 MAC higher that permitting the first response to command and that associated with the first response. In contrast, N2O hardly affected the MLAEPs, even at the concentrations producing unresponsiveness. Two patients did not lose responsiveness even at the highest concentration tested (70%). CONCLUSIONS: The MLAEP is closely associated with responsiveness to verbal command during emergence from anesthesia with xenon, isoflurane, and sevoflurane but not with N2O.

Adult↗

Gender- and age-related differences in corneal topography.

PURPOSE: To investigate gender- and age-related differences in the corneal topography of a normal population. METHODS: One hundred thirty-two topographic examinations were collected from 100 patients ranging in age from 23 to 83 years (average, 57.35+/-17.38 years). Data were segregated by gender and further divided into younger (less than 50 years) and older (50 years or more) age groups. The topographic indices of Surface Regularity Index, Surface Asymmetry Index, Irregular Astigmatism Index, Standard Deviation of Corneal Power, Corneal Eccentricity Index, Coefficient of Variation of Corneal Power, Simulated Keratometry 1 and 2, and Average Corneal Power were examined. The astigmatism pattern and corneal irregularity were determined and compared with respect to gender and age. RESULTS: The corneas of older men were flatter than those of older women (p < 0.001). The vertical corneal meridian, but not the horizontal meridian, showed statistically significant gender-related changes with aging (p < 0.001). Older men had a significantly higher potential for against-the-rule astigmatism than women (p < 0.001). Corneal irregularity (measured in terms of the Surface Regularity Index and Irregular Astigmatism Index) increased with age (p < 0.001 and p < 0.001, respectively), although there was no gender-related difference. In the younger group, no gender-related differences in corneal curvature or astigmatism pattern were found. CONCLUSION: Aging influences changes in patterns of astigmatism differently in men and women. Decreases in levels of sex hormones may play a role in gender-related changes in corneal structure with age.

Adult↗

Atypical pleomorphic astrocytoma in the pineal gland: case report.

OBJECTIVE AND IMPORTANCE: We report a rare case of pleomorphic astrocytoma in the pineal region that took a benign course despite pleomorphism. CLINICAL PRESENTATION: A 30-year-old woman suddenly developed right hemiparesis followed by loss of consciousness. A computed tomographic scan revealed a mass in the pineal region accompanied by obstructive hydrocephalus. Her symptoms improved after ventriculoperitoneal shunt surgery. INTERVENTION: The tumor was totally removed in an en bloc fashion using the occipital interhemispheric transtentorial route. Light microscopy revealed that the tumor had marked pleomorphism and multinucleated, bizarre giant cells, but neither mitosis nor necrosis was seen. Glial fibrillary acid protein was immunohistochemically positive in a few tumor cells. Retinal soluble antigen was negative. No reticulin network between the tumor cells was observed. A histological diagnosis of atypical pleomorphic astrocytoma was made. CONCLUSION: No signs of recurrence have been observed for 7 years after surgery without adjuvant therapy. Histologically, the tumor resembled pleomorphic xanthoastrocytoma or pleomorphic granular cell astrocytoma, but the immunohistochemical findings were not completely compatible with either diagnosis. This benign astrocytoma in the pineal gland with unique features is the first such case reported.

Adult↗

Anti-human immunodeficiency virus activity of YK-FH312 (a betulinic acid derivative), a novel compound blocking viral maturation.

Betulinic acid, a triterpenoid isolated from the methyl alcohol extract of the leaves of Syzigium claviflorum, was found to have a potent inhibitory activity against human immunodeficiency virus type 1 (HIV-1). Betulinic acid derivatives were synthesized to enhance the anti-HIV activity. Among the derivatives, 3-O-(3',3'-dimethylsuccinyl) betulinic acid, designated YK-FH312, showed the highest activity against HIV-induced cytopathic effects in HIV-1-infected MT-4 cells. To determine the step(s) of HIV replication affected by YK-FH312, a syncytium formation inhibition assay in MOLT-4/HIV-1(IIIB) and MOLT-4 coculture, a multinuclear-activation-of-galactosidase-indicator (MAGI) assay in MAGI-CCR5 cells, electron microscopic observation, and a time-of-addition assay were performed. In the syncytium formation inhibition assay or in the MAGI assay for de novo infection, the compound did not show inhibitory effects against HIV replication. Conversely, no virions were detected in HIV-1-infected cell cultures treated with YK-FH312 either by electron microscopic observation or by viral yield in the supernatant. In accordance with a p24 enzyme-linked immunosorbent assay of culture supernatant in the time-of-addition assay, YK-FH312 inhibited virus expression in the supernatant when it was added 18 h postinfection. However, Western blot analysis of the cells in the time-of-addition assay revealed that the production of viral proteins in the cells was not inhibited completely by YK-FH312. These results suggest that YK-FH312 might affect the step(s) of virion assembly and/or budding of virions, and this is a novel mechanism of action of an anti-HIV compound.

Anti-HIV Agents↗

Glandular and extraglandular expression of costimulatory molecules in patients with Sjögren's syndrome.

OBJECTIVES: To investigate the expression and regulation of CD80, CD86, and CD28 costimulatory molecules in sialoadenitis and interstitial nephritis in patients with Sjögren's syndrome (SS). METHODS: Expression of CD80, CD86, and CD28 molecules was studied by immunohistochemical staining of lip biopsy specimens obtained from patients who had sialoadenitis associated with SS, and renal biopsy specimens obtained from patients who had interstitial nephritis associated with SS. To elucidate the mechanism of de novo expression of CD80 and CD86 antigens, their induction by cytokines in human salivary duct cell line (HSG) and renal cortical epithelial cells (HRCE) by cell enzyme linked immunosorbent assay (ELISA) was quantitatively investigated. RESULTS: In patients with severe sialoadenitis, CD80 and CD86 were strongly expressed on ductal epithelial cells. In contrast, these antigens were not found in the minor salivary glands of normal subjects or of patients with mild sialoadenitis. Some infiltrating cells expressed CD28. In patients who had interstitial nephritis associated with SS, some tubular epithelial cells expressed CD86 but not the CD80 antigen. Unstimulated HSG cells did not express CD80 or CD86. Interferon gamma (IFNgamma) consistently up regulated levels of CD80 and CD86. In contrast, tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), IL2, and IL4 had no effect on either CD80 or CD86 levels. Unstimulated HRCE did not express CD80 or CD86. IFNgamma consistently up regulated CD86 expression. No CD80 expression was found on tubular cells. TNFalpha, IL1beta, IL2, and IL4 had no discernible effects. CONCLUSIONS: Salivary ductal cells in patients with SS can express CD80 and CD86 costimulatory molecules in response to IFNgamma. Tubular epithelial cells in patients who have interstitial nephritis associated with SS express only CD86 molecules. In patients with SS, salivary ductal cells and tubular epithelial cells may activate infiltrating CD28 positive T lymphocytes by presenting antigens to T cells, potentially leading to tissue destruction.

Adult↗