[Future aspects and possibility in study of small fishes(discussion)].
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Biomedical subjects
Publications and source records attributed to H Takeda.
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It is known that the incompetence of stress adaptation mechanisms is a primary factor affecting disorders such as anxiety and depression. Increased clinical evidence indicates that hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis and dysfunction of the brain serotonin (5-HT) nervous system are risk factors associated with these disorders. Given the high sensitivity of hippocampal 5-HT responses to glucocorticoids, functional changes in the hippocampal 5-HT nervous system induced by chronic hypercorticism are attracting more attention. Repeated exposure to stress stimuli or chronic administration of corticosterone produces hippocampal 5-HT1A receptor dysfunction as well as an imbalance in mineralocorticoid and glucocorticoid receptors. We recently demonstrated that activation of the 5-HT1A receptors facilitates the adaptive responses to stress stimuli by acting on the HPA axis. These findings suggest that abnormal coupling of glucocorticoid-mineralocorticoid/glucocorticoid receptors-5-HT1A receptors in the hippocampus may be one factor disrupting adaptation to stress situations. Moreover, it is shown that activation of the coupling system affects learning and memory processes associated with stress stimuli. These findings suggest that the functional coupling of glucocorticoid-mineralocorticoid/glucocorticoid receptors and serotonergic neurons in the brain may play a significant role in the recognition of stress stimuli and induction of stress adaptation, and dysfunction of this coupling system may be related to the onset of affective disorders.
Magnetic resonance spectroscopy (MRS) is a safe and non-invasive technique for the in vivo study of brain chemistry and metabolism. As such, it is highly applicable to the study of living brain tissue in psychiatric diseases. Several neuropathological and neuroimaging studies have suggested that abnormalities of the basal ganglia nuclei might be implicated in patients with obsessive-compulsive disorder (OCD). In the present study, we performed proton [1H]MRS of the lenticular nuclei in 12 patients with OCD and 12 healthy normal comparison subjects. The peaks of N-acetyl-aspartate (NAA), creatine (Cr), and choline-containing compounds (Cho) were measured. No differences between OCD patients and normal subjects were found in the NAA/Cr, Cho/Cr and NAA/Cho ratios. Our results suggest the normal viability of neuronal cells, as indicated by the quantification of NAA, Cr and Cho in the lenticular nuclei of patients with OCD.
PURPOSE: This retrospective study was designed to compare treatment results of the chemoradiation protocol with conventional surgery for thoracic T1-T2 esophageal squamous cell carcinoma. METHODS AND MATERIALS: Sixty-six patients with esophageal carcinoma, clinically diagnosed as T1 (tumor invading lamina propria or submucosa) or T2 (tumor invading muscularis propria) were treated for 12 consecutive years, from July 1986 to January 1998. The conventional surgery group included 30 patients who underwent esophagectomy with regional lymph node dissection. Twenty-one of them received postoperative radiotherapy. Thirty-six patients were assigned to the chemoradiation protocol, consisting of neoadjuvant chemoradiotherapy (44 Gy; CDDP: 60 mg/m2, day 1, bolus; 5-FU: 400 mg/m2, day 1-4, continuous), followed by either definitive radiotherapy with high-dose-rate intraluminal brachytherapy (total 70 Gy) for responders or surgery for nonresponders as in the conventional surgery group. Surgical candidates in both groups received intraoperative radiotherapy for abdominal lymphatics since 1991. RESULTS: In the protocol group, 4 patients underwent radical surgery after neoadjuvant chemoradiotherapy, and the remaining 32 underwent definitive chemoradiotherapy. Local control rates at 1 and 3 years were 85% and 70% in the T1/protocol group versus 91% and 80% in the T1/surgery group, and 83% and 83% in the T2/protocol group versus 94% and 80% in the T2/surgery group, respectively. There was no statistical significance. Overall 1- and 3-year survival rates were 100% and 83% in the T1/protocol group versus 82% and 72% in the T1/surgery group (p = 0.36), and 100% and 51% in the T2/protocol group, versus 95% and 68% in the T2/surgery group p = 0.61), respectively. There was no treatment-related mortality in either group. The rates of esophageal conservation were 92% in the T1/protocol group and 58% in the T2/protocol group. CONCLUSION: The chemoradiation protocol can result in comparable survival with conventional surgery for patients with T1-T2 esophageal carcinoma. A randomized trial between definitive chemoradiotherapy and surgery is required.
Following a preliminary revisitation of the nomenclatures in use for mica polytypes, the properties of the periodic intensity distribution (PID) function, which represents the Fourier transform of the stacking sequence, are analysed. On the basis of the relative rotations of neighbouring layers, mica polytypes are classified into three types; for each type, the PID exists in different subspaces of the reciprocal space. A revised procedure to compute the PID, in which further restrictions on the structural model orientation are introduced, is presented. A unifying terminology based upon the most common symbols used to describe mica polytypes (RTW, Z and TS) is derived; these symbols represent the geometrical basis for the computation of the PID. Results are presented for up to four layer polytypes and are compared with the reflection conditions derived by means of Zvyagin's functions. Both the PID values and the reflection conditions are expressed in suitable axial settings and compared with previous partial reports, revealing some errors in previous analyses. A computer program to compute PID from the stacking symbols is available.
Our aim was to analyze the relationship between the proliferative activity of cancer cells, assessed using some cell cycle markers, and clinicopathological factors in colorectal carcinoma patients. Immunostaining for Ki-67 (pan-cell cycle marker), cyclin D1 (G1-phase marker) and cyclin A (S- to G2-phase marker), and in situ hybridization for histone H3 mRNA (S-phase marker) were carried out. Immunoreactivity was evaluated semiquantitatively using a scoring system to calculate a staining index (SI). The expression of cyclin D1, histone H3 mRNA and cyclin A correlated significantly with Ki-67 antigen expression. The SIs of Ki-67, cyclin A and histone H3 mRNA were significantly higher in patients > or = 65 years of age than in those < 65. The SIs of Ki-67 and cyclin D1 in poorly differentiated adenocarcinomas were significantly higher than in the other tumor types. Furthermore, the SI of cyclin D1 in carcinomas with lymph node metastasis was higher than in carcinomas without metastasis and was higher in advanced carcinomas than early carcinomas. The overall survival was significantly lower in patients with cyclin A overexpression than in those without. Multivariate analysis indicated that cyclin A overexpression is an independent prognostic factor in patients with colorectal adenocarcinoma. Our results indicate that cyclin D1 overexpression correlates with poor adenocarcinoma differentiation and tumor progression, and cyclin A overexpression is a superior indicator of poor prognosis compared with the other cell cycle markers tested.
Gradient-modulus star copolymers were synthesized by crosslinking of polystyrene/isoprene tapered anions with divinylbenzene in benzene. The styrene content in the tapered arm was determined by 1H-nuclear magnetic resonance as a parameter of conversion. The composition of the arm showed the gradient structure and was in good agreement with that calculated by reactivity ratios. The solution properties of gradient-modulus star copolymers were examined by static and dynamic light scatterings. The structural ordering of gradient-modulus star copolymers were investigated by means of small-angle X-ray scattering. Gradient-modulus star copolymers formed a body-centered cubic (BCC) structure near the overlap threshold (C*). Above C*, this structure changed to the mixed lattice of BCC and face-centered cubic (FCC) structures. Copyright 1999 Academic Press.
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Sulfatide is a major acidic glycolipid in human gastric mucosa, and its sulfation is catalyzed by cerebroside sulfotransferase (CST). To investigate the expression of the CST gene in human gastric cancer, a reverse transcription PCR method was developed with the use of endoscopic bioptic specimens. By this method, we examined the CST mRNA expression in 11 cases of gastric cancer, and in all the cases we detected various levels of the expression both in cancer tissues and in uninvolved adjacent tissues. The present assay method was suggested to be useful in the detection of CST mRNA from a limited amount of bioptic samples.
Classic cadherins can be grouped based on their deduced primary structures. Among them the type I cadherins have been well characterized; however, little is known about non-type I cadherins. In this study we characterized two human type II cadherins, cadherin-6 and cadherin-14, using a cDNA transfection system. They were each detected as two bands electrophoretically, were expressed on the external cell surface at cell-cell contact sites, and were associated with caten- ins. Direct sequencing of the N-terminal amino acids showed that the two bands of cadherin-14 corresponded to precursor and mature forms, whereas the two bands of cadherin-6 both had the N-terminal sequence of the mature form. Unlike type I cadherins, both cadherin-6 and -14 were not protected from trypsin degradation by Ca2+. We evaluated their adhesive functions by a long term cell aggregation method. The results suggest that both cadherin-6 and -14 have cell-cell binding strengths virtually equivalent to that of E-cadherin and that their binding specificities are distinct from that of E-cadherin. Cadherin-6 and -14 interacted with each other in an incomplete manner. They have a QAI tripeptide in the first extracellular subdomain instead of the HAV motif that is characteristic of type I cadherins and is intimately involved in the adhesive function. The QAI tripeptide, however, appeared not to be involved in the adhesive functions of cadherin-6 and -14.
We examined the effect of a specific cysteinyl leukotriene (LT) receptor antagonist, 4-oxo-8-[4-(4-phenylbutoxy)benzoylamino]-2-(tetrazol-5-yl)-4 H-1-benzopyran hemihydrate (pranlukast), on a novel model of allergic rhinitis induced by repeated intranasal ovalbumin challenge in actively sensitized guinea pigs. Repeated intranasal ovalbumin challenge caused a biphasic increase of nasal airway resistance, peaking 0.5 and 4 h after the final challenge. The early-phase response was accompanied by an increase in sneezing and nasal secretion, while that in the late phase was associated with edema and eosinophil infiltration of the nasal mucosa. Analysis of nasal lavage fluid showed that cysteinyl LTs increased in both phases. Pranlukast, when administered 1 h before every ovalbumin challenge, dose-dependently suppressed the increase of nasal airway resistance in the early- and late phase with evidence of histopathological improvements in the late phase. Pranlukast, however, failed to suppress sneezing and nasal secretion. We suggest that cysteinyl LTs play an important role in allergic rhinitis especially in the nasal obstruction due to edema of the nasal mucosa membrane.
Several reports have indicated that various stress stimuli modulate learning and memory processes. In the present study, the effects of adrenocortical suppression with the 11beta-hydroxylase inhibitor metyrapone on the psychological stress-induced changes in memory storage in inhibitory avoidance training and in serotonin turnover in various brain regions were investigated in rats. Retention of one-trial inhibitory avoidance and the plasma corticosterone level were significantly enhanced by post-training exposure to psychological stress for 1 h. Pretreatment with metyrapone (12.5 or 25 mg/kg, s.c.) 90 min beforehand dose-dependently blocked the enhancement of memory storage and of the plasma corticosterone level produced by psychological stress. These results suggest that the adrenocortical system may contribute to the memory-enhancing effect of psychological stress. In a neurochemical study, a significant increase in serotonin turnover in the hippocampus and limbic forebrain, including the nucleus accumbens, were observed in rats that were exposed to psychological stress. In contrast to the behavioral experiments, these changes in serotonin turnover produced by exposure to psychological stress were not antagonized by pretreatment with metyrapone; instead, a further increase in serotonin turnover was observed only in the hippocampus. These results suggest that the serotonergic system in the hippocampus might be selectively regulated by adrenal steroids in response to stress, and imply the existence of negative feedback mechanisms via a hippocampal serotonergic system in the memory enhancement associated with corticosterone and psychological stress.
Receptors coupled to the inhibitory G protein Gi, such as that for lysophosphatidic acid (LPA), have been shown to activate MAP kinase through a RAS-dependent pathway. However, LPA (but not insulin) has now been shown to activate MAP kinase in a RAS-independent manner in CHO cells that overexpress a dominant-negative mutant of the guanine nucleotide exchange protein SOS (CHO-DeltaSOS cells). LPA also induced the activation of MAP kinase kinase (MEK), but not that of RAF1, in CHO-DeltaSOS cells. The RAS-independent activation of MAP kinase by LPA was blocked by inhibitors of phosphatidylinositol 3-kinase (PI3K) or by overexpression of a dominant-negative mutant of the gamma isoform of PI3K. Furthermore, LPA induced the activation of the atypical zeta isoform of protein kinase C (PKC-zeta) in CHO-DeltaSOS cells in a manner that was sensitive to wortmannin or to the dominant-negative mutant of PI3Kgamma, and overexpression of a dominant-negative mutant of PKC-zeta inhibited LPA-induced activation of MAP kinase. These observations indicate that Gi protein-coupled receptors induce activation of MEK and MAP kinase through a RAS-independent pathway that involves PI3Kgamma-dependent activation of atypical PKC-zeta.
The present study was designed to clarify the time-dependent changes in brain monoamine turnover in the frontal cortex, hypothalamus, hippocampus, septum and amygdala after ovariectomy, and the difference in behavioral responses to psychological stress between sham-operated and ovariectomized (OVX) rats. At 2 and 4 weeks after ovariectomy, the turnover rates of dopamine and norepinephrine in all of the brain regions examined did not differ significantly between the sham-operated and OVX rats. However, 5-hydroxytryptamine (5-HT) turnover in all of the brain regions at 2 weeks after OVX was significantly lower than that in sham-operated rats. This difference was greater in the hypothalamus than in other brain regions. At 4 weeks after ovariectomy, 5-HT turnover in all of the brain regions examined was not significantly different between sham-operated and OVX rats. At 2 and 4 weeks after ovariectomy, exploratory behaviour (e.g., locomotor activity, head- dipping, crossing and rearing behaviours) in a non-stressed ovariectomy group did not differ from that in a non-stressed sham-operation group. Locomotor activity and the number of head-dips and crossings significantly (P<0.05) increased after repeated exposure to psychological stress for 5 days in sham-operated rats, but not in those at 2 weeks after OVX. At 4 weeks after ovariectomy, locomotor activity and the number of crossings and rearings in sham-operated and OVX rats were not significantly different in the psychological stress and non-stress groups. However, the number of head-dips significantly (P<0.05) increased with psychological stress in the sham-operated rats, but not in OVX rats. These results suggest that female gonadal hormones may play an important role in the regulation of brain 5-HTergic systems. These interactions between gonadal hormones and 5-HT metabolism may be related to 5-HT-related neuropsychiatric disorders.
: Two nanoplanktonic marine coccolithophores, Emiliania huxleyi and Gephyrocapsa oceanica, were grown at 23 degrees C with a 16-hour light and 8-hour darkness regimen. The cells were dried at room temperature and then subjected to pyrolysis at 100 degrees to 500 degrees C under anoxygenic conditions to produce hydrocarbons. Temperature-dependent profiles of the liquid-saturated hydrocarbons (saturates) produced during pyrolysis were very similar for the two strains, although the total amount was higher in E. huxleyi than in G. oceanica. The amount of saturates produced was only 0.05% to 0.15% below 200 degrees C, but about 2.1% to 2.8% at 300 degrees C. Their major components were normal alkanes in a series ranging from nC(11) to nC(35) with the predominant peak at nC(15). At 400 degrees and 500 degrees C most of saturates transformed into gaseous compounds. The major saturates identified in all pyrolysates were normal C(31) monounsaturated and diunsaturated alkenes, a series of normal alkanes, phytenes, C(28) sterenes, and steranes. Profiles of saturates in gas chromatography-mass spectroscopy varied with increasing pyrolysis temperature and also differed between E. huxleyi and G. oceanica. The two coccolithophores are useful candidates for the production of renewable liquid fuel through pyrolysis-especially E. huxleyi, which has higher production. The results also provide information for further studies on the characterization, source, and paleogeographic distribution of marine sediment.
A closed YAC contig spanning the mh locus was assembled by STS content mapping with seven microsatellite markers, eight genes or EST, and nine STS corresponding to YAC ends. The contig comprises 27 YACs, has an average depth of 4.3 YACs, and spans an estimated 1.2 Mb. A linkage map was constructed based on five of the microsatellite markers anchored to the contig and shown to span 7 cM, yielding a ratio of 160 kb/1 cM for the corresponding chromosome region. Comparative mapping data indicate that the constructed contig spans an evolutionary breakpoint connecting two chromosome segments that are syntenic but not adjacent in the human. Consolidation of human gene order by means of whole genome radiation hybrids and its comparison with the bovine order as inferred from the contig confirm conservation of gene order within segments.