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M Segawa

Publications and source records attributed to M Segawa.

At least 19 recordsLinked to original sources
PubMed2006

[Pleomorphic carcinoma of the lung rapidly developed multiple metastases after surgery].

Pleomorphic carcinoma of the lung is a type of carcinoma with spindle and/or giant cells with a poor diagnosis. A 73-year-old male was referred to our hospital because of the pulmonary tumor. Lung biopsy revealed that the tumor was poorly differentiated adenocarcinoma. No distant metastasis were observed by systemic examination. A right middle lobectomy with partial resection of the right upper lobe and lymph node dissection were performed, because the tumor (5.3 x 4.0 x 4.0 cm) was located in peripheral S' and invaded S3 via the interlobular space. Histological findings showed adenocarcinoma comprised of spindle cell components that reacted positively to epithelial membrane antigen (EMA) and no lymph node metastasis. Therefore, he was diagnosed with pleomorphic carcinoma of the lung, pT2N0M0, stage IB. But metastatic lesions newly appeared in the thoracic skin, the liver, the diaphragm, the bilateral adrenal glands, and the retroperitoneal space on the 30th postoperative day. He died of peritonitis and pleuritis on only 60 days after the operation.

Adenocarcinoma↗
PubMed2005

Differential effects of sex steroid hormones on the expression of multiple first exons including a novel first exon of prolactin receptor gene in the rat liver.

In addition to the known four alternative first exons E1(1), E1(2), E1(3) and E1(4) of the rat prolactin receptor (PRL-R) gene, a novel first exon, E1(5), was identified by cDNA cloning of the 5'-end region of PRL-R mRNA in the rat liver. Genomic fragments containing E1(5) and its 5'- or 3'-flanking regions were also cloned from rat kidney genomic DNA. A sequence search for E1(5) revealed that E1(5) is located 49 kb upstream of exon 2 of the PRL-R gene in rat chromosome 2q16. RT-PCR analysis revealed that E1(5) was preferentially expressed in the liver, brain and kidney. Expression profiles of E1(2)-, E1(3)- and E1(5)-PRL-R mRNAs in the liver of male and female rats at 5 days of age and those at 8 weeks of age were examined by RT-PCR. The levels of E1(2)-PRL-R mRNA in the female rat increased remarkably in rats at 8 weeks of age compared with those at 5 days of age, and the levels of E1(5)-PRL-R mRNA in the male rat decreased markedly at 8 weeks of age compared with those at 5 days of age. In the female rat, the levels of E1(2)-PRL-R mRNA at 8 weeks of age decreased with ovariectomy performed at 4 weeks of age and recovered with the administration of beta-oestradiol. On the contrary, the levels of E1(5)-PRL-R mRNA increased with ovariectomy and decreased with the oestrogen treatment. In the male rat liver, the levels of E1(2)-PRL-R mRNA at 8 weeks of age increased strikingly with castration performed at 4 weeks of age and became undetectable with the administration of testosterone. The levels of E1(5)-PRL-R mRNA increased slightly with castration and were restored by testosterone treatment. Removal of gonadal tissues and sex steroid hormone treatment had no effect on the expression levels of E1(3)-PRL-R mRNA in both female and male rat livers. These results indicated that the expression of the PRL-R gene in the liver is regulated by the differential effects of sex steroid hormones on the transcription of the multiple first exons including the novel one.

Animals↗
PubMed2003

Heterogeneity in residual function of MeCP2 carrying missense mutations in the methyl CpG binding domain.

Rett syndrome is a neurodevelopmental disorder with severe mental retardation caused by mutations in the MECP2 gene. Mutations in the MECP2 gene are also associated with other genetic disorders, including X linked mental retardation in males. Missense mutations identified so far are present primarily in the methyl CpG binding domain (MBD) of MECP2. Here, the functional significance of 28 MBD missense mutations identified in patients were analysed by transient expression of the mutant proteins in cultured cells. The effects of mutations were evaluated by analysis of the affinity of MeCP2 to pericentromeric heterochromatin in mouse L929 cells and on transcriptional repressive activity of MeCP2 in Drosophila SL2 cells. These analyses showed that approximately one-third (9/28) of MBD missense mutations showed strong impairment of MeCP2 function. The mutation of the R111 residue, which directly interacts with the methyl group of methyl cytosine, completely abolished MeCP2 function and mutations affecting beta-sheets and a hairpin loop have substantial functional consequences. In contrast, mutations that showed marginal or mild impairment of the function fell in unstructured regions with no DNA interaction. Since each of these mutations is known to be pathogenic, the mutations may indicate residues that are important for specific functions of MeCP2 in neurones.

Animals↗
PubMed2001

HBV-related fulminant hepatic failure: successful intensive medical therapy in a candidate for liver transplantation.

Fulminant hepatic failure (FHF) usually has a fatal prognosis without liver transplantation. We describe the case of a woman who developed FHF, and was evaluated as a candidate for liver transplantation, but who was cured without transplantation through intensive medical care that included glucagon-insulin therapy, methylprednisolone pulse therapy, interferon beta and lamivudine administration, cyclosporine administration, and high-volume hemodiafiltration and plasma exchange. In a patient with FHF who is a candidate for liver transplantation but for whom the transplantation cannot be performed for some reason, intensive medical therapy, including regeneration-promoting therapy, immunosuppressive therapy, antiviral therapy, and vigorous hepatic support, should be carried out.

Antiviral Agents↗
PubMed2001

Guidelines for reporting clinical features in cases with MECP2 mutations.

An international group recommends that papers relating phenotypes to genotypes involving mutations in the X chromosome gene MECP2 should provide a minimum data set reporting the range of disturbances frequently encountered in Rett Syndrome. A simple scoring system is suggested which will facilitate comparison among the various clinical profiles. Features are described which should prompt screening for MECP2 mutations.

Chromosomal Proteins, Non-Histone↗
PubMed2001

Functional analyses of MeCP2 mutations associated with Rett syndrome using transient expression systems.

Rett syndrome, an X-linked neurodevelopmental disorder, is a major cause of mental retardation in females. Recent genetic analyses have revealed that mutations in the methyl-CpG-binding protein gene encoding MeCP2 are associated with Rett syndrome. In this study, we used transient expression systems to investigate the functional significance of mutations seen in patients with Rett syndrome. Missense mutations in the methyl-CpG-binding domain were analyzed by the transfection in mouse L929 cells and Drosophila SL2 cells. The L929 cells were utilized to investigate the effects of mutations on the affinity for heterochromatin, where methylated CpG dinucleotides are extremely enriched. The SL2 cells were utilized to analyze their effects on transcriptional repression activities. R106W and F155S mutations led to the substantial impairment of MeCP2 functions, showing the loss of accumulation of the mutated protein to mouse heterochromatin and the reduction of the transcriptional repressive activity in Drosophila SL2 cells. Intriguingly, the R133C mutant retained the functionality equivalent to MeCP2 in these analyses. On the other hand, the T158M mutation exhibited the intermediate level of the impairment of functions in both analyses. Thus, these functional assays are useful to evaluate the consequences of mutation in the methyl-CpG-binding domain of MeCP2 and provide an insight into the relationship between the genotype and the severity of Rett syndrome.

Animals↗
PubMed2001

Pathophysiology of Rett syndrome from the stand point of clinical characteristics.

In this report, we reviewed the characteristics of motor development and motor symptoms of Rett Syndrome (RTT) and demarcated the early and pathognomonic motor symptom which correlates to the impairment of the higher cortical function (HCF) assessed by the ability of language. It is suggested that failure of locomotion in late infancy is the primary and pathognomonic symptom. Thus, the impairment of the neurons or neuronal systems involving locomotion is suggested as the primary lesion in the pathophysiology of RTT not only for motor dysfunction but also for the failure in the development of language and cognitive function. On the other hand the neuronal systems involving the loss of purposeful hand use and the stereotyped hand movement, the most characteristic and diagnostic symptoms of RTT appearing in early childhood, are affected later or secondarily but induce further degradation of the HCF. Hypofunction of the aminergic neurons in the brainstem and midbrain is suggested as the cause of dysfunction of these neuronal systems, for those of locomotion, the noradrenarlin (NA) and/or the serotonin (5HT) neurons and for the stereotyped hand movement the dopamine (DA) neurons. The NA and/or the 5HT neurons in the brain stem may be involved primarily and may cause dysfunction of the midbrain DA neuron directly or indirectly through affecting the pedunculopontine nuclei.

Adolescent↗
PubMed2001

Development of language in Rett syndrome.

Ninety-nine cases of Rett syndrome (RTT) diagnosed clinically (age range 3 years 6 months to 29 years 9 months) were evaluated for the ability of language. The presence of meaningful words, vocabularies, and ages at the start and disappearance of speech were assessed. Phenotype/genotype correlation was evaluated in 22 cases in whom mutations of the genes of methyl-CpG-binding protein 2 (MECP2) existed. Fifty-five cases (55.5%) could speak some words, and of them eight cases (14.5%) spoke two-word sentences. No case had more than 40 words. The vocabularies were mainly bilabial words, known as the characteristics of the initial words in normal children. They began to utter a word between 12 and 48 months, and most of them (85.4%) before 20 months. Those who spoke two-word sentence(s) began to utter a word earlier (10.4+/-3.7 months) than others (17.1+/-9.8 months). Thirty-three cases lost their word(s) in 12-36 months. Among 22 gene-proven cases two cases with mutation of R133C and two cases with R294X had word(s), but another two cases with T158M had not. In RTT a delay in the neuronal systems involved in normal speech development was suggested and its severity seemed to depend on the loci of mutation.

Adolescent↗
PubMed2001

Discussant--pathophysiologies of Rett syndrome.

Studies on sleep parameters of Rett syndrome revealed hypoactivity of the noradrenaline (NA) and the serotonin (5HT) neuron in early infancy while preserving the function of the dopamine (DA) and the cholinergic neurons of the pons normally. The sleep-wake cycle remains in its development at the level of 4 months of age. Polysomnographies also showed a decrease of the function of the nigrostriatal (NS)-DA neuron in early childhood and suggested the development of receptor supersensitivity in late childhood. Neurohistochemical and neuroimaging (PET) studies revealed the hypofunction of the NS-DA neuron with receptor supersensitivity and of involvement of the cholinergic neurons to the cortical pathology, whereas no substantial pathological or histochemical abnormalities were observed in the NA and the 5HT neurons in the brainstem. The decrease of tyrosine hydroxylase without neurodegenerative changes observed in the substantia nigra of Rett syndrome had similarity to the pathology caused by excitotoxic lesion of the pedunculopontine nuclei (PPN) observed in an animal experiments. Clinically the grade of disability of locomotion was shown to correlate to the grade of the disabilities of language. These clinical manifestations were also correlated to the specific loci of the mutation in the methyl binding domain of the MECP2 gene. In rodents the axons of the brainstem 5HT neuron involved in the morphogenesis of the brain in the early developmental course disappear in neonates without apoptotic or degenerative changes in the neurons. This period corresponds to the first 1.5-2 years in humans. Thus, in Rett syndrome, the primary lesion appears in the brainstem NA and 5HT neurons which affects development of synaptogenesis of the cortex and also dysfunction of the PPN. The latter causes dysfunction of the DA neuron and the cholinergic neuron in the midbrain. The mutation of the MECP2 gene may cause early transcription of the genes which prune the axons of the aminergic neurons for the developmental morphogenesis of the central nervous system in early infancy.

Adolescent↗
PubMed2001

R133C and R168X mutations in Japanese Rett syndrome patients: a caution for misdiagnosis.

Rett syndrome is a neurodevelopmental disorder characterized by regression of motor and mental abilities in females after a period of normal development. The gene, MECP2, has been reported to be responsible for Rett syndrome. Here, we report the cases who were at first misdiagnosed as having homozygous mutations, and later corrected as heterozygous ones. We analyzed the MECP2 gene in three sporadic Japanese patients with Rett syndrome. Direct sequencing by using a primer set that was originally used in the first report of MECP2 mutation suggested two types of homozygous mutations (R133C and R168X). Previous reports of these mutations with heterozygous status, as well as the general nature of dominant inheritance in Rett syndrome females and lethality in hemizygous males, urged us to confirm the homozygosity of these mutations. By using a newly designed PCR primer, we found that these mutations actually occurred heterozygously in these patients. Sequence analyses of PCR products suggested that a C/T polymorphism found upstream of these mutations caused the preferential PCR amplification of the mutated alleles. These results recommend paying attention to biased PCR amplification that may lead to misjudgment of the result for mutational analysis of the MECP2 gene.

Adolescent↗
PubMed2001

Fluorimetric determination of isatin in human urine and serum by liquid chromatography postcolumn photoirradiation.

For the fluorimetric determination of isatin in human urine and serum, HPLC-postcolumn photoirradiation using a mobile phase has been developed. Isatin in the urine or serum sample was separated on a Capcell Pak C1 column (250 x 4.6 mm id). The mobile phase consisted of 70 mmol l-1 phosphate buffer (pH 7.2)-tetrahydrofuran (85 + 15% v/v) containing 5 mmol l-1 hydrogen peroxide, which was irradiated with germicidal light to induce fluorescence (lambda ex 302 nm, lambda em 418 nm). The addition of tetrahydrofuran to the mobile phase led to the peaks showing good separation as well as increased sensitivity. The calibration graph for isatin was linear over the range of 0.16-10.7 ng. The pretreatment of the acidified urine or serum samples consisted of diluting steps or deproteinizing steps using perchloric acid, respectively. The mean recovery of isatin from urine and serum was greater than 94%.

Biomarkers↗
PubMed2001

Bradykinin induces a rapid cyclooxygenase-2 mRNA expression via Ca2+ mobilization in human gingival fibroblasts primed with interleukin-1 beta.

We have previously demonstrated that bradykinin potentiates prostaglandin E(2)release in human gingival fibroblasts pretreated with interleukin-1 beta (priming). In this study, we demonstrate a potentiating effect of bradykinin on cyclooxygenase-2 mRNA expression in the interleukin-1 beta-primed fibroblasts. Interleukin-1 beta (200 pg/ml) induced cyclooxygenase-2 mRNA expression, but not bradykinin (1 microM). However, bradykinin rapidly and markedly increased the cyclooxygenase-2 mRNA expression in the fibroblasts primed with interleukin-1 beta. In the primed fibroblasts, ionomycin and thapsigargin mimicked the potentiating effect of bradykinin on the cyclooxygenase-2 mRNA expression. Dexamethasone and actinomycin D completely suppressed not only the interleukin-1 beta-induced cyclooxygenase-2 mRNA expression, but also the bradykinin-induced cyclooxygenase-2 mRNA expression in the interleukin-1 beta-primed fibroblasts, although cycloheximide did not inhibit the effects of interleukin-1 beta and bradykinin. These results suggest that bradykinin-induced prostaglandin E2 synthesis is regulated at the level of the transcription of cyclooxygenase-2 mRNA via Ca2+ mobilization in the interleukin-1 beta-primed human gingival fibroblasts.

Bradykinin↗
PubMed2001

[Th1/Th2 imbalance in HCV-related liver cirrhosis].

The mechanism by which Hepatitis C virus(HCV) infection promotes the development of hepatocellular carcinoma(HCC) is not known exactly. HCV related HCC occurs frequency in the patients with cirrhosis. There have been reports indicating that Th2-type cytokines down-regulated antitumor immunity, and the activation of type 1 T cell responses produced antitumor immunity. We thought Th1/Th2 imbalance in HCV-related liver cirrhosis might be closely related to the development of HCC. In this study, therefore, we investigated the Th1/Th2 balance at the single lymphocyte level of the patients with HCV-related liver cirrhosis and compared with normal controls by using flow cytometry. Th1-type cytokines(IFN-gamma, IL-2) production was significantly decreased in patients with cirrhosis, whereas Th2-type cytokine production(IL-10) was increased. These suggest Th1/Th2 imbalance in HCV-related cirrhosis would decrease the antitumor immunity and its improvement might present the protective effect from HCC.

Carcinoma, Hepatocellular↗
PubMed2000

New efficient chiral derivatizing agent, alpha-cyano-alpha-fluoro(2-naphthyl)acetic acid (2-CFNA). application to the EE determination of (-)-3-acetoxy-2-fluoro-2-(hexadecyloxymethyl)propan-1-ol.

The new chiral derivatizing agent (CDA), alpha-cyano-alpha-fluoro(2-naphthyl)-acetic acid (2-CFNA) 1 was prepared in optically pure form by chiral HPLC separation of racemic 2-CFNA methyl ester (2-CFNA Me ester) (+/-)-2. The ester was obtained by fluorination of methyl alpha-cyano(2-naphthyl)acetate with FClO3. 2-CFNA 1 has proven to be a significantly superior CDA for determination of enantiomeric excess (ee) of a primary alcohol when compared to alpha-methoxy-alpha-trifluoromethylphenylacetic acid (MTPA, Mosher's agent) and alpha-cyano-alpha-fluoro(p-tolyl)acetic acid (CFTA). The ee of (-)-3-acetoxy-2-fluoro-2-(hexadecyloxymethyl)propan-1-ol (-)-9, a fluorinated analog of anticancer active ether lipids, was determined using (+)-2-CFNA (+)-1.

Journal Article↗