[Multicystic encephalopathy].
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Brain Diseases↗
Biomedical subjects
T Enomoto
Publications and source records attributed to T Enomoto.
[Surgical treatment of middle cranial fossa arachnoid cyst in children with atypical symptoms--report of three cases].
We report three cases of symptomatic arachnoid cyst in the middle cranial fossa who presented with atypical symptoms including speech delay, vomiting and personality changes. They were improved by a cyst-peritoneal shunt operation. In many patients with a small or middle sized arachnoid cyst in the middle cranial fossa, their symptom tends to be so trivial that surgery is not the choice of treatment. The present cases suggest that peculiar symptoms caused by a limbic system lesion may be improved by treating the arachnoid cyst in the middle cranial fossa.
Arachnoid Cysts↗
LbrA, a protein predicted to have a role in vesicle trafficking, is necessary for normal morphogenesis in Polysphondylium pallidum.
The fruiting body of Polysphondylium pallidum is composed of whorls of branches along the axis of a central stalk. In the course of fruiting body formation, the interval between neighboring whorls, and the number and the spacing of branches in a whorl are highly regulated. In this study, using the REMI (restriction-enzyme-mediated integration) insertional mutagenesis method, we obtained a mutant (strain M2323) with longer branches than those of the wild-type strain PN500. The sequence analyses revealed the presence of an ORF of 206 aa residues (23 kDa) near the vector insertion site. Disruption of the gene, lbrA (long branch A), by homologous recombination causes the same phenotype as that of M2323. A lbrA transcript is expressed maximally at the early aggregation stage in the parental strain, but is not detectable in the REMI mutant. A homology search showed that LbrA is a member of the p24 family proteins, which have been proposed to function as receptors for cargo proteins that are transported by COP I- (coat protein I) and/or COP II-coated vesicles between the endoplasmic reticulum and the Golgi complex. As far as we know, this is the first paper to show that a p24 family member is implicated in morphogenesis.
Amino Acid Sequence↗
Nonpathogenic common variants of IFNGR1 and IFNGR2 in association with total serum IgE levels.
Atopy is an immune disorder in which a Th2 dominant mechanism leads to high IgE levels and the clinical disorder asthma. It has been postulated that the Th1 cytokine IFNgamma, acting through its heterodimeric receptors, IFNgammaR1 and IFNgammaR2, in the induction/proliferation of Th1 cells, might suppress the Th2 responses that may underlie atopic asthma. However, neither murine nor human variants of IFNgamma associate with atopy. Several dysfunctional mutations have been identified in IFNgamma receptor genes (IFNGR1 and IFNGR2) in relation to severe and selective infections with poorly pathogenic organisms. However, little is known about common polymorphisms and their functional role in atopy. To test whether such variants of IFNGR1 and IFNGR2 relate to atopic asthma, we conducted a genetic association study in both British (n = 300) and Japanese (n = 200) populations. An intronic variant of IFNGR1 showed marginal association with total serum IgE levels in the British population compared with those with total IgE levels <30 IU/ml and those with >120-500 IU/ml [odds ratio = 2.00 (95% CI 1. 00-4.07), P = 0.048]. A coding variant, Gln64Arg of the IFNGR2, also associated with total serum IgE levels in the British population [chi(2) = 5.08, P = 0.024]. Further genetic and functional analyses are needed to clarify the role of variants of IFNgamma receptor genes in atopic immune disorder among different ethnic groups.
Asthma↗
Malignant transformation of NIH3T3 cells by overexpression of early lymphocyte activation antigen CD98.
CD98, which forms a heterodimer of relative molecular mass (M(r)) 125, 000, was originally identified as an early T cell activation antigen. It consists of a heavy chain of M(r) 85,000 that bears the CD98 epitope and a light chain of M(r) 40, 000. CD98 is strongly expressed on the surface of activated lymphocytes and various tumor cells irrespective of tissue origins. To investigate the participation of CD98 in cellular proliferation and malignant transformation, we established and characterized human CD98-transfected NIH3T3 clones. Although the doubling times of the control cells and CD98-transfected clones were almost the same, CD98-transfected clones grew to a higher saturation density than control cells. Effciency of colony formation in soft agar was augmented in CD98-transfected clones, and this augmentation was significantly reduced by anti-human CD98 mAb. Furthermore, CD98-transfected clones developed tumors in athymic mice. These results indicated that overexpression of CD98 participates in the process of malignant transformation, suggesting that CD98 has oncogenic potential.
3T3 Cells↗
Variants of endothelin-1 and its receptors in atopic asthma.
Endothelin-1 (ET-1) is a 21 amino acid peptide released from several types of bronchial cells. It operates through two types of receptors, type A(ET-RA) and type B(ET-RB) and has various activities in the pathophysiology of atopic asthma. These genes are localised on different chromosomes where genome-wide searches have identified linkage for atopic asthma, thus supporting the candidacy of ET-1 and its receptors for atopic asthma. A genetic association study was performed with variants of these three genes in both British (n = 300) and Japanese populations (n = 200). No significant association was found between variants of EDN1 and EDNRB genes, and atopic asthma in either population. However, variants of EDNRA gene showed a marginal association with atopy [odds = 0.39(95% CI: 0.17-0.89), p = 0.022, Pc = 0.066], especially with antigen specific IgE levels [odds = 0.31 (95% CI: 0.20-0.77), p = 0.006, Pc = 0.018] in the British population. These findings suggest that EDNRA is a major candidate locus for atopy on chromosome 4.
Antibody Specificity↗
Cutting edge: dominant effect of Ile50Val variant of the human IL-4 receptor alpha-chain in IgE synthesis.
Two variants of the IL-4R alpha-chain (IL-4Ralpha) gene have been recently identified in association with different atopic disorders. To clarify the etiological relationship between the two variants, we analyzed responsiveness to IL-4 of transfectants with four kinds of IL-4Ralpha carrying either Val or Ile at 50 and either Gln or Arg at 551. The substitution of Ile for Val augmented STAT6 activation, proliferation, and transcription activity of the Iepsilon promoter by IL-4, whereas that of Arg for Gln did not change these IL-4 signals. Arg551 was not associated with atopic asthma in the Japanese population. CD23 expression and IgE synthesis by IL-4 were augmented in Ile50-bearing PBMC, compared with those bearing Val50. Taken together, substitution of Arg551 does not enhance the IL-4 signal for generation of germline epsilon transcript, whereas the substitution of Ile50 contributes to enhancement of IgE synthesis.
Amino Acid Substitution↗
Detection by epitope-defined monoclonal antibodies of Werner DNA helicases in the nucleoplasm and their upregulation by cell transformation and immortalization.
We prepared several monoclonal antibodies (mAbs) specific for the NH2- and COOH-terminal regions of the DNA helicase (WRN helicase) responsible for Werner's syndrome known as a premature aging disease. With these antibodies, we detected by immunoblot analysis the endogenous WRN helicase of a relative mass of 180 kD in several lines of cultured cells, but not in patient cells with a defined mutation. Immunocytochemical staining of proliferating fibroblasts and tumor cells showed that the major part of WRN helicase is in the nucleoplasm and not in the nucleolus. Similar experiments with a rat mAb specific to the mouse homologue of human WRN helicase yielded an identical conclusion. Although this nucleoplasmic staining was evident in cells in interphase, the condensed chromatin structure in metaphase was not stained by the same mAbs, suggesting that WRN helicases exist perhaps in a soluble form or bound to the unfolded chromatin structure. From quantitative immunoblot analysis, higher levels of WRN helicase were observed in all transformed cells and tumor cells examined than those of normal cells. The expression of WRN helicase was enhanced consistently in fibroblasts and B-lymphoblastoid cells by transformation with SV-40 and Epstein-Barr virus, respectively, suggesting that rapidly proliferating cells require a high copy numbers of WRN helicase.
Animals↗
Disordered expression of the sucrase-isomaltase complex in the small intestine in Otsuka Long-Evans tokushima fatty rats, a model of non-insulin-dependent diabetes mellitus with insulin resistance.
To clarify the relationship between diabetes mellitus and carbohydrate digestion, the activities of sucrase and isomaltase, which form a complex enzyme (SI complex) on the brush border membranes, were compared in the progression of diabetes mellitus in Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of human non-insulin-dependent diabetes mellitus with insulin resistance, and Long-Evans Tokushima Otsuka (LETO) rats as non-diabetic controls. Until 40 weeks of age, OLETF rats were obese and had a high plasma glucose level, compared to age-matched LETO rats, but the sucrase and isomaltase activities showed no significant differences between the two strains. Oral glucose tolerance test revealed that during 40-48 weeks of age, NIDDM became very severe with advancing insulin resistance in OLETF rats. In OLETF rats, in contrast to LETO rats, at 48 weeks of age, abnormal increases in the sucrase and isomaltase activities occurred, along with a remarkable decrease in body weight and a further great increase in the plasma glucose level in the non-fasting state. Hyperinsulinemia occurred in 20-week-old OLETF rats; however, at 40 and 48 weeks of age, the plasma insulin level in the non-fasting state in OLETF rats was not significantly different from that in LETO rats. The level of mRNA encoding the SI complex increased abnormally in 48-week-old OLETF rats. These results suggest that the advance of insulin resistance leads to an increase in the expression of the SI complex on the transcriptional level.
Age Factors↗
Intracranial hemorrhage in an infant owing to vitamin K deficiency despite prophylaxis.
A 3-month-old male infant with intracranial hemorrhage attributable to a vitamin K deficiency is reported. Vitamin K2 was administered orally at birth and then at 5 days and I month of age. Oral antibiotics were also given 2 days before the onset of bleeding. Although the incidence of intracranial hemorrhage resulting from vitamin K deficiency has decreased since the introduction of vitamin K2 prophylaxis, spontaneous intracranial hemorrhages are still being reported in infants. We suggest that vitamin K prophylaxis is needed especially for breast-fed infants and for those undergoing antibiotic therapy.
Cerebral Hemorrhage↗
neu mutation in schwannomas induced transplacentally in Syrian golden hamsters by N-nitrosoethylurea: high incidence but low allelic representation.
Peripheral nerve tumors (PNT) and melanomas induced transplacentally on day 14 of gestation in Syrian golden hamsters by N-nitrosoethylurea were analyzed for activated oncogenes by the NIH 3T3 transfection assay, and for mutations in the neu oncogene by direct sequencing, allele-specific oligonucleotide hybridization, MnlI restriction-fragment-length polymorphism, single-strand conformation polymorphism, and mismatch amplification mutation assays. All (67/67) of the PNT, but none of the melanomas, contained a somatic missense T --> A transversion within the neu oncogene transmembrane domain at a site corresponding to that which also occurs in rat schwannomas transplacentally induced by N-nitrosoethylurea. In only 2 of the 67 individual hamster PNT did the majority of tumor cells appear to carry the mutant neu allele, in contrast to comparable rat schwannomas in which it overwhelmingly predominates. The low fraction of hamster tumor cells carrying the mutation was stable through multiple transplantation passages. In the hamster, as in the rat, specific point-mutational activation of the neu oncogene thus constitutes the major pathway for induction of PNT by transplacental exposure to an alkylating agent, but the low allelic representation of mutant neu in hamster PNT suggests a significant difference in mechanism by which the mutant oncogene acts in this species.
Alkylating Agents↗
Activation of neu by missense point mutation in the transmembrane domain in schwannomas induced in C3H/HeNCr mice by transplacental exposure to N-nitrosoethylurea.
Transplacentally initiated schwannomas in mice and rats arise preferentially in the Gasserian ganglion of the trigeminal nerve and spinal root ganglia, while those of the Syrian golden hamster most commonly occur subcutaneously. Rat and hamster schwannomas almost invariably contain a mutationally activated neu oncogene. In rat schwannomas, the mutant allele predominates, while the relative abundance of mutant alleles is very low in hamster nerve tumors. We investigated whether neu is mutated in mouse schwannomas and whether the pattern and allelic ratio of the mutation resemble those for the hamster or the rat. Pregnant C3H/HeNCr mice received 0.4 micromol N-nitrosoethylurea/g body weight on day 19 of gestation. Ten trigeminal and one peripheral nerve schwannomas developed in 11 of the 201 offspring. Missense T --> A transversion mutations were detected in the neu transmembrane domain in eight of ten schwannomas analyzed, as determined by MnlI digestion of polymerase chain reaction products. The mutant allele was predominantly detected in two tumors and was abundant in six others. Transfection of eight out of ten mouse tumor DNAs into hamster cells yielded transformed foci; seven out of eight contained mutant mouse neu. Mouse schwannomas closely resembled those of rats both in the preferred anatomical site and in the mutant/wild-type neu allele ratios.
3T3 Cells↗
Chronic progressive hematomyelia: case reports and review of the literature.
BACKGROUND: Hematomyelia usually has an acute onset and rapid progression, which results in a poor prognosis. However, there have been a few cases in which the clinical symptoms have progressed chronically, with a good prognosis. These two different clinical courses should be analyzed separately. The differential diagnosis of spinal tumor and other chronic progressive diseases due to the similarity of the clinical courses is also important. CASE DESCRIPTION: Two cases of hematomyelia with slowly progressive symptoms are reported. Unlike the acute onset and rapid progression or recurrent episodic deterioration usually seen in hematomyelia, the symptoms of chronic hematomyelia progressed over months and resulted in a better clinical prognosis than the acute course. The cases of "chronic progressive hematomyelia" from the literature are briefly summarized. CONCLUSIONS: Chronic progressive hematomyelia should be considered as a different clinical entity from the acute version because of its slowly progressive clinical course and good outcome. Magnetic resonance imaging is the procedure of choice to exclude spinal tumors or other slowly progressive intraspinal diseases.
Chronic Disease↗
Chromosome 11q13 and atopic asthma.
Asthma is a complex syndrome in which bronchial inflammation and smooth muscle hyperactivity lead to labile airflow obstruction. The commonest form of asthma is that due to atopy, which is an immune disorder where production of IgE to inhaled antigens leads to bronchial mucosal inflammation. The ultimate origins of asthma are interactive environmental and genetic factors. The genetics is acknowledged to be heterogeneous, and one chromosomal region of interest and controversy has been 11q13. To clarify the nature of the chromosome 11q13 effect in atopy and asthma, we conducted a genetic association study in subjects with marked atopic asthma and matched controls, which incorporated the study of 13 genetic variants over a distance of 10-12 cM and which took account of detailed immune and clinical phenotyping. Association with high IgE levels was limited to the interval flanked by D11S1335 and CD20 in a 0.8-Mb interval and was greatest for variants of Fc epsilonRIbeta and HTm4; these variants also associated with asthma (recurrent wheeze with labile airflow obstruction and need for regular inhaler treatment). At the more telomeric marker, D11S480, variants associated with asthma, but not with high IgE levels. The data might support the possibility of multiple loci relevant to atopic asthma on chromosome 11q13.
Alleles↗
Alteration of p16 and p15 genes in human uterine tumours.
The roles of the p16 and p15 inhibitor of cyclin-dependent kinase tumour suppressor genes were examined in human uterine cervical and endometrial cancers. p16 mRNA, examined by reverse transcription polymerase chain reaction (RT-PCR), was significantly reduced in five of 19 (26%) cervical and four of 25 (16%) endometrial tumours. Reduced expression of p16 protein, detected by immunohistochemistry, occurred even more frequently, in nine of 33 (27%) cervical and seven of 37 (19%) endometrial tumours. Hypermethylation of a site within the 5'-CpG island of the p16 gene was detected in only one of 32 (3%) cervical tumours and none of 26 endometrial tumours. Homozygous p16 gene deletion, evaluated by differential PCR analysis, was found in four of 40 (10%) cervical tumours and one of 38 (3%) endometrial tumours. Homozygous deletion of p15 was found in three of 40 (8%) cervical tumours and one of 38 (3%) endometrial tumours. PCR-SSCP (single-strand conformation polymorphism) analysis detected point mutations in the p16 gene in six (8%) of 78 uterine tumours (four of 40 (10%) cervical tumours and two of 38 (5%) endometrial tumours). Three were mis-sense mutations, one in codon 74 (CTG-->ATG) and one in codon 129 (ACC-->ATC), both in cervical carcinomas, and the other was in codon 127 (GGG-->GAG) in an endometrial carcinoma. There was one non-sense mutation, in codon 50 (CGA-->TGA), in an endometrial carcinoma. The remaining two were silent somatic cell mutations, both in cervical carcinomas, resulting in no amino acid change. These observations suggest that inactivation of the p16 gene, either by homologous deletion, mutation or loss of expression, occurs in a subset of uterine tumours.
Animals↗
Effects of a small dose of triazolam on P300.
Ten healthy men (mean age, 33.9 years) participated in two experimental sessions cross-overed randomly in a double-blind manner: one with the placebo and another with 0.125 mg of triazolam (TRZ). Resting electroencephalography and event-related potential under oddball paradigm were recorded before the drug administration, and 1, 2, 4, 6 and 8 h after that. P300 waveforms were analyzed by peak amplitudes and 30-ms bin data. Triazolam may cause cognitive dysfunction without general sedation or apparent sleepiness, and this effect appeared 2 h, 4 h and 6 h, most prominently 6 h, after TRZ administration.
Adult↗
K-ras mutations appear in the premalignant phase of both microsatellite stable and unstable endometrial carcinogenesis.
AIMS: Sequential events of endometrial tumorigenesis can be studied by comparison of genetic lesions seen in normal, premalignant, and malignant tissues. The distribution of k-ras mutations in microsatellite stable and unstable premalignant lesions was studied to determine whether this gene is implicated in both tumorigenic pathways. METHODS: K-ras mutations were analysed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing in matched endometrial normal, premalignant (atypical hyperplasias), and adenocarcinoma tissues from individual patients. Identification of precancers solely by their appearance as atypical endometrial hyperplasias is very subjective; therefore, in addition to histopathological assessment, we performed molecular testing (non-random X inactivation or clonal altered microsatellites) for an expected feature of precancers--that is, monoclonality. RESULTS: Equivalent K-ras mutation frequencies were seen in microsatellite stable (six of 33) and unstable (three of 23) cancers. In both types, K-ras mutation in monoclonal precancers usually corresponded to a change from normal to an equivocal (two of 12) or hyperplastic (10 of 12) histology. Divergent K-ras genotypes among multiple neoplastic tissues of individual patients (two of six patients) are exceptions explained either by multicentric premalignant disease, or acquisition of K-ras mutation late in neoplastic progression. CONCLUSIONS: K-ras mutation occurs in both premalignant microsatellite stable and unstable endometrial neoplasia, sometimes before acquisition of features readily diagnostic as atypical endometrial hyperplasia.
Adenocarcinoma↗