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Biomedical subjects

T Ikeuchi

Publications and source records attributed to T Ikeuchi.

At least 145 records · Page 8Linked to original sources
PubMed1995

Dentatorubral-pallidoluysian atrophy (DRPLA). Molecular basis for wide clinical features of DRPLA.

Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder characterized clinically by various combinations of myoclonus, epilepsy, cerebellar ataxia, choreoathetosis, dementia and psychiatric symptoms. Based on the phenomenon of anticipation, the gene for DRPLA was recently identified. DRPLA is caused by unstable expansion of a CAG repeat in the gene located on the short arm of chromosome 12. As have been observed in Huntington's disease and SCA1, there is a strong correlation between the age of onset and the size of CAG repeats. Furthermore, patients with larger repeats tend to show a PME (progressive myoclonus epilepsy) phenotype as well as earlier ages of onset. More prominent anticipation and larger intergenerational increase of CAG repeats in paternal transmission can be accounted for by the meiotic instability of CAG repeats in male gametogenesis. Comparison of size distributions of CAG repeats in Japanese, African-American and white populations revealed that 7.4% of the Japanese alleles had greater than 19 repeats, whereas none of the whites and 1% of the African-American alleles were of this size. The results may account for the ethnic predilection of DRPLA.

Adult↗
PubMed1995

[A sporadic dentatorubral-pallidoluysian atrophy (DRPLA) diagnosed by gene analysis].

We report a 48-year-old woman with dentatorubral-pallidoluysian atrophy (DRPLA). She is the only patient in her 15 family members in two generations. She developed cerebellar ataxia and epilepsy at age 43. On admission at 48, she showed mild dementia and choreic movement in her face and extremities as well as truncal and limb ataxia. Routine laboratory examinations were normal. The point mutations in the tRNALys gene of mitochondrial DNA specific for MERRF were not found. A cranial CT scan and MRI showed mild atrophy of the cerebellum and prominent atrophy in the pons, especially in the tegmentum. Although she was thought to have DRPLA from the clinical point of view, absence of family history made the diagnosis difficult. Her parents were healthy until their 80's and died of cerebrovascular diseases and her 5 siblings had no symptoms. Hereditary DRPLA is known as an autosomal dominant disorder, with a high rate of penetrance and low rate of new mutation. According to our recent findings of a CAG repeat expansion in the DRPLA gene, this patient was diagnosed as a sporadic DRPLA. Considering the wide varieties of clinical manifestations, it is essential to examine this gene abnormality for diagnosing sporadic DRPLA.

Atrophy↗
PubMed1995

[Expression of PCNA/cyclin, p53, C-erbB-2 versus histological grade in transitional cell carcinoma of urinary bladder].

It is important to know the proliferating ability and the malignant potential of tumor tissues. We have examined the expression of PCNA/cyclin, p53 and C-erbB-2 in transitional cell carcinoma of the human urinary bladder by an immunohistochemical method, and compared the results with the histological grade, stage and survival rate. Immunohistochemical studies, using monoclonal and polyclonal antibodies, on these proteins were performed with formaline fixed-paraffin sections of tumor tissue from 40 patients with bladder cancer. Generally, a higher grade and higher stage tumors expressed PCNA/cyclin, p53 and C-erbB-2 with a greater frequency than the tumors with a lower grade and lower stage and strongly stained cases had a lower survival rate than weakly stained cases. These findings suggest that the detection of each antigen is useful for estimating the malignant potential of transitional cell carcinoma as the adjuvant studies, because of its applicability to paraffin-embedded tissue sections and its simple, rapid technique.

Adult↗
PubMed1995

[Familial myopathy associated with tubular aggregates--report of two siblings].

We reported two siblings with slowly progressive muscle weakness in proximal and peroneal muscles without atrophy, myalgia, cramps, or episodic weakness. The serum creatine kinase level was moderately elevated. The prominent features of their muscle pathology were accumulation of tubular aggregates in type 2 fibers, predominantly in type 2B fibers, and marked type 1 fiber atrophy. Three to eleven % of muscle fibers contained tubular aggregates. Electron microscopic examination revealed accumulation of double-walled tubular structures. Familial myopathy with tubular aggregates as a hallmark of muscle pathology is considered to be a new clinical form of childhood-onset familial myopathies.

Child↗
PubMed1994

Sustained tyrosine phosphorylation of p140trkA in PC12h-R cells responding rapidly to NGF.

The PC12h cell, a subclone of PC12 cells, has considerable activities of tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) and shows an NGF-induced increase in both enzyme activities. The TH activity and its inducibility by NGF in PC12h cells were stably maintained in the passage of > 200 generations whereas the ChAT activity was not. We isolated a new cell line, PC12h-R (originally clone 8), from a long-term culture of PC12h cells. PC12h-R cells still showed the considerable TH activity, but not the ChAT activity, and maintained the inducibility of TH activity by NGF. Thus, the responses of PC12h-R cells to NGF were similar to those of chromaffin cells and sympathetic neurons. PC12h-R cells were found to extend neurites and differentiate into sympathetic neuron-like cells in response to NGF much more rapidly than PC12h cells. In addition, PC12h-R cells showed sustained NGF-induced tyrosine phosphorylation of p140trkA and several cellular proteins, including 42-, 44- and 54-kDa proteins, in comparison with PC12h cells. We suggest that the NGF-induced sustained tyrosine phosphorylation signal in PC12h-R cells may be correlated closely with their rapid NGF-induced differentiation into neuron-like cells.

Animals↗
PubMed1994

Nerve growth factor induces trkA mRNA expression in cultured basal forebrain cholinergic neurons from 17-day fetal rats.

We first examined the basal forebrain tissues for developmental changes in expression of the high-affinity NGF receptor (trkA) gene. Our reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed that trkA mRNA is present in those tissues of postnatal rats, but not in those of fetal rats. Then we determined the effect of NGF on trkA gene expression in serum-free cultures of basal forebrain neurons from 17-day fetal rats. NGF was found to induce trkA mRNA 36 h after the addition of NGF, while no trkA mRNA was detected in the absence of NGF.

Animals↗
PubMed1994

In vitro growth suppression and morphological change in a human renal cell carcinoma cell line by the introduction of normal chromosome 3 via microcell fusion.

Cytogenetic and molecular studies of human renal cell carcinoma (RCC) have suggested that the genetic and functional losses of one or more putative tumor suppressor genes on the short arm of chromosome 3 play a crucial role in the development of this disease. To examine whether the introduction of chromosome 3 has any effects on the biology of RCC cells, we introduced either chromosome 3, 7, or 11 from normal human fibroblasts into a newly established human RCC cell line with loss of heterozygosity for 3p, via microcell-mediated chromosome transfer. Microcell hybrids containing an introduced, intact chromosome 3 showed a significant reduction in in vitro growth rate and saturation density together with morphological alteration; these properties were not altered in microcell hybrids containing an introduced chromosome 7 or 11. During long-term cultivation, one of the clones that had lost the introduced chromosome 3 showed growth properties and morphology similar to those of the parental cell lines. Thus, our findings provide additional evidence for the presence of a putative tumor suppressor gene or genes on normal chromosome 3p and indicate that the gene is a dominant, negative growth regulator whose loss promotes progressive features of the neoplastic phenotype.

Carcinoma, Renal Cell↗
PubMed1994

Gastrointestinal invasion by herpes simplex virus type 1 inoculated cutaneously into the immunosuppressed mice.

The pathogenesis of infection in mice with herpes simplex virus type 1 (HSV-1) strain 7401H was studied. Mice immunosuppressed by intraperitoneal injection of cyclophosphamide were inoculated cutaneously into the flank with the virus and developed severe zosteriform skin lesions. All of them died within 2 weeks after the infection, while most of the normal mice survived the viral infection with healing of the lesions. In the gastrointestinal tract of the immunosuppressed mice, macroscopic abnormalities were frequently observed, and infectious viruses were detected on days 7 to 9. The viruses were also detectable in the dorsal root ganglia and the spinal cord of thoracolumbar area on days 5 to 7, and in the celiac plexus on day 7. However, no viruses were detected in the blood. Immunohistological examination of the gastrointestinal tract revealed that the viral antigens were localized in Auerbach's myenteric plexus. These results suggest that HSV-1 inoculated into the flank skin invaded the gastrointestinal tract via the nervous system, which gastrointestinal involvement might possibly have caused the death of the mice.

Animals↗
PubMed1994

Direct mapping of the human TATA box-binding protein (TBP) gene to 6q27 by fluorescence in situ hybridization.

TBP (TATA box-binding protein) participates in the expression of eukaryotic genes transcribed by RNA polymerases I, II, and III. Molecular cloning of human TBP revealed that the N-terminal region contains a polymorphic (CAG)n repeat. We report here the direct localization of human TBP gene to chromosome 6q2705-->qter region by fluorescence in situ hybridization, using the cDNA clone with or without the (CAG)n repeat as a probe.

Chromosome Mapping↗
PubMed1994

Chromosome 1q terminal deletion resulting from de novo translocation with an acrocentric chromosome.

Distal deletion of chromosome 1q has been reported in nearly 30 patients, all being associated with a deletion ranging from the 1q42 or q43 band to 1qter region. Here, we describe a girl with 1q terminal deletion resulting from an unbalanced de novo translocation t(1;D or G)(q44;p11), as revealed by the presence of a satellited feature and an NOR-stained region at the tip of 1q. We suggest that most of the phenotypic abnormalities seen in patients with 1q distal deletion are attributable to the monosomy for band 1q44.

Child, Preschool↗
PubMed1994

Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA).

Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurologic disorder characterized by variable combinations of myoclonus, epilepsy, cerebellar ataxia, choreoathetosis and dementia. By specifically searching published brain cDNA sequences for the presence of CAG repeats we identified unstable expansion of a CAG in a gene on chromosome 12 in all the 22 DRPLA patients examined. A good correlation between the size of the CAG repeat expansion and the ages of disease onset is found in this group. Patients with earlier onset tended to have a phenotype of progressive myoclonus epilepsy and larger expansions. We propose that the wide variety of clinical manifestations of DRPLA can now be explained by the variable unstable expansion of the CAG repeat.

Adolescent↗
PubMed1994

Characterization of the translocation breakpoint on chromosome 22q12.2 in a patient with neurofibromatosis type 2 (NF2).

We previously described a patient with neurofibromatosis type 2 (NF2) who showed a constitutional balanced translocation, t(4;22). To characterize the breakpoint on chromosome 22 in this patient in relation to a candidate gene (NF2) responsible for NF2, we analyzed DNAs from this patient and her parents using parts of NF2 cDNA as probes. Southern analyses and DNA sequencing revealed that the chromosome 22 breakpoint in this patient lies within the intron between exons 14 and 15 of NF2. The results lend support to the conclusion that NF2 is the gene responsible for the CNS form of neurofibromatosis.

Base Sequence↗
PubMed1994

Anti-angiogenesis agent DS-4152 is a potent and selective inhibitor of HIV-1 replication in vitro.

OBJECTIVE: To determine whether the anti-angiogenesis agent DS-4152 inhibits the replication of HIV-1 in vitro. DESIGN: A sulfated polysaccharide-peptidoglycan DS-4152 has recently been identified as a potent and selective inhibitor of Kaposi's sarcoma (KS). Therefore, it is important to evaluate the anti-HIV-1 activity of DS-4152 alone and in combination with dideoxynucleosides. METHODS: Activity of DS-4152 against HIV-1 replication was examined in MT-4, Molt-4, and peripheral blood lymphocyte cells. The inhibitory effect of the compound on syncytium-formation was determined by cocultivation of Molt-4 cells with Molt-4/IIIB cells. Inhibition of virus adsorption to the host cells was measured by a p24 antigen capture enzyme-linked immunosorbent assay. RESULTS: DS-4152 showed potent and selective inhibition of HIV-1 replication in the cell systems. Its 50% effective concentration for HIV-1 (IIIB strain) in MT-4 cells was 0.7 microgram/ml. The compound was not cytotoxic at concentrations < or = 100 micrograms/ml. DS-4125 proved inhibitory to syncytium-formation and virus adsorption. The anti-HIV-1 activities of zidovudine, dideoxycytidine and dideoxyinosine were not affected by the presence of DS-4152. CONCLUSION: DS-4152 has the potential, from these in vitro studies, to function as an anti-HIV-1 as well as an anti-angiogenesis agent. In order to determine this possibility, consequences of DS-4152 infusion on HIV-1 p24 serum levels and CD4+ cell counts over time are being examined in ongoing clinical trials in the United States on patients with AIDS-associated KS.

Antiviral Agents↗
PubMed1994

Cloning, characterization, and chromosomal mapping of human aquaporin of collecting duct.

We recently cloned a cDNA of the collecting duct apical membrane water channel of rat kidney, which is important for the formation of concentrated urine (Fushima, K., S. Uchida, Y. Hara, Y. Hirata, F. Marumo, and S. Sasaki. 1993. Nature [Lond.]. 361:549-552). Since urine concentrating ability varies among mammalian species, we examined whether an homologous protein is present in human kidney. By screening a human kidney cDNA library, we isolated a cDNA clone, designated human aquaporin of collecting duct (hAQP-CD), that encodes a 271-amino acid protein with 91% identity to rat AQP-CD. mRNA expression of hAQP-CD was predominant in the kidney medulla compared with the cortex, immunohistochemical staining of hAQP-CD was observed only in the collecting duct cells, and the staining was dominant in the apical domain. Functional expression study in Xenopus oocytes confirmed that hAQP-CD worked as a water channel. Western blot analysis of human kidney medulla indicated that the molecular mass of hAQP-CD is 29 kD, which is the same mass expected from the amino acid sequence. Chromosomal mapping of the hAQP-CD gene assigned its location to chromosome 12q13. These results could be important for future studies of the pathophysiology of human urinary concentration mechanisms in normal and abnormal states.

Amino Acid Sequence↗
PubMed1994

Regio- and stereoselective synthesis of carbocyclic 2',3'-dideoxy-3'-fluoro nucleosides as potential antiviral agents.

The synthesis and antiviral activity of racemic carbocyclic 2',3'-dideoxy-3'-fluoro nucleosides are reported. Carbocyclic 2',3'-dideoxy-3'-fluoro nucleosides were obtained from the 3-fluoro cyclopentane derivative 4, which was prepared by two methods. The SN2-displacement of the hydroxyl group of (+/-)-(1 beta, 2 alpha, 3 beta, 4 beta)-4-acetamido-2-fluoro-3-hydroxycyclopentylmethyl acetate (1) with Ph3P-I2 followed by tin hydride reduction afforded the 3-fluoroamino alcohol derivative 3. Alternatively, the protected fluoroamino alcohol 3 was prepared by regio- and stereoselective bromo-fluorination of cis-4 beta-acetamidocyclopent-2-enemethyl acetate (5) with hydrogen fluoride-pyridine/N-bromosuccinimide followed by tin hydride reduction to remove the bromine atom. Carbocyclic 2',3'-dideoxy-3'-fluoroguanosine (14) thus obtained was moderately active against herpes simplex virus in vitro.

Adenoviridae↗
PubMed1994

[Studies on skin irritation with urostomy--the gross and histologic evaluation of the attached area with urostomy].

The degree of damage on the peristomal skin of 42 patients who accepted the urostomy was visually and histologically evaluated. The incidence of damages on the areas of the skin where the materials was applied was 85.7%. The occurrence of non-active lesions (mainly permanent pigment change) was statistically more significant than the active lesions (mainly redness) [p < 0.05]. The incidence of skin lesions using the skin barrier agents was significantly lower statistically than the incidence with the adhesive medication indicating a superior treatment for the skin condition [p < 0.05]. Although the gross appearances were normal, the microscopic and electron microscopic evaluations detected chronic damages indicating comparatively evident changes. The results suggest that these histological evaluations are useful in examining the damage on peristomal skin.

Adult↗