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Biomedical subjects

T Ikeuchi

Publications and source records attributed to T Ikeuchi.

At least 109 records · Page 6Linked to original sources
PubMed1997

Potent and selective inhibition of human immunodeficiency virus type 1 transcription by piperazinyloxoquinoline derivatives.

We have found novel piperazinyloxoquinoline derivatives to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in both acutely and chronically infected cells. 8-Difluoromethoxy-1-ethyl-6-fluoro-1,4-didehydro-7-[4-(2-met hoxyphenyl)-1-piperazinyl]-4-oxoquinoline-3-carboxylic acid (K-12), the most potent congener of the series, completely inhibited HIV-1 replication in acutely infected MOLT-4 cells at a concentration of 0.16 to 0.8 microM without showing any cytotoxicity. The compound completely suppressed tumor necrosis factor alpha (TNF-alpha)-induced HIV-1 expression in latently infected cells (OM-10.1) and constitutive viral production in chronically infected cells (MOLT-4/III(B)) at a concentration of 0.8 microM. K-12 could also inhibit HIV-1 antigen expression in OM-10.1 and MOLT-4/III(B) cells at this concentration. Northern blot analysis revealed that K-12 selectively prevented the accumulation of HIV-1 mRNA in MOLT-4/III(B) and TNF-alpha-treated OM-10.1 cells in a dose-dependent fashion. It was not inhibitory to HIV-1 Tat or the cellular transcription factors NF-kappaB and Sp1, suggesting that the piperazinyloxoquinoline derivatives are a group of HIV-1 transcription inhibitors with a unique mechanism of action.

Anti-HIV Agents↗
PubMed1997

Atrophy of the cerebellum and brainstem in dentatorubral pallidoluysian atrophy. Influence of CAG repeat size on MRI findings.

To elucidate how the size of the expanded CAG repeat of the gene for dentatorubral pallidoluysian atrophy (DRPLA) and other factors affect the atrophy of the brainstem and cerebellum, and the appearance of high-intensity signals on T2-weighted MRI of the cerebral white matter of patients with DRPLA, we quantitatively analyzed the MRI findings of 26 patients with DRPLA, the diagnosis of which was confirmed by molecular analysis of the DRPLA gene. When we classified the patients into two groups based on the size of the expanded CAG repeat of the DRPLA gene (group 1, number of CAG repeat units > or = 66; group 2, number of CAG repeat units < or = 65), we found strong inverse correlations between the age at MRI and the areas of midsagittal structures of the cerebellum and brainstem in group 1 but not in group 2. Multiple regression analysis, however, revealed that both the patient's age at MRI and the size of the expanded CAG repeat correlated with the areas of midsagittal structures. Involvement of the cerebral white matter as detected on T2-weighted images was observed more frequently in patients belonging to group 2 than in group 1 patients. Furthermore it was demonstrated that high-intensity signals can be detected on T2-weighted images of the cerebral white matter of patients with a largely expanded CAG repeat (group 1) in their thirties. These results suggest that patient age as well as the size of the expanded CAG repeat are related to the degree of atrophy of the brainstem and cerebellum, and the white matter changes in patients with DRPLA.

Adolescent↗
PubMed1997

[Percutaneous transcatheter thermotherapy (PTCT): use of hotwire for local tumor control].

We developed a Hotwire for use in percutaneous transcatheter thermotherapy (PTCT) for local tumor control. The Hotwire has a temperature sensor and a heater, and is inserted into the hepatic artery through a Y-connector and an angiocatheter. It can then warm fluid from the Y-connector to 45 degrees C under electorical control PTCT was performed on liver tumors using 4 mg of MMC and 10 mg Epirubicin. The antitumor effects and indications for PTCT were investigated in patients with unresectable liver tumors, including 3 patients who had hepatocellular carcinoma (HCC) with intraportal invasion and collateral vessels, one patient with liver metastasis of rectal cancer, and two gastric cancer patients. In all patients, tumor marker levels decreased (PIVKA-II; 8.5-->0.9, 2.9-->0.9, AFP; 1154-->753, CEA; 300-->226, TPA; 6319-->4227, 3312-->943), and CRP levels were markedly elevated with tumor fever. The only adverse reaction to PTCT was nausea and vomiting in one female patient. We repeated PTCT 6 times for giant HCC, and performance status was improved (2-->0). In conclusion, PTCT using the Hotwire is useful for treating hypervascular tumors limited to the liver, especially HCC with intraportal invasion and collateral vessels.

Aged↗
PubMed1997

[Extending the capabilities of human chromosome analysis: from high-resolution banding to chromatin fiber-FISH].

The rapid development in human chromosome studies during the past 2 decades has opened up a variety of new avenues in both basic and clinical human genetics. This has been due to the extended resolution of chromosome analysis especially by the introduction of high-resolution banding and fluorescence in situ hybridization (FISH) techniques. High-resolution banding methods using elongated chromosomes from cells at early mitotic stage can be divided into two main categories: one involves S-phase synchronization using methotrexate or thymidine with subsequent release from the block, and the other involves the application of DNA-binding agents, such as ethidium bromide, which inhibit mitotic chromosome condensation. High-resolution band analysis facilitates refined determination of the breakpoints on rearranged chromosomes, and thus minute deletions, small translocations and other subtle chromosome mutations can readily be detected and identified. It has also proved to be valuable for accurate gene mapping and comparative cytogenetics. Each of the high-resolution bands consists of DNA molecules as long as approximately 3Mb on the average, and this resolution limitation has been overcome by the introduction of the FISH method, which enables chromosome and genomic analyses to be carried out at the DNA molecule level. For FISH analysis, appropriate DNA probes of various insert sizes can be chosen for different purposes, and FISH with specific probes permits high-resolution analysis of chromosome DNA constitution at particular loci. For instance, it is possible to detect and map unique sequences more than 1 kb in size on mitotic chromosomes, and to identify cryptic chromosome rearrangements not recognizable even by high-resolution band analysis. Better resolution of breakpoint determination can also be expected by FISH using an adequate series of DNA clones arrayed on the physical map within the relevant chromosome region. An even better genomic resolution by FISH can be obtained by utilizing free chromatin DNA fibers released from interphase nuclei as a hybrization target. The FISH signals on the chromatin fiber preparations are shown to be "linear", unlike the standard FISH signals that have a "dot" appearance, and the resolution attainable should be comparable to analysis of a straight DNA double helix itself. The degree of resolution in the so-called fiber-FISH method ranges from a few to 300 kb, and thus the method can readily be applied to the high-resolution assessment of ordering and overlapping of isolated DNA clones from a specific chromosome region, as well as sizing of gaps between the clones. Fiber-FISH may prove most valuable for the precise determination of breakpoints at the kilobase level, and also for identifying minute deletions and duplications. By presenting some examples of our own recent works, this review attempts to summarize the current contribution of the above strategies in mediating the two separate ranges of resolution achieved by the classical chromosome and molecular DNA analyses.

Chromatin↗
PubMed1997

Two types of micturitions of ileal neobladder.

Eight patients were evaluated clinically, radiologically, and urodynamically to determine the outcome of continent urinary diversion with ileal neobladder performed to treat the recurrent superficial bladder cancer after cystectomy with subcapsular prostatectomy. The mean age of the patients was 55.3 years. After descending dissection of the urinary bladder without ligation or dissection of Santorini's plexus, the prostate was cut to the bladder neck distally for 2 cm under the subcapular prostatectomy. One patient who had a short 3 cm intestinal segment between the pouch and the urethra, had severely prolonged micturition with peristalsis in this short segment, and required a re-operation. Micturition was good in the other seven patients, all with detubularized neobladder directly to the prostate capsule in anastomosis. Pressure flow studies performed on these seven patients revealed two types of micturition; "fast bladder" and "intermittent flow", the latter resembling detrusor sphincter dyssynergia.

Electromyography↗
PubMed1997

[Distal myopathy with rimmed vacuoles(DMRV)].

Distal myopathy with rimmed vacuoles (DMRV) is an autosomal recessive muscular disorder that has been predominantly reported to occur in Japanese population. This disease is characterized clinically by weakness of the distal muscles in the lower limbs in early adulthood, most typically in the tibialis anterior muscle presenting with footdrop. Recently, the gene locus for familial vacuolar myopathy sparing quadriceps muscle with autosomal recessive inheritance (hereditary inclusion body myopathy, HIBM), which was reported to occur in Jews of Persian origin, was mapped to chromosome 9. Since DMRV and HIBM share similar clinical, genetic, and histopathological features, we performed linkage analysis on seven DMRV families. Detection of obligate recombination events as well as pairwise and multipoint linkage analyses revealed that the most likely location of the DMRV gene is in a 23.3 cM interval defined by D9S319 and D9S276 on chromosome 9, which overlap the critical region for HIBM locus. The results raise the possibility that DMRV and HIBM are allelic disease. Identification of the gene(s) for DMRV and HIBM using positional cloning strategy will lead to clarification of the genetic homogeniety for these diseases as well as the understanding in common pathways causing muscle degeneration with vacuolar formation.

Chromosome Mapping↗
PubMed1996

A 1.6-Mb P1-based physical map of the Down syndrome region on chromosome 21.

The Down syndrome (DS) region on chromosome 21, which is responsible for the main features of DS such as characteristic facial features, a congenital heart defect, and mental retardation, has been defined by molecular analysis of DS patients with partial trisomy 21. The 2. 5-Mb region around the marker D21S55 between D21S17 and ERG in 21q22 is thought to be important, although contributions of other regions cannot be excluded. In this region, we focused on a 1.6-Mb region between a NotI site, LA68 (D21S396, which is mapped distal to D21S17) and ERG, because analysis of a Japanese DS family with partial trisomy 21 revealed that the proximal border of its triplicated region was distal to LA68. We constructed P1 contigs with 46 P1 clones covering more than 95% of the 1.6-Mb region. A high-resolution restriction map using BamHI was also constructed for more detailed analysis. Our P1 contig map supplements other physical maps previously reported and provides useful materials for further analysis including gene isolation and sequencing of the DS region.

Base Sequence↗
PubMed1996

PC12h-R cell, a subclone of PC12 cells, shows EGF-induced neuronal differentiation and sustained signaling.

Unlike nerve growth factor (NGF), epidermal growth factor (EGF) does not induce neuronal differentiation but promotes proliferation of the rat pheochromocytoma PC12 cells. We found that PC12h-R, a subclone of PC12 cells, differentiated into neuron-like cells in response to EGF as well as to NGF. PC12h-R cells treated with EGF extended neurites, attenuated cell proliferation, and increased the levels of tyrosine hydroxylase protein synthesis and of acetylcholinesterase activity as those treated with NGF. The EGF-induced differentiation of PC12h-R cells was not mediated by the indirect activation of p140trkA by EGF. In addition, EGF induced the sustained tyrosine phosphorylation of the EGF receptor, mitogen-activated protein (MAP) kinases, and 46 and 52 kDa proteins, and the prolonged activation of MAP kinases in PC12h-R cells compared with the parent PC12h, which does not show EGF-induced differentiation. The response of PC12h-R cells to EGF was not simply due to an increase in the level of EGF receptor protein. These results indicated that the duration of EGF-induced signaling might determine the cellular response of PC12 cells between cell proliferation and neuronal differentiation.

Adrenal Gland Neoplasms↗
PubMed1996

High-resolution chromosome R-banding in lymphoblastoid cell lines by the combined use of cell synchronization and ethidium bromide treatment.

A reliable method for obtaining high-resolution R-banded chromosomes from lymphoblastoid cell lines is described. The cell cultures are subjected to S-phase synchronization in the presence of excess thymidine (300 micrograms/ml) for 17 to 19 hr, followed by BrdU treatment (30 micrograms/ml) for 6.5 hr. Prior to harvest, they are exposed to ethidium bromide (7.5 micrograms/ml) for 1.5 hr and Colcemid (0.02 microgram/ml) for 30 min. Using this method, high-resolution R-banded chromosomes at the 550-850 band level were obtained with frequencies as high as 70% of all mitotic cells.

Cell Cycle↗
PubMed1996

EGF-induced sustained tyrosine phosphorylation and decreased rate of down-regulation of EGF receptor in PC12h-R cells which show neuronal differentiation in response to EGF.

PC12h-R cell, a subclone of PC12 cells, exhibited a neuron-like phenotype, including neurite outgrowth and increased acetylcholinesterase activity, in response to epidermal growth factor (EGF) as well as nerve growth factor (NGF). We examined the mechanism by which EGF induced the neuronal differentiation in PC12h-R cells. The EGF-induced neuronal differentiation of PC12h-R cells was not blocked by K252a, whereas that induced by NGF was. EGF induced sustained tyrosine phosphorylation of the EGF receptor in PC12h-R cells, but not in the parent PC12h cells, which do not show neuronal differentiation in response to EGF. In addition, the rate of EGF-induced down-regulation of the EGF receptor in PC12h-R cells was decreased compared with that in PC12h cells. Furthermore, we found that the duration of EGF-induced tyrosine phosphorylation of the EGF receptor in PC12h-R cells was similar to that of NGF-induced tyrosine phosphorylation of p140trkA in PC12h cells. The EGF-induced phosphorylation of the EGF receptor in PC12h cells was less sustained than that of p140trkA by NGF in PC12h cells. These findings suggested that the EGF-induced neuronal differentiation of PC12h-R cells is due to the sustained activation of the EGF receptor, resulting from the decreased down-regulation of the EGF receptor and that the duration of the receptor tyrosine kinase activity determines the cellular responses of PC12 cells. We concluded that sustained activation of the receptor tyrosine kinase induces neuronal differentiation, although transient activation promotes proliferation of PC12 cells.

Acetylcholinesterase↗
PubMed1996

Antibody responses and protection in mice immunized orally against influenza virus.

Antibody responses and protection were studied in BALB/c mice immunized orally with formalin-inactivated influenza viruses (A/PR/8/34) combined with cholera toxin B subunit as adjuvant. Influenza virus-specific IgA as well as IgG antibody responses were induced in the mice, depending on the oral dosage frequency. The oral immunization by multiple doses resulted in reduction of viral replication in the nose and prevention of development of infection in the lung after intranasal (i.n.) challenge. The protective effect in the nose was thought to be related to the nasal IgA antibody response. The oral immunization was, however, less efficient for induction of the IgA antibody response and protection in the nose, compared with an i.n. immunization. The oral immunization following subcutaneous priming led to the complete protection in the nose, accompanied-by a prompt local IgA antibody response.

Adjuvants, Immunologic↗
PubMed1996

Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant, neurodegenerative disorder that affects the cerebellum and other areas of the central nervous system. We have devised a novel strategy, the direct identification of repeat expansion and cloning technique (DIRECT), which allows selective detection of expanded CAG repeats and cloning of the genes involved. By applying DIRECT, we identified an expanded CAG repeat of the gene for SCA2. CAG repeats of normal alleles range in size from 15 to 24 repeat units, while those of SCA2 chromosomes are expanded to 35 to 59 repeat units. The SCA2 cDNA is predicted to code for 1,313 amino acids-with the CAG repeats coding for a polyglutamine tract. DIRECT is a robust strategy for identification of pathologically expanded trinucleotide repeats and will dramatically accelerate the search for causative genes of neuropsychiatric diseases caused by trinucleotide repeat expansions.

Amino Acid Sequence↗
PubMed1996

[Random biopsy and recurrence risk in patients with bladder cancer].

BACKGROUND: We studied the relationship between the recurrence rate of primary superficial bladder cancer and random biopsy. METHODS: We performed transurethral resection of primary superficial bladder cancer in 144 patients, and in 55 of those cases a random biopsy was also performed. The non-recurrence rate was examined in many recurrence facters. RESULTS: The non-recurrence rate in the group with random biopsy was not significantly different from that observed in the group (100 patients) without random biopsy (chi 2 test, Generalized Wilcoxon test and multivariate analysis). Because the intravesical instillation therapy is an important inhibition factor in the recurrence rate of the primary superficial bladder cancer, we further analysed the recurrence rate in two non treated groups with or without random biopsy (13 and 35 patients respectively). No significant difference in the rate of recurrence between the two groups was observed. However, we noted recurrence of bladder cancer at biopsy positions in 8/13 patients. CONCLUSION: It appears that random biopsy may have an effect on the recurrence or the implantation of tumor cells. Further studies are needed to clarify whether random biopsy is a risk factor in the recurrence rate of primary superficial bladder cancer.

Aged↗
PubMed1996

[Immunohistochemical study of androgen receptor in adenocarcinoma of the human prostatic cancer].

BACKGROUND: The anti-androgen therapy usually used to manage prostatic cancer is effective because the growth of adenocarcinoma of the prostate is influenced by androgens. However, some prostatic cancers do not respond to hormone therapy. Many studies have been conducted with the objective being to assess the responsiveness of prostatic cancer tissues by measuring the amount of androgen receptors (AR). The present study investigates the expression of AR in adenocarcinoma and in benign adenoma of the human prostate. METHODS: Formaline fixed paraffin sections of adenocarcinoma were prepared using 86 patients with primary prostatic cancer, seven patients with relapsed prostatic cancer, and 26 patients with BPH (as the control). Specimens were obtained by needle biopsy and immunohistochemical staining was performed. RESULTS: The benign adenoma AR were stained in the nuclei of the glandular epithelial cells. The receptor-positive and receptor-negative cells were intermingled with the malignant prostatic cells. The labelling indexes (LI) of the androgen receptor stain values in adenocarcinoma of the prostate (57.8 +/- 14.5%) in 86 patients were significantly lower than benign adenoma (86.4 +/- 6.3%) (p = 0.0001). And the LI were decreased with the progress of grades in malignancy: 72.8 +/- 7.5% in well differentiated; 58.7 +/- 7.3% in moderately differentiated; and 41.4 +/- 8.2% in poorly differentiated adenocarcinoma (p = 0.0001). Moreover, LI in relapsed case, all of which were poorly differentiated (22.9 +/- 13.6%), were significantly lower than the LI values of the primary cancer cases with poorly differentiated adenocarcinoma (p = 0.0004). Responders to anti-androgen therapy had high AR positive rate (p = 0.0001) and weakly stained cases had a lower survival rate than strongly stained cases (p = 0.03). CONCLUSION: These results suggest that the detection of AR with immunohistochemical study is useful for estimating the prognosis of the patients undergone anti-androgen therapy. And prostatic cancer cells are heterogeneously composed of clones of both androgen dependent and independent cancer cells before hormonal therapy is begun. And one reason why these tumors easily relapse with the progress of grades in hormonal therapy.

Adenocarcinoma↗