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Biomedical subjects

T Ichikawa

Publications and source records attributed to T Ichikawa.

At least 37 records · Page 2Linked to original sources
PubMed2002

Full-length sequence and functional analysis of hepatitis B virus genome in a virus carrier: a case report suggesting the impact of pre-S and core promoter mutations on the progression of the disease.

In chronic hepatitis B virus (HBV) infection, the quiescent immunotolerant phase evolves into the immunoactive phase. The aim of the present study was to clarify the virological alterations relevant to progression. Serial serum samples obtained from a patient with HBV during long-term follow-up were analysed by sequencing of the full-length HBV-DNA using polymerase chain reaction (PCR). In addition, PCR products of HBV genome from each serum sample were transfected into HuH-7 human hepatoma cells for the functional analysis of the transfected viral genomes. Based on the HBV-DNA sequence analysis, the patient had the genotype C virus, and the mutant HBV with common core promoter mutations (T(1762)A(1764)) and deletion of the pre-S region responsible for large surface protein transcription emerged before the onset of hepatitis. When the vigorous host immune response developed (indicated by the flare-up of hepatitis), the mutant HBV containing common core promoter mutations and another pre-S deletion causing lack of the surface protein promoter became predominant. The HBV-DNA sequences, other than pre-S and core promoter regions were identical to the wild-type sequence throughout the study. Transfection of PCR products containing the mutant HBV sequences resulted in increased amounts of intracellular replicative intermediates but the decreased secretion of HBsAg and HBeAg into culture media, suggesting accumulation of nonenveloped viral core particles within the cells. These results indicate that pre-S deletion and core promoter mutations may participate cooperatively in progression of the disease.

Adult↗
PubMed2002

Laparoscopic adrenalectomy: comparison of transperitoneal and retroperitoneal approaches.

OBJECTIVE: To compare the effectiveness and efficiency of transperitoneal anterior laparoscopic adrenalectomy with that of retroperitoneal posterior laparoscopic adrenalectomy. PATIENTS AND METHODS: A retrospective comparison was undertaken of 28 patients who underwent transperitoneal anterior laparoscopy with 22 patients who underwent retroperitoneal posterior laparoscopy between April 1994 and November 2000. There were 18 men and 32 women (mean age 51.0 years, range 23-68) with varying diagnoses. Of the 50 patients, 31 had primary aldosteronism, eight had Cushing's syndrome, three had phaeochromocytoma, one had an 18-hydroxydeoxycorticosterone-induced adenoma and seven had non-functioning adrenal adenoma. Adrenal tumours were confirmed by hormonal assays, biochemical tests and computed tomography. To determine the site of the functioning adenoma, hormones were assayed from adrenal vein sampling. Thirty adrenal tumours were located on the right and 20 on the left. RESULTS: There were no significant differences in general demographic variables between the transperitoneal and retroperitoneal groups. The mean duration of surgery for transperitoneal and retroperitoneal laparoscopy was 202 and 221 min, respectively, and the mean blood loss 113 and 192 mL, respectively. The time to first oral intake, days to full diet, time until ambulatory and duration of hospitalization did not differ significantly between the two approaches. As the body mass index increased, the duration of surgery increased for both approaches. As more procedures were performed the duration of surgery decreased for both approaches. CONCLUSIONS: There were no significant differences between the transperitoneal and retroperitoneal approaches for laparoscopic adrenalectomy.

Adrenal Gland Diseases↗
PubMed2001

Chondroblastoma of the temporal bone.

A rare case of chondroblastoma arising from the temporal bone that occurred in a 60-year-old woman is reported. The tumor appeared well demarcated and osteolytic on the radiographs. CT scan clearly depicted marginal and central calcification in the tumor. MR imaging demonstrated two components in the tumor: a solid component with predominantly low signal intensities on both T1- and T2-weighted sequences, and a multilocular cystic component with T1- and T2-elongation and fluid-fluid levels on the T2-weighted images. Postcontrast MR imaging revealed marked enhancement in the solid component and the septa of the cystic component.

Chondroblastoma↗
PubMed2001

Hypermethylation of the CD44 gene is associated with progression and metastasis of human prostate cancer.

BACKGROUND: CD44 is a metastasis suppressor gene for prostate cancer and the down-regulation of CD44 and its variants is associated with the progression of prostate cancer. Also, hypermethylation of the CpG islands of the CD44 gene is closely associated with transcriptional inactivation, resulting in the decreased expression of CD44. To clarify the exact role of methylation status of CpG islands of CD44 gene in the progression and metastasis of prostate cancer, we investigated the methylation status of this gene in primary and metastatic human prostate tumors obtained from surgery or autopsy. METHODS: We examined 97 samples from 40 Japanese patients with adenocarcinoma of the prostate. Tumor tissues were obtained from radical prostatectomy specimens from eight patients with stage B, 12 patients with stage C and three patients with stage D1 and at autopsy from 17 hormone-refractory metastatic cases, who had initially responded to the therapy and thereafter relapsed. Distant metastatic tissues were also obtained at autopsy (i.e., liver, lung, kidney, mammary gland, and pelvic lymph nodes) from 10 of 17 hormone-refractory cases. We analyzed the hypermethylation status of CD44 promotor region by PCR using genomic DNAs digested with the m(5)C-sensitive restriction enzyme HpaII. RESULTS: The correlation between the methylation status of CD44 gene and the stage progression of prostate cancer was statistically significant (P = 0.0438). In two of 10 hormone-refractory cases, a comparison of the methylation status of the CD44 gene in metastases to that in primary tumors revealed interfocal heterogeneity of CD44 methylation status. CONCLUSIONS: These results indicate an important role of CD44 methylation in the progression and metastasis of prostate cancer, although the amount of methylational heterogeneity is substantial among metastatic sites within the same patient.

Adenocarcinoma↗
PubMed2001

Comparative analyses of transgene delivery and expression in tumors inoculated with a replication-conditional or -defective viral vector.

Viral vectors for cancer can be classified into those that do not replicate (replication-defective vectors) and those that selectively replicate in neoplastic cells (replication-conditional or oncolytic vectors). Both of these can deliver anticancer cDNAs for therapeutic purposes. Opposite hypotheses can be made regarding the advantages of each vector type with regard to anatomic transgene expression. For the former vector, because cDNA delivery occurs in neoplastic cells that have the ability to migrate into the tumor mass, relatively extensive anatomic and temporal expression of anticancer functions may occur. For the latter vector, active viral replication may permit anatomically and temporally extensive delivery of the foreign cDNA into the tumor mass. Herein, we performed a simple comparative analysis to test which of these hypotheses is valid. Direct inoculation of s.c. tumors with a replication-conditional or a replication-defective viral vector, each of which expressed lacZ cDNA, was performed. Tumors were excised and analyzed for anatomic delivery of beta-galactosidase and for neoplastic viral titers. We find that lacZ cDNA expression is observed in approximately 40% of the tumor area 3, 7, and 14 days after injection with the replication-conditional vector, whereas approximately 10% of the tumor area expresses the transgene 3 days after injection with the replication-defective vector, with a rapid decline in expression thereafter. Titers of the replication-conditional virus remain stable within injected tumors for the 14 days of the assay (approximately 1:1,000 of the initial injection dose), whereas titers of the replication-defective vector decrease rapidly after injection (to a value of 1:100,000 of the initial injection dose). Taken in conjunction, these studies show that transgene delivery and expression in tumors last longer and are found throughout an anatomically more extensive area after injection with replication-conditional gene therapy vectors than after injection with replication-defective gene therapy vectors.

Animals↗
PubMed2001

The suppression of ornithine decarboxylase expression and cell proliferation at the promotion stage of lung tumorigenesis in mice by alpha-tocopheryloxybutyric acid.

It is known that vitamin E inhibits tumor cell growth in vitro irrespective of its antioxidative effect. However, it is unclear whether the effect in vitro can be applied to the in vivo situation. In order to address this question, we estimated if alpha-tocopheryloxybutyric acid (TSE), a non-antioxidative vitamin E derivative in vivo, could inhibit cell proliferation during the tumorigenic process of lung in mice treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), the most potent carcinogen among tobacco-specific nitrosamines. TSE administration suppressed the labeling index of the proliferating cell nuclear antigen, a marker of cell proliferation at a promotion phase of NNK-induced lung tumorigenesis in mice. Similarly, TSE administration inhibited the elevation of ornithine decarboxylase (ODC) activity and its mRNA at the promotion phase. Of four transcription factors contributing to ODC induction, the change in the level of the c-Myc/Max-consensus oligonucleotide complex was only proportional to the change in ODC mRNA level. These results suggest that vitamin E can inhibit cell proliferation linked with ODC induction at the promotion phase of lung tumorigenesis irrespective of its antioxidative effect and that modulation of the transactivation of the c-Myc/Max complex for the ODC gene by TSE in part contributes to the suppression of ODC induction.

Animals↗
PubMed2001

Mitogen-activated protein kinase kinase 4 metastasis suppressor gene expression is inversely related to histological pattern in advancing human prostatic cancers.

We have shown recently (B. A. Yoshida et al., Cancer Res., 59: 5483-5487) that mitogen-activated protein kinase kinase 4 (MKK4) can suppress AT6.1 rat prostate cancer metastases in vivo. Evaluation of the expression of components of the MKK4 signaling cascade showed a loss or down-regulation of expression of MKK4 or c-Jun, a downstream mediator of MKK4, in six of eight human prostate cancer cell lines. Given these findings, we next assessed whether MKK4 dysregulation occurs during the development of clinical prostate cancer. Immunohistochemical studies showed high levels of MKK4 expression in the epithelial but not the stromal compartment of normal prostatic tissues. In neoplastic tissues, a statistically significant, direct, inverse relationship between Gleason pattern and MKK4 was established. These results demonstrate that MKK4 protein is consistently down-regulated during prostate cancer progression and support a role for dysregulation of its signaling cascade in clinical disease. To test the possibility that down-regulation of MKK4 protein is the result of allelic loss, metastatic prostate cancer lesions were examined for loss of heterozygosity (LOH) within the MKK4 locus (D17S969). These studies showed a 31% (5 of 16) LOH of MKK4 that is not associated with coding region mutations, which suggests that the nucleotide sequence of the gene in the remaining allele is infrequently mutated.

Enzyme Activation↗
PubMed2001

Structural studies of the antigen III cell wall polysaccharide of Trichosporon domesticum.

Cell wall and soluble polysaccharides that reacted with Trichosporon domesticum factor III serum were isolated from the type strain of T. domesticum. The fractions contained O-acetyl groups, which contributed to the serological reactivity. The antigenic structure was characterized by chromatographic and spectroscopic methods. The polysaccharide has an alpha-(1-->3)-D-mannan backbone with hetero-oligosaccharide side chains consisting of a 2-O-substituted beta-D-glucuronic acid residue bound to O-2 of the mannose residue, beta-D-xylopyranosyl residues located in the middle of the side chain, and a nonreducing terminal alpha-L-arabinopyranosyl residue bound to 0-4 of xylose. The mannan backbone is O-acetylated at O-6 of the mannose residues.

Acetylation↗
PubMed2001

Mutual coupling among insect neurosecretory cells with an ultradian firing rhythm.

Firing correlations were examined among four pairs of cerebral neurosecretory cells with an ultradian bursting rhythm in the pupal silkmoth Bombyx mori. Cross-correlation analyses of spiking activities between pairs of simultaneously active cells usually revealed a significant correlation of firings: 20-50% of spikes of a cell fired within 0.2 s before or after the other cell's spikes fired. The mutual, excitatory communication among neurosecretory cells make the set of cells a weakly coupled multi-oscillator system that may generates a pulsatile release pattern of their product, an insulin-related neuropeptide (bombyxin).

Action Potentials↗
PubMed2001

The untranslated region of (mu)-opioid receptor mRNA contributes to reduced opioid sensitivity in CXBK mice.

It is well known that there are individual differences in a sensitivity to analgesics. Several lines of evidence have suggested that the level of opioid-induced analgesia is dependent on the level of expression of the mu-opioid receptor (mu-OR). However, the molecular mechanisms underlying the diversity of the level of the opioid receptor and the opioid sensitivity among individuals remain to be elucidated. In the present study, we analyzed the opioid-receptor genes of CXBK recombinant-inbred mice, which show reduced sensitivity to opioids. Northern blotting, nucleotide sequencing, and in situ hybridization histochemical analyses demonstrated that CXBK mice possessed mu-OR mRNA with a normal coding region but an abnormally long untranslated region (UTR). In addition, the mu-OR mRNA level in CXBK mice was less than in the control mice. Next, we produced littermate mice that had inherited two copies of the wild-type mu-OR gene, had inherited two copies of the CXBK mu-OR gene, and had inherited both copies of the mu-OR genes. In these mice, inheritance of the CXBK mu-OR gene was well correlated with less mu-OR mRNA and reduced opioid effects on nociception and locomotor activity. We conclude that the CXBK mu-OR gene is responsible for the CXBK phenotypes. Because UTR differences are known to affect the level of the corresponding mRNA and protein and because UTRs are more divergent among individuals than coding regions, the present findings suggest that opioid sensitivity may vary, depending on different mu-OR levels attributable to divergent UTR of mu-OR mRNA.

Animals↗
PubMed2001

Intraneoplastic polymer-based delivery of cyclophosphamide for intratumoral bioconversion by a replicating oncolytic viral vector.

rRp450 is an oncolytic herpesvirus that expresses the CYP2B1 cDNA, responsible for bioconverting cyclophosphamide (CPA) into the active metabolites 4-hydroxyCPA/aldophosphamide (AP). However, formal proof of prodrug activation is lacking. We report that activation of CPA in cells infected with rRp450 generates a time-dependent increase of diffusible 4-hydroxyCPA/AP. For in vivo applications, a CPA-impregnated polymer was implanted into human tumor xenografts inoculated with rRp450. The area under the curve for 4-hydroxyCPA/AP was 806 microg/g of tumor tissue/h when CPA was administered via intraneoplastic polymer and 3 microg/g of tumor tissue/h when CPA was administered i.p. Therefore, (a) a lytic virus expressing a "suicide" gene can activate a prodrug; and (b) within rRp450-infected tumor, more prolonged and higher concentrations of activated metabolites are generated by intraneoplastic compared with systemic administration of prodrug.

Animals↗
PubMed2001

Geranylgeranylacetone induces antiviral gene expression in human hepatoma cells.

Geranylgeranylacetone (GGA), an isoprenoid compound, is used clinically as an anti-ulcer drug. Since some isoprenoids including retinoids have anti-tumor and anti-viral activities in a variety of cell types, we investigated whether GGA could induce anti-viral proteins in human hepatoma cells. The HuH-7 and HepG2 cells were treated with GGA, and expression of anti-viral proteins such as 2'5'-oligoadenylate synthetase (2'5'-OAS) and double-stranded RNA-dependent protein kinase (PKR) in these cells was analyzed. GGA stimulated 2'5'-OAS and PKR gene expression at the transcriptional level through the formation of interferon-stimulated gene factor 3 (ISGF3), which regulates both gene transcription. By Western blotting, GGA induced expression of signal transducers and activators of transcription 1, 2 (STAT1, STAT2) and p48 proteins, components of ISGF3, together with the phosphorylation of STAT1. These results suggest that GGA acts as a potent inducer of anti-viral gene expression by stimulating the ISGF3 formation in human hepatoma cells.

2',5'-Oligoadenylate Synthetase↗
PubMed2001

Improved helper virus-free packaging system for HSV amplicon vectors using an ICP27-deleted, oversized HSV-1 DNA in a bacterial artificial chromosome.

Herpes simplex virus type 1 (HSV-1) amplicons are prokaryotic plasmids containing one or more transcriptional units and two cis-acting HSV-1 sequences: a viral origin of DNA replication and a viral DNA cleavage/packaging signal. In the presence of HSV-1 "helper" functions, amplicons are replicated and packaged into HSV-1 virions. Despite recent improvements in packaging methods, stocks of amplicon vectors are still contaminated with replication-competent helper virus at a frequency of 10(-4)-10(-6). To overcome this problem, we report that: (i) genetic modifications of HSV-1 genomes can be routinely achieved in Escherichia coli, either by homologous or site-specific recombination, (ii) a novel HSV-1 bacterial artificial chromosome (fHSVDeltapacDelta27 0+), which has a deletion in the essential gene encoding ICP27 and an addition of ICP0 "stuffer" sequences to increase its size to 178 kb, supports the replication and packaging of cotransfected amplicon DNA without generating replication-competent helper virus (<1 helper virus per 10(8) TU amplicon vectors), and (iii) the resulting amplicon stocks have titers of up to 3-10 x 10(8) TU/ml after concentration. Elimination of replication-competent helper virus from HSV-1 amplicon vector stocks further improves safety in gene transfer applications.

Animals↗
PubMed2001

Primary pericardial mesothelioma: a case report.

The imaging features of primary pericardial mesothelioma have rarely been described. Herein we present a case report of its diagnostic-pathologic features. Chest computed tomography (CT) revealed an irregularly enhanced mass occupying the entire pericardial space and surrounding the superior vena cava. At autopsy, the tumor was found to fill the pericardial space completely, and to extend to the superior vena cava through the superior pericardial sinus. The CT features of the tumor were correlated well with those revealed at autopsy, and provided satisfactory information regarding the presence and the extension of the tumor.

Aged↗
PubMed2001

Bone mineral density after total joint arthroplasty of lower extremities in rheumatoid arthritis patients.

We studied the effects on the axial bone mass of total joint arthroplasty (TJA) for lower extremities in 48 female rheumatoid arthritis (RA) patients by using dual-energy X-ray absorptiometry (DXA). Twenty-nine postmenopausal RA patients treated only with nonsteroidal anti-inflammatory drugs (NSAIDs) served as controls. They were studied for an average duration of 63 months. The reduction in the bone mineral density (BMD) of the lumbar spine (L2-4) was significant in both groups (p < 0.01-0.05), but it was not statistically different between the two groups. The BMD of the femoral neck decreased significantly in both groups (p < 0.01-0.05) after 2 years, but it was not statistically different between the two groups. Our data suggest that TJA slowed the rapid axial bone loss usually associated with advanced RA.

Absorptiometry, Photon↗
PubMed2001

A new strategy for evaluation of the eradication treatment of Helicobacter pylori: validation of the analysis of mucin composition in human gastric juice.

The change in the mucin composition of human gastric juice has been investigated in patients before and after the eradication of the Helicobacter pylori (H. pylori) infection. We confirmed the successful eradication of H. pylori in all 17 patients. The gastric luminal mucins were divided into three fractions by ion-exchange chromatography using a discontinuous salt gradient with three salt steps. Although there was a significant variation in the proportion of the mucin content in each fraction among the individual patients, a decrease in the acidic mucin content after the eradication of H. pylori was commonly observed in all the patients. These results indicate that the mucin compositional analysis in the gastric luminal mucin may be a very useful tool for the assessment of H. pylori eradication.

Chromatography, Ion Exchange↗
PubMed2001

Proximal motor conduction evaluated by transcranial magnetic stimulation in acquired inflammatory demyelinating neuropathies.

OBJECTIVES: To evaluate conduction abnormalities in the proximal motor nerve in patients with acquired inflammatory demyelinating neuropathies by transcranial magnetic stimulation (TMS). METHODS: TMS intensity and background voluntary contraction (BVC) to evoke maximal size of motor evoked potential (MEP) in hand muscle were investigated in 24 normal subjects. Effect of experimentally induced conduction block by injecting local anesthetics in the peripheral nerve on MEP size was also studied in two normal subjects. In 22 patients with inflammatory demyelinating neuropathies, maximal MEPs were recorded in the deteriorating and recovery stages of the illness. RESULTS: In normal subjects, the MEP became maximal with 30-50% of maximal BVC and at more than 80% the maximal stimulator output of the 2.0 T circular coil. The change in MEP size well reflected the degree of conduction block induced by local anesthetics. Findings for patients suggested conduction abnormalities proximal to axilla in 9 patients, and that the abnormal reduction of Erb CMAP was the result of submaximal stimulation, not true conduction block, in 3 patients. The increase in MEP/wrist CMAP ratio was better correlated with improvement in muscle strength than with change in the axilla or Erb CMAP/wrist CMAP ratio. CONCLUSIONS: Problems such as conduction abnormalities in the motor tract of the central nervous system could not fully be excluded, but we consider that maximal MEP size can be used to predict proximal motor nerve conduction abnormalities.

Action Potentials↗