Biomedical subjects

H Tahara

Publications and source records attributed to H Tahara.

At least 91 records · Page 5Linked to original sources

PubMed1998

IFN-gamma-inducing factor/IL-18 administration mediates IFN-gamma- and IL-12-independent antitumor effects.

We evaluated the mechanism of the antitumor effects of mouse rIFN-gamma-inducing factor/IL-18 protein on the growth of mouse tumor cell lines in vivo. Mice received IL-18 before or after challenge with CL8-1, a mouse melanoma cell line. Both regimens significantly suppressed tumor growth and reduced the number of mice with growth of tumor from 60% (3/5) to 20% (1/5). Furthermore, IL-18 administered before and after tumor inoculation completely abrogated the establishment of CL8-1 in all animals. IL-18 administration also significantly suppressed the growth of MCA205, a sarcoma cell line, even when treatment was delayed to 7 days following tumor inoculation. Although IL-18/IL-12 combination therapy had the most significant and immediate antitumor effects, many mice so treated succumbed with markedly elevated serum IFN-gamma levels. The antitumor effects of IL-18 were abrogated almost completely when NK cells were eliminated using anti-asialo GM1 Ab administration, but only marginally impaired in IFN-gamma or IL-12 gene-disrupted mice. Immunohistochemical staining revealed that the number of the CD8+ T cells, but not CD4+ T cells, found at the tumor site was reduced in animals treated with IL-18. These results indicate that IL-18 has potent antitumor effects mediated by CD4+ T cells and NK cells, but in IFN-gamma- and IL-12-independent pathways.

Adjuvants, Immunologic↗

PubMed1998

Spontaneous rupture of the stomach in preschool age children: a report of two cases.

The cases of two preschool-age children who suffered spontaneous gastric ruptures are reported herein. The first was a 2-year-old girl with tetralogy of Fallot, transferred to our hospital due to shock. A laparotomy was performed under the diagnosis of gastrointestinal perforation, and two perforations of the posterior wall of the gastric fundus were found. The second case, a 4-year-old girl who had previously experienced an episode of gastric dilatation, was admitted to our department with abdominal distention and vomiting. An abdominal X-ray film revealed a pneumoperitoneum, and an emergency laparotomy was performed, confirming a round rupture in the posterior wall of the stomach. Both patients had a satisfactory postoperative course.

Child, Preschool↗

PubMed1998

Intra-abdominal testis with mature teratoma.

Tumors in an undescended testis are rare in children. We report a mature teratoma arising in the intra-abdominal testis (IAT) of a 1-year-old boy. Preoperative laparoscopy revealed a right IAT near the inguinal ring. As the right testis exposed through the inguinal incision seemed to be a neoplastic mass, an orchidectomy was performed. Histologic examination disclosed a mature teratoma. This is a review of seven cases (including the present one) of a prepubertal tumor originating in an IAT. We speculate that the undescended testes did not cause the neoplasia, but were induced by it.

Cryptorchidism↗

PubMed1998

Viral vectors for gene therapy.

Gene therapy is now being applied to the treatment of wide variety of acquired and inherited diseases. One of the rate-limiting steps for successful gene therapy is the efficiency of gene transfer. A number of different viral systems are being developed for use as vectors for ex vivo and in vivo gene transfer, including retroviruses, adenoviruses, herpes-simplex viruses and adeno-associated viruses. These viral vectors have a number of specific advantages and disadvantages that make them suited to particular gene-therapeutic applications. This review will summarize the current status of the development of viral vectors for gene therapy.

Adenoviridae↗

PubMed1998

Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas.

Telomerase is a specialized type of reverse transcriptase which catalyzes the synthesis and extension of telomeric DNA (for review, see ref.1). This enzyme is highly active in most cancer cells, but is inactive in most somatic cells. This striking observation led to the suggestion that telomerase might be important for the continued growth or progression of cancer cells. However, little is known about the molecular mechanism of telomerase activation in cancer cells. Human telomerase reverse transcriptase (hTRT) has recently been identified as a putative human telomerase catalytic subunit. We transfected the gene encoding hTRT into telomerase-negative human normal fibroblast cells and demonstrated that expression of wild-type hTRT induces telomerase activity, whereas hTRT mutants containing mutations in regions conserved among other reverse transcriptases did not. Hepatocellular carcinoma (20 samples) and non-cancerous liver tissues (19 samples) were examined for telomerase activity and expression of hTRT, the human telomerase RNA component (hTR; encoded by TERC) and the human telomerase-associated protein (hTLP1; encoded by TEP1). A significant correlation between hTRT expression and telomerase activity was observed. These results indicate that the hTRT protein is the catalytic subunit of human telomerase, and that it plays a key role in the activation of telomerase in cancer cells.

Amino Acid Sequence↗

PubMed1998

Interleukin-12 gene therapy prevents establishment of SCC VII squamous cell carcinomas, inhibits tumor growth, and elicits long-term antitumor immunity in syngeneic C3H mice.

Interleukin-12 (IL-12) is an immunostimulatory agent with very promising antitumor activity. Using a retroviral expression vector, the authors have successfully transduced the genes encoding the two subunits of murine IL-12 to the squamous cell carcinoma cell line, SCC VII. Once IL-12 gene transcription and protein production were successfully verified, IL-12 expression was found to inhibit the establishment of SCC VII tumors in syngeneic C3H/HeJ mice inoculated with 1 x 10(6) SCC VII/IL-12 viable tumor cells. Mice immunized in this manner and rechallenged with parent SCC VII were capable of rejecting tumor up to 40% of the time. Treatment of established SCC VII tumors with irradiated IL-12-producing tumors cells led to significant tumor regression in a high percentage of animals.

Animals↗

PubMed1998

Expression of telomerase catalytic component, telomerase reverse transcriptase, in human gastric carcinomas.

Telomerase activity is believed to be crucial for cellular immortality, which is considered to participate in the development of a majority of human cancers. Human telomerase reverse transcriptase (TERT) has recently been identified as a catalytic subunit of telomerase. We examined the expression of TERT and other telomerase components such as human telomerase RNA component (hTR, encoded by TERC) and human telomerase-associated protein (TEP1) by reverse transcription-polymerase chain reaction in human gastric carcinomas and non-neoplastic mucosa, in addition to measuring the telomerase activity. Of 20 gastric carcinomas examined, 18 (90%) and 18 (90%) showed increased expression of TERT and higher telomerase activity in comparison with corresponding non-neoplastic mucosa, respectively. Increased expression of hTR/TERC was also observed in 15 (75%) of the gastric carcinomas. Immunohistochemically, strong expression of TERT protein was detected in the nuclei of the tumor cells of all carcinoma tissues, while the expression of TERT in non-neoplastic mucosal cells as well as stromal elements (except lymphocytes) was weak or negative. These findings suggest that increased TERT expression associated with telomerase activity may serve as a novel marker for the diagnosis of stomach cancer.

Aged↗

PubMed1998

In situ mRNA hybridization technique for analysis of human telomerase RNA in gastric precancerous and cancerous lesions.

Telomerase, the ribonucleoprotein enzyme that elongates telomerase, is repressed in normal somatic cells but is reactivated during tumor progression. The purpose of this study was to investigate the localization of human telomerase RNA (hTR) expression in human gastric precancerous and cancerous lesions by using in situ mRNA hybridization (ISH) with avidin-biotin staining. We also examined telomerase activity in these lesions by using hybridization protection assay connected with a telomeric repeat amplification protocol (TRAP/HPA). Analyzed tissue samples were as follows; 132 cases of chronic atrophic gastritis without intestinal metaplasia, 115 incomplete-type intestinal metaplasias, 40 complete-type intestinal metaplasias, 23 hyperplastic polyps, 23 tubular adenomas and 26 adenocarcinomas. In ISH analysis, high levels of hTR expression were observed preferentially in the nuclei at the single-cell level. hTR-expressing cells in carcinomas and adenomas were significantly more frequent than those of the other lesions (P < 0.001). The expression pattern of hTR in carcinoma and adenoma tissues was heterogeneous and similar intratumor heterogeneity was detected in Ki-67 immunoreactivity. Infiltrating lymphocytes in tissue also exhibited high levels of hTR expression. In TRAP/HPA analysis, carcinomas had significantly more frequent positivity for telomerase activity and a higher level of telomerase activity than the other lesions (P < 0.05). However, the amount of telomerase activity did not parallel the expression level of hTR. Our data suggest that hTR expression increases in the early stages of stomach carcinogenesis and that sufficient synthesis of hTR is a prerequisite for telomerase reactivation in tumorigenesis.

Humans↗

PubMed1998

Novel chromosomal abnormalities identified by comparative genomic hybridization in parathyroid adenomas.

The molecular basis of parathyroid adenomatosis includes defects in the cyclin D1/PRAD1 and MEN1 genes but is, in large part, unknown. To identify new locations of parathyroid oncogenes or tumor suppressor genes, and to further establish the importance of DNA losses described by molecular allelotyping, we performed comparative genomic hybridization (CGH) on a panel of 53 typical sporadic (nonfamilial) parathyroid adenomas. CGH is a new molecular cytogenetic technique in which the entire tumor genome is screened for chromosomal gains and/or losses. Two abnormalities, not previously described, were found recurrently: gain of chromosome 16p (6 of 53 tumors, or 11%) and gain of chromosome 19p (5 of 53, or 9%). Losses were found frequently on 11p (14 of 53, or 26%), as well as 11q (18 of 53, or 34%). Recurrent losses were also seen on chromosomes 1p, 1q, 6q, 9p, 9q, 13q, and 15q, with frequencies ranging from 8-19%. Twenty-four of the 53 adenomas were also extensively analyzed with polymorphic microsatellite markers for allelic losses, either in this study (11 cases) or previously (13 cases). Molecular allelotyping results were highly concordant with CGH results in these tumors (concordance level of 97.5% for all informative markers/chromosome arms examined). In conclusion, CGH has identified the first two known chromosomal gain defects in parathyroid adenomas, suggesting the existence of direct-acting parathyroid oncogenes on chromosomes 16 and 19. CGH has confirmed the locations of putative parathyroid tumor suppressor genes, also defined by molecular allelotyping, on chromosomes 1p, 6q, 9p, 11q, 13q, and 15q. Finally, CGH has provided new evidence favoring the possibility that distinct parathyroid tumor suppressors exist on 1p and 1q, and has raised the possibility of a parathyroid tumor suppressor gene on 11p, distinct from the MEN1 gene on 11q. CGH can identify recurrent genetic abnormalities in hyperparathyroidism, especially chromosomal gains, that other methods to not detect.

Adenoma↗

PubMed1998

[Myxoid liposarcoma surrounding non-functioning transplanted kidney after living renal transplantation: a case report].

A 19-year-old male visited our clinic with the complaint of lower abdominal distention, January 1992. He had undergone living renal transplantation from his mother as a donor on June 15, 1988. But the transplanted kidney had become functional loss by chronic rejection 3 years after transplantation. The computed tomography showed huge low density mass around the non-functioning transplanted kidney. En block resection of the tumor and the transplanted kidney was performed. The tumor was pathologically diagnosed as mixoid liposarcoma. It was proved that the tumor cells were derived from recipient cells by the investigation of HLA-DRB1 DNA typing.

Adult↗

PubMed1998

New brominated and halogen-less derivatives and structure-activity relationship of azaphilones inhibiting gp120-CD4 binding.

Novel brominated and halogen-less azaphilone (oxoisochromane) derivatives, 5-bromoochrephilone and dechloroisochromophilone IV, and known derivatives, dechloroisochromophilone III and isorotiorin, were isolated from the culture broth of a producing organism of isochromophilones I and II (azaphilones inhibiting gp120-CD4 binding), Penicillium multicolor FO-2338, fermented in a medium containing potassium bromide. Nineteen azaphilone-related compounds isolated from the above strain and from other fungi were tested for the inhibition of gp120-CD4 binding and the structure-activity relationship is discussed. Consequently, 5-bromoochrephilone is the strongest inhibitor (IC50, 2.5 microM). A halogen atom at C-5, a proton at C-8 and a diene structure in C-3 side chain of 6-oxoisochromane ring are necessary for gp120-CD4 binding.

Benzopyrans↗

PubMed1998

[Application of antisense human telomerase RNA toward cancer therapy].

We overviewed recent results of anti-tumor effects and inhibition of telomerase activity in tumor cells through antisense human telomerase RNA(hTR). By introducing antisense hTR expression construct into tumor cells, reduction of telomeric DNAs and crisis or cellular senescence occurred in several human cancer cell lines. Antisense oligonucleotides to hTR synthesized with peptide nucleic acids and phosphorothioate deoxyribonucleic acids(PS) also inhibited telomerase activity in vitro. Furthermore, PS antisense hTR had significant effect to decrease tumor size and a number of metastatic nodules in a xenograft human cancer-nude mouse model. Taken together, the telomerase inhibitors targeting to hTR are expected to be novel anti-tumor agents.

Animals↗

PubMed1998

[Analysis of expression of human telomerase RNA in gastric precancerous and cancerous lesions by using in situ mRNA hybridization].

We described the localization of human telomerase RNA (hTR) expression in human gastric precancerous and cancerous lesions by using in situ mRNA hybridization. Diffusely high hTR expression was found in all carcinoma and adenoma tissues. Partially high hTR expression was seen in 75% hyperplastic polyps, 47% complete-type intestinal metaplasia and 21% incomplete-type intestinal metaplasia. All chronic gastritis without intestinal metaplasia possessed normal levels of hTR expression. The expression of hTR was heterogeneous and infiltrating lymphoid cells also expressed high levels of hTR expression. Taken together, overexpression of hTR due to stem cell hyperplasia is an early event of carcinogenesis of the stomach.

Adenoma↗

PubMed1998

Telomerase activity in lesions of the thyroid: application to diagnosis of clinical samples including fine-needle aspirates.

The telomerase enzyme is capable of replacing telomeric DNA sequences that are lost at each cell division. It has been suggested that the function of this enzyme is necessary for cells to become immortal, and in concordance with this hypothesis, telomerase activity has been detected in malignant tumor cells, whereas the enzyme is inactive in normal somatic cells. The measurement of this activity in human tissue samples may have diagnostic value, and in this study, we examined whether such a measurement may be useful for the detection of malignant cells within the thyroid. Telomerase activity was assayed using the telomeric repeat amplification protocol and related to the histological diagnosis of thyroid biopsy tissue samples and of cells obtained from the thyroid by fine-needle aspiration (FNA). Extracts from 9 of 11 (82%) carcinoma biopsy tissue samples contained telomerase activity, whereas enzyme activity was detected in only 2 of 14 (14%) benign tissue sample extracts. These two positive cases were subsequently diagnosed as Graves' disease with severe lymphocytic infiltration. Five of six (83.3%) histologically confirmed carcinoma FNA samples were identified by using the telomeric repeat amplification protocol assay, and two samples considered to be suspicious by FNA cytology were also positive. Conversely, only 4 of 48 (8.3%) benign FNA samples had telomerase. These promising data indicate that this sensitive assay could become a useful adjunct to microscopic cytopathology in the detection of cancer cells in small tissue biopsies and in fine-needle aspirates of the thyroid.

Biopsy, Needle↗

PubMed1998

New method to measure telomerase activity by transcription-mediated amplification and hybridization protection assay.

Telomerase is a ribonucleoprotein complex that uses RNA as a template for the addition of telomeric repeats. The development of the telomeric repeat amplification protocol (TRAP), a sensitive PCR-based assay, has facilitated the detection of telomerase activity in small tissue and tumor samples. Telomerase activity is expected to be a new diagnostic and prognostic marker of human cancer. In this study, we applied a non-PCR-based transcription-mediated amplification (TMA) and hybridization protection assay (HPA) to the measurement of telomerase activity by modification of both primers in TMA. We demonstrated that the modified TMA can detect and measure telomerase activity. TMA/HPA is as sensitive and reproducible as conventional TRAP, but is both faster and easier to perform. Furthermore, we found that TMA/HPA was influenced minimally by TRAP inhibitors that may come from clinical samples. TMA/HPA, which is easy, rapid, and applicable to a high-throughput format, should be clinically useful for the detection and monitoring of telomerase activity.

Carcinoma, Hepatocellular↗

PubMed1998

[Histopathological examination of transurethral electrovaporization of the prostate].

Transurethral electrovaporization of the prostate (TVP) has been devised to eliminate prostatic tissue by electric vaporization and to create a dry coagulation layer beneath to minimize bleeding from the site of TVP. However, vaporization induces degeneration due to thermal coagulation deep in the tissue beneath the vaporized layer, and local tissue damage is thus greater than that caused by the standard transurethral resection of prostate (TURP) loop. Since this results in difficulty with histopathological examination, the percentages of tissue-diagnosable area were determined in sections resected using various vaporization electrodes (Roller Loop, Band & Wedge Loop). The percentage of tissue-diagnosable area was 92.0 +/- 3.3% with the standard TUR loop, 2.4 +/- 0.9% with the Roller Loop, 42.7 +/- 21.1% with the Band Loop, and 39.7 +/- 24.4% with the Wedge Loop. Concerning speed of resection, the best vaporization effect was obtained when the speed of operation was 1/2 or 1/3 that with the standard TUR loop. Since the region in which tissue diagnosis was smaller with the vaporization electrode than with standard TURP, more careful examination was required for diagnosis of incidental cancers. Therefore, postoperative observation by PSA measurement appeared to be important.

Aged↗

PubMed1997

Abnormal telomere dynamics of B-lymphoblastoid cell strains from Werner's syndrome patients transformed by Epstein-Barr virus.

The characteristics of B-lymphoblastoid cell strains transformed by Epstein-Barr virus (EBV) from normal individuals and Werner's syndrome (WRN) patients were compared. We continuously passaged cell strains from 28 WRN patients and 20 normal individuals for about 2 years corresponding to over 160 population doubling levels (PDLs). First, the WRN mutation significantly suppressed the immortalization: all the 28 cell strains from WRN patients, as well as 15 out of 20 cell strains from normal individuals, died out before 160 PDLs mostly without developing a significant telomerase activity. The remaining five cell strains from normal individuals became moderately/strongly telomerase-positive and, three of them were apparently immortalized with an infinitively proliferating activity. Second, the monitoring of the telomere length of both normal and WRN cell strains during the culture period suggests that the WRN gene mutation causes abnormal dynamics of the telomere: (1) a significant proportion of WRN cell strains showed drastic shortening or lengthening of telomere lengths during cell passages compared with normal cell strains, and (2) WRN cell strains terminated their life-span at a wide range of telomere length (between 3.5 and 18.5 Kbp), whereas normal cell strains terminated within a narrow telomere length range (between 5.5 and 9 Kbp). The chromosomal aberration characteristic of WRN cells, including translocation was confirmed in our experiment. We discussed the correlation between the chromosomal instability, abnormal telomere dynamics and inability of immortalization of the WRN B-lymphobloastoid cell strains.

B-Lymphocytes↗

PubMed1997

Decrease in amplified telomeric sequences and induction of senescence markers by introduction of human chromosome 7 or its segments in SUSM-1.

Introduction of human chromosome 7 by microcell-mediated chromosome transfer suppresses indefinite division of SUSM-1, an in vitro established human fibroblast line. This cell line has unusually long telomeric sequences although it lacks detectable telomerase activity. Thus, we examined whether such telomeric sequences change upon introduction of chromosome 7 or its segments. In the microcell hybrids that stopped dividing by introduction of chromosome 7, the telomeric sequences were found to be lost or markedly diminished. Introduction of various fragments (2-40 Mb) of chromosome 7 contained in radiation hybrids gave similar results. On the other hand, the telomeric sequences were not altered significantly in the unsuppressed hybrids, a revertant of one suppressed clone, or subclones of SUSM-1 used as controls. In the suppressed microcell hybrids, the distribution of a mortality marker, mortalin, was changed to the cytosolic type of mortal cells from the immortal type of perinuclear fibres. Also, senescence-associated beta-galactosidase was induced to a level similar to that of normally senesced diploid fibroblasts. These results suggest that human chromosome 7 induces senescence in SUSM-1 by suppressing its telomere maintenance mechanism, which does not depend on telomerase.

Animals↗