Biomedical subjects

Ken-Ichi Nakamura

Publications and source records attributed to Ken-Ichi Nakamura.

8 recordsLinked to original sources

PubMed2003

Demonstration of human telomerase reverse transcriptase (hTERT) in human parathyroid tumours by in situ hybridization with a new oligonucleotide probe.

BACKGROUND AND OBJECTIVE: Telomerase activity is present in most malignant tumours and might provide a mechanism for unlimited replication of neoplastic cells. Expression of the gene encoding human telomerase reverse transcriptase (hTERT), the telomerase catalytic subunit gene, is associated with telomerase activity, and it is overexpressed in most parathyroid carcinomas. We have therefore studied hTERT expression in parathyroid tumours. METHODS: In the present study, we assayed telomerase activity by the telomeric repeat amplification protocol (TRAP) and used in situ hybridization (ISH) to study hTERT mRNA expression in four parathyroid metastatic cancers, six adenomas and two parathyroid hyperplasia tissue specimens. RESULTS: Telomerase activity was detected by the TRAP assay in all of the parathyroid cancers (100%) but in none of the eight parathyroid benign lesions. hTERT gene expression was detected in the nuclei of the parathyroid cancer cells in all of the lesions (100%) but in none of the eight parathyroid benign lesions. CONCLUSIONS: Our results demonstrate a correlation between telomerase activity and hTERT gene expression measured by ISH (P < 0.001) in parathyroid tumours. We succeeded in very clearly and sensitively demonstrating hTERT mRNA in parathyroid tissues by using a new probe.

Adenoma↗

PubMed2003

Clinical application of human telomerase reverse transcriptase gene expression in thyroid follicular tumors by fine-needle aspirations using in situ hybridization.

Most of fine-needle aspiration (FNA) biopsies for follicular tumors of the thyroid are deemed 'indeterminate' or 'suspicious' with regard to malignancy, even though most of these lesions are benign. Therefore, additional diagnostic markers of malignancy are needed. Telomerase activity is present in most malignant tumors. Expression of the gene encoding human telomerase reverse transcriptase (hTERT) is very closely associated with telomerase activity, this gene is overexpressed in most thyroid carcinomas. We examined telomerase activity by the telomeric repeat amplification protocol (TRAP) and hTERT gene expression by in situ hybridization (ISH) in thyroid tissue including 6 follicular carcinomas and 15 follicular adenomas. ISH for hTERT gene was performed using FNA samples from the same patients. Telomerase activity was detected in all six of the follicular carcinomas and in five (33%) of the 15 follicular adenoma tissue specimens. hTERT gene expression was detected the follicular cancer cells in all of the lesions and in one (7%) of the 15 thyroid adenomas. Moreover, we demonstrated that hTERT gene expression was occurring in four (67%) of the 6 follicular carcinoma biopsy specimens obtained using FNA. These results suggest that the detection of hTERT gene expression using ISH tissue specimens can be used to distinguish between benign and malignant follicular lesions of the thyroid, however the detection of hTERT gene in FNA samples using ISH cannot be used to definitively diagnose follicular tumors of the thyroid.

Adenocarcinoma, Follicular↗

PubMed2002

Consistent decrease in telomere length in parathyroid tumors but alteration in telomerase activity limited to malignancies: preliminary report.

Telomerase is known to be activated and telomere length altered in various types of malignant and benign tumors, but whether this is also the case for parathyroid lesions has hitherto been unclear. We therefore investigated telomerase activity and telomere length in 3 parathyroid metastatic cancers, 6 adenomas, 2 cases of parathyroid hyperplasia, and 16 samples of normal parathyroid tissue. Telomerase activity, assayed by the telomeric repeat amplification protocol, was detected in all of the parathyroid cancers (100%), in none of the 8 parathyroid benign lesions, and in only 1 of the 16 normal parathyroid samples (8.3%). Telomere length, determined by the terminal restriction fragment assay, was reduced in the tumor tissues with a mean telomere length of 8.23 +/- 0.86 kbp compared with the 12.61 +/- 0.81 kbp for the 16 age-matched subjects (p = 0.002). The results indicate that telomerase activity and telomere length may reflect the biologic behavior of individual parathyroid lesions.

Adenoma↗

PubMed2002

Telomere shortening with aging in human thyroid and parathyroid tissue.

Progressive telomere shortening with aging was studied using normal thyroid tissue specimens from 46 human subjects aged between 0 and 98 yr and normal parathyroid tissue specimens from 21 human subjects aged between 0 and 83 yrs. There has hitherto been no information documented about telomere length in such thyroid and parathyroid tissues. Age-related shortening at rates of 91 and 92 base pairs (bp) per year, respectively, were observed. Telomere lengths of normal thyroid tissues were 16.53 +/- 1.10 (mean +/- SE), 14.31 +/- 0.80, 11.27 +/- 0.68 and 8.73 +/- 1.08 kbp for age groups less than 2, 20-50, 51-80 and more than 80 yr. Telomere lengths of normal parathyroid tissues were 15.80 +/- 1.46 (mean +/- SE), 15.36 +/- 0.86 and 10.93 +/- 0.78 kbp for age groups less than 4, 20-50 and 51-80 yr. Telomere shortening occurred after 50 yr of age in thyroid and parathyroid tissues. Human thyroid and parathyroid tissues do not seem to show the rapid reduction in telomere length early in life that was reported for some human cell types, suggesting that the rate of telomere shortening has tissue-specific characteristics.

Adult↗

PubMed2002

Telomere lengths are characteristic in each human individual.

BACKGROUND: A great deal of attention has been focused on telomeres in relation to cellular aging, immortality, and cancer. However, there is no simple link between telomeres and tissue turnover. We recently proposed a hypothesis that telomere shortening with aging and telomere lengths in different organs are characteristic for human individuals. METHODS: To test this, telomere lengths were measured using DNA from cerebral cortex, myocardium, liver, renal cortex and spleen tissues obtained from human subjects ranging in age from neonates to centenarians. RESULTS: Regression analyses demonstrated telomere reduction rates of 29-60 base pair (bp) per year in the liver, renal cortex and spleen, but no such decrease in the cerebral cortex and myocardium. Significant correlation was found between tissues within individuals, such as cerebral cortex versus (vs) myocardium, cerebral cortex vs liver, cerebral cortex vs renal cortex, myocardium vs liver, myocardium vs renal cortex, and liver vs renal cortex. In most cases, the longest telomeres were observed in the myocardium and the shortest in the liver or renal cortex. CONCLUSIONS: Telomere lengths did not show clear correlation with tissue renewal times in vivo, but rather were characteristic for individuals.

Adolescent↗

PubMed2002

Comparative analysis of telomere lengths and erosion with age in human epidermis and lingual epithelium.

We investigated progressive telomere shortening in normal human epidermis and lingual epithelium during aging, and attempted, in particular, to ascertain whether the telomere shortening that accompanies aging occurs at the same rate in different tissues. We studied telomeric DNA integrity, and estimated annual telomere loss, in 52 specimens of epidermis and 48 specimens of lingual epithelium collected at autopsy from subjects who had died at ages between 0 and 101 y. Most of the DNA samples were measured twice by southern blot hybridization. In addition, the correlation between telomere lengths in the two types of tissues was examined. The telomere reduction rates in epidermis and lingual epithelium were 36 bp and 30 bp per y, respectively, and these were significantly different. The rates obtained by the second measurements in epidermis and lingual epithelium were 39 and 32 bp per y, respectively, and these were also significantly different. The mean telomere lengths in the epidermis of eight neonates and the lingual epithelium of seven neonates were 13.2+/-1.0 and 13.8+/-1.0 kb, respectively. Comparison of telomere lengths in the two tissues for 41 paired samples showed that the mean telomere length in the epidermis (10.7+/-2.3 kb) was less than that in the lingual epithelium (12.4+/-2.5 kb); however, statistical analysis revealed a very significant relationship between epidermal and lingual epithelial telomere length (r=0.842, p<0.0001). These results indicate that the telomeres in epidermis and lingual epithelium are characterized by tissue-specific loss rates.

Adolescent↗

PubMed2002

Demonstration of human telomerase reverse transcriptase in human colorectal carcinomas by in situ hybridization.

Telomerase activity is present in most malignant tumors and provides a mechanism for unlimited replication of neoplastic cells. Expression of the gene encoding human telomerase reverse transcriptase (hTERT), the telomerase catalytic subunit gene, is associated with telomerase activity, and it is overexpressed in most colorectal carcinomas. In the present study we assayed telomerase activity by the telomeric repeat amplification protocol (TRAP) and used in situ hybridization (ISH) and the reverse transcription polymerase chain reaction (RT-PCR) to study hTERT expression in colorectal carcinomas and adjacent normal tissues. Telomerase activity was found in 30/35 (85.7%) of normal mucosae and 35/35 (100%) of adenocarcinomas, and RT-PCR detected hTERT in 33/35 (94.3%) of the carcinomas. ISH, on the other hand, detected weak but significant expression of hTERT in a significant percentage of lymphocytes infiltrating normal colorectal mucosa. hTERT gene expression was detected in the nuclei of adenocarcinoma cells in 27/35 (77.1%) of the lesions. The results of our comparison of telomerase activity and hTERT gene expression by RT-PCR-based ISH appeared contradictory, but a careful review suggested that the discrepancy was attributable to contamination by infiltrating lymphocytes. Our findings suggest that ISH-based analysis of hTERT gene expression is superior to both TRAP telomerase activity and hTERT mRNA RT-PCR analysis as a means of determining telomerase status during carcinogenesis.

Aged↗

PubMed2001

The Effects of the Hepatitis B Virus and Occupational and Lifestyle Factors on Liver Function Among Workers in Shanghai.

The hepatitis B virus (HBV) infection is a major health problem in China. This study examined liver function in relation to HBV infection, and the occupational and lifestyle factors among workers in Shanghai. The study included 690 male workers aged 20-59 employed at a steel manufacturing company. The occupational and lifestyle factors were evaluated by self-administered questionnaire addressing worksite, exposure to dust or chemicals, history of cigarette smoking and habitual alcohol consumption. The prevalence of hepatitis B surface antigen(HBsAg) seropositivity was 21.4%. Elevated values of aspartate aminotransferase (AST, >30IU/liter) appeared in HBsAg-positive and current alcohol drinking groups but statistically on the borderline. There was a positive linear trend in the odds ratios(ORs) among age groups and ethanol consumption levels for elevated values of g-glutamyl transferase (GGT, >50IU/liter). There was no clear association between occupational exposure and liver functions. When the effects of HBsAg and the current alcohol drinking status on the elevated value of AST were examined simultaneously, OR for cases with HBsAg-positive and current alcohol drinking rose to 2.85(95%CI.98-8.28) against reference cases with HBsAg-negative and non-alcohol drinking, although this association was statistically on the borderline. The results indicated that some interventional attempts including educational strategy for alcohol drinking would be important among the HBsAg-positive cases to reduce the risk of liver dysfunction and further, hepatocellular carcinoma.

Journal Article↗