Biomedical subjects

H J Harn

Publications and source records attributed to H J Harn.

At least 19 recordsLinked to original sources

PubMed2001

Correlation of human papillomavirus 16 and 18 with cervical neoplasia in histological typing and clinical stage in Taiwan: an in-situ polymerase chain reaction approach.

BACKGROUND AND OBJECTIVES: In situ polymerase chain reaction (ISPCR) promises to considerably enhance our ability to detect a few copies of target nucleic acid sequences in fixed tissues and cells. The aim of this study was to investigate cervical carcinoma to determine the human papillomavirus (HPV) types on paraffin-embedded tissue sections by ISPCR and standard in situ hybridization. The results will correlate the morphological characteristics of lesions with viral typing results. METHODS: This study examined prevalence of HPV 16 and 18 DNA in biopsies from 85 cervical cancer patients by ISPCR, employing HPV 16, 18 consensus primers. There are 45 patients with squamous cell carcinomas, 13 with adenocarcinoma, 2 with adenosquamous carcinomas, 3 with small cell carcinomas, and 22 carcinoma in situ. The relation between the types of HPV detected, tumor type, and clinical stage were analyzed. RESULTS: Fifty-two of 85 biopsies were HPV 16- or 18-positive, HPV 16 being the most prevalent type. Squamous cell carcinoma had a high prevalence of HPV 16 and adenocarcinoma had a high prevalence of HPV 18. HPV 18 was the predominant type among high clinical stage (III-IV) cases while HPV 16 and mixed HPV 16 with HPV18 were significantly correlated with low clinical stage (0-I-II). CONCLUSION: Our results indicate that certain malignant cervical tumor phenotypes and stages correlate with specific HPV type, and that ISPCR is a sensitive and fast method to detect HPV in these patients.

Adenocarcinoma↗

PubMed2001

In situ detection of hTERT mRNA relates to Ki-67 labeling index in papillary thyroid carcinoma.

BACKGROUND: Telomerase is activated in most human cancers but is inactivate in adult somatic tissues except for some proliferating cell lineages. The maintenance of telomerase activity may be a critical step of cellular immortalization and transformation. MATERIALS AND METHODS: We analyzed the expression of human telomerase reverse transcriptase (hTERT) using in situ hybridization and compared it to Ki-67 immunoreactivity in 29 cases of papillary thyroid carcinoma (PTC) and 17 cases of benign thyroid disease. RESULTS: The hTERT messenger RNA (mRNA) was expressed in the cytoplasm of carcinoma cells with moderate (n = 10) to strong intensity (n = 10) in 69% (20 of 29) PTC cases. Human TERT was found in only 29% (5 of 17) cases of benign thyroid disease. Human TERT gene expression was preferentially detected in PTC (P = 0.021). The Ki-67 labeling index was observed in 16 cases of PTC (16 of 29; 55.2%). This result was significantly different from that of benign thyroid disease (P = 0.014). The Ki-67 labeling index related to the intensity of hTERT mRNA expression (r = 0.51; P = 0.005) and was inversely associated with the follicular variant of PTC (r = -0.413; P = 0.026). No statistically significant difference was found between hTERT expression and histological subtype of PTC. CONCLUSIONS: Our results demonstrated that expression of hTERT could be detected using in situ hybridization in PTCs and was significantly distinguishable from that of benign thyroid disease. Human TERT expression was related to the Ki-67 labeling index, indicating that coupling of telomerase activation with cell proliferation was the associated mechanism for tumorigenesis.

Adolescent↗

PubMed2001

Polymorphism of the beta(2)-adrenoceptor in COPD in Chinese subjects.

STUDY OBJECTIVES: To assess the frequencies of three polymorphisms at amino acid positions 16, 27, and 164 of the beta(2)-adrenoceptor (beta(2)-AR) gene and their effects on COPD patients. DESIGN: Prospective, case-control study PATIENTS: Sixty-five patients with COPD and 41 healthy subjects were included. MEASUREMENTS: Polymorphisms of the beta(2)-AR coding block were delineated using an allele-specific polymerase chain reaction (PCR) approach. The allele-specific PCR technique was verified by direct dideoxy sequencing of PCR products. Pulmonary function tests were performed in all patients. RESULTS: The Arg16 beta(2)-AR polymorphism was less prevalent in COPD patients than in healthy populations (p = 0.01). A significant correlation (p < 0.018) between the Gln27 beta(2)-AR polymorphism and FEV(1) percent predicted value was found. Patients with the Gln27 polymorphism had a higher percentage of low FEV(1) percent predicted than did patients with the GlnGlu and GluGlu variants. CONCLUSIONS: The polymorphism of Gly16 may increase the patient's susceptibility to the development of COPD. The Gln27 beta(2)-AR polymorphism may be associated with the severity of COPD in a Chinese population.

Aged↗

PubMed2000

Microsatellite alterations on human chromosome 11 in in situ and invasive breast cancer: a microdissection microsatellite analysis and correlation with p53, ER (estrogen receptor), and PR (progesterone receptor) protein immunoreactivity.

BACKGROUND AND OBJECTIVES: Microsatellite instability (MSI) has been documented in a subset of sporadic tumors. Loss of heterozygosity (LOH) on chromosome 11 loci in breast cancer is a frequent event. The purpose of the present study is to examine the incidence of microsatellite alterations in in situ and invasive human breast carcinoma and to clarify their significance in regulating the dynamics of cancer progression. METHODS: Four highly polymorphic (CA)n repeat microsatellites were used to determine microsatellite alterations in ten ductal carcinoma in situ (DCIS) and 19 invasive ductal carcinoma (IDC). To investigate the expression of p53, ER (estrogen receptor), and PR (progesterone receptor) association with MSI, immunohistochemistry staining was applied. RESULTS: MSI were detected in 20% (2/10) of DCIS and in 47.4% (9/19) of IDC. The frequency of MSI in IDC was significantly higher than that in DCIS (P < 0.001). Also, the MSI seemed to correlate with clinical stage (P = 0.0001) and tumor size (P = 0.004) but not histological grade or age. In addition, we found that 27% of the tumors showed LOH at 11q23.3-24 region between loci D11S934 and D11S912. Seven of nine MSI cases demonstrated low or no expression of p53. However, there was significantly reduced expression of PR, but not ER in MSI cases. CONCLUSIONS: Our results suggest that breast cancer acquires the RER phenotype (replication-error phenotype) in the relatively late stages, and that the RER phenotype is associated with aggressiveness of IDC (infiltrative duct carcinoma). The result also implicated that mismatch repair failure can alter the expression of PR but not ER and p53.

Adult↗

PubMed2000

CD34, CD117, and actin expression in phyllodes tumor of the breast.

BACKGROUND: This study investigated the immunophenotypic patterns of CD34, CD117 (a product of the c-kit proto-oncogene), and actin (HHF35) in benign and malignant phyllodes tumors (PTs). We correlated the expression of CD34, CD117, and actin with histopathological grade. MATERIALS AND RESULTS: We analyzed 19 cases (7 benign and 12 malignant cases) of PTs using immunohistochemical analysis. Six of 7 benign PT stromal lesions stained positively for CD34, while only 3 of 12 cases of malignant PT were focally CD34 positive (P = 0.0106). Only 1 of the 7 benign PTs stromal lesions expressed CD117. Nine of the malignant PTs were composed CD117-positive fibroblasts. This result demonstrated that CD117 expression is associated with the malignant potential of PTs (P = 0. 0106). Actin (HHF-35) expression was found in 8 of 12 cases of malignant PTs (P = 0.027), but in only 1 of 7 cases of benign PTs. Actin expression was significantly (P = 0.04) correlated to frequent mitotic activity (>5 mitoses per 10 high-power fields). The immunophenotypic markers were not related to tumor size. Additionally, we sequenced part of the juxtamembrane region of the c-kit proto-oncogene and found point mutations in two malignant PTs. CONCLUSION: Our results demonstrated that expression of CD34 was associated with benign PTs, while CD117 and actin were preferentially expressed in malignant PTs. Our results implied that these immunohistological markers might be used for the histopathological grading of PTs.

Actins↗

PubMed2000

Telomerase activity correlates with cell cycle regulators in human hepatocellular carcinoma.

AIMS/BACKGROUND: Mutation in cell cycle genes is the most common genetic change in malignant tumor cells. Telomerase activation, considered as essential in the immortality of cancer cells, is found in most cancers, where there may be an association with an active cell cycle. METHODS: In this study study we used the TRAP assay to determine telomerase activity in liver tumor specimens from 25 cases of hepatocellular carcinoma (HCCs) as well as in corresponding non-cancerous liver tissue in each patient. The expression of cyclin D1, cdk2, and cdk4 protein was also examined by Western blot. RESULTS: Twenty-one of the 25 cases of HCC were found to have increased telomerase activity, whereas only five out of the 25 non-cancerous liver samples were found to have weak telomerase activity. Telomerase activity was not found to be related to tumor size, HBsAg, HBeAg, anti-HCV, transaminase, or alpha-fetoprotein serum titer. Furthermore, three out of the 25 cases of HCC showed cyclin D1 overexpression, whereas 15 of the 23 cases of HCC showed decreased cyclin D1 expression. Down regulation of cyclin D1, cdk2, cdk4 protein correlated with telomerase activity (p<0.004, p<0.013, and p<0.001 respectively). CONCLUSION: The results indicate that genetic defects in HCC facilitate the reactivation of telomerase activity, a process which may be dependent on cyclin D1 with its cyclin dependent kinase (cdk) partner defect.

Adult↗

PubMed2000

Malignant meningioma with rhabdoid transformation.

We report a rare case of recurrent meningioma with malignant change and rhabdoid transformation in a 54-year-old woman who presented with severe headache and progressive weakness of the right extremities. The patient had a history of atypical meningioma and had undergone a craniotomy to remove a tumor nine years earlier. We discuss the distinctive morphologic, immunohistochemical staining and ultrastructural features of a recurrent malignant meningioma. A meningioma with rhabdoid transformation may indicate aggressive biologic and clinical behavior of the tumor.

Female↗

PubMed2000

Lack of association between angiotensin I-converting enzyme gene deletion polymorphism and cerebrovascular disease in Taiwanese.

BACKGROUND AND PURPOSE: Angiotensin I-converting enzyme (ACE) gene deletion polymorphism (D) has recently been suggested as a significant risk factor for cerebrovascular disease in studies involving Japanese and white populations. We investigated the role of ACE D polymorphism in the pathogenesis of cerebrovascular disease in Taiwanese. METHODS: To examine the association of ACE genotype and allele frequency with cerebrovascular disease, we conducted a study of 306 stroke patients and 300 control subjects matched by age and sex. RESULTS: Although the frequencies of both the homozygous deletion (DD) genotype and the D allele were greater in stroke patients than in control subjects, these differences were not significant. Further comparison of the frequencies of the DD genotype and the D allele in the three stroke subgroups (intracerebral hemorrhage, probable large-vessel disease, and probable small-vessel lacunar infarction) with the control group revealed no significant associations. Moreover, ACE gene polymorphism was not significantly associated with age of onset of stroke. Stepwise logistic regression analysis of the presence of the D allele and data on risk factors confirmed the lack of significant association between ACE deletion polymorphism and cerebrovascular disease. Moreover, no association was identified between ACE genotypes and any of the relative risk factors for cerebral infarction or severity of carotid atherosclerosis. CONCLUSIONS: Our results suggest that deletion polymorphism of the ACE gene is not associated with the pathogenesis of cerebrovascular disease in Taiwanese.

Alleles↗

PubMed1999

Adrenal insufficiency caused by primary aggressive non-Hodgkin's lymphoma of bilateral adrenal glands: report of a case and literature review.

A 64-year-old woman was hospitalized because of poor general condition, gastrointestinal upset, unexplained fever, electrolyte imbalances, and an incidental finding of bilateral huge adrenal masses on computerized tomography (CT) of the abdomen. Non-Hodgkin's lymphoma (NHL) of B-cell origin was proven by ultrasound-guided aspiration biopsy of the left adrenal gland. Meanwhile, primary adrenal insufficiency was confirmed by her low serum cortisol level, high ACTH level, and inadequate adrenal response to the rapid ACTH stimulation test. The diagnosis of primary adrenal NHL was supported by detailed physical examinations, bone marrow examination, and such imaging studies as CT scan and sonography. She received three courses of chemotherapy with cyclophosphamide, vincristine, and prednisolone and there was an initial transient response, but she died of sepsis and progression of NHL three and a half months later.

Adrenal Gland Neoplasms↗

PubMed1999

Expression of nuclear retinoid receptors in normal, premalignant and malignant gastric tissues determined by in situ hybridization.

Retinoids exhibit multiple functions through interaction with nuclear retinoid receptors and have growth-suppressive activity on gastric cancer cells. To better understand the roles of nuclear retinoid receptors during gastric carcinogenesis, we have used in situ hybridization to investigate expression of retinoic acid receptors (RARs) and retinoid x receptors (RXRs) in premalignant and malignant formalin-fixed paraffin-embedded gastric tissues. Histological sections of eight normal, 17 distal normal and nine gastric cancer tissues were hybridized with non-radioactive RNA probes for subtypes of RAR and RXR. Expression of RAR alpha, RAR beta, RAR gamma, RXR alpha and RXR beta was found in most cell types in gastric mucosa tissues from normal individuals as well as in distal normal tissues from cancer patients. Expression of RAR alpha and RAR beta were found in three and seven cancer tissues, respectively, and levels of RXR alpha mRNA were significantly decreased in poorly differentiated cancer tissues. Among the five investigated nuclear retinoid receptors, only expression of RAR alpha mRNA was significantly decreased in intestinal metaplasia, dysplasia and cancer tissues when compared to adjacent normal tissues. In conclusion, normal gastric mucosa expressed both RARs and RXRs, which supports the physiological role of retinoic acid on normal gastric mucosa. The decrease in RAR alpha expression in premalignant and malignant gastric tissues suggests a significant role of RAR alpha during gastric carcinogenesis.

Gastric Mucosa↗

PubMed1999

Molecular studies into the role of CD44 variants in metastasis in gastric cancer.

CD44, an integral membrane glycoprotein expressed by many cell types, serves as the principal transmembrane hyaluronate receptor and might be a determinant of metastatic and invasive behaviour in carcinomas. The generation of CD44 splice variants might be linked closely with gastric carcinoma tumorigenesis and differentiation. Some studies have reported that the magnitude of CD44 variant synthesis at the protein level correlates with lymph node metastasis. A number of studies have examined the possible mechanism of involvement of the CD44 variant in tumour metastasis. Most studies have reported that the regulation of CD44 binding to hyaluronate results from glycosylation of variably spliced exons. Direct hyaluronate binding studies of CD44 V4-V7 isoforms transfected into the human gastric carcinoma cell line, SC-M1, have indicated that the V4-V7 isoforms themselves, in addition to glycosylation, can alter hyaluronate binding.

DNA, Complementary↗

PubMed1999

Lack of association between deletion polymorphism of the ACE gene and ischemic vascular diseases in a Chinese population in Taiwan.

BACKGROUND: The association between deletion/insertion polymorphism of the angiotensin I-converting enzyme (ACE) gene and ischemic vascular diseases (IVDs) is still unclear. This study was designed to evaluate the role of ACE gene polymorphism in the pathogenesis of IVDs in a Chinese population living in Taiwan. METHODS: A case-control study was carried out to examine the association of the ACE gene genotype and the allele frequency in 400 IVD patients, including 214 patients with ischemic cerebrovascular disease (ICVD) and 186 patients with ischemic heart disease (IHD), compared with 200 control individuals. RESULTS: Although the patients with ICVD and IHD were found to have higher frequencies of the D/D genotype (22% and 43%) and the D allele (20% and 42%) than the controls (16% and 39%), the statistical differences were not significant, as shown by chi 2 analysis (p > 0.05). Upon further comparison of the frequencies of the D allele among the two sexes and different age subgroups, there was still no significant association. CONCLUSIONS: Deletion polymorphism of the ACE gene was not associated with IVD in a Chinese population in Taiwan. The unique or synergistic effect of other genes that might contribute to the pathogenesis of IVDs needs further investigation.

Aged↗

PubMed1998

The extent of proliferative and apoptotic activity in intraductal and invasive ductal breast carcinomas detected by Ki-67 labeling and terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling.

BACKGROUND: The balance among cell proliferation, cell differentiation, and cell death determines the cell number in a population as well as the size or even the stage of a tumor. Thus, to improve our understanding of the pathogenesis of neoplasms, it is important to investigate the regulation of both cell proliferation and cell death. METHODS: This study examined the occurrence of apoptosis and proliferative capacity in 46 breast carcinomas: 20 intraductal carcinomas (ductal carcinomas in situ [DCIS]) and 26 infiltrative ductal carcinomas (IDC). Terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling (TUNEL) and immunostaining with the Ki-67 antibody were used in the examination. A ladder of DNA fragments induced by apoptosis was demonstrated by means of DNA agarose gel electrophoresis in 10 of the available TUNEL positive and negative samples. RESULTS: The results were correlated with p53, bcl-2, estrogen receptor (ER), and progesterone receptor (PR) protein expression, which would suggest association with apoptosis by immunohistochemistry. The apoptosis and proliferation of each cancer were expressed as the number of tumor cells undergoing apoptosis and proliferation per 1000 tumor cells. The extent of apoptosis was more frequently observed in DCIS than in IDC (21.9+/-6.8 vs. 4.0+/-0.9, P < 0.001), and the proliferation activity was significantly higher in IDC than in DCIS (16.8+/-6.5 vs. 3.5+/-0.8, P < 0.006). Apoptosis associated with MIB-1 positive cells and TUNEL labeling was significantly higher in IDC than in DCIS (3.26 vs. 0.42, P=0.001). In DCIS, apoptosis was correlated with p53 (r=0.663, P=0.005), and p53 had a reverse correlation with bcl-2 (r=0.620, P= 0.018). Moreover, bcl-2 expression was associated with ER (P=0.028) and PR (P= 0.005) expression in both DCIS and IDC. CONCLUSIONS: The results of this study show that a higher degree of apoptosis and lower proliferation activity in intraductal carcinoma result in a steady-state, self-renewing condition in which net growth of the tumor is rare. The results also indicate that apoptosis was altered by the expression of p53, bcl-2, ER, and PR.

Apoptosis↗

PubMed1998

Hyaluronate binding assay study of transfected CD44 V4-V7 isoforms into the human gastric carcinoma cell line SC-M1.

The potential human metastasis molecule CD44 and its isoforms V5 and V6 are overexpressed in human gastric carcinoma. Among the numerous extracellular matrix components, hyaluronate, a CD44 ligand, is of increasing interest in relation to its role in cancer cell development and invasion. By using the dynabead separation method, the SC-M1 cell line was separated into V5 and V6 isoform-positive and -negative populations. The V5 and V6 isoform-negative populations exhibited significantly higher hyaluronate binding activity than the corresponding positive cells. The hyaluronate binding activity of V5 and V6-positive cells could be restored by pretreatment with anti-CD44 V5 and V6 monoclonal antibodies (MAbs). In addition, transfection of aVV5 and V6-negative cells decreased their hyaluronate binding activity to the levels of CD44 V5 and V6-positive cells. Cells transfected with V5 and V6 recovered their hyaluronate binding activity after pretreatment with MAbs against V5 and V6. These data suggest that cell adhesion involving hyaluronate can be regulated by multiple mechanisms, one of which involves alternative splicing of CD44 isoforms.

Adenocarcinoma↗

PubMed1998

Plasminogen activator inhibitor-1 and angiotensin I converting enzyme gene polymorphism in patients with hypertension.

Deletion polymorphism of angiotensin I-converting enzyme (ACE) gene has been reported to be an independent risk factor for myocardial infarction. Plasminogen activator inhibitor-1 (PAI-1) was proposed to be a link between the renin-angiotensin system and thrombotic risk. This study was undertaken to investigate the possible association between the insertion/deletion (I/D) polymorphism of the ACE gene and plasma PAI-1 levels in 160 patients with mild-to-moderate hypertension. The I/D genotypes were determined by polymerase chain reaction with oligonucleotide primers flanking the polymorphic region in intron 16 of the ACE gene. Baseline levels of PAI-1 antigen and activity and tissue plasminogen activator (t-PA) antigen were determined in fasting morning plasma samples. It was found that patients with homozygote deletion (DD, n = 37) ACE genotype did not have significantly higher plasma levels of PAI-1 antigen (31.2 +/- 15.6 ng/mL v 28.4 +/- 15.1 ng/mL or 27.2 +/- 13.2 ng/mL, P = .42), PAI-1 activity (16.2 +/- 10.6 IU/mL v 14.1 +/- 9.4 IU/ mL or 15.0 +/- 9.9 IU/mL, P = .60), or t-PA antigen (14.6 +/- 6.0 ng/mL v 13.4 +/- 4.9 ng/mL or 14.6 +/- 5.7 ng/mL, P = .40) as compared to those with heterozygote (DI, n = 67) or homozygote insertion (II, n = 56) genotypes. On multiple regression analysis, the ACE genotypes did not appear to be significant predictors for plasma PAI-1 levels and t-PA antigen after adjustment with age, sex, body mass index, plasma triglyceride, cholesterol, and glucose. In conclusion, the results indicated that the I/D polymorphism of the ACE gene was not related to plasma PAI-1 levels in a Chinese population with hypertension. The ACE genotypes may not have a role in influencing the fibrinolysis in hypertension.

Adult↗

PubMed1998

Apoptosis in nasopharyngeal carcinoma as related to histopathological characteristics and clinical stage.

AIMS: We investigated the significance of apoptosis, using the terminal deoxynucleotidyl transferase mediated dUTP-digoxigenin nick end-labelling method, in nasopharyngeal carcinoma biopsy samples. METHODS AND RESULTS: The apoptotic index (AI) in 50 nasopharyngeal carcinomas was compared with various histopathological features and clinical stage. Also, the AI was correlated with p53, bcl-2 and Ki67 expression by immunohistochemistry. In histopathological studies, the AI was significantly higher in mixed cellular type (MC) than in keratizing squamous cell type (KS) and spindle cell type (SC) (P < 0.001) which worsens prognosis. In tumour stage analyses, AI was higher in early stage (stage 2 and 3) than in high stage (stage 4). In addition, there was a significant correlation between the AI and p53 expression (P < 0.001) but not with proliferative activity (P = 0.15). In NPC containing p53 protein positive tumour cells, there was a significantly higher apoptotic rate. CONCLUSIONS: These findings indicate that apoptosis is related to type and stage of nasopharyngeal carcinoma. They also confirm the role of p53 in regulating tumour apoptosis.

Adult↗

PubMed1998

Diagnosis of cerebral toxoplasmosis by a nested polymerase chain reaction: a case report.

A 24-year-old man infected with human immunodeficiency virus type I rapidly progressed to acquired immune deficiency syndrome. His clinical picture was compatible with a presumptive diagnosis of cerebral toxoplasmosis. Application of a nested polymerase chain reaction (PCR) succeeded in detecting Toxoplasma gondii DNA in both the venous blood and cerebrospinal fluid specimens. This result indicates that PCR is a convenient tool for making a rapid and accurate diagnosis of cerebral toxoplasmosis, especially in developing countries.

Adult↗

PubMed1997

Angiotensin I converting enzyme gene polymorphism in Chinese patients with hypertension.

Reports from different ethnic populations failed to show consistent findings on the association of hypertension with insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene. In this population association study in Chinese, we compared the distribution of the ACE genotypes and allele frequency in 150 healthy controls with normal blood pressure and 148 hypertensive patients categorized by age. Although the frequencies of homozygote deletion (DD) genotype and deletion allele were greater in Chinese with hypertension than in normotensive controls (0.23 vs 0.13 and 0.44 v 0.37, respectively), the differences were not significant by chi2 analysis (P = .07 and .09, respectively). Furthermore, we did not find the trend of decreasing number of DD genotype in older hypertensive Chinese patients. The results indicated a much lower prevalence of ACE/DD genotype in Chinese than in Caucasians and a modest association between I/D polymorphism of the ACE gene and hypertension in Chinese.

Asian People↗