Biomedical subjects

Y Hiasa

Publications and source records attributed to Y Hiasa.

At least 55 records · Page 3Linked to original sources

PubMed1997

Risk factors and incidence of coronary artery lesions in patients with abdominal aortic aneurysms.

We determined the incidence of coronary lesions by coronary angiography and the associated risk factors in 102 patients with abdominal aortic aneurysms (AAA). Old myocardial infarction was observed in 33 patients and angina pectoris in 27 patients. Coronary angiography revealed significant stenosis (> or = 75%) in 66 patients, including single-vessel disease in 22 patients and multiple-vessel disease in 44 patients. Angiography detected 21 coronary artery ectasia lesions, consisting of 10 saccular and 11 fusiform aneurysms in 18 patients. Significant coronary stenosis was present in approximately two-thirds of patients with AAA, suggesting that coronary angiography is a useful preoperative examination in patients with AAA. The incidence of coronary ectasia was also high in patients with this disease, perhaps because AAA and coronary ectasia involve similar pathogenic processes. There was considerable overlap in risk factors in patients with AAA and patients with coronary artery disease without AAA. However, advanced age and hypertension were more strongly associated with AAA than with coronary artery disease.

Adult↗

PubMed1997

Different patterns of DNA alterations detected by restriction landmark genomic scanning in heterogeneous prostate carcinomas.

Alterations in the genomic DNAs of six heterogeneous prostate carcinomas, as well as that of individual and histologically distinct foci within the tumors, were examined using restriction landmark genomic scanning, a method employing two-dimensional gel analysis of a large number of DNA fragments generated by digestion with highly specific endonucleases. Upon autoradiographic imaging, these fragments appear as spots of varying intensity and location specific for each sample. In our study, comparison of cancer DNAs against normal prostate DNA controls yielded alterations in at least 35 spots. Despite differences in the histological grading of tumors, 3 spots common to all tumor samples showed consistent amplification of intensity and 8 other common spots demonstrated consistent reduction of intensity when compared with control. In addition, spot alterations occurred between histologically identical foci isolated from within single tumors. We suggest that these spot changes detected in DNA profiles generated by restriction landmark genomic scanning reflect aberrations in as yet unidentified oncogenes and tumor suppressor genes and indicate that prostate cancer is not only histologically heterogeneous and multifocal but also genetically multicentric.

Aged↗

PubMed1997

[Identification of predictive factors associated with recurrent restenosis after second percutaneous transluminal coronary angioplasty].

The predictive factors of a second restenosis after repeated percutaneous transluminal coronary angioplasty (PTCA) were investigated by review of the records of 100 consecutive patients who underwent second angioplasty for restenosis of the same site. PTCA was successful in 97 (97%) of these patients, but 38 patients (39%) developed a second restenosis (recurrent restenosis group) and 59 did not (no recurrent restenosis group). The clinical, angiographic and procedural factors at the second PTCA of the two groups of patients were compared. The major risk factors (hypertension, diabetes mellitus, hyperlipidemia) and type and morphology of the lesion (eccentricity, calcification, length, bend) at repeat PTCA did not differ significantly between the recurrent restenosis and no recurrent restenosis groups. The mean intervals from the initial to the second PTCA were significantly shorter in the recurrent stenosis group than in the no recurrent restenosis group (2.1 +/- 1.1 vs 3.4 +/- 1.3 months, p < 0.001). Sixteen (76%) of 21 patients had a second restenosis at an interval between the two PTCAs of < 3 months, compared with 22 (29%) of 76 patients with an interval of > or = 3 months (p < 0.001). Patients who undergo a second angioplasty procedure within 3 months from the previous procedure at the same site have a much higher risk of recurrent restenosis and these patients may benefit from an alternative therapeutic approach.

Aged↗

PubMed1997

Genetic variations in human benign prostatic hyperplasia detected by restriction landmark genomic scanning.

Alterations in the genomic DNAs of benign prostatic hyperplasias were examined using restriction landmark genomic scanning. This methodology allows the visual comparison of a large number of loci as spots within a gel that has been electrophoresed in 2 dimensions. Within each of the 16 hyperplasias examined, we found 2 to 10 spots with altered intensities, as compared to equivalent spots from normal prostate, but could detect few common spot profiles for any hyperplasia samples. These data conflict with data from previous studies and suggest that there may be no consistent genetic changes in the pathogenesis of some forms of human benign prostatic hyperplasia.

Aged↗

PubMed1997

[Influence of low high-density lipoprotein cholesterolemia induced by probucol on the progression of coronary atherosclerosis].

The influence of probucol-induced low high-density lipoprotein (HDL) cholesterolemia on the progression of coronary atherosclerosis was studied in 320 patients with angina pectoris or myocardial infarction, 32 patients with probucol 500 mg/day, 288 patients without probucol, who underwent follow-up angiography at intervals of at least 2 years. The 288 patients were divided into two groups depending on the serum HDL-cholesterol (HDL-C) level at the follow-up angiography: the low HDL-C group had a serum HDL-C level below 40 mg/dl (152 patients) and the control group had 40 mg/dl or above (136 patients). Coronary sclerosis index was defined as the total products of coronary scores (0-6) by segments according to the American Heart Association reporting system in the branches without angioplasty and was compared between the three groups. In the probucol group, serum HDL-C level was significantly reduced from 43.9 +/- 10.6 (at baseline) to 31.1 +/- 7.6 mg/dl (at follow-up, p < 0.01) and was lower than that in the other two groups (low HDL-C group 33.1 +/- 5.0 mg/dl, p < 0.07; control group 52.6 +/- 9.8 mg/dl, p < 0.01). Coronary sclerosis index was most increased in the low HDL-C group (8.3 +/- 5.4-->11.9 +/- 6.1, p < 0.01), whereas there was no significant change in the probucol group (7.2 +/- 5.9-->9.1 +/- 6.8, p = 0.24). Our results showed that treatment with probucol inhibits the progression of coronary atherosclerosis despite the decrease in HDL-C level. One possible reason may be remarkable improvement in the other lipid factors, especially the low-density lipoprotein cholesterol level (165.7 +/- 33.9-->123.7 +/- 29.0 mg/dl, p < 0.01).

Aged↗

PubMed1996

Alterations of retinoblastoma, p53, p16(CDKN2), and p15 genes in human astrocytomas.

BACKGROUND: Alterations of the suppressor genes, such as the retinoblastoma (RB), p53, p16(CDKN2), and p15 genes, have been reported in human gliomas. These genes have been suggested as the cell cycle regulatory genes at the G1-S checkpoint. METHODS: Alterations of the RB, p53, p16(CDKN2), and p15 genes in human astrocytomas were screened by single strand conformation polymorphism analysis of polymerase chain reaction products (PCR-SSCP analysis) and then confirmed by dideoxy sequencing. In addition, the expression of RB and p16 protein was examined by Western blot analysis. RESULTS: Aberrations of the RB gene were found in 3 of 23 surgical astrocytoma specimens (13%). Mutations were found at codon 754 in exon 22 (Val-->Gly), codon 519 in exon 17 (Thr-->Pro), and one base deletion at codon 903 resulting in stop codon at codon 905 in exon 26. These mutational locations were all near the regions associated with the functional domains of the RB gene. Aberrations of the p53 gene were found in 4 cases (17.4%). These mutations were found at codons 146 (Trp-->Gly) and 165 (Gln-->His) in exon 5, codon 73 (Val-->Glu) in exon 4, and codon 313 (Ser-->Asn) in exon 9. In addition, alterations of the p16(CDKN2) gene were found, with 5 cases (21.7%) having homozygous deletions, and 2 cases (8.7%) harboring point mutations. No p15 gene alteration was detected. The expression of p16 protein was undetectable in 10 cases (43.5%) by Western blot analysis, demonstrating an inverse correlation with the expression of RB protein. CONCLUSIONS: A few cases had overlapping alterations, and the incidence of one or more RB, p53, or p16(CDKN2) changes appeared to be relatively high in human astrocytomas. These results suggest that cell cycle regulatory gene alterations may play an important role in the development of gliomas.

Astrocytoma↗

PubMed1996

Establishment of a rat thyroid carcinoma cell line in vitro demonstrating high DNA synthesis in response to insulin-like growth factor I.

We previously established transplantable rat thyroid carcinoma cell lines in vivo from primary thyroid tumors induced by N-bis-(2-hydroxypropyl)nitrosamine (DHPN). In the present study, an insulin-like growth factor I (IGF-I)-responsive cell line (TRTC-G1-C-A4) in culture was derived from one (well differentiated papillary type) of these carcinoma cell lines G1. TRTC-G1-C-A4 cells were found to exhibit specific saturable binding of IGF-I with a Kd of 1.16 nM at approximately 43.6 fmol/10(5) cells. Inclusion of IGF-I (10 and 50 ng/ml) in the culture medium resulted in a significant increase of [3H]thymidine incorporation and marked cell proliferation. IGF-II (10 ng/ml) and insulin (1 microgram) produced no such effects. The molecular weight of IGF-I receptors on the cell membrane was determined by Western blotting analysis, a single band of binding proteins with a molecular weight of 125 kDa being evident under non-reducing conditions. Reverse transcriptase polymerase chain reaction (RT-PCR) showed that the TRTC-G1-C-A4 cells contained IGF-I receptor mRNA with a sequence corresponding to that determined from rat uterus. These results demonstrate that the IGF-I receptor can be expressed in a thyroid carcinoma with an important contribution to cell growth.

Animals↗

PubMed1996

Lack of p16/CDKN2 alterations in thyroid carcinomas.

Exons 1-3 of the p16/CDKN2 gene and exons 4-9 of the p53 gene were screened for mutations by single-strand conformation polymorphism (SSCP) analysis and direct sequencing of PCR-amplified DNA from human primary thyroid carcinomas and thyroid carcinoma cell lines. The samples included 21 papillary carcinomas, 2 undifferentiated carcinomas, 1 follicular carcinoma, 1 medullary carcinoma and 2 cell lines originating from thyroid undifferentiated carcinomas. No homozygous deletions and mutations in the p16/CDKN2 were observed in any of the primary tumors or cell lined. In contrast, one of the two undifferentiated carcinomas an both cell lines demonstrated point mutations in the p53 gene. These results that p16/CDKN2 gene alteration is not required for malignant transformation in the thyroid, while p53 gene mutations may play a role in the progression from differentiated to undifferentiated carcinoma.

Adenocarcinoma, Follicular↗

PubMed1996

G --> A mutation of ras genes and infrequent p53 gene mutation in rat transplantable thyroid carcinoma lines from tumors induced in vivo by N-bis(2-hydroxypropyl)nitrosamine.

In a comparative study, we have investigated mutational activation of three kinds of ras genes and the p53 gene (exons 5-8) in 19 rat transplantable thyroid carcinoma lines derived from in vivo tumors induced by DHPN. Mutations were identified using single-strand conformation polymorphism and DNA sequencing analysis, and activated ras oncogenes were detected in 6 lines (31%). These all had mutations in Ki-ras codons at 12 or 63, and one of them also possessed a Ha-ras mutation at codon 12 as a double mutation. Three mutations of Ki-ras at codon 12 involved the second nucleotide and two the first position, the other being found at the first nucleotide in codon 63. Base alterations of p53 gene were found in two lines. One had an insertion of 1 base (thymine) between codon 206 and codon 207. Historically, it was diagnosed as a poorly differentiated papillary carcinoma (scirrhous pattern). In the another case, there was no amino acid change although one base substitution occurred at codon 283 (GAG --> GAA) of exon 8. These results indicate that, in the ras family, DHPN induces Ki-ras gene activation preferentially and that p53 mutation may be infrequent in thyroid carcinogenesis in rats, our data thus corresponding well with the previous reports that an inactivated p53 gene only plays a major role in human undifferentiated thyroid carcinomas.

Adenine↗

PubMed1996

Alterations of p16/CDKN2, p53 and ras genes in oral squamous cell carcinomas and premalignant lesions.

Exons 1-3 of the p16/CDKN2 gene, exons 4-9 of the p53 gene and exons 1 and 2 of H-, K- and N-ras genes were screened for mutations by a combination of immunohistochemistry and single-strand conformational polymorphism (SSCP) analyses of polymerase chain reaction products from human surgical samples of both frank oral squamous cell carcinomas and premalignant lesions. The samples included 20 squamous cell carcinomas, 10 epithelial dysplasias and 10 epithelial hyperplasias. No identifiable gene mutations were detected in any of the dysplasias or hyperplasias, while 2 (10%) deletions and 2 (10%) mutations of p16/CDKN2, along with 5 (25%) p53 mutations were found in the advanced carcinomas, yielding characteristic p16/ CDKN2 and p53 changes. A mutation in the K-ras gene was found in single carcinoma and dysplastic samples. From the data, it can be argued that p16/CDKN2 and p53 mutations are relatively late occurrences in human oral tumorigenesis and that genetic alterations of the ras genes may not play a significant role in squamous neoplasia.

Carcinoma, Squamous Cell↗

PubMed1996

Association between Helicobacter pylori infection and serum pepsinogen concentrations in gastroduodenal disease.

AIM: To investigate the association between Helicobacter pylori infection and serum pepsinogen (PG) 1 and 2 concentrations in various gastroduodenal diseases. METHODS: Serum PG1 and 2 concentrations and antibodies to H pylori were measured by enzyme linked immunosorbent assay (ELISA); gastric mucosal pH was assessed and urease activity in biopsy tissue was determined. A comparison of the ELISA and urease test results permitted division of the cases into positive, false positive, false negative and negative categories for control, gastritis, and ulcer groups. RESULTS: The gastric mucosal pH and serum PG2 in cases positive for H pylori were significantly increased in ulcer and gastritis cases compared with H pylori negative cases. Similar tendencies were observed for the false positive and false negative categories. CONCLUSIONS: A positive ELISA reaction for antibodies and an increased serum PG2 concentration are reliable indicators of H pylori infection.

Adult↗

PubMed1996

Tumor cell proliferation and apoptosis associated with the Gamma Knife effect.

In this study, the expression of proliferating-cell nuclear antigen (PCNA) and Bcl-2 protein was examined in neurinomas, meningiomas, pituitary adenomas, and malignant lymphomas before treatment with Gamma Knife radiosurgery. Tumor volume was rapidly reduced by radiosurgery in all malignant lymphomas and in some benign tumors. The latter had been characterized by strong positive immunohistochemical staining for PCNA and Bcl-2. Radiation-induced apoptosis is thought to contribute to the low-dose effects of Gamma Knife radiosurgery. A population with a large proportion of proliferating cells may be susceptible to the induction of apoptosis, and the presence of Bcl-2 may not suppress this Gamma Knife effect.

Apoptosis↗

PubMed1996

[The importance of serum lipid level for restenosis following initial successful percutaneous transluminal coronary angioplasty in patients with unstable angina].

Serum lipids were investigated as a risk factor for restenosis following initial percutaneous transluminal coronary angioplasty (PTCA) for unstable angina (Braunwald III-B2). Follow-up angiography was used to classify 41 patients who received successful emergency PTCA into two groups: 21 patients with and 20 without restenosis. The clinical factors (age, sex), lesion characteristics and extent of coronary narrowing before and after PTCA were similar in the two groups. In the group without restenosis, the serum cholesterol level was significantly reduced from 225 +/- 48 (before PTCA) to 188 +/- 34 mg/dl (at the follow-up PTCA; p < 0.01), but in the group with restenosis serum cholesterol level showed no difference between before PTCA (211 +/- 42) and at the follow-up (201 +/- 32 mg/dl). The levels of triglycerides and high-density lipoprotein (HDL) cholesterol were not significantly different between before PTCA and at the follow-up in both groups. The restenosis rate in patients with serum cholesterol level reduced by 30 mg/dl or more at the follow-up after PTCA was significantly lower (three of 15 patients, 20%) compared with the restenosis rate in patients with serum cholesterol level lowered by less than 30 mg/dl (18 of 26 patients, 69%; p < 0.01). Moreover, the restenosis rate in patients with serum cholesterol level below 180 mg/dl at the follow-up angiography was significantly lower (six of 19 patients, 32%) compared with patients with serum cholesterol levels above 180 mg/dl (15 of 22 patients, 68%; p < 0.05). A high level of serum cholesterol may be a predictor of restenosis following PTCA in patients with unstable angina.

Angina, Unstable↗

PubMed1996

Genomic alterations in human prostate carcinoma cell lines by two-dimensional gel analysis.

To explore the molecular abnormalities in human prostate carcinoma, the genomic DNAs extracted from 3 prostate cell lines--LNCaP, PC-3 and DU-145--were examined using restriction landmark genomic scanning (RLGS) methodology, a 2-dimensional gel analysis which allows evaluation of approximately 2,000 Not I landmarks. We detected 24, 18 and 23 amplified spots in LNCaP, PC-3 and DU-145, respectively. Eleven spots were commonly intensified in all 3 cell lines, with a range of amplification of 2.1 to 134.1-fold over normal. An additional 4 spots were detected in both LNCaP and Pc-3 at similar amplification intensities, but were not observed in DNA from DU-145. Ten amplified spots were located on several chromosomes, while other five spots seemed to result from the hypomethylation. These results suggest that common genetic abnormalities may occur in carcinomas of the human prostate.

Carcinoma↗

PubMed1995

Frequent mutations of Ki-ras codon 12 in N-bis (2-hydroxypropyl)-nitrosamine-initiated thyroid, kidney and lung tumors in Wistar rats.

N-Bis (2-hydroxypropyl) nitrosamine (DHPN) is a very potent mutagen and wide spectrum carcinogen in rodents. In the present study, we investigated mutational activation of the Ki-ras gene in eight thyroid, five kidney (four mesenchymal and one transitional cell lesion) and two lung tumors induced with DHPN. Mutations were identified using single-strand conformation polymorphism, restriction fragment length polymorphism and DNA sequencing analysis. All of the 15 neoplasms could be shown to have mutations in codon 12 (GGT-->GAT). These results suggest that Ki-ras mutations are frequent events during the development of DHPN-induced carcinomas in these organs. In a separate experiment, moreover, we analyzed the presence of Ki-ras mutations in various tissues 8 weeks after DHPN treatment. One of five thyroid tissues treated with DHPN was found to have the same characteristic mutation, suggesting that it may represent an early event during carcinogen-induced tumor formation in the thyroid.

Animals↗

PubMed1995

p53 mutations occur in clinical, but not latent, human prostate carcinoma.

To elucidate the role of the p53 tumor suppressor gene in prostate tumorigenesis, we probed for mutations in latent and clinical prostate cancers using single strand conformation polymorphism (SSCP) and restriction fragment length polymorphism (RFLP) analysis in combination with direct gene sequencing and immunohistochemical methodologies. Fifteen cases of subclinical and 32 cases of clinical carcinoma, the latter graded in stages A through D, were available for study. While p53 point mutations were detected in only 5 of 32 (16%) clinical cancers, no mutations were detected in latent disease. Of the carcinomas in stages B, C and D, 15% (2/13), 29% (2/7) and 9% (1/11) were positive for p53 mutations, respectively. Although no specific mutational patterns were observed, the aberrations found were predominantly single base missense substitutions. The data suggest not only an association of p53 mutation and progression of clinical prostate cancer, but also imply that some other mechanism(s) are at work in latent carcinoma.

Base Sequence↗

PubMed1995

Tissue and serum pepsinogen I and II in gastric cancer identified using immunohistochemistry and rapid ELISA.

AIMS: To investigate the immunohistochemical expression and the serum concentrations of pepsinogen I and II in different histological types of gastric cancer as compared with other gastric disorders. METHODS: Formalin fixed, paraffin wax embedded tissue specimens of 38 gastric cancers obtained from surgical cases were used for the immunohistochemical studies performed with the avidin-biotin complex method using monoclonal antibodies against purified pepsinogen I and II. Pepsinogen concentrations from serum obtained from the above patients, from patients with various other gastric disorders, and from normal controls were measured with a rapid non-radioactive one step enzyme linked immunosorbent assay (ELISA). RESULTS: Eight of 38 (21%) and seven of 38 (18%) gastric carcinomas showed immunoreactivity to pepsinogen I and pepsinogen II, respectively, without any correlation to histological classification or differentiation. Decreased pepsinogen I concentrations and low pepsinogen I:II ratios were found specifically in cases of gastric carcinoma and polyp, in good accordance with the immunohistochemical results. CONCLUSIONS: Low serum pepsinogen I concentrations and a low pepsinogen I:II ratio are predictive of gastric neoplasia, correlating with low tissue immunoreactivity to monoclonal antibodies raised against pepsinogen I and II. For mass screening of gastric disease including carcinoma, ELISA using a one step immunoassay performed in the present study is a rapid and reliable non-radioactive method of detecting serum pepsinogen. In addition, immunohistochemical studies showed that pepsinogen production may be increased or diminished as a result of tumour histogenesis, depending on the area of origin and the processes of cell transformation and dedifferentiation.

Biomarkers, Tumor↗

PubMed1995

Progression of coronary artery disease in patients receiving percutaneous transluminal coronary angioplasty: angiographic comparison of angioplasty and non-angioplasty sites.

Long-term follow-up of coronary artery stenosis was carried out in 81 patients undergoing successful percutaneous transluminal coronary angioplasty (PTCA). Progression of coronary stenosis was observed in 38 patients with 52 sites, and regression was seen in 23 patients with 23 sites during 2 years or more of follow-up. Progressive change occurred in three sites of 97 PTCA lesions and 49 of 1,090 non-PTCA lesions (no significant difference). On the other hand, regressive change was observed in 19 sites of PTCA lesions and four of non-PTCA lesions (p < 0.05). The percentage of narrowing in PTCA lesions was 28.0 +/- 14.4% at 3-6 months after PTCA, and this improved to 22.8 +/- 15.8% at late study angiography. Coronary score changes were -0.16 +/- 0.54 in PTCA lesions, and 0.08 +/- 0.46 in non-PTCA lesions (p < 0.01). We concluded that the progression of obstructive coronary artery disease in sites with previous PTCA is less than in those with non-PTCA.

Aged↗