Biomedical subjects

Y Hiasa

Publications and source records attributed to Y Hiasa.

At least 19 recordsLinked to original sources

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↗

PubMed1995

[Initial and short-term results of percutaneous transluminal coronary angioplasty in patients over 70 years old: recent improvements in effectiveness].

Elderly patients have a higher incidence of procedure-related complications and recurrent angina after percutaneous transluminal coronary angioplasty (PTCA). However, early success rates seem to have improved. To determine whether outcome of PTCA in the elderly has changed recently, we compared initial results and short-term outcome in patients over 70 years old in two groups; 64 patients with 70 PTCA lesions who underwent first elective PTCA in 1982-1989 (early group) and 140 patients with 153 PTCA lesions in 1990-1993 (late group). The mean age of the late group was significantly older than that of the early group (74 +/- 3 vs 73 +/- 2 years, p < 0.01). The two groups had similar clinical characteristics including sex, prior myocardial infarction and multivessel disease. The overall success rate of PTCA was significantly higher in the late group than in the early group (92.8% vs 82.8%, p < 0.05). The rate of abrupt closure was similar in the two groups (2.9% vs 2.6%). Major complications (procedural myocardial infarction, emergency bypass surgery, hospital death) occurred in 4.7% of the early group and in 3.6% of the late group. Angiographic restenosis occurred in 41.5% of the early group and in 33.6% of the late group. Cardiac events (cardiac death and/or myocardial infarction) occurred in 6.6% of the early group and in 1.5% of the late group (p = 0.06). The initial success rate of PTCA has improved in the elderly as well as younger patients (< 70; 92.8% vs 91.6%). We conclude that PTCA can be performed with high initial success and satisfactory short-term outcome in patients over 70 years old.

Aged↗

PubMed1995

Intratumor cellular heterogeneity and alterations in ras oncogene and p53 tumor suppressor gene in human prostate carcinoma.

To assess the potential role of ras oncogene activation and p53 tumor suppressor gene mutations in the development of human prostate carcinoma, nine cases of histologically heterogeneous prostate tumors obtained from total prostatectomies were probed for these specific events. Each tumor was divided into 5 to 10 areas according to different growth or histological patterns. Targeted DNA sequences coding for ras and p53 were amplified by the polymerase chain reaction, analyzed by single-strand conformational polymorphisms, and confirmed by direct DNA sequencing. Point mutations of the ras gene were found in three of the nine tumors. Two contained K-ras codon 13 and H-ras codon 61 mutations, found in only one and three areas of each lesion, respectively. The third tumor contained two different point mutations in K-ras codons 13 and 61 in different foci of the sample. Loss of heterozygosity at the polymorphic codon 72 in the p53 gene was detected in two of four informative cases (50%) showing fragment cleavage by restriction fragment length polymorphism analysis. Mutations in p53, missense transversions, single base insertions, and two base deletions were also detected in three tumors. The present results reveal mutated ras and p53 occasionally occurring in small foci of the tumor and that genetic mutations in p53, as opposed to those in ras, are more closely associated with invasive growth of heterogeneous prostate carcinoma.

Carcinoma↗

PubMed1995

[Efficacy and safety of percutaneous transluminal coronary angioplasty of other coronary arteries in patients with chronic total occlusion of the left anterior descending artery].

The acute and long-term outcomes of percutaneous transluminal coronary angioplasty (PTCA) of the right coronary artery (RCA) or left circumflex branch (LCS) in patients with chronic occlusion of the left anterior descending branch (LAD) (group A) were compared with those of sex and age matched patients undergoing PTCA of the RCA or LCX with a normal LAD (group B). Before the procedure, group A had more frequent prior myocardial infarction (96% vs 33%, p < 0.001), and a lower left ventricular ejection fraction (LVEF) (49 +/- 14% vs 71 +/- 13%, p < 0.001). The acute results were similar in the two groups with respect to primary success (group A 90%, group B 91%) and major complications (group A 6%, group B 2%). At 3 months, the rate of restenosis was 33% in group A and 27% in group B. In group A, LVEF increased significantly in patients without restenosis (53 +/- 11% vs 62 +/- 11%, p < 0.01). At long-term follow-up, group A had higher rates of persistent angina but there was no difference in outcome between the two groups. In patients with chronic total occlusion of LAD, PTCA for RCA or LCX can be performed with a low complication rate and provides a significant improvement in LVEF at 3 months in the absence of restenosis. However, at short-term follow-up, these patients have a greater incidence of persistent angina.

Adult↗

PubMed1995

[Newly developed detection system for serum Helicobacter pylori antibodies using ELISA and its clinical significance].

Using ELISA, a specific and sensitive system that detects serum immunoglobulin G antibodies against all soluble antigens of Helicobacter pylori (Hp) has been developed. This system is used at three different concentrations of Hp antigens coated on the solid phase of the ELISA. Anti-Hp antibodies were judged positive when the difference in the ELISA values between high and middle or middle and low concentrations of antigen were over the specific values. For the ELISA system, called the three point antigen method, sensitivity and specificity of urease activity were 86.9% and 70.8%, respectively. Positive rate for antibodies to serum Helicobacter pylori in dyspeptic patients was higher than that in healthy subjects.

Antibodies, Bacterial↗

PubMed1995

[Immunohistochemical study of the endomyocardial biopsy of systemic lupus erythematosus].

The mechanisms of cardiac involvement in systemic lupus erythematosus (SLE) were studied using immunohistochemical staining of endomyocardial biopsy specimens from 14 patients with SLE and normal coronary arteriograms. All 14 specimens showed mild interstitial edema, 11 showed mild cardiac fibrosis, and another two cases showed moderate cardiac fibrosis with myocardial derangements. Four specimens showed moderate cell infiltration in the interstitium. Area of fibrosis, diameter of myocardium and area of interstitial edema were increased in the SLE patients compared to the control cases. Immunofluorescence showed IgG and fibrinogen deposition in the membrane of cardiac myocytes and in the interstitium. Immunohistochemistry found no B lymphocytes in any of the seven SLE cases. T lymphocytes were observed in all seven SLE cases, and OKT 8 lymphocytes were increased significantly in the interstitial tissue as compared with OKT 4 lymphocytes. At endomyocardial biopsy, all 14 patients were receiving corticosteroid therapy and had low activity disease. The results suggest that cardiac tissue damage was associated with immunological abnormalities and might progress silently under conditions in which the disease activity was suppressed by corticosteroid therapy.

Adult↗

PubMed1994

Expression of the estrogen receptor in human thyroid neoplasms.

The expression and quantitation of the estrogen receptor (ER) in human thyroid tumors were examined by biochemical, immunohistochemical, and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. For this study, neoplasms, adenomatous goiters and adjacent normal thyroid tissues were obtained from 35 patients which included 10 cases of papillary carcinomas, 17 cases of adenomas and 8 cases of adenomatous goiters. Regardless of the histopathological subtype, ER was detected in 19% (5/27) of the neoplastic tissues with the mean value of ER content of 5.0 +/- 1.3 fmol/mg protein and the mean Kd value of 0.38 +/- 0.28 nM. ER was also detected, but at a lower concentration (2.8 +/- 1.6 fmol/mg protein), in the surrounding normal tissues. There was no significant difference between the neoplasms and adenomatous goiters with respect to the incidence of ER positivity and ER content. Furthermore, ER-positive specimens, as determined by both biochemical and immunohistochemical techniques, also showed the expression of ER mRNA detected by RT-PCR method. These results demonstrate that both ER mRNA as well as ER protein are expressed in thyroid neoplasms. This suggests the possibility that estrogen may affect the tumorigenesis or the progression of some thyroid neoplasms.

Adenoma↗

PubMed1994

Restenosis after successful emergency coronary angioplasty for acute myocardial infarction: comparison with elective angioplasty.

We investigated the initial and late restenosis rate after successful emergency coronary angioplasty in 64 patients with acute myocardial infarction, and compared these results with those of 100 patients (110 lesions) who had successful angioplasty on an elective basis. The majority of the baseline clinical and angiographic variables were similar in the myocardial infarction and elective groups. The restenosis rate at 1 month was high in patients undergoing emergency angioplasty for acute myocardial infarction (23 vs. 12%). At 3-6 months, the angiographic restenosis rate was low for the infarction group (26 vs. 37%). The overall restenosis rate was similar in the infarction and elective groups (39 vs. 40%). Lesion regression after coronary angioplasty was more frequent in the infarction than in the elective angioplasty group (27 vs. 14%, P < 0.05). These findings suggest that considering the high restenosis rate at 1 month and the lower, but still 20% or more, rate at 3-6 months, a follow-up angiography should be performed both prior to discharge and at 3-6 months after the procedure, in patients with acute myocardial infarction.

Aged↗

PubMed1994

Primary plasmacytoma of the thyroid: a case report and comparative literature study between Western nations and Japan.

A 52 year old man presented with primary thyroid plasmacytoma. The patient was initially followed up for thyroid dysfunction. The histological examination of the removed thyroid revealed a proliferation of mature and immature plasma cells indicative of plasmacytoma with Hashimoto's disease. After radiotherapy (40 Gy) to the neck following right hemi-thyroidectomy, the patient is currently alive and well 3 years after diagnosis without any evidence of tumor. The immunohistological examination of the removed thyroid showed monoclonality for immunoglobulin G-Kappa light chains. Sixty-six literature cases of primary thyroid plasmacytoma were reviewed and comparison of the clinical and histological characteristics between Japanese and Western cases noted. The incidence of the patients with antithyroid antibody was significantly lower (P < 0.01) in Western patients (42.9%) than in Japanese patients (87.5%). The higher incidence of thyroid dysfunction and Hashimoto's disease in Japan in comparison with Western nations was well reflected in the incidence of antithyroid antibody.

Autoantibodies↗

PubMed1994

Progressive activity in latent prostate carcinoma defined by argyrophilic staining of the nucleolar organizer regions (AgNOR).

Argyrophilic staining of the nucleolar organizer regions (AgNOR) was studied in 30 cases of benign prostatic hyperplasias (BPH), 17 cases of latent prostate carcinomas, 50 cases of clinical carcinomas and seven cases of metastatic lesions from prostate carcinomas. The criteria for these comparisons were the number of positive-staining dots per nucleus, the area of the dots, and a relative score determined by multiplying the number of positive-staining dots in the nuclei by the areas of the dots. Overall, there were no significant differences in these three parameters between BPH and latent carcinomas. Among latent carcinomas, however, significantly higher AgNOR scores were observed for infiltrative lesions than for non-infiltrative lesions. AgNOR dot number, area and score increased as tumors became less differentiated, with no significant differences detected in metastatic versus non-metastatic carcinomas. These results suggest that some latent tumors are similar in biological behavior, such as cell proliferation, to clinical carcinoma.

Carcinoma↗

PubMed1993

Expression of nm23-H1 and nm23-H2 proteins in prostate carcinoma.

The nm23 gene products/nucleoside diphosphate (NDP) kinase expression in prostate carcinomas and benign hyperplasias was evaluated immunohistochemically. Monoclonal antibodies against nm23-H1 and nm23-H2 proteins were prepared using the corresponding proteins fused with glutathione S-transferase as immunogens. Of the 80 cases of nonmetastatic prostate carcinoma examined, 74% (59/80) and 60% (48/80) were immunoreactive for nm23-H1 or nm23-H2 protein, respectively. Negative staining for nm23-H1 occurred in 83% of metastatic lesions, while 34% were negative for nm23-H2. All primary tumors corresponding to the metastases examined showed positive immunostaining for nm23-H1, indicating an inverse relationship between expression of this protein and metastatic status. nm23-H2 protein was detected in 83% of primary tumors and its expression appeared to be significantly correlated to the degree of histological differentiation. In contrast, all cases of benign prostatic hyperplasia showed elevated levels of both nm23-H1 and nm23-H2 expression. These data suggest that the nm23/NDP kinase may play a role in suppressing the expression of malignant potential in prostate carcinomas.

Adenocarcinoma↗

PubMed1993

Inhibitory effect of potassium citrate on rat renal tumors induced by N-ethyl-N-hydroxyethylnitrosamine followed by potassium dibasic phosphate.

Potassium dibasic phosphate (PDP) was administered at a concentration of 10% by weight in basal diet to unilaterally nephrectomized Wistar rats previously given 1000 ppm N-ethyl-N-hydroxyethyl-nitrosamine (EHEN) in the diet for 2 weeks. To study the effect of alkalinization on renal mineralization, some animals concomitantly received 5% potassium citrate (PC). Feeding PDP alone promoted adenomatous hyperplasias, which were regarded as preneoplastic lesions, as well as renal cell tumors in EHEN-initiated rats, whereas the addition of PC to PDP diets reduced the promoting effect. Histopathology, serum biochemistry and urinalysis indicated retardation of renal calcium crystallization by PC. Two other phosphate salts, sodium phosphate (SP) and calcium phosphate (CP), were also administered. SP showed a slight promoting effect on adenomatous hyperplasias and a 2-fold increase in the yield of renal cell tumors, while CP induced a clear reduction of both lesions, over EHEN alone. The promoting effects of both PDP and SP and the inhibitory effect of PC were somewhat correlated to 5-bromo-2'-deoxyuridine labeling indices, the degree of nephropathy, and mineralization in the kidney. Immunohistochemically, the nephropathy induced by phosphate salts was not linked to alpha 2u-globulin. A pathogenesis for renal carcinogenesis is suggested in which nephropathy associated with mineralization enhances the development of renal cell tumors.

Alpha-Globulins↗

PubMed1992

Carcinogenicity study in rats of phytic acid 'Daiichi', a natural food additive.

The carcinogenicity of phytic acid 'Daiichi' (PA), a natural food additive, was examined in Fischer 344 rats of both sexes. PA was added to the drinking-water of groups of 60 male and 60 female rats at levels of 1.25 or 2.5% for 100-108 wk. There was a dose-dependent reduction in the mean final body weights of rats treated with PA. Necrosis and calcification of the renal papillae were observed in PA-treated rats, but not in the controls. The incidences of necrosis (calcification) were as follows: one (three) out of 57 males given 2.5% PA; one (none) out of 59 males given 1.25% PA; 10 (17) out of 55 females given 2.5% PA; six (six) out of 58 females given 1.25% PA. Renal papillomas occurred in three of the high-dose male rats, four of the high-dose female rats, and three of the low-dose female rats. The development of papillomas seemed to be related to calcification and necrosis of the renal papillae induced by PA. While many other tumours developed in all groups, including the controls, the organ distribution of these neoplasms and their histological characteristics did not differ significantly from those known to occur spontaneously in this strain of rats.

Animals↗

PubMed1992

Promoting effects of potassium dibasic phosphate on early-stage renal carcinogenesis in unilaterally nephrectomized rats treated with N-ethyl-N-hydroxyethylnitrosamine.

The effects of potassium dibasic phosphate (PDP), potassium aluminum sulfate (PAS) and copper sulfate (CS) on early-stage renal carcinogenesis were investigated in unilaterally nephrectomized male Wistar rats after N-ethyl-N-hydroxyethylnitrosamine (EHEN) administration. After feeding 1,000 ppm EHEN, or basal diet for 2 weeks and removal of the left kidney at week 3, male Wistar rats were divided into 8 groups of 20 rats each. These groups received the following dietary treatments: 50,000 ppm PDP, 50,000 ppm PAS, 5,000 ppm CS or basal diet, respectively, for 18 weeks from weeks 3 to 20. The average numbers of adenomatous hyperplasias counted as preneoplastic lesions in the EHEN with 50,000 ppm PDP group were significantly higher than in the EHEN alone group or the EHEN followed by 50,000 ppm PAS or 5,000 ppm CS group. The treatment with 50,000 ppm PDP induced renal calcification and promoted the development of preneoplastic lesions in unilaterally nephrectomized rats treated with EHEN, but that with 50,000 ppm PAS or 5,000 ppm CS did not.

Animals↗

PubMed1992

Immunohistochemical study of a newly defined oncofetal antigen (HGR-Ag) in tumors of the central nervous system.

The oncofetal antigen (HGR-Ag) in brain tumors was newly defined using the monoclonal antibody derived from tissue extracts of an anaplastic astrocytoma. The HGR-Ag was purified through sequential chromatography using diethylaminoethyl-Sephadex A-50 and Con-A Sepharose affinity columns. The latter method indicated that HGR-Ag is not a glycoprotein, and Western blot analysis indicated a molecular weight of 80-90 kd. Purified antigen was used to produce antibody. This new antibody, designated H1H2, was shown to be an immunoglobulin G1 by immunodiffusion assay. Histological/immunohistochemical studies using the H1H2 antibody on paraffin and frozen tissue sections showed HGR-Ag to be intracellular rather than membrane-associated. The immunoreactivity of H1H2 was highest in malignant astrocytomas, glioblastomas, and normal fetal brain tissue. Neurinomas and certain carcinomas of other organs showed lesser, variable reactivity to H1H2. The strength of the antigen-antibody binding was correlated with the degree of malignancy in human gliomas. H1H2 bound to fetal brain tissue and undifferentiated neural tumors, but not to normal adult brain tissue, so HGR-Ag is probably a fetal oncoantigen.

Animals↗