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Biomedical subjects

T Shiraishi

Publications and source records attributed to T Shiraishi.

At least 19 recordsLinked to original sources

Presence of ras oncogene mutations and human papillomavirus DNA in human prostate carcinomas.

The frequency of H-ras, K-ras, and N-ras mutations and the presence of high-risk human papillomavirus (HPV 16, 18, and 33) DNA were studied in 75 paraffin-embedded specimens obtained from 68 Japanese patients with a variety of prostate carcinomas by using polymerase chain reaction and DNA hybridization with sequence-specific oligonucleotides. Ten specimens each of normal and benign hyperplastic prostatic tissues from the same number of patients were also examined for this analysis. Of 68 carcinoma cases, ras gene mutations were present in 16 cases (24%) and HPV DNAs in 28 cases (41%). Eleven mutations were detected in codon 61 of H-ras, 4 in codon 12 of N-ras, and 2 in codon 61 of K-ras. HPV 16, 18, and 33 DNAs were found in 11, 17, and 5 cases, respectively. Eight of the 16 cases with ras mutation also harbored HPV DNAs. The frequency of ras mutations and the HPV infection increased in patients with advanced stages of the tumor and with the higher Gleason score. There was the predominant presence of H-ras codon 61.2 (CAG-->CTG) mutation and HPV 18 DNA in prostatic carcinomas metastasizing to the bone. None of the normal or benign hyperplastic prostatic specimens contained either ras mutation or HPV DNA. Our results suggest that ras gene mutations and HPV infections are relatively frequent, at least in prostate carcinoma of Japanese patients. These two factors appear to be related to the progression of the tumor. Moreover, H-ras codon 61.2 mutation and HPV 18 infection may have some predictive roles for bone metastasis in prostate carcinoma.

Aged

Resolution of 9-(c-4,t-5-bishydroxymethylcyclopent-2-en-r-1-yl)-9H-adenine and selective inhibition of human immunodeficiency virus by the (-) enantiomer.

Two enantiomers of 9-(c-4,t-5-bishydroxymethylcyclopent-2-en-r-1-yl)-9H- adenine (BCA) which showed a potent and selective anti-HIV effects have been synthesized and evaluated against human immunodeficiency virus type 1. The result demonstrated that the potent-HIV activity of racemic BCA is expressed solely by the (-) isomer.

Adenine

Comparative study of prostatic carcinoma bone metastasis among Japanese in Japan and Japanese Americans and whites in Hawaii.

Metastatic prostate carcinomas in autopsy cases from three populations 49 cases of indigenous Japanese, 29 cases of Japanese Americans and 14 from whites in Hawaii) were compared in terms of their clinicopathological, immunohistochemical (tenascin and ras p21) and lectin binding (Helix Pomatia antigen, HPA) properties. Only the clinicopathological features were analyzed in the cases of whites in Hawaii. The results indicate that poorly differentiated carcinoma is less common, whereas distant metastasis is more frequent, in indigenous Japanese. Some of the Japanese-American cases with poorly differentiated carcinomas did not show any distant metastases. HPA and ras p21 expression are more common, but tenascin is less common in indigenous Japanese. HPA expression is more common in cases with metastasis, especially with metastasis to the bone and other organs, than nonmetastatic cases. Prostatic cancer cases in indigenous Japanese were more aggressive biologically than those in Japanese Americans, but no phenotypic differences were seen relevant to the presence or absence of bone metastases.

Aged

Comparative effects of a recombinant and a mutein type of granulocyte colony stimulating factor on the growth of Meth-A fibrosarcoma with 5-fluorouracil chemotherapy.

The present study was designed to evaluate the effects of a recombinant human G-CSF (rhG-CSF) and a mutein G-CSF (KW-2228) on leucopenia and tumor growth in mice treated with 5-fluorouracil (5-FU). In normal mice, the number of leucocytes (white blood cell, WBC) reached the peak 12 hours after a single injection of either type of G-CSF and decreased to the normal level after 24 hours. Daily administration induced a continuous increase in the WBC count, however, administrations at intervals did not. Meth-A fibrosarcoma was subcutaneously inoculated into the backs of syngeneic BALB/c mice. The mice were treated with 5-FU alone or with G-CSFs. Chemotherapy with 5-FU alone resulted in leucopenia and an insignificant inhibition of tumor growth. The conjunctive administration of G-CSFs with 5-FU resulted in a significantly augmented inhibition of tumour growth, and leukopenia was not seen. This augmenting effect was more prominent with KW-2228. These results suggest that in 5-FU chemotherapy G-CSFs may be beneficial in restoring the number of leucocytes from leucopenic state and in augmenting the tumor inhibitory effect. Furthermore, KW-2228 may be more beneficial than the natural type rhG-CSF.

Amino Acid Sequence

Immunomodulation by orally administered protein-bound polysaccharide PSK in patients with gastrointestinal cancer.

The present study was designed to assess the effects of the protein-bound polysaccharide PSK on the immunological status of patients with gastrointestinal cancer. Twenty-nine gastric and 18 colorectal cancer patients were randomly assigned to either the control or PSK group. Patients in the PSK group were given 3.0 g of PSK orally before surgery, either daily or every other day. Patients in the control group received no PSK. The data of peripheral blood lymphocytes (PBL) were compared before and after administration of PSK, and those of the regional node lymphocytes (RNL) were compared between the control and the PSK group. The results indicate that the effects of PSK were significantly influenced by the duration of administration, but not by the frequency of administration. In the patients belonging to the short term PSK group (administration less than 14 days), the response of the PBL to PSK and Con A become significantly stronger compared to before the administration of PSK, whereas the cytotoxicity against K562 and KATO-3, and the proportion of CD16+ cells increased significantly in those patients belonging to the long term PSK group (greater than or equal to 14 days). In addition, the proportion of CD9 + 11b + suppressor T cells decreased in the RNL of the short term PSK group, whereas the proportion of CD4 + Leu8 - helper T cells in the RNL increased in the long term PSK group. These results suggest that the oral administration of PSK leads to the suppression of suppressor cells in the RNL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic

Synergistic induction of erythroid differentiation of mouse erythroleukemia (MEL) cells by inhibitors of topoisomerases and protein tyrosine kinases.

In vitro erythroid differentiation of mouse erythroleukemia (MEL) cells was induced by combinations of topoisomerase and protein kinase inhibitors. Neither inhibitor alone exhibited inducing activity. Although inhibitors of topoisomerases I and II were equally effective in the synergistic induction of erythroid differentiation, only inhibitors of tyrosine kinases, not of serine/threonine kinases, exhibited synergistic activity. The erythroid differentiation induced by the combination of topoisomerase and protein tyrosine kinase inhibitors was distinguished from that induced by typical erythroid inducing agents such as DMSO or HMBA by (1) earlier hemoglobin accumulation in the cells and (2) insensitivity to specific inhibitors (dexamethasone and sodium orthovanadate) of MEL cell differentiation.

Acetamides

[Clinicopathological study of autopsy cases of pancreatic carcinoma in the elderly].

A total of 257 autopsy cases of pancreatic carcinoma, including 160 male and 97 female cases with an average age of 68.2 years, were divided into an aged group (70 years or older, 136 cases) and a control group (younger than 70 years, 121 cases), and their respective clinicopathological features were compared. The male to female ratio was 1.2:1 in the aged group and 2.6:1 in the control group. In both groups, abdominal pain was noted in about one-third of the cases as the primary symptom, followed by appetite loss and icterus. Concerning the primary symptoms, the two groups did not differ from each other. The rate of surgical resection was higher in the control group (24.0%) than the aged group (10.3%). Mean survival times were similar in both groups (5.71 months for the aged group and 6.01 for the control group). Intrapancreatic location of the tumor showed similar tendencies in both groups. However, cancer of the head of the pancreas was 2.3 times more common than body/tail cancer in cases aged 80 or more. Approximately 90% of the cases were diagnosed as ductal carcinoma by histological examination. The degree of differentiation was similar in both groups, but the well differentiated type was somewhat predominant in cases 80 years or older. Metastasis or direct invasion was noted to the liver, peritoneum and lung in this order in both groups. Liver and lymph node metastasis were less frequent in cases 80 years or older. Multiple primary cancers were noted in 8.8% of the aged group and 9.1% of the control.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Immunohistochemical demonstration of pepsinogens I and II in the gallbladder].

The immunohistochemical expression of pepsinogen I (PI) and pepsinogen II (PII) was studied in 103 gallbladder carcinomas, 25 non tumoral gallbladder lesions and 23 gallbladder cancer metastases. PI was positive in 6% of carcinomas and only in 2% of non tumoral contiguous mucosa. PII was positive in 46% of carcinomas and 43% of controls. Metastases were negative for both enzymes. Pyloric gland metaplasia of non tumoral mucosa adjacent to the tumor expressed PII in 68.9% and PI in 3.4% of cases. The same lesion in non tumoral gallbladders was positive for PII in 66.6% of cases, and no case expressed PI. There was no relationship between PI expression and the histological degree of differentiation. Only tumors with serosal or subserosal involvement were positive for PI. PII had a higher expression in early or well differentiated tumors. Tumors with pyloric gland metaplasia in the contiguous non tumoral mucosa expressed PII more frequently. Our results, based on the expression of PI and PII, suggest a relationship between the presence of pyloric gland metaplasia and some types of gallbladder cancer.

Biomarkers, Tumor

[A case of verrucous carcinoma showing a good partial response by C.P.E. (CDDP, PEP, etoposide) chemotherapy].

A 60-year-old woman was admitted to our hospital with a complaint of rough feeling on the oral mucosa and diagnosed as verrucous carcinoma with histopathological examination. She was treated with CPE chemotherapy, and showed a good response and improvement of clinical symptoms. Toxicities were leukopenia, alopecia and anorexia. However, these were slight side effects. The patient is currently healthy with no recurrence after two years and 3 months. CPE chemotherapy is considered to be effective for a patient with verrucous carcinoma.

Antineoplastic Combined Chemotherapy Protocols

[Endoscopic brushing cytology of esophageal lesions].

Endoscopic esophageal biopsy and brushing cytology were performed simultaneously in 121 cases, 25 of which were diagnosed as esophageal cancer by histologic examination of surgically resected material or at autopsy. Correct diagnosis was made in 88% of the cancer cases by endoscopic biopsy, and the same diagnostic rate was obtained by brushing cytology. Combination of the two methods revealed the cancer in 96% of the cases. There were no cases diagnosed as false-positive or false-negative by cytology. Three cancer cases were diagnosed as suspicious by cytology. Definite diagnosis was not made because of paucity of cells on the slide or of cellular atypism. For the improvement of accuracy in cytologic diagnosis it is important to sample adequate amount of cells, and in situ carcinoma cells should be differentiated from benign atypical cells in esophagitis.

Adult

[Clinical evaluation of intra-arterial methotrexate, vinblastine, doxorubicin and cis-platinum for bladder cancer].

Chemotherapy regimens including Methotrexate, Vinblastine. Doxorubicin and Cis-platinum (M-VAC) have shown objective responses in more than 50% of uroepithelial tumors. And intra-arterial chemotherapy can theoretically increase the drug concentration delivered to the tumor with maximum efficacy and less toxicity. In this report we review our experience at Matsuyama Red Cross Hospital between September 1987 and February 1991 using intra-arterial M-VAC in 21 evaluable patients with bladder cancer. Response was observed in 62% of the treated patients, two with complete remission and eleven with partial remission. WBC nadir and platelet nadir were mild to moderate. Other adverse effects such as mucositis, hair loss and creatinine elevation were seen in a small number of patients. Intra-arterial M-VAC can be one of the most useful forms of chemotherapy for patients with bladder cancer.

Adult

[Thallium-201 myocardial perfusion imaging during adenosine-induced coronary vasodilation in patients with ischemic heart disease].

201Tl myocardial perfusion imaging during adenosine infusion was performed in consecutive 55 patients with suspected coronary artery disease. Adenosine was infused intravenously at a rate of 0.14 mg/kg/min for 6 minutes and a dose of 111 MBq of 201Tl was administered in a separate vein at the end of third minute of infusion. Myocardial SPECT imaging was begun 5 minutes and 3 hours after the end of adenosine infusion. For evaluating the presence of perfusion defects, 2 short axis images at the basal and apical levels and a vertical long axis image at the mid left ventricle were used. The regions with decreased 201Tl uptake were assessed semi-quantitatively. Adenosine infusion caused a slight reduction in systolic blood pressure and an increase in heart rate. The rate pressure products increased slightly (9314 +/- 2377 vs. 10360 +/- 2148, p < 0.001). Chest pain (24%) and headache (13%) were the frequent side effects. The second-degree atrioventricular block was developed in 11 of 55 (20%) patients. All symptoms and hemodynamic changes were well tolerated and disappeared within 1 or 2 minutes after discontinuing adenosine infusion. The sensitivity and specificity for the detection of patients with coronary artery disease were 100% (31/31) and 88% (7/8), respectively. 201Tl myocardial imaging during adenosine infusion was considered to be safe and useful for evaluating the patients with ischemic heart disease.

Adenosine

EDTA induces differentiation and suppresses proliferation of promyelocytic leukemia cell line HL-60--possible participation of zinc.

Effects of ethylenediaminetetraacetic acid (EDTA), a chelator of divalent cations, on the proliferation and differentiation of human promyelocytic leukemia cell line HL-60 were examined. Incubation of HL-60 cells with 200 microM of EDTA suppressed cell proliferation, and induced differentiation assessed by reductivity of nitro blue tetrazolium and activity of alpha-naphthyl butyrate esterase. These effects were inhibited by zinc (Zn) dose-dependently at concentrations of up to 20 microM, but not by other divalent cations including Ca, Mg, Fe, Cu, Ni, or Cd. Although addition of 200 microM EDTA for 24 hr decreased the c-myc mRNA level of HL-60 cells, coaddition of 20 microM of Zn also reversed this effect on c-myc mRNA level. Treatment with EDTA did not change the half-life time of degradation of c-myc mRNA after addition of actinomycin D (5 micrograms/ml). These findings suggest that Zn deficiency suppresses c-myc gene transcription which is followed by suppression of proliferation and induction of differentiation of HL-60 cells.

Blotting, Northern

[An experimental study on the development of congenital spinal deformity--with special reference to the occurrence and significance of disc anomaly].

This is a histopathological study in mice, using the tail segment of the vertebral column, to investigate the role of intervertebral disc anomalies in the development of congenital spinal deformities. The study was conducted on 222 embryos and 169 postnatal CTT (Crooked-Tailed Toden) mice, a ddY strain with hereditary crooked tails. The earliest detectable anomaly was a serpiginous deformation of the notochord during the notochord stage. Irregular lamination of dense and sparse cell layers of the sclerotome during the membrane stage followed. Then vertebral body and intervertebral disc anomalies clustered around the abnormal notochord, failing to appear separately during the cartilage stage. It was concluded that anomalies of the vertebral body do not appear independently but occur simultaneously with those of the intervertebral disc in the development of congenital spinal deformities. Disc and vertebral body anomalies appear to have equal significance in the pathogenesis of congenital spinal deformities.

Animals

[Studies on the T-cell subset in lung tissue and BALF from patients with interstitial pneumonia].

The cellular components in bronchoalveolar lavage fluids (BALF) have been analyzed to obtain information on cellular kinetics in lung tissues of patients with diffuse pulmonary diseases. While various cells, alveolar macrophages, lymphocytes, and granulocytes appear in BALF, an increase in the percentage of lymphocytes has been noted in a variety of interstitial pneumonia. The T-cell subset of lymphocytes in BALF and biopsied lung tissues was, therefore, examined in patients with hypersensitivity pneumonitis (HP), sarcoidosis (Sar), idiopathic interstitial pneumonia (IIP) and rheumatoid arthritis with interstitial pneumonia (RA+IP) to compare the ratios of CD4/CD8 in BALF and lung tissues. The T-cell subset in BALF was analyzed by flow cytometry and the T-cell subset in lung tissues was detected with fresh frozen and thin-sliced specimens using an avidine-biotin complex (ABC) kit (Vecta Co. Ltd). The mean CD4/CD8 ratio in BALF was 0.36 in HP, 3.1 in Sar, 1.07 in IIP and 2.59 in RA+IP, while the mean CD4/CD8 ratio in lung tissues was 0.52 in HP, 2.59 in Sar, 1.11 in IIP and 2.25 in RA+IP, respectively. The ratios of CD4/CD8 in BALF and lung tissues from patients with these various interstitial pneumonia showed a positive correlation indicating that the changes of cellular components in BALF would reflect the changes in the lung tissues. Furthermore, CD4/CD8 ratios of lymphocytes infiltrating the alveolar portion and granuloma in lung tissues of HP were analyzed separately, because the CD4/CD8 ratios varied considerably from part to part of the lung tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic