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Biomedical subjects

Y Ohtsuki

Publications and source records attributed to Y Ohtsuki.

At least 73 records · Page 4Linked to original sources
PubMed2000

Clinical features of three fatal cases of non-specific interstitial pneumonia.

We describe the clinical courses of the 3 fatal patients (2 females and 1 male) with idiopathic non-specific interstitial pneumonia (NSIP) among 24 patients with NSIP. Lung biopsies were diagnosed to be NSIP group II in all patients. The clinical courses from onset to death of these 3 patients were 41 months, 46 months, and 91 months. A follow-up chest CT demonstrated no apparent honey-comb formation. We found that i) about 20% of patients with NSIP died of respiratory failure, ii) in the chest CT findings, apparent honey-comb formation was rare even just before death, iii) prediction of the prognosis based on the histological findings was difficult. This is the first report to describe the clinical features of deceased patients with idiopathic NSIP; the incidence of fatal cases was considered to range from 10 to 20%.

Aged↗
PubMed2000

A new human pleomorphic rhabdomyosarcoma cell-line, HS-RMS-1, exhibiting MyoD1 and myogenin.

A number of human cell lines derived from alveolar or embryonal rhabdomyosarcoma (RMS) have been described. To our knowledge, however, no cell line established from pleomorphic RMS has been reported. We describe here the establishment and characterization of a new human cell line, HS-RMS-1, which originated from a typical pleomorphic RMS arising in the gluteal muscle of a 26-year-old man. HS-RMS-1 cells had pseudotetraploid complex karyotypes with no specific abnormalities. Both in vitro and in vivo the cells on light microscopic examination exhibited pleomorphic features with immunopositive reaction for myogenic antigens including MyoD1 and myogenin, although no Z band-like structures were detected electron-microscopically. RT-PCR demonstrated the expression of MyoD1 and myogenin in HS-RMS-1 cells at the mRNA level, and direct sequencing analysis revealed cDNAs of MyoD1 and myogenin identical to those previously reported. This cell line, HS-RMS-1, established from pleomophic RMS will be useful for further studies including the molecular aspects of human RMS.

Adult↗
PubMed2000

A new human malignant peripheral nerve sheath tumour-cell line, HS-sch-2, harbouring p53 point mutation.

Only a few human malignant peripheral nerve sheath tumour (MPNST)-cell lines have been reported, and their characteristics have not been fully established. In this study, we established a new human cell line, HS-Sch-2, from an MPNST of the ordinary type which arose in a 54-year-old woman without von Recklinghausen's disease. This cell line was characterized by chromosome analysis, immunohistochemistry, ultrastructural examination, and direct sequencing of the p53 gene. The HS-Sch-2 cells have grown for more than 48 months in vitro, and exhibited hypotriploid karyotypes with complex chromosome abnormalities lacking a specific pattern. Histological features of the heterotranplanted nude mouse tumours were essentially the same as those of the original MPNST, with positive reactions for S-100 protein and neuron-specific enolase but not for epithelial membrane antigen, fibronectin or CD34. Ultrastructural examination in vivo revealed intricate interdigitation of long cytoplasmic processes and basal lamina-like structures. In addition, direct sequencing of the p53 gene detected a point mutation from CGT to CAT at codon 273 in exon 8. This HS-Sch-2 cell line, which exhibits distinctive morphological characteristics of MPNST and a p53 point mutation, will be useful for biological and pathological investigations of MPNST.

Animals↗
PubMed2000

Cancer regression induced by modified CTL therapy is regulated by HLA class II and class I antigens in Japanese patients with advanced cancer.

Autologous cancer-specific bulk CTLs are unlikely to be induced by in vitro CTL generation (ivtCTLG) using peripheral blood mononuclear cells (PBMCs) of cancer patients when autologous cancer cells are used as in vitro stimulators. However, autologous cancer-specific bulk CTLs are frequently activated when allogeneic cancer cells are used as in vitro stimulators, regardless of the type of cancer cell. We have developed a cancer-specific immunotherapy called modified CTL therapy, which involves adoptive immunotherapy of autologous cancer-specific bulk CTLs after active immunization of autologous or allogeneic cancer cells screened as in vitro stimulators according to their ability to induce autologous cancer-specific CTLs (ACS. CTLs). Cancer did not regress in patients in whom ACS.CTLs were not induced by ivtCTLG using the patients' PBMCs in therapy. Cancer regression, albeit temporary, occurred solely in patients under the immunological condition that ACS.CTLs were induced by ivtCTLG using PBMCs through the therapy. The induction of ACS.CTLs by ivtCTLG using patient PBMCs in therapy was related to patients' HLA class II antigens. HLA DR8 was seen more frequently in ACS.CTL-inducible patients than in ACS.CTL-uninducible patients (P=0.051). On the contrary, HLA DQ3 was seen more frequently in ACS.CTL-uninducible patients (P=0.055). On the other hand, the success in therapy, albeit temporary, was related mainly to patients' HLA class I antigens. HLA B61 was seen more frequently in patients whose therapy proved effective than in patients whose therapy proved ineffective (P=0.018). HLA Cw7 was seen more frequently in therapy-ineffective patients (P=0.040).

Adult↗
PubMed2000

Missense mutation of the hMSH6 and p53 genes in sporadic urothelial transitional cell carcinoma.

Functional defects in DNA mismatch repair genes have been shown to be associated mainly with hereditary human malignancies. We examined genomic DNA from 88 sporadic transitional cell carcinomas (TCCs) of the urinary tract for mutations in hMSH6 gene by polymerase chain reaction and direct sequencing analysis. Mutational status of p53 gene was also studied as a potential target of genetic instability secondary to hMSH6 dysfunction. A total of 5 cases (5.7%: 5/88) displayed hMSH6 mutations all consisted of transition and located in exon 4, including three cases with missense mutation and two without change of corresponding amino acid. These three tumors with hMSH6 missense mutation had no microsatellite instability with five microsatellite markers tested. p53 gene mutations were detected in 22 cases (25.0%: 22/88). No tumors with p53 mutation had any hMSH6 missense mutations. Compared to the cases without hMSH6 alterations, the three patients with hMSH6 alterations had more frequent additional primary cancer (P<0.05). These findings provide the first in vivo evidence for the type of alterations and frequency of possible involvement of the hMSH6 mutations in sporadic type urothelial TCCs.

Aged↗
PubMed1999

A new human synovial sarcoma cell line, HS-SY-3, with a truncated form of hybrid SYT/SSX1 gene.

Recent cytogenetical and molecular studies have indicated that synovial sarcoma harbors a t(X;18)(p11.2;q11.2) translocation, resulting in the formation of a hybrid SYT/SSX (SSX1 or SSX2) gene. We newly established a human cell line, HS-SY-3, from a synovial sarcoma. HS-SY-3 cells were shown to harbor the pathognomonic t(X;18)(p11.2;q11.2) translocation by chromosome analysis but not to exhibit the classical hybrid SYT/SSX transcripts induced by this translocation, using RT-PCR. To determine the reason for this discrepancy, we analyzed cDNA from HS-SY-3 cells, as well as the original sarcoma tissue by the rapid amplification of cDNA 3' end assay, and found that the chimaeric cDNA was 240 bp shorter than the previously established SYT/SSX1 cDNA due to truncation of the 3' side of SSX1. The HS-SY-3 cells should be useful for future functional studies of the SYT/SSX chimeric gene.

Aged↗
PubMed1999

Endometrial stromal sarcoma with clonal complex chromosome abnormalities. Report of a case and review of the literature.

Only eleven endometrial stromal sarcomas (ESS) with clonal chromosomal abnormalities have been reported in the literature. Of these, four have been reported to harbor the t(7;17) translocation. We report here an additional ESS that exhibited clonal complex chromosome abnormalities not described earlier: 38,XX,-1,del(1)(q11),-2,add(2)(p13),-3,der(4)add(4)(p12)psu dic(4;14)(q35;q11.2), add(6)(p21.3),add(7)(q22),del(7)(p11.2p13),-8,-9,add(9)(q34),- 10,add(10)(q24),-11,-11,ins(12;?) (q13;?),-14,-14,-15,ins(15;?)(q22;?),add(16)(q22),add(17)(q11.2),- 18,der(18)t(7;18)(q11.2;p11.2),-19, add(20)(p13),add(21)(p11.2),-22,add(22)(p11.2),+6mar in metaphase cells from primary short-term culture.

Adult↗
PubMed1999

Expression of cytokeratin 19 mRNA in human lung cancer cell lines.

The present study was designed to clarify the mechanism by which some lung cancer cell lines can produce cytokeratin 19 (CK19) fragment and others cannot. We hypothesized that some lung cancer cell lines which cannot release CK19 express an incomplete sequence of CK19 mRNA. Expression of mRNA was evaluated by RT-PCR using several primer pairs for CK19. CK19 in the culture supernatant was measured by an immuno-radiometric assay. CK19 protein synthesis was evaluated by Western immunoblot and immunohistochemistry. Among 16 lung cancer cell lines, 7 released significant amounts of CK19 in the supernatant. In some cell lines, expression of CK19 mRNA was observed only in some combinations of primers, suggesting that incomplete mRNA was expressed. 3'-RACE analysis detected amplified products of a shorter size compared with normal amplified products in cell lines which expressed incomplete CK19 mRNA, suggesting that 3'-ends of mRNA for CK19 were deleted. Results of Western immunoblot and immuno-histochemical staining using anti-human CK19 monoclonal antibody completely correlated with the results on CK19 levels in culture supernatants as well as with complete expression of mRNA. We conclude that levels of CK19 closely relate to the expression of complete mRNA for CK19.

Adenocarcinoma↗
PubMed1999

Late pathologic changes in guinea pig kidneys irradiated with conventional fractionation and hyperfractionation.

PURPOSE: The aim of this study was to determine the differences in renal damage particularly associated with the effect of a small dose per fraction with a constant total dose. METHODS AND MATERIALS: Guinea pigs, 12-week-old English Hartley females, were used. The animals were divided into five groups according to irradiation schedule: No irradiation (control group); 2.0 Gy x 1/day, 5 fraction (f)/week (wk), 40 f, total 80 Gy (Group CF-2.0 [CF = conventional fractionation]); 1.0 Gy x 2/day, 10 f/wk, 80 f, total 80 Gy (Group HF-1.0 [HF = hyperfractionation]); 3.0 Gy x 1/day, 5 f/wk, 27 f, total 81 Gy (Group CF-3.0); and 1.5 Gy x 2/day, 10 f/wk, 54 f, total 81 Gy (Group HF-1.5). Only unilateral irradiation was performed. A histologic analysis was performed before irradiation and at 6 and 12 months after the completion of irradiation. The severity and severity ratios of urinary tubule atrophy, the number of large nuclei per unit area in the renal tubules, the average diameter of the glomeruli, and the number of cells composing the glomerulus were used as parameters for evaluating renal damage. RESULTS: In Groups CF-2.0 and CF-3.0 (the conventional fractionation [CF] groups), all the renal tubules showed severe atrophy 12 months after irradiation. On the other hand, only 20% of the renal tubules showed slight atrophy in Group HF-1.0 at 12 months. In Group HF-1.5, 70% of the renal tubules were atrophic at 12 months. The number of large nuclei markedly increased in Groups HF-1.0 and HF-1.5 (the hyperfractionation [HF] groups) at 12 months, whereas the number was very low in the CF groups at 12 months. Only in Group HF-1.0 had the average diameter of glomeruli not shrunk at 12 months. The number of cells composing the glomerulus in the CF groups markedly decreased at 12 months. The number of cells in the HF groups was also reduced, however the reduction was not as severe as that observed in the CF groups. CONCLUSION: 1.0 Gy per fraction delivered by HF greatly reduces renal damage even in the 80 Gy-irradiated kidney, which is one of the most radiosensitive organs.

Animals↗
PubMed1999

Human mismatch repair gene (hMSH2) product expression in relation to recurrence of transitional cell carcinoma of the urinary bladder.

BACKGROUND: Several convincing studies have shown that the hMSH2 gene plays major roles in mismatch repair by recognizing mismatched bases and preventing mutations during DNA replication. Loss of this function may result in the accumulation of DNA replication errors or even the mutator phenotype (which may be responsible for the multiple mutations required for multistep carcinogenesis), and it has been found to affect the prognosis of patients. Thus, the authors felt that it would be of interest to study the expression patterns of hMSH2 protein in malignant tumors and to assess the correlation of hMSH2 protein to various clinical and pathologic features in these patients. METHODS: The authors examined the expression patterns of hMSH2 protein in 115 patients with transitional cell carcinoma (TCC) of the urinary bladder by immunohistochemical technique using monoclonal antibody to hMSH2 protein. RESULTS: The group in which hMSH2 was preserved (>20% of nuclei were positive for staining by anti-hMSH2 antibody) included 86 of 115 (75%) of the TCCs, whereas the remaining 29 cases (25%) belonged to the group in which hMSH2 was preserved (< or = 20% of tumor nuclei were positive), including 2 negative cases. Univariate analysis indicated that reduced expression of hMSH2 protein was significantly more frequent in high grade tumors than in low grade tumors (P = 0.04). Furthermore, statistical multivariate analysis revealed that hMSH2 reduction was significantly related to the recurrence (P = 0.02). CONCLUSIONS: These results suggest that abnormal expression of hMSH2 protein might be involved in tumorigenic processes and in the progression of some TCCs, and that the loss of hMSH2 protein expression might be a useful predictor of recurrence of TCC.

Aged↗
PubMed1999

Further characterization of the human clear cell sarcoma cell line HS-MM demonstrating a specific t(12;22)(q13;q12) translocation and hybrid EWS/ATF-1 transcript.

Only a small number of clear cell sarcoma (CCS) cell lines have been reported, including the cell line HS-MM. In the present study, this cell line, maintained for more than 4 years since establishment, was further characterized by cytogenetic studies, fluorescence in situ hybridization (FISH) analysis, and reverse transcriptase-polymerase chain reaction (RT-PCR). HS-MM cells both in vitro and in vivo exhibited pseudodiploid karyotypes with the specific t(12;22)(q13;q12) translocation. The translocation between chromosomes 12 and 22 was confirmed by FISH analysis and the hybrid EWS/ATF-1 transcript induced by this translocation was detected by RT-PCR. The HS-MM cell line will be useful for further studies of CCS.

Chromosome Aberrations↗
PubMed1999

Elevation of anti-cytokeratin 19 antibody in sera of the patients with idiopathic pulmonary fibrosis and pulmonary fibrosis associated with collagen vascular disorders.

It has been suggested that cytokeratin 19 is expressed in regenerated bronchoepithelial cells in patients with pulmonary fibrosis, and serum cytokeratin 19 fragment is elevated in patients with pulmonary fibrosis. We hypothesized that serum antibodies to cytokeratin 19 may be formed in patients with pulmonary fibrosis. To prove the existence of anti-cytokeratin 19 antibodies in patients' sera, human recombinant cytokeratin 19 was stained with patients' sera by a Western immunoblot. Then, we tried to establish an enzyme-linked immunosorbent assay to quantitate anti-cytokeratin 19 antibody in the sera of patients with idiopathic pulmonary fibrosis (IPF) and pulmonary fibrosis associated with collagen vascular disorders (PF-CVD). We demonstrated the anti-cytokeratin 19 antibody in patient' sera by a Western immunoblot. In patients with IPF and PF-CVD, significantly high anti-cytokeratin 19 antibody was demonstrated compared with normal volunteers, patients with chronic bronchitis, and patients with pneumonia. These results suggest that anti-cytokeratin 19 antibody may have played a role in the process of lung injury in pulmonary fibrosis.

Adult↗
PubMed1999

Determination of the prognostic significance of cyclin B1 overexpression in patients with esophageal squamous cell carcinoma.

Recent studies have identified a family of proteins referred to as cyclins, which control the cell cycle. Cyclin B1 activates cdc2, which regulates cell progression through the G2 and M phases. The main aim of this study was to examine the relationships between the cyclin B1 expression in human esophageal squamous cell carcinoma (SCC) and clinicopathological factors and prognosis of the patients. Eighty-seven cases of primary human SCC consecutively obtained at esophagectomy were immunohistochemically studied using an anti-human cyclin B1 protein antibody (2H1-H6). The relationship between cyclin B1 expression and clinicopathological factors, including prognosis, were also statistically assessed. Positive immunostaining of cancer cells, mainly in the cytoplasm, was detected in 72.4% (63/87): heterogeneous pattern in 37.9% (33/87) and homogeneous pattern in 34.5% (30/87). The prevalence of cyclin B1 expression was significantly higher in cases with invasion deeper than the muscularis propria (P<0.005) and with venous invasion (P<0.01) than in other cases. Patients whose SCCs expressed high levels of cyclin B1 protein had a significantly poorer prognosis than did the other patients (P<0.05). Multivariate analysis demonstrated that cyclin B1 status was an important factor affecting survival (P<0.05). These findings demonstrated that overexpression of cyclin B1 protein is associated with tumor behavior and prognosis for patients with human esophageal SCC.

Adult↗
PubMed1999

Sun-exposure- and aging-dependent p53 protein accumulation results in growth advantage for tumour cells in carcinogenesis of nonmelanocytic skin cancer.

Three hundred and sixteen patients with nonmelanocytic skin cancer, including 46 cases of Bowen's disease (BOD), 134 cases of squamous cell carcinoma (SCC), and 136 cases of basal cell carcinoma (BCC), were examined immunohistochemically using monoclonal antibody DO-7 to assess p53 protein accumulation related to sun exposure and ageing, and growth and differentiation of skin cancer and its precursors. The rates of p53 immunostaining of BOD, SCC and BCC were 80.4%, 76.1% and 70.6%, respectively. p53-positive cells were present not only in cancer nests, but also in dysplastic and even morphologically normal epidermis adjoining cancers. Sun exposure was statistically correlated with the p53 immunostaining scores in morphologically normal epidermis of the three skin cancers and in cancer nests of SCC and BCC. The positivity and score of p53 protein often differed significantly among the three types of cancer, especially in regions of dysplasia. Interestingly, differentiation of SCC was correlated with individual p53 scores for dysplasia and cancer nests, especially for dysplasia. BOD, as the precursor of SCC, demonstrated the strongest p53 expression. Furthermore, 12.3% cases with p53 negative cancer nests showed p53-positive reaction in dysplasia and in morphologically normal epidermis. It seems that the accumulation of p53 protein plays a part in precancerous lesions and in the genesis of more highly differentiated types of skin cancer and affects mainly the growth of tumour cells rather than their differentiation. For BCC, however, age was significantly related to p53 expression. Our findings suggest that overexpression of p53 in normal skin and cancer nests of SCC and BCC is significantly related to sun exposure, that the expression of p53 in BCC is an age-dependent process, and that the early accumulation of p53 protein may be a useful predictor for the detection of nonmelanocytic skin cancer.

Adult↗
PubMed1999

Overexpression of c-Met protein in human thyroid tumors correlated with lymph node metastasis and clinicopathologic stage.

To examine the expression of c-Met protein in thyroid tumors and the correlation of c-MET protein expression with lymph node metastasis (LNM) and pathological stage, 111 papillary thyroid carcinomas (PTC), including 44 with synchronous LNM, and 117 follicular adenomas (FA) were immunohistochemically examined using dewaxed sections of formalin-fixed, paraffin-embedded tissues. Immunohistochemical results were confirmed by Western blot analysis. For PTC, positive immunostaining was observed in 107 of 111 (96.4%) cases and was diffusely present in either cytoplasm and nucleus, or only cytoplasm or only nucleus of cancer cells at varying intensities. Staining tended to be stronger in the periphery of cancer cell nests. Positive reaction was also found in 44 of 117 (37.6%) cases of FA. However, the extent and intensity of c-Met immunostaining in FA were far less than those in PTC (p < 0.0001). Forty-four PTC cases (39.6%) exhibited LNM, and the extent and intensity of c-Met expression were significantly correlated with both LNM (p < 0.0001) and pathological stage (p < 0.0001). No significant correlation of c-Met expression with age, sex or tumor size was found. Our findings suggest that PTC expresses c-Met protein much more strongly and intensively than does FA, and that strong and intense overexpression of c-Met protein may be an indicator of the presence of lymph node metastasis and advanced pathological stage of papillary thyroid carcinoma.

Blotting, Western↗
PubMed1999

Clinical features of non-specific interstitial pneumonia.

The clinical features of 24 patients with non-specific interstitial pneumonia (NIP) were evaluated. The patients consisted of seven men and 17 women, with a median age of 60 years. In seven patients, the disease was idiopathic and eight had collagen vascular diseases. Cough, dyspnoea and fever were frequently observed. The time interval between the onset of symptoms and open lung biopsy was 3 months. Mild increases of IgG, CRP, and LDH were also frequently observed. The average per cent VC was 65.1 +/- 3.2% and the average PaO2 was 71.3 +/- 2.4 Torr. Bronchoalveolar lavage was done in 20 patients, and a moderate increase in lymphocytes (27.8 +/- 6.7%) with a low CD4/CD8 ratio (0.86 +/- 0.22) was observed. Multiple patchy infiltration or diffuse interstitial shadows, located predominantly in the lower fields of both lungs were the characteristic chest CT findings. Lung biopsies in this group were characterized by varying proportions of chronic interstitial inflammation and fibrosis which was temporarily uniform. Patients were given steroid pulse therapy or oral steroids. The results were mild to marked improvements in chest roentgenographic findings and lung functions. Four patients (16.7%) died because of respiratory failure caused by NIP. This is the first report to describe clinical features of NIP since the original report by Katzenstein and Fiorelli.

Adrenal Cortex Hormones↗