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Biomedical subjects

J Saito

Publications and source records attributed to J Saito.

At least 19 recordsLinked to original sources

Fine-scale deletion mapping of the distal long arm of chromosome 6 in 70 human ovarian cancers.

To define a small region on chromosome 6q containing a putative tumor suppressor gene for ovarian cancer, we examined loss of heterozygosity in 70 ovarian tumors of three histological types with nine restriction fragment length polymorphism markers located at 6q24-27. Among 33 cancers of serous type that were informative at one or more loci, 17 showed allelic loss at a few or all loci examined, whereas only 1 of 15 mucinous-type tumors and 2 of 12 clear-cell tumors revealed loss of heterozygosity. This result supported our earlier suggestion that alteration of a gene on chromosome 6q may play an important role during development of serous ovarian tumors (Sato et al., Cancer Res., 51: 5118-5122, 1991). Frequent losses were observed between loci defined by CI6-119 (D6S195) at 6q26 and CI6-49 (D6S161) at 6q27. A detailed deletion map indicated a commonly deleted region between loci defined by CI6-111 (D6S193) and CI6-24 (D6S149); these two markers are estimated to be 1.9 cM apart on the basis of linkage analysis. Our results further define a region containing a tumor suppressor gene involved in ovarian carcinoma within an approximately 2-megabase-long segment of chromosome 6q.

Blotting, Southern

On the mechanism of termination and perpetuation of atrial fibrillation.

In an effort to further clarify the mechanism of termination and perpetuation of atrial fibrillation (AF), the intraatrial potentials during AF induced by programmable electrical stimulation were analyzed using the concept of wavelength which represents the size of a microreentrant circuit. Thirty patients with inducible AF were divided into 2 groups: 20 patients with AF that terminated spontaneously (group 1) and 10 patients with AF that did not terminate spontaneously (group 2). Wavelength is the product of refractory period and conduction velocity. During AF, the refractory period of the local atrial tissue was considered to correlate with the mean interval between each intraatrial potential (mean ff). An inverse relation was considered present between conduction velocity of the impulse and the width of intraatrial potentials (f width). Thus, the wavelength index was defined as (mean ff)/(mean f width). Ten intraatrial potentials at the high right atrium were sampled for measurement. Group 1 had higher wavelength indexes just after the induction of AF than did group 2 (1.33 +/- 0.31 vs 1.10 +/- 0.05, p less than 0.05). In group 1, the wavelength indexes were increased from the initial value to 1.49 +/- 0.36 just before termination of AF (p less than 0.001). In 3 group 2 patients, AF stopped after disopyramide was administered intravenously, whereas the wavelength indexes at the end of AF were higher than those before drug administration (1.27 +/- 0.08 vs 1.16 +/- 0.04, p less than 0.05). In conclusion, prolongation of the wavelength appears to be a major determinant for termination of AF, and shorter wavelengths are necessary for perpetuation of AF.

Adult

Detection of human papillomavirus types 16 and 18 in the exfoliated cervical cells using the polymerase chain reaction.

We applied the polymerase chain reaction (PCR) to detect HPV 16 and 18 in cytological samples obtained from the uterine cervices of Japanese women. HPV infection was detected in 17 (25%) of 67 with CIN and 11 (37%) of 30 with cervical carcinoma. It is notable that 11 (16%) of 69 women with normal cervices were infected with either HPV 16 or 18. The polymerase chain reaction is sensitive and useful for epidemiological studies.

Adolescent

Hepatocellular carcinoma containing endocrine cells. An autopsy report of triplecancer involving the liver, kidney and thyroid.

An autopsy case of triplecancer (hepatocellular carcinoma of the liver, renal cell carcinoma of the kidney, and papillary carcinoma of the thyroid) was reported. Histological features of primary hepatic tumor suggested undifferentiated hepatocellular carcinoma (Edmondson-Steiner's Grade IV). However, certain tumor cells showed distinctive argyrophilic reactions and electron microscopy revealed small round granules resembling electron dense endocrine secretory granules in their cytoplasm. Immunohistochemistry demonstrated that tumor cells showed a positive reaction for AFP while some others were positive for chromogranin-A. Immunohistochemical demonstration of AFP production by tumor cells indicated their hepatocyte origin. No endocrine syndrome had been present and no alternative primary source of the endocrine tumor was detected. Tumors of the kidney and thyroid were considered to be incidentally combined.

Aged

Changes in serum erythropoietin levels during chemotherapy for lung cancer.

Serial serum erythropoietin (EPO) levels were measured in 12 adult lung cancer patients during cancer chemotherapy. In major cases, EPO levels increased significantly after chemotherapy while the hemoglobin (Hb) remained at initial levels. EPO fell gradually or rapidly to initial levels after a peak, although the patients were anemic. The increase of EPO levels was linearly related to the decrease in Hb (y = 17.48x + 1.003). The mechanism of the rapid increase of EPO is not simply explained by anemia, but might be related to new synthesis, corresponding to depressed bone marrow.

Adult

Chemotherapy in small cell lung cancer--from view point of dose intensity.

Results of chemotherapy trials for small cell lung cancer carried out for the past 5 years were analyzed from view point of dose intensity. Early study of CDDP+EP+ADM (1985 to 1987) showed moderate response rate (RR) of 72% with MST of 369 days. Succeeding alternative protocol of CDDP+EP+VCR/CPM+ADM+MTX (1989-1990) showed improved RR of 88% and MST of 13 months. Actual dose and interval for the alternating regimen was superior to the single arm regimen. Projected relative dose intensity against MAOP protocol including 6 drugs common to our regimen was 0.86 and delivered RDI was 0.61 with comparable RR and MST. The results may indicate that change of dose intensity within the conventional range does not result in major advantage or disadvantage for substantial prolongation of the survival in SCLC patients.

Antineoplastic Combined Chemotherapy Protocols

Detection of human papillomavirus DNA in the normal cervices of Japanese women by the dot-blot (Vira Pap) method.

Exfoliated cervical cells obtained from 9 patients with cervical intraepithelial neoplasia (CIN) I and II, 11 with CIN III, 22 with cervical carcinoma, and 599 with cytologically normal cervices (including 63 pregnant women) were evaluated for the presence of human papillomavirus (HPV) by the dot-blot (Vira Pap) method. HPV infection was detected in 33.3% of the CIN I and II cases, in 54.5% of the CIN III cases, in 68.2% of invasive cervical carcinoma cases, and in 4.2% of the normal group. The rate of detectable HPV infection increased in exfoliated cervical cells during pregnancy. These results suggested that a few Japanese women with cytologically normal cervices were infected with HPV.

Adolescent

[Respiratory infections associated with lung cancer].

We have analyzed the clinical significance of secondary infections associated with lung cancer patients. The incidence of secondary infections was 51.4% in 214 in-patients with lung cancer admitted to our institution in 1988 and 1989, and almost all of them had respiratory tract infections. The incidence was high in patients with cell types other than adenocarcinoma, and in those with hypoproteinemia, impaired cellular immunity and obstruction of the airway. The prognosis in patients with infection was much poorer than that in patients without infection. Major causative pathogens were Staphylococcus aureus including methicillin-resistant S. aureus (MRSA), Haemophilus influenzae, Klebsiella spp. and Pseudomonas aeruginosa. These pathogens except for H. influenzae were isolated at the terminal stage, in cases with airway obstruction and in post cancer-chemotherapeutic phase. The efficacy rate of 194 chemotherapeutic regimens against infection was 57.7%. Although the efficacy rate in 1988 and 1989 exceeded that in the 1970s, there was no significant difference in the efficacy rate between monotherapy (57.1%) and combined therapy (59.3%). The effectiveness was very poor for infections caused by P. aeruginosa and MRSA, or for cases with airway obstruction and marked impairment of pulmonary blood flow. The above results showed that a new combined therapy as well as the measures to improve the general condition of compromised hosts are required in the treatment of secondary infections in these patients.

Adult

[Clinical significance of respiratory infections associated with lung cancer patients].

An attempt was made to interpret the clinical significance of secondary infections associated with lung cancer. The incidence of secondary infections was 51.4% in 214 in-patients with lung cancer in our institution in 1988 and 1989, and almost all of them had respiratory infections caused by commonly encountered bacteria. The incidence of infection was high in lung cancer of cell types other than adenocarcinoma, and in those with hypoalbuminemia, impaired cellular immunity and obstruction of the airway. The prognosis in patients with infection was much poorer than that in patients without infection. Major pathogens responsible for infection were Staphylococcus aureus including methicillin-resistant S. aureus (MRSA), Haemophilus influenzae, Klebsiella spp. and Pseudomonas aeruginosa. These pathogens, except for H. influenzae, were isolated in the terminal stage in cases with airway obstruction and post cancer chemotherapy. The efficacy rate of 194 therapeutic regimens against infection was 57.7%. It was thus found that the efficacy rate in 1988 and 1989 exceeded that in the 1970s. The effectiveness was very poor for infections caused by S. aureus and P. aeruginosa, and for cases with airway obstruction and marked impairment of pulmonary blood flow. The efficacy rate of single-drug regimens was 57.1% (80/140) and that of combined regimens was 59.3% (32/54). The above results indicate that a new combined therapy which includes a beta-lactam antibiotic as well as measures to improve the general health of compromised hosts are required in the treatment of secondary infections in these patients.

Adult

Cloning and characterization of human papillomavirus type 52 from cervical carcinoma in Indonesia.

Human papillomavirus (HPV) type 52 from a cervical carcinoma in Indonesia was molecularly cloned and characterized. By hybridization with cervical carcinoma DNAs from Indonesian patients, HPV 52 was detected in 3 of 52 cases (6%), whereas HPV 16 and 18 were detected in 8 and 7 cases, respectively (15% and 13%). Sequence analysis revealed that the E6-E7 ORFs contained several DNA binding motifs (Cys-X-X-Cys) like previously sequenced HPVs. The E6 ORF also contained splice donor and acceptor signals, which may allow the expression of E6* protein. The E7 ORF encoded an amino acid sequence that is conserved in some DNA tumor viruses and is involved in binding to Rb protein and in cellular transformation. Transfection of a subgenomic fragment of HPV 52 under the control of a heterologous promoter showed that the E7 ORF alone induced anchorage-independent growth of established rodent cells and immortalized primary rat embryo fibroblasts (REF), and that in cooperation with activated ras, it induced malignant transformation of REF. The E6 ORF also induced, less efficiently, anchorage-independent growth. These results strongly suggest that HPV 52, like HPV 16 and 18, has oncogenic potential.

Amino Acid Sequence

Contribution of the gene linked to the T cell receptor beta chain gene complex of NZW mice to the autoimmunity of (NZB x NZW)F1 mice.

We have investigated the contribution to the autoimmune disease of (NZB x NZW)F1 (NZB/W) mice made by the T cell receptor beta (TcR beta) chain gene complex, or genes linked to it, that are derived from the NZW strain. For this we developed the NZW.TcR beta NZB strain, a NZW congenic line carrying the TcR beta of NZB type, and produced NZB x NZW.TcR beta NZB (NZB/W.TcR beta NZB)F1 mice. We compared the amounts of anti-DNA and anti-histone antibodies and also the severity of lupus nephritis in these mice with those in the original NZB/W F1 mice. We obtained evidence for significantly lower serum levels of autoantibodies to double-stranded and single-stranded DNA and histone, and a later onset and a lower incidence of proteinuria in the NZB/W.TcR beta NZB F1 mice than in the original NZB/W F1 mice. These findings clearly indicate that the gene(s) within or closely linked to the TcR beta chain gene complex on chromosome 6 of the NZW strain acts to intensify the feature of systemic lupus erythematosus in the NZB/W F1 strain. The significant relationship of this finding to the strict dependency of NZB/W F1 disease on the H-2d/H-2z heterozygosity is discussed.

Animals