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Biomedical subjects

K Sekine

Publications and source records attributed to K Sekine.

At least 19 recordsLinked to original sources

Cell electrophoretic characterization of abnormally expanded lymphocytes in autoimmune lprcg, lpr, gld and Yaa mice, and of thymocyte subsets.

Autoimmune mice carrying the lprcg/lprcg(lprcg),lpr/lpr(lpr),gld/gld(gld) and Yaa genes exhibit massive lymphoproliferation and a systemic lupus erythematosus-like syndrome. The surface markers of abnormally expanded lymphocytes used were Thy-1+, CD4-CD8- (double negative, DN) and CD45+ for lprcg, lpr, gld and (lprcg X gld) hybrid (F1-lprcg-gld) mice, and Ig+ for Yaa mice. To characterize the cell surface properties and differentiation pathway of lymphocytes in autoimmune mice, the cell electrophoretic mobility (EPM) was determined for the lymph node (LN), spleen and thymus cells. The EPM of lymphocytes derived from swollen LN was of the T cell type in lprcg, lpr, gld and F1-lprcg-gld mice, but of the B cell type in Yaa mice, indicating that the EPM of abnormally proliferated lymphocytes in autoimmune mice reflects their origin, and that the surface properties detected as a net negative charge were the same in abnormal and normal lymphocytes. The electrophoretic behavior of whole thymocytes was also the same in autoimmune and normal mice. The DN, and CD4+CD8- and CD4-CD8+ (single positive, SP) thymocytes from normal mice exhibited high EPM, while CD4+CD8+ (double positive, DP) thymocytes exhibited low EPM. According to the recent concept of intrathymic T cell differentiation (Schwartz, R. H., Cell. 1989, 57, 1073-1081), it is suggested that EPM of thymocytes may change with maturation in the following manner: DN thymocytes with high EPM----DP thymocytes with low EPM----SP thymocytes and autoimmune DN T cells with high EPM.

Animals

[Clinical study of combination chemotherapy with cisplatin, ifosfamide, 5-FU (CIF therapy) of inoperable adenocarcinoma and large cell carcinoma of the lung].

Forty seven patients with inoperable adenocarcinoma and large cell carcinoma of the lung were treated with a combination of cisplatin (25 mg/m2), ifosfamide (1.5 g/m2), 5-FU (1.0 g/m2 c.i.) on day 1 through 4. The overall response rate (PR) was 34.8% with 16 partial responses. The median duration of response was 81 days. The median duration to show 50% decrease was 27 days. The median survival time was 359 days for all evaluable patients and 555 days for responders versus 196 days for non-responders. The side effects were mild and tolerable. The response rate of CIF therapy was same as the one reported in recent years but the survival time for responders was long and side effects were mild, suggesting that CIF therapy is an effective chemotherapy.

Adenocarcinoma

[Cisplatin, ifosfamide and vindesine in the chemotherapy of squamous cell carcinoma of the lung].

Thirty-one patients with inoperable squamous cell carcinoma of the lung were treated with a combination of cis-platin (CDDP, 100 mg/m2 day 1), ifosfamide (IFX, 2 g/m2 day 1, 2, 3; with mesna) and vindesine (VDS, 3 mg/m2 day 1). The overall response rate (PR) was 71.0% with 22 partial responses. The median duration of response was 180 days. The median duration to show 50% decrease was 29 days. Myelosuppression and renal toxicity were severe. We concluded that the CIV regimen against squamous cell carcinoma of the lung was more effective yet more toxic than the other regimen containing CDDP and that candidates for this therapy must be carefully chosen.

Antineoplastic Combined Chemotherapy Protocols

PDN-21: possible tumor marker for medullary thyroid carcinoma.

The plasma level of PDN-21 was measured by RIA in 10 patients with medullary thyroid carcinoma (MTC). All 10 patients with MTC had extremely elevated PDN-21 levels. The correlations between PDN-21, calcitonin gene-related peptide, and calcitonin, (all of which are calcitonin gene products) were significant (P less than .001) in the 10 MTC patients. This study suggests that PDN-21, as well as calcitonin, may be a useful marker for the detection of patients with MTC.

Adult

Lymphocyte electrophoresis as an indicator of modulation of concanavalin A-induced suppressor T-cells in vivo by anti-cancer drugs.

We have previously reported that concanavalin A (Con A)-induced suppressor T-cells in vivo are located in the lower electrophoretic mobility (EPM) zone as judged by the ratio of low mobility T-cells to high mobility T-cells (LMT/HMT ratio) in terms of lymphocyte electrophoresis, and that the administration of 5-fluorouracil (5-FU) eliminates their suppressor activity as assayed by Con A-induced lymphocyte blastogenesis in vitro. The current study was undertaken to clarify the relation between changes in EPM and suppressor activity of Con A-induced suppressor T-cells by the administration of antitumor drugs such as cyclophosphamide (CY) and 5-FU when assayed by production of anti-sheep red blood cell antibody in vitro. The pretreatment with 5-FU, but not CY, abrogated the suppressor activity of Con A-induced T-cells followed by restoration of the LMT/HMT ratio of Con A-induced T-cells to that of normal T-cells. These finding suggest that lymphocyte electrophoresis can be applied to an assay for screening immunomodulating agents in Con A-induced suppressor T-cells.

Animals

[A case of hepatocellular carcinoma treated by intrahepatic arterial administration of anticancer agents: serial determination of the concentration of the chemotherapeutic agents in serum and dialysate during hemodialysis].

The concentration of adriamycin (ADR) and mitomycin C (MMC) were measured in serum and dialysate in a patient with hepatocellular carcinoma complicating chronic renal failure. ADR at a dose of 20 mg and MMC at 10 mg were administered through the hepatic artery or peripheral vein during hemodialysis. ADR and MMC became undetectable after 24 hours and 2 hours, respectively. On the other hand, while MMC was detected in dialysate, but ADR was not. Consequently, it was speculated smaller molecular weight of MMC (334.34) than that of ADR (579.99) might be responsible for the appearance of MMC in dialysate. These results suggest that hemodialysis may be effective in reducing side effects of certain anticancer agents. Serum concentration of the anticancer agents injected through hepatic artery was similar to that injected intravenously.

Adult

[Diagnosis of cancer using lymphocyte electrophoresis (3): Electrophoretic mobility, interleukin 1 and prostaglandin E2 productions of monocytes in peripheral blood of cancer patients].

The S/F ratio of slow electrophoretic mobility cells (less than 0.95 micron/sec/V/cm) to fast mobility cells (greater than or equal to 0.95) increased significantly in the peripheral blood mononuclear cells of cancer patients. Since one of slow mobility cells was mainly composed of monocytes, the relationship between the mobility and the functions of monocytes in the peripheral blood of patients with cancer was examined. The cancer patients (total 27) consisted of 12 patients with rectum, 7 with colon, 3 with stomach, one with ovary and 4 with recurrent cancers and of 3 with stage 1, 11 with stage 2, 3 with stage 3 and 6 with stage 4 + 5. We determined the releases of interleukin 1 (IL-1) and prostaglandin E2 (PGE2) from monocytes, which were stimulated with lipopolysaccharide, as an index for the function of monocytes. The mobility of monocytes and productions of IL-1 and PGE2 from monocytes decreased with the stage of cancer patients, indicating a decreased function of monocytes in the patients. These findings suggest that S/F ratio of the peripheral blood mononuclear cells and mobility, IL-1 and PGE2 productions of monocytes are a good index for the judgement of treatment efficacy of cancer.

Colorectal Neoplasms

Establishment and characterization of a small round cell sarcoma cell line, SCCH-196, with t(11;22)(q24;q12).

A cell line designated SCCH-196 was established from an extraskeletal small round cell sarcoma developed in a 16-year-old Japanese girl. The cells grew as a monolayer, and have been continuously propagated by serial subcultures during the past 26 months. Cells from the primary tumor and those from the SCCH-196 cell line at passage 10 both showed the same karyotype, 51,XX, +8, +20, +21, t(11;22)(q24;q12), +i(1q), +i(1q). Histologically the primary tumor was difficult to classify as either Ewing's sarcoma (ES) or peripheral neuroepithelioma (NE). Neuron-specific enolase-positive cells in the primary tumor and the occurrence in the upper extremity were in favor of NE, while positive reaction of SCCH-196 cells to an ES-specific monoclonal antibody 5C11 suggested a diagnosis of ES. The SCCH-196 cell line may be useful for basic studies on differentiation of neuroectodermal tumors, and for future cloning of still unidentified genes which may be located at the breakpoints of the 11;22 translocation.

Adolescent

[Selenium content and glutathione peroxidase activity in the red blood cell in non-pregnant and pregnant women].

The red blood cell (RBC) glutathione peroxidase (GSHPx) activity and selenium (Se) concentration were measured in healthy Japanese pregnant women and in non-pregnant controls. The GSHPx activities in RBC of full-term pregnant women were significantly higher than in non-pregnant women (p less than 0.01). The Se concentrations in RBC of full-term pregnant women were significantly higher than in non-pregnant controls (p less than 0.05). In the whole blood of full-term pregnant women a positive correlation was found between Se concentration and hemoglobin content (p less than 0.05). The Se concentrations in RBC of cord blood were significantly higher than in non-pregnant controls (p less than 0.01). The GSHPx activities in RBC of cord blood were significantly lower than in non-pregnant controls (p less than 0.01).

Erythrocytes

[Molecular-epidemiological and phylogenic analysis of herpes simplex virus type 1 from seven areas in Japan].

Two-hundred and seventy-five epidemiologically unrelated herpes simplex virus type 1 (HVS-1) strains isolated from seven areas (Sapporo, Akita, Nagoya, Kyoto, Tottori, Kagawa and Kurume) in Japan were compared with the standard laboratory strain F, based on cleavage analysis of HSV-1 DNAs with three restriction endonucleases, BamHI, KpnI and SalI. The results obtained were as follows: 1) Using gains and losses of 19 cleavage sites selected from 114 sites, the total of 275 strains could be classified into 87 distinct cleavage patterns. Also, it was found that the isolates were clustered in four predominant patterns, the pattern 27, 6, and 76, containing 62, 24, 15 and 12 strains, respectively. 2) There were highly significant differences in the incidence of isolates classified into the pattern 27 that were obtained in Kagawa as compared with those in Sapporo, Akita, Nagoya and Kurume, and those in Tottori as compared with those in Sapporo, Akita, Nagoya and Kurume. There was also a significant difference in the incidence of isolates classified into the pattern 76 that were obtained in Kagawa as compared with those isolated in Kurume. 3) There were significant correlation coefficients (p less than 0.05) between some stets, e.g. loss of the site between A and A' and gain of a site in A cleaved with BamHI, in every pair of 18 cleavage sites. 4) The phylogenic tree of 87 patterns based on genomic similarities of the Japanese HSV-1 isolates was established, and it was considered that HSV-1 isolates from Japanese could be phylogenetically classified into two to six major groups. These results suggest that HSV-1 strains have mutated and evolved independently by the transmission of the viruses among geographically separated hosts over an extremely long period, and that the genetically characteristic variants have accumulated and persisted in the present Japanese population.

Biological Evolution

[Indications for thoracotomy in pulmonary metastatic sarcoma and its prognosis].

Between 1960 and 1987, 46 patients underwent thoracotomy for pulmonary metastatic sarcoma. The histologic classification of the sarcoma was osteosarcoma in 33 patients, other malignant bone tumors in 6 and soft tissue sarcoma in 7. The cumulative five-year survival rate of the 33 patients with osteosarcoma was 23%. Ten patients survived more than 3 years and 8 of them are still alive without pulmonary metastasis. Prognosis was significantly better with intensive multidrug chemotherapy. In this series, prognosis was not significantly related to the interval from initial onset to initial treatment, that from initial treatment to pulmonary metastasis and that from pulmonary metastasis to initial thoracotomy. The five-year survival rate of the 6 patients with other malignant bone tumors was 35%, and that of the 7 patients with soft tissue sarcoma 26%. Good indications for thoracotomy in pulmonary metastatic osteosarcoma are: (1) the primary sarcoma is resected, (2) the interval from initial treatment to pulmonary metastases is more than 6 months, (3) the number of pulmonary metastases is less than 4 or 5 nodules, and (4) the number and diameter of pulmonary metastases is controlled with chemotherapy within 2 or 3 months after occurrence of metastasis.

Adolescent

Genomic comparison of herpes simplex virus type 1 isolates from Japan, Sweden and Kenya.

One-hundred and seventy-two epidemiologically unrelated herpes simplex virus type 1 (HSV-1) strains isolated in Japan (104 strains) and Sweden (68 strains) were compared by analysis of their genome structures using four restriction endonucleases, BamHI, KpnI, SalI and HindIII. In addition, 32 Kenyan HSV-1 isolates previously compared to Japanese isolates were included for further comparison with the Swedish isolates. Remarkable and statistically significant differences were found between the HSV-1 isolates from the three countries. One-hundred and thirty cleavage sites were examined, and it was shown that isolates from two of the three countries were statistically distinguishable at 27 of these loci. Pairwise comparison between isolates from Japan and Sweden, Kenya and Sweden, and Japan and Kenya revealed variation in 18, 16 and 23 sites, respectively. By considering gains and losses of 19 sites, the total of 204 strains could be classified into 92 distinct cleavage patterns. Isolates from the three countries could be distinguished from each other by the pattern, except for one Swedish and two Kenyan isolates which shared a pattern. Twenty-one fragments that were present or absent only in individual isolates from one or other of the three countries could be detected. These results show that HSV-1 strains from geographically separate countries or anthropologically different races have distinct distributions of endonuclease recognition sites.

DNA Restriction Enzymes

Participation of the dnaK and dnaJ gene products in phosphorylation of glutaminyl-tRNA synthetase and threonyl-tRNA synthetase of Escherichia coli K-12.

The heat shock proteins DnaK and DnaJ of Escherichia coli participate in phosphorylation of both glutaminyl-tRNA synthetase and threonyl-tRNA synthetase. When cellular proteins extracted from the dnaK7(Ts) and dnaJ259(Ts) mutant cells labeled with 32Pi at 42 degrees C were analyzed by two-dimensional gel electrophoresis, no phosphorylation of these proteins was observed when they were compared with those from wild-type cells.

Amino Acyl-tRNA Synthetases

Two outbreaks of herpes simplex virus type 1 nosocomial infection among newborns.

Two outbreaks of herpes simplex virus type 1 (HSV-1) infection occurred in three newborns at each of two hospitals, and two of the infants in each case died of disseminated HSV-1 infection. Restriction endonuclease profiles of HSV-1 DNAs isolated from the three in each instance were essentially identical, indicating that they were epidemiologically related. In the first instance, each of three infants born in the same hospital at intervals of approximately 2 years or 1 year was infected with HSV-1. In this case, it was suggested that periodically reactivated HSV-1 strains from hospital personnel had been transmitted to three newborns. In the second instance (infants G-36, G-37, and G-38), the radiant warmer that had been occupied by infant G-36, who was infected with HSV-1, was used for infant G-37. Infant G-38 was in another radiant warmer 2 m from the radiant warmer occupied by infant G-37. Therefore, it was suggested that the virus had possibly been transmitted via radiant warmer and by hospital personnel in the two instances.

Cross Infection

[Study of cerebral blood flow in patients with cerebral infarction by 133Xe inhalation method--comparison between affected and unaffected hemispheres, and sequential changes].

Cerebral blood flow in both hemispheres was studied by the 133Xe inhalation method in 49 patients with cerebral infarction in the unilateral hemisphere. They were classified into three groups by computed tomographic findings as follows; relatively large low density lesion including the cerebral cortex and subcortex (cortical: C group), relatively large low density lesion including the subcortical white matter and basal ganglia (large subcortical: L group), and small low density lesion including the subcortical white matter (small subcortical: S group), respectively. Mean cerebral blood flow (mCBF) in the affected hemispheres was markedly low in C group, moderately low in L group, and slightly low in S group, in all of the examinations. Several cases in C and L groups revealed remarkable changes of mCBF less than one month after the onset. MCBF in both hemispheres was lower in C group than in L and S groups less than one week after the onset. Seven to twelve weeks after the onset, mCBF in the affected hemisphere was lower in C and L groups than in S group, and than in the unaffected hemisphere of C and L groups. There was no difference between mCBF in the affected hemisphere and that in the unaffected hemisphere in most of S group. Sequential changes of mCBF in both hemispheres were divided into seven types in 27 cases, who were examined first less than one week and repeatedly then. However, the sequential changes were classified roughly into two patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Antihypertensive therapy with a single daily dose of acebutolol in essential hypertension, response and ophthalmological assessment in the Japanese.

Twenty patients with essential hypertension were given 400 mg acebutolol once daily for 24 weeks. In order to study if side effects resembling the "Practolol syndrome" developed, ocular effects were sought and antinuclear antibody (ANA) in blood was assessed before and after treatment. ANA was negative both before and after the study in 17 patients; in one patient ANA was positive, but the titre (1:10) was low and did not change during the study. Acebutolol produced no undesirable effects on cornea, conjunctiva or lens. During acebutolol treatment, tear secretion was reduced but tear lysozyme concentration was not significantly altered. Overall, acebutolol had no undesirable action similar to the practolol-induced syndrome, nor did it cause such common clinical ocular symptoms such as dry or gritty eyes.

Acebutolol