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Biomedical subjects

Y Kusunoki

Publications and source records attributed to Y Kusunoki.

At least 109 records · Page 6Linked to original sources
PubMed1991

Urinary excretion of terminal complement complexes in glomerular disease.

To evaluate renal terminal complement activation in patients with glomerular diseases, we measured terminal complement complexes (TCCs) in plasma and urine with sandwich enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody against a C9 neoepitope expressed on TCC and a polyclonal antihuman C7 antibody. TCCs were detectable in plasma but not in urine in most of normal controls. In plasma, TCC levels were elevated in 4 of 22 patients with lupus nephritis and in 6 of 12 with membranoproliferative glomerulonephritis. However all patients with IgA nephritis, focal glomerulosclerosis, idiopathic membranous nephritis and idiopathic minimal change nephrotic syndrome (MC) showed normal values. In urine, TCCs were detectable in almost all patients with heavy proteinuria (greater than or equal to 100 mg/ml) except MC. The TCCs present in urine were partially purified by gel filtration using Sepharose 6B and were found to contain C5, C6, C7, C8, C9 and S protein by ELISA. Although the molecular weight of TCC is similar to that of IgM, the fractional excretion rate of TCC was about 100 times higher than that of IgM. These results suggest that TCCs detectable in urine contain SC5b-9 complexes and are mostly of renal origin.

Adolescent↗
PubMed1991

Somatic cell mutations in atomic bomb survivors.

Mutant frequencies in peripheral blood lymphocytes and erythrocytes have been measured for atomic bomb survivors having various DS86 doses. Among the four assay systems utilized so far, erythrocyte glycophorin A assay revealed a dose related increase of mutant frequency, similar to the results obtained with in vitro mutagenesis studies at HPRT locus using human diploid cells. Mutant T-lymphocyte frequency of the HPRT locus detected as resistant to 6-thioguanine significantly increased with DS86 dose however the slope was very shallow compared with that of in vitro study. Mutation at T-cell receptor genes and the HLA-A gene did not show a significant increase in frequency with dose in cells of survivors studied.

Humans↗
PubMed1991

Overview of immunological studies on A-bomb survivors.

Among the peripheral blood lymphocytes, T-cells and B-cells significantly decreased in number with age. Radiation exposure resulted in further significant decrease of T-cell count (but not B cells) in the elderly. T-cell response to PHA and allo-antigens also decreased with dose in the elderly group. In contrast, NK cell number and function increased with age while a significant dose effect was not observed.

Aging↗
PubMed1991

A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Current summary of lymphocyte survival study.

A recently developed dose-survival assay in vitro using human G0 T-lymphocytes from peripheral blood was employed to assess possible interindividual variation of cellular radiosensitivity. Currently lymphocytes from a total of 99 atomic bomb survivors were tested and D10, the X-ray dose required to kill 90% of the cells, was calculated for each test. The mean +/- SD of D10 value was 3.35 +/- 0.22 Gy for 61 survivors whose DS86 dose is below 0.004 Gy and for 38 survivors of DS86 dose above 1.5 Gy it was 3.31 +/- 0.26 Gy. So far, the results do not show any evidence in support of the hypothesis of a selective elimination of a radiosensitive subcohort among the survivors exposed to high doses.

Cell Survival↗
PubMed1991

Establishment and characterization of 20 human non-small cell lung cancer cell lines in a serum-free defined medium (ACL-4).

To facilitate the studies in cell biology and drug sensitivity of non-small cell lung cancer, cell samples from 55 patients have been used to establish cell lines in culture using a chemically defined medium (ACL-4). A total of 20 cell lines (36 percent) were directly established and characterized: 14 (44 percent) from pleural effusions, five (29 percent) from resected primary tumors, and one (25 percent) from ascitic fluids. They comprised 16 adenocarcinoma, two large cell carcinoma, one squamous cell carcinoma, and one malignant mesothelioma. Each cell line had distinct gross morphologic features and population doubling times from 21 to 75 h. The plating efficiency was 0.01 to 9.51 percent. The modal chromosome number varied from 45 to 108. Secretion of tumor markers (carcinoembryonic antigen, sialyl Lewis Xi, CA 50, CA 125, and CA 19-9) into the medium was also different in each cell line. Most of the cell lines have been xenografted into nude mice and found to be tumorigenic. Survival of 20 patients whose tumor cell specimens continually grew in culture at any time during their clinical course was significantly shorter than that of 35 patients with no in vitro tumour growth (median survival time of 28 weeks vs 53 weeks, p = 0.0093). Our study indicates that in vitro tumor cell growth appears to be an adverse prognostic factor in patients with non-small cell lung cancer.

Adult↗
PubMed1991

[The significance of CA-50, SLX and ST-439 in lung cancer].

Serum levels of CA-50, SLX and ST-439 were measured in 213 patients with lung cancer (92 adenocarcinomas, 63 squamous cell carcinomas, 37 small cell carcinomas and 21 large cell carcinomas) and 87 patients with benign lung disease. The overall positive rates in patients with lung cancer were 12.8% for CA-50, 29.7% for SLX and 25.3% for ST-439. The positive rates for CA-50, SLX and ST-439 in adenocarcinoma patients were 22.8%, 42.4% and 38.0%, respectively. Of the patients with benign lung disease, 4.8% were false positive for CA-50, 15.3% for SLX and 3.6% for ST-439. In the patients with adenocarcinoma of the lung, the combination assay of CEA and ST-439 had a highly accurate rate (61.9%).

Adenocarcinoma↗
PubMed1991

A randomized trial comparing imipenem/cilastatine alone with latamoxef plus tobramycin in febrile neutropenic patients with lung cancer.

We conducted a randomized trial to compare the efficacy of imipenem/cilastatine (IPM/CS) monotherapy with that of a combination of latamoxef (LMOX) and tobramycin (TOB) in the initial management of fever and neutropenia in patients with lung cancer. Leukocytopenic febrile patients (less than 3,000 leukocytes per microliters; temperature greater than 38 degrees C) with lung cancer given induction therapy were randomly assigned to receive intravenous treatment with either 1 g IPM/CS twice daily or 2 g LMOX plus 90 mg TOB twice daily. A total 101 febrile episodes were studied. Fifty-one episodes were treated with IPM/CS and 50 with LMOX+TOB. Fifty-nine of the febrile episodes were bacteriologically confirmed, while an organism could not be isolated despite the presence of obvious clinical infection in the remaining 42. The response rate was 82% with IPM/CS and 80% with combination therapy. This difference was not statistically significant. The response rate regarding gram-negative infections was 10 out of 14 (71%) in the IPM/CS group and seven out of 12 (58%) in the LMOX+TOB group. This difference was also not significant (P = 0.484). The response rate in severely neutropenic patients (neutrophils less than 100/microliters) was low (P = 0.078). Three patients in the IPM/CS group were withdrawn from the study due to skin rash and vomiting. Therapy with IPM/CS monotherapy was as effective as a combination regimen.

Adult↗
PubMed1991

[Exacerbation of partial seizures in a case with heterotopic gray matter using antiepileptic drugs].

A two-year-old, right-handed girl was admitted to our hospital with a history of partial seizures. The first seizure, conjugated eye movements and head turning to the right, occurred at the age of 24 months. Later, she suffered from several seizures daily at the age of 34 months. At the age of 35 months, she was admitted to our hospital. On admission her neurological examination was normal. EEG showed a left parietal spike focus. A computed tomographic scan showed a small hyperdense area in the left parietal lobe without contrast enhancement. She was treated with carbamazepine (CBZ : 6 mg/kg/day). When seizures occurred several times within an hour, intravenous or rectal administration of diazepam (DZP : 0.3 mg/kg/dose) was added. However, she complained of sleepiness. The seizures occurred more frequently than before, 50 to 80 times daily, and became secondarily generalized. We thought that the exacerbation of the seizures resulted from the somnolence caused by DZP and CBZ. Consequently, these drugs were discontinued, and phenytoin was begun. She has since been free of seizures for two years. Approximately one year after the discontinuance of DZP and CBZ, heterotopic gray matter and abnormal gyri involving the left parieto-temporal lobe were found by magnetic resonance imaging (MRI). MRI is useful for detecting small heterotopic gray matter. To summarize this case, one should consider the possibility that excessive polytherapy induces seizures, particularly in patients with structural brain abnormalities such as heterotopic gray matter.

Brain↗
PubMed1991

[A case of pulmonary aspergillosis with a tumor shadow, diagnosed by transbronchial aspiration cytology].

A 41-year-old female was admitted because of cough and hemosputum. She had no underlying disease and the presence of respiratory disease had not been pointed out. Chest X-ray and CT scan showed a solid, homogeneous tumor with a distinct margin near the right hilum. The tumor measured approximately 5 x 4 cm. Because other laboratory data concerning the serum levels of tumor marker and anti-aspergillus antibody were normal, benign lung tumor or malignant lymphoma was suspected at first. Transbronchial cytology and biopsy were performed, but there were no significant findings. However transbronchial aspiration cytology of the specimen obtained from the bifurcation between the right upper lobe bronchus and the truncus intermedius demonstrated Aspergillus. After the administration of antifungal drugs, the tumor decreased in size, and an air crescent sign appeared. This was thought to be a very rare case of locally invasive form of pulmonary aspergillosis, as described by Sider et al demonstrating a necrotic fungal ball during its clinical course.

Adult↗
PubMed1991

[High-dose Tegafur (FT) for primary lung cancer: a phase I trial].

A phase I clinical study of intravenous Tegafur was conducted in nineteen previously treated patients with primary lung cancer. The dose of Tegafur was elevated from 1.0 to 3.0 g/m2/day for five consecutive days to determine the maximum tolerated dose. The dose-limiting factors were gastrointestinal and neurological toxicity and fatigability observed with the dose level of 2.5 g/m2/day for 5 days. Hematologic, hepatic and renal toxicities were not observed. Gastrointestinal toxicity including nausea, vomiting, anorexia and diarrhea of over grade 2 were seen to result from the dose of 2.5 g/m2/day. Neurological toxicity consisted of headache, dizziness, anxiety and depression. At the dose level of 2.0 g/m2/day, one patient, who had epileptic seizures in the past, experienced a psychomotor seizure. Depression (Grade 2 CNS toxicity) was observed at the dose level of 3.0 g/m2/day. Dose limiting factors were neurological toxicities. The pharmacokinetics of tegafur and 5-FU (the active form of Tegafur) has been studied in all patients. Serum level of tegafur was measured by HPLC method, and serum level of 5-FU was analyzed by GC-MS method. At the dose level greater than 2.0 g/m2/day for 5 days, the mean serum 5-FU values appear over the therapeutic range (0.1 micrograms/ml). In conclusion, 2.5 g/m2/day for 5 days was considered to be MTD, and 2.0 g/m2/day for 5 days intravenous administration was recommended for the phase II trial of single agent chemotherapy.

Drug Administration Schedule↗
PubMed1990

Spontaneous loss and alteration of antigen receptor expression in mature CD4+ T cells.

The TCR/CD3 complex plays a central role in antigen recognition and activation of mature T cells, and, therefore, abnormalities in the expression of the complex should induce unresponsiveness of T cells to antigen stimulus. Using flow cytometry, we detected and enumerated variant cells with loss or alteration of the surface TCR/CD3 expression among human mature CD4+ T cells. The presence of variant CD4+ T cells was demonstrated by isolating and cloning them from peripheral blood, and their abnormalities can be accounted for by alterations in TCR expression such as defects of protein expression and partial protein deletion. The variant frequency in peripheral blood increased with aging in normal donors and was highly elevated in patients with ataxia telangiectasia, an autosomal recessive inherited disease with defective DNA repair and variable T cell immunodeficiency. These findings suggest that such alterations in TCR expression are induced by somatic mutagenesis of TCR genes and can be important factors related to age-dependent and genetic disease-associated T cell dysfunction.

Adult↗
PubMed1990

Combination chemotherapy with or without radiation therapy in small cell lung cancer. An analysis of a 5-year follow-up.

From January 1978 to March 1984, a series of 159 patients with newly diagnosed small cell lung cancer (SCLC) was treated with combination chemotherapy with or without chest radiation at the Osaka Prefectural Habikino Hospital. By March 31, 1989, ten patients (6.3%) had survived for 5 years or more after the initial chemotherapy, including nine of 95 patients (9.5%) with limited disease and one of 64 patients (1.6%) with extensive disease. All these 5-year disease-free survivors, except for one patient whose response could not be assessed by chest radiograph because of radiation fibrosis, had a complete response. Nine of the 71 patients (12.7%) treated with combination regimens containing doxorubicin survived 5 years or more, and only one of the 88 (1.1%) treated with regimens without doxorubicin had long-term survival (P less than 0.01). The sex, performance status (PS), and chest radiation after systemic chemotherapy did not correlate statistically with long-term survival (P greater than 0.05). Three of the ten patients died free of SCLC. Two of the ten patients (20%) developed second malignancies and died. The remaining patient died of pneumonia. The Cox regression analysis identified the PS and doxorubicin-containing regimens as important factors indicating improved survival. Combination regimens containing doxorubicin have, therefore, been found to be very effective in improving survival and achieving long-term survival.

Adult↗
PubMed1990

Isolation and characterization of VP-16 resistant human leukemia cell line.

VP-16 resistant cells, designated VP-16K6-1 (K6-1) were isolated from human acute lymphoblastic leukemia cell line RPMI 8402. IC50 value against VP-16 were 11-fold higher than their sensitive parental cell line. The membrane permeability of the drug was not responsible for resistance in K6-1 cells. K6-1 cells showed resistance in drug-induced DNA strand breaks (single strand breaks) determined by the alkaline sucrose gradient sedimentation method. Dot-blot analysis of RNA extracted from 2 cell lines showed that the mRNA levels of DNA topoisomerase II in K6-1 cells decreased slightly compared with that of parent cells. However, Topo II activities were similar in wild-type and K6-1 cells. In addition, K6-1 cells exhibited cross-resistance only to VM-26. These data suggest that a reduced intracellular Topo II level may contribute to drug resistance as an important factor in K6-1 cells.

DNA Replication↗
PubMed1990

Aggressive natural killer cell leukaemia/lymphoma: report of four cases and review of the literature. Possible existence of a new clinical entity originating from the third lineage of lymphoid cells.

The morphologic, immunologic, genotypic and functional properties of peripheral blood and bone marrow cells or cultured cells from four patients with a clinically aggressive non-T, non-B natural killer cell leukaemia/lymphoma (ANKL/L) are described. The leukaemic cells possessed medium to large granules in the cytoplasm, antigens against CD38, CD2, OKIa 1 and NKH-1 CD56) monoclonal antibodies on their cell-surface, and also showed natural killer (NK) activity. In addition, these ANKL/L belonged to neither T- nor B-cell lineage, proved by studying clonal gene rearrangement for the T beta, T gamma and T delta receptors, and immunoglobulin. After comparing them with the seven cases of ANKL/L reported in other institutions, with regard to immunophenotype, genotype and function, we conclude that ANKL/L originating from a third lineage of lymphoid cells is a distinct clinical entity.

Adolescent↗
PubMed1990

Using polymerized C9 to produce a monoclonal antibody against a neoantigen of the human terminal complement complex.

The terminal complement complex (TCC), consisting of C5b, C6, C7, C8, and C9, contains neoantigens that are absent from the individual native components. Neoantigens are present both in the membrane-bound (MAC) and the fluid-phase (SC5b-9) complex. The present study describes production of monoclonal antibodies (MoAbs) against neoantigens of both forms of the TCC using human C9 polymerized in Zn2+ as an immunogen. One of ten MoAbs obtained, MoAb 1B4, reacted with the tubular C9 polymer, but not with either the native or sodium dodecyl sulfate-denatured monomeric C9, as shown by enzyme-linked immunosorbent assay and Western blotting. Moreover, MoAb 1B4 cross-reacted both with MAC and SC5b-9. This suggests MoAb 1B4 recognized a neoantigen in the moiety of C9 polymer in the TCC. MoAb 1B4 will be of value for definitive identification of MAC and for quantitation of SC5b-9 in plasma and urine.

Antibodies, Monoclonal↗