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S Jitsukawa

Publications and source records attributed to S Jitsukawa.

At least 55 records · Page 3Linked to original sources
PubMed1989

cDNA cloning of functional T cell receptor gamma/delta chains expressed in human peripheral blood lymphocytes.

We have identified in earlier studies two V delta rearrangements corresponding to a 4.5-kb Eco RI fragment detected with a V delta1 probe and to a 7-kb Eco RI band detected with a V delta2 probe. These rearrangements have been found in two human T cell clones, F6C7 and G6, displaying surface phenotypes unfrequent in human peripheral blood, namely Ti gamma A+ BB3- (F6C7) and Ti gamma A- BB3+ (G6). Herein, we report the sequences of the functional transcripts encoded by these rearranged genes and show that the 4.5- and the 7-kb Eco RI fragments correspond to V1/D3/J delta 3 and to V2/D3/J delta 3 recombinations, respectively. In addition, we have sequenced the V2/D3/J1/C delta transcripts expressed in two clones, AB12 and VTC, which have a Ti gamma A+ BB3+ surface phenotype corresponding to that of most gamma/delta peripheral lymphocytes. Analyses of the delta transcripts expressed by these four cells further strengthen the hypothesis that anti-BB3 and anti-delta-TCS-1 monoclonal antibodies recognize a V delta 2- and a V1/(D)/J delta 1-encoded epitope, respectively. Sequence of the gamma transcripts expressed by AB12 and F6C7 cells shows that they encode a V9/JP/C gamma 1 chain. Finally, we confirm that non-combinatorial diversity in the gamma and delta proteins is generated by both junctional flexibility and N-region addition without any somatic mutation.

Amino Acid Sequence↗
PubMed1989

Immunologic study of human recombinant interleukin-2 (low-dose) in patients with advanced renal cell carcinoma.

Immunologic and antitumor effects of human recombinant interleukin-2 was studied in patients with advanced renal cell carcinoma. Intravenous drip infusion for inpatients or subsequent subcutaneous injection for outpatients at a daily dose of 1 x 10(6) units of interleukin-2 was given over a period varying from twenty-one to two hundred forty days to 13 patients. Natural killer cell activity increased 20 percent or more in 11 of the 13 patients, and lymphokine-activated killer cell activity increased 40 percent or more in 9 of the patients tested. Interleukin-2-receptor positive cells and HLA-DR positive cells in peripheral blood lymphocytes increased in 12 and 11 patients, respectively. Two patients achieved complete response; 1 had a partial response; 6 had no change; and 2 had progressive disease. Two patients were not evaluated because the therapy had been discontinued in less than four weeks. We conclude that low-dose interleukin-2 enhances patients' immunity and has a potential antitumor activity against renal cell carcinoma.

Adult↗
PubMed1989

[A comparative study of the sensitivity of bladder washing flow cytometry, voided urine cytology and bladder washing cytology in the detection of bladder carcinoma].

In order to evaluate flow cytometric deoxyribonucleic acid measurement (FCM) of bladder washing in the diagnosis of bladder carcinoma, the sensitivity of voided urine cytology, bladder washing cytology and bladder washing FCM was tested in 76 samples from 56 patients with histologically proven bladder carcinomas. The positive rates were 43.2% and 75.7% in bladder washing cytology and bladder washing FCM, respectively. On the other hand, 36.5% and 57.1% positive rates for once- and three-times-voided urine cytology, respectively, were obtained. Bladder washing cytology and bladder washing FCM were positive in 20% and 70% patients with a histological diagnosis of atypia or dysplasia, respectively. The sensitivity of bladder washing FCM according to the tumor grade was 33.3%, 81.9% and 88.9% for grade-1 (G-1), G-2 and G-3 tumors, respectively. The sensitivity of bladder washing cytology according to the tumor grade was 0, 40.9% and 77.8% for G-1, G-2 and G-3 tumors, respectively. The sensitivity of three-times-voided urine cytology was 25.0%, 55.6% and 83.3% for G-1, G-2 and G-3 bladder tumors, respectively, and it was superior to that of single bladder washing cytology. These results indicate that FCM is more sensitive than voided urine cytology and/or bladder washing cytology in patients with bladder carcinoma. FCM may indicate urothelial neoplasia before it is apparent on urine cytology, especially against a background of inflammation. Therefore, FCM is valuable for case finding in suspect populations or for follow-up cases with diagnosed bladder cancer.

DNA, Neoplasm↗
PubMed1989

[Flow cytometric DNA analysis of normal adrenal tissues and adrenal tumors].

Flow cytometric DNA analysis (FCM) of adrenal tumors was studied to evaluate whether FCM will be a useful examination for differentiating between benign and malignant adrenal tumors. 10 specimens of surgically resected (for renal cell carcinoma confined within the middle or lower pole) normal adrenal glands and 20 specimens of surgically resected adrenal tumors were submitted for the study. Hyperplastic adrenal cortex as well as normal adrenal gland showed normal diploid pattern. On the other hand, some of the cortical adenomas showed tetraploid patterns, which has been known to be an index of malignancy in most of the flow cytometric intervention to other solid tumors. Conn adenomas were especially apt to show this tendency, in which as much as 86% showed tetraploid pattern. Proliferation Index (PI) (ratio of S + G2 +M cells for the whole population of analyzed cells) were as much as 9.45 +/- 6.97% in normal adrenal cells, whereas it was much higher in cortical adenomas (17.75 +/- 8.53%). As a matter of fact, PI of hyperplastic adrenal cortex was within the same range as that of the normal adrenal glands. In pheochromocytomas, aneuploid pattern, which has been believed to be a definite index of malignancy, was shown in 60% of the cases, tetraploid pattern in 20%, and normal diploid pattern in only 20%. As a matter of fact, a case of non functioning cortical adenocarcinoma and a case of malignant pheochromocytoma were judged to show typical aneuploid pattern. Thus, the application of the flow cytometric diagnosis for adrenal tumors was supposed to require some refinement in understanding the significance of aneuploidy or tetraploidy.

Adrenal Gland Neoplasms↗
PubMed1989

[Clinical experience with Ureteromat in transurethral ureterorenoscopy].

By September 1988, we performed 58 ureterorenoscopies (52 for primary ureteral calculi, 3 for ureteral biopsy, 2 for ureteral stricture and 1 for ureteral foreign body) using a Ureteromat (Uromat Storz, West Germany). Continuous saline irrigation with the Ureteromat has obviated mechanical dilation of the ureteral orifice in 93.1% of the cases, which made this endoscopy as easy as the conventional cystourethroscopy. In 4 cases (6.9%), however, balloon dilation of the ureteral orifice was necessary for the passage of a rigid ureterorenoscope. Of 52 ureteral calculi, 37 were assigned for transurethral ureterolithotripsy (TUL), whereas transurethral ureterorenoscopy (TUURS) was indicated to flush the remaining 15 calculi up into renal pelvis for later extracorporeal shock wave lithotripsy. TUL was successful in 81.1% (30/37). The causes of failure were stone migration in 6 cases and ureteral avulsion by electrohydraulic lithotripsy necessitating open surgery in 1 case. The irrigation with the Ureteromat facilitated the manipulation of intraluminal ureteral lesions always under clear vision; by-passing the impacted stone with a guide wire and flushing-up of the calculi were successfully performed in 100%, in spite of the co-existing edematous and inflammatory mucosal changes. In 7 cases where ureteroscope could not be advanced well up to the lesion because of spasm in the iliac ureter, the irrigation pressure was transiently increased up to 200 mmHg to allow safe and easy dislodgement of impacted calculi under fluoroscopic guidance. This procedure was also effective to introduced a ureteral stent over a guide wire in 2 cases of ureteral stricture, which could not be achieved by conventional cystoscopic procedure. Immediate postoperative complications were fever in 8.6% and gross hematuria lasting for more than 4 days in 8.6%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

[Studies on biological characteristics of transitional cell carcinoma of the bladder in patients under 30 years of age].

The incidence of transitional cell carcinoma (TCC) of the bladder has been increasing in men with a peak incidence occurring in the sixth decade. However, development of tumors under the age of 30 is relatively rare. In this regard, it has been reported that vesical tumors in the young group is less malignant and rare to recur when compared with those in the elderly group. Recently, flow cytometric DNA histograms (FCM) provides quantitative and objective informations for detection and evaluation of malignant potential of bladder neoplasms. Here we report patients with tumor of the bladder under 30 years old and assess the clinical properties and biological characteristics of their tumors based on FCM. A total of 11 patients from 1975 through 1988 were reviewed. Their mean age at the diagnosis was 22.6 years old (range from 22 to 29 years old). Male/female ratio was 2.7:1. The mean follow-up period was 4 years and 7 months (range from 8 months to over 13 years). An asymptomatic gross hematuria was found in all of the patients, which is the most common sign. Filling defects of the bladder on excretory urograms were observed in six out of the 11 patients (54.5%). Cystoscopically, the size of tumors was less than 2 cm in diameter. Ten patients had a single tumor and one patient had multiple tumors at the time of the initial diagnosis. Endoscopically tumors were papillary in all but one patient, who had a non-papillary tumor. Their urine cytology showed class I in one, class II in eight, class III in one, class IV in one and class V in none.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Comparative study on prophylactic intravesical instillation of bacillus Calmette-Guerin (BCG) and adriamycin for superficial bladder cancers].

In this study we evaluated 77 patients with superficial bladder cancer who were treated with either intravesical bacillus Calmette-Guerin (BCG) (44 patients) or doxorubicin hydrochloride (Adriamycin, ADR) (33 patients) for prophylaxis of tumor recurrence after transurethral resection. The estimated actuarial probability of non-recurrence rate at three years for the BCG group was 73.0%, and the actuarial non-recurrence rate for the ADR group was 27.3%; a statistically significant difference (p = 0.0013). A comparison between the two groups was also made according to the patient's background, including whether the tumor was initial or recurrent, solitary or multiple, and the tumor grade. In all areas of the study, except for grade-1 tumors, the BCG group was significantly superior to the ADR group. The efficacy of BCG therapy as a result of different BCG treatment protocol was evaluated for six weekly instillations 1) without further maintenance instillation, 2) followed by 12 months of maintenance, and 3) followed by more than 18 months of maintenance. Long-term maintenance BCG instillation group (more than 18 months) showed the most favorable results, however, the differences were not statistically significant. These results indicate that intravesical BCG instillation was significantly superior to ADR in the prevention of bladder cancer recurrence and that six weekly intravesical BCG instillations may provide adequate prophylactic effects against recurrence of superficial bladder cancers.

Actuarial Analysis↗
PubMed1989

[Long-term results of M-VAC for the treatment of advanced urothelial cancer].

Total of 37 patients with measurable lesions originating in advanced urothelial cancers received M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) combination chemotherapy and have been followed for a minimum of 12 months. The study included initial diagnoses of 24 bladder cancers and 13 upper urinary tract cancers in patients whose mean age was 62 years. The patients received a mean of three cycles of M-VAC. Clinical complete remission was observed in five of the 37 patients (13.5%) and partial remission was achieved in 10 patients (27.0%) after mean treatment of 2.4 and 2.1 cycles, respectively, for an over-all objective response rate of 40.5%. The mean duration of response was 11.6 +/- 7.1 months and 4.4 +/- 3.5 months for complete and partial remissions, respectively. A mean of 5.2 +/- 1.7 cycles of M-VAC was given for complete remissions and 3.5 +/- 1.4 cycles in partial remissions. An over-all survival rates after one and two years were 28.125% and 5.859%, respectively. Two of the five patients who had once marked complete remissions died after a mean survival time of 14.5 +/- 4.5 months and three survived with a mean duration of 20.3 +/- 5.4 months. Meanwhile, all of the patients who had achieved partial remissions died after a mean survival of 9.1 +/- 5.4 months except for one patient who survived more than 12 months. These results indicate that M-VAC combination chemotherapy for advanced urothelial cancer is extremely efficacious in initial responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Characterization of human peripheral lymphocytes expressing the CD3-gamma/delta complex with anti-receptor monoclonal antibodies.

Three mAb, anti-Ti gamma A, anti-TCR delta 1, and anti-delta TCS1, have been developed against the CD3-associated gamma/delta molecular complex. One of this antibody anti-Ti gamma A is specific for an epitope encoded by the V9 gamma-gene. The two others react with the delta-chain but their fine epitopic specificity has not been characterized previously. In the present study, we have compared the surface expression of these three antigenic determinants on 27 cloned and 5 polyclonal CD3+ TCR gamma/delta + cell lines derived from human peripheral blood of 13 distinct individuals. It was found that all CD3+ TCR alpha/beta- clones and polyclonal cell lines tested were recognized by anti-TCR delta 1. In contrast, only a fraction of both clones and cell lines reacted with either anti-Ti gamma A or anti-delta TCS1 mAb. In fact reactivity of the latter reagents was found to be mutually exclusive on the cell panel. Northern blot analysis of RNA extracted from a series representative clones showed a positive correlation between the surface expression of the delta TCS1 epitope and the transcription of the V-delta gene isolated from the IDP2 cell line. These data support the view that anti-TCR delta 1 can be used to positively define the entire TCR gamma/delta+ fraction. Moreover, the reciprocal reactivity of anti-delta TCS1 and anti-Ti gamma A on cultured cell lines suggests that these reagents should delineate in human peripheral blood distinct, essentially non-overlapping, subsets. Taken together, the present results indicate that the complementary use of these three antibodies will be helpful to further characterize the TCR gamma/delta + peripheral lymphocyte fraction.

Adult↗
PubMed1988

Identification of a CD2- CD3+ T cell receptor-gamma+ peripheral blood lymphocyte subpopulation.

We have identified, in a healthy individual, a sub-population of human peripheral lymphocytes which surface express a CD3-TCR-gamma complex recognized by anti-Ti gamma A mAb, while being unreactive with a phycoerythrin-conjugated anti-CD2 antibody with T11/1 specificity. Further immunofluorescence analyses performed on uncultured cells indicated that such a putative CD2-CD3+ phenotype was restricted to a fraction of those T lymphocytes which carry a surface receptor of the "second family" (gamma/delta). The actual lack of CD2 expression was confirmed by a subsequent series of cloning experiments which showed that none of the three well characterized CD2 epitopic clusters, namely T11/1, T11/2, and T11/3, were detectable on the surface of the relevant cells. The cultured CD2-, CD3+/TCR gamma + lymphocytes were found to display, as well as their CD2+ counterparts, both non-MHC-restricted cytotoxic function and proliferative responses induced via the gamma receptor complex. In contrast, the proliferative capacity of the CD2-, CD3+/TCR-gamma + cells observed in a culture system designed for in vitro expansion of lymphocytes with undefined specificity was extremely limited. This may relate to an impaired interaction of the CD2- cloned lymphocytes with lymphocyte function-associated (LFA)3+ irradiated cells present in the feeder layer. Further characterization of such minor CD2- T lymphocytes subsets may help to better understand the biologic relevance of the CD2/LFA3 pathway of cell-cell interaction.

Adult↗
PubMed1988

CD3/Ti gamma A: a functional gamma-receptor complex expressed on human peripheral lymphocytes.

We have recently developed a mAb designated anti-Ti gamma A, which was found to immunoprecipitate from the well characterized CD3+ TCR alpha/beta- F6C7 fetal clone a CD3-associated disulfide-linked gamma-glycoprotein. This antibody recognizes approximately 3% of adult peripheral lymphocytes and delineates a CD2+ CD3+ TCR alpha/beta- CD4- NKH1- subset where expression of CD8 appears to vary widely from one individual to another. In the present study, we have used anti-Ti gamma A mAb to assess whether gamma-chains expressed on these adult lymphocytes are used as functional R. The two activities which have been associated thus far with TCR gamma+ cells, that is, IL-2-dependent proliferation and non-MHC-restricted cytotoxicity, were investigated here by using either resting or activated Ti gamma A+ lymphocytes. On the resting state, these cells (which appear as a very homogeneous population of granular lymphocytes) mediate little if any NK activity that could not be augmented by anti-Ti gamma A mAb. In contrast, after initial stimulation by PHA plus rIL-2 and subsequent culture in the presence of IL-2, activated Ti gamma A+ lymphocytes were strongly lytic against a series of conventional NK target cell lines. This cytotoxic function was either blocked or enhanced by anti-Ti gamma A mAb, depending upon experimental conditions. With respect to proliferation, it was possible to induce responses of resting Ti gamma A+ lymphocytes with antibody-coated CNBr beads only in the presence of exogenous IL-2, whereas, in culture, the same cells proliferated directly and secreted IL-2 after treatment by anti-Ti gamma A beads. Taken together, these data demonstrate that a major subset of circulating CD3+ TCR alpha/beta- lymphocytes use protein products of T cell gamma rearranging genes as functional R structures.

Animals↗
PubMed1988

A unique V-J-C-rearranged gene encodes a gamma protein expressed on the majority of CD3+ T cell receptor-alpha/beta- circulating lymphocytes.

We have recently described an mAb, anti-Ti gamma A, that recognizes an antigenic determinant carried by a TCR gamma chain. This antibody binds to approximately 3% of human PBLs and delineates a CD2+, CD3+, TCR-alpha/beta-, CD4-, CD8+/-, CD5+, NKH1-, and HLA class II- subset. The present study was designed to identify the gene encoding the Ti gamma A epitope. A first analysis was carried out on a previously characterized TCR gamma + fetal-cloned cell line termed F6C7. It was found that F6C7 cells have one gamma rearrangement on each chromosome: one joins V gamma 3 to J gamma 1, and the second joins V gamma 9 to J gamma P. Because only the latter allele appeared to be transcribed in the F6C7 lymphocytes, these data strongly suggested that anti-Ti gamma A mAb is specific for either a V gamma 9 or a V gamma 9-J gamma P-encoded peptide. To confirm this point, we studied an additional series of 13 randomly selected Ti gamma A+ cloned cells derived from peripheral blood of three distinct adult individuals. Each one of these lymphocytes was shown to both possess and transcribe a V gamma 9-J gamma P-C gamma 1-rearranged gene. It is therefore concluded that a predominant subpopulation of CD3+ TCR-alpha/beta- human circulating T lymphocytes (namely, the subset defined by anti-Ti gamma A mAb) surface expresses a gamma protein with a limited potential of variability from one cell to another.

Adult↗
PubMed1988

Cloned CD3+ TcR alpha/beta- Ti gamma A- peripheral blood lymphocytes compared to the Ti gamma A+ counterparts: structural differences of the gamma/delta receptor and functional heterogeneity.

We have assessed the organization of T cell gamma rearranging genes (TRG) in circulating TcR gamma/delta+ lymphocytes which do not express V gamma 9-encoded Ti gamma A+ gamma chain. Following purification of the minor TcR gamma/delta+ Ti gamma A- fraction, cloned cell lines were developed from peripheral blood of 5 individuals. Out of the 26 clones studied, only 3 TcR gamma/delta+ Ti gamma A- cells were found to express a disulfide-linked C1-encoded gamma chain. The remaining 23 Ti gamma A- clones with a C2-encoded nondisulfide-linked receptor were found to display rearrangements of various V genes to J2 segments on both chromosomes; there was no predominance of a unique rearrangement even though the TRG-V3 and -V4 genes belonging to subgroup I were frequently employed. Together, these findings further strengthen the hypothesis that lymphocytes with a C gamma 1 encoded chain are produced earlier in T cell ontogeny than the C gamma 2 counterparts. The "non-major histocompatibility complex (MHC) requiring" (i.e., "natural killer-like") cytotoxicity mediated by many TcR gamma/delta+ Ti gamma A- cells appeared to be very low as compared to that of Ti gamma A+ clones. Yet, treatment by the OKT3 monoclonal antibody revealed a strong lytic potential in the Ti gamma A- lymphocytes with little, if any, natural killer-like activity. Thus, with respect to the latter function, a substantial heterogeneity is found in cells expressing distinct gamma chains. In an attempt to characterize undefined specificities of Ti gamma A- lymphocytes, they were screened against a panel of Epstein-Barr virus-transformed B cell lines homozygous for HLA-DR1 to DR10 determinants; one of the clones was found to recognize DR7. In light of reports from other groups describing class I-related specificities, it is apparent that TcR gamma/delta+ lymphocytes are able, like the TcR alpha/beta+, to recognize and kill target cells through either an MHC-dependent (with involvement of either class I or class II gene products) or a non-MHC-requiring pathway.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

A novel human V delta gene expressed predominantly in the Ti gamma A fraction of gamma/delta+ peripheral lymphocytes.

We have characterized a functional T cell receptor (TcR) delta transcript in a Ti gamma A+ human cloned cell line derived from peripheral blood. This cDNA includes a novel V gene (V-AB12), whose expression was initially studied in a series of TcR gamma/delta+ clones. Nine Ti gamma A+ clones derived independently from distinct donors have been tested: each of them was found to possess a unique V-AB12/J-IDP2 5.5-kb Eco RI rearrangement, which was constantly transcribed. Surface expression of the protein encoded by this unique rearranged gene was demonstrated by immunoprecipitations performed on three Ti gamma A+ polyclonal cell lines using a specific rabbit heteroantiserum. Further analysis strongly suggested that a monoclonal antibody (mAb), designated anti-BB3, detects a V-AB12-encoded antigenic determinant on the cell surface. Double-color immunofluorescence analysis of peripheral blood lymphocytes from ten donors indicated that most BB3+ cells are recognized by anti-Ti gamma A mAb. In previous studies, we have shown that a majority of TcR gamma/delta+ peripheral T cells expresses a gamma chain including V9 (Ti gamma A) and most frequently JP-encoded peptides. Given the present results on the delta chain, it can be concluded that, in many individuals, a predominant fraction (V gamma 9+/V-AB12+) of circulating CD3+ TcR alpha/beta- T lymphocytes expresses a receptor with little, if any, combinatorial diversity.

Amino Acid Sequence↗
PubMed1987

A novel subset of human lymphocytes with a T cell receptor-gamma complex.

We have previously characterized a CD3+ T cell receptor (TCR) alpha/beta- human fetal cloned cell line, termed F6C7, which surface-expresses a CD3-associated gamma chain identified by anti-NKFi, an mAb with a restricted clonotypic reactivity. Here, we have produced an additional antibody, anti-Ti-gamma A, which recognizes a public epitope of the gamma molecule defined by anti-NKFi. Ti-gamma A is present on approximately 3% of circulating lymphocytes with a wide range (1-15%) among 30 healthy individuals tested. Two-color immunofluorescence experiments performed with anti-Ti-gamma A and BMA 031 mAb (a reagent specific for the TCR-alpha/beta receptor) showed that surface expression of Ti-alpha/beta and Ti-gamma A is mutually exclusive. Moreover, it was found that most Ti-gamma A+ cells are CD2+, CD3+, CD4-, CD5+, NKH1-, HLA class II-negative. In contrast, the expression of the CD8 molecule on these T lymphocytes appears to be variable from one individual to another. Finally, we found that Ti-gamma A+ cells represent a majority of peripheral lymphocytes that express CD3 proteins but not the TCR-alpha/beta heterodimer. The delineation of this unique lymphocyte subset should help further studies on the biology of cells with a CD3-associated gamma complex.

Animals↗