Biomedical subjects

S Jitsukawa

Publications and source records attributed to S Jitsukawa.

At least 37 records · Page 2Linked to original sources

PubMed1991

TCT.1, a target molecule for gamma/delta T cells, is encoded by an immunoglobulin superfamily gene (Blast-1) located in the CD1 region of human chromosome 1.

We have recently generated a series of gamma/delta T cell clones able to kill, after in vitro immunization, an Epstein-Barr Virus-transformed B cell line (designated E418) in a non-major histocompatibility complex-requiring fashion. A monoclonal antibody, termed anti-10H3, produced against E418 was selected by its ability to block these cytotoxic interactions. Further analysis indicated that the inhibitory effects of anti-10H3 were highly selective (i.e., no blocking activity with multiple control clones used as effector cells; no alteration of the natural killer-like function mediated by the relevant gamma/delta clones against 10H3+ tumor cells such as Rex). The molecule immunoprecipitated by anti-10H3, termed TCT.1, was characterized as a 43-kD protein broadly distributed in the hematopoietic system. The TCT.1 molecule has been further studied here by protein microsequencing. Results show that the TCT.1-derived peptide sequences are virtually identical to corresponding regions of Blast-1, a previously described surface protein with unknown function. The likely identity of the two molecules has been strengthened by analyzing the susceptibility of TCT.1 to phosphatidylinositol-specific phospholipase C digestion in light of the known anchorage of Blast-1 to the cell membrane through a glycosyl-phosphatidylinositol-containing lipid. The TCT.1/Blast-1-encoding gene is well characterized; it belongs to the immunoglobulin gene superfamily and it is located in the same band of chromosome 1 as the CD1 gene cluster. Together, these data further support the view that proteins distinct from the conventional class I/II histocompatibility molecules are involved in specific T cell recognition.

Amino Acid Sequence↗

PubMed1991

SCID mice: a suitable model for experimental studies of urologic malignancies.

In vivo studies on human malignant tumors are limited because of a lack of suitable animal models. In this study, the usefulness of SCID (severe combined immunodeficiency) mice, deficient in functions of both T- and B-lymphocytes, was evaluated. Inbred SCID mice were kept in isolated cages and 2 x 10(7) cells of KU-7, an established bladder carcinoma cell line, were inoculated in the subcutaneous tissue of the flank region of six SCID mice. Athymic nude mice were inoculated by the same method and served as the controls. The KU-7 cells were taken within 14 days in the injected region in all six SCID mice, while in only five out of eight nude mice. Tumors subsequently formed at the site of inoculation in these mice were confirmed to be transitional cell carcinomas histologically and intra-abdominal metastases were noted in two SCID mice. We conclude that SCID mice provide an ideal in vivo model for experimental studies of human urologic malignant tumors.

Abdominal Neoplasms↗

PubMed1991

Multivariate analysis of flow cytometric deoxyribonucleic acid parameters and histological features for prognosis of bladder cancer patients.

We studied whether flow cytometry provides significant prognosticators beyond the classical histological evaluation in the patient with bladder cancer. A total of 203 patients with untreated bladder cancer was evaluated using fresh bladder tumor specimens. Tumor grading and stage were the histological prognostic parameters. Deoxyribonucleic acid (DNA) index, percentage S-phase cells, percentage G2/M-phase cells and hypertetraploid cell presence were assessed as flow cytometric prognostic parameters. Multivariate survival analysis was performed using Cox's proportional regression model to study statistical individual prognostic values of histological and flow cytometric parameters. Hypertetraploid cell presence was the single most important prognostic factor (p less than 0.01), with tumor grade being nearly as important (p less than 0.01), followed by tetraploidy (p less than 0.01) and tumor stage (p less than 0.05). No other parameters, including the DNA index or cell phase fractions, contributed to the model. These results indicated that combined use of histological and flow cytometric parameters may provide additional information regarding the clinical outcome for bladder cancer patients.

Adult↗

PubMed1991

Quantification of cell kinetic characteristics using flow cytometric measurements of deoxyribonucleic acid and bromodeoxyuridine for bladder cancer.

A total of 56 human bladder tumors that were histologically proved to be transitional cell carcinoma was analyzed by simultaneous flow cytometric 2-color measurements of deoxyribonucleic acid (DNA) and bromodeoxyuridine. Bromodeoxyuridine in vitro labeling was performed by sample incubation with bromodeoxyuridine under high atmospheric pressure oxygen. Grade 1 tumors showed 33.3% aneuploidy with a mean bromodeoxyuridine positive stained ratio (labeling index) of 5.1 +/- 3.4%. Grade 2 tumors featured 51.7% aneuploidy with a mean labeling index of 8.9 +/- 7.7%. On the other hand, a markedly increased labeling index of 15.2 +/- 8.2% with aneuploidy was observed in all but 1 grade 3 tumors. When DNA ploidy and labeling indexes were compared according to the presence or absence of muscular invasion of tumors, all 16 muscle invasive tumors showed aneuploidy (mean labeling index 18.7 +/- 8.0%), while 17 of 40 nonmuscle invasive tumors showed aneuploidy (mean labeling index 8.6 +/- 5.4%). This labeling index difference was statistically significant (p less than 0.01). These results indicate that bromodeoxyuridine/DNA 2-color flow cytometry may provide an objective parameter for quantification of the malignant potential of bladder cancers.

Aneuploidy↗

PubMed1991

Efficacy of gadolinium-diethylenetriaminepentaacetic acid-enhanced magnetic resonance imaging for differentiation between superficial and muscle-invasive tumor of the bladder: a comparative study with computerized tomography and transurethral ultrasonography.

Gadolinium-labeled diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) was evaluated in an effort to clarify whether MRI could replace or be proved to be superior to computerized tomography (CT) and/or transurethral ultrasonography. A total of 57 bladder cancer patients was evaluated. MRI was performed with a superconducting magnet operating at 1.5 Tesla. The images acquired were multisections, having a fast spin-echo pulse sequence of less than a 14-second breath holding. Serial scans were performed before and immediately after Gd-DTPA venous injection. The findings on different imaging techniques were compared with the histological stagings. A proper diagnosis was made in 42 of 57 cases (73.7%) by Gd-DTPA-enhanced MRI, in 27 of 57 (47.4%) by CT and in 31 of 57 (54.4%) by transurethral ultrasonography when comparing the histological findings. The sensitivity and specificity for differentiating superficial and muscle-invasive tumor of each imaging method were, respectively, 96.2 and 83.3% in Gd-DTPA-enhanced MRI, 96.0 and 58.3% in CT, and 88.0 and 66.7% in transurethral ultrasonography. These data suggest that the staging of bladder cancer by Gd-DTPA-enhanced MRI appears to be superior and more accurate than the staging obtained by CT and transurethral ultrasonography.

Adult↗

PubMed1991

Antitumor effects of interleukin 2 against renal cell carcinoma: basic study and clinical application.

In order to determine an optimum mode for systemic administration of recombinant interleukin 2 (rIL2), the effects of rIL2 on lymphocyte-mediated cytotoxicity against renal carcinoma cells were studied in vitro. Augmentation of the cytotoxicity by rIL2 was dose- and time-dependent. The optimum dose of rIL2 was 100-500 units (Jurkat units)/ml, and cytotoxicity increased significantly even at a low concentration such as 4 units/ml. We thus chose daily administration of multiple repeated dose for inpatients. To prevent withdrawal from the therapy as a result of untolerable adverse effects, the daily dose was set at 1 X 10(6) units, and rIL2 was given to 12 patients with metastatic renal cell carcinoma. Two-hour intravenous drip infusions containing 5 X 10(5) units of rIL2 was given daily 2 times to inpatients and after at least 28 days of this mode of administration, subcutaneous injection at a dose of 1 X 10(6) units was given 6 days a week to outpatients. Three patients showed complete response, 7 patients no change, and 2 patients progressive disease. Serious adverse effects due to capillary leak syndrome were not observed. We conclude that low-dose rIL2 is safe and has potential antitumor effects.

Aged↗

PubMed1991

[Transurethral microwave thermotherapy of benign prostatic hypertrophy].

Transurethral microwave thermotherapy using Prostatron was performed in 31 patients with benign prostatic hypertrophy, and the clinical effectiveness was evaluated by analyzing the subjective and objective responses following the treatment. The 22F balloon catheter to be placed in the prostatic urethra incorporates the microwave antenna, a cooling system and a fiberoptic thermosensor which allow an effective delivery of microwave energy to the center of the prostate, while preserving the mucosa and periurethral tissue. The maximum urethral temperature during the treatment ranged from 43.3 to 45.5 degrees C (44.7 +/- 0.96 degrees C: mean +/- S.D.) and the average power output was 27.4 Watt. The treatment was performed in a single session of an hour on the outpatient basis. In one patient who could not be relieved of the indwelling catheter underwent a transurethral resection, and the histological effect of thermotherapy on the resected specimen was examined. In the prostatic tissue, heat-induced necrotic change of the interstitial tissue as well as degenerative change of the acinar epithelium were remarkable, whereas the urethral mucosa was well preserved. In the remaining 30 patients, the clinical effects were evaluated 8 weeks after the treatment by a score scale for subjective symptoms, residual urine and maximum urinary flow rate, which was compared with the pretreatment score. Improvement of both subjective symptoms and objective findings was observed in 13 subjects (43.3%), that of subjective symptoms only in 14 cases, and that of objective findings only in 2 cases, resulting in a notable improvement in total 29 cases (97.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

[Kidney preserving surgery for renal cell carcinoma in patients with a solitary kidney or bilateral tumors--with special regard to indication and limitation of enucleation].

We performed kidney preserving surgery for renal cell carcinoma in 10 patients with a solitary kidney or bilateral tumors. Two had cancer in a solitary kidney (contralateral kidney was nephrectomized for benign disease) and 8 had bilateral renal tumors, 3 and 5 of the latter 8 patients being asynchronous and synchronous, respectively. The kidney preserving surgery included partial nephrectomy in 3 patients and enucleation in 7 patients and was performed in situ and ex vivo followed by renal autotransplantation in 4 and 6 patients, respectively. Of the 10 patients, 4 are still alive after 2 years and 11 months-5 years and 6 months. Death occurred in 6 patients. Excluding one non-resectable patient and 2 patients of non-cancer death, 3 patients survived for 3 years-8 years and 8 months. The 10 patients, excluding one non-resectable, showed actuarial survival rates of 89, 89 and 63.3% for 1, 3 and 5 years, respectively, and excluding patients of non-cancer death, the above rates were 100, 100 and 85.7%, respectively. Postoperative local recurrence was found in 1 of 3 patients of partial resection and 2 of 7 patients of enucleation, and the latter 2 patients were those who had synchronous bilateral tumors and underwent renal autotransplantation following enucleation of a number of tumor nodules from seemingly less involved kidneys and contralateral radical nephrectomy; recurrence in the grafted kidney was already observable in the early postoperative period, which indicated re-growth of the residual tumor rather than recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

[Clinicopathological studies and flow cytometric analysis on renal cell carcinoma after incidental finding].

Of 173 patients with renal cell carcinoma treated at the Keio University Hospital between 1979 and 1989, 48 cases were found to have their tumors incidentally (group 1), and the remaining patients presented with signs and/or symptoms related to their tumors (group 2). In this study we attempted to define the clinicopathological and ploidy characteristics of the tumors in the patients of the two groups. The number of patients having tumor stages not exceeding pT2NOMOV- was significantly higher in group 1 (81.3%) than in group 2 (36.0%) (p less than 0.001), and the median tumor size was significantly smaller in group 1 (4.32 +/- 2.38 cm) than in group 2 (7.86 +/- 4.07 cm) (p less than 0.001). The survival rate in group 1 was significantly favorable when compared with group 2 (p less than 0.005). And even in the same stage (pT1-2NOMOV-) there were statistical significance in the survival and relapse rate between the two groups (p less than 0.05), which indicate that renal cell carcinomas detected incidentally are associated with biologically low malignant potential. From 1985, flow cytometric DNA analysis was performed in 32 tumors from the group 1 and in 50 from the group 2. The frequency of occurrence of aneuploid pattern was significantly lower in tumors from the group 1 (25.0% in the overall patients and 16.0% in those with stage pT1-2NOMOV- tumors of group 1) than in those from the group 2 (52.0% in the overall patients and 42.9% in those with stage pT1-2NOMOV- tumors) (p less than 0.05). These results also suggest that renal cell carcinomas detected incidentally are associated with low malignant potential biologically.

Adult↗

PubMed1990

LAG-3, a novel lymphocyte activation gene closely related to CD4.

We have identified a novel human gene of the Ig superfamily, designated LAG-3. Expression of this gene is undetectable in resting PBL, while it is found (a 2-kb message) in activated T and NK cells. The LAG-3 gene includes eight exons; the corresponding cDNA encodes a 498-amino acid membrane protein with four extracellular IgSF domains. The first one belongs to the V-SET; it is particular since it includes an extra loop in the middle of the domain and an unusual intrachain disulphide bridge. The three other domains belong to the C2-SET. Strong internal homologies are found in the LAG-3 molecule between domains 1 and 3, as well as between domains 2 and 4. It is therefore likely that LAG-3 has evolved by duplication of a pre-existing gene encoding a two IgSF-domain structure. The compared analysis of LAG-3 and CD4, with respect to both their peptidic sequence as well as their exon/intron organization, indicated that the two molecules are closely related. This point is strengthened by the finding that both genes are located on the distal part of the short arm of chromosome 12.

Amino Acid Sequence↗

PubMed1990

Further analysis of the T cell receptor gamma/delta+ peripheral lymphocyte subset. The V delta 1 gene segment is expressed with either C alpha or C delta.

In the present study, we have characterized the reactivity of two mAbs that are directed at the human TCR-gamma/delta. These reagents, designated anti-A13 and anti-TiV delta 2, were found to recognize antigenic determinants encoded by the TCR V delta 1 and V delta 2 gene segments, respectively. Immunofluorescence analyses performed with the antibodies confirmed that, in the TCR-gamma/delta+ cell subpopulation, the expression of V delta 2+ delta chains is largely predominant, as compared with the V delta 1+ counterparts. However, these experiments led to an apparently discrepant finding. Indeed, the total number of cells recognized by the anti-A13 plus the anti-TiV delta 2 antibodies was often greater than that detected with anti-TCR-delta 1, a reagent specific for a constant epitope of the human delta chain. Further investigation showed that the presence of a sizeable peripheral lymphocyte subset coexpressing the BMA031 and the A13 epitopes. Because the former antibody is known to recognize an invariant antigenic determinant of the TCR-alpha/beta dimer, these results suggested that the V delta 1 gene segment may be expressed with either C delta or C alpha. This hypothesis was confirmed using T2, an IL-2-dependent BMA031+ A13+ polyclonal cell line developed from peripheral blood of a healthy adult donor. Indeed, T2 cells were found to have productively rearranged the V delta 1 gene. Together, results of Northern blot analysis and cDNA cloning indicated that V delta 1 was expressed in these cells as part of a 1.6-kb full-length message including J alpha-C alpha segments.

Animals↗

PubMed1990

CD1c as a target recognition structure for human T lymphocytes: analysis with peripheral blood gamma/delta cells.

It has been shown recently that one gamma/delta cell line, termed IDP2, derived from a immunodeficient patient recognizes the CD1c molecule on the surface of target cells. In light of these data, we have tested 43 cloned and 11 polyclonal gamma/delta cell lines derived from peripheral blood of 19 donors following nonspecific mitogenic stimulation. In this panel, which included lymphocytes expressing various combinations of gamma and delta chains, only one clone, termed J2B7, was found to interact with target cells via a CD1c-dependent recognition pathway. These J2B7 lymphocytes have, like IDP2, a delta chain which results from the frequent V1/J1 rearrangement while they use a distinct V gamma gene segment. The data support the view that the CD1c major histocompatibility complex "class I-like" gene product does not have a pivotal contribution to the repertoire of peripheral blood gamma/delta cells in adult individuals.

Antibodies, Monoclonal↗

PubMed1990

Cloning and expression of a lymphocyte activation gene (LAG-1).

Using subtractive hybridization of a cDNA library we have identified a human gene, termed LAG-1 (for "Lymphocyte Activation Gene-1"). This cDNA codes for a 69 amino-acid polypeptide which belongs to a new class of recently described proteins secreted by activated lymphocytes and/or monocytes. The LAG-1 gene was cloned, sequenced and its chromosomal location assigned to chromosome 17 (q21 band). The promoter region of the LAG-1 gene was shown to include a GM-CSF-like decanucleotide sequence. Using a baculovirus vector expression system, we found that a 10 kDa recombinant LAG-1 protein is secreted by AcNPV infected SF9 cells, as determined in Western blot experiments by the reactivity of specific anti-peptidic heteroantibodies. Finally the natural LAG-1 protein was precipitated from the supernatant of internally labeled activated Nk cells and shown to migrate as a single entity of 14 kDa in SDS-PAGE analysis.

Amino Acid Sequence↗

PubMed1990

[Chromosome analysis of renal cell carcinoma].

Of 8 tumors surgically extirpated from 8 patients with renal cell carcinoma, 7 were successfully processed in short-term culture by collagenase method, and 130 metaphases were extracted from these 7 tumors and were subjected to chromosomal analysis according to the G banding technique. As for karyotype, 4, 2 and 1 cases were mainly diploid, hypodiploid and aneuploid, respectively. The highest incidence of chromosome aberration was marked by #3 chromosome (5 of 7 cases of which 4 and 1 showed monosomy as clonal aberration and trisomy as non-clonal aberration, respectively). The commonest gain of chromosome was noted for #7 trisomy (4 of 7 cases). Two cases had already had metastases at the time of surgery, each showing #7 trisomy. Marker chromosome was noted in 6 of 7 cases. Structural chromosome aberration had a lesser incidence compared with numerical aberration; only clonal aberrations were long-arm aberrations (2q+, 6q+) of #2 and #6 chromosomes. Short-arm aberrations (3p-, 8p-) of #3 and #8 chromosomes were noted in one case each. 3p deletion, which is reported to be predominant in the literature, was noted only in one case. This was observed in triploid cells. However, all of metaphases showing 2q+ and 6q+ had concomitant #3 monosomy, and excess portions of #2 and #6 chromosomes were in good agreement with the band pattern of #3 chromosomal long-arm. Therefore, translocation of 3q12-qter in #2 and #6 chromosomes is supposed to lead to 3p deletion. A similar mechanism seems to be involved in the formation of marker chromosomes, suggesting the involvement of deleted #3 chromosome in marker chromosomes.

Aged↗

PubMed1990

[Analysis of histopathological prognostic factors in patients who underwent radical cystectomy in cancer of the bladder].

The relationship between histopathological characteristics and their long-term prognosis was studied on a total of 110 patients with bladder cancer who underwent total cystectomy from 1978 to 1985 at Keio University Hospital in the period after computer tomography (CT) was initiated for the evaluation of tumor stagings. The actuarial five-year survival rate in the 110 patients estimated by Kaplan-Meier method was 54.3%. Disclosed as histological poor prognostic factors (p less than 0.05) were the presence of non-transitional cell elements (actuarial five-year survival rate: 26.3%), IFN gamma for growth patterns (26.3%), grade-3 for histological grades (39.1%), lymph-duct involvement ly(+) (28.2%), venous involvement v(+) (25.2%), muscle-invaded tumor and extravesical lymphnode involvement. As for the comparative relation among these histological factors, grade-3 tumors tended to have a high incidence of lymph-duct involvement (73.2%), venous involvement (26.8%) and positive lymph-nodes (35.7%) when compared to grade-2 tumors. The analysis of the degree of influence of those histological prognostic factors using the non-proportional hazard model revealed that the major priorities were positive lymphnodes (p = 0.0006), histological types (p = 0.0036) and lymph-duct involvement (p = 0.0839). These results suggest that intensive adjuvant treatment should be indicated for improving the prognosis of patients with bladder cancer who have undergone total cystectomy when non-transitional cell elements and/or vascular involvement are evidenced.

Aged↗

PubMed1990

[A case of everting ectopic ureterocele in child--controversy in the surgical treatment].

A 4-year-old girl with the history of repeated urinary tract infections was referred from the pediatric department to our department on January, 1987. Under the diagnosis of right ectopic ureterocele of everting type with complete duplication of renal unit, the one-stage operation, that is, right hemi-nephroureterectomy with complete excision of the ureterocele and ureteral stump was carried out on January 27, 1987. Reimplantation of the orthotopic mate ureter was done because of injury to lower part of the mate ureter during operation, although reflux of the mate ureter did not exist. After the operation, the voiding symptom became better except for large residual urine volume (300 ml). In order to protect renal function, intermittent catheterization was carried out. Two years and 8 months after that operation, residual urine volume was reduced to 20 ml. Judging from the literature and our experience, if the patient is not in a severe condition, we recommend one-stage operation, that is, total correction (a single operation designed to correct abnormalities of the upper and lower urinary tract) for ectopic ureterocele in children.

Age Factors↗

PubMed1990

[Percutaneous removal of renal and upper ureteral stones: clinical results and complications of 103 cases].

We report the results and complications of 103 consecutive patients who underwent percutaneous removal of renal and ureteral stones. The overall clinical success rate was 80.6%. For the recent 33 cases in which UL-arm fluoroscopy was used, however, the success rate was as high as 87.9%, which was considered to be due to easier establishment of percutaneous direct access. The most common complications were bleeding (18.5%), extravasation (15.5%) and fever (9.7%). Four cases with significant bleeding required arteriography, but there were no sign of arteriovenous fistula nor pseudoaneurysms in any cases. To study renal parenchymal damage in the percutaneous procedures, plasma renin activities (PRA) were compared in 54 cases after six months. However, significant elevation of PRA did not occur in any case.

Adult↗

PubMed1989

A monoclonal antibody recognizing 68- to 75-kilodalton protein(s) associated with the human IL-1 receptor.

We produced an IgM mAb termed 4.9 against an EBV-containing lymphoblastoid cell line, termed 3B6. This mAb reacted with both various B and T cell lines such as HSB2 cells, with an NK-like cell line YT-C3 cells, and with human fibroblast MCR-5 cells. It also reacted with normal resting peripheral B lymphocytes, monocytes, and anti-CD2- or anti-CD3-activated T lymphocytes. The 4.9 mAb immunoprecipitated two bands estimated to be of Mr 68 and 75 kDa from iodinated 3B6 cells. The 4.9 mAb inhibited the proliferation of peripheral T lymphocytes induced either by anti-CD3 mAb or anti-CD2 mAb. The 4.9 mAb inhibited also the proliferation of murine thymocytes both in the presence of PHA and IL-1 and the proliferation of human fibroblasts in the presence of IL-1. Radiolabeled IL-1 binding on 3B6 cells revealed two types of IL-1 binding sites with high and low affinity for IL-1 (300 sites/cell with a Kd of 6 x 10(-11)M and 6000 sites/cell with a Kd of 3 x 10(-9)M). On both 3B6 and YT-C3 cells, mAb 4.9 inhibited specifically the binding of 125I-labeled rIL-1, alpha or beta, whereas the irrelevant IgM mAb did not. Conversely, rIL-1, alpha or beta, could inhibit specifically the binding of radioiodinated 4.9 mAb to 3B6 or YT-C3 cells, whereas rIL-2, rIFN, or the irrelevant IgM mAb were ineffective. 125I-4.9 mAb bound 3B6 cells with an association constant (Ka) of 2 x 10(8)/M and demonstrated 6000 binding sites/cell. We thus conclude that mAb 4.9 recognizes a protein complex (68 to 75 kDa) closely associated with the IL-1R.

Adult↗