Biomedical subjects

R Suzuki

Publications and source records attributed to R Suzuki.

At least 307 records · Page 17Linked to original sources

PubMed1997

Vesnarinone prolongs action potential duration without reverse frequency dependence in rabbit ventricular muscle by blocking the delayed rectifier K+ current.

BACKGROUND: Methanesulfonanilide derivatives, selective inhibitors of the rapidly activating component (I(Kr)) of the delayed rectifier potassium current (I(K)), prolong action potential duration (APD) of cardiac muscles with reverse frequency dependence, which limits their clinical use because of proarrhythmia. Vesnarinone, a quinolinone derivative developed as a cardiotonic agent, has complex pharmacological properties, but its clinical efficacy is explained in part by I(K) reduction. Therefore, we investigated the mode of I(K) block by vesnarinone. METHODS AND RESULTS: I(K) of the rabbit ventricular myocyte was activated by voltage-clamp steps applied from a holding potential to various depolarizing levels. The development of I(K) block at depolarization (+10 mV) and its recovery process at hyperpolarization (-75 mV) were compared between vesnarinone and E-4031. The I(K) block by vesnarinone (3 micromol/L) developed and recovered monoexponentially, with time constants of 361 ms (n=5) and 1.87 seconds (n=4), respectively. I(K) block by E-4031 (0.3 micromol/L) developed instantaneously, with no recovery from the block at hyperpolarization. The I(K) block by vesnarinone, estimated by I(K) tail after a train of depolarizing pulses (for 30 seconds at 0.2 to 2 Hz), was increased with increasing frequency (twofold at 2 from 0.2 Hz), but that by E-4031 was unchanged. In rabbit papillary muscles, vesnarinone (10 micromol/L) prolonged APD at stimulation frequencies >0.2 Hz, whereas E-4031 (0.3 micromol/L) prolonged that in a reverse frequency-dependent manner. CONCLUSIONS: Vesnarinone may prolong the repolarization of human cardiac muscle without reverse frequency dependence, because I(Kr) is expressed in humans as well as in the rabbit. Thus, this drug may be a model for an ideal class III drug without the risk of proarrhythmia.

Action Potentials↗

PubMed1997

Cloning and characterization of novel CIS family genes.

We have reported two JAK-signaling modulators, CIS (cytokine-inducible SH2 protein) and JAB (JAK2 binding protein), which are structurally related. Here we cloned three additional CIS family genes (CIS2, CIS3, and CIS4) on the basis of an expression sequence tag (EST) database search. We also found at least two additional candidates of this gene family in the database. These genes were induced by erythropoietin and granulocyte-macrophage colony stimulating factor in certain hematopoietic cell lines. The SH2 domain and a C-terminal 40 amino acid region, designated the CIS homology domain (CH domain), are highly conserved in this family, while the N-terminal regions of these proteins share little similarity. A yeast two-hybrid assay and in vitro and in vivo binding assays revealed that in addition to JAB, CIS3 bound to the JAK2 tyrosine kinase domain (JH1), although the interaction of CIS3 with the JAK2-JH1 domain was much weaker than that of JAB. Transient expression of JAB and CIS3, but not other CISs, strongly inhibited leukemia inhibitory factor (LIF)-induced STAT3-reporter gene activation in 293 cells. Furthermore, constitutive overexpression of JAB and CIS3 in M1 leukemia cells prevented LIF-induced differentiation and growth arrest. Although the physiological function remains to be investigated, CIS family genes could play a role in the negative regulation of cytokine signaling by interacting with specific targets.

Amino Acid Sequence↗

PubMed1997

Synthesis and evaluation of novel fluorinated methotrexate derivatives for application to rheumatoid arthritis treatment.

An ongoing search for new antifolate drugs useful against rheumatoid arthritis (RA) led us to prepare new methotrexate (MTX) derivatives containing enantiomerically pure L-erythro- or L-threo-gamma-fluoroglutamic acid. The derivatives in which the phenyl ring was replaced by a 3'-substituted phenyl or methylthiophene ring showed potent immunosuppressive activities, including in vitro inhibition of mitogen responses to both T and B cells and in vivo inhibition of antibody production in mice. These compounds also exhibited inhibitory activity in adjuvant arthritis in rats. Their toxicity was lower than that of MTX, which was probably due to the strong electronegativity of fluorine, which increases the acidity of the gamma-carboxyl group and thereby decreases polyglutamylation in normal cells. These results revealed the potential of the fluorinated MTX derivatives as candidate drugs for the treatment of RA.

Animals↗

PubMed1997

CD7+ and CD56+ myeloid/natural killer cell precursor acute leukemia: a distinct hematolymphoid disease entity.

The disease spectrum of natural killer (NK) cell leukemias and lymphomas has recently been expanding with the continuing evolution in diagnostic concepts. We describe here seven cases of acute leukemia of conceivable myeloid and NK cell precursor phenotype in six men and one woman varying from 19 to 59 years of age (median, 46 years). Striking extramedullary involvement was evident at initial presentation, with peripheral lymphadenopathy and/or mediastinal masses. Two lacked any leukemic cells in the bone marrow at diagnosis. Using cytochemical myeloperoxidase staining, less than 3% of the leukemic cells showed positive reactivity. However, expression of CD7, CD33, CD34, CD56, and frequently HLA-DR, but not other NK, T-cell, and B-cell markers was observed. Cytoplasmic CD3 was detected in three of the cases by flow cytometry and in six by Northern blotting, suggesting an origin from common progenitors between the NK cell and myeloid lineages. All but one presented germline configurations of the T-cell receptor beta and gamma chain genes and Ig heavy chain gene. With regard to morphology, the cells were generally L2-shaped, with variation in cell size, round to moderately irregular nuclei and prominent nucleoli, pale cytoplasm, and a lack of azurophilic granules. Histopathologic examination of biopsied specimens of extramedullary tumors showed a lymphoblast-like morphology, implying the differential diagnostic problem from lymphoblastic lymphomas, especially in cases lacking bone marrow involvement. Three patients were successfully treated with chemotherapy for acute myeloid leukemia (AML), whereas three other patients proved refractory to chemotherapeutic regimens for lymphoid malignancies, although two responded to subsequent AML chemotherapy. However, despite intensive chemotherapy, including allogeneic bone marrow transplantation, most persued fatal courses within 41 months. These data suggested that the CD7+ and CD56+ myeloid/NK cell precursor acute leukemia might constitute a distinct biologic and clinical disease entity. Its recognition appears to be particularly important for the clinicopathologic evaluation of CD56+ hematolymphoid malignancies and the development of therapeutic approaches to such disease.

Acute Disease↗

PubMed1997

Cloning and characterization of APS, an adaptor molecule containing PH and SH2 domains that is tyrosine phosphorylated upon B-cell receptor stimulation.

Stimulation of B lymphocytes through their antigen receptor (BCR) results in rapid increases in tyrosine phosphorylation of a number of proteins, which leads to a cascade of biochemical changes that initiates B cell proliferation and differentiation or growth inhibition. A novel cDNA, designed APS, encoding an adaptor protein with a Pleckstrin homology (PH) domain, Src homology 2 (SH2) domain, and a tyrosine phosphorylation site was cloned from a B cell cDNA library using a yeast two hybrid system. APS is structurally similar to SH2-B, an SH2 protein that potentially binds to the immunoreceptor tyrosine-based activation motif (ITAM) as well as Lnk which is postulated to be a signal transducer that links T-cell receptor to phospholipase Cgamma, Grb2 and phosphatidylinositol 3-kinase. APS expressed only in human Burkitt's lymphoma cells among cell lines we examined and tyrosine phosphorylated in response to BCR stimulation. APS bound to Shc irrespective of stimulation and bound to Grb2 after stimulation, suggesting that it plays a role in linkage from BCR to Shc/Grb2 pathway. These results indicate that APS, SH2-B and Lnk form a new adaptor family that links immune receptors to signaling pathways involved in tyrosine-phosphorylation.

Adaptor Proteins, Signal Transducing↗

PubMed1997

A new protein containing an SH2 domain that inhibits JAK kinases.

The proliferation and differentiation of cells of many lineages are regulated by secreted proteins known as cytokines. Cytokines exert their biological effect through binding to cell-surface receptors that are associated with one or more members of the JAK family of cytoplasmic tyrosine kinases. Cytokine-induced receptor dimerization leads to the activation of JAKs, rapid tyrosine-phosphorylation of the cytoplasmic domains, and subsequent recruitment of various signalling proteins, including members of the STAT family of transcription factors, to the receptor complex. Using the yeast two-hybrid system, we have now isolated a new SH2-domain-containing protein, JAB, which is a JAK-binding protein that interacts with the Jak2 tyrosine-kinase JH1 domain. JAB is structurally related to CIS, a cytokine-inducible SH2 protein. Interaction of JAB with Jak1, Jak2 or Jak3 markedly reduces their tyrosine-kinase activity and suppresses the tyrosine-phosphorylation and activation of STATs. JAB and CIS appear to function as negative regulators in the JAK signalling pathway.

Amino Acid Sequence↗

PubMed1997

Inhibitory effects of pituitary adenylate cyclase activating polypeptide on histamine-induced respiratory resistance in anesthetized guinea pigs.

Asthma is a chronic inflammatory disorder of the airways in which many cells participate. This inflammation causes recurrent episodes and symptoms that are associated with widespread but variable airflow limitation that is at least partly reversible either spontaneously or with treatment. Therefore, an investigation of useful remedies for the treatment of bronchial asthma is proposed. In this study, we determined whether both forms of pituitary adenylate cyclase activating polypeptide (PACAP 38 and PACAP 27) belonging to the vasoactive intestinal peptide (VIP) family of peptides could inhibit the effects of histamine-induced respiratory resistance (Rr) in anesthetized guinea pigs, when compared with VIP. The order for 50% suppression (ED50) of Rr induced by peptides was VIP > PACAP 27 > PACAP 38. The inhibitory effects induced by PACAP 38 on histamine-induced Rr in guinea pigs were more prolonged than with the other two peptides. Moreover, adding the endopeptidase inhibitor phosphoramidon prolonged the inhibitory effects of PACAPs. These results suggested that the exogenous peptides of the inhibitory nonadrenergic noncholinergic nervous (i-NANC) peptides could become a useful remedy for treatment of bronchial asthma, because these belong to an important intrinsic hormone.

Airway Resistance↗

PubMed1997

Quantitative analysis of the usage of human T cell receptor alpha and beta chain variable regions by reverse dot blot hybridization.

We previously developed an adaptor ligation-mediated PCR method to amplify the T cell receptor (TCR) cDNA pools. In the present study we applied reverse dot blot hybridization to PCR-amplified specimens for quantitative analysis of the usage of TCR alpha and beta chain variable (V) region. 44 VA sequence-specific oligonucleotide probes (SSOPs) and 38 VB SSOPs were synthesized corresponding to unique sequences of VA and VB subfamilies. Peripheral blood lymphocytes of ten healthy donors and five T cell clones established from bone marrow cells were examined for VA and VB usage using this method. The results were consistent with those obtained by a colony hybridization method and those by immunofluorescence staining using monoclonal antibodies to VA and VB. Thus, reverse dot blot hybridization for TCR V(alpha) and Vbeta is a new, easy and dependable technique useful for analysis of VA and VB usage by human T cells.

Base Sequence↗

PubMed1997

A comparison of blood pressure changes in phacoemulsification cataract surgery with topical and retrobulbar block local anesthesia.

BACKGROUND: Changes are observed in blood pressure (BP) levels during cataract surgery, although BPs are considered to remain stable under local anesthesia. We evaluated the daily, pre- and postoperative BPs of 2270 patients after cataract surgery performed under either topical anesthesia or retrobulbar block. METHODS: All operations were performed by the same surgeon using the same method of phacoemulsification and aspiration with posterior chamber intraocular lens implantation under local anesthesia. RESULTS: The mean daily BP was 99.3 +/- 14.2 mm Hg; the mean preoperative BPs increased and then the postoperative BPs decreased. The postoperative BPs of the retrobulbar injection group decreased significantly more than those of the topical application group. In 833 cases, the systolic BP changed by more than 20 mm Hg. Even when the patients were hypertensive, the preoperative and postoperative BPs decreased in the same manner. CONCLUSION: The present study shows that, following surgery with retrobulbar block anesthesia, BP decreases to a greater extent than with topical anesthesia. Physicians should be aware of the high proportion of cases in which the systolic BP changes by more than 20 mm Hg.

Administration, Topical↗

PubMed1997

Phase I/II trial of cure-oriented high-dose chemoradiotherapy with transplantation of CD34+ peripheral blood stem cells purified by the immunomagnetic bead method for refractory hematological malignancies. Nagoya CD34+ PBSCT Study Group.

A multicenter phase I/II clinical trial was conducted to evaluate the safety of a device (Isolex System; Baxter Health Corporation, Irvine, Calif., USA) using the immunomagnetic bead method to purify CD34+ stem cells from peripheral blood and to assess the efficacy and toxicity of high-dose chemoradiotherapy with peripheral blood stem-cell transplantation (PBSCT) using purified CD34+ stem cells in patients with refractory hematological malignancies. Patients eligible for the study included those who had T-cell acute lymphoblastic leukemia (T-ALL), lymphoblastic lymphoma (LBL), mantle-cell lymphoma (MCL), high-risk aggressive non-Hodgkin's lymphoma (NHL), and adult T-cell leukemia/lymphoma (ATLL) in first complete remission (CR) and those who had standard-risk aggressive NHL, indolent lymphoma, Hodgkin's disease, or acute promyelocytic leukemia (APL) in second CR or first partial remission (PR) after the completion of first-line chemotherapy and were chemosensitive to salvage chemotherapy, in whom tumor contamination of harvested peripheral blood stem cells (PBSCs) was possible due to bone marrow or peripheral blood involvement. Lack of CD34 expression by tumor cells was an important selection factor. Eight patients with hematological malignancies (six NHL patients, one ATLL patients, and one APL patient) were enrolled; their median age was 41 years (range 26-49 years). After consolidation and mobilization chemotherapy, two or three courses of apheresis were performed in each patient. After high-dose chemo(radio)therapy, in each patient a median of 1.8 x 10(6) cells/kg (range 8.2 x 10(5)-5.1 x 10(6) cells/kg) purified CD34+ PBSCs were infused; granulocyte colony-stimulating factor was given from day 1. Median times to hematopoietic recovery were as follows: WBC of > or = 1,000/microliter, day 11; platelet count of > or = 50,000/microliter, day 19; and reticulocyte count of > or = 10/1000, day 15. Two NHL patients relapsed at 23 and 9 months after PBSCT, respectively; the remaining six patients are alive and in CR. No severe toxicity was observed in any patient. Tumor contamination as measured using a polymerase chain reaction-mediated RNase protection assay at the 10-4 level was detected in the CD34(+)-purified fractions of 2 of the 5 samples analyzed; however, a reduction in contaminating lymphoma cells from the autograft of at least 1,000 to 10,000 orders of magnitude was achieved by CD34+ selection using the immunomagnetic bead method. High-dose chemoradiotherapy with transplantation of CD34+ PBSCs purified by the immunomagnetic bead method was thus shown to be an active and safe therapy for refractory hematological malignancies with bone marrow or peripheral blood involvement. However, it is too early for evaluation of the long-term survival benefit.

Adolescent↗

PubMed1997

The effects of phacoemulsification cataract surgery via local anesthesia on preoperative and postoperative blood pressure levels.

PURPOSE: The authors prospectively evaluated the preoperative and postoperative blood pressure (BP) levels of 2270 patients with cataracts. METHODS: All surgeries were performed by the same surgeon using the same method of phacoemulsification and aspiration (PEA) with posterior chamber intraocular lens implantation with the patients under local anesthesia. RESULTS: The daily systolic BP was 140.7 +/- 22.9 mmHg; the preoperative and postoperative systolic BPs were 149.5 +/- 23.9 and 145.6 +/- 23.8, respectively. The tendency for the preoperative BPs to increase and the postoperative BPs to decrease also was evident in the diastolic and the mean BPs. However, when the authors categorized the cases into normal, intermediate, and hypertension groups, the preoperative BP increased less and the postoperative BP decreased more when the daily BP was higher. CONCLUSION: Overall, the daily, preoperative, and postoperative BPs were relatively stable with the patients under local anesthesia. However, the BP change was characteristic of each group when the patients were categorized as normal, intermediate, and hypertensive. Surgeons should be aware of the greater-than-anticipated BP change during cataract surgery.

Adult↗

PubMed1997

Overexpression of PRAD1/cyclin D1 in plasma cell leukemia with t(11;14)(q13;q32).

Two patients with plasma cell leukemia (PCL) with a t(11;14)(q13;q32) translocation are reported. Case 1 is a 64-year-old woman diagnosed as having primary PCL (IgA/lambda, Stage III) with high serum LDH and beta 2-microglobulin (beta 2MG) levels. She was treated with combination chemotherapy but died of gastrointestinal bleeding on the 45th hospital day. Case 2 is a 52-year-old man, initially diagnosed with multiple myeloma (IgG/kappa, Stage III) in August 1993. Relapse several months after primary chemotherapy was characterized by a rapid increase in plasma cells in peripheral blood, high serum LDH and beta 2MG levels, and resistance to further chemotherapy. Both cases showed complex karyotypic abnormalities including t(11;14), and Northern analysis revealed overexpression of the PRAD1/ cyclin D1 gene. The PRAD1 gene is found on chromosome band 11q13 and encodes cyclin D1. Cyclin D1 plays an important role in control of the cell cycle, and overexpression of PRAD1/cyclin D1 may be involved in disease progression in these cases.

Chromosomes, Human, Pair 11↗

PubMed1997

Presence of Vicia graminea lectin- and Vicia unijuga lectin-binding (Vgu) glycoprotein in human amniotic fluid and some of its chemical and serological properties.

Vicia graminea- and Vicia unijuga-binding glycoprotein (Vgu glycoprotein) has been reported as a malignant tumor-associated antigen, which is found in various kinds of malignant tumor-tissues and ascitic and cyst fluids of malignant tumor patients, but not found in 20 kinds of normal human tissues. The glycoprotein reacts with anti-N lectins of Vicia-graminea (VGA) and Vicia unijuga (VUA), but does not react with anti-blood group M and N sera. The existence of Vgu glycoprotein in human amniotic fluid is reported here. A perchloric acid-soluble glycoprotein fraction (PASF) was prepared from human amniotic fluid (AF-PASF). Sialoglycoprotein was then separated from AF-PASF by consecutive gel filtration on Sephacryl S-300, HPLC on Asahipak GS-710 and affinity chromatography in VUA-conjugated formyl-cellulofine columns. The sialoglycoprotein with 9.6% (w/w) carbohydrate content showed a molecular mass of 2940 kDa estimated by HPLC gel filtration. The sialoglycoprotein showed reactivity with VGA and VUA, but did not react with anti-M and -N sera. In addition, the sialoglycoprotein reacted with lectins of Ulex europeus, Arachis hypogaea, Maclura pomifera, Canavalia ensiformis, Ricinus communis, Phaseolus vulgaris, Sambucus nigra and Sophora japonica. These results show that Vgu glycoprotein exists in human amniotic fluid, and that Vgu glycoprotein obtained from human amniotic fluid has a similar serological property to Vgu glycoproteins found in malignant tumor-tissues, but its chemical property is significantly different from that of malignant-tumor associated Vgu glycoproteins.

Amino Acids↗

PubMed1997

Complete cytogenetic response with host-derived hematopoiesis induced by cyclosporin A discontinuation in a patient with relapsed chronic myelogenous leukemia after bone marrow transplantation.

A 46-year-old woman with Ph-positive CML received an unmanipulated BMT from an HLA-identical brother, conditioned with busulfan-cyclophosphamide. Five months after BMT, cytogenetic relapse occurred, and CsA was decreased and then discontinued. Mild acute GVHD occurred, but gradually improved with no immunosuppression. Forty days after CsA discontinuation, both cytogenetic and fluorescence in situ hybridization analyses showed a host-derived normal karyotype, 46,XX, and no evidence of leukemic cells or donor graft. The sustained host-derived hematopoiesis lasted for 2 years until sudden recurrence of CML. In this case, the discontinuation of CsA led to GVHD and also suppression of the relapsed leukemia, presumably by a 'specific' GVL effect. There was also graft failure. The observation that subsequent hematologic recovery was of host origin implies that, at least in this case, the GVL effect was not directed against normal host-type hematopoiesis.

Bone Marrow Transplantation↗

PubMed1997

Internal tandem duplication of FLT3 associated with leukocytosis in acute promyelocytic leukemia. Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho).

FLT3 is a member of receptor tyrosine kinases expressed in leukemia cells, as well as in hematopoietic stem cells. Recently, a somatic alteration of the FLT3 gene was found in acute myeloid leukemia, as an internal tandem duplication (FLT3/ITD) which caused elongation of the juxtamembrane (JM) domain of FLT3. Here we characterized the FLT3/ITD and investigated its clinical significance in acute promyelocytic leukemia (APL). Seventy-four newly diagnosed patients with APL, who were treated with the same protocol in a multi-institutional study, were studied for the FLT3/ITD. Genomic and message sequences of the FLT3 gene were amplified by means of polymerase chain reaction (PCR), and elongated PCR products were sequenced. Fifteen patients (20.3%) had FLT3/ITD, all of which were transcribed in frame. Location of the duplicated fragments (six to 30 amino acids) varied from patient to patient. However, they always contained either Y591 or Y599, but the tyrosine kinase domain was not significantly affected. This finding implied that signal transduction of FLT3 is amplified by the duplication. Clinically, the presence of FLT3/ITD was related to high peripheral white blood cell counts as well as peripheral leukemia cell counts (P < 0.0001), high LDH level (P = 0.04), and low fibrinogen concentration (P = 0.04). These data suggest that FLT3/ITD plays a significant role in progression of APL.

Adult↗

PubMed1997

Non-restricted T cell receptor (TCR)-V alpha and -V beta gene usage in patients with pulmonary sarcoidosis.

Sarcoidosis is a systemic granulomatous disease of unknown etiology characterized by the pronounced accumulation of CD4+ T cells and macrophages in the affected organs. TCR variable (V) alpha and V beta gene usage in patients with sarcoidosis is still a matter of discussion. In this investigation, we analysed TCR-V alpha and -V beta gene usage in bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) of 30 patients with active pulmonary sarcoidosis using an adapter ligation method, reverse transcriptase-polymerase chain reaction (RT-PCR), and sequence-specific oligonucleotide probe (SSOP) analyses. There was no significant difference in TCR-V alpha or -V beta gene usage between BALF (n = 12) or PBMC (n = 27) of patients and PBMC of healthy subjects (n = 10). Neither selective TCR-V alpha nor -V beta expansion was observed in the paired BALF and PBMC from seven of nine patients. However, selective expansions were observed in a few TCR-V alpha or -V beta subsets in the BALF or PBMC of some individuals. Although a modest increase in a few TCR-V alpha or -V beta subsets was observed in the BALF or PBMC of some individuals, the increased TCR-V alpha or -V beta subsets were not closely associated with the HLA-DRB1, DQA1, DQB1, and DPB1 alleles of these patients. These results suggest that TCR-V alpha or -V beta gene usage is not restricted in both lung and peripheral blood in the majority of patients with active pulmonary sarcoidosis.

Adult↗

PubMed1997

Phase I study of cladribine (2-chlorodeoxyadenosine) in lymphoid malignancies. Cladribine Study Group.

Cladribine (2-chlorodeoxyadenosine;) is a purine analogue with clinical activity against hairy cell leukemia, chronic lymphocytic leukemia and indolent lymphoma. To clarify the toxicity profiles of cladribine, we conducted a phase I and pharmacological study of cladribine with a schedule of seven-day continuous intravenous infusion every 28 days up to a maximum of three cycles. We enrolled 10 previously-treated patients with various lymphoid malignancies. No dose-limiting toxicity (grade 4 hematologic and/or grade 3 or more non-hematologic) was observed in the three patients who received 0.06 mg/kg/day (Level 1). Of the seven patients who received 0.09 mg/kg/day (Level 2), one patient developed grade 4 hypoxemia and grade 4 thrombocytopenia, and another developed grade 4 neutropenia. Of the seven patients treated at Level 2, one with cutaneous T-cell lymphoma attained complete remission, and one with mantle cell lymphoma, one with chronic lymphocytic leukemia and one with adult T-cell leukemia-lymphoma attained partial remission. A pharmacokinetic analysis of the seven patients without leukemic cells showed that their area under the concentration versus time curves of plasma cladribine increased dose-dependently from 2661.3 +/- 300.4 nM x h at Level 1 (n = 3) to 3411.3 +/- 341.0 nM x h at Level 2 (n = 4) (P = 0.034). We conclude that the recommended phase II dose of cladribine (0.09 mg/kg/day as a seven-day continuous i.v. infusion) in Caucasian patients can be safely administered to Japanese patients. The encouraging results prompted us to plan subsequent phase II studies of cladribine against adult T-cell leukemia-lymphoma, hairy cell leukemia and indolent lymphoma.

Aged↗

PubMed1997

A nodal gamma/delta T-cell lymphoma with an association of Epstein-Barr virus.

The postthymic gamma/delta T-cell lymphoma is rare, and most occur as extranodal tumors, e.g., in hepatosplenic or cutaneous forms. We here report an unusual nodal case that initially presented as a T-zone lymphoma. The neoplasm recurred as systemic lymphadenopathy 25 months after complete remission with terminal high-grade transformation. Phenotypic analysis showed CD1-, CD2+, CD3+, CD4-, CD5-, CD7+, CD8+, CD10-, CD16-, CD19-, CD20-, CD21-, CD25-, CD56-, CD57-, T-cell receptor (TCR) alpha/beta antigens negative, TCR gamma/delta antigens positive, and an HLA-DR+ phenotype. Cytogenetic studies showed clonal chromosomal translocations involving chromosomes 1, 5, 6, 8, 15, and X in eight of 15 cells; t(X;5;1)(q13;q13;p22) and t(6;15;8)(p22;q26;q13). Genotypic analysis showed the same clone, characterized by the TCR gamma-chain gene rearrangement pattern, to be present in both initial and recurrent tumors. The lymphoma cells were also demonstrated to express the latent membrane protein-1 by immunohistochemistry and EBV-encoded small RNAs by in situ hybridization. Southern blot analysis using the probe of the terminal repeat demonstrated incorporation of multiple copies of EBV in the recurrent tumor. However, the initial lesion, which contained a smaller number of EBV-positive cells, showed no such evidence of clonal proliferation. These data suggest that EBV may be associated with high-grade transformation, although its exact role in lymphomagenesis remains uncertain. The present study also adds to our understanding of the clinicopathologic spectrum of gamma/delta T-cell neoplasia.

Aged↗