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S Konda

Publications and source records attributed to S Konda.

At least 37 records · Page 2Linked to original sources

Interleukin-7 (IL-7)-induced proliferation of CD8+ T-chronic lymphocytic leukemia cells.

Interleukin-7 (IL-7) is a growth factor for pro-B cells, pre-B cells, and thymocytes and is known to induce the proliferation of normal human peripheral T cells. Moreover, human B and T acute leukemia cells with immature surface markers proliferate in response to IL-7. Here we describe a case of T-chronic lymphocytic leukemia, in which the leukemic cells showed a proliferative response to human recombinant IL-7 in vitro. The patient was a 74-year-old woman with anemia and thrombocytopenia, whose bone marrow was fibrosed and infiltrated with pathologic cells. Surface markers of the leukemic cells were CD2(+), CD3(+), CD5(+), CD7(+), CD8(+), and CD4(-). Both T-cell receptor beta-chain and gamma-chain genes were found to be rearranged by immunogenotypic analysis. The leukemic cells proliferated in response to IL-7 dose dependently. The DNA synthesis of CLL cells was stimulated by not only IL-7 but also IL-2 and IL-4. The IL-7-induced proliferation was not inhibited by antibodies to IL-2 receptors or the anti-IL-4 antibody. These findings indicate that IL-7 may induce the proliferation of peripheral CD8+ T cells, even on its pathological counterpart.

Aged↗

[Malignant lymphoma developing from the wall of chronic empyema following artificial pneumothorax].

A 60-year-old man who had had chronic empyema following an artificial pneumothorax for pulmonary tuberculosis when he was 26 years old developed malignant lymphoma of the chest wall. The patient was admitted because of right pyothorax as a result of pseudomonas aeruginosa infection and underwent right thoracotomy. During lavage of the right thoracic cavity a tumor was found arising from the empyematic wall. Pathologic examination revealed that it was malignant lymphoma (diffuse large, immunoblastic, B cell type). Treatment with VEAP-Bleomycin elicited a good response. Seven months after chemotherapy, the patient underwent thoracoplasty in addition to packing the cavity with the latissimus dorsi and the greater omentum. Following this, the patient received chemotherapy once a month for one and a half years, after which he was kept under close observation without treatment. Complete remission has now lasted for 49 months since the initial treatment. This is the first reported lymphoma case with closure of the empyematic wall and is remarkable since this patient has remained in complete remission for the last two years without any treatment.

Empyema, Pleural↗

Microtubule organization in lymphoid malignancies.

The abnormal organization of actin-containing microfilaments and vimentin-containing intermediate filaments in neoplastic lymphocytes of T and B cell origin has been described. We investigated microtubules of pathologic cells from 34 lymphoid malignancies, by immunofluorescence microscopy, using monoclonal tubulin antibody. In most cases, apart from two cases of lymphoma, one T cell lymphoma and one B cell lymphoma, interphase leukemia cells, lymphoma cells, and myeloma cells were shown to contain well-organized microtubules which were associated with a microtubule organization center at one end. In the cells of a patient with T cell lymphoma, although microtubules were not visible in the lymphoma cells from lymph nodes, they became visible after 72 hours in culture with concanavalin A (Con A) and interferon alpha. Cap formation was observed with antitubulin monoclonal antibody in the peripheral blood lymphocytes from a chronic lymphocytic leukemia patient, but well-developed microtubules were observed on other occasions in the same patient. There were no obvious structural differences between microtubules in T and B cell lymphoid malignancies, but leukemia cells and lymphoma cells with irregularly shaped nuclei, such as adult T cell leukemia cells and B cell lymphoma cells with cleaved nuclei, had complicated microtubules surrounding their irregular nuclei. In general, after blastogenic stimuli with phytohemagglutinin-P (PHA-P), Con A, and pokeweed mitogen (PWM), the development of the microtubules was proportional to the incorporation of 3H thymidine (3H-TDR). In most cases, after incubation with granulocyte colony-stimulating factor (G-CSF) and interferon alpha, the number of intact cells decreased and the number of degenerated cells increased, but the intact cells had intact microtubules.

Adolescent↗

Enzyme histochemical, immuno histochemical and electron microscopic studies of two cases of leukemic malignant histiocytosis.

Two cases of leukemic malignant histiocytosis had similar morphologic and enzyme histochemical findings. Large blasts with low nuclear/cytoplasmic ratios, occasional azurophilic granules, and immature nuclei with nucleoli were seen in peripheral blood and bone marrow smears. Case 1 had occasional erythrophagocytosis, while in Case 2 it was rare. They were peroxidase negative, and very strongly positive by alpha-naphthyl butyrate esterase stain, the latter being inhibited by sodium fluoride. Acid phosphatase stains were also very strongly positive and were inhibited with tartaric acid. They were also stained granularly with PAS. Surface marker analysis revealed myeloid surface antigens, CD11+, CD13+ and HLA-DR+ in Case 1, and CD11+, CD13+, CD33+ and HLA-DR+ in Case 2. Immunoperoxidase stains of bone marrow biopsies revealed that lysozyme was positive in both cases. S-100 protein was strongly positive in Case 1, but weakly so in the skin tumor and negative in the bone marrow of Case 2. Electron microscopy showed both cases to be myeloperoxidase negative and rich in cytoplasmic organelles, such as lysosomes, mitochondria, and endoplasmic reticuli. Nuclei were irregularly shaped and nucleoli were present in virtually all the cells. These findings suggest that the malignant histiocytes in these two cases derive from bone marrow macrophages, and S-100 protein can also be detected in monocyte-macrophage derived histiocytes.

Adenocarcinoma↗

DNA autosensitivity in two Japanese sisters.

Two cases of DNA autosensitivity in Japanese sisters are reported. Both patients developed painful ecchymoses and other bleeding disorders. Skin tests with autologous leukocyte lysates and calf thymus DNA produced intermediate-type reactions that were identical to spontaneous skin reactions. Pretreatment of DNA with either DNase or chloroquine sulfate inhibited these reactions. Our studies suggest that anti-DNA antibodies might contribute to the clinical symptoms of this disorder.

Adult↗

Light and electron microscopic study of vacuolated cells in immunoblastic lymphadenopathy-like T-cell lymphoma.

Three cases of immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma were analyzed immunologically, and the ultrastructure of mononuclear cells in the lymph nodes and peripheral blood was examined. In the peripheral blood, light microscopic examination revealed vacuolated lymphocytes. These vacuolated lymphocytes formed rosettes with sheep erythrocytes, and they were CD3- and CD4-positive using the avidin-biotin method in cases 1 and 2. Electron microscopic examination revealed two kinds of abnormal lymphocytes. One kind was of B-cell nature with rich lamellated rough-surfaced endoplasmic reticulum and mitochondria. The other kind had a large cytoplasm, in which Golgi apparatus, some endoplasmic reticulum, some mitochondria and a few vacuoles were seen. Some of these vacuoles had remnants of mitochondrial cristae or were enlarged endoplasmic reticulum. The vacuolated T lymphocytes and activated lymphocytes of B-cell nature disappeared with chemotherapy but reappeared with relapse of the disease. These observations suggest that vacuolated cells are related to pale cells in lymph node sections. In other words when these vacuolated cells are found in the peripheral blood of patients with lymphoid malignancies, IBL-like T-cell lymphoma can be suspected.

Aged↗

Establishment of two interleukin 6 (B cell stimulatory factor 2/interferon beta 2)-dependent human bone marrow-derived myeloma cell lines.

Two IL-6-dependent human multiple myeloma cell lines, ILKM2 and ILKM3, were established from the bone marrow of patients with IgG-K multiple myeloma. Both cell lines had the typical morphology and immunocytochemical features of myeloma cells. The surface phenotype of both cell lines was PCA-1+, OKT10+, CD10(J-5)-, CD19(B4)-, CD20(B1)-, CD21(B2)-, and OKIa-1-. A monoclonal cytoplasmic Ig, IgG-K or K L chain, was positive in ILKM2 or ILKM3, respectively. EBV nuclear antigen was negative in both cell lines. They proliferated in the presence of macrophages or macrophage-derived factors (MDF). Among the recombinant cytokines examined, IL-6 most strongly augmented the growth of both cell lines. The anti-IL-6 antibody completely inhibited the IL-6-dependent growth and almost completely inhibited the MDF- or purified MDF-dependent growth of both cell lines, ILKM2 and ILKM3 are now being maintained in the culture medium containing 2 ng/ml rIL-6. These results suggest that IL-6 produced by macrophages may play an important role in the growth of myeloma cells in vivo and that macrophages or IL-6 can be used for establishing human myeloma cell lines.

Antigen-Antibody Reactions↗

A high incidence of rheumatoid factor idiotypes in monoclonal proteins in the serum and in lymphoma cells in patients with Sjögren's syndrome.

Patients with Sjögren's syndrome (SS) develop lymphoproliferative disorders such as monoclonal gammopathies and non-Hodgkin's lymphomas. Cross-reactive idiotypes (CRI) were studied in 22 serum monoclonal immunoglobulins (Igs) and in cytoplasmic Ig in four B-cell lymphoma cells in patients with SS. This was done by utilizing monoclonal anti-idiotypic antibodies which were produced against monoclonal rheumatoid factors (RF) derived from three patients with SS and one patient with Waldenström's macroglobulinemia. By the Western blotting or dot immunobinding technique, CRI was detected not only in monoclonal RFs but in monoclonal Igs which had different heavy- or light-chains from the original monoclonal RF used for immunization. A higher incidence of CRI was found in 22 monoclonal Igs associated with SS than in 27 monoclonal Igs in patients with Waldenström's macroglobulinemia, multiple myeloma or malignant lymphoma. In four patients with malignant lymphoma associated with SS, three showed one or three CRI in the lymphoma cells, whereas only two out of 20 patients with other malignant lymphoma showed CRI, demonstrating a significant difference between two groups. These data indicate that monoclonal proliferation of B-cell lineage in patients with SS, benign or malignant, takes place more often among RF-producing clones than other B-cell disorders.

Antibodies, Monoclonal↗

[HTLV-I carriers in ATL/L-nonendemic area--with reference to blood transfusions].

Sera from 5,705 persons were tested for antibodies to human T-cell leukemia virus type 1 (HTLV-I) by gelatin particle agglutination test (PA) and enzyme immunoassay (EIA) as screening methods, and the antibodies were confirmed by indirect immunofluorescence assay (IF) and Western blotting method (WB). The antibodies were detected in 30 (1.34%) of 2,239 patients who had received blood transfusions, 3 (0.29%) of 1,022 healthy blood donors, all 18 adult T-cell leukemia/lymphoma (ATL/L) patients, 23 (47%) of 49 family members of the ATL/L patients and 10 (0.53%) of the other 1,898 persons. Before the introduction of the mass screening of healthy blood donors by the Japan Red Cross Blood Center, 17 (2.29%) of 743 recipients tested were positive for the antibodies by PA and most of them were confirmed by IF and WB. Ten of these 17 recipients tested were negative for the antibodies before the blood transfusions. After the introduction of mass screening, 13 (0.87%) of 1,496 recipients tested were positive for the antibodies by PA, but the seroconversion of the antibodies by blood transfusions could not be confirmed clearly. In persons with low titers (1:16-1:64) in PA, the coincident rate of positive reaction with EIA, IF and WB was only 9.5%, 0.0% and 23.8%, respectively, and most of the immunoglobulin (Ig) class was IgM. On the other hand, in those with titers of 1:128 or greater in PA, the coincident rate was 72.7%, 81.8% and 90.9%, respectively, and the Ig class was IgG or IgG + IgM.

Adolescent↗

[A double blind trial of alfacalcidol on patients with rheumatoid arthritis (RA)].

A double blind comparative trial was performed in order to study the efficacy and safety of alfacalcidol (1 alpha-OH-D3) in a total of 140 patients with RA admitted to 31 institutes, using a placebo as the control. The treatment period was 16 weeks. The doses of 1 alpha-OH-D3 were 1.0 microgram/day and 2.0 micrograms/day. It was permissible to use non-steroid anti-inflammatory drugs for basic treatment and oral steroidal preparations for maintenance treatment without changing the doses of these drugs during the study period in patients who had been treated with them before participating in the study (for oral steroidal preparations, the dose was limited to 5 mg/day or less as prednisolone). The percentage of patients with slight improvement was about 10% higher in 1 alpha-OH-D3 groups than in placebo group, but the difference between them was not significant. The results tended to be better in the treated groups than in the placebo group, but there was no significant difference between them with regard to duration of morning stiffness, number of joints with pain, number of joints with swelling and Lansbury's index. The effects of 1 alpha-OH-D3 on various immunological parameters including lymphocyte subsets were not clearly demonstrated. However, interestingly, the ratio of OKT-4/OKT-8 was found not to change in patients whose initial value was normal, while it tended to decrease after 1 alpha-OH-D3 treatment in patients whose initial value was abnormally high. The improvement of bone atrophy was judged by microdensitometry (MD) method using X-ray picture of hands. The indexes of bone density (GS max, GS min and sigma GS/D) demonstrated that 1 alpha-OH-D3 prevents reduction in bone density. 1 alpha-OH-D3 did not trigger hypercalcemia in any case. However there was a slight but significant increase of serum Ca value in the group with higher dose (2.0 micrograms/day). Taking the efficacy into consideration, the dose of 1.0 microgram/day was judged to be suitable for long-term treatment.

Aged↗

[Ga-67 citrate accumulation in heart in malignant lymphoma of B-cell type accompanied with repeated ECG abnormalities which were normalized with chemotherapy--report of an autopsy case].

A 37y/o male developed mass formation in right tibia in Oct. 1986. He had generalized lymphadenopathy. Diagnosis of malignant lymphoma of B cell type (follicular, large cell type) stage IV B was made because of bone marrow involvement. Surface marker analysis of pathologic cells in the peripheral blood, bone marrow, lymph nodes revealed that they were of B cell type with positive EA gamma rosette formation, positive surface immunoglobulin with IgM-kappa and cytoplasmic immunoglobulin with IgM-kappa and positive responses to monoclonal antibodies of OKIal and B1. He responded partially to VEPAM therapy but in Jan. 1987 he developed Ga accumulation in heart and ECG abnormalities such as depression of ST and inverted T in II, III, AVF, V1-V6 leads. After treatment with VEP, ECG abnormalities disappeared in a month. The same ECG abnormalities recurred once more and disappeared again. Autopsy findings revealed accumulation of lymphoma cells in epicardium and myocardial degeneration in right ventricle. Ga scan appears to be a valuable method for detection of early cardiac involvement by malignant lymphoma.

Adult↗

Ultrastructural observations on the cytomegalic inclusion cell in peripheral blood.

A 31-year-old woman with adult T-cell leukemia developed interstitial pneumonitis. Large abnormal cells different from those of adult T-cell leukemia appeared in the peripheral blood. Hematoxylin-eosin staining of the buffy coat of peripheral blood revealed these cells to be cytomegalic inclusion cells. Electron microscopy disclosed cytomegalovirus particles in these inclusion cells. Virus particles were seen in both the nuclei and cytoplasm. Dense bodies characteristic of cytomegalovirus infection were also seen in the cytoplasm. This is the first report of cytomegalovirus particles found in the peripheral blood mononuclear cells.

Adult↗

Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin's lymphoma treated with VEPA or VEPA-M.

One hundred sixty-three patients with advanced non-Hodgkin's lymphoma including adult T cell leukemia/lymphoma (ATL) were treated from 1981 to 1983 with VEPA (vincristine, cyclophosphamide, prednisolone, and doxorubicin) or VEPA-M (VEPA plus methotrexate) in randomized fashion after stratification by surface marker. The complete response (CR) rate and the 4-year survival rate of patients treated with VEPA-M was 62.2% and 36.9%, respectively, while for those treated with VEPA the rates were 51.9% and 26.6, respectively. The difference was not statistically significant, but pretreatment characteristics predictive for response and survival were interesting. Three factors, leukemic change, poor performance status (PS), and T cell marker, were negatively associated with both CR and survival rates, and high-grade pathology was adversely associated with survival rate in a multivariate analysis. These prognostic factors are somewhat different from those in Western lymphomas. This may be reflection of major differences in patients' characteristics between Japanese and Western lymphomas: in this study, there was a high incidence of T cell lymphoma/leukemia (50%) including ATL (33%), leukemic manifestation (34%), poor PS (34%), and a low incidence of follicular lymphoma (9%). The statistically significant three factors for both CR and survival rates were used to construct a model containing eight categories of patients at increasing risk for poor response and shortened survival. These categories were divided into four groups, with respective CR and 4-year survival rates of 91% and 73%, 67% and 35%, 27% and 7%, and 10% and 5%. Ninety-three patients in whom CR was induced by VEPA or VEPA-M therapy were evaluated for prognostic factors predictive for disease-free survival. A shorter period (less than 28 days) required to achieve CR, a clinical diagnosis of ATL, and a lower hemoglobin level were found to affect disease-free survival adversely. These results have important implications for both the design of prospective randomized therapeutic trials and the determination of optimal therapy for individual patients.

Antineoplastic Combined Chemotherapy Protocols↗

Major prognostic factors of adult patients with advanced T-cell lymphoma/leukemia.

Eighty-one adult patients with advanced T-cell lymphoma/leukemia including 54 with adult T-cell leukemia/lymphoma (ATL), who were treated between 1981 and 1983 with vincristine, cyclophosphamide, prednisolone, and doxorubicin (VEPA) or VEPA plus methotrexate (VEPA-M) in randomized fashion, were evaluated for pretreatment characteristics. The overall complete response (CR) and the 4-year survival rates were 39.5% and 19.4%, respectively, and 69% of 32 CR patients had relapses, indicating the need for development of new effective regimens for the disease. In a multiple logistic regression analysis, only three factors, leukemic manifestation, poor performance status (PS), and a high lactate dehydrogenase (LDH) level, were significantly associated with the poor response rate. In a Cox proportional hazards model analysis, shortened survival was again significantly associated with poor PS and a high LDH level, but not with a clinical diagnosis of ATL. The two factors, PS and LDH level, that were found to be significantly associated with both CR and survival rates, were used to construct a model containing six categories of patients at increasing risk for poor response and shortened survival. These categories divided the patients into three groups with respective CR and 4-year survival rates of 75% and 53% for low-risk, 45% and 15% for moderate-risk, and 15% and 0% for high-risk. The results indicate that PS and LDH levels were the most important in predicting the response and survival of an adult patient with advanced T-cell lymphoma/leukemia. The prognosis of patients with usual peripheral T-cell lymphoma, excluding ATL, was comparable with that of advanced B-cell lymphoma. These results have important implications for the design of new prospective therapeutic trials.

Antineoplastic Combined Chemotherapy Protocols↗

Monoclonal gammopathies in patients with Sjögren's syndrome.

We studied 18 sera of Sjögren's syndrome (SS) with monoclonal gammopathy. Monoclonality was established by typical immunoelectrophoretic findings in all patients and confirmed by idiotypic (Id) studies in 12 patients. Four of the monoclonal gammopathies were of the IgG class, 8 were of the IgA class and 4 were of the IgM class, and 2 patients had 2 M proteins (IgMK/IgGK and IgAK/IgGK). The monoclonal rheumatoid factor (RF) was found in 6 patients (4 IgA and 2 IgM). A review of the literature revealed additional 19 monoclonal gammopathies (2 IgG, 9 IgA, 7 IgM and one Bence Jones protein) in Japanese SS patients. In non-Japanese SS patients, 27 monoclonal gammopathies (4 IgG, 2 IgA, 20 IgM and once Bence Jones protein) were reported. Both Japanese and non-Japanese patients showed a higher incidence of monoclonal gammopathies in primary than in secondary SS. The non-IgM class monoclonal gammopathies were predominant in Japanese SS patients, whereas monoclonal gammopathies were mostly confined to the IgM class in non-Japanese SS patients. These results indicate that monoclonal gammopathy is another significant complication of SS.

Aged↗