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Biomedical subjects

A Sawitsky

Publications and source records attributed to A Sawitsky.

18 recordsLinked to original sources
PubMed1990

Distinct characteristics of lymphokine-activated killer (LAK) cells derived from patients with B-cell chronic lymphocytic leukemia (B-CLL). A factor in B-CLL serum promotes natural killer cell-like LAK cell growth.

We show that lymphokine-activated killer (LAK) cell precursors derived from patients with B-cell chronic lymphocytic leukemia (B-CLL) and cultured in the presence of recombinant interleukin-2 and normal human serum (NHS), develop into primarily NK cell-like (CD 57+) LAK cells, whereas identically prepared LAK cell precursors from normal subjects develop into mainly T cell-like (CD 3+, CD 8+) LAK cells. B-CLL LAK cells exhibited greater proliferative capacity than did normal LAK cells. When normal LAK cells were grown in B-CLL serum instead of NHS, their proliferation increased; NK cell levels also increased to those found in B-CLL LAK cells, suggesting that B-CLL serum contains a factor that promotes NK cell-like growth, LAK cells derived from normal or B-CLL patients demonstrated similar lytic activity toward K562 and Raji cells. Growth in B-CLL serum did not reduce their lytic potential. Thus, the altered phenotype and growth exhibited by B-CLL LAK cells and normal LAK cells grown in B-CLL serum does not lead to abnormalities in their cytolytic functions. We propose instead that the predominance of NK-like cells in B-CLL LAK cell populations and the presence of an NK cell-like growth factor in B-CLL serum reflect abnormalities related to NK cell-mediated B-cell regulation; ie, either inhibition of normal B-cell growth and/or growth stimulation of the leukemic clone in B-CLL.

Antigens, CD↗
PubMed1979

A comparative study of a BCNU containing 4-drug program versus MOPP versus 3-drug combinations in advanced Hodgkin's disease: a cooperative study by the Cancer and Leukemia Group B.

A prospective randomized trial by CALGB examined the relative value of four chemotherapy regimens in 537 patients with stage III B and IV Hodgkin's disease. A new combination BOPP, derived by substitution of BCNU for nitrogen mustard in the MOPP regimen, was compared to MOPP and to two 3-drug regimens, derived by removing the procarbazine in BOPP (BOP) or removing the alkylating agent (OPP). The 4-drug programs gave significantly higher frequency of complete remissions (BOPP 67%, MOPP 63%) than the 3-drug regimens (BOP 40%, OPP 42%), and significantly longer duration of remission and survival. BOPP had a therapeutic activity equal to MOPP, and was accompanied by less toxicity. After 6 cycles of induction chemotherapy, responding patients, both CR and PR, were continued on maintenance chemotherapy for 3 years. No significant difference in relapse rate was demonstrated following maintenance treatment with either vinblastine, chlorambucil, or chlorambucil plus monthly vincristine + prednisone doses. Nor could a reinforcement phase late in the maintenance program be shown to influence the relapse rate. The median survival for all patients entered on the 4-drug programs was 5 years, while the median has not yet been reached at 6 years for those patients, who obtained CR.

Adult↗
PubMed1979

The low ionic strength reaction of human blood: relationship between the binding of serum immunoglobulin and complement of red blood cells and surface charge of the cells.

Using the sucrose haemolysis reaction of Hartmann & Jenkins (1966) as a basic model, the low ionic strength reaction (LISR) of human blood was studied to determine: (1) serum Ig uptake by RBC with saline elution and 125I-IgG uptake, and (2) complement fixation (CF) to RBC with lysis of PNH cells and C3H/C4 antiglobulin haemagglutination (AH) of normal cells. The saline eluates were found to contain IgG and IgM with traces of IgA; their pH optima for the uptake by RBC were 6.0 +/- 0.5, 5.5 +/- 0.5 and c 5.0 respectively. The ratio of bound IgG to IgM was linearly related to the uptake pH. Both C4 AH and lysis were found to be optimum at pH 6.0--7.5, whereas the maximum C3 AH was at pH 6.0 +/- 0.5. The LISR performed at a constant pH (6.1 +/- 0.1) showed that an increasing concentration of neuraminidase (VCN) used in pretreatment of RBC was associated with a decrease in both IgG uptake and CF activity. A maximum VCN effect reduced the Ig uptake to c 20% of normal and abolished almost all the CF activity. An impaired LISR to various degrees was also observed with RBC pretreated with ficin, papain, bromelin, trypsin or protamine, and RBC from two individuals of En(a-) type. Preincubation of serum at LIS with and without RBC resulted in respectively a 'complete' and partial consumption of C in the fluid phase. The latter was not enhanced or inhibited by the addition of VCN-treated RBC for preincubation. A hypothesis is proposed suggesting that in the LSR the Ig uptake by RBC is an electrostatic interaction of the oppositely charged RBC and Ig and the CF to RBC results from C activation by the cell-bound IgG and IgM. In addition, a pH-dependent inactivation of the cell-bound C3 in the LISR is demonstrated.

Complement Fixation Tests↗
PubMed1979

C3d antiglobulin haemagglutination of human red blood cells. A demonstration of two types of cell-bound C3d by means of typsin digestion.

Washed human red blood cells from blood collected in EDTA were tested by Auto-Analyzer for a percentage of maximum antiglobulin haemagglutination (AH) using monospecific antisera to human C3d and C3c. The cells from normal persons were found to be agglutinated by anti-C3d but not by anti-C3c. To a fixed dilution of antiserum, the normal C3d AH values (X +/- 2 SD) were 34 +/- 19% for adult cells (n = 29) and 14 +/- 19% for cord cells (n = 19); the difference was significant (P less than 0.0001). By pretreatment of these cells with trypsin the C3d AH was either completely abolished or markedly reduced. Its difference between the adult and cord cells was eliminated as the observed values were 4 +/- 7% and 3 +/- 4% respectively (P = 0.15). The supernatant fluid of cell-trypsin mixture, treated with trypsin inhibitors, was found to be inhibitory to C3d AH but not to C3c AH. In contrast, the AH of C3d-coated red blood cells resulting from complement fixation in vivo (ie, cold agglutinin disease) or in vitro (eg, sucrose water reaction) was resistant to trypsin treatment. The difference between the trypsin-sensitive and trypsin-resistant cell-bound C3d is postulated to be at its attachment mechanism to the cell membranes. In addition, both the advantage and limitation of using trypsinised cells for C3d antiglobulin tests are demonstrated.

Adult↗
PubMed1979

Correlation of total body potassium and leukemic cell mass in patients with chronic lymphocytic leukemia.

Total body leukemic mass in patients with chronic lymphocytic leukemia (CLL) was measured by quantitation of total body potassium (TBK) with a whole-body counter. In addition, the predicted normal total body potassium (Kp) for each patient was calculated from an empirically derived relationship involving height, weight, age, and sex. Both the absolute TBK and the relative excess of total body potassium (TBK/Kp) were related to the stage of disease. Patients in the early stages of CLL were found to have lower TBK and TBK Kp than patients in the late stages of disease. Both of these parameters increased with the successively advanced stages of the disease. The clinically monitored reduction of leukemic cell mass following therapy was accompanied by reductions in TBK and TBK/Kp. Data presented support the notion that TBK/Kp is a useful indicator of the total body leukemic mass. Furthermore, the results of these studies quantitatively validate the proposed clinical staging system for CLL. Quantitation of TBK by a whole-body counter is an accurate and noninvasive procedure and does not require administration of isotopes.

Humans↗
PubMed1978

Guidelines for protocol studies in chronic lymphocytic leukemia.

The treatment of any malignant disease requires appropriate criteria for diagnosis of the disease, appropriate methods for study, and techniques for evaluating response to treatment. In the past five years, there have been a number of proposed guidelines for studies in chronic lymphocytic leukemia (CLL). These submitted guidelines represent a further re-evaluation of concepts in CLL, and are currently in use by Cancer and Leukemia Group B for protocol studies. It is clear that revisions will continue to be make as new knowledge accumulates. In the meantime, these are submitted for publication for use by other investigators.

Drug Therapy↗
PubMed1978

A new form of Niemann-Pick disease characterised by temperature-labile sphingomyelinase.

A new type (F) of Niemann-Pick disease characterised by childhood onset of splenomegaly, lack of neurological involvement, and diminished sphingomyelinase activity is described. The clinical presentation and heat-labile sphingomyelinase activity of this type F Niemann-Pick disease distinguishes it from other types of Niemann-Pick disease.

Cells, Cultured↗
PubMed1977

Comparison of daily versus intermittent chlorambucil and prednisone therapy in the treatment of patients with chronic lymphocytic leukemia.

Ninety-six patients with stage III and stage IV chronic lymphocytic leukemia (CLL) were randomized into one of three treatment schedules. Prednisone was common to all three schedules and was given daily in an initial dosage of 0.8 mg/kg for the first 14 days, with successive halving of the daily dose on days 15 and 29 for a total 6-wk course. Prednisone was then given once a month at 0.8 mg/kg once a day for each of 7 consecutive days. Schedule I was prednisone plus chlorambucil (CLB) given as a once-a-month dose of 0.4-0.8 mg/kg; schedule II was both drugs, but the CLB was given as a daily dose of 0.08 mg/kg; schedule III was prednisone alone. Complete and partial remission (CR + PR) was 47% for schedule I, 38% for schedule II, and 11% for schedule III. Patients who responded (CR + PR) in each of the treatment schedules survived longer than the nonresponders. Complete remission was obtained in both CLB treatment schedules, but not with the prednisone alone regimen. Although overall survival was best in the intermittent CLB arm, there was no significant difference in survival time between the three treatment schedules. Toxicity was minimal in all three regimens. Augmentation of the intermittent monthly CLB, even to 1.5 and 2.0 mg/kg, was tolerated without undue marrow toxicity. About 22% of these patients either had diabetes mellitus at the time of entry on the study or manifested hyperglycemia during the course of treatment and observation.

Anemia↗
PubMed1976

Mediastinal irradiation for chronic lymphocytic leukemia.

Thirty-one patients with chronic lymphocytic leukemia were treated with mediastinal radiation. In none of the patients was complete remission achieved; either partial remission or clinical improvement was achieved in 52 per cent, but the duration of response was short. The response rate was 77 per cent for the patients receiving a total radiation dose greater than 3,000 rads and 45 per cent for those receiving less than 3,000 rads. Severe life-threatening toxicity was noted in 11 patients and seven of these patients died; two patients died with progressive disease. Severe toxicity was manifested by one or more of the following: bone marrow aplasia, pancytopenia, gram-negative sepsis, generalized herpes zoster and severe esophagitis. Neither the total dose of radiation nor the dose per week correlated withe the severity of reaction or death.

Aged↗
PubMed1976

Factor IX deficiency in Gaucher disease. An in vitro phenomenon.

Low factor IX coagulant activity was demonstrated in a patient with Gaucher disease before and after splenectomy. The same abnormality was found in seven of ten additional patients studied. Possibly, abnormally retained sphingolipids inactivate or interfere with the action of certain procoagulants.

Blood Coagulation Tests↗
PubMed1975

Clinical staging of chronic lymphocytic leukemia.

A method of clinical staging of chronic lymphocytic leukemia (CLL) has been proposed which is based on the concept that CLL is a disease of progressive accumulation of nonfunctioning lymphocytes: stage O, bone marrow and blood lymphocytosis only; stage 1, lymphocytosis with enlarged nodes; stage II, lymphocytosis with enlarged spleen or liver or both; stage III, lymphocytosis with anemia; and stage IV:lymphocytosis with thrombocytopenia. Analysis of 125 patients. in the present series showed the following median survival times (in months) from diagnosis: stage 0, is greater than 150; stage I 101; stage II, 71; stage III, 19; stage IV, 19, The median survival for the entire series was 71 mo. The prognostic significance of the stage remained even after adjustment was made for age and sex. However, both sex and age were shown to be poor predictors of survival after adjustment for stage. The method of staging proved to be a reliable predictor of survival whether used at diagnosis or during the course of the disease. The proposed staging system was an equally accurate indicator for survival when applied to two other previously published studies of large series of patients

Adrenal Cortex Hormones↗
PubMedDate not supplied

Anti-Holley (hy): characterization of another example.

Anti-Hy, in a serum of a black man who had received multiple blood transfusions, was found to be a warm reactive and polyclonal IgG antibody which did not bind complement in vitro. 51Cr-labeled Hy-positive red blood cells in the patient showed a shortened "2-component" survival curve. Hy antigens were not detected on leukocytes, platelets, or in the serum of Hy-positive individuals.

Adsorption↗
PubMedDate not supplied

Ripley-like anti-Rh associated with red blood cell-bound IgG aggregates.

A commercial Rho (D) immune globulin after heating at 63 C became Ripley-like in the Rh-positive red blood cells coated with this heated globulin carried biologic activities similar to those of red blood cells coated with Ripley anti-CD serum. These coated red blood cells fixed complement and were agglutinated by all 20 sera containing rheumatoid factor (RF). The RF-Rh-hemagglutinations were more readily inhibited by heated than by unheated human IgG. The heated globulin had no such effect on Rh-negative red blood cells. Fractionation studies by Na2SO4 precipitation and/or Sephadex G-200 gel filtration revealed that heat-induced IgG aggregates in heated globulin were responsible for the biological activities. In contrast, these activities in Ripley serum were carried by IgG monomers. Another anti-CD serum (Heyman), tested in paralledl, was found to be indistinguishable from Ripley. a pooled RF serum, after multiple adsorptions with red blood cells coated with globulin, lost its agglutination activity to red blood cells coated with Ripley or Heyman serum.

Chemical Precipitation↗
PubMedDate not supplied

Lymphocyte response to phytomitogens in iron deficiency.

The lymphocytes of iron-deficient anemic and nonanemic patients have a decreased response to phytomitogens. Treatment of these patients with iron is followed by restoration of the lymphocyte response to normal. These findings indicate an important nonhemoglobin function of iron. Iron deficiency may be a factor in the production or potentiation of immune deficiency.

Adult↗