Lennert's lymphoma: response to 2'-deoxycoformycin.
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Adult↗
Biomedical subjects
R M Lowenthal
Publications and source records attributed to R M Lowenthal.
Defective glycosylation of erythrocyte membrane glycoconjugates in a variant of congenital dyserythropoietic anemia type II: association of low level of membrane-bound form of galactosyltransferase.
Congenital dyserythropoietic anemia type II (CDA II) or HEMPAS is a genetic disease caused by plasma membrane abnormality. The enzymic defect of HEMPAS has been suggested to be the lowered activity of N-acetylglucosaminyltransferase II, resulting in lack of polylactosamine formation on proteins and leading to accumulation of polylactosaminyl lipids. In contrast to typical HEMPAS cases, cell-surface labeling of the erythrocytes of a HEMPAS variant G.K. showed an absence of polylactosamines either on proteins or on lipids. Fast-atom bombardment mass spectrometry analysis of G.K.'s erythrocyte glycopeptides detected a series of high mannose-type oligosaccharides, which were not detected in erythrocyte N-glycans of normal cells or of other HEMPAS cases: The former contains polylactosaminoglycans and the latter contains hybrid-type oligosaccharides. Keratansulfate (sulfated polylactosamines) in this patient's serum was abnormally low. The galactosyltransferase activity in microsomal membranes prepared from G.K.'s mononucleated cells was 24% of the normal level, whereas this enzyme activity in G.K.'s serum was comparatively higher than normal. Western blotting of G.K.'s membranes using antigalactosyltransferase antibodies showed that G.K. has reduced amounts of this enzyme present. The results collectively suggest that variant G.K. is defective in polylactosamine synthesis owing to the decreased quantity of the membrane-bound form of galactosyltransferase.
Anemia, Dyserythropoietic, Congenital↗
Human T lymphocyte colonies require IL2 and are inhibited by anti-Tac.
Human T lymphocyte colony formation can be induced in a two-step culture system with phytohaemagglutinin (PHA) as the only exogenous growth factor. In this system the first step is the overnight pre-incubation of mononuclear cells in a liquid medium in the presence of PHA ('activation step'). The second step is the seeding of these PHA-activated cells into semi-solid agar, again in the presence of PHA, and their culture for 7 days ('proliferative step'). We have previously proposed that interleukin 2 (IL2) is produced during the second (proliferative) step and that this IL2 facilitates the production of colonies from PHA-activated colony-forming cells. Here we substantiate this proposal by demonstrating that both highly purified IL2 and recombinant IL2 stimulate T colony formation from PHA-treated cells. The monoclonal antibody anti-Tac, which is specifically directed against the IL2 receptor, dramatically inhibited colony formation when it was included during the agar culture (proliferative step). There was no effect when anti-Tac was included during the liquid pre-incubation culture (activation step). These results provide strong evidence that IL2 is the critical factor in the development of T lymphocyte colonies at the stage of conversion of PHA-activated cells into colonies.
Antibodies↗
Comparison of immunofluorescence and immunoperoxidase techniques for demonstration of phenotype and monoclonality in lymphoproliferative disorders.
To determine whether a simple immunoperoxidase (IP) technique could replace the traditional immunofluorescence (IF) technique (by fluorescence microscopy) for determination of phenotype and monoclonality in cell suspensions from patients with lymphoproliferative disorders, we tested samples from 48 cases by both methods, using small panels of antibodies designed to determine proportions of B-cells, T-cells and cells bearing immunoglobulin light chains. There were 27 cases of chronic lymphocytic leukaemia (CLL), 6 of prolymphocytic leukaemia (ProLL), and 15 of non-Hodgkin's lymphoma (NHL). We found that IP was at least as reliable as IF in all cases. In the 47 B-cell cases, the mean proportion of cells apparently belonging to the malignant clone was higher by IP than by IF; conversely, the proportion of B-cells displaying the non-malignant light chain marker and the proportion of residual T-cells was apparently lower by IP. We conclude that IP is a useful and reliable technique for determining phenotype and monoclonality in lymphoproliferative disorders; because it is tolerant of delays to samples in transit and requires only simple facilities, it may be particularly suitable for small laboratories.
Antibodies, Monoclonal↗
Malassezia furfur fungemia as a treatable cause of obscure fever in a leukemia patient receiving parenteral nutrition.
We describe a 46-year-old man with acute non-lymphocytic leukemia (ANLL) and Crohn's disease who, while receiving total parenteral nutrition (TPN), developed a protracted febrile illness with thrombocytopenia, pulmonary infiltrates and jaundice. Malassezia furfur, a lipophilic fungus, was identified from blood culture on lipid-enriched media. The patient improved rapidly with cessation of TPN and removal of his central venous catheter. M. furfur may cause a severe illness in immunosuppressed patients receiving TPN.
Acute Disease↗
Invasive Trichosporon cutaneum infection: an increasing problem in immunosuppressed patients.
Trichosporon cutaneum (syn. T. beigelii), a saprophytic fungal organism normally found in the soil, is increasingly being recognized as a cause of life-threatening systemic illness in immunosuppressed patients. Of 42 cases reported in the literature, 27 (64%) have died, including all four occurring after bone marrow transplantation. We report here a 44-year-old man who developed an invasive pulmonary infection and fungemia with T. cutaneum following bone marrow transplantation. The infection was manifest by severe respiratory distress and hypoxemia despite a clear chest X-ray, and was diagnosed by the identification of fungal hyphae on a percutaneous lung aspirate and by culture of the organism from the blood. Despite the previous reports indicating that there is a high mortality rate in this situation, the patient recovered following treatment with amphotericin B, miconazole and ketoconazole. T. cutaneum needs to be recognized as a potentially serious but treatable pathogen in severely immunosuppressed patients, including bone marrow transplant recipients.
Adult↗
Oral idarubicin as single-agent treatment of acute nonlymphocytic leukemia in poor-risk patients.
Oral idarubicin was given as single-agent treatment of acute nonlymphocytic leukemia in 18 poor-risk patients. They comprised nine previously untreated elderly patients, age range 69-86, and nine relapsed pretreated patients, age range 41-76. Overall, two patients achieved complete remission (including one with preceding refractory anemia with excess of blasts) and seven achieved partial responses. Dose-limiting toxic effects were diarrhea and sepsis. In this limited study, oral idarubicin at a dose of 20-25 mg/m2/day X 3 was a well-tolerated drug with potent antileukemic effects. The oral formulation deserves more widespread evaluation.
Administration, Oral↗
A rapid, simple method for leukemia immunophenotyping using air-dried blood and bone marrow smears.
This paper describes a modification of the peroxidase technique by which immunophenotyping may be carried out on routinely air-dried blood and bone marrow (BM) smears. The method is simple and quick, requires no special equipment, can be performed on fresh or stored specimens and gives a standard of morphological detail equal to that of routine blood films. With a monoclonal anti-HLA-DR antibody as a prototype, it was possible to demonstrate reliably, the presence of positively and negatively stained cells of appropriate morphological types in the peripheral blood of leukemia patients. Although only about one-third of antibodies tested were effective with the technique, we identified monoclonal antibodies capable of demonstrating myelomonocyte, granulocyte, monocyte, pan-leukocyte, transferrin, platelet, pan-T, 'cALLA plus B cell' and other antigens. However, we have not yet found antibodies able to identify T cell subsets, nor to distinguish 'common' acute lymphoblastic leukemia from its rare B-cell counterpart. With these limitations the method is suitable for routine use alongside cytochemistry in the differential diagnosis of leukemias and lymphomas.
Blood Cells↗
Corticosteroid drugs: their role in oncological practice.
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Adrenal Cortex Hormones↗
A phase I-II study of cytosine arabinoside, daunorubicin, and VP16-213 in adult patients with acute non-lymphocytic leukemia.
The combination cytosine arabinoside (ara-C), daunorubicin, and VP 16-213 was studied in 28 patients with acute non-lymphocytic leukemia to define the toxicity of the combination and assess its efficacy. Of 21 previously untreated patients, 16 (76%) achieved a complete response (CR) with the median remission duration not reached but exceeding 25 weeks. For CR patients, the median number of days with neutrophils less than 500/microliter was 19. The median survival for patients with CR is 60 weeks. Two of seven previously treated patients achieved CR for 11 weeks and in excess of 36 weeks, respectively. At the initial VP16-213 dose of 100 mg m-2 per day for seven days, severe stomatitis was seen in 38% of courses but was less with dose reduction to 75 mg m-2 per day for seven days. Other toxicity was similar to previous experience with ara-C and daunorubicin alone.
Acute Disease↗
Functional and phenotypic analysis of a T cell prolymphocytic leukemia.
Peripheral blood mononuclear cells obtained from a patient with prolymphocytic leukemia expressed the surface membrane markers characteristic of resting mature T helper lymphocytes. These cells responded to the T cell mitogens PHA and Con A in a blast transformation assay but not the anti-T cell monoclonal antibody Leu 4 and the B cell mitogen, PWM. The concentration of PHA or Con A eliciting maximum blast transformation was less than that required by normal mononuclear cells. The leukemic cells recognised and responded to allogeneic pooled mononuclear cells in a mixed lymphocyte culture. In addition, although they did not express Ia antigens, they served as effective stimulators in the mixed lymphocyte reaction. Consistent with the helper phenotype, the leukemic cells did not produce suppressor factors, but provided help for normal B-enriched lymphocytes to respond to PWM as assessed by both blast transformation and IgG production. T lymphocyte colonies developed when the leukemic cells were treated with PHA during a 20 h liquid culture prior to being seeded into semisolid agar medium containing either PHA or an IL2-containing lymphokine. There was no growth when untreated cells were seeded directly into IL2-containing agar. Analysis of colony formation indicated that, as with normal resting T lymphocytes, proliferation occurred in two distinct steps; activation in response to PHA and replication in response to IL2-like growth factors. These findings demonstrate that in this case the helper T prolymphocytes have the functional capabilities of normal mature T lymphocytes as predicted from their helper phenotype.
Aged↗
A sensitive method for immunophenotyping stored leukemia and lymphoma cells with preservation of morphological detail.
We describe a method by which density-separated mononuclear preparations of blood and bone marrow may be stored and batch-processed for immunophenotyping by the indirect immunoperoxidase (IP) technique. The method gives excellent preservation of cellular detail thus permitting clear morphological categorization of IP-positive and IP-negative cells. We compared the immunofluorescence (IF) and IP techniques for estimation of the proportions of cells displaying a variety of antigens; with normal blood cells the results were closely similar but with chronic lymphocytic leukemia (CLL) cells, IP was superior to conventional IF. Using 910 D7, a new anti-la antibody, we were able to observe directly the presence of la-positive lymphocytes and monocytes in normal peripheral blood and la-positive granulocyte precursor cells from 2 cases of chronic granulocytic leukemia (CGL) in transformation. The method is useful for immunophenotyping of cases of lymphoproliferative disorder (LPD) and for morphological identification of specific antigen-positive cells.
Antibodies, Monoclonal↗
How zealously should a patient with relapsed acute myeloid leukaemia be treated? Good survival after five simultaneous, potentially lethal, complications.
A relapse of acute myeloid leukaemia occurred in a 45-year-old woman 18 months after the disease was initially diagnosed and treated. During remission reinduction therapy, she developed a Gram-negative septicaemia, acute respiratory failure, acute renal failure, diabetic hyperglycaemia with ketoacidosis, and probable bacterial meningitis. She required assisted respiration for two days, received peritoneal dialysis for five days, and was unconscious for seven days. The patient eventually recovered, achieved full remission of her leukaemia, and survived a further 2 1/2 years, mostly in excellent health. Oncologists are often criticized for unjustifiable optimism and excessive zeal in the treatment of patients with malignant disease. This case illustrates that such optimism and zeal may be justified, and that intensive efforts to save the lives of seriously ill patients with chemosensitive malignant diseases are worthwhile.
Adult↗
Myeloproliferative and lymphoproliferative disorders in Tasmania, 1972-80: patterns in space and time.
During the period 1972-80, 866 patients with myeloproliferative (MP) and lymphoproliferative (LP) disorders were diagnosed in Tasmania. The residential histories of these cases were compared with those of population-based controls. No space-time clustering was demonstrated by individuals of any single diagnosis or group of diagnoses, nor were any regional differences in incidence detected. However, urban-rural differences were observed. Rural exposures were important especially in early childhood and at specific intervals before onset for certain diagnoses. Farm residence in early life yielded heightened relative risks, especially for sufferers from chronic lymphocytic leukemia and acute nonlymphoblastic leukemia. Regional analysis demonstrated elevated risks of residence in orcharding and dairying regions and in an urban-industrial municipality. High risks were associated with latent periods before diagnosis. The findings suggest environmental agents, acting prenatally or in early life, as well as in adult life, as important risk factors in the later development of MP and LP disorders.
Adult↗
Myeloproliferative and lymphoproliferative disorders in Tasmania, 1972-80: occupational and familial aspects.
All cases in a population-based series of myeloproliferative and lymphoproliferative (LP) disorders diagnosed in usual residents of Tasmania between 1972 and 1980 were asked for occupational histories and the occurrence of similar diseases in their close relatives. Occupational risks were observed for males who had farmed, mined, or worked in foundries and for women who had farmed or had been hairdressers. For individual diagnoses, the risk to farmers was seen to vary with age at diagnosis, sex, and region. With regard to familial risks, the LP and MP groups seemed to breed true, relatives being affected with a disorder from the other group not more often than would be expected by chance. The risks were of two kinds: Those to siblings and that between parent and child, particularly between mother and son. Occupational risks for the familial cases were limited to farming particularly in males diagnosed at 65 years of age or older. Females possessed elevated risks for the LP group only, and their highest relative risk was for those diagnosed before age 65. This evidence suggests that familial clustering of these disorders partly may be due to common environmental exposures in males from rural kindreds.
Adult↗
Cellular interactions and IL2 requirements of PHA-induced human T-lymphocyte colonies.
A number of conflicting proposals have been put forward as to the roles and identities of cooperating cells involved with human T-lymphocyte colony formation. To resolve this conflict, the principal cellular interactions of human T-lymphocyte colonies were analyzed using a two-step culture technique. Through mathematical analysis of cell dose-response curves the requirement for at least two populations of cooperating cells in addition to the colony-forming cell was demonstrated. By removing adherent cells prior to the first but not the second step, colony formation was inhibited, which suggests a restricted role for these cells during the early stages of colony formation. The dependence of the second step on interleukin 2 (IL2) availability implied that IL2-producing cells composed the other population of cooperating cells. We therefore propose that colony formation can be described by the two interdependent reactions of activation (T----T') and proliferation (T'----nT'). The first reaction requires an adherent cell (monocyte) population that together with PHA provides the necessary signals for cellular activation. Cell contact is needed to allow the expression of this adherent cell or interleukin 1 ( IL1 ) activity. As a result of these signals at least two subpopulations of lymphocytes are activated, the T-lymphocyte colony-forming cells themselves ( TLCFC ) and a population of cooperating T cells. These activated T cells interact during the second or proliferative reaction. In response to PHA the cooperating T cells release IL2, thereby enabling the activated TLCFs to proliferate into colonies. Thus for PHA-induced T-colony formation, TLCFCs required the cooperation of adherent cells for the activation reaction and IL2-producing T cells for proliferative reaction.
Agar↗
Effects of irradiation on PHA-induced T-lymphocyte colonies: differential effects according to the timing of irradiation.
To investigate the effect of irradiation on lymphocyte mitosis we utilized a T-lymphocyte colony assay; this sensitive technique avoided the methodological problems associated with previous techniques such as tritiated thymidine uptake. Irradiation doses in the range of 0.5 to 4 Gy had the effect of decreasing the lymphocytes' capacity to divide as shown by their reduced T-colony-forming ability. This radiosensitivity, however, was found to vary according to the timing of irradiation in relation to the stage of colony growth. Through survival curve analysis it was shown that the colony-forming cells could withstand higher irradiation doses without losing their replicative ability when they were irradiated prior to or during early stages of PHA stimulation. A similar "protection" by PHA stimulation has been well documented for nondividing T-lymphocyte functions but, due to the lack of a suitable methodology, had hitherto not been described for dividing T-lymphocytes. These results provide evidence that the early events associated with PHA stimulation might lead to an improved ability of T-lymphocytes to withstand higher doses of irradiation before mitotic death is registered.
Cell Division↗
Normal infant after combination chemotherapy including teniposide for Burkitt's lymphoma in pregnancy.
A 32-year-old woman was treated for Burkitt's lymphoma diagnosed during the 22nd week of pregnancy. Chemotherapy consisting of doxorubicin (Adriamycin), vincristine, teniposide (VM-26), cyclophosphamide, and prednisolone (AVTEP) was given each 2.5 to 3 weeks from the time of the diagnosis until delivery in the 37th week. Bleomycin and intrathecal methotrexate were also given from the 35th week. The infant was born after an assisted vaginal delivery and was fully developed and normal in all respects. This paper confirms prior reports that cytotoxic chemotherapy may safely be given during the second and third trimesters of pregnancy without adverse effects on the fetus. To our knowledge it is the first report of the use of teniposide, a new podophyllin derivative, during pregnancy.
Adult↗