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Biomedical subjects

C Kaplinsky

Publications and source records attributed to C Kaplinsky.

At least 55 records · Page 3Linked to original sources
PubMed1989

Biologic and cytogenetic characteristics of leukemia in infants.

Clinical features, leukemic cell characterization, chromosomal findings, and treatment outcome were analyzed in a retrospective study of 30 cases with acute leukemia of infancy, 24 infants with acute lymphoblastic leukemia (ALL), and six cases with acute nonlymphoblastic leukemia (ANLL). Extensive bulky disease with organomegaly, central nervous system (CNS), and skin involvement were prominent features at diagnosis with a higher frequency in ANLL as compared to ALL. Four of six ANLL patients were classified as monocytic or myelomonocytic. In the ALL group nine of 24 (36%) were non-L1 morphology and six of 17 (33%) were common ALL antigen (CALLA) negative, the majority of them (five of six) were included in the non-L1 group. Immunophenotyping revealed four cases with early B-cell (three patients: Ia+B4+, and one patient: Ia+) and two cases with T-cell. Mixed lineage leukemia was found in five infants. Heavy chain immunoglobulin gene rearrangement was present in six cases tested, two CALLA+, two with Ia+B4+, and two were undifferentiated mixed lineage leukemia. Chromosomal aberrations were detected in ten of 18 patients, mostly in ANLL and CALLA negative ALL. Translocations were detected in six patients, involving 4q21-23 and 11q23 in three and two cases, respectively. The probability of five-year DFS were 27% for the whole group. The worst prognosis was observed in infants younger than 6 months of age, in whom the leukemia cell characteristics was compatible with stem cell: ANLL, very early pre-B, or undifferentiated mixed type. The chromosomal aberrations found in all cases included translocation with the seemingly nonrandom breakpoints at 4q21 and 11q23, and breakpoints that corresponded to known fragile sites. This finding may be suggestive of an underlying genetic predisposition associated with the poor prognosis of leukemia of infancy.

Female↗
PubMed1988

Phenotypic and molecular characterization of inducible human neuroblastoma cell lines.

Two new neuroblastoma (NB) cell lines, NUB-6 and NUB-7, were established from recurrent and primary NB tumours respectively and identified conclusively as NB by their phenotypic characteristics, catecholamine production and N-myc amplification. The cell lines could be distinguished on the bases of distinctive growth patterns in monolayer culture and semi-solid media (collagen gel and agarose), neurite formation and their response to four classes of growth and differentiation modulators. The NUB-6 cell line consisted of two distinct cell subtypes, small typical neuroblasts and larger spheroid-forming cells, while NUB-7 was homogeneously neuroblastic. Class-I agents (dibutyrl cyclic AMP [dbcAMP], butyrate, and papaverine) inhibited growth of both cell lines, while only dbcAMP stimulated the formation of short neurites by NUB-6 neuroblast cells in monolayer culture and collagen. Of the class-II agents (vitamins), retinoic acid inhibited growth of both cell lines and stimulated formation of long neurites by NUB-6 cells and NUB-7 cells in later passages. In contrast, vitamin E inhibited growth of NUB-6 and late-passage NUB-7, but stimulated early passage NUB-7. The class III agent (nerve growth factor) resembled vitamin E. The class-IV agents (interferons; rIFN-alpha 2a and rIFN-gamma 1) inhibited growth of both cell lines in monolayer culture and agarose, but stimulated NUB-6 neuroblasts and early passage NUB-7 cells to form long neurites. Thus phenotypically distinct NB cell lines were established in vitro and shown to be differentially influenced by various growth and differentiation modulators. The potent effect of IFN suggests a role for these modulators in NB behaviour in vivo.

Cell Aggregation↗
PubMed1988

Deferoxamine (Desferal)-induced ocular toxicity.

A 4-year-old girl with juvenile chronic myeloid leukemia relapsed after an allogeneic bone marrow transplantation (BMT) and became refractory to conventional chemotherapy. Treatment with two courses of high-dose deferoxamine, an iron chelator (130-180 mg/kg/day), along with low-dose ARA-c (5 mg/kg/day) caused a remarkable decrease of the WBC and fetal Hb. Three days following the last dose of deferoxamine, the patient experienced an acute visual loss, confirmed by electroretinogram (ERG) and visual evoked response (VER). Slight improvement occurred a few days later, but the patient developed severe pancytopenia and died of Klebsiella septic shock. The ocular manifestations were attributed to deferoxamine toxicity in light of the rapid onset after first exposure, the electrophysiological pattern of metabolic damage in the ERG and VER, and the long interval between the last chemotherapy and BMT. The pathogenesis of deferoxamine toxicity is discussed.

Blindness↗
PubMed1988

Eosinophilic granulomatous lymphadenopathy: association with hyper-IgE and eosinophilia.

Cervical lymph node enlargement is probably the most frequently detected childhood lymphadenopathy. We report 2 cases of cervical lymphadenopathy in children associated with hyper-IgE and eosinophilia, displaying the features of necrotizing eosinophilic granulomatosis. Immunohistochemical analysis and a serological work-up failed to elucidate the underlying etiology. We would like to call the attention of physicians and pathologists to this unusual clinical picture, different from the fatal form of necrotizing eosinophilic granulomatosis, and we suggest a role for the eosinophils in the pathologic appearance of the lymph nodes.

Child, Preschool↗
PubMed1987

Effect of deferoxamine on DNA synthesis, DNA repair, cell proliferation, and differentiation of HL-60 cells.

The ribonucleotide reductase inhibitors deferoxamine and hydroxyurea induce monocyte-macrophage cell differentiation in the leukemic cell line HL-60 as judged by the expression of cell surface antigens, nonspecific esterase activity, and morphological changes. Treatment of HL-60 cells with deferoxamine results in inhibition of DNA synthesis and irreversible loss of colony-forming ability. In addition, both deferoxamine and hydroxyurea caused an increase in the number of DNA strand breaks in HL-60 cells. A DNA methylating agent, N-methyl-N'-nitro-N-nitrosoguanidine, also caused cellular differentiation in HL-60 cells associated with DNA strand breaks. These observations are consistent with a role for DNA damage or for inhibition of DNA synthesis and repair in the differentiation process of HL-60 cells.

Antigens, Surface↗
PubMed1986

Selective protection of tubercidin toxicity by nitrobenzyl thioinosine in normal tissues but not in human neuroblastoma cells.

Tubercidin, an adenosine analogue, is toxic to human neuroblastoma cell lines, to peripheral blood mononuclear cells (PBMCs), and to myeloid colony-forming cells (CFU-C) as tested by a short-term labeled precursor uptake and by a clonogenic assay. When it was co-administered with a potent purine transport inhibitor, nitrobenzyl thioinosine (NBTI), the cytotoxic effect of tubercidin was abolished in PBMCs but not in neuroblastoma cells. Studies of nucleoside transport in neuroblastoma cells demonstrate that although [3H]NBTI binds to the plasma membrane of these cells, the transport of thymidine into the cells is only partially inhibited in the presence of excess NBTI. These data imply that neuroblastoma cells contain a nucleoside transport mechanism which is insensitive to NBTI. "Host protection" with a nucleoside transport inhibitor such as NBTI, may allow effective therapy with otherwise toxic dosages of tubercidin and other cytotoxic nucleosides in patients with neuroblastoma.

Biological Transport↗
PubMed1986

Modification of ribonucleotide and deoxyribonucleotide metabolism in interferon-treated human B-lymphoblastoid cells.

The effect of recombinant interferon-alpha 2 (IFN-alpha 2) (50 U/ml) on the cell cycle, nucleotide metabolism, and protein and nucleic acid synthesis was studied in human B-lymphoblastoid (Daudi) cells. Cell cycle analysis showed that IFN treatment resulted in G0/G1 arrest (69%) as compared to control cells (42% at G0/G1). IFN inhibited the incorporation of radioactive thymidine and uridine into DNA and RNA, respectively, but had only slight effect on incorporation of radioactive threonine, leucine, or valine into proteins. IFN inhibited ribonucleotide biosynthesis by de novo and salvage pathways and decreased level of the P-ribose-PP. Both pathways of deoxyribonucleotide biosynthesis, ribonucleotide reduction and deoxyribonucleoside salvage, were also markedly inhibited by IFN., In contrast, ribonucleotide catabolism was significantly increased in the presence of IFN. No changes in ribonucleotide interconversion were found. Intracellular concentrations of both ribonucleotides and deoxyribonucleotides were markedly diminished by IFN. These results suggest that inhibition of both ribonucleotide and deoxyribonucleotide biosynthesis, together with increased rate of nucleotide catabolism, may significantly decrease intracellular nucleotide availability. Decrease of the supply of nucleic acid precursors, as well as limitation of nucleotides for energy metabolism and other processes, may result in the inhibition of cell multiplications.

B-Lymphocytes↗
PubMed1986

Induction of differentiation in HL-60 promyelocytic cells: a comparative study in two sublines.

Two variants of HL-60 promyelocytic leukemia cells (HSC, OCI) that were indistinguishable by morphology, cell surface markers, DNA histograms, and by their inability to reduce nitroblue tetrazolium, were induced to differentiate by retinoic acid (RA), 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and by phytohemagglutinin-leucocyte conditioned medium (PHA-LCM). Only OCI cells were induced to differentiate to mature granulocytes by TPA. Both cell lines expressed, however, the monocytic associated cell surface antigen detected by MO1 monoclonal antibody in response to TPA. MO1 expression was detected as early as 32 hours after initiation of differentiation by TPA, whereas partial morphologic changes were apparent only after 72 hours. Induction of differentiation by retinoic acid led to a significant inhibition of colony formation in HSC variant (from 1522 +/- 60 to 523 +/- 20/10(4) cells plated) and in the OCI variant (from 628 +/- 20 to 185 +/- 33 colonies/10(4) cells plated). The addition of PHA-LCM further inhibited colony growth of both RA-induced cell lines (155 +/- 7/10(4) cells plated in HSC, and 59 +/- 4 in OCI). PHA-LCM by itself reduced HL-60 colony numbers in a dose-related manner, and also increased the expression of MO1 on noninduced HSC and OCI cells. These observations suggest that differentiation of HL-60 cells is not necessarily accompanied by concomitant change in morphology, cell surface characteristics, and proliferation potentials, and may be dependent on different degrees of cellular commitment. They also suggest a role for growth factors in the induction to maturation of leukemic cells.

Antibodies, Monoclonal↗
PubMed1981

Maturation of renal tubular transport of digoxin.

Previous data have suggested an age-related increase in renal tubular secretion of digoxin in infants and children receiving long-term digoxin therapy. This phenomenon could be the result of a maturational process or secondary to chronic substrate stimulation. To investigate this question, two groups of 2-week-old paired littermate rats received intraperitoneal injections of either digoxin or an equal volume of normal saline (control) on alternate days until sacrificed at 4, 6, and 8 wk of age. An additional group of 12-wk-old rats were studied as controls. 125I-labeled digoxin uptake was measured in renal cortical slices as the cPM/mg wet tissue slice/medium ratio (S/M). Both digoxin-treated and control rats demonstrated significant age-related increments in digoxin uptake. S/M ratios at 4, 6, 8, and 12 wk in he control group were 1.34 +/- 0.06, 1.39 +/- 0.14, 1.62 +/- 0.18 and 1.93 +/- 0.23, respectively (mean +/- S.D.) (r = 0.81; P less than 0.001). S/M ratios in the digoxin-treated animals at 4, 6, and 8 wk were 1.28 +/- 0.16, 1.33 +/- 0.09, and 1.52 +/- 0.23, respectively (r = 0.50; P less than 0.025), but did not differ significantly at each age from those in the control group. 125I uptake was significantly reduced by both dinitrophenol and sodium azide, as well as by a 100% nitrogen atmosphere. These results indicate that renal tubular transport of digoxin is an age-related energy dependent process which probably is not subject to substrate stimulation.

Age Factors↗
PubMed1980

Familial cholestatic cirrhosis associated with Kayser-Fleischer rings.

A brother and sister who suffered from pruritus since infancy developed hepatic cirrhosis early in life. Although this clinical picture has never been seen in Wilson's disease, Kayser-Fleischer rings in the boy made further studies necessary. Oral radiocopper loading tests administered to both children and to their parents served to exclude Wilson's disease conclusively. Determinations of the concentrations and patterns of bile acids in the serum indicated that the abnormalities observed in these children are not related to errors in bile acid synthesis. Although a defect in bile acid transport is present, it appears to have occurred as a consequence of the liver disease.

Child↗
PubMed1980

Digoxin-quinidine interaction: in vitro studies in rat tissue.

Clinically, the administration of quinidine to digitalized patients results in an elevation of serum digoxin concentration. It has been suggested that quinidine displaces tissue-bound digoxin and that renal digoxin clearance is reduced. We studied the influence of digoxin-quinidine interaction on 125I-digoxin uptake by various rat tissues in vitro, employing the tissue slice method. S/M digoxin ratios were kidney 1.72 +/- 0.24 (mean +/- S.D.), heart 2.36 +/- 0.31, muscle 2.05 +/- 0.21 (n = 23 for each), and fat 0.25 +/- 0.10 (n = 9). Addition of quinidine to the incubation medium resulted in a 17.4% reduction of digoxin uptake by kidney tissue to 1.42 +/- 0.38 (n = 24) (p < 0.01). Quinidine failed to reduce digoxin uptake in both heart and striated muscle. Metabolic blockade resulted in a significant reduction in digoxin uptake in kidney slices from 1.93 +/- 0.23 to 1.34 +/- 0.18 with DNP (n = 10) and to 1.30 +/- 0.15 (n = 10) with sodium azide (p < 0.001). Digoxin uptake in either heart or muscle was uninfluenced by metabolic blockers. We conclude that active energy-dependent transport mechanism for digoxin exists in renal cortical tissue. This mechanism is inhibited by either quinidine or metabolic blockers. In contrast, uptake in heart or muscle represents a different transport mechanism unaffected by quinidine or metabolic blockers.

Animals↗