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Biomedical subjects

S Ladisch

Publications and source records attributed to S Ladisch.

At least 91 records · Page 5Linked to original sources
PubMed1983

Identification by a monoclonal antibody of a glycolipid highly expressed by cells from the human myeloid lineage.

A monoclonal antibody (MAb) HL-C5, which bound selectively to cells of the myeloid lineage tested, was derived from a fusion between P3/NS2/1-AG8 myeloma cells and splenocytes from a mouse immunized with cells of the promyelocytic leukemia line HL-60. Among a panel of 29 human cell lines derived from either hematopoietic or solid tumors, MAb HL-C5 was found to react exclusively with cells from the five differentiated acute myeloid leukemia lines, HL-60, ML1, ML2, ML3, KG-1B and not with the less differentiated myeloid lines. Fluorescence-activated cell sorter analysis of normal bone marrow samples confirmed that the reactivity of MAb HL-C5 was limited to myeloid cells, from the promyelocytic stage of differentiation to the mature granulocytes. Indirect immunoperoxidase staining of cytocentrifuge preparations of normal bone marrow and peripheral blood leukocytes confirmed these results and showed that MAb HL-C5 stained neutrophils but not eosinophils or basophils. The antigen recognized by HL-C5 was recovered in the upper phase of chloroform-methanol-water lipid extracts prepared from HL-60 cells. By competitive binding experiments, it was found that MAb HL-C5 recognizes the same antigenic determinant as MAb WGHS 29-1, which has been reported to react with glycolipids containing the sugar sequence lacto-N-fucopentaose 111. Autoradiographs of thin layer chromatograms of HL-60 glycolipid extracts which were revealed by incubation with MAb HL-C5 or WGHS 29-1 followed by the addition of 125I-labelled rabbit anti-mouse immunoglobulin antibody confirmed that the two MAbs reacted with the same or structurally very similar glycolipids.

Animals↗
PubMed1983

Hepatic ganglioside abnormalities in a patient with familial erythrophagocytic lymphohistiocytosis.

Familial erythrophagocytic lymphohistiocytosis (FEL) is an autosomal recessive disease of unknown pathogenesis. Because of evidence of increased circulating and hepatic lipids in FEL, we performed a comprehensive analysis of the hepatic lipids of a patient with this disease. In contrast to normal qualitative characteristics and to normal or only mildly elevated concentrations of total lipids, neutral lipids, phospholipids, and neutral glycosphingolipids, this study reports a significant elevation of acidic glycosphingolipids, gangliosides (387 versus 147 nmole lipid-bound sialic acid/g wet weight, patient versus control). This quantitative abnormality was unusual in that it included disproportionately increased concentrations of most of the minor hepatic ganglioside species rather than either a marked increase in one single or a generalized nonspecific increase in all gangliosides, which is characteristic of known disorders exhibiting hepatic ganglioside storage. Activities of the hepatic lysosomal glycosylhydrolases which are important in ganglioside metabolism were therefore assessed by using artificial substrates. Of the enzymes tested, beta-galactosidase activity alone was remarkable, being moderately reduced (33% of that of the normal liver); no biochemical explanation for the reduction was found. The findings suggest FEL may be associated with a unique quantitative and qualitative abnormality in hepatic gangliosides, the cause of which remains to be elucidated.

Child, Preschool↗
PubMed1983

Shedding and immunoregulatory activity of YAC-1 lymphoma cell gangliosides.

YAC-1 lymphoma cells, both when cultured in vitro and when passaged in ascites form in vivo, synthesize gangliosides (means of 22.1 and 14.7 nmol lipid-bound sialic acid isolated per 10(8) cells, respectively) with potent inhibitory effects on mitogen- and antigen-induced lymphoproliferation: 10 to 30 nmol highly purified YAC-1 gangliosides/ml caused greater than 90% inhibition of proliferative responses of murine lymphocytes to concanavalin A, lysozyme (a soluble specific antigen), and allogeneic cells (mixed-lymphocyte response). Measureable quantities of these gangliosides were shed by the tumor cells in vitro and also were recovered from the ascites fluid in vivo. Furthermore, the gangliosides isolated from ascites fluid (mean of 15.3 nmol/ml) had inhibitory activity of a magnitude similar to that of the gangliosides isolated from the tumor cells. Therefore, significant inhibition of normal lymphoproliferative responses by tumor-derived gangliosides occurred at ganglioside concentrations which are actually present in the fluid surrounding the tumor cells in vivo. These results support the hypothesis that shedding of gangliosides may serve to protect tumor cells from host immune destruction.

Cells, Cultured↗
PubMed1983

Retention of gangliosides in serum delipidated by diisopropyl ether-1-butanol extraction.

Extraction with diisopropyl ether-1-butanol is a rapid method for the delipidation of serum without protein denaturation. We sought to confirm that this solvent system would also extract the highly polar acidic glycosphingolipids, gangliosides. In fact, however, both endogenous serum gangliosides and radiolabeled rat brain gangliosides added to serum were nearly quantitatively retained (87.5% and 98.7%, respectively) in the aqueous phase after two extractions. Therefore, while useful for the extraction of most lipids, this delipidation procedure cannot be used to remove gangliosides from serum or plasma.

1-Butanol↗
PubMed1982

Influence of monovalent cation concentrations on monocyte-mediated ADCC.

Monocyte-mediated ADCC was inhibited by ouabain, which blocks active transport of Na+ and K+ by the membrane Na+K+-ATPase. Inhibition of ADCC was incomplete, however, even when monovalent cation transport was completely inhibited. On the other hand, increasing the duration of exposure to ouabain did result in complete inhibition of ADCC. ADCC was also depressed by incubation of monocytes in media with low (less than or equal to 1.5 mEq/l) or high (greater than or equal to mEq/l) K+ concentrations. The results suggest that monocyte ADCC is dependent upon monovalent cation concentrations (secondarily altered by ouabain exposure) but not upon active Na+K+ transport per se. Finally, since monovalent cation transport-related glycolysis accounted for essentially all of the previously observed increase in monocyte glycolysis associated with monocyte ADCC, we hypothesize that exposure of monocytes to sensitizing antiserum in the ADCC assay results in increased monocyte membrane permeability to monovalent cations.

Animals↗
PubMed1982

Plasma inhibition of lymphocyte proliferation in nephrotic syndrome: correlation with hyperlipidemia.

Plasma-mediated inhibition of normal lymphoproliferation is an unexplained immunologic abnormality frequently observed in nephrotic syndrome. Since hyperlipidemia, also common in nephrotic syndrome, has been linked with in vitro and in vivo immunodeficiency in other diseases, we have quantitated plasma-mediated inhibition of lymphoproliferation and related it to the degree of hyperlipidemia in 19 patients with nephrotic syndrome. Fifteen patients were hyperlipidemic; the plasma of 9 of these 15 caused greater than 60% inhibition of antigen-specific proliferative responses of normal lymphocytes. None of the four normolipidemic plasmas, nor a hyperlipidemic plasma depleted of lipoproteins by ultracentrifugation, was inhibitory. A highly significant correlation between the degree of inhibition and the plasma triglyceride levels in patients with nephrotic syndrome was observed (P less than 0.001). The results suggest that elevated plasma lipids may be the cause of the plasma-mediated inhibition of lymphoproliferation in nephrotic syndrome.

Adolescent↗
PubMed1982

Inhibition of monocyte-mediated antibody-dependent cellular cytotoxicity by ouabain: relationship between cytotoxic function, glycolysis, and intracellular cation homeostasis.

Ouabain, a specific inhibitor of membrane Na+K+-ATPase, was used to study the relationship between monovalent cation, homeostasis and cytotoxic effector function. 5 X 10(-6) M ouabain completely inhibited monocyte monovalent cation active transport within 30 min but caused only 50% inhibition of monocyte-mediated antibody-dependent cellular cytotoxicity (MMADCC) in a subsequent 20-hr assay. Longer (6-hr) preincubation of monocytes in ouabain was required for nearly complete inhibition of cytotoxic function. The previously reported augmentation of monocyte glycolysis caused by the sensitizing antiserum was decreased by 71% in 5 X 10(-6) M ouabain, identifying monovalent cation transport as the cellular function utilizing a major portion of the ATP generated by this augmentation of glycolysis. The lag in inhibition of MMADCC indicated, however, that a delayed effect of ouabain (e.g., changes in intracellular [K+] and [Na+]), and not the rapid ouabain inhibition of cation transport, caused inhibition of cytotoxic function. Four additional findings support this interpretation: i) a 30-min preincubation in ouabain caused little inhibition of MMADCC in a 4-hr assay; ii) monocytes lost cytotoxic activity when incubated in medium (0.2 mEq/cytotoxic activity when incubated in medium (0.2 mEq/liter) that reduces intracellular [K+]; iii) the rapid recovery of cytotoxic activity after readjustment of extracellular [K+] to 6 mEq/liter was blocked by ouabain; iv) increasing membrane K+ permeability by valinomycin while blocking active transport by ouabain caused 50% inhibition under conditions in which neither agent alone significantly affected MMADCC. Thus, it is suggested that homeostasis of monocyte intracellular [K+] and [Na+], but not monovalent cation active transport per se, is required for cytotoxic function.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1982

Immunologic and clinical effects of repeated blood exchange in familial erythrophagocytic lymphohistiocytosis.

Depressed cellular immune function and increased susceptibility to infection characterize familial erythrophagocytic lymphohistiocytosis (FEL), a usually fatal autosomal recessive disease. One component of the immunodeficiency is plasma-mediated inhibition of lymphocyte proliferation. We have tested whether repeated plasma or blood exchange would decrease plasma inhibitory activity and improve cellular immune function in FEL. Following this treatment, reduction in plasma inhibitory activity, reversal of depressed antigen-specific lymphocyte proliferative responses and monocyte antibody-dependent cytotoxic function in vitro, and clinical improvement were complete in two and partial in one of three patients studied. Relapse, which was ultimately fatal, was associated with recurrence of the immune defects. These findings suggest that cellular immunodeficiency in FEL is acquired and possibly related to circulating immunosuppressive activity, the removal of which is associated with transient immunologic and clinical recovery.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1980

Improved treatment results in the management of single and multiple relapses of acute lymphoblastic leukemia.

One hundred twenty-five hematologic relapses of acute lymphoblastic leukemia (ALL) were treated with a four-drug reinduction regimen consisting of L-asparaginase, vincristine, daunomycin, and prednisone (Asp-VDP). Complete remission was achieved in 114 of 125 (91%) treatment courses. The regimen also proved to be highly effective in the management of multiple subsequent relapses which occurred in patients who had previously attained complete remissions with this regimen. The rates of remission induction for second and third reinduction attempts were 89% and 90%, respectively. Ten patients received this regimen for the treatment of four or more consecutive relapses and achieved complete remissions on each occasion. Toxicities related to therapy were not excessive. Although myelosuppression was the most frequently encountered toxicity, documented infection complicated only 14% of the treatment courses. These results constitute a considerable improvement in the management of recurrent ALL.

Adolescent↗
PubMed1980

Treatment of gram-positive septicemia in cancer patients.

Seventy-eight pediatric cancer patients were treated for gram-positive bacterial septicemia during a 10-year period (1968-1977). Sixty-one (78%) of the patients were granulocytopenic (PMNs less than 500/mm3) at the onset of the septic episode. All the patients whose granulocytopenia resolved (PMNs greater than 500/mm3) within one week of therapy recovered without sequelae. However, 7 of 15 patients (47%) who remained granulocytopenic for more than 7 days and who were treated with a single antibiotic developed a second sepsis with a gram-negative organism. In contrast, second infections were not observed in 24 patients with PMNs less than 500/mm3 for more than 7 days who were treated with broad spectrum antibiotics (p less than 0.002), suggesting that a broad-spectrum antibiotic regimen may be preferable when a cancer patient has prolonged granulocytopenia.

Agranulocytosis↗
PubMed1979

Extrapulmonary manifestations of adenovirus type 7 pneumonia simulating Reye syndrome and the possible role of an adenovirus toxin.

Three children developed extensive extrapulmonary disease in the course of fatal adenovirus type 7 pneumonia. Several clinical features, including the unexpected onset of coma, suggested the development of Reye syndrome, but biochemical and histopathologic findings were inconsistent with this diagnosis. Virologic and pathologic studies did not reveal evidence of extrapulmonary adenovirus infection, despite clinical involvement of the liver, skeletal muscle, and central nervous system. The detection in premortem sera from all three patients of adenovirus penton antigen, known to be cytotoxic in vitro, suggests a possible mechanism for the production of extrapulmonary pathology in the absence of extrapulmonary virus infection.

Adenoviridae Infections↗
PubMed1979

Bacillus Calmette-Guérin enhancement of colony-stimulating activity and myeloid colony formation following administration of cyclophosphamide.

Pretreatment of mice with Bacillus Calmette-Guérin (BCG) enhances recovery of the peripheral granulocyte count from cyclophosphamide (CTX)-induced leukopenia. In the present study, in vitro bone marrow culture was used to assess the effect of BCG pretreatment on serum levels of myeloid colony-stimulating activity and on regeneration of bone marrow myeloid colony-forming units (CFU-c) following CTX. C57BL/6 mice received either BCG or 0.9% NaCl solution i.p. 8 days prior to the administration of CTX (300 mg/kg i.p.). Following CTX, peak serum levels of myeloid colony-stimulating activity were strikingly higher in the BCG-pretreated mice [1320 +/- 30 (S.E.) units] than in the 0.9% NaCl solution-pretreated mice (764 +/- 37 units). BCG pretreatment also resulted in higher numbers of marrow CFU-c during recovery from CTX (e.g., 43.9 +/- 1.8 versus 20.0 +/- 0.9 myeloid colonies/10(5) marrow cells, Day 3 post-CTX). However, neither the rate of decline nor the absolute nadir of CFU-c, nor CFU-c cell cycle characteristics were affected by the pretreatment. The initial effect of i.p. BCG pretreatment on recovery from CTX-induced granulocytopenia is an augmentation of serum myeloid colony-stimulating activity which precedes the enhanced regeneration of CFU-c and the accelerated recovery of the peripheral granulocyte count.

Animals↗
PubMed1978

Immunodeficiency in familial erythrophagocytic lymphohistiocytosis.

4 children with familial erythrophagocytic lymphohistiocytosis and hyperlipidaemia were found to have a previously unrecognised immunological deficiency syndrome which included defects in both humoral and cellular immunity and a plasma inhibitor of in-vitro lymphocyte blastogenesis. The inhibitory activity was proportional to the increase in the triglyceride concentration in the patients' plasma. Immunological deficiency, to which hyperlipidaemia may be a contributing factor, appears to be a significant feature of familial erythrophagocytic lymphohistiocytosis.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1978

Alpha-hemolytic streptococci: clinical significance in the cancer patient.

Alpha-hemolytic Streptococci were associated with 29 episodes of sepsis (12 polymicrobial) in 27 patients with cancer during a nine year period. Only two patients had dental manipulation prior to the onset of sepsis, but each had received chemotherapy and 75% were granulocytopenic (PMN less than 500/mm3) at the time of the infection. None of the patients developed bacterial endocarditis. Unlike the normal host in whom a transient bacteria with alpha-hemolytic Streptococci may occur following dental extraction or periodontal procedures, the cancer patient is at risk for more clinically significant sepsis. This risk is probably related to the presence of chemotherapy-induced oral mucusitis and granulocytopenia, and our results suggests that isolation of alpha-hemolytic Streptococci in febrile cancer patients should not be dismissed as a contaminent.

Adolescent↗
PubMed1978

Increasing incidence of Gram-positive sepsis in cancer patients.

A review of the agents causing septicemia in cancer patients during a nine-year period (1968--76) revealed that Gram-positive organisms (especially S aureus) have become the most frequent isolates during the last two years. This unanticipated increase (P less than 0.001) in the number of Gram-positive isolates could not be related to horizontal transmission nor to changes in patient characteristics or therapy.

Adolescent↗
PubMed1978

Staphylococcus aureus sepsis in children with cancer.

Seventy episodes of Staphylococcus aureus sepsis occurring over a nine-year period in pediatric cancer patients are reviewed. Prominent findings at the time of diagnosis included fever, granulocytopenia, and active malignancy. Probable or suspected sites of primary infection were present in 40 episodes (57%). Serious direct complications of staphylococcal sepsis included only three cases of pneumonia and one of myositis. However, second infections by other organisms developed in 16 episodes (24%), resulting in nine nonstaphylococcal infectious deaths during therapy. Endocarditis and osteomyelitis never occurred in this group of patients. The median duration of antistaphylococcal therapy was 15 days.

Acute Disease↗
PubMed1978

Acceleration of myeloid recovery from cyclophosphamide-induced leukopenia by pretreatment with Bacillus Calmette-Guérin.

Treatment of C57BL/6 mice with Bacillus Calmette-Guérin i.p. 8 days prior to the induction of leukopenia by cyclophosphamide (300 mg/kg i.p.) significantly (p less than 0.002) increased peripheral granulocyte counts on each day during the recovery from leukopenia. The recovery of lymphocyte counts was unaffected by Bacillus Calmette-Guérin treatment. Further experiments indicated that the accelerated granulocyte recovery was the result of an earlier initiation of the recovery process rather than of the release of stored granulocytes. Bacillus Calmette-Guérin may have clinical value as a stimulator of myelopoiesis in patients rendered leukopenic by antineoplastic chemotherapy.

Animals↗