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Biomedical subjects

D Aderka

Publications and source records attributed to D Aderka.

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

IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice.

Incubation of the human U937 histiocytic lymphoma cell line with granulocyte-macrophage colony stimulating factor (GM-CSF) rendered the cells responsive to induction of TNF by LPS. Treatment with IL-6 reduced TNF production in GM-CSF-primed U937 cells. The inhibitory effect was most pronounced (approximately equal to 80%) when IL-6 was added either along with GM-CSF or within the first 3 h of GM-CSF treatment. Both GM-CSF or IL-6 inhibited [3H]TdR uptake in U937 cells, and simultaneous treatment with GM-CSF and IL-6 resulted in an additive inhibitory effect on cell proliferation. However, the inhibition of TNF production could not be explained by the inhibitory effect of IL-6 on cell growth, nor was it due to a reduction in cell viability. An inhibition of TNF production by IL-6 was also demonstrated in cultured human peripheral blood monocytes. Treatment with IL-6 also resulted in a dose-dependent reduction of the 17-kDa TNF band revealed by SDS-PAGE after labeling monocytes with [35S]cysteine and immunoprecipitation with anti-TNF mAb. In addition, treatment with IL-6 resulted in a reduction of monocyte in vitro cytotoxicity for tumor target cells. Finally, in mice sensitized by the administration of Bacillus Calmette-Guérin, the injection of IL-6 significantly reduced the levels of TNF found in the serum upon challenge with LPS. Inasmuch as TNF is known to be an inducer of IL-6, the inhibitory action of IL-6 on TNF production may represent the negative arm of a regulatory circuit. The inhibitory action of IL-6 on TNF production is consistent with a predominantly antiinflammatory role of IL-6 in the intact organism.

Animals↗
PubMed1989

A tumor necrosis factor-binding protein purified to homogeneity from human urine protects cells from tumor necrosis factor toxicity.

Unfractionated preparations of the proteins of human urine provided protection against the in vitro cytocidal effect of tumor necrosis factor (TNF). In certain cells, the proteins decreased expression of the receptors for TNF in a temperature-dependent way. In all cells examined, the proteins were found to interfere also with the binding of both TNF and interleukin-1 when applied directly into the binding assays. That effect could be observed in the cold, suggesting that it was independent of cellular metabolism. A protein which protects cells against the cytotoxicity of TNF was purified from human urine by chromatography on CM-Sepharose followed by high performance liquid chromatography on Mono Q and Mono S columns and reversed phase high performance liquid chromatography. This protein is a very minor constituent of normal urine, with an apparent molecular weight of about 27,000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under both reducing and nonreducing conditions. Homogeneity of the purified protein was confirmed by microsequence analysis which revealed a single N-terminal sequence: Asp-Ser-Val-Cys-Pro-. The protein protected cells from TNF toxicity at concentrations of a few nanograms per ml and interfered with the binding of both TNF-alpha and TNF-beta to cells, when applied simultaneously with the cytokines. However, unlike crude preparations of the urinary proteins, the purified protein did not induce in cells a decrease in ability to bind TNF nor did it interfere with the binding of interleukin-1 to its receptor. Direct, specific binding to the protein of TNF-alpha and, to a lesser extent, also TNF-beta, but not of interleukin-1 nor interferon-gamma could be demonstrated. It is suggested that this protein blocks the function of TNF by competing for TNF with the TNF receptor and not by interacting with the target cell.

Binding, Competitive↗
PubMed1988

Recombinant interferon alpha-C for advanced hairy cell leukemia. An Israeli multicenter study.

Thirteen patients with advanced hairy cell leukemia were treated with a new subspecies of interferon (IFN): recombinant IFN (rIFN)-alpha-C. The timing of the peripheral hematologic remission of individual blood elements was similar to that reported for other interferons, and 60% of patients attained a complete peripheral hematologic remission at 9 months. Two patients relapsed despite a good initial response to IFN. No anti-IFN antibodies could be detected in their sera. In vitro studies of colony formation from the peripheral blood of all responding patients showed that rIFN-alpha-C did not inhibit the growth of colonies but favorably affected the maturation of their elements towards monocytes, granulocytes, and erythroid elements. The relapsing patient examined initially experienced a similar beneficial in vitro response which paralleled his in vivo improvement. During relapse, rIFN-alpha-C inhibited both the colony formation and the myelomonocytic differentiation in the in vitro cultures. These findings may suggest that the acquired resistance to IFN in our patient could be due either to an acquired stem cell maturation arrest in response to IFN or to emergence of a new clone indifferent to IFN-alpha-C differentiation effect.

Age Factors↗
PubMed1988

Amylase-creatinine clearance ratio. A simple test to predict gentamicin nephrotoxicity.

The initial target of aminoglycoside nephrotoxicity is the proximal tubule. Yet, no simple test is available to predict such toxicity. Taking advantage of the fact that amylase is filtered in the glomerulus and reabsorbed by the proximal tubules, we prospectively examined in 23 patients if changes in renal amylase creatinine clearance ratio (ACCR) can predict gentamicin nephrotoxicity. Eighteen of these patients had an initial creatinine clearance (rCcr) above 30 mL/min. Eleven of them (group A) had an ACCR above 3.5% (control 3% +/- 1.03%) and all exhibited an average reduction of 32.2% +/- 11.6% in rCcr following one week of gentamicin therapy. In contrast, only one of seven patients (group B) with an initial ACCR below 3.5% had a reduction, albeit transient, in rCcr. During gentamicin therapy, group A patients had a further increase in ACCR which was proportional to the reduction observed in rCcr (r = -.54). Our preliminary data suggest that ACCR may prove a simple and possibly a reliable predictor of kidney function deterioration during gentamicin therapy in patients with rCcr above 30 mL/min: patients with pretherapy ACCR above 3.5% may exhibit a deterioration in the creatinine clearance during the first week of therapy. For patients with pretherapy renal failure (rCcr less than 30 mL/min) the creatinine levels (but not the ACCR) seem to retain their significance in predicting and monitoring further renal function deterioration during aminoglycoside therapy.

Acute Kidney Injury↗
PubMed1988

Interferon-beta induced remission in a hairy cell leukemia patient resistant to interferon-alpha.

Two patients with advanced hairy cell leukemia and pancytopenia responded successfully to intramuscular injections of recombinant interferon-beta, with normalisation of blood counts. One of the patients had developed resistance to interferon-alpha. The in-vivo response was predicted by in-vitro studies showing a beneficial effect of IFN-beta on erythropoiesis in cell cultures derived from these patients.

Bone Marrow↗
PubMed1988

Does tumor necrosis factor play a role in the pathogenesis of fulminant hepatitis?

Fulminant hepatitis is associated with an 80% mortality rate. Surviving patients do not develop chronic liver disease. Failure to produce adequate amounts of interferon and to achieve an antiviral state seem to be the basic defects in this condition. Tumor necrosis factor (TNF) has been shown to be induced by viruses. By rapid lysis of virus infected cells, it also prevents optimal viral replication thus reducing the viral yield and the infection rate and extent. On the other hand, it has growth promoting characteristics. We postulate that TNF has a dual role in fulminant hepatitis: (a) It acts as an antiviral agent by eliminating virus infected cells thus reducing viral yields and limiting spread of infection; (b) it may be the signal for hepatocyte regeneration. Only those patients, in whom the regeneration rate exceeds lysis of infected hepatocyte by TNF, survive.

Hepatitis, Viral, Human↗
PubMed1988

Fulminant Wilsonian hepatitis: difficulties in diagnosis and treatment.

We present herein the case of a 16-yr-old girl with fulminant Wilsonian hepatitis. Complications included renal tubular damage, hemolysis, marked hypocomplementemia and hypergammaglobulinemia, spontaneous bacterial peritonitis, and Candida sepsis. The difficulties in diagnosis and treatment are discussed.

Adolescent↗
PubMed1987

Reduced production of tumor necrosis factor by mononuclear cells in hairy cell leukemia patients and improvement following interferon therapy.

In 16 patients with hairy cell leukemia (HCL) there was a marked reduction in the production of cytotoxins (CTXs) by peripheral blood mononuclear leukocytes in response to stimulation in vitro by phytohemagglutinin (PHA), 4 beta-phorbol-12-myristate-13-acetate (PMA), or Sendai virus. CTX yields of 23.5 +/- 21.5 U/ml, 15 +/- 18 U/ml, and 12.1 +/- 12.1 U/ml were obtained in response to PHA, PMA, and Sendai virus, respectively, as compared with corresponding yields of 207.3 +/- 93.1, 154 +/- 37.4, and 205.2 +/- 62.4 in healthy controls. The extent of reduced production of CTXs appeared to be correlated with the severity of the disease. Systemic interferon (IFN) administered to four patients caused CTX production to improve in response to PHA (147.5 +/- 55.1 U/ml compared with pretreatment values of 14.1 +/- 6 U/ml, P less than 0.05). However, CTX production in response to Sendai virus remained low. The extent to which CTX production by hairy cell leukemia mononuclear cells was reduced was proportionate to the observed decrease in monocyte counts. However, the degree to which CTX production improved after IFN treatment was significantly greater than the observed increase in monocyte counts. The major CTX induced by PHA in mononuclear cells of healthy donors and of IFN-treated HCL patients was identified as tumor necrosis factor-alpha.

Adult↗
PubMed1987

Bacteremic hypocalcemia. A comparison between the calcium levels of bacteremic and nonbacteremic patients with infection.

Hypocalcemia has been documented in critically ill patients, including those with sepsis and shock. However, its incidence and significance in bacteremic patients without shock has not been established. In the present study the presence of hypocalcemia was evaluated in a group of 67 consecutive bacteremic patients, as compared with 64 infected but nonbacteremic patients. After correction of serum calcium level for serum protein, 25 of the bacteremic patients (37.3%) had "corrected" hypocalcemia (less than 8.5 mg/dL [2.12 mmol/L]), compared with only three in the nonbacteremic group (4.5%). The incidence and magnitude of hypocalcemia in gram-positive and gram-negative infections was similar. In hypocalcemic patients, the "corrected" calcium level was found to be inversely correlated with day of disease and attained a nadir on day 6 to 8 of bacteremia. This nadir was significantly lower in male than in female subjects. Hypocalcemic patients had a significantly higher maximal temperature than normocalcemic ones, but hypocalcemia was unrelated to serum levels of albumin, transaminase, and creatinine.

Aged↗
PubMed1986

Idiopathic deep vein thrombosis in an apparently healthy patient as a premonitory sign of occult cancer.

An association between migratory venous thrombosis or acute pulmonary embolism and occult cancer has been previously suggested. The relationship between the commoner deep venous thrombosis (DVT) in an otherwise healthy individual and occult cancer is not known. The incidence of cancer in 35 otherwise healthy patients with idiopathic DVT (group A) was compared to 48 patients with DVT due to a known etiology, excluding cancer (group B). In 12 patients of group A (34%), a diagnosis of cancer was established 4-68 months after the DVT episode, compared to 2 patients of group B (4%) (P = 0.001). The origin of the earliest discovered cancer (up to 8 months) was the reproductive organs (ovary, endometrium, prostate, breast), while the later discovered malignancies were of colon, pancreas, lung and a lymphoma. At the initial idiopathic DVT episode, patients found subsequently to have cancer, were older than the control group (P less than 0.01), had hemoglobin concentration lower than 12.4 g/dl (P less than 0.02), and had eosinophil counts higher than 3% (P less than 0.01). A score devised from these parameters could identify 83% of the patients with cancer and 91% of those without malignancy (P = 0.00003). These findings indicate that there is a correlation between idiopathic DVT and occult cancer and that the majority of the patients at risk may probably be identified early by the score devised.

Age Factors↗
PubMed1986

Tumor necrosis factor induction by Sendai virus.

Supernatants of peripheral blood mononuclear leukocytes (PBMC) treated with Sendai virus were found to exert significant cytotoxic effects mediated by leukocyte-produced proteins distinct from interferon. Fractionation of the PBMC into adherent and nonadherent cells indicated that these virus-induced cytotoxins (CTX) were produced primarily in the mononuclear phagocytes. Cells of the monocyte-like U937 line pretreated with 4 beta-phorbol-12-myristate-13-acetate could also be induced with Sendai virus to produce CTX. The nonadherent mononuclear cells of the peripheral blood responded poorly to the virus with regard to CTX production, even though they could be induced to produce CTX with phytohemagglutinin (PHA). With the use of monospecific antibodies to tumor necrosis factor (TNF) and to lymphotoxin (LT), it was found that TNF is the major CTX produced by PBMC and by the U937 cells after 24 hr stimulation by the virus, whereas LT is not induced under these conditions to any measurable extent. TNF was also found to be produced in significant amounts together with LT upon stimulation of the nonadherent fraction of the PBMC by PHA. These findings indicate that besides bacterial lipopolysaccharides, other biological agents including viruses can be effective inducers of tumor necrosis factor, suggesting implications regarding the physiologic role of this protein.

Cell Adhesion↗
PubMed1986

Bleeding due to thrombocytopenia in acute leukemias and reevaluation of the prophylactic platelet transfusion policy.

Prophylactic platelet administration is indicated at counts below 20 X 10(9)/l. The bleeding tendency and severity were compared between thrombocytopenic patients with acute-lymphocytic leukemia (ALL) and acute non-lymphocytic leukemia (ANLL) in the ranges of 10-20 X 10(9)/l platelets, while prophylactic platelet administration was given only below 10 X 10(9)/l. The bleeding tendency for ALL was quite similar at platelet counts above or below 10 X 10(9)/l. The bleeding tendency was significantly lower (p less than 0.001) when the platelets were above this level in ANLL patients. When the thrombocytopenia was caused by chemotherapy, the bleeding was significantly lower in both types of leukemia above 10 X 10(9)/l (p less than 0.05 for ALL, p less than 0.001 for ANLL) as compared with lower counts. When the thrombocytopenia was caused by leukemia, the bleeding tendency was similar in both types of leukemia and at all platelet counts (below 20 X 10(9)/l). Fever, not associated with sepsis, augmented the bleeding severity of patients with ANLL. Stable or rising counts of platelets were associated with significantly lower bleeding tendency above 10 X 10(9)/l only in ANLL patients. The decision for prophylactic platelet administration at counts below 20 X 10(9)/l should be guided by the type of the leukemia (ALL vs. ANLL), the cause of thrombocytopenia (chemotherapy vs. leukemia per se), the trend of the platelet counts, presence of fever and patient's age (below or above 18 years).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗