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Biomedical subjects

M Shaklai

Publications and source records attributed to M Shaklai.

At least 73 records · Page 4Linked to original sources
PubMed1988

Phorbol-myristate-acetate-induced platelet aggregation in the presence of inhibitors.

4 beta-Phorbol-12-myristate-13-acetate (PMA) at 100 ng/ml was able to induce platelet aggregation in the presence of agents which inhibited aggregation, triggered by other agonists such as adenosine diphosphate sodium salt (ADP), thrombin and collagen. PMA induced aggregation in acid-citrate-dextrose platelet-rich plasma. 100 microM tetracaine, 5 microM bromophenacyl bromide and 0.2 mM mepacrine decreased PMA-induced aggregation by only 10% in contrast to their high inhibitory effect on other aggregation systems. However, 0.4 mM mepacrine did inhibit PMA-induced aggregation at the same rate as the other aggregation systems. 100 mg/ml vincristine slightly affected PMA-induced platelet aggregation, whereas cytochalasin B rather enhanced it. Nordihydroguaiaretic acid, 5, 8, 11, 14-eicosatetraynoic acid and p-nitrophenyl-phosphorylcholine had no effect on PMA- or collagen-induced platelet aggregation, partially inhibited aggregation triggered by ADP and strongly inhibited aggregation caused by thrombin. It is suggested that PMA exerts its effect on platelets mainly due to its ability to alter their membranes.

Blood Glucose↗
PubMed1988

Inhibition by retinoic acid of myeloid progenitors in chronic myeloid leukemia and myeloproliferative disease: increased sensitivity in blastic phase of chronic myeloid leukemia.

The effects of all-trans retinoic acid (RA) were tested on the growth in vitro of myeloid progenitors from peripheral blood or bone marrow, in 25 patients with chronic myeloid leukemia (CML), ten of whom were either in accelerated or blastic phase, and in nine patients with myeloproliferative disease (MPD). The responses were compared with 12 normal bone marrow controls obtained from patients with lymphoma. Clonal growth in CML blastic and accelerated phase was inhibited to the greatest degree (mean 49 +/- 9% (SEM) of control at 0.3 microM RA). The responses in CML chronic phase and MPD were more heterogeneous, but significant inhibition was seen at higher concentrations of RA (50 +/- 12% CML chronic phase, 58 +/- 26% MPD at 3.0 microM RA). At 0.3 microM and 1.0 microM RA there were significant differences between the CML chronic phase and the CML blastic phase patients (p less than 0.02 and p less than 0.05 respectively). At these concentrations there was no significant inhibition on normal bone marrow myeloid progenitors. Inhibition was independent of the proportions of progenitors in S phase, as assessed by tritiated thymidine suicide. Preincubation of cells from selected patients with RA for 48 hours before culture in agar resulted in a significant degree of inhibition (48 +/- 8% of control). Inhibition was prevented by delaying the addition of RA from 24 to 48 hours from the beginning of the culture, indicating that RA exerts an early direct effect on myeloid progenitors.

Blast Crisis↗
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

Increased porphobilinogen deaminase activity in patients with malignant lymphoproliferative diseases. A helpful diagnostic test.

Patients with malignant lymphoproliferative diseases, ie, chronic lymphocytic leukemia and lymphoma, were found to have higher porphobilinogen deaminase (PBGD) activity in their peripheral lymphocytes than normal control subjects, patients with other malignant neoplasms, and patients with various infectious diseases. The specificity and sensitivity of the test were 99% and 87%, respectively. The sensitivity of the test was 100% in patients with chronic lymphocytic leukemia and 82% in patients with lymphoma. The diagnostic value of PBGD determinations was shown in a prospective study of a group of patients evaluated because of fever of unknown origin, anemia, or other constitutional symptoms with or without lymphadenopathy or a mediastinal mass. The positive and negative predictive values in these patients were 91% and 100%, respectively. Nearly all patients who were in remission had normal enzyme activity. Lymphocyte PBGD determinations also may be of value in determining when to terminate or reinitiate drug treatment.

Adult↗
PubMed1987

Lymphocyte urosynthase in non-Hodgkin's lymphoma. An indicator of disease extensiveness.

The activity of lymphocyte uroporphyrinogen synthase (URO-S) was examined in 51 non-Hodgkin's lymphoma (NHL) patients at various follow-up periods. Mean +/- SD activity (pmol porphyrin/mg protein/hr) at diagnosis (n = 24), on relapse (n = 14) and during active disease (n = 14) were 31.7 +/- 19.8, 31.7 +/- 27.2 and 29.4 +/- 18.5, respectively. These values were significantly higher than the enzyme activity during remission (14.1 +/- 4.0), which was in the normal range (14.5 +/- 3.8). Abnormally high activity was found in 65.4% of determinations at diagnosis, on relapse and during active disease, compared to 5.5% during remission (P less than 0.001). Significant association of abnormal URO-S activity was found with advanced clinical stage (P less than 0.01), spleen enlargement (P = 0.048), involvement of bone marrow (P = 0.02), as well as lymphoma cell spread to peripheral blood (P = 0.03). Highly significant correlation (r = 0.65, P less than 0.001) was found between URO-S activity and serum lactic dehydrogenase (LDH) levels. Excessively high levels of URO-S activity were found only in patients with lymphoma cells in peripheral blood. No association was found with histopathologic classification and liver size. The authors conclude that URO-S activity is a biochemical indicator for patients in all stages of NHL and seems to be a specific marker for the extensiveness of the disease.

Adolescent↗
PubMed1987

Cholestasis and liver failure with lambda-AL amyloidosis.

Clinically significant liver involvement in systemic amyloidosis, especially with cholestasis, is rare. We report a case of primary amyloidosis with severe intrahepatic cholestasis leading to terminal liver failure. The present case is the first of its kind reported involving Lambda light chains only as the associated paraprotein. Conventional treatment and a therapeutic trial with dimethyl sulphoxide were unsuccessful.

Aged↗
PubMed1987

Primary malignant neoplasms associated with chronic lymphocytic leukaemia.

The relationship between chronic lymphocytic leukaemia (CLL) and primary malignant neoplasms was evaluated using data from the Hematology Division in Beilinson Medical Center and the Israel Cancer Registry. The study population consisted of 81 patients diagnosed between 1962 and 1984. A total of 16 patients were found to have 21 malignant neoplasms in addition to their CLL. Excluding patients with nonmelanoma skin tumours, a 1.7 increased risk (statistically not significant) for developing second malignant neoplasms in CLL patients was detected. The only tumour which occurred significantly more than expected subsequent to CLL diagnosis was brain cancer. The coexistence of multiple cancers in the same patient was diagnosed in four of the patients. The results of this study further support the hypothesis that patients with CLL are prone to develop second neoplasms.

Aged↗
PubMed1987

New monoclonal antibody enzymoassay for the specific measurement of placental ferritin isotype in hematologic malignancies.

A new enzymoimmunoassay, specific for the measurement of placental ferritin (PLF) isotype, has been described. Two monoclonal antibodies (McAbs) with different binding specificities to placental ferritin have been used in this assay. One antibody (CM-G-8) binds to all ferritins, whereas the second (CM-H-9) binds to placental ferritin only. In addition, a second enzymoassay was developed for the measurement of total common serum ferritin using CM-G-8 McAb. Serum levels of total ferritin and PLF were measured in healthy individuals and in patients with lymphoproliferative diseases and multiple myeloma. The majority of normal subjects were deficient in PLF in the serum. Increased serum levels of PLF were observed in patients with Hodgkin's lymphoma and non-Hodgkin's lymphoma of low and intermediate grades, as well as in patients with acute lymphocytic leukemia (ALL). Total ferritin was also elevated in these patients. Chronic lymphocytic leukemia (CLL) and multiple myeloma patients exhibited normal levels of common serum ferritin, whereas PLF in the serum was lacking.

Antibodies, Monoclonal↗
PubMed1986

Erythrocyte enzymes in polycythemia vera: a comparison to erythrocyte enzyme activities of patients with iron deficiency anemia.

Fifteen cytoplasmic erythrocyte enzyme activities were determined in patients with polycythemia vera (PV), iron deficiency anemia (IDA), and a group of healthy volunteers. Among the PV patients, the erythrocyte enzyme activities were compared between 2 groups: patients treated solely with phlebotomy and patients treated with phlebotomy, Myleran (busulfan) and/or radioactive phosphorus 32P. Significant reduction in glutathione reductase activity was found in the PV group of patients. This activity was normalized by the addition of flavin adenine dinucleotide. In contrast to previous reports, no other enzyme activity was found to be significantly reduced. The activities of the enzymes known to be age-dependent were significantly elevated in all the groups tested except for phosphofructokinase and 3-phosphoglycerate mutase. The former was not elevated in any of the groups studied, while the latter was elevated only in the group of patients treated with Myleran and/or 32P. It was concluded that glutathione reductase (GR) deficiency is the only acquired enzyme deficiency in our group of PV patients and that radiation and chemotherapy did not induce further reduction in the activities of any of the enzymes tested. The possible involvement of GR deficiency in the etiology of the red cell life span shortening was discussed.

Anemia, Hypochromic↗
PubMed1986

Expression of p53 in human leukemia and lymphoma.

Analysis of fresh human tumors have indicated that patients with B type lymphoproliferative diseases and the majority of patients with acute lymphoblastic leukemia (ALL) express elevated levels of p53 production. It is suggested that in these human malignancies, p53 may provide a novel tool for monitoring cancer activity. Conversely, p53 is not expressed in acute myeloid leukemias, myeloproliferative diseases, or myeloid leukemic cell lines. Analysis of the p53 gene structure indicated the existence of similar patterns of p53 restriction fragments in producer and nonproducer cells, which suggests that the p53 gene is not altered in the latter. However, in one case of acute promyelocytic leukemia (APL), we have observed a rearrangement in the p53 gene. Karyotype analysis has indicated that these APL cells do not contain the typical 15;17 translocation. In other APL patients who exhibit a 15;17 translocation, we found no genomic changes of the p53, suggesting that the p53 gene, which was recently mapped to the short arm of chromosome 17 in the human, is not structurally related to the typical chromosomal break point found in the long arm of chromosome 17 of APL patients.

Antibodies, Monoclonal↗
PubMed1986

Disintegration of red cell membrane cytoskeleton by hemin.

Spectrin and actin were isolated and their oligomeric state after association with hemin at various conditions was studied. Intact cytoskeletons were prepared by Triton X-100 extraction of red blood cells and incubated with hemin and their stability analyzed by the appearance of dissociated proteins in the supernatant. The cytoskeletons dissociated in a time, temperature and hemin concentration-dependent manner. Following 18 hours incubation in the presence of 0.3 mM hemin there was no dissociation at 4 degrees C, while at the same hemin concentration after 2 hours complete dissociation of the cytoskeletons occurred at 37 degrees C. Microscopy indicated that the cytoskeletons incubated with hemin lost their "cell like" shapes in a time dependent manner. Hemin applied to intact cells also caused dissociation of their cytoskeletons as judged by the failure to separate integer cytoskeletons from red cells treated with hemin. From hemin-induced dissociation profiles of separated actin, spectrin and whole cytoskeletons under various conditions, a mechanism of cytoskeleton breakdown was analyzed, as a release of band 4.1 in the first step which is followed by spectrin dimerization and eventually dissociation of the entire cytoskeletons.

Actins↗
PubMed1985

Evidence of abnormality of lymphocyte uroporphyrinogen synthase in family members of patients with lymphoproliferative diseases.

Patients with active lymphoproliferative diseases (LPD) were shown to have high activity of lymphocyte uroporphyrinogen synthase (L-UROS), the enzyme which converts porphobilinogen to uroporphyrinogen. The mean L-UROS activity of 64 first-degree relatives of patients with LPD was significantly higher than that of a control group and 45% of these relatives had pathological values of L-UROS. L-UROS activity was also determined in the spouses of 2 patients and was pathologically elevated in both. The pattern of pathological values among family members may indicate the presence of a communicable agent.

Adult↗
PubMed1985

Hemophagocytosis simulating malignant histiocytosis: a terminal event of the myelodysplastic syndrome.

We describe a patient with hemophagocytic syndrome resembling malignant histiocytosis which was complicating myelodysplastic disease of 3 years duration. Detailed morphological and ultrastructural studies indicate that the histiocytic component did not demonstrate features of malignancy. A review of other known malignancies ending up in the hemophagocytic syndrome is given, and the significance of this syndrome is discussed.

Aged↗
PubMed1985

Persistent lymphocytosis: an unusual feature in sarcoidosis.

Persistent lymphocytosis as a presenting sign in sarcoidosis is described in a 61-year-old man. Lymphocytosis is an unusual finding in sarcoidosis. The case presented seems to suggest that sarcoidosis should be considered in the differential diagnosis of lymphocytosis.

Diagnosis, Differential↗
PubMed1985

A therapeutic trial with low-dose cytarabine in myelodysplastic syndromes and acute leukemia.

The myelodysplastic syndromes are a group of bone marrow stem cell disorders which were considered refractory to chemotherapy until recently. Low-dose cytarabine was given to 6 patients with symptomatic myelodysplastic syndromes and 2 patients with acute leukemia. 5 patients responded to therapy, 3 of whom with refractory anemia achieved normalization of peripheral blood counts. Therapy was well tolerated, myelosuppression was the predominant side effect. This preliminary trial demonstrates that patients with symptomatic myelodysplastic syndromes, particularly patients with refractory anemia may be benefited by low-dose cytarabine therapy.

Acute Disease↗
PubMed1984

Immune modulation of a T-suppressor cell lymphoma by thymic humoral factor, a thymic hormone.

Lymphoid cells obtained from a mediastinal mass and bone marrow as well as peripheral blood of a patient with poorly differentiated diffuse malignant lymphoma were found to have both E and complement receptors. Addition of the bone marrow lymphoblasts to normal human T-lymphocytes induced a suppression of normal T functional activity as measured by a local xenogeneic graft versus host reaction. Incubation of the same cells with thymic humoral factor (THF), a thymic hormone, reversed their functional activity from suppression to help. Control studies with normal T-suppressor lymphocytes also showed a reversal of function to helper activity upon incubation with THF. In studies of normal T-lymphocytes with monoclonal antibodies, incubation with THF induced no change in phenotype in either theophylline-sensitive (suppressor) cells or theophylline-resistant (helper) cells. The ability of THF to modulate helper and suppressor activities suggests that this or similar agents may provide a useful means of therapy for disorders of immunoregulation.

Adult↗