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Biomedical subjects

J Moreb

Publications and source records attributed to J Moreb.

At least 37 records · Page 2Linked to original sources
PubMed1990

The effects of tumor necrosis factor-alpha on early human hematopoietic progenitor cells treated with 4-hydroperoxycyclophosphamide.

We have previously reported that 20 hours' preincubation of human bone marrow cells with interleukin-1 beta (IL-1) can protect early progenitor cells from 4-hydroperoxycyclophosphamide (4-HC) cytotoxicity. Since tumor necrosis factor-alpha (TNF alpha) shares many of the biologic properties of IL-1, we have compared the protective effects of TNF alpha with IL-1 against 4-HC. Incubation of human bone marrow mononuclear cells or an enriched progenitor population for 20 hours with either TNF alpha or IL-1 resulted in the survival of an increased number of single- and mixed-lineage colonies, including replatable blast cell colonies, while only rare colonies were seen in the control group. Antibodies to TNF alpha completely abolished the protection observed with IL-1, while antibodies to IL-1 alpha and IL-1 beta decreased but did not abolish the protection seen with TNF alpha. Combinations of low doses of TNF alpha and IL-1 showed synergy in their protective effects. Furthermore, no protection was observed by IL-1, IL-1 bone-marrow-conditioned medium (IL-1-BMCM), or TNF alpha for HL-60, K562, KG1, KG1a, and DU.528 leukemic-cell lines or primary acute myelogenous leukemic (AML) blast cells from the lethal effects of 4-HC. In the case of HL-60 and KG1a cell lines, TNF alpha preincubation resulted in increased cytotoxicity. Furthermore, preincubation of a mixture of AML cells and normal bone-marrow cells with IL-1 + TNF alpha before 4-HC resulted in the protection of normal but not leukemic progenitors. These results suggest that TNF alpha is necessary for the protection of normal, early, human hematopoietic progenitors from 4-HC, while IL-1 is not mandatory but will synergize with TNF alpha to offer increased protection. In addition, no protection from 4-HC is observed by TNF alpha, IL-1, or IL-1-BMCM for primary leukemic blast cells or leukemic cell lines.

Cell Line↗
PubMed1990

Human N-terminal analogs of interleukin 1 beta demonstrate altered binding and function in hematopoiesis.

This study describes the structure-function relationship of interleukin 1 beta (IL-1 beta) using two amino-terminal muteins of human IL-1 beta. One mutein, clone 18, which substitutes a threonine and methionine for the alanine and proline at positions 1 and 2 of the N-terminus of fully processed and active IL-1 beta, demonstrated similar activity to that of native IL-1 beta in inducing granulocyte-macrophage colony-stimulating activity (GM-CSA) from cultured fibroblasts. Clone 18 also demonstrated similar binding to IL-1 beta receptors on fibroblasts when using a competitive binding assay. The second mutein was GLU-4, which in addition to substituting alanine and proline by threonine and methionine also substituted glutamine for arginine at position 4 of the processed IL-1 beta molecule. GLU-4 required a 3-log increase in concentration to obtain the same GM-CSA release from fibroblasts and to produce the same amount of competitive binding inhibition as clone 18 and native IL-1 beta. In addition, preincubation of bone marrow cells with clone 18 and native IL-1 beta demonstrated a greater ability to protect early hematopoietic progenitors from the lethal effects of 4-hydroperoxycyclophosphamide when compared to similar concentrations of GLU-4. A greater number of large granulocyte-macrophage, erythroid, and mixed colonies as well as blast cell colonies were observed when bone marrow cells were preincubated for 20 h with clone 18 or native IL-1 beta as compared to preincubation with GLU-4 or medium alone. Therefore, arginine at position 4 of the processed IL-1 beta molecule was shown to be a key residue in the function of IL-1 beta as a hematopoietic regulator. These results also suggest that minor changes in the N-terminal sequence of IL-1 beta result in decreased interaction with its receptor and a subsequent reduction in biological activity.

Binding, Competitive↗
PubMed1989

High-grade B-cell lymphoma presenting as polyserosal disease. Diagnosis by flow cytometry.

Two patients presenting with anasarca were found to have aggressive B-cell lymphoma. No bulky disease was detected. The diagnosis was rapidly established by the flow cytometric analysis of cell surface immunophenotype and cell cycle fractions of pleural or peritoneal cells. Such presentation of lymphoma is unusual and previously undescribed, and it may have a significant negative prognostic impact. The authors' observations indicate that lymphoma be included in the differential diagnosis of anasarca and that flow cytometry can be useful for a fast confirmation of the diagnosis.

Aged↗
PubMed1989

Protective effects of IL-1 on human hematopoietic progenitor cells treated in vitro with 4-hydroperoxycyclophosphamide.

Based on recently published data, IL-1 has been shown to provide radioprotective effects when given to mice 20 h before a lethal dose of irradiation and to enhance granulocyte recovery in mice treated with cyclophosphamide. In this study, we have investigated whether IL-1 can provide protection for human bone marrow colony-forming cells treated with high doses of 4-hydroperoxycyclophosphamide (4-HC), a potent derivative of cyclophosphamide. We have established an in vitro model system which demonstrates that prior incubation with IL-1 protects early human hematopoietic progenitor cells from the lethal effects of high doses of 4-HC. These early progenitors give rise to blast cell colonies which appear late in the culture and are characterized by their ability to give rise to different types of secondary colonies when replated. Furthermore, prior incubation with IL-1 was shown not to protect HL-60 or K562 leukemic cells from the lethal effects of 4-HC. We conclude that IL-1 is able to protect early human hematopoietic progenitors from a non-cell cycle-specific chemotherapeutic agent such as 4-HC, whereas providing no protection for the leukemic cell lines HL-60 and K562.

Adult↗
PubMed1989

Role of interleukin-1 in 4-hydroperoxycyclophosphamide toxicity to bone marrow progenitor cells: a review.

We have demonstrated that in vitro preincubation with IL-1 or TNFa for 20 hours can protect human hematopoietic progenitors from lethal doses of 4-HC. On the other hand, preincubation with IL-6 or IL-3, in a similar fashion, did not provide any protection but in fact demonstrated a slight increase in 4-HC toxicity in the same experiments. The observation that IL-1 was still protective even when a purified cell population depleted of accessory cells was used is suggestive of a direct effect of IL-1. Our data also suggest that early progenitor cells including the replatable B;-CFC are the main target of that protection. We believe that using this in vitro assay system will enable us to investigate the possible mechanisms responsible for the protection of these primitive progenitors. From a clinical perspective, future studies should attempt to clarify whether protection by IL-1 is selective for normal hematopoietic cells versus malignant cells and whether these protected primitive progenitors represent the pluripotent stem cells responsible for engraftment of transplanted bone marrow by using an animal model system.

Animals↗
PubMed1989

The role of interleukin 3 and interleukin 6 in the protection from 4-hydroperoxycyclophosphamide and the proliferation of early human hematopoietic progenitor cells.

Previous reports have shown that interleukin 1 (IL-1) has radioprotective effects when given to mice 20 h before a lethal dose of irradiation and enhances granulocyte recovery in mice treated with cyclophosphamide. We have recently reported that IL-1 can provide protection for human bone marrow colony-forming cells including blast colony-forming cells (B1-CFC) treated with high doses of 4-hydroperoxycyclophosphamide (4-HC). In view of the recent reports that IL-1 induces interleukin 6 (IL-6) in fibroblasts and macrophages and that IL-6 and interleukin 3 (IL-3) are the main growth factors for B1-CFC, we have examined the ability of these interleukins to protect early human hematopoietic progenitor cells from the cytotoxic effects of 4-HC. In addition, we have also studied the ability of IL-3 to promote colony formation by 4-HC-treated bone marrow cells with or without IL-1 preincubation. In this study, we report that preincubation of bone marrow mononuclear cells with IL-3 or IL-6 prior to 4-HC results in no protection and, in fact, may be detrimental to early hematopoietic progenitor cells. On the other hand, addition of IL-3 to 5637-conditioned medium and erythropoietin enhanced colony formation by early progenitors following 4-HC treatment. These findings suggest that IL-3 and IL-6 are not responsible for the protection of early progenitor cells from 4-HC seen with IL-1, but that IL-3 does promote colony formation following 4-HC treatment.

Cell Division↗
PubMed1988

Diagnostic value of ferritin in malignant pleural and peritoneal effusions.

The diagnostic usefulness of ferritin measurements in pleural and peritoneal effusions has been evaluated in 57 patients. Mean (+/- standard error [SE]) ferritin levels were 291 +/- 50 ng/ml in 24 patients with noninflammatory transudates (Group I), 942 +/- 253 in 15 patients with nonmalignant exudates (Group II), and 1805 +/- 257 in 18 patients with malignant exudates (Group III). The mean (+/- SE) ratio of effusion/serum ferritin in Groups I, II, and III was 0.7 +/- 0.1, 2.7 +/- 0.7, and 5.7 +/- 1.2, respectively. The specificity and predictive value of a ferritin ratio in excess of 1.5 in distinguishing transudates from all exudates and in distinguishing transudates from malignant exudates were both very high (94%) to 96%). In the lower range of values considerable overlap existed between ferritin ratios obtained in patients with benign versus malignant inflammatory exudates. However, very high ferritin levels (greater than 3000 ng/ml) and ferritin ratios (greater than 20:1) were only encountered in malignant exudates. These results indicate that the measurement of ferritin levels and ferritin ratios may be a useful aid in the diagnosis of malignant pleural and peritoneal effusions.

Adult↗
PubMed1988

Cancer of the male breast with prolonged survival.

A retrospective review of patients suffering from male breast cancer was carried out at the Shands Teaching Hospital of the University of Florida. Thirteen evaluable cases were analyzed. Three patients were in Stage I, two patients in Stage II, none in Stage III, and eight in Stage IV. Two of the patients with Stage IV disease have had remarkably prolonged survivals of 194 months and 128 months. Such prolonged survivals are unusual. It is possible that the biology of male breast cancer is different from the female, and the disease should be approached more optimistically than it has in the past.

Adult↗
PubMed1988

Noninvasive assessment of skin iron content in hemodialysis patients. An index of parenchymal tissue iron content?

Iron overload has been described in patients undergoing chronic hemodialysis. The present study was undertaken to evaluate a rapid, noninvasive method for determination of skin iron by the technique of diagnostic x-ray spectrometry (DXS). Thirty-five patients receiving chronic hemodialysis treatment entered the study and were compared with 25 normal controls. Since pathological skin iron deposition occurs mainly at the dermal-epidermal junction in the basal cells of the epidermis, measurements were made in the thenar eminence representing mainly epidermal tissue (FeE), and in the forearm representative mainly of dermis (FeD). The mean +/- SD FeE iron concentrations were equivalent to 14.5 +/- 8.8 and 18.2 +/- 10.2 parts per million wet weight tissue (ppm) and both were significantly higher than in normal controls in which they averaged 9.2 +/- 2.5 ppm (P less than 0.005) and 10.2 +/- 3.2 ppm (P less than 0.001), respectively. There was significant positive correlation between individual skin iron determinations with the total number of blood transfusions received, the rate of blood transfusion, and with serum ferritin levels. Bone marrow hemosiderin was examined in six patients and showed a similar trend. Despite correlation only with indirect indices of tissue iron, our findings suggest that DXS may serve as a reliable quick method for noninvasive estimation of nonreticuloendothelial tissue iron deposition in hemodialysis patients suspected of having transfusional iron overload. The method may be valuable in monitoring the effects of chelation therapy.

Adult↗
PubMed1988

Factitious injury of an extremity: a Munchausen variant.

Self-induced injury of one or more of the extremities may represent a distinct variety of Munchausen syndrome. The nature of the injury may be infectious, dermatologic or orthopedic. The mechanism may be secondary gain or another unconscious motivation that causes a craving for attention. In many cases, the underlying psychopathology is personality disorder.

Abscess↗
PubMed1985

Combined use of zinc protoporphyrin (ZPP), mean corpuscular volume and haemoglobin measurements for classifying microcytic RBC disorders in children and young adults.

The diagnostic potential of the combined use of zinc-protoporphyrin (ZPP), mean corpuscular volume (MCV) and haemoglobin measurements for discriminating between iron deficiency anaemia, beta-thalassaemia minor and lead poisoning has been studied. Lead poisoning could be identified by ZPP greater than 50 micrograms/dl in the presence of normal MCV or ZPP greater than 150 micrograms/dl in the presence of microcytosis (MCV less than 80 fl) with a sensitivity of 97% and specificity 94%. Beta-thalassaemia minor was identified by the coexistence of microcytosis and ZPP less than 50 micrograms/dl with a sensitivity of 91% and specificity 79%. Iron deficiency anaemia defined by the combination of microcytosis and ZPP ranging from 50 to 150 micrograms/dl was identified with a sensitivity of 95%, but the specificity was only 51%, with many of the patients overlapping with thalassaemia minor. This problem did not exist in iron-deficiency anaemia with haemoglobin less than 10 g/dl as at that range no patients with uncomplicated thalassaemia minor have been encountered. A great advantage of the combined use of ZPP, MCV and haemoglobin for the initial screening of microcytic anaemia is its ease of performance and low cost. However, this information should only be regarded as presumptive evidence of disease, requiring subsequent confirmation by appropriate direct measurements such as transferrin saturation, serum ferritin, haemoglobin electrophoresis, or blood lead determinations.

Adolescent↗
PubMed1985

Increased leucocyte alkaline phosphatase and transcobalamin III in chronic myeloid leukaemia associated with lithium therapy.

A 38-year-old woman developed chronic myeloid leukaemia after 2 years of lithium carbonate therapy. A peculiar feature of her leukaemia, as well as of the 5 patients previously reported in whom CML has developed in the course of lithium therapy, was the unusually high degree of granulocyte maturation manifested in normal leucocyte alkaline phosphatase (LAP) score and, in 1 case, selective increase of transcobalamin III. Although a cause and effect relation between lithium therapy and CML has not yet been established, in view of the stimulatory effect of lithium on granulocyte proliferation, such treatment should be avoided in patients with established myeloproliferative disorders, or in patients at high risk of developing leukaemia.

Adult↗
PubMed1985

Is common variable hypogammaglobulinemia linked to HLA? A family study.

Two patients with common variable hypogammaglobulinemia (CVH) and their families, who came from different ethnic backgrounds, were surveyed for the level of immunoglobulins (Ig) and HLA genotypes. Six of 10 siblings and the mother in one family had a decreased level of one of the major classes of Ig (IgA in 5, IgM in 1 and IgG in the mother). A similar decrease was found in three of six siblings in the other family (IgG in one, IgA in one and IgM in one). HLA genotyping disclosed that affected and nonaffected family members had identical genotypes, suggesting that hypogammaglobulinemia in CVH is not linked to a specific HLA genotype.

Adolescent↗
PubMed1985

Identification of community flour mills as the source of lead poisoning in West Bank Arabs.

Following the discovery of severe lead poisoning in members of several households in a West Bank village, studies were carried out to establish the magnitude of the problem in the community and to identify the source of lead poisoning. Forty-three patients with Centers for Disease Control risk group IV lead poisoning were identified and treated in three villages within a radius of about 10 km of each other. The prevalence of increased lead burden among 563 schoolchildren aged 10 to 18 years was 19% for Centers for Disease Control risk groups I and II and 11% for groups III and IV. A survey of potential sources excluded all items, except for locally ground flour, which was heavily contaminated in all affected households. Examination of community flour mills revealed that, in contrast to unprocessed grain, freshly ground flour contained large amounts of lead originating from lead fillings employed to fasten the housing of the driveshafts to the millstones. Systematic screening of 146 community stone mills in 92 West Bank villages showed significant lead contamination of flour in 33 mills (23%). In all cases, the source of lead contamination was identical. As methods of milling in the area are similar, a prompt investigation of this potential source of lead poisoning in other near-Eastern countries is indicated.

Adolescent↗