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Biomedical subjects

M Rachmilewitz

Publications and source records attributed to M Rachmilewitz.

At least 19 recordsLinked to original sources

The modulation of transcobalamin II (TC-II) production by cyclic adenosine 3',5'-monophosphate in the murine macrophage cell line J774: relationship to growth behavior.

We undertook a study to define the role of cyclic AMP [cAMP] in modulating the secretion of transcobalamin II (TC-II) in the mouse macrophage like cell line J774. J774 was observed to secrete large amounts of TC-II, particularly in the presence of 8-bromo cAMP or cholera toxin or when grown in medium supplemented with low concentrations of horse serum (1% or 5%) or in serum-free medium. Variant cell lines derived from J774 and deficient either in adenylate cyclase (ac -) or cAMP-dependent protein kinase (pk -) activity showed very low and intermediate levels of basal secretory activity of TC-II, respectively, compared to J774. Maximum secretory activity of TC-II was observed in J774 under conditions in which growth was poorest (in the presence of 8-bromo-cAMP or 1% or 5% horse serum-supplemented medium or in serum-free medium). Cells grown in serum-free medium were found to have elevated basal adenylate cyclase activity and cAMP levels compared to those grown in medium supplemented with 20% horse serum. The data from this study demonstrate a negative correlation between growth activity and TC-II secretion in the J774 cell line. The stimulatory effect of exogenous cAMP on TC-II secretion by J774, the reduced secretory activity of the variant lines ac- and pk- and the observed increase in cell cAMP levels under conditions of serum starvation in which TC-II secretion is considerably enhanced, suggest that cell cAMP is an important modulator of TC-II secretion and growth behavior in the J774 cell line.

8-Bromo Cyclic Adenosine Monophosphate↗

Effect of dexamethasone on serum transcobalamin II concentration in women undergoing pelvic surgery.

Dexamethasone (120 mg/day for 2 days) was administered intramuscularly to young females undergoing pelvic surgery for infertility. The therapy was shown to cause a transient increase in the serum level of the granulocyte-produced transcobalamins (TCI and TCIII) and more significantly in the monocyte-produced transcobalamin (TCII), from 1220 +/- 70 to 1980 +/- 158 pg/ml (P less than 0.001). The change closely followed a transient elevation of EA rosette forming cells in the peripheral blood (from 20 to 50% of the total mononuclear cell population), which are mainly monocytes. The observed effects were shown to be independent of the surgical trauma. The results indicate that the increase in serum TCII can be attributed to an effect of dexamethasone on monocytes.

Blood Cell Count↗

Serum transcobalamin levels as an early indicator of bone marrow engraftment following transplantation.

Three B12 binding proteins, the transcobalamins TCI, TCII and TCIII, were determined serially in the serum of five patients who underwent bone marrow transplantation. The increase in TCII, followed by the increase in TCI, proved to be an early indicator of bone marrow regeneration, reaching a peak of up to twice its normal levels at least 5 d prior to the rise of the peripheral white blood cell count.

Adolescent↗

Prognostic significance of changes in serum transcobalamin levels in cancer patients with chemotherapy-induced granulocytopenia.

Serum transcobalamin (TC) levels were determined daily in 14 adults suffering from advanced nonhematological malignancies and hospitalized because of chemotherapy-induced leukopenia and fever. Even during the nadir leukocyte count, TCI and TCIII serum levels were normal or only slightly decreased indicating that bone marrow activity was not completely suppressed. A significant increase in serum TCII level was observed in all patients, with peak values occurring an average of 4.5 days from admission at a time when the median leukocyte count was 2,300/mm 3. Full white cell count recovery followed this peak TCII elevation within a mean of 5.5 days in all patients, coinciding with a fall in TCII levels to basal values. The rise in serum TCII level appears to be an early indicator for imminent bone marrow recovery in myelosuppressed patients.

Agranulocytosis↗

Production of transcobalamin II by various murine and human cells in culture.

The ability of various murine and human cell types to secrete in vitro transcobalamin II (TCII), the vitamin B12 transport protein, was investigated. All cell types tested were found to secrete into the culture medium biologically active TCII molecules, capable of facilitating B12 uptake. The largest amounts of TCII were produced by primary cultures of murine fibroblasts and macrophages. Large quantities of TCII were also secreted by myeloma, erythroid leukemia, and macrophage-like tumor cell lines. Murine thymus cells of T lymphocyte tumors secreted only small quantities of TCII. Mouse monocytes and fibroblasts secreted considerably larger quantities of TCII than did their human counterparts. The data indicate that many cell types have the potential to produce biologically active TCII in vitro. Whether this in vitro potential also reflects in vivo biosynthetic activity is discussed.

Animals↗

The transcobalamins in polycythaemia vera.

The unsaturated B12 binding capacity (UBBC) of the serum and the binding capacity of each of the 3 vitamin B12 binders--the transcobalamins (TC) I, II and III were determined in 21 patients with polycythaemia vera (PV) during the course of the disease and following treatment, using the recently described charged cellulose filter technique. High serum UBBC due to elevated serum TCIII was found in all patients. TCI was moderately elevated in patients who had leucocytosis with a shift to the left. The changes in serum TCIII and UBBC correlated with the activity of the disease. Chemotherapy resulted in a decrease in TCIII and UBBC. The decrease in TCIII and UBBC folowing chemotherapy may be observed before a decrease in the haematocrit and the leucocyte count occurs. Activation of the disease may be assessed by the elevation of TCIII and UBBC. The onset of acute myeloblastic crisis in 1 patient was associated with a decrease in TCIII and TCI levels and a rise in serum TCII. The determination of TCIII and UBBC may be helpful in differentiating true from secondary polycythaemia.

Blood Proteins↗

The synthesis of transcobalamin II, a vitamin B12 transport protein, by stimulated mouse peritoneal macrophages.

The concentration of transcobalamin II (TCII), the vitamin B12 binding protein which delivers vitamin B12 to the tissues, was determined in stimulated and non stimulated mouse peritoneal exudate cells (PEC). Following a single intraperitoneal thioglycollate injection there was a marked increase in TCII which was shown to be produced by the adherent cells of the PEC i.e. the macrophages. It has been concluded that the PEC macrophages synthesize TCII.

Animals↗

Serum and erythrocyte folates in combined iron and folate deficiency.

A high incidence of iron and folate deficiency was found in 80 female subjects living in a private institution. Iron therapy in individuals with low serum iron values resulted in a significant increase in hemoglobin levels. An improvement in serum and RBC folate levels was also found following iron therapy but this could not be attributed to treatment since a similar increase was observed in untreated control subjects, probably due to an increased dietary intake of folates during the study period. In subsequent studies small amounts of pteroylglutamic acid were given to all patients and their response to therapy was related to initial serum and RBC folate values. No correlation between serum folate levels and response to folate therapy could be demonstrated. Red cell folate levels on the other hand correlated well with response to therapy. A significant increase in hemoglobin was found following folate therapy in patients with low RBC folates, but not increase in subjects with normal RBC folates. Conversely, the increase in hemoglobin following iron therapy in subjects with normal RBC folates was three times as much as in patients with low RBC folates. Thus, unlike serum folate determinations, RBC folate measurements are a reliable index of tissue folate stores, and useful in the prediction of response to folate therapy in both the iron-deficient and iron-replete states.

Adult↗

Nutritional survey in an iron- and folate-deficient population.

A high prevalence of folate and iron-deficiency anemia was found in women and children of Kiryat Shmoneh, an Upper Galilee community. Malnutrition was assumed to be partially responsible for these deficiencies. To verify this assumption, a detailed nutrition survey was carried out in 30 families, comprising 232 individuals in this community. A low overall caloric intake was found in 30% of the population studied. The dietary folates consumed were much below the recommended dietary allowance in all subjects. In over 60% of the subjects investigated, the daily iron intake was also below the recommended allowance. These data support the role of malnutrition in the development of folate and iron deficiencies in the community studied.

Adolescent↗

Utilization of yeast polyglutamate folates in man.

Ingestion by healthy humans of small amounts of polyglutamate folates from yeast, equivalent to 300 mug of monoglutamate folate and containing 30 mug of "free folate," resulted in an appreciable elevation of the serum folate corresponding to 300 mug of synthetic pteroylmonoglutamate (PGA). Ingestion of higher amounts of polyglutamate folate did not result in higher serum folate elevations than did 300 mug. It is concluded that small amounts of polyglutamate folate from yeast are fully utilized, presumably by deconjugation in the gut prior to absorption. The relative ineffectiveness of larger doses of polyglutamate folates from yeast may be due to limiting conjugase activity in the gut, unfavorable conditions for its activity (such as unsuitable pH) or to an inhibitor of the enzyme present in impure preparations.

Folic Acid↗