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Biomedical subjects

G Brecher

Publications and source records attributed to G Brecher.

16 recordsLinked to original sources
PubMed1991

Short- and long-term repopulation of lethally irradiated mice by bone marrow stem cells enriched on the basis of light scatter and Hoechst 33342 fluorescence.

Murine bone marrow subpopulations enriched in hemopoietic stem cells were transfused into lethally irradiated hosts to determine the contribution of host cells and two types of donor cells to marrow repopulation. Donor cell suspensions were a mixture of marrows from two congenic lines of mice containing electrophoretically distinguishable alloenzymes of phosphoglycerate kinase (PGK-A and PGK-B). The donor cells were sorted by high forward light scatter, low-to-intermediate perpendicular light scatter, and low Hoechst 33342 fluorescence intensity. The congenic hosts contained a third distinct marker, glucose phosphate isomerase (GPI-A). The two markers in the donor cells allowed determination of the clones generated by the seeded cells over a 36-week period of observation. The clone number declined rapidly during the first 12 weeks following transplantation and reached stable levels at 20 weeks, indicating the number of long-term repopulating cells (LTRC). The sorted subpopulation was enriched 170-fold for day-13 spleen colony-forming units (CFU-S), 235-fold for cells providing a 30-day survival, and 136- to 160-fold for LTRC. Survival for the 36-week observation period was 40%-100% for groups of hosts receiving 100-3000 sorted cells and 80% for controls receiving 2 x 10(5) unsorted cells. In all groups, similar distribution of phenotypes among peripheral blood erythrocytes, platelets, and lymphocytes at 36 weeks suggested that the repopulating donor stem cells were pluripotential. Transfusion of 3000 sorted cells, containing about 5 LTRC and 60 CFU-S, assured continuous repopulation with 95%-100% donor cells 4 to 36 weeks after transplantation, whereas significant numbers of host cells re-emerged temporarily or permanently when lower numbers of LTRC and CFU-S were transfused. The data indicate that both the quality and quantity of pluripotential stem cells in sorted bone marrow are important for complete long-term marrow reconstitution.

Animals↗
PubMed1979

Transplantation of murine bone marrow without prior host irradiation.

The experiments presented test the hypothesis that pluripotential stem cells (assayed in the mouse as CFU-S) are normally not in cycle and that the failure of normal marrow transfusions to take in normal recipients is due to the absence of a stimulus to turn CFU-S into cycle. Following marrow transfusion from male donors into female isogeneic recipients, spleen, liver, and various parts of the skeleton were shielded to protect transfused donor cells from lethal doses of radiation gives to the rest of the body. Percentages of hemopoietic donor and host cells were subsequently determined by karyotyping C banded marrow and spleen metaphases and identifying of Y chromosome. The results support the notion that the failure of normal marrow to take in normal recipients is not due to inadequate numbers of transfused cells. Permanent colonization by donor cells, however, requires not only triggering CFU-S into cycle, but also emptying of 'niches' normally occupied by endogenous CFU-S. Partial body radiation meets both requirements. In addition, the results indicate that recently arrived donor cells, protected in the shielded portion of the body, seed more readily into the irradiated areas of the skeleton than do similarly protected host cells.

Animals↗
PubMed1979

Suppressive effects of chlorphenesin on lymphocyte function in mice and humans.

The immunosuppressive action of chlorphenesin was investigated in a wide variety of in vitro assays for cellular immunity in humans and mice. Chlorphenesin, at doses of 20-50 micrograms/ml, inhibited mitogenic responses of both mouse and human B and T cells. These doses did not kill cells exposed to the drug for 72 hr. Mixed lymphocyte reactions in inbred strains of mice and in unrelated humans were also inhibited at concentrations of about 50 micrograms/ml. However, the generation of cytotoxic T cells in cell-mediated lympholysis assays was not inhibited to the same degree as proliferation in mixed lymphocyte reaction and the cytotoxic potential of presensitized mouse T cells for allogeneic targets was totally unaffected. These studies suggest that chlorphenesin may have a broad spectrum of suppressive effects both on T and B cells and that the predominant inhibition of proliferative responses in these cells may reduce the expansion of clones of immunocompetent cells in vivo.

Animals↗
PubMed1977

Clinical laboratory use in the evaluation of anemia.

Follow-up tests ordered on 258 consecutively examined inpatients with low hemoglobin values on admission were analyzed. The appropriateness of the follow-up tests was evaluated by chart review after preselection by an algorithm. When the cause of the anemia was known or was irrelevant in view of the patient's clinical status, the laboratory use was judged to be adequate. Seventy-one percent of patients studied had an adequate follow-up, though 11% had nonindicated tests performed, scored as laboratory overuse. Twenty-four percent had no follow-up, scored as laboratory underuse. Five percent did not have all indicated tests done and had nonindicated tests done, scored as a mixture of underuse and overuse. Potential remedies to correct misuse are discussed.

Anemia↗
PubMed1977

Pluripotential and committed hemopoietic stem cells. A hypothesis.

The hypothesis is proposed that regulation of hemopoiesis is largely accomplished by expansion or contraction of the committed stem cell compartments and that pluripotential stem cells are normally not involved or in cycle. The thesis appears supported by the fact that erythropoietin affects the committed red cell precursors, that 98% of marrow mitoses have been shown to occur in cells clearly recognizable as red or white cell precursors (while the pluripotential stem cells by definition are not so recognizable), and that it has been shown (by the spleen nodule assay) that the pluripotential stem cell compartment in the marrow cannot be readily expanded. The major objection to the proposed hypothesis are tritiated thymidine suicide data, which suggest that up to 20% of pluripotential stem cells may be constantly in cycle in some stains of mice. Preliminary experimental evidence supporting the hypothesis has been obtained: normal pluripotential stem cells which transfused into normal isologous mice are not lost as has been assumed but proliferate after irradiation, suggesting that it takes a special stimulus to "turn-on" the normally quiescent pluripotential stem cells.

Animals↗
PubMed1976

Developmental change in red blood cell volume: implication in screening infants and children for iron deficiency and thalassemia trait.

The mean corpuscular volumen when determined by electronic counter is an accurate tool for identification of children with microcytosis due to either iron deficiency or thalassemia trait. The purpose of this report is to describe the normal developmental changes in MCV that occur in children afler 6 months of age. In 211 healthy infants and children screened to exclude those with borderline or overt iron deficiency, thalassemia trait, or hemoglobinopathy, we found that the lower limit of normal for MCV is 70 ft between 10 and 17 months of age and that there is a gradual increase of MCV with age; the lower limit is 74 between 1 1/2 and 4 years and 76 between 4 and 7 years. All of these values are well below the minimum adult level of 80 fl.

Anemia, Hypochromic↗
PubMed1976

Marrow regeneration after mechanical depletion.

The origin of marrow regeneration after mechanical depletion was reinvestigated in mouse chimeras. The results were compatible with the local origin of stem cells from remnants of incompletely removed marrow, but not with their origin from a common precursor of both bone and hemopoietic cell lines. In transplanted femurs depleted by a modified technique of in vivo evacuation of marrow, hemopoietic regeneration failed to occur. The presence of hemopoietic stem cells in the Haversian canals was thus excluded. The demonstration of ample hemopoiesis with minimal bone formation in nondepleted controls in which bone marrow initially became necrotic provided new evidence that osteogenesis was not a prerequisite of hemopoietic regeneration.

Animals↗
PubMed1975

Hematopoietic differentiative properties of murine spleen implanted in the omenta of irradiated and nonirradiated hosts.

Whole body irradiation of the recipients of syngeneic splenic implants into the omentum greatly enchances hematopoiesis and permits survial of and repopulation by stem cells of donor origin. Donor hematopioetic stem cells do not survive in spleen implants of the nonirradiated host; irradiated hosts were therfore used in the bulk of the experiments. Differentiation in the implants of splenic fragments is predominantly erythrocytic at 10 days and shifts to predominantly granulocytic differentiation at 21 days. Suspensions of spleen cells injected into the ometntum are predominantly granulocytopioetic at 10 days. The differntiation in fragments of spleen depleted of stem cells by irradtion, seeded with bone marrow cells and implanted into the omentum results in mixed erythocytic and granulocytic hematopoiesis, with granulocytic predominance. Lymphocytic cells appeared late in the implants of irrdiated recipients even at a time of prolific lymphocytopoiesis in the host's own spleens. The cause of the delay in the implants is not clear. The data are consisent with the concept that differntiation of hematopioetic stem cells is influenced by the stromal cells of the parent organ. The erythrocytic inductive capacity of the stromal cells may be lost by mechanical disruption or modified by irraidation or a prolonged period of implantation.

Animals↗
PubMedDate not supplied

Origin of stress macroreticulocytes from macronormoblasts.

Stress erythropoiesis was induced in rats and guinea-pigs by graded amounts of bleeding and phenyl-hydrazine administration. Hemoglobin and DNA content was measured by microspectrophometry of single erythroblasts in the process of nuclear extrusion. DNA content was always 2 C. Hemoglobin content was in all cases superior to the normal value, occasionally reaching a value of almost twice normal.

Animals↗