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Biomedical subjects

S R Weinberg

Publications and source records attributed to S R Weinberg.

At least 19 recordsLinked to original sources

Biologic preparation of diseased root surfaces. An in vitro study.

The study evaluated the effect of 2% sodium desoxycholate combined with whole plasma from a single donor on gingival fibroblast attachment to diseased root surfaces. Twenty extracted periodontally involved teeth were cut into halves buccolingually and sterilized by moist heat under high pressure. The diseased root surface of each control half was rubbed with a sterile cotton pellet saturated with Dulbecco's phosphate-buffered saline (PBS). The diseased root surface of each experimental half was rubbed with a sterile cotton pellet saturated with 2% sodium desoxycholate and then rubbed with a pellet soaked in human plasma. The control and experimental halves were placed in separate petri dishes, and a fibroblast cell suspension was added to each dish. The mean number of attached cells per half tooth was calculated for each group. Tooth surfaces treated with PBS (controls) showed a mean of 307 +/- 63 attached cells for 17 tooth halves; the experimental treated surfaces exhibited a mean of 650 +/- 130 attached cells for 16 halves. The difference between these numbers was statistically significant (P less than 0.01). These findings suggest that the desoxycholate/plasma combination enhanced in vitro fibroblast attachment to diseased root surfaces.

Adult

Modulations in mouse hemopoiesis after engraftment with Lewis lung (3LL) carcinoma cells.

Hemopoietic changes in male C57BL/6Cum BR mice engrafted with Lewis lung carcinoma (3LL) were evaluated between day 7, when palpable tumors were present, to day 30 postengraftment. All experimental animals demonstrated decreasing hematocrits (down 40% by day 30) with concurrent leukocytosis which by day 30 postengraftment had reached levels 13.4 times normal. The myelocytic/erythrocytic ratio for normal animals was 1:3 (bone marrow: spleen). The ratio for engrafted animals ranged between 10:1 and 40:1. This apparent shift in production priorities is even more significant in light of the fact that femoral bone marrow cellularity had decreased by 33% on day 17. Splenomegaly, evident by day 7, was seven times control by day 17. Clonogenic analysis of erythroprogenitor cell concentrations revealed an inverse relationship between bone marrow and spleen. 27 days after engraftment, splenic populations demonstrated significant increases in colony forming unit-erythroid (115-fold), burst forming unit-erythroid (7.4-fold), whereas bone marrow concentrations had decreased (6-fold). This report suggests that initiation of 3LL tumor in mice results in a change in the degree of hematopoietic priorities and participation of erythroid organs.

Animals

Hemopoiesis in pregnant beagles following low-dose total-body irradiation and surgery.

Hemopoietic perturbations were observed in gravid beagles subjected to whole-body ionizing radiation during midpregnancy followed by the additional trauma of surgery, with alterations in peripheral blood hemogram parameters, bone marrow morphology, and concentration of marrow-derived granulocytic- and erythrocytic-committed stem cells. However, the trauma of surgery combined with irradiation had no apparent effects on the contralateral uterine horn with the remaining pups, with no indications of miscarriage, absorption of pups, or other complications of pregnancy.

Animals

Effects of prenatal irradiation on fetal, neonate, and young adult murine hemopoiesis.

B6D2F1 mice received cobalt-60 radiation on day 10.5 of gestation at doses of 50 to 300 rad at a dose rate of 40 rad per min. These animals were studied at four selected age periods: (a) day 14.5 of gestation, (b) neonate, (c) juvenile, and (d) 13 week-old adult. Fetal liver cellularity, morphology, and hemopoietic progenitor cell concentration reflected injury after 200 rad. The 15 day-old mouse spleen cellularity was affected more than bone marrow cellularity, but greater radiation injury was reflected by bone marrow hemopoietic progenitor cells. Fluctuations from normal hematopoietic values were greater in the 15 day-old juvenile than in the 9 day-old neonate, commencing with 50 rad. These included peripheral blood parameters and marrow- and spleen-derived erythroid-, granulocytic- and megakaryocytic-progenitor cells. The consequences of prenatal irradiation (150 rad) were evident in the 13 week-old mouse. This was manifested by a reduced spleen cellularity and perturbations in concentrations of hemopoietic progenitor cells in the bone marrow.

Aging

Haemopoiesis in the beagle foetus after in utero irradiation.

On day 33 of gestation, foetal beagles were irradiated in utero (0.9 Gy of 60Co gamma-irradiation, 0.4 Gy/min). Foetal haematocytopoiesis was studied during the third trimester of gestation (days 42-55). Peripheral blood nucleated cell counts were 33 per cent lower than normal on day 44 and continued to be lower until day 49, when values became higher than normal. Splenic cellularities of irradiated pups on day 44 were more than 3 times those of the nonirradiated, but thereafter they were similar to normal. Differences in haemopoietic progenitor cell activity between irradiated and normal foetuses were observed. In comparison with the other foetal tissues, the foetal liver appeared to experience greater radiation injury. For example, on day 44, the irradiated liver BFU-E, CFU-E, and GM-CFC per 10(5) cells were almost fivefold lower than normal values. Spleens of irradiated foetal beagles contained a marked increase in all haemopoietic progenitor cells (BFU-E, CFU-E, and GM-CFC) and recognizable proliferative granulocytic cells and nucleated erythroid cells. The haemopoietic activity of the irradiated bone marrow during days 42-44 was similar to that of the irradiated spleen, and compensated for the damaged liver. However, unlike the irradiated spleen, the irradiated bone marrow had decreased BFU-E activity compared with the values for the nonirradiated bone marrow during days 48-55. Until day 50, the irradiated marrow contained fewer recognizable proliferative granulocytic cells but more nucleated erythroid cells.

Animals

Murine neonate hemopoiesis following in utero total-body irradiation.

Irradiation (50-200 rad of cobalt-60 gamma rays) on day 10.5 of gestation in the mouse had the following residual effects on neonate and juvenile hemopoiesis: (a) greater damage observed in the day-15 juvenile than in the day-9 neonate; (b) greater fluctuation of peripheral blood hemogram indices from normal values in the day-15 animal than in the day-9 animal; (c) spleen cellularity affected more than bone marrow cellularity; (d) greater radiation injury reflected by bone marrow hemopoietic progenitor cells (erythroid: BFU-E and CFU-E; granulocyte-macrophage: GM-CFC; megakaryocyte: Meg-CFC), and (e) a more pronounced decrease in medulla- and spleen-erythropoietic activity with each increase in dose of irradiation.

Animals

Effect of low-dose irradiation on pregnant mouse haemopoiesis.

The effects of low-dose gamma radiation to haemopoietic progenitor cell compartments of the marrow and spleen of virgin female mice and pregnant mice were studied. Microplasma clot cultures were used to asses burst-forming unit-erythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) activity, and double-layer agar cultures were established to evaluate granulocyte-macrophage colony-forming cell (GM-CFC) and macrophage colony-forming cell (M-CFC). The apparent shift in maternal erythropoiesis from the bone marrow to the enlarged spleen was reflected by an increase in the numbers of CFU-E and BFU-E per spleen and a concomitant decrease in CFU-E and BFU-E per femur. Whereas maternal GM-CFC values per femur increased 36%, maternal GM-CFC per spleen increased by 172% compared to virgin values. There was a greater decrease in M-CFC per spleen than per femur in the pregnant animal when values were compared to the virgin animal. Total-body irradiation to the day-10.5 pregnant mouse caused a further suppression of day-14.5 medullary erythropoiesis (i.e. decreased CFU-E values) compared to the response of the virgin female mouse. An ability of the maternal spleen to support further compensatory erythropoiesis following increasing doses of radiation was demonstrated. 4 d after 1.0 Gy exposure, maternal values for GM-CFC per femur or spleen decreased to nonirradiated virgin mice values. M-CFC per maternal femur decreased following 1.5 Gy, but M-CFC per spleen appeared to be unaffected with doses from 0.5 to 2.0 Gy.

Animals

Hemopoiesis in the splenectomized-pregnant mouse following low-dose total-body irradiation.

The effect of splenectomy (SPLX) and total-body irradiation (TBI) (50-200 rad) on virgin and pregnant mouse hemopoiesis was studied, using peripheral blood hemogram values and femoral marrow hemopoietic progenitor cell activity (i.e., CFUE, BFUE, and GM-CFC). The SPLX-maternal red cell counts and hematocrit values were lower than those of SPLX-virgin mice, reflecting the anemia of pregnancy. But the white cell counts of both SPLX-virgin and SPLX-day-14.5 pregnant mice were significantly higher (P less than 0.005) than normal-virgin mice. Both nonirradiated and day-4 irradiated SPLX-maternal marrow Ep-independent and Ep-dependent CFUE were higher than the nonirradiated and day-4 irradiated SPLX-virgin values (respectively, for each TBI dose studied). On the other hand, nonirradiated and day-4 irradiated SPLX-maternal GM-CFC were lower than the nonirradiated and day-4 irradiated SPLX-virgin GM-CFC values. The data demonstrate the potential of the SPLX-maternal femoral marrow to respond to the stress of low-dose TBI with effective compensatory erythropoiesis, possibly at the expense of granulopoiesis.

Anemia

Effects of low-dose total-body irradiation on canine bone marrow function and canine lymphoma.

Low-dose total-body irradiation, 150 rad given in 10 fractions over 5 weeks, is a useful treatment modality for favorable-prognosis lymphomas. Little is known, however, about the effects of this regimen on normal bone marrow. Six healthy beagle dogs and 5 dogs of various breeds with lymphoma were treated with total-body irradiation. Three of the 5 lymphomatous dogs achieved remissions of limited duration. No changes in hemograms or in bone marrow cellularity (as assessed by needle marrow biopsies) could be detected during or after treatment. Bone marrow progenitor cells were studied weekly during treatment and for 4 weeks thereafter using in vitro growth assays for GM-CFC and M-CFC. These studies demonstrated significant reductions (P less than 0.001) of granulocyte and macrophage progenitor cells with subsequent recovery toward normal pre-irradiation and sham irradiation values. Two additional dogs were injected with sublethal doses of Salmonella typhosa endotoxin 2 weeks after completion of the irradiation regimen. Their bone marrow GM-CFC responses were dramatically blunted compared to nonirradiated controls whereas their peripheral leukocyte responses and serum CSF levels were comparable to nonirradiated controls. These studies suggest that total-body irradiation may induce bone marrow injury that may be clinically significant if patients so treated are further stressed by infections or myelosuppressive drugs.

Animals

Hematopoietic response of splenectomized C3HeB/FeJ and C3H/HeJ mice to lipopolysaccharide.

The paired, inbred mouse strains C3HeB/FeJ and C3H/HeJ differ in their extramedullary hemopoietic response to lipopolysaccharide (LPS). The C3H/HeJ exhibit reduced responses relative to the C3HeB/FeJ in terms of colony-stimulating factor, endogenous and exogenous spleen-derived stem cells (CFUS), and spleen-derived granulocyte-macrophage colony-forming cells (GM-CFC) whereas equivocal responses were noted for the marrow-derived CFUS and GM-CFC. In an effort to determine if the mutational defect was specifically limited to extramedullary expression, we utilized C3HeB/FeJ mice and C3H/HeJ mice at 6 weeks postsplenectomy. The splenectomy emphasizes the medullary response to an i.p. injection of 10 microgram Escherichia coli, LPS-W. Significant differences were revealed in the responses of C3HeB/FeJ and C3H/HeJ marrow-derived cells. Total cells, CFUS, GM-CFC, and the macrophage colony-forming cell (M-CFC) in the C3HeB/FeJ strain all decreased significantly from their saline-injected control values as well as from their counterpart C3H/HeJ values within 48 h after injection of LPS-W. The decline in C3HeB/FeJ CFUS, GM-CFC, and M-CFC was followed by an overshoot, with subsequent return to control values. The total nucleated cells, CFUs, GM-CFC, and M-CFC derived from the C3H/HeJ marrow were characteristically nonresponsive and never varied significantly from their saline-injected control values over the observation period. These results suggest that the phenotypic effect of the defective gene can extend to all hemopoietic tissue, medullary and extramedullary, that normally respond to the factors released through expression of the LPS locus.

Animals

Factors regulating yolk sac hematopoiesis in diffusion chambers: various types of sera, cyclophosphamide, irradiation and long-term culture.

A series of studies were conducted using suspensions of murine 10 1/2 day yolk sac cells, cultured in diffusion chambers (DC), to evaluate the effects of several variables on cell growth and differentiation. The variables evaluated were: treatment of chamber recipients with cyclophosphamide (Cy) or sublethal total body irradiation (TBI), culture medium supplementation with different sera, and long-term culture. The growth of cells in Cy- and TBI-groups was parallel to that of the control group (C) until day 7 of culture. Thereafter, cells in the chambers of each group proliferated at a different rate. Whereas, cell growth in Cy-hosts was significantly greater than in C-hosts, growth of TBI-hosts was less than that in C-hosts. Horse serum supported chamber cellularity better than syngeneic mouse serum or fetal calf serum. Long-term cultures showed an increase in cell numbers until day 56, followed by a steady decrease to day 70, reaching a new level that was maintained until day 98. By day 14 of culture, and throughout the long-term culture study, there was no difference in the pattern of differentiation of DC cultured yolk sac cells. Regardless of the type of host treatment or culture medium the cells harvested were macrophages, plasma cells and lymphocytes.

Animals

Cell growth and differentiation of murine extra-embryonic fetal and adult hematopoietic tissues in diffusion chamber cultures.

Studies were conducted with diffusion chambers (DC) filled with cell suspensions from different CF1 murine hematopoietic tissues: adult peripheral blood; adult tibial marrow; day 17-5 of gestation fetal liver, spleen and thymus; day 14-5 gestation fetal liver; day 10-5 of gestation yolk sac. After an initial decrease in DC cell numbers on day 2 of culture, growth of each cell group continued, but, at different rates. ATM had the highest growth ratio and FT-D17-5(2) had the lowest. The growth rates for APB and FL-D17-5 were similar. FS-D17-5 and FL-D14-5 cultures did not recover from the day 2 values (i.e. FL-D14-5 DC values on day 13-14 of culture were half that recorded on day 2). The YS-D10-5 DC cell numbers continued to increase throughout the 14 days of study. The profile of cellular elements from the DCs did not reflect the original cell suspensions. The predominant cell type recovered from peripheral blood cultured for 14 days was the macrophage. By day 10-14 of culture, the populations of cells harvested from the fetal tissue DC groups were similar to that of tibial marrow. Both proliferative and mature granulocytes, and macrophages were the predominant cell types. The yolk-sac pattern of cytodifferentiation recorded on day 7-14 was unlike that of the other groups. These DC cultures were comprised of mainly macrophages and plasma cells.

Animals

Growth of mouse yolk sac cells cultured in vivo.

The proliferation and differentiation of yolk sac cells from 10 1/2-day-old mouse embryos were studied in diffusion chambers implanted into syngeneic and allogeneic hosts. The most striking observation was the appearance, proliferation and predominance of immature and mature plasma cells. The data suggested that the differentiation into plasma cells and the rate of growth of yolk sac cells cultured in vivo may be dependent on the genetics of the strain of mouse and host. This demonstration of differentiation of plasma cells from yolk sac cells cultured in vivo adds further information to the origin and ontogeny of potentially immunocompetent cells.

Animals