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S K Nilsson

Publications and source records attributed to S K Nilsson.

11 recordsLinked to original sources
PubMed1995

Granulocyte-macrophage colony-stimulating factor is not responsible for the correction of hematopoietic deficiencies in the maturing op/op mouse.

Osteopetrotic (op/op) mice are characterized by an autosomal recessive inactivating mutation resulting in the absence of biologically active colony-stimulating factor-1 (CSF-1). Consequently, young op/op mice have a severe deficiency of macrophages and osteoclasts resulting in excessive bone formation, occlusion of the marrow cavity, and reduced marrow hematopoietic activity. Recently, we showed that the osteopetrosis and hematopoietic deficiencies evident in young op/op mice are not permanent but are progressively corrected with age. There are increases in osteoclast activity; bone resorption; femoral marrow space; and marrow hematopoietic activity, cellularity, and macrophage content. In the present study we show that CSF-1-/- granulocyte-macrophage colony-stimulating factor (GM-CSF)(-/-)-deficient mice also undergo the same pattern of hematopoietic correction as the op/op mouse. Also, like the op/op mouse, the peritoneal cellularity and macrophage content of CSF-1/GM-CSF-deficient mice remains severely reduced. Our data show that the "knockout" of GM-CSF does not change the op/op phenotype, and that GM-CSF is not essential for the correction of the hematopoietic deficiencies in the op/op mouse. Importantly, the data also show that neither GM-CSF nor CSF-1 is an absolute requirement for the commitment of primitive hematopoietic stem cells to the macrophage lineage or for the differentiation of at least some classes of macrophages. This finding suggests that an alternate regulatory factor can be involved in macrophage and osteoclast commitment, differentiation, and function in vivo.

Age Factors↗
PubMed1995

Haematopoietic radioprotection by Cremophor EL: a polyethoxylated castor oil.

The polyethoxylated castor oil, Cremophor EL (Cremophor) is approved for human use as a vehicle for oral and intravenous administration of water-insoluble compounds. Cremophor has also previously been shown to reverse the multidrug resistance phenotype at clinically acceptable doses. This study demonstrates that doses of Cremophor in the range of 25-50 microliters/kg intravenously (i.v.) administered 1 day prior to near-lethal irradiation protected the regenerative capacity of the marrow, resulting in haematopoietic radioprotection and long-term survival of near-lethally-irradiated mice. In normal mice, Cremophor administration (1) markedly reduced the level of serum haematopoietic inhibitory activity 4-8 h following injection; (2) resulted in a transient decrease in femoral bone marrow cellularity and upregulated B220 (B cells), and 7/4 (neutrophils and activated macrophages), but not Thy-1 (T-cells) surface antigen expression in bone marrow cells within 24 h of injection; and (3) transiently elevated the incidence of both primitive and committed haematopoietic progenitor cells detected in clonal agar culture within 48 h of injection. Bone marrow progenitor cell content, and peripheral blood white cell, platelet and reticulocyte counts were unaffected. This suggests that the haematopoietic radioprotection and recovery observed in irradiated mice pretreated with Cremophor may be the result of accessory cell activation and/or modulation of accessory factors regulating haematopoietic progenitor cells. Our data suggest a potential clinical use of Cremophor as an adjunct to, or as a substitute for, cytokines to minimize myelosuppression following cytotoxic therapy.

Animals↗
PubMed1994

The development and establishment of hemopoiesis in fetal and newborn osteopetrotic (op/op) mice.

Previous studies of young CSF-1-less osteopetrotic (op/op) mice demonstrate a severe deficiency of both macrophages and osteoclasts, resulting in excessive bone formation, occlusion of the marrow cavity, and reduced hemopoietic activity. The accompanying splenomegaly and prolonged splenic hemopoiesis observed in these mice suggests that osteopetrosis may perturb the normal progression of fetal hemopoietic development and obstruct the seeding of hemopoietic precursors into the bone marrow. This study demonstrates that the absence of CSF-1 does not affect the progression of hemopoietic development in fetal op/op mice until after colonization of the bone marrow. Significant deficiencies in marrow cellularity and progenitor cell content in the long bones of op/op mice were not evident prior to Day 2 postnatal, suggesting that the altered hemopoietic state of young op/op mice is not a consequence of abnormal fetal hemopoietic development, but is primarily due to the lack of functional osteoclasts in op/op fetuses and hence, impaired remodeling of the marrow cavity after birth.

Animals↗
PubMed1994

Age-related changes in extramedullary hematopoiesis in the spleen of normal and perturbed osteopetrotic (op/op) mice.

Occlusion of the marrow cavity by excessive bone formation in young osteopetrotic (op/op) mice results in a significant reduction in the space available for hematopoiesis. At this time, splenomegaly is evident, and the spleen is a site of significant extramedullary hematopoiesis. In vitro clonal assays of spleen cell suspensions in young op/op mice demonstrated a 22-fold elevation in the content of high proliferative potential colony-forming cells (HPP-CFC) (4 weeks of age) and a 14-fold elevation in the content of committed progenitors responsive to colony-stimulating factor-1 (CSF-1) (6 weeks of age). Flow-cytometric analysis also demonstrated a shift in the myeloid:lymphoid cell ratio in the spleens of young op/op mice, with a 35% reduction in the number of B220+ cells, and a two-fold increase in myeloid cells expressing the hematopoietic cell surface lineage antigens Mac-1 and Gr-1. However, the hematopoietic deficiencies of op/op mice are not permanent. An age-related progressive remodeling of the bone marrow cavity results in the correction of bone marrow parameters by 22 weeks of age. This correction in marrow hematopoietic activity is accompanied by a resolution of the splenomegaly, a progressive decrease in splenic hematopoietic activity at both the primitive and committed progenitor cell levels, and a correction of the lymphoid:myeloid cell ratio. Negative immunomagnetic selection of splenic hematopoietic progenitor cells from op/op and control littermate mice, followed by analysis of their expansion in liquid culture, demonstrated that primitive hematopoietic progenitor cells of high proliferative potential continued to reside in the spleen of old op/op mice. The response of these mice to a 5-fluorouracil (5-FU) cytotoxic challenge suggested that this pool of primitive progenitor cells acted as a hematopoietic reserve capable of rapidly responding to hematopoietic perturbation.

Aging↗
PubMed1981

Delayed primary closure. Blood-flow in healing rat skin incisions.

In an earlier study delayed primary closure (DPC) wounds were shown to develop higher biomechanical strength than primary closure (PC) wounds. In order to elucidate the underlying mechanism, local clearance of 133Xenon and thermography studies were undertaken. A paired comparison design with deposits of 133Xenon injected in the wound margins 3 and 4 days postoperatively, and directly into the wound tissue 10, 20 and 60 days postoperatively was used. Very pronounced differences, with higher blood-flows for DPC wounds, were found in the early measurements. In the later measurements there were significant but less obvious differences. With thermography no differences could be detected. It is concluded that DPC wound have a higher blood-flow, especially in the initial wound healing phase. This supports the hypothesis that an increased blood-flowing during early wound healing is beneficial for the development of mechanical strength in the maturing normal scar.

Animals↗
PubMed1980

Calculation of skin temperature increase caused by subcutaneous veins perpendicular to the skin surface.

A graphical solution of the temperature increase at the surface of a homogeneous solid due to a linear heat source perpendicular to the surface is given. The calculations correspond to clinical situations for studies of the skin temperature increase over vessels approaching the surface from deeper layers of tissue. Estimations have been made of the maximum distance from the skin surface at which a vein of given diameter may be positioned to be detected in a thermogram. The necessary heat source power to produce a detectable increase in skin temperature is presented graphically as a function of heat source depth. The results can be used for the analysis of the skin temperature pattern by infrared thermography.

Breast Neoplasms↗
PubMed1978

Temperature gradients in low-flow vessels.

A graphical representation of heat transfer measurements and a graphical solution of the heat transfer equation, describing the temperature changes in a fluid flowing in a pipe localised in a heated or cooled region, are given. The solution is applicable to the axial temperature distribution of the blood in a vessel passing a region of high or lower temperature. An experimental study of the temperature distribution in small pipes with various flow rates and pipe diameters is presented. The results add information on conductive heat distribution in vessels to available knowledge of conductive heat distribution in tissues. The results can be used for the analysis of temperature changes in the vicinity of pathological processes accompanied by vascular changes, e.g. primary venous or arterial disease, inflammatory conditions or neoplasia.

Blood Flow Velocity↗
PubMed1975

Analytical calculation of the skin temperature distribution due to subcutaneous heat production in a spherical heat source.

An analytical solution of the thermal conductivity equation describing the surface temperature distribution over a buried heat source is given in tabular form. The solution is applicable to experimental models for studies of the surface temperature over an implanted artificial heat source. The results can also be used for the analysis of the skin temperature over biological heat sources such as breat tumours.

Body Temperature Regulation↗
PubMed1975

Skin temperature over an artificial heat source implanted in man.

The medical application of infrared thermography makes use of the skin temperature as an indication of an underlying pathological process. In order to study the relation between the heat production from a source in living tissue and the overlying skin temperature, artificial heat sources were implanted subcutaneously in human volunteers. The experimental results show that a detectable surface temperature increase over the heat sources presupposes high power output or superficial implantation. The effect of forced convective heat loss from the skin surface and lowered ambient temperature was studied. Forced convection markedly decreased the temperature contrast. An implicit conclusion from experimental and theoretical work is that a localized 'hot spot' can only exceptionally be attributed to metabolic heat production conducted to the skin surface from a buried pathological process. The thermal pattern over a breast tumour, a septic or aseptic inflammation or a tissue injury mainly reflects the vascular reaction.

Adult↗