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Biomedical subjects

R D Lange

Publications and source records attributed to R D Lange.

At least 73 records · Page 4Linked to original sources

Progenitor cells in canine cyclic hematopoiesis.

Granulocytic (colony-forming units in culture, or CFU-c) and erythrocytic (erythropoietin-responsive cells, or ERC) progenitor cells in canine cyclic hematopoiesis (CH) have been shown to fluctuate over the cycle and in the same phases as one another. The ERC cycle is preceded by 3 or 4 days by a rise in serum erythroid-stimulating activity and is followed by a reticulocytosis. During the cycle CFU-c show a differential sensitivity to two sera, one normal and one containing elevated amounts of colony-stimulating activity. The proliferation rate of CFU-c also fluctuates from well above normal to considerably less than normal over the cycle. These results are discussed in the light of present knowledge of the pathogenesis of canine CH. We suggest that these results support the contention that CH is a disorder of hemopoietic stem cells and that the cycling of humoral factors and peripheral blood cells may follow as a consequence.

Animals↗

Hormonal control of erythropoiesis in canine cyclic haematopoiesis.

The results of erythropoietin (ESF) studies in dogs with cyclic haematopoiesis are presented. Even though the dogs were exposed to a constant stimulus of hypoxia, cycles in the plasma ESF levels occurred at 11 to 12 day intervals. In some dogs, minor midcycle peaks were observed and the amount of ESF produced varied with the different animals. The peaks of ESF characteristically appeared approximately five days after onset of neutropenia. A hypothesis is presented to explain the known facts concerning canine cyclic haematopoiesis. It suggests that a poietin controlling factor is produced and that this assumed factor then stimulates the production of specific factors leading to increases of reticulocytes, platelets, and monocytes. The monocytes in turn produce more colony stimulating factor (CSF) leading to the formation of granulocytes. Such a sequence of events would explain the apogee of reticulocyte, platelet, and monocyte counts at a time when the nadir of granulocyte counts is reached.

Animals↗

Erythropoiesis and erythrocytic survival in dogs with cyclic hematopoiesis.

Erythrocytic survival and ferrokinetic studies were carried out in dogs with cyclic hematopoiesis. The serum iron values varied during different phases of the cycle. The highest values occurred when the bone marrow predominantly contained granulocytic cells. The erythrocytic survival and the remainder of the ferrokinetic variables were comparable to those in normal dogs of a similar age.

Agranulocytosis↗

Cyclic hematopoiesis in a colony of dogs.

A laboratory-maintained colony of dogs heterozygous for cyclic hematopoiesis (ch) has been established. The colony consists of Collies and Collie-Beagle mixed dogs. Matings between dogs heterozygous for ch resulted in 110 pups, 28 of which were homozygous for ch. Each of the 28 homozygous ch pups (15 females and 13 males) was gray and white. Ninetten of them survived the preweaning period and were found to have cyclic fluctuations of neutrophils, platelets, and reticulocytes.

Animals↗

Canine cyclic haematopoiesis: marrow transplantation between littermates.

Dogs affected with cyclic haematopoiesis (CH) and experiencing recurrent 12-day cycles of neutropenia were supralethally irradiated and transplanted with marrow from their normal littermates. Following transplantation of the normal marrow, dogs with CH experienced no further cycles of neutropenia. Platelet and reticulocyte numbers also ceased to fluctuate cyclically in these dogs. The marrows of dogs with CH were transplanted into unaffected supralethally irradiated littermates. Prompt engraftment occurred in the recipient dogs with subsequent cyclic rises and falls of the numbers of platelets, reticulocytes and neutrophils. In the post-transplant period, immunosuppressant drugs were not used in three of the recipients and the fourth received only a single 5 mg dose of methotrexate.

Animals↗

Thrombopoietin production by human embryonic kidney cells in culture.

Human embryonic kidney cells were maintained in culture in a medium containing lactalbumin hydrolysate for 5 to 6 weeks and the supernatant fluid tested for thrombopoietin content. Thrombopoietin was determined by a bioassay procedure which utilized mice that were in rebound thrombocytosis. The results indicate that the medium from kidney cells in culture contained a factor that stimulates thrombopoiesis in assay mice as measured by per cent 35-S incorporation into platelets. A dose-response relationship was demonstrated between the volume of thrombopoietically active production medium injected and the level of isotope that subsequently appeared in the circulating platelets. Thrombopoietin was not found in control production media. Moreover, thrombopoietin-rich production medium did not contain erythropoietin, erythroginin, or white blood cell-stimulating factors. The results of this study indicate that kidney cells in culture produce a specific thrombopoietic stimulating factor. It seems probable from these in virto data that a site of production of thrombopoietin in vivo is the kidney.

Animals↗

Response in mice to an erythropoietin-generating factor.

The bioassay for erythropoietin-stimulating factor (ESF) was compared in 3 strains of mice. One strain was made polycythemic by hypertransfusion and the other 2 by hypoxia. An erythropoiesis-generating factor (EGF) measured in the 3 strains generated approximately the same amounts of ESF, determined with log dose-log response curves for the respective techniques, after incubation with normal rabbit serum (NRS). The amount of ESF generated by EGF without prior incubation with NRS was also approximately the same in the 3 strains of mice.

Altitude↗

Canine cyclic neutropenia: Erythropoietin and platelet cycles after bone marrow transplantation.

The marrow of a dog affected with cyclic neutropenia (CN) was transplanted into an unaffected supralethally irradiated litermate. Prompt engraftment occurred, and cyclic rises and falls in numbers of platelets, reticulocytes, and granulocytes were noted in the recipient soon after engraftment. Prior to transplantation and under hypoxic conditions, the donor had serum erythropoietin (ESF) peak levels at 11-12-day intervals. Following transplatation and under hypoxic conditions, cyclic peaks of ESF occurred in the transplanted dog.

Agranulocytosis↗

Sepharose-bound erythropoientin. Studies with anti-erythropoietin.

Anti-erythropoietin antibodies (anti-ESF) were determined by the capacity of the immunoglobulins to neutralize the biological activity of erythropoietin (ESF). Affinity chromatographic methods were used to initiate the purification of anti-ESF by use of ESF covalently linked to Sepharose. It was observed that anti-ESF bound the ESF-Sepharose. In order to remove the nonspecific immunoglobulins, the anti-ESF preparation was subjected to further chromatography on affinity colums where either serum or urinary proteins from a polycythemic patient were covalently linked to Sepharose. It was demonstrated the affinity chromatography could be used as a method isolate anti-ESF.

Animals↗