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Biomedical subjects

S H Robinson

Publications and source records attributed to S H Robinson.

At least 37 records · Page 2Linked to original sources

Lymphoma with autoimmune neutropenia and hepatic sinusoidal infiltration: a syndrome.

A relation between lymphoma and autoimmune neutropenia, unlike autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura, has not previously been well documented. We report a patient with a disorder presenting as autoimmune agranulocytosis, splenomegaly, and infiltration of the hepatic sinusoids by lymphocytes. Antineutrophil antibodies were present. Over a 2 1/2-year period, the illness progressed to an aggressive, poorly differentiated lymphocytic lymphoma with terminal liver failure and fibrosis. Peripheral blood lymphocyte markers identified the tumor as a proliferation of T-cells of the helper class. A review of previous literature disclosed other reports of similar patients who had neutropenia, a lymphoproliferative illness, and hepatic disease. Our case is representative of a previously unrecognized syndrome characterized by autoimmune neutropenia in the setting of a lymphoproliferative disorder of T cells, with a predilection for liver involvement.

Agranulocytosis↗

Two classes of murine granulocyte progenitor cells expressed in plasma clot diffusion chamber cultures.

Two distinct classes of granulocyte progenitor cells present in normal mouse bone marrow are expressed sequentially in the vivo plasma clot diffusion chamber culture system. By several criteria, progenitor cells giving rise to granulocyte colonies on day 4 of culture (CFU-D4) are different from those giving rise to colonies on day 7 (CFU-D7). These differences include: cell cycle activity as measured by in vitro incubation with cytosine arabinoside, residual concentration in the bone marrow after in vivo treatment of donor mice with cytosine arabinoside or methotrexate, resistance to osmotic lysis, size as determined by velocity sedimentation, and the morphology of the granulocyte colonies to which these cells give rise. The CFU-D7 appears to represent an earlier progenitor cell than the CFU-D4 in the differentiation pathway of the granulocyte and is analagous in many respects to the BFU-E in the erythroid pathway.

Animals↗

Transferrin-binding and iron-binding proteins of rabbit reticulocyte plasma membranes. Three distinct moieties.

1. Transferrin-membrane complexes and iron-binding membrane complexes were solubilized with sodium dodecyl sulfate from the plasma membranes of reticulocytes that had been incubated with (59Fe,125I)-labeled transferrin. Gel filtration of solubilized material demonstrated 125I-labeled transferrin complexed to two moieties, a minor component (Peak I) of apparent molecular weight 435,000 and a major component (Peak II) of apparent molecular weight 200,000. Most of the membrane 59Fe was located in Peak I. 2. Sepharose-bound anti-transferrin was used to purify the 125I-labeled transferrin-membrane complexes. The 59Fe/125I ratio in the transferrin complex purified from Peak I was the same as in the original transferrin and thus contained membrane-bound transferrin to which the 59Fe was still attached. The 59Fe/125I ratio in the purified Peak II transferrin complex was 0.33 times that of the original transferrin, indicating that more than 60% of its 59Fe had been delivered to the reticulocyte. 3. The purified transferrin complexes analyzed by SDS-polyacrylamide gel electrophoresis demonstrated a single band of apparent molecular weight 78,000 both by Coomassie blue stain for protein and by 125I radioactivity. The specific activity of this material was 0.27 and 0.56 times that of the original transferrin for Peak I and Peak II, respectively, indicating that transferrin in Peak I and II was bound to a membrane component with a molecular weight similar to that of transferrin. 4. The isoelectric focusing pattern of the Peak II transferrin complex showed isoelectric points of pH 6.7 and 6.2 compared to pH 5.4 for transferrin. 5. On the basis of these studies we propose that transferrin is first bound to a membrane protein and then delivers iron to a membrane component distinct and separate from the transferrin-binding moiety. Prior to its release, transferrin markedly depleted of iron is still bound to a component in the plasma membrane.

Animals↗

Chronic granulomatous disease. Expression of the metabolic defect by in vitro culture of bone marrow progenitors.

Chronic granulomatous disease (CGD), an often fatal syndrome of recurrent infections results from the inability of patients' peripheral blood phagocytic leukocytes to generate superoxide despite otherwise normal phagocytic functions such as ingestion and degranulation. Circulating granulocytes and monocytes are the progeny of bone marrow progenitor cells, colony-forming units in culture. We compared the function of cells grown in two different in vitro cuture systems from the bone marrow of a CGD patient with those from normal subjects. The cells of normal colony-forming unit in culture colonies grown in semisolid medium reduced nitroblue tetrazolium dye when stimulated by phorbol myristate acetate; none of the cells from colonies derived from CGD marrow did so. Cells grown in liquid suspension culture from normal marrow generated superoxide nearly as well as normal peripheral blood granulocytes; those from CGD marrow produced no superoxide, similarly cultured cells from both normal and CGD marrow ingested opsonized bacteria at rates equal to peripheral blood granulocytes. CGD marrow-derived cells showed increased exocytic degranulation relative to both normal marrow-derived cells and normal peripheral blood granulocytes. These studies demonstrate that the basic functional characteristics of CGD are embedded in the genetic program of granulocyte progenitors.

Adolescent↗

Increased erythropoietin sensitivity of murine CFU-E and BFU-E in in vivo cultures.

The in vivo PCDC assay was used to reassess the erythropoietin requirements for growth in culture of the erythroid precursor cells CFU-E and BFU-E. Both CFU-E and BFU-E are expressed with the physiologically low erythropoietin concentrations present in normal host mice. Moreover, the same number of CFU-E-derived colonies is observed in hypertransfused host animals. No BFU-E are observed under these conditions. Increased numbers of both CFU-E and BFU-E are expressed in anemic host animals; these values are moderately lower than those found with in vitro cultures containing large concentrations of erythropoietin. Thus, at high levels of erythropoietin, the in vivo PCDC assay appears to be somewhat less sensitive than conventional in vitro assays. However, this culture system is more sensitive at low levels of erythropoietin and demonstrates a much smaller erythropoietin requirement for the differentiation of both CFU-E and BFU-E than has hitherto been recognized. This is as should be expected if these progenitor cells play a role in normal erythropoiesis in vivo. Experiments concerning the effects of anemia or hypertransfusion in donor rather than host mice reconfirm that the population size in the marrow of CFU-E but not BFU-E is highly sensitive to erythropoietin. However, phenylhydrazine treatment of donor mice leads to the transient development of a new subclass of BFU-E which gives rise to colonies relatively late in culture, suggesting that erythropoietin does have a direct effect on the physiological status of BFU-E in the bone marrow.

Anemia↗

Transferrin binding and iron transport in iron-deficient and iron-replete rat reticulocytes.

Three aspects of iron metabolism were studies in reticulocytes from iron-deficient, phlebotomized, and phenylhydrazine-treated rats: (1) the number of transferrin binding sites; (2) the uptake of 59Fe-transferrin; and (3) the ability of cytosol to mobilize 59Fe from 59Fe-labeled reticulocyte plasma membrane. The number of transferrin binding sites, assayed by measuring the binding of 125I-labeled transferrin to reticulocytes, were similar in iron-deficient and phlebotomy-induced reticulocytes, 66,000 and 75,000 binding sites/cell, respectively, but were about doubled, 120,000 binding sites/cell, in phenylhydrazine-induced reticulocytes. Uptake of 59Fe into iron-deficient reticulocytes was about one-half that for phlebotomy-induced reticulocytes and one-quarter that for phenylhydrazine-induced reticulocytes, the rates of uptake being measured as 21,540, 41,233, and 79,600 molecules of 59Fe per minute per cell, respectively. The mobilizing activity of cytosol free iron-deficient reticulocytes was also about one-half that of cytosol from phlebotomy-induced reticulocytes and about one-quarter that of cytosol from phenylhydrazine-induced reticulocytes. These results indicate that instead of a compensatory increase in these aspects of iron metabolism, the iron-deficient reticulocyte had a decreased ability to transport iron.

Anemia, Hypochromic↗

Mobilization of iron from the plasma membrane of the murine reticulocyte. The role of ferritin.

1. Plasma membranes prepared by pre-incumbation of mouse reticulocytes with 125I, 59Fe-labeled murine transferrin were able to release 59Fe in preference to 125I when incubated in the presence of murine reticulocyte cytosol, demonstrating that the latter mobilized iron which had been dissociated from transferrin. 2. 59Fe in cytosol was associated with at least two components in addition to hemoglobin, a high molecular weight component, identified as ferritin by specific immunoprecipitation, and an as yet unidentified, low molecular weight component of approx 17 00. 3. Ferritin itself, in the absence of added cytosol, was abloe to mobilize 59Fe from s9Fe-labeled reticulocyte plasma membranes. 4. Lysates of reticulocytes synthesized 59Fe-labeled heme when incubated with 59Fe-labeled ferritin. 5. These findings reflect a pathway of iron uptake and incorporation into heme in which ferritin plays an active role.

Animals↗

Renal cyst puncture: utilization of pediatric guide wire technique and upright radiographic changers.

After puncture of a renal cyst with a polytetrafluoroethylene needle a pediatric 0.021-inch guide wire is inserted through a polytetrafluoroethylene sheath needle. The sheath is then advanced over the wire. The technique is controlled by fluoroscopy or performed under ultrasonography. Aspiration of the contrast material is performed, and then air and diatrizoate meglumine and diatrizoate sodium are injected to outline the borders of the cyst. The patient is then taken to an upright and lateral radiographic changer for routine radiography in the upright and decubitus positions.

Humans↗

Gray-scale ultrasound: utility preoperatively and postoperatively in a patient with obstructive jaundice.

We present a case of obstructing calculi of the common bile duct diagnosed by ultrasonography. Postoperatively, a sterile abscess due to bile leakage at the distal common bile duct developed, and was also diagnosed by ultrasound Ultrasonography was useful in following the course of clearing of the bile collection. Preoperative ultrasound evaluation of the jaundiced patient should be followed by postoperative sonography, especially if complications occur.

Aged↗

Transferrin receptors in developing murine erythroid cells.

Techniques of cell separation were used to isolate murine erythroid cells at different stages of maturation. The number of transferrin receptors in these cell populations was assayed by measuring binding of 125I-labelled transferrin. Nearly 23 times as many receptors were found in the least mature cells, chiefly pronormoblasts, as in reticulocytes. Iron transport, determined by measurement of the rate of 59Fe uptake from 59Fe-labelled transferrin, was proportional to the number of receptors at all stages of differentiation. Electron microscope radioautographic studies of the interaction of 125I-labelled transferrin with erythroid precursor cells demonstrated that 15-33% of cell associated transferrin was intracellular in erythroid precursors.

Animals↗

Maintenance of hemopoietic stem cells in diffusion chamber cultures.

When murine bone marrow cells are cultured in DC's in irradiated host mice, there is an initial phase of rapid white cell growth followed by prolonged maintenance of steady-state granulopoiesis. This study examined the role of hemopoietic stem cells in this culture system. During the initial growth phase there was a rapid increase in both pluripotential stem cells, CFU-S, and commmitted white cell precursors, CFU-C. The increase in CFU-C was larger, occurred more rapidly, and was biphasic in nature. After day 7 and until at least day 16, the numbers of CUF-S, CFU-C and total white cells were all maintained at relatively constant plateau levels which were typically well below the maximal capacity of the culture system. During the plateau phase the number of CFU-S was slightly greater than the number initially placed in culture, whereas CFU-C had increased by a factor of 2.3 and total white cells by a factor of 10. This appears to reflect a system of growth amplification, with preferential differentiation of CFU-S into CFU-C and thence into the pathway of white cell development. The plateau phase of culture has received very little attention but appears to represent a model, in a closed culture system, of finely regulated granulopoiesis, with an equilibrium between constant numbers of hemopoietic stem cells and their differentiating white cell progeny.

Animals↗