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991.
Stromal cells from human long-term marrow cultures are mesenchymal cells that differentiate following a vascular smooth muscle differentiation pathway 总被引:20,自引:2,他引:20
In human long-term marrow cultures connective tissue-forming stromal cells are an essential cellular component of the adherent layer where granulomonocytic progenitors are generated from week 2 onward. We have previously found that most stromal cells in confluent cultures were stained by monoclonal antibodies directed against smooth muscle- specific actin isoforms. The present study was carried out to evaluate the time course of alpha-SM-positive stromal cells and to search for other cytoskeletal proteins specific for smooth muscle cells. It was found that the expression of alpha-SM in stromal cells was time dependent. Most of the adherent spindle-shaped, vimentin-positive stromal cells observed during the first 2 weeks of culture were alpha- SM negative. On the contrary, from week 3 to week 7, most interdigitated stromal cells contained stress fibers whose backbone was made of alpha-SM-positive microfilaments. In addition, in confluent cultures, other proteins specific for smooth muscle were detected: metavinculin, h-caldesmon, smooth muscle myosin heavy chains, and calponin. This study confirms the similarity between stromal cells and smooth muscle cells. Moreover, our results reveal that cells in vivo with the phenotype closest to that of stromal cells are immature fetal smooth muscle cells and subendothelial intimal smooth muscle cells; a cell subset with limited development following birth but extensively recruited in atherosclerotic lesions. Stromal cells very probably derive from mesenchymal cells that differentiate along this distinctive vascular smooth muscle cell pathway. In humans, this differentiation seems crucial for the maintenance of granulomonopoiesis. These in vitro studies were completed by examination of trephine bone marrow biopsies from adults without hematologic abnormalities. These studies revealed the presence of alpha-SM-positive cells at diverse locations: vascular smooth muscle cells in the media of arteries and arterioles, pericytes lining capillaries, myoid cells lining sinuses at the abluminal side of endothelial cells or found within the hematopoietic logettes, and endosteal cells lining bone trabeculae. More or less mature cells of the granulocytic series were in intimate contact with the thin cytoplasmic extensions of myoid cells. Myoid cells may be the in vivo counterpart of stromal cells with the above-described vascular smooth muscle phenotype. 相似文献
992.
Platelet transfusions from donors matched for cross-reactive antigens have been shown to be effective in providing hemostasis in alloimmunized thrombocytopenic patients. A significant number of these transfusions, however, fail to provide posttransfusion platelet recoveries. We investigated incompatibility in the Bw4/bw6 system as a possible explanation for these failures. The Bw4/Bw6 system is a biallelic antigen system closely associated with HLA-B. HLA-B locus antigens that are cross-reactive frequently differ in their Bw4/Bw6 specificity. Posttransfusion platelet recoveries from 21 alloimmunized thrombocytopenic patients homozygous for Bw4 or Bw6 and transfused with both Bw4/Bw6 compatible and incompatible platelets were analyzed. The mean 1-hr posttransfusion recovery was 84% following Bw4/Bw6-compatible platelets versus 52% with Bw4/Bw6-incompatible platelets (p less than 0.02). Twenty-four hours following transfusion, mean recoveries were 44% and 24%, respectively, (p less than 0.01). A subgroup of 8 patients (38%) was identified who had markedly lower responses following Bw4/Bw6- incompatible transfusions as compared to Bw4/Bw6-compatible transfusions (mean recoveries: 1 hr--compatible 100%, incompatible 27%, p less than 0.001; 24 hr--compatible 45%, incompatible 7%, p less than 0.01). These data suggest that the Bw4/Bw6 antigen system has clinical significance for some patients requiring platelet transfusion therapy and, when appropriate, should be considered in the selection of donors. 相似文献
993.
We evaluated neutrophil adhesive function in patients undergoing chronic hemodialysis using either prostacyclin or heparin as antithrombotic agents. Patients underwent successive hemodialyses with prostacyclin (4 ng/kg/min) and heparin. There were no significant differences noted in neutrophil adhesive function during either dialysis: transient neutropenia developed in each case; impaired neutrophil adhesiveness to plastic developed during both dialyses; neutrophil aggregation was diminished when compared to predialysis responses during both dialyses. Furthermore, the number of circulating Fc-receptor-bearing neutrophils fell significantly during both prostacyclin and heparin hemodialysis. Our study demonstrates that substitution of prostacyclin for heparin in doses that do not cause hypotension, does not prevent neutropenia or alter the diminished neutrophil adhesiveness that occurs during heparin hemodialysis. 相似文献
994.
995.
Thomas J. Lescher M.D. Major MC David K. Teegarden M.D. Major MC Basil A. Pruitt Jr. M.D. Colonel MC 《Diseases of the colon and rectum》1978,21(8):618-622
Summary and Conclusions Five (1 per cent) of 529 thermally injured patients experienced pseudo-obstruction of the colon over a two-year period. All
patients had classic non-painful abdominal distention. Infection was the most common associated problem and possible triggering
mechanism in these patients. After confirmation of the colonic dilation on a plain abdominal roentgenogram, distal obstruction
was ruled out by contrast enema. Occasionally, Gastrografin enema seemed to ameliorate the distention.
Conservative medical management should be attempted initially. Colonoscopy should be employed at the earliest possible time.
Exploratory laparotomy and tube cecostomy are usually adequate when surgical decompression is necessary.
Patients who have accompanying small-intestinal distention seemed to tolerate this condition better, possibly due to a decompressing
effect of an incompetent ileocecal valve. “Hinge-type” kinks, which occur in time at both hepatic and splenic flexures, become
obstructing in themselves, and can be a barrier to conservative treatment.
Read at the meeting of the American Society of Colon and Rectal Surgeons, San Diego, California, June 11 to 15, 1978.
The opinions or assertions contained herein are the private view of the authors and are not to be construed as official or
as reflecting the view of the Department of the Army or the Department of Defense. 相似文献
996.
997.
A phase 1B trial of humanized monoclonal antibody M195 (anti-CD33) in myeloid leukemia: specific targeting without immunogenicity 总被引:5,自引:1,他引:5
Caron PC; Jurcic JG; Scott AM; Finn RD; Divgi CR; Graham MC; Jureidini IM; Sgouros G; Tyson D; Old LJ 《Blood》1994,83(7):1760-1768
This trial studied the biodistribution, pharmacology, toxicity, immunogenicity, and biologic characteristics of a trace-labeled, anti- CD33, humanized monoclonal antibody M195 (Hu-M195) in patients with relapsed and refractory myeloid leukemia. Hu-M195 is a computer- modeled, "complementarity-determining region-grafted," IgG1, humanized version of M195. M195 is a murine monoclonal antibody that reacts with CD33, a 67-kD glycoprotein expressed on early myeloid progenitor cells and myeloid leukemia (acute myelogenous leukemia and chronic myelogenous leukemia) cells, but not normal stem cells. 131I-murine- M195 has already shown significant ability to cytoreduce patients with relapsed or refractory myeloid leukemias. Hu-M195 has higher avidity than the original mouse monoclonal antibody and, unlike murine M195, has the capability to mediate antibody-dependent cellular cytotoxicity against leukemia targets. Thirteen patients with relapsed or refractory myelogenous leukemia were treated with Hu-M195 at 4 levels of 0.5, 1.0, 3.0, and 10.0 mg/m2 in a phase I trial. Patients received a total of 6 doses per patient over 18 days. Two patients were retreated for a total of 12 doses. The first dose of Hu-M195 was trace-labeled with 131I to allow detailed pharmacokinetic and biodistribution studies by serial sampling of blood, radioimmunoassays of cells, and whole-body gamma- camera imaging. Cumulative total doses of up to 216 mg of Hu-M195 were administered safely. Reversible fever and rigors were observed after infusion at the highest dose levels. The entire bone marrow was specifically and clearly imaged within hours after infusion, with optimal biodistribution occurring at the 3 mg/m2 level. Adsorption of Hu-M195 onto targets in vivo was demonstrated by flow cytometry; near saturation of available sites occurred at the 3 mg/m2 dose level. Plasma and whole body half lives were 38 and 51 hours, respectively, which may reflect continual replenishment of target sites on new leukemia cells. 131I-Hu-M195 was rapidly internalized into the target cells in vivo within 1 hour. Human antihuman antibody responses were not observed. In conclusion, Hu-M195 can be administered safely in multiple doses, without significant toxicity or any evidence of immunogenicity, and can localize rapidly and efficiently to the bone marrow in patients with myeloid leukemias. Additional phase II trials with this agent alone or in combination with cytokines or isotopes are warranted at the optimal biologic dose. 相似文献
998.
Walters MC; Sullivan KM; Bernaudin F; Souillet G; Vannier JP; Johnson FL; Lenarsky C; Powars D; Bunin N; Ohene-Frempong K 《Blood》1995,85(4):879-884
Seven of 21 patients with sickle cell anemia developed neurologic complications 5 to 243 days (median, 33 days) after allogeneic marrow transplantation. Among these 7 patients, indications for transplantation included either a past history of stroke (4 patients) or recurrent severe vaso-occlusive events (3 patients). All received marrow from an HLA-identical sibling after preparation with busulfan and cyclophosphamide, and in 4 patients with antithymocyte globulin. Five of 6 patients developing seizures received anticonvulsant and supportive treatment with resolution of neurologic abnormalities. Three patients experienced intracranial bleeding, which was fatal in two. Of the 14 patients free of neurologic complications, 4 patients had experienced stroke before transplantation. However, among all patients with prior stroke, the incidence of intracranial hemorrhage was 38% (3/8), whereas none of the 13 patients without prior stroke developed posttransplant intracranial bleeding (P = .026). We conclude that patients with sickle cell anemia are at increased risk for neurologic complications after marrow ablative therapy and that patients with prior stroke are at increased risk for intracranial hemorrhage. Transplantation of patients before the onset of overt stroke may reduce this risk. 相似文献
999.
Sp alpha I/78: a mutation of the alpha I spectrin domain in a white kindred with HE and HPP phenotypes 总被引:5,自引:2,他引:5
Lecomte MC; Garbarz M; Grandchamp B; Feo C; Gautero H; Devaux I; Bournier O; Galand C; d'Auriol L; Galibert F 《Blood》1989,74(3):1126-1133
Limited tryptic digestion of spectrin (Sp) from seven related individuals manifesting hereditary elliptocytosis (HE) or hereditary pyropoikilocytosis (HPP) phenotypes revealed the presence of a novel peptide with a molecular weight of 78 Kd and a concomitant decrease in the alpha I domain (80-Kd peptide), which is the domain involved in the dimer self-association process. Sp from the normal members of this white family exhibited a normal peptide pattern, as compared with controls. The abnormal peptide pattern was associated with a decreased ability of Sp dimer to self-associate. In this kindred in which three generations were available for study, the clinical manifestations were quite variable and ranged from the asymptomatic HE carrier state to hemolytic HE or to severe anemia requiring splenectomy. The severity of the disease appeared to be correlated both with the amount of mutant spectrin (31% to 69%) and with the excess of the Sp dimer found in the membrane (26% to 60%, compared with a normal value of 5.6% +/- 2.2%). Partial amino acid sequencing showed that the alpha I/78-Kd peptide resulted from cleavage at lysine residue 10 of the alpha I/80-Kd domain. Knowledge of the exon/intron structure of cloned genomic DNA encoding the alpha I domain allowed us to amplify in vitro a DNA fragment containing the third exon of the alpha-spectrin gene. The amplified fragment was subcloned and sequenced. A G to T transversion was found in the 39th codon (AGT for AGG), which changed the normal arginine to a serine. Hybridization of amplified DNAs with allele- specific oligonucleotides corresponding to the normal and mutant sequences confirmed the presence of the mutation in three other HE members of the family (the propositus mother, brother, and sister). 相似文献
1000.
John O. Simmons MD MPH MAJ MC Dr. Gordon L. Noel MD Louis F. Diehl MD LTC MC 《Journal of general internal medicine》1989,4(6):473-481
Sixty-five physicians were tested to determine the effect of their reviews of red blood cell morphology on their subsequent
diagnoses of and workup plans for common anemias. The subjects read clinical and laboratory data for six pairs of cases of
anemia, reviewing the blood smear for one case in each pair. They correctly identified the presence or absence of morphologic
features on the blood smears 82% of the time. In spite of excellent morphologic discrimination, the number of tests ordered
was not affected by blood smear review. In fact, the quality of the physicians’ workup plans, measured by numbers of tests
appropriately ordered and excluded, was slightly but significantly better when they did not review the smears (p<0.005). In
addition, smear review did not significantly improve diagnostic accuracy for any of the common anemias studied. Significantly
more correct diagnoses were made without smear review for vitamin B12-folate deficiency anemia (p<0.015) and thalassemia (p<0.0001). Although routine review of blood smears by physicians in the
management of common anemias may provide useful information, the authors were unable to demonstrate an improvement in the
number or appropriateness of tests ordered or diagnostic accuracy in spite of excellent morphologic discrimination.
Received from the Divisions of General Internal Medicine and Hematology, Department of Medicine, Walter Reed Army Medical
Center, Washington, DC, and the Uniformed Services University of the Health Sciences, Bethesda, Maryland. Dr. Simmons is now
Chief, Division of General Internal Medicine, Brooke Army Medical Center, San Antonio, Texas.
Presented in part at the annual meeting of the American Federation of Clinical Research, Washington, DC, May 3, 1986.
Supported by a grant from the Department of Clinical Investigation (WU 1013), Walter Reed Army Medical Center, Washington,
DC 20307-5001.
The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or
as reflecting the views of the Department of Defense, the Department of the Army, or the Uniformed Services University of
the Health Sciences. 相似文献