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111.
Isolation and structural characterization of the polypeptide subunits of membrane glycoprotein IIb-IIIa from human platelets 总被引:6,自引:1,他引:6
We have previously demonstrated the isolation of platelet membrane glycoprotein IIb-IIIa by affinity chromatography with a specific monoclonal antibody. We have now separated the polypeptide subunits IIb and IIIa of the isolated glycoprotein by preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis and have compared their structural features. Both IIb and IIIa contain approximately 15% carbohydrate, but IIIa contains a larger percentage of mannose residues, suggesting the presence of high mannose as well as complex N- linked oligosaccharide chains. The amino acid compositions are sufficiently similar to imply areas of sequence homology between the two subunits. To examine further the relationship between the subunits, we digested a mixture of 125I-IIb and 131I-IIIa with trypsin and then separated the radiolabeled peptides by high performance liquid chromatography. The resultant peptide maps of IIb and IIIa are completely different. This indicates that neither subunit is derived from the other and suggests that polypeptides IIb and IIIa are products of separate genes. 相似文献
112.
Eight patients with Ph1-positive chronic myelogenous leukemia (CML) in chronic or accelerated phase received high-dose cyclophosphamide, total body irradiation, and bone marrow transplantation from an HLA-identical sibling donor. All patients had prompt engraftment and achieved complete hematologic remission. Six patients remain alive and in continuous remission with a normal bone marrow karyotype 3-20+ mo posttransplant. One patient died from cytomegalovirus interstitial pneumonitis. Only one patient who was transplanted in accelerated phase relapsed 6.5 mo posttransplant and died in blast crisis. High-dose combined modality therapy is capable of producing sustained complete remissions in patients with CML treated during chronic or accelerated phase. 相似文献
113.
NFS-60 and FDCP-Mix cells are interleukin-3--dependent multipotent hematopoietic cells that can differentiate in vitro into mature myeloid and erythroid cells. Retrovirus-mediated transfer of the human colony- stimulating factor-1 (CSF-1) receptor gene (c-fms) enabled NFS-60 cells but not FDCP-Mix cells to proliferate in response to CSF-1. The phenotype of NFS-60 cells expressing the human CSF-1 receptor (CSF-1R) grown in CSF-1 did not grossly differ from that of original NFS-60 as assessed by cytochemical and surface markers. Importantly, these cells retained their erythroid potentiality. In contrast, a CSF-1-dependent variant of NFS-60, strongly expressing murine CSF-1R, differentiated into monocyte/macrophages upon CSF-1 stimulation and almost totally lost its erythroid potentiality. We also observed that NFS-60 but not FDCP-Mix cells could grow in response to stem cell factor, (SCF), although both cell lines express relatively high amounts of SCF receptors. This suggests that SCF-R and CSF-1R signalling pathways share at least one component that may be missing or insufficiently expressed in FDCP-Mix cells. Taken together, these results suggest that human CSF-1R can use the SCF-R signalling pathway in murine multipotent cells and thereby favor self-renewal versus differentiation. 相似文献
114.
Absence of an association between mannose-binding lectin polymorphism and rheumatoid arthritis 总被引:2,自引:0,他引:2
Stanworth SJ; Donn RP; Hassall A; Dawes P; Ollier W; Snowden N 《Rheumatology (Oxford, England)》1998,37(2):186-188
It has been proposed that mannose-binding lectin (MBL) interactions with
agalactosyl forms of IgG immunoglobulins found in rheumatoid synovial fluid
might lead to enhanced complement activation, an important mediator of the
joint damage in rheumatoid arthritis (RA). In order to investigate this
possible link between increased MBL-mediated activation of complement and
perpetuation of rheumatoid synovitis, we have compared the frequency of an
allelic form of MBL, known to be incapable of activating complement, in a
group of hospital patients with severe RA and control subjects. No evidence
was found to support an association between the presence of this MBL allele
and protection from rheumatoid disease; genotype frequencies were similar
in both groups. This suggests that complement activation via
MBL-agalactosyl IgG complexes is unlikely to play a major role in the
pathophysiology of RA.
相似文献
115.
Loss of bone mineral density in Chinese pre-menopausal women with systemic lupus erythematosus treated with corticosteroids 总被引:7,自引:1,他引:7
The adverse effect of disease and chronic corticosteroid therapy on bone
mineral density (BMD) in patients with systemic lupus erythematosus (SLE)
has been reported in several studies of Caucasian populations. As the
factors controlling bone homeostasis may be different in Asian populations,
we measured BMD in 52 pre-menopausal Chinese women (mean age 34.1 +/- 8.0
yr) with SLE (mean disease duration 6.4 +/- 4.5 yr) treated with prednisone
(mean daily dose 11.4 +/- 10.8 mg/day). Lumbar spine, hip (total and
subregions) and total body BMDs were measured in the SLE patients using
dual-energy X-ray absorptiometry (DEXA), and compared with those from
healthy controls matched for age, sex and body mass index. Compared to
controls, SLE patients were found to have lower BMD (g/cm2) at several
sites: the lumbar spine (0.98 vs 0.90, P = 0.001), Ward's triangle (0.72 vs
0.67, P = 0.03), total body (1.04 vs 1.01, P = 0.04) and total hip (0.87 vs
0.82, P = 0.05). There was no correlation between BMD at any region and
duration of disease, activity of disease or prednisone therapy (mean daily
dose, cumulative dose or treatment duration). When BMDs were compared
between controls and SLE patients, subgrouped according to those not on
calcium and those arbitrarily receiving calcium supplements (1 g/day),
significantly lower BMDs were found in those not on calcium compared to
both controls and SLE patients on calcium. BMDs in SLE patients on calcium
were not different from those in controls. The low prevalence of
osteoporosis in our SLE patients (4-6%) suggests significant loss of BMD in
Chinese SLE patients on corticosteroid therapy is less than that reported
in Caucasians (12-18%).
相似文献
116.
Abnormal deposition of hemichrome on the inner aspect of the sickle red cell membrane promotes premature cell demise. The steps proximate to hemichrome formation in these cells are poorly understood. To test the hypothesis that the pathologic deposits of free ferric iron located on the inner aspect of sickle cell membranes would be redox active and promote oxidation of soluble oxyhemoglobin, we incubated native versus iron-stripped sickle or normal ghost membranes with oxyhemoglobin S. We found that sickle membranes exerted an exaggerated effect on methemoglobin formation in solution, an effect completely accounted for by their abnormal content of free iron. This ability of sickle membranes to promote hemoglobin oxidation was not diminished by catalase or by presence of a high-affinity, iron-inactivating chelator that is unable to remove membrane iron. Examination of those membranes likewise revealed that their free iron content promoted deposition of additional heme-protein. These results establish that the potential redox couple formed by membrane-associated ferric iron and cytoplasmic oxyhemoglobin is promotive of hemoglobin oxidation and deposition of hemichrome on the membrane. This predicts that removal of pathologic membrane iron might help prevent the detrimental formation of methemoglobin and hemichrome in vivo, insofar as this is accelerated by transition metal. 相似文献
117.
Human mast cells synthesize new granules during recovery from degranulation. In vitro studies with mast cells purified from human lungs 总被引:3,自引:0,他引:3
Secretory cells undergoing release and recovery events related to constitutive and/or stimulus-initiated secretion might be expected to undergo distinctive changes in morphology as well. We studied the release and recovery events of human mast cell secretion stimulated by antibody to immunoglobulin E. We used enzymatically digested mast cells from human lung specimens further purified by countercurrent centrifugation elutriation. Release kinetics were like those reported for isolated human lung mast cells. In two complete kinetic experiments we restudied these early release patterns (0 to 30 minutes). Mast cells, either stimulated or controls, were then cultured and sampled for electronmicroscopic studies at periodic intervals (3 to 48 hours). We describe events of the late recovery period here, although some overlap with processes seen in early recovery samples occurred. Mast cells that released nearly all their cytoplasmic granules and exteriorized the containers, eg, granule-channel membranes, underwent progressive enlargement of Golgi structures and development of numerous small cytoplasmic vesicles and small, membrane-bound granules filled with particulate and dense content. Ultimately, new mature cytoplasmic granules of all substructural patterns occurred. Nuclear blast changes and expansion of cytoplasmic mass accompanied this period of new granule synthesis. Mixed recovery patterns were present in individual cells. These represented the morphological expression of a variety of recovery events. Thus, some cells showed a combination of channel recovery and remodeling to form new granule containers within which condensation of content produced crystalline patterns, as well as synthesis of new granules, as described here. This morphological versatility resulted in multiple mast cell morphological phenotypes during these release and recovery processes. 相似文献
118.
Therapeutic and neurotoxic effects of 2-chlorodeoxyadenosine in adults with acute myeloid leukemia 总被引:1,自引:3,他引:1
Despite expectations that 2-chlorodeoxyadenosine (2-CdA) would prove active primarily in lymphoproliferative diseases, early reports suggested unexpected high activity of this drug in heavily pretreated children with acute myeloblastic leukemia (AML) at a maximally tolerated dose of 8.9 mg/m2/day for 5 days. In view of these findings, we conducted an escalating dose trial of 2-CdA in adult patients with relapsed or resistant AML. Thirty-six patients who had received extensive prior therapy were treated at 9 dose levels of 2-CdA at daily doses ranging from 5 to 21 mg/m2 for 5 days. 2-CdA eliminated leukemic blasts from the peripheral blood in 32 of 36 cases; however, bone marrow hypoplasia was seen only at daily dose levels > or = 15 mg/m2. We observed a total of 3 complete remissions: 1 at the 15 mg/m2/d dose level and 2 at the 21 mg/m2/d dose level; these responses persisted for 3, 2, and 3 months, respectively. Although prolonged myelosuppression would have been dose-limiting at 21 mg/m2/d for 5 days, the most important adverse effect was the development of a sensorimotor peripheral neuropathy. This reaction, whose onset was substantially delayed after completion of drug treatment, was observed in 2 of 5 patients at the 19 mg/m2/d level and in 4 of 4 evaluable patients at the 21 mg/m2/d level. Pathologically, this process was characterized by axonal degeneration and secondary demyelination. Other side effects included reactivation of a posttransplant Epstein-Barr virus-related lymphoma in 1 patient and tumor lysis syndrome. We conclude that the maximally tolerable dose of 2-CdA in adult patients (17 mg/m2/d for 5 days) in approximately twofold in excess of that previously reported in children and that the limiting toxic effect is a degenerative neuropathic disorder. We confirm that this drug has definite activity in AML, but the magnitude of this effect needs to be determined in larger numbers of patients who have received less extensive therapy. This agent deserves further evaluation in patients with both AML and acute lymphoblastic leukemia at these higher doses and perhaps as part of a preparative regimen for patients undergoing bone marrow transplantation. 相似文献
119.
H. J. SCHINDLER J. LENZ J. C. TÜRP K. SCHWEIZERHOF & S. RUES 《Journal of oral rehabilitation》2009,36(10):710-718
Summary After complex prosthetic reconstructions, small differences in vertical distances between the left and right side of the jaw may occur during jaw closing, nevertheless providing bilateral tooth contacts in intercuspation by small deformations of the mandible. Their effects on the co-contraction of the masticatory muscles, the temporomandibular joint reaction forces, and the point of application of the resultant bite force vector in the maxillary occlusion plane – the so-called reduction point – have not been investigated, thus far simultaneously in one sample. The main goal of this study was to investigate variations of these measures in an experimental intercuspation simulated by one anterior and two posterior force transmission points. 相似文献
120.