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Biomedical subjects

V Graves

Publications and source records attributed to V Graves.

10 recordsLinked to original sources

Simultaneous mobilization of Mac-1 (CD11b/CD18) and formyl peptide chemoattractant receptors in human neutrophils.

Mobilization of a distinct subset of specific granules provides a physiologically important mechanism to recruit Mac-1 (CD11b/CD18) from an intracellular pool to the external surface of the neutrophil plasma membrane, where the functionally active heterodimer mediates several adherence-dependent processes that are crucial for adequate host defense and cellular inflammatory responses. We observed similar characteristics for translocation of Mac-1 and neutrophil formyl peptide receptors (FPR) and hypothesize that the readily accessible pools of both Mac-1 and FPR are colocalized within this specific granule subset. Plasma membrane levels of both FPR (assessed with 3H-FMLP) and Mac-1 (assessed by fluorescence-activated cell sorter analysis of fluorescein isothiocyanate [FITC]-Mo-1-labeled cells) were markedly downregulated in cells prepared at low temperature from blood cooled to 4 degrees C immediately after removal from the circulation. Levels of both FPR and Mac-1 remained low on cells held at 4 degrees C. Upon warming, spontaneous upregulation of Mac-1 and FPR occurred with similar kinetics and temperature dependency. Translocation of both Mac-1 and FPR was markedly potentiated by exposure of cells to either fluoride ion (which has been shown by others to specifically elicit exocytosis of gelatinase-rich and vitamin B-12 binding protein-poor granules) or granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that markedly potentiates the neutrophils' host defense capabilities. Levels of both FPR and Mac-1 on F-- or GM-CSF-treated neutrophils exceeded those present on cells incubated at 37 degrees C for extended time intervals, indicating that stimulated translocation may involve mobilization of an additional granule subset. Scatchard analysis showed that only low-affinity FPR were translocated during spontaneous and stimulus-dependent upregulation. To directly compare FPR levels on the surface of cells displaying varying levels of Mac-1 within a single cell suspension, cells were labeled with FITC-Mo-1 and sorted into subpopulations based on fluorescence intensity. After sorting, the individual populations were held at 4 degrees C to prevent further spontaneous upregulation, concentrated by centrifugation, and assayed for FPR levels. Under a variety of conditions, FPR levels correlated with Mac-1 (CD11b) expression on cell populations selected on the basis of CD11b fluorescence intensity. Analysis of subcellular fractions obtained from disrupted neutrophils before and after upregulation provided additional support for the hypothesis that Mac-1 and FPR are colocalized within a readily accessible subset of neutrophil granules.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Membrane

Growth characteristics and expansion of human umbilical cord blood and estimation of its potential for transplantation in adults.

We estimated whether single collections of cord blood contained sufficient cells for hematopoietic engraftment of adults by evaluating numbers of cord blood and adult bone marrow myeloid progenitor cells (MPCs) as detected in vitro with steel factor (SLF) and hematopoietic colony-stimulating factors (CSFs). SLF plus granulocyte-macrophage (GM)-CSF detected 8- to 11-fold more cord blood GM progenitors [colony-forming units (CFU)-GM] than cells stimulated with GM-CSF or 5637 conditioned medium (CM), growth factors previously used to estimate cord blood CFU-GM numbers. SLF plus erythropoietin (Epo) plus interleukin 3 (IL-3) enhanced detection of cord blood multipotential (CFU-GEMM) progenitors 15-fold compared to stimulation with Epo plus IL-3. Under the same conditions, bone marrow CFU-GM and CFU-GEMM were only enhanced in detection 2- to 4- and 6- to 8-fold. Increased detection of cord blood CFU-GEMM correlated directly with decreased detection of cord blood erythroid burst-forming units (BFU-E). In contrast, adult bone marrow CFU-GEMM and BFU-E numbers were both enhanced by SLF plus Epo plus IL-3. This suggests that most cord blood BFU-E may actually be CFU-GEMM. Cord blood collections (n = 17) contained numbers of MPCs (especially CFU-GM) similar to the number found in nine autologous bone marrow collections. To assess additional sources of MPCs, the peripheral blood of 1-day-old infants was assessed. However, average concentrations of MPCs circulating in these infants were only 30-46% that in their cord blood. Expansion of cord blood MPCs was also evaluated. Incubation of cord blood cells for 7 days with SLF resulted in 7.9-, 2.2-, and 2.7-fold increases in numbers of CFU-GM, BFU-E, and CFU-GEMM compared to starting numbers; addition of a CSF with SLF resulted in even greater expansion of MPCs. The results suggest that cord blood contains a larger number of early profile MPCs than previously recognized and that there are probably sufficient numbers of cells in a single cord blood collection to engraft an adult. Although the expansion data must be considered with caution, as human marrow repopulating cells cannot be assessed directly, in vitro expansion of cord blood stem and progenitor cells may be feasible for clinical transplantation.

Age Factors

Endovascular treatment of posterior circulation aneurysms by electrothrombosis using electrically detachable coils.

In a multicenter study, 120 patients with intracranial aneurysms presenting a high surgical risk were treated using electrolytically detachable coils and electrothrombosis via an endovascular approach. The results of treatment in patients with posterior fossa aneurysms (42 patients with 43 aneurysms) are presented. The most frequent clinical presentation was subarachnoid hemorrhage (24 cases). The clinical follow-up periods ranged from 1 week to 18 months. Complete aneurysm occlusion was obtained in 13 of 16 aneurysms with a small neck and in four of 26 wide-necked aneurysms. A 70% to 98% thrombosis of the aneurysm was achieved in 22 of 26 aneurysms with a wide neck and in three of 16 small-necked aneurysms. One aneurysm could not be treated due to a technical complication. Two cases required postprocedural surgical clipping of a residual aneurysm. One patient (originally in Hunt and Hess Grade V) experienced procedural rupture of the aneurysm requiring an emergency parent artery occlusion. He eventually died 5 days later. Another patient (originally in Grade IV) had coil migration and posterior cerebral artery territory ischemia. A third patient developed a permanent neurological deficit (hemianopsia) after complete occlusion of a wide-necked basilar bifurcation aneurysm. One patient, harboring an inoperable giant basilar bifurcation aneurysm, died from aneurysm bleeding 18 months after partial occlusion. Overall morbidity and mortality rates related to treatment were 4.8% (two cases) and 2.4% (one case), respectively (2.6% and 0% if considering only patients in Hunt and Hess Grades I, II, and III). It is suggested that this technique is a viable alternative in the management of patients with posterior fossa aneurysms associated with high surgical risk. Longer angiographic and clinical follow-up study is necessary to determine the long-term efficacy of this recently developed endovascular occlusion technique. Close postoperative angiographic and clinical monitoring of patients with wide-necked subtotally occluded aneurysms is mandatory to check for potential aneurysmal recanalization, regrowth, and rupture.

Adolescent

Hypothalamic-pituitary dysfunction following CNS prophylaxis in acute lymphocytic leukemia: correlation with CT scan abnormalities.

In an attempt to identify possible adverse effects of CNS prophylaxis (cranial radiation and intrathecal chemotherapy), we examined hypothalamic-pituitary function in 23 patients with acute lymphocytic leukemia (ALL). Of 18 patients who had received both cranial radiation and intrathecal chemotherapy, nine had abnormally low growth hormone responses to insulin-induced hypoglycemia (less than 7.0 ng/ml). Seven of the nine patients with abnormally low growth hormone responses also manifested ventricular dilatation on computed tomography (CT) brain scans, whereas only one of the nine patients with normal growth hormone responses demonstrated this CT scan finding (P = 0.015). The remaining patients, who had not received cranial radiation, had normal growth hormone responses and normal CT scans. There is significant correlation between ventricular dilatation on CT and abnormally low peak growth hormone responses following CNS prophylaxis in ALL.

Adolescent

Thrombus formation and structure and the evolution of mass effect in intracranial aneurysms treated by balloon embolization: emphasis on MR findings.

This study was designed to further assess the capabilities of MR as a tool for the diagnostic evaluation of patients with giant intracranial aneurysms, to determine MR's ability to define the degree of thrombosis present within giant aneurysms before and after treatment with balloon occlusion, and to delineate the MR characteristics of both spontaneous and induced thrombus within giant aneurysms. Nine patients with unclippable intracranial aneurysms treated by parent artery occlusion with detachable balloons were evaluated with MR, angiography, and CT. Pretreatment and posttreatment MR studies were evaluated for their ability to (1) define the size, configuration, and anatomic relationships of an aneurysm; (2) detect and characterize thrombus within an aneurysm; and (3) determine if treatment successfully caused complete aneurysm thrombosis. MR imaging does not replace angiography in either the pretreatment or the posttreatment evaluation of patients with giant intracranial aneurysms. Thrombus formation and dissolution is a complex, dynamic process. Active thrombus in incompletely thrombosed aneurysms differs from isolated organizing thrombus in completely thrombosed aneurysms. Induced and spontaneous thrombi differ in mechanisms of formation and in composition; their MR characteristics are also different. Reduction in mass effect is common after complete thrombosis of giant intracranial aneurysms.

Catheterization