A novel human leukocyte antigen-A*01 allele, A*010104, identified by polymerase chain reaction-sequence-based typing in a Caucasian hematopoietic stem cell donor.
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Alleles↗
Biomedical subjects
M O'Gorman
Publications and source records attributed to M O'Gorman.
Rapid immune reconstitution following autologous hematopoietic stem cell transplantation in children: a single institution experience.
In this retrospective study, we review the immune reconstitution of children undergoing autologous hematopoietic stem cell transplantation. A total of 125 patients underwent autologous transplantation between 1992 and 2000. The report includes data on 58 patients. Data were not available on the remaining patients who either died before testing or data were not obtained. The parameters evaluated include: (a) immunophenotype by flow cytometry to quantify lymphocyte subpopulations (b) mitogen stimulation assays, and (c) quantitative immunoglobulins. The analysis reveals that CD3+ cells did not reach the normal range during the first year post-transplant. The median percentage of CD4+ cells was below normal up to 6 months post-transplant, while the absolute number remain low throughout the first year. The CD8+ percentage and absolute numbers remain normal at all times post-transplant. The CD19+ cells were also normal post-transplantation. The mitogen lymphocyte stimulation was normal in 27 out of 31 patients tested after 6 months post-transplant. Our analysis of immune reconstitution shows a similar pattern to previous studies with a faster recovery of the CD4/CD8 ratio, especially in those patients who did not receive TBI. In conclusion, the observed deficiencies are transient and have very little clinical significance because, historically, the rate of serious infections is low despite prolonged immune suppression. The recovery post-autologous transplant is fast.
Antigens, CD↗
Epidermal growth factor receptor glycosylation is required for ganglioside GM3 binding and GM3-mediated suppression [correction of suppresion] of activation.
Gangliosides are able to bind to the epidermal growth factor receptor and inhibit its activation, but the mechanism of this inhibition is unknown. To address the role of receptor carbohydrates in facilitating interaction with gangliosides, we examined the ability of GM3 to bind the deglycosylated receptor and inhibit its autophosphorylation. Flow cytometry studies demonstrated that deglycosylation of the receptor did not affect its ability to be transported to the cell membrane. In contrast with the native (fully glycosylated) receptor, GM3 did not coimmunoprecipitate with the deglycosylated receptor. Using a novel colorimetric bead binding assay, GM3 was shown to bind well to the immunoprecipitated native receptor but not at all to the deglycosylated receptor. Finally, the addition of GM3 to cells with deglycosylated epidermal growth factor receptors did not result in significant further inhibition of autophosphorylation of the receptor, despite a 10-fold decrease in phosphorylation of the native epidermal growth factor receptor by 200 microM GM3. These studies suggest that ganglioside affects epidermal growth factor receptor activity through a direct interaction that requires receptor glycosylation, and contribute to our understanding of the role of gangliosides in cell membrane function.
Cell Line↗
Surface and cytoplasmic immunoglobulin expression in circulating B-lymphocytes in acute Kawasaki disease.
Kawasaki disease (KD) is an acute vasculitis of young childhood predominantly affecting the coronary arteries. IgA plasma cells have been found to infiltrate vascular and nonvascular tissues in fatal acute KD. To determine whether IgA B-lymphocytes were increased in the peripheral blood of patients with KD, we performed three-color flow cytometry to detect surface and cytoplasmic immunoglobulin expression (IgA, IgM, IgD, and IgG) of peripheral B-lymphocytes in KD patients during the acute, subacute, and convalescent stages of illness and in age-matched febrile and afebrile pediatric controls. Surprisingly, absolute numbers of B-lymphocytes expressing IgA were found to be significantly lower in peripheral blood of acute KD patients compared with febrile and afebrile pediatric controls. These findings indicate that IgA plasma cells are not present in KD tissue as a result of excess numbers of these IgA B-lymphocytes in peripheral blood. We speculate that IgA B-lymphocytes are selectively withdrawn from the peripheral circulation into KD target tissues as part of a specific IgA immune response.
Acute Disease↗
Intestinal lactobezoars in twins receiving a reconstituted elemental formula.
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Bezoars↗
Yersinia enterocolitis mimicking Crohn's disease in a toddler.
A 31/2-year-old girl presented with persistent abdominal pain, fever, vomiting, and diarrhea accompanied by rash, oral ulceration, anemia, and an elevated sedimentation rate. Initial evaluation revealed no pathogens and was extended to include abdominal ultrasound and computed tomography showing marked ileocecal edema and mesenteric adenopathy. Colonoscopy revealed focal ulceration from rectum to cecum with histology of severe active colitis with mild chronic changes. Enteroclysis demonstrated a nodular, edematous terminal ileum. Because of the patient's clinical deterioration despite antibiotics, these features were construed consistent with Crohn's disease, and glucocorticoid therapy was begun. By the ninth hospital day, admission cultures grew Yersinia enterocolitica, and trimethoprim/sulfamethoxazole was begun followed by prompt clinical improvement. The delay in diagnosis afforded an unusually comprehensive clinical description of the presentation and diagnosis of Yersinia enterocolitis in childhood.
Child, Preschool↗
Integrin alpha 5 beta 1 expression is required for inhibition of keratinocyte migration by ganglioside GT1b.
Polysialoganglioside GT1b, a keratinocyte membrane glycosphingolipid, inhibits normal keratinocyte adhesion and migration on a fibronectin matrix. The specificity of the inhibition for cells plated on a fibronectin matrix and competition of GT1b inhibition with peptide RGDS suggest that GT1b abrogates the alpha 5 beta 1/fibronectin interaction. We examined the effects of GT1b on the adhesion and migration of keratinocyte-derived cell lines and correlated GT1b responsiveness and alpha 5 beta 1 integrin expression. GT1b (5 nM) significantly inhibited migration of normal human keratinocytes, immortalized keratinocytes, and squamous cell carcinoma SCC12F2 cells on fibronectin, but not on collagen I. Concentrations as high as 5 microM had no effect on SCC13 or HaCaT cells. Likewise, GT1b inhibited fibronectin-dependent cell adhesion of normal human keratinocytes, immortalized keratinocytes, and SCC12F2 cells, but had no effect on SCC13 or HaCaT cells. Flow cytometric and Western immunoblot analysis of integrin expression showed significantly decreased alpha 5 and beta 1 integrin expression in SCC13 and HaCaT cells compared to normal keratinocytes, immortalized keratinocytes, and SCC12F2 cells. Incubation with TGF-beta 1 increased alpha 5 beta 1 integrin expression and induced responsiveness to GT1b in HaCaT cells. These data imply that GT1b "response" requires sufficient expression of alpha 5 beta 1 and further suggest that the mechanism of the inhibitory effect of GT1b involves GT1b/alpha 5 beta 1 interaction.
Carcinoma, Squamous Cell↗
Flow cytometric determination of ganciclovir susceptibilities of human cytomegalovirus clinical isolates.
A flow cytometric assay has been developed for the measurement of susceptibilities to ganciclovir of laboratory strains and clinical isolates of human cytomegalovirus (HCMV). The assay uses fluorochrome-labeled monoclonal antibodies to HCMV immediate-early and late antigens to identify HCMV-infected cells and flow cytometry to detect and quantitate the number of antigen-positive cells. By this assay, the 50 and 90% inhibitory concentrations (IC50 and IC90, respectively) of ganciclovir for the AD169 strain of HCMV were 1.7 and 9.2 microM, respectively, and the IC50 for the ganciclovir-resistant D6/3/1 derivative of the AD169 strain was greater than 12 microM. The ganciclovir susceptibilities of 17 HCMV clinical isolates were also determined by flow cytometric analysis of the effect of ganciclovir on late-antigen synthesis in HCMV-infected cells. The average IC50 of ganciclovir for drug-sensitive HCMV clinical isolates was 3.79 microM (+/-2.60). The plaque-reduction assay for these clinical isolates yielded an average IC50 of 2.80 microM (+/-1.46). Comparison of the results of the flow cytometry assays with those obtained from the plaque-reduction assays demonstrated acceptable bias and precision. Flow cytometric and plaque-reduction analysis of cells infected with ganciclovir-resistant clinical isolates failed to show a reduction in the percentage of late-antigen-positive cells or PFU, even at 96 microM ganciclovir. The flow cytometric assay for determining ganciclovir susceptibility of HCMV is quantitative, and objective, and potentially automatable, and its results are reproducible among laboratories.
Antigens, Viral↗
Anti-nuclear antibodies in Sydenham's chorea.
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Acute Disease↗
Virologic and serologic markers of rapid progression to AIDS after HIV-1 seroconversion.
The association between early virologic and immunologic events after human immunodeficiency virus type 1 (HIV-1) infection and progression of HIV-1 infection to acquired immunodeficiency syndrome (AIDS) was studied among 59 homosexual men with documented time of seroconversion. Epidemiologic factors, such as number of lifetime sexual partners, history of sexually transmitted diseases, and other factors, also were studied. All 17 seroconverters in the cohort who developed AIDS within 3 years (rapid progressors = RPs) were compared with 42 men without AIDS for at least 6 years seroconversion (nonrapid progressors = non-RPs). Plasma levels of HIV-1 RNA, p24 antigen, antibodies to HIV-1 structural genes, beta-2 microglobulin, neopterin, and interferon-alpha were measured at four time points: (a) the last seronegative visit, (b) the first seropositive visit, (c) the visit closest to AIDS (or the corresponding visit for the non-RPs) and (d) 6 years after seroconversion (for non-RPs). Up to seroconversion, the RPs had a significantly higher number of lifetime sexual partners than non-RPs (503 versus 171, respectively). At the first seropositive visit, RPs had significantly higher concentrations of plasma HIV-1 RNA (p < 0.01) and prevalence of p24 antigenemia (p < 0.001) and significantly lower levels of antibodies to the HIV-1 gag proteins p17 and p24 (p < 0.01-0.001) compared with non-RPs. These differences increased during follow-up visits. Antibodies to p66 and gp120 were significantly different only at the visit closet to AIDS (p < 0.001), as were beta-2 microglobulin and interferon alpha. These findings suggest that early virologic-immunologic events after HIV-1 infection may determine the rate of progression to AIDS. Anti-gag immune response may prevent rapid progression of HIV-1 disease and should be considered for future vaccine studies.
Acquired Immunodeficiency Syndrome↗
Phase I/II study of combined granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor administration for the mobilization of hematopoietic progenitor cells.
PURPOSE: To study the toxicity and efficacy of combined granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) administration for mobilization of hematopoietic progenitor cells (HPCs). MATERIALS AND METHODS: Cohorts of a minimum of five patients each were treated subcutaneously as follows: G-CSF 5 micrograms/kg on days 1 to 12 and GM-CSF at .5, 1, or 5 micrograms/kg on days 7 to 12 (cohorts 1, 2, and 3); GM-CSF 5 micrograms/kg on days 1 to 12 and G-CSF 5 micrograms/kg on days 7 to 12 (cohort 4); and G-CSF and GM-CSF 5 micrograms/kg each on days 1 to 12 (cohort 5). Ten-liter aphereses were performed on days 1 (baseline, pre-CSF), 5, 7, 11, and 13. Colony assays for granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) were performed on each harvest. RESULTS: The principal toxicities were myalgias, bone pain, fever, nausea, and mild thrombocytopenia, but none was dose-limiting. Four days of treatment with either G-CSF or GM-CSF resulted in dramatic and sustained increases in the numbers of CFU-GM per kilogram collected per harvest that represented 35.6 +/- 8.9- and 33.7 +/- 13.0-fold increases over baseline, respectively. This increment was attributable both to increased numbers of mononuclear cells collected per 10-L apheresis and to increased concentrations of progenitors within each collection. The administration of G-CSF to patients already receiving GM-CSF (cohort 4) caused the HPC content to surge to nearly 80-fold the baseline (P = .024); the reverse sequence, ie, the addition of GM-CSF to G-CSF, was less effective. The CFU-GM content of the baseline aphereses correlated with the maximal mobilization achieved (r = .74, P = .001). CONCLUSION: Combined G-CSF and GM-CSF administration effectively and predictably mobilizes HPCs and facilitates apheresis.
Adolescent↗
Simplified nuclear grading of fine-needle aspirates of breast carcinoma: concordance with corresponding histologic nuclear grading and flow cytometric data.
Although histologic grading of breast carcinoma is widely practiced by most pathologists, cytologic grading of fine-needle aspirates (FNA) of this neoplasm is not commonly done. This study addresses the issue of the accuracy of a new classification system, a simplified Nuclear Grading (NG) system based on the criteria proposed by Black et al. (Surg Gynecol Obstet 1955;100:543) in FNA of breast carcinoma. We reviewed 100 cases of breast carcinoma, initially diagnosed by fine-needle aspiration biopsy (FNAB) with subsequent histologic confirmation, consisting of 94 ductal, five lobular, and one medullary carcinoma. NG of Papanicolaou's stained materials were reviewed twice independently by two pathologists and then were compared to the original histologic NG. The concordance rate with histology ranged from 80-90%. Intraobserver reproducibility was 86 and 88%, while interobserver reproducibility ranged from 84-88%. Of the 88 cases with corresponding flow cytometic (FCM) data, there were 35 diploid and 53 aneuploid cases. Fifty-nine (95%) of histologic high NG were aneuploid or diploid with high S-phase fraction (SPF), while 20 (77%) of histologic low NG were diploid with low SPF. This study confirms that nuclear grading of FNA of breast carcinoma using a simplified NG system has a high concordance with histology, has high intraobserver and interobserver reproducibility, and that this grading system correlates well with FCM analysis when tumors are simply divided based on NG as high or low grade.
Biopsy, Needle↗
Comparative study of interphase cytogenetics, flow cytometric analysis, and nuclear grade of fine-needle aspirates of breast carcinoma.
The correlation between DNA ploidy and S-phase fraction (SPF) by flow cytometry (FCM) and the detection of numerical chromosomal abnormalities (NCA) by interphase cytogenetics (IC) involving chromosomes 8 and 12 was studied in 20 human breast lesions (17 breast carcinomas, 2 fibroadenomas, and 1 sclerosing adenosis). Initial diagnosis was performed on fine-needle aspiration biopsy (FNAB) material with subsequent histologic confirmation. FCM was performed on formalin-fixed paraffin-embedded tissue while IC by fluorescence in situ hybridization (FISH) was done on alcohol fixed FNAB materials. Sixteen (80%) cases showed concordance between FCM and IC with respect to the presence or absence of aneuploidy. The remainder of the cases (20%), which were all malignant neoplasms, showed discrepancies between the two methods, all four were DNA-diploid with low SPF by FCM but showed various NCA by IC. Nuclear grades (NG) of all the malignant samples were also evaluated and correlated with both FCM and IC studies. Although a good correlation was observed between NG and FCM, a better correlation was seen between NG and IC. This study shows that although IC by FISH correlated well with FCM analysis, it can detect NCA in DNA-diploid, low SPF tumors. It also correlates well with the NG of the tumor. The increased sensitivity provided by IC in detecting aneuploidy may be of great prognostic significance in low stage, DNA-diploid, low SPF breast carcinomas.
Biopsy, Needle↗
Leukocyte adhesion deficiency: recurrent childhood skin infections.
Leukocyte adhesion deficiency is a rare autosomal recessive disorder caused by the absent or severely reduced cell surface expression of a subfamily of leukocyte integrin molecular (beta 2 leukocyte integrins, CD11a/CD18, CD11b/CD18, CD11c/CD18). These molecules are required for the normal processes of leukocyte adherence and chemotaxis. Patients often die during the first years of life of a severe bacterial or fungal infection. We describe a 13-year-old boy with leukocyte adhesion deficiency who had intermittent cutaneous infections that were recalcitrant to treatment. Except for periodontitis, he had no other clinical problems. The diagnosis of leukocyte adhesion deficiency should be considered in patients with recurrent cutaneous infections that do not respond well to therapy, even in the absence of more serious manifestations. Evaluation should include flow cytometry studies to detect surface expression of the beta 2 leukocyte integrins on both resting and activated polymorphonuclear leukocytes.
Adolescent↗
Chronic inflammatory bowel disease in childhood.
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Child↗
Zero-time prehospital i.v.
Advances in prehospital stabilization and resuscitation of traumatized victims continue to have an impact on morbidity and mortality. Certain aspects of Advanced Trauma Life Support still remain controversial. Recent reports have questioned the usefulness of IV's started in the prehospital phase both because of delay in transport and because of the actual or theoretical lack of adequate volume infusion during transport. If IV lines can be started while an accident victim is en route to the hospital with no delay in transport, then much of the argument against prehospital IV's becomes irrelevant. From October 1985 through November 1986 we prospectively studied IV access attempts in 350 consecutive patients. Overall IV's started at the scene were 77% successful (n = 70) and en route 81% (n = 213) of attempts were successful. Of those with BP less than 100 mm Hg, there were 66% successful on-scene attempts and 72% successful en-route attempts. Protocols for IV administration in non-trapped patients should initiate IV access only en route to the hospital while the ambulance is moving. Even if delay at the scene is minimal, it is not possible to justify any delay, since IV's can be successfully instituted en route.
Emergency Medical Services↗
Changes in immune function in relapsing multiple sclerosis correlate with disease activity as assessed by magnetic resonance imaging.
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Concanavalin A↗
Endothelial proliferation in paroxysmal nocturnal hemoglobinuria.
Paroxysmal nocturnal hemoglobinuria (PNH) is a disorder of stem cells that is associated with venous thrombosis in multiple organ sites. We present a patient with necrotizing pharyngitis and intestinal infarction who has classic laboratory findings for PNH: positive complement-mediated acid and sucrose hemolysis and absence of decay accelerating factor (DAF) in peripheral blood leukocytes. Histopathologic examination of tissue from tonsil and large bowel demonstrated not only venous thrombosis but unusual proliferation of endothelial cells (papillary endothelial hyperplasia). This has not been described previously. We speculate that the endothelial cell in PNH may share in the defective regulation of complement activity. Venous thrombosis could precipitate or be a consequence of these vascular changes.
Adolescent↗