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Biomedical subjects

D N Howell

Publications and source records attributed to D N Howell.

At least 55 records · Page 3Linked to original sources
PubMed1996

Clinical, biochemical and pathological predictors of poor response to intravenous cyclophosphamide in patients with proliferative lupus nephritis.

BACKGROUND: Reports in the literature on the outcome of lupus nephritis (LN) treated with intravenous (i.v.) cyclophosphamide have varied considerably. Previous studies have suggested that less than 25% of patients with LN will progress to end stage renal failure (ESRD) after 5 years. In addition it has been reported that serum creatinine and chronic histologic changes on kidney biopsy are useful markers of renal prognosis. Whether treatment with cyclophosphamide alters the predictive value of these markers in LN patients is not clear. The aim of this study was to review our experience of treating a large cohort of patients with LN treated with i.v. cyclophosphamide and to identify biochemical and histological features at the time renal biopsy which predict outcome in these patients. DESIGN: We retrospectively reviewed our experience with 43 consecutive patients who met criteria for either World Health Organization (WHO) classification III (focal proliferative) or IV (diffuse proliferative) LN and were treated with monthly i.v. cyclophosphamide. Biochemical indices of renal function and lupus disease activity were recorded. Renal biopsies, performed within two months of commencing therapy, were reviewed by two experienced pathologists and classified according to WHO classification as well as activity and chronicity index. The primary outcome variable for the analysis was the development of ESRD. RESULTS: Patients were followed for a mean of 2 years after renal biopsy. The mean dose of cyclophosphamide received by patients was 8.3 g. One patient died during follow up and 22 (51%) progressed to ESRD. A higher serum creatinine (p = 0.003) and higher score for interstitial fibrosis (p = 0.001) were associated with shorter renal survival. There was no significant association between activity index or its components or in the total chronicity score and survival free from the need for dialysis. CONCLUSION: In our experience more than half of patients treated with i.v. cyclophosphamide for LN progress to ESRD and a high serum Cr and a high degree of interstitial fibrosis on renal biopsy before treatment are associated with a worse renal prognosis.

Adult↗
PubMed1995

Immunohistochemical analysis of the pathogenesis of posterior polymorphous dystrophy.

The pathogenesis of posterior polymorphous dystrophy was analyzed by immunohistologic methods. Sections of corneal buttons from two patients undergoing transplantation owing to posterior polymorphous dystrophy were stained with 2B4.14.1, a monoclonal antibody that reacts with human corneal endothelium, and with a cocktail of antihuman cytokeratin monoclonal antibodies that do not react with normal corneal endothelium. Single-stained sections revealed a variegated, intermittent staining pattern of antibody reactive and nonreactive cells. Double-stained sections revealed some cells that stained with only one of the antibodies and many cells that stained with both antibodies. The presence of cells staining positively for both 2B4.14.1 antigen and cytokeratins supports the hypothesis that the cytokeratin-expressing epithelial-like cells found in corneas with posterior polymorphous dystrophy arise via a metaplastic process in which the phenotype of endothelial cells becomes progressively abnormal.

Adult↗
PubMed1995

Identification of two subpopulations of rat monocytes expressing disparate molecular forms and quantities of CD43.

Expression of CD43 (leukosialin, sialophorin) by rat blood monocytes was analyzed by flow cytometric, microscopic, and biochemical techniques. Monocytes were identified cytometrically using a combination of light-scatter parameters and binding of the anti-monocyte/macrophage monoclonal antibody (mAb) OX-41. Two-color flow cytometry studies with W3/13 and HIS 17, two anti-CD43 mAb that react with different antigenic epitopes, revealed two subpopulations of monocytes expressing disparate levels of CD43 (referred to hereafter as hi-CD43 MO and lo-CD43 MO). In three-color flow cytometry studies, hi-CD43 MO were found to express higher levels of CD4 than lo-CD43 MO; in contrast, lo-CD43 MO bound higher levels of RP-3, a mAb raised against rat neutrophils. Hi- and lo-CD43 MO expressed comparable amounts of CD14, CD45, and intercellular adhesion molecule-1 (CD54); hi-CD43 MO expressed somewhat more lymphocyte function-associated antigen-1 alpha chain (CD11a) and CD18 than their lo-CD43 MO counterparts. A minority of cells in both subpopulations expressed class II histocompatibility antigens. Hi- and lo-CD43 MO isolated by fluorescence-activated cell sorting had features typical of monocytes as assessed by light and electron microscopy. In Western blotting experiments, lo-CD43 MO and elicited peritoneal macrophages were found to express a less heavily sialylated form of CD43 than hi-CD43 MO.

Animals↗
PubMed1995

Clinical and pathologic features of familial focal segmental glomerulosclerosis.

The occurrence of focal segmental glomerulosclerosis (FSGS) in a familial pattern has been rarely reported previously. Over the last 10 years we have treated 31 patients among eight families with familial FSGS. The diagnosis was confirmed by renal biopsy in 18 cases, and each family had at least two members in whom the diagnosis was confirmed histologically. Both males and females were affected, as were both blacks and whites. The mean age at presentation was 28 years, with a range of 8 to 56 years. The mean serum creatinine at presentation was 3.7 mg/dL. Twenty-five of the 31 patients progressed to end-stage renal disease; and treatment with prednisone did not appear to retard the progression to end-stage renal disease. Seven patients received a cadaveric renal transplant and none of them showed evidence of recurrence of disease in the graft. The pattern of inheritance in two families appeared to be autosomal dominant; in the other families the pattern of inheritance was less clear and may have been autosomal recessive, although a familial exposure to an unidentified environmental toxin cannot be excluded. Histologic examination of the renal tissue revealed a variety of changes previously described as occurring in FSGS. We conclude that FSGS may occur in a familial pattern that carries a poor prognosis. Further studies of these families may shed light on the pathogenesis of sporadic FSGS.

Adolescent↗
PubMed1995

Identification of selective immunoglobulin a deficiency by renal biopsy.

We report three cases of selective immunoglobulin A (IgA) deficiency in which lack of direct immunofluorescent staining for IgA on renal biopsy specimens contributed to the diagnosis. In two patients, one with systemic lupus erythematosus and the other having asthma with nephrotic syndrome, the diagnosis of IgA deficiency was suggested by the complete absence of IgA on the renal biopsy. In the third patient, a renal transplant recipient, initial biopsies demonstrated donor-derived IgA, which disappeared on subsequent biopsies. The diagnosis of IgA deficiency was confirmed in all three patients by serologic quantification of IgA.

Adolescent↗
PubMed1995

The renal manifestations and outcome of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in adults.

Thrombotic thrombocytopenic purpura/Hemolytic uremic syndrome (TTP/HUS) is generally regarded to be a rare disease. The present study was undertaken to identify presenting features, prognostic variables, pathological features and outcome associated with TTP/HUS. The present study is a retrospective chart review of 68 patients treated with plasmapheresis for TTP/HUS at a single tertiary referral medical institution from 1980-1992. The annual number of patients with TTP/HUS treated with plasmapheresis increased from an average of one case per year in 1980 to nine cases per a year in 1992. The in-hospital mortality for patients presenting with TTP/HUS was 25%. Forty four percent of patients presented with an elevated serum creatinine, and 16% required hemodialysis support. Of the seven patients who survived and required hemodialysis support only two patients continued on dialysis. None of the patients presenting with a normal serum creatinine required dialysis at any time in their course. Patient age, sex, presenting platelet count, white blood cell count, hemoglobin level and presence of neurological disease were not significantly associated with death or need for dialysis. The histopathological features of TTP/HUS (fibrin/platelet thrombi in renal vessels and glomeruli, fibrinoid necrosis of vessel walls) were found in all five cases autopsied. The incidence of TTP/HUS may be increasing. Alternative possibilities for the increased frequency of cases seen include greater diagnostic suspicion and referral bias. Despite the use of plasmapheresis, mortality during the initial hospital admission was almost 25%. In retrospect prognosis could not be predicted based on admission biochemical or clinical variables. The majority of patients who developed acute renal failure and survived to hospital discharge recovered renal function and became independent of dialysis.

Adult↗
PubMed1994

Differential expression of CD43 (leukosialin, sialophorin) by mononuclear phagocyte populations.

CD43 is a hematopoietic cell antigen whose distribution includes T lymphocytes, plasma cells, neutrophils, and platelets. Although it has been detected on peripheral blood monocytes, its expression by other mononuclear phagocytes has not been well documented. Possible changes in monocyte/macrophage CD43 expression in response to inflammation are also poorly defined. To examine these questions, the expression of CD43 by rat peripheral blood monocytes and both resident and elicited peritoneal macrophages was examined. By flow cytometry with two anti-CD43 monoclonal antibodies, blood monocytes were found to express large amounts of surface CD43, whereas surface CD43 expression by resident peritoneal macrophages was negligible. Peritoneal macrophage populations elicited by intraperitoneal injection of thioglycollate were uniformly positive for surface CD43, although the level of expression was lower than that found on monocytes. By labeling resident macrophages with a fluorescent tracer dye, this phenotypic shift was found to reflect an influx of CD43-positive elicited macrophages coupled with a disappearance of CD43-negative resident cells. Evidence from both flow cytometry and Western blotting studies suggests that the CD43 expressed by elicited peritoneal macrophages is less heavily sialylated than that expressed by blood monocytes. These findings, coupled with recent evidence that CD43 influences cellular adhesion, indicate that differential expression of CD43 may play a role in monocyte/macrophage trafficking.

Animals↗
PubMed1994

Creutzfeldt-Jakob disease in a pregnant woman with an implanted dura mater graft.

A 28-year-old woman with prior neurosurgery involving the placement of a cadaveric dural graft developed a rapidly progressive neurodegenerative disorder with prominent cerebellar dysfunction that was proven at autopsy to be Creutzfeldt-Jakob disease. She represents the second American to develop Creutzfeldt-Jakob disease in association with a dural graft. The unusual features of the case include the patient's initial clinical presentation with cerebellar ataxia in the absence of dementia, the widespread presence of kuru-type amyloid plaques on a histological examination of the brain, the development of clinical symptoms during pregnancy, and the subsequent delivery of a child who remains healthy at the age of 3 years.

Adult↗
PubMed1994

Histopathologic features of rejecting orthotopic corneal xenografts.

Discordant xenogeneic Hartley guinea pig corneal buttons were transplanted orthotopically to either naive or pre-immune Lewis rats. Recipients were sacrificed serially and grafts were immediately frozen and subsequently examined using standard immunohistologic techniques. Corneal xenografts remained clear in naive recipients for 7 days, at which point they rapidly became opaque and edematous. In pre-immunized recipients, corneal xenografts were rejected much more quickly, becoming opaque and edematous by day 3 post-transplantation. Histologic examination of grafts revealed severe stromal edema and diffuse inflammatory cell infiltrates composed of mononuclear cells and neutrophils. Infiltrates were present as early as day 2 in xenografts from both presensitized and naive recipients. The infiltrates were densest in the posterior half of the grafts with fewer cells penetrating into the epithelium. Immunoperoxidase staining confirmed the presence of OX-19+ T cells as well as a substantial infiltrate of OX-42+ neutrophils/macrophages. Additionally, IgG was deposited throughout the grafts in a diffuse manner. Deposition of IgG was accelerated in presensitized recipients, with intense staining of the entire graft detected by day 2. Examination of the rejected grafts suggests that rejection occurs via mechanisms similar to those seen in corneal allografts. This, in turn, implies corneal xenografts may be amenable to standard immunosuppressive regimens.

Animals↗
PubMed1994

Characterization of a novel family of ciliary body glycoproteins.

PURPOSE: To isolate and characterize ciliary body epithelial antigens reactive with a monoclonal antibody, 2B4.14.1. METHODS: A mouse monoclonal antibody generated against human corneal endothelium, 2B4.14.1 reacts with nonpigmented epithelium of human and guinea pig ciliary bodies. The ciliary body proteins reactive with 2B4.14.1 were identified by Western blotting and were partially purified by affinity chromatography with 2B4.14.1 coupled to a solid support matrix. Carbohydrate components of the antigenic molecules were analyzed by lectin chromatography and by digestion with the enzymes N-glycosidase F and endoglycosidase F. The cellular and subcellular distribution of the antigens was examined by immunoperoxidase staining and by immunoelectron microscopy of ultracryotome sections of ciliary body. RESULTS: 2B4.14.1 reacted with families of guinea pig and human ciliary body glycoproteins with estimated molecular weights ranging from 250 to 325 kD. In Western blots of samples reduced before electrophoresis, the high molecular weight bands were replaced by weakly reactive bands at 115 to 130 and 210 kD, indicating that the 2B4.14.1 ligands have disulfide bonds. 2B4.14.1 ligands from both guinea pig and human ciliary body were bound by immobilized lectins, including concanavalin A, Datura stramonium lectin, and Lens culinaris hemagglutinin, which recognize components of N-linked oligosaccharides. Guinea pig ciliary body antigens digested with N-glycosidase F and endoglycosidase F failed to react with 2B4.14.1 in Western blots, confirming the presence of N-linked oligosaccharide chains and indicating that they form an integral part of the 2B4.14.1-reactive antigenic site. Molecular weight shifts of glycosidase-digested antigens were consistent with the presence of two to four N-linked oligosaccharide units. In immunoperoxidase-stained sections of guinea pig and human ciliary body, 2B4.14.1 reacted primarily with nonpigmented epithelial cells. Staining of guinea pig epithelial cells was fairly uniform; staining of human epithelial cells was concentrated on the basal surface. By immunoelectron microscopy, a majority of the 2B4.14.1 antigenic reactivity was localized immediately external to the nonpigmented epithelial cell plasma membrane. CONCLUSIONS: 2B4.14.1 reacts with a novel family of high molecular weight glycoproteins associated with the nonpigmented epithelial cell surface in guinea pig and human ciliary body.

Aged↗
PubMed1993

Characterization of human anti-porcine "natural antibodies" recovered from ex vivo perfused hearts--predominance of IgM and IgG2.

Hyperacute rejection is a major obstacle to successful transplantation of vascularized xenogeneic organs and is believed to be mediated at least in part by performed xenoreactive "natural antibodies" (NAb). In this study, human NAb that could be involved in hyperacute rejection of pig heart xenografts were identified and characterized using an ex vivo model in which pig hearts were perfused with whole blood from individual human or pig donors. This ex vivo perfusion model allows for the continuous monitoring of physiologic parameters of cardiac function as well as sequential sampling of tissue and blood. Pig hearts perfused with allogeneic pig blood maintained normal function for at least 4 hr, whereas those perfused with xenogeneic AB+ human blood never achieved normal function and rejected completely after 30 min. In three separate experiments involving different human blood donors and pig hearts, sequential samples of perfused blood revealed a progressive depletion of anti-porcine NAb. Samples of all three rejected cardiac xenografts were homogenized, and the specifically bound human anti-porcine antibodies were eluted with citric acid. The eluted antibodies were enriched approximately 50-120-fold for anti-porcine reactivity compared with serum from the corresponding donor. Eluates contained NAb of predominantly IgM and IgG2 isotypes. Immunofluorescence histology confirmed the deposition of IgM and IgG2 but not other IgG subclasses in the rejected pig hearts. Since IgG2 utilized predominantly in response to bacterial polysaccharide antigens, our findings are consistent with the possibility that some NAb arise via crossreactivity with microbial antigens and are predominantly directed against carbohydrate rather than protein antigens.

Animals↗
PubMed1993

The association of enhancement of renal allograft survival by donor-specific blood transfusion with host MHC-linked inhibition of IgG anti-donor class I alloantibody responses.

Donor-specific blood transfusion (DSBT) in animals and humans can either promote subsequent renal graft survival or lead to sensitization and graft rejection. Using a rat renal allograft model, we have examined whether the effects of DSBT on renal allograft outcome and IgG alloantibody responses are linked to the host MHC. In F1 rats produced by mating PVG (RT1c), a low IgG alloantibody responder to transfused ACI (RT1a) blood, with 3 different high-IgG responders [W/F (RT1u), LOU (RT1u), and LEW (RT1l)], high IgG alloantibody production was found to be inherited as a dominant trait and associated with acute rejection of ACI renal allografts. DSBT given to offspring of (PVG x W/F)F1 rats backcrossed to W/F with either RT1u/c (u/c) or RT1u/u) (u/u) phenotype induced high-IgG-alloantibody responses that were associated with acute renal allograft rejection. Likewise, offspring of (PVG x W/F)F1 rats backcrossed to PVG expressing the u/c phenotype had high IgG responses to ACI DSBT associated with acute renal allograft rejection. In contrast, DSBT given to backcrossed recipients expressing the RT1c/c (c/c) phenotype elicited a transient IgM response that switched to a very low IgG response and was associated with renal allograft acceptance. Analysis of IgG isotypes demonstrated that DSBT prevented production of IgG1 and IgG2a, and to a lesser extent IgG2b and IgG2c alloantibodies in c/c but not u/c renal allograft recipients. The differences in the level and isotype of IgG alloantibody responses found in sera of DSBT-pretreated backcross rats of u/c and c/c phenotypes were also present in allograft eluates and splenocyte cultures. Likewise, DSBT-pretreated renal allograft recipients of the c/c phenotype produced lower levels of alloantibodies directed to class I RT1.Aa antigens compared with their u/c counterparts; in contrast, no difference was found in alloantibody responses to class II RT1.Ba antigens. These findings demonstrate that the variable ability of DSBT to enhance renal allograft survival correlates with the inhibition of antidonor class I alloantibody responses of all IgG subclasses by a mechanism that is linked to host MHC.

Animals↗
PubMed1993

The azaspirane SKF 105685 ameliorates renal allograft rejection in rats.

The azaspirane SKF 105685 (N,N-dimethyl-8, 8-dipropyl-2-azaspiro (4.5) decane-2-propanamine dihydrochloride) has been shown to attenuate or reverse the course of immunologic disease in several animal models, possibly through the induction of nonspecific suppressor activity. To investigate its effects on immune-mediated renal disease, SKF 105685 was administered by gavage to rats with kidney allografts. Six days after transplantation, GFR (inulin clearance, 1.46 +/- 0.27 versus 0.41 +/- 0.15 mL/min per kg; P < 0.005) and RPF (p-aminohippurate clearance, 5.48 +/- 0.98 versus 1.99 +/- 0.72 mL/min per kg; P < 0.01) were significantly higher in SKF 105685-treated rats compared with vehicle-treated control rats. In addition, mononuclear inflammatory cell infiltrates were significantly reduced in SKF 105685-treated animals compared with controls. Treatment also reduced renal production of thromboxane B2 (81 +/- 22 versus 424 +/- 76 pg/min per mg of protein; P < 0.0005), prostaglandin E2 (612 +/- 165 versus 2,059 +/- 351 pg/min per mg of protein; P < 0.005), and 6-keto prostaglandin F1 alpha (217 +/- 56 versus 943 +/- 186 pg/min per mg of protein; P < 0.005), but interleukin-1 beta mRNA levels within kidney allografts were not affected by treatment. Thus, the azaspirane SKF 105685 is a novel immunosuppressive agent that substantially ameliorates renal allograft rejection in the rat. Although the mechanism of action is unknown, the beneficial effects of SKF 105685 in rejection may relate to its ability to induce suppressor activity and/or its effects on eicosanoid production.

Animals↗
PubMed1993

Characteristics of corneal xenograft rejection in a discordant species combination.

PURPOSE: To characterize the fate of Lewis rat corneas transplanted to Hartley guinea pigs. METHODS: Full-thickness Lewis rat corneal buttons were grafted orthotopically to Hartley guinea pigs (xenografts), ACI rats (allografts), or Lewis rats (isografts). Two panels of recipients were presensitized with xenogeneic skin grafts or allogeneic skin grafts. Serum samples were collected pre- and post-transplant and analyzed by flow cytometry and indirect immunofluorescence. RESULTS: Unlike vascularized xenografts that reject within 30 min, corneal xenografts had a mean survival time of 8 days. Presensitization with guinea pig skin grafts increased recipient IgM and IgG xenoantibody levels, as measured by flow cytometry on guinea pig hematopoietic cells, and significantly accelerated corneal xenograft rejection with a mean survival time of 5 days. Presensitization with allogeneic ACI skin grafts had no effect on xenoantibody levels or xenogeneic corneal graft survival. Guinea pig corneas stained by indirect immunofluorescence with normal rat serum exhibited low (1+) but significant binding of IgG and IgM, primarily on epithelium and stroma. Serum from Lewis rats that rejected a corneal xenograft had elevated IgG and IgM xenoantibodies that reacted strongly (4+) with guinea pig cornea and heart. CONCLUSIONS: In the discordant guinea pig-to-rat species combination, donor corneas express xenoantigens; rejection of corneal xenografts stimulates IgM and IgG xenoantibody production; sensitization to xenoantigens can accelerate corneal xenograft rejection; and discordant corneal xenografts, unlike vascularized organs, are not hyperacutely rejected.

Acute Disease↗
PubMed1992

The effects of donor-specific blood transfusion enhancement of rat renal allografts on host NK cell responses.

Donor-specific blood transfusion (DSBT) given 1-2 weeks prior to transplantation prolongs the survival of fully allogeneic ACI (RT1a) renal allografts in PVG (RT1c) recipients from 6-8 days to greater than 100 days. We have previously demonstrated that ACI kidneys transplanted to autologous blood transfusion (ABT)- or DSBT-pretreated PVG recipients stimulated an increase in CD8+ (OX8+) cells in the peripheral blood by 6 days after transplantation. To determine whether this increase represents a general expansion of the entire CD8+ population or only a subpopulation of CD8+ cells, subset analysis was performed on peripheral blood lymphocytes depleted of cells reactive with monoclonal antibodies against rat alpha beta T cell receptor (TCR), CD8, or NK cells (R7.3, OX8, or 3.2.3, respectively). Phenotypic studies of PBL depleted of CD8+ cells demonstrated that all 3.2.3+ NK cells coexpressed CD8; depletion of 3.2.3+ PBL revealed a second subpopulation of CD8+3.2.3- cells comprised predominantly of alpha beta TCR+ T cells. In naive PVG rats the prevalence of these two CD8+ subpopulations was approximately equal. Both ABT- and DSBT-pretreated renal allograft recipients demonstrated a significant and equivalent expansion of the CD8+ cell subpopulation that coexpresses the 3.2.3 NK marker. In contrast, the second subpopulation of CD8+3.2.3- cells did not change significantly after allografting. There were also no differences between DSBT and ABT pretreated rats in activity of PBL against the NK targets YAC-1 and Doxie at 6 days after renal transplantation, though the level of activity was modestly increased compared with naive controls. These findings indicate that renal transplantation in the rat is associated with a significant increase in PBL with the NK phenotype (CD8+3.2.3+) and a modest increase of NK activity, but that DSBT enhancement does not affect this NK cell response.

Animals↗
PubMed1991

The effects of donor-specific blood transfusion enhancement of rat renal allografts on cytotoxic activity and phenotypes of peripheral blood lymphocytes, splenocytes, and graft-infiltrating cells.

Donor-specific blood transfusion prolongs survival of fully allogeneic ACI (RT1a) renal grafts in PVG (RT1a) recipients from 6-8 days to greater than 100 days. To determine how DSBT alters effector cytotoxic cell responses, we tested freshly isolated peripheral blood lymphocytes, spleen cells, and graft infiltrating cells (GIC) from pairs of PVG recipients of ACI kidneys pretreated with DSBT or autologous blood transfusion (ABT) for cell-mediated lympholysis, antibody-dependent cellular cytotoxicity (ADCC), and natural killer activity at the day of transplantation (day 0) and days 3 and 6 posttransplantation. PBL and GIC from the same pairs of animals were examined for their phenotypic profile (CD4, CD8, 3.2.3 NK cell marker, IL-2 receptor). CML, ADCC, and NK activity were higher in PBL than splenocytes of GIC of both ABT and DSBT groups at all time points examined. CML activity of PBL at day 3 was significantly higher in DSBT vs. ABT recipients (P less than 0.01), while at day 6 both groups were equally elevated. Splenocytes demonstrated significantly lower CML activity in DSBT vs. ABT recipients at day 6 (P less than 0.05). CML activity of GIC eluted from ABT and DSBT kidneys was not detected at day 3, but was significantly elevated and equivalent in both groups at day 6. ADCC and NK activities of PBL did not differ between ABT and DSBT groups, and were negligible in splenocytes. GIC demonstrated higher NK activity in DSBT vs. ABT recipients at day 3 (P less than 0.05), while ADCC activity was not detectable at any time in either group. Phenotypic analysis of PBL and GIC at day 3 showed no significant differences between ABT and DSBT groups in the percentage of CD4 or CD8 cells. However, in both ABT and DSBT groups the ratio of CD4:CD8 cells was markedly lower in GIC than PBL. By day 6, PBL from both ABT and DSBT groups showed equivalent and significant decreases in CD4+ cells and increases in CD8+ and 3.2.3+ (NK) cells. The percentage of IL-2R+ cells remained low (less than 5%) in both groups at day 3. In contrast, at day 6 there was a significant increase in IL-2R+ (and to a lesser extent CD4+) GIC in ABT- but not DSBT-treated recipients, while CD8+ cells were significantly increased in both groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Characterization of a novel human corneal endothelial antigen.

The antigenic composition of the human corneal endothelium, a cellular layer essential for maintaining corneal function, has not been well characterized. A novel corneal endothelial antigen was identified by generating a monoclonal antibody (MAb) against normal human corneal endothelial cells. This MAb, designated 2B4.14.1, reacted strongly by immunoperoxidase staining with the endothelium of corneas from all human donors tested but not with other corneal components, including epithelium and stroma. Positive immunohistologic reactions of 2B4.14.1 with several other human tissues, including kidney (parietal epithelium of Bowman's capsule, proximal convoluted tubule, ascending limb of Henle's loop, and distal convoluted tubule), glandular epithelia of numerous organs, and mesothelial linings of several thoracic and abdominal viscera, also were observed. One of the renal antigens recognized by 2B4.14.1 was identified as Tamm-Horsfall glycoprotein (THGP), based on the ability of the antibody to recognize THGP in western immunoblots and the abrogation of immunohistologic reactivity of the antibody by preincubation with purified THGP. These findings raise the possibility that the human cornea expresses a molecule with homeostatic properties similar to those ascribed to THGP. However, it is unlikely that the corneal antigen recognized by 2B4.14.1 is conventional THGP; a MAb specific for THGP did not react with corneal endothelium.

Animals↗