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Biomedical subjects

G Nunez

Publications and source records attributed to G Nunez.

At least 55 records · Page 3Linked to original sources
PubMed1986

Juvenile chronic myelogenous leukemia: surface antigen phenotyping by monoclonal antibodies and cytogenetic studies.

Cells from three children with juvenile chronic myelogenous leukemia were studied using culture in semisolid media, cytogenetic analysis, and surface staining with the monocyte-specific monoclonal antibodies 61D3 and 63D3. The percentage of bone marrow mononuclear cells that were 61D3- and 63D3-positive was markedly increased in all three patients. Bone marrow and peripheral blood mononuclear cells exhibited exceptionally bright immunofluorescence with these antibodies. The presence of monocyte-specific antigens on the surface of juvenile chronic myelogenous leukemia cells suggests that they are derived from a precursor with monocytic characteristics. A specific chromosomal abnormality (47,XY+21) was present in fresh bone marrow cells from one patient; in contrast, 50 metaphases from phytohemagglutinin-stimulated peripheral blood contained a normal karyotype. The chromosomal abnormality was also identified in myeloid colonies grown in vitro from this patient. Granulocytic elements were demonstrated in tissue sections and in cultured myeloid colonies from this child. Our data suggest that malignant transformation in juvenile chronic myelogenous leukemia involves a myeloid progenitor population capable of differentiation in vitro to cells with monocytic or granulocytic characteristics.

Animals↗
PubMed1985

Bronchoalveolar cells from sarcoid patients demonstrate enhanced antigen presentation.

The recognition of foreign antigens by T lymphocytes in association with lung antigen-presenting cells may be critical in the initiation of the mononuclear alveolitis and granuloma formation of pulmonary sarcoidosis. However, it has been shown that bronchoalveolar cells (BAC) from normal volunteers function poorly as antigen-presenting cells. Therefore, the ability of sarcoid BAC to serve as accessory cells for antigen-dependent autologous T cell proliferation, as measured by tritiated thymidine uptake, was compared with that of normal BAC. Although irradiated sarcoid BAC supported antigen-induced T cell proliferation, normal BAC did so poorly (p less than 0.005). Because it has been shown that sarcoid BAC produce more interleukin 1 (IL 1) than normal BAC, it was considered that the enhancement of antigen-induced proliferative responses could result from an increased amount of IL 1, and that contaminating monocytes in the peripheral blood T cell preparations displayed the antigen for T cell recognition. Therefore, it was necessary to establish that antigen-induced T cell responses required HLA-D region compatibility between the sarcoid BAC and T lymphocytes. BAC from sarcoid patients stimulated antigen-specific proliferation in T cells lines matched for at least one HLA-D-region antigen, but failed to stimulate T cell lines that were unmatched for both antigens. This finding indicates that cells in bronchoalveolar lavage fluids from sarcoid patients were fully capable of acting as antigen-presenting cells. The identification of antigen-presenting cells in the lungs of patients with sarcoidosis together with the previous findings of activated T cells, enhanced IL 1 production, and spontaneous interleukin 2 release in sarcoid patients is compatible with the hypothesis that local cell-mediated immunity is involved in the pathogenesis of pulmonary sarcoidosis.

Adult↗
PubMed1984

Molecular localization of human class II MT2 and MT3 determinants.

The specificities of the monoclonal antibodies I-LR2 and 109d6, which recognize MT2- and MT3-like serologic determinants, respectively, have been confirmed by panel testing. In addition, the relationships of these antibodies to other monoclonal antibodies and alloantisera have been studied by means of cell surface fluorescence, complement-dependent cytotoxicity and immunoprecipitation. Using these monoclonal antibodies, molecules encoded by the HLA-D region have been isolated and characterized by amino acid sequencing and peptide mapping. By these criteria, the major populations of molecules bearing MT2- and MT3-like determinants are indistinguishable from DR molecules.

Amino Acid Sequence↗
PubMed1984

HLA-A, B, C; -DR; -MT, -MB, and SB antigens on unstimulated human endothelial cells.

Since major histocompatibility complex (MHC) antigens of class II play an important role in organ transplantation, we attempted to demonstrate their expression on endothelial cells which are abundant in transplants with vascular blood supply. Our analysis was performed with monomorphic and polymorphic monoclonal antibodies employing a microscopic immunofluorescence assay and flow cytometry on unstimulated endothelial cells isolated from umbilical cord veins. No evidence was found for the presence of HLA-DR antigens and determinants associated with MT, MB and SB. MHC class I antigens exhibited reduced expression. These findings were confirmed in respect to alloantigens by the use of conventional cytotoxic tissue typing antisera. MB and SB antigens were present on most cord B lymphocytes, but could only be demonstrated on a subpopulation of monocytes exhibiting a lower antigen density at the cell surface. MT and DR antigens were found on most cord monocytes and B lymphocytes.

Antigens, Surface↗
PubMed1984

The accessory cell function of human alveolar macrophages in specific T cell proliferation.

The capacity of alveolar macrophages to support mitogen- and antigen-induced proliferation of autologous, monocyte-depleted T cells in normal, nonsmoking volunteers was studied. Purified T cells failed to proliferate in response to mitogen or antigen, whereas co-culture with peripheral blood monocytes restored responsiveness. Alveolar macrophages (AM) reconstituted the response of T cells to mitogen, indicating that AM can deliver a second proliferative signal. AM, however, were markedly inferior to monocytes in supporting antigen-induced proliferation. Thus, in 19 normal volunteers, the mean response of immune T cells to diphtheria toxoid in cultures reconstituted with normal AM was only 25% of the proliferative response to diphtheria in cultures with monocytes. Although four volunteers demonstrated antigen-presenting function equivalent to monocytes, in the remaining 15 antigen-presenting ability of AM was less than 15% that of monocytes. The difference in antigen-presenting function between AM and monocytes was not due to a difference in their display of HLA-D/DR determinants because 80% of AM were HLA-DR positive. The role of suppression in the diminished antigen-presenting function of AM was assessed in 12 volunteers utilizing mixing experiments. Eight volunteers demonstrated suppressor AM but four did not, suggesting that AM from at least some normal individuals have a faulty antigen-processing mechanism. Taken together, these studies demonstrate that AM may play three different roles in modulating T lymphocyte responses, i.e., they may present antigen, they may suppress normal responses, or they may remain immunologically inert. The factors that determine which function is expressed in vivo may determine the pulmonary response to inhaled antigen.

Adult↗
PubMed1984

Study of HLA antigens in ten multiple-case rheumatoid arthritis families.

We studied the inheritance of HLA haplotypes in 10 families with more than one member affected with adult onset rheumatoid arthritis (RA). The frequency of DR4 was 81% among these patients. Nine families had DR4 bearing haplotypes and homozygosity for DR4 existed in 4 families. In 6 of these families DR4 positive haplotypes were shared among affected members. All but one of the affected sibs shared at least one haplotype with their index case. Ten percent of the unaffected relatives had rheumatoid factor (RF). HLA-DR4 or associated genes appeared to confer susceptibility for RF production and development of RA. However, these haplotypes were inherited also by many sibs who did not develop any manifestations of disease.

Arthritis, Rheumatoid↗
PubMed1983

Structural analysis of a human I-A homologue using a monoclonal antibody that recognizes an MB3-like specificity.

Monoclonal antibody IVD12 was used to isolate and characterize a human Ia molecule present on B cells that generally display DR4 or DR5 phenotypes. The specificity of binding of IVD12 to human peripheral blood B cells from 75 normal individuals and 19 homozygous human lymphoblastoid B cell lines was identical to the supertypic specificity MB3 previously defined. Furthermore, IVD12-reactivity was shown to segregate with HLA in three informative families. In each family, individuals positive for IVD12 binding were also positive for DR4 or DR5. Using IVD12, a molecule has been isolated from the homozygous cell line PRIESS (DR4/4) and has been shown by amino acid sequence analysis to be homologous to the murine I-A and human HLA-DS molecules. These findings suggest that the MB3 specificity is found on a molecule encoded by loci distinct from those loci which encode HLA-DR molecules. This molecule represents the third family of HLA-D region molecules isolated from the cell line PRIESS. Both HLA-DR and HLA-SB molecules from this cell line were previously shown by amino acid sequence analysis to be I-E-like but distinct from one another. Collectively, these data provide evidence that the HLA-D region contains at least six loci encoding distinct alpha and beta chains for the HLA-SB, HLA-DR, and HLA-DS molecules.

Amino Acid Sequence↗
PubMed1983

Cytofluorometric analysis of major histocompatibility antigens on human monocytes using monoclonal antibodies.

The expression of HLA-A, B, C, and DR antigens was investigated on monocyte preparations by flow cytometry using various monoclonal antibodies. Essentially all human monocytes, either freshly isolated or after culture for several days, were stained for HLA-A, B, C, and DR antigens. When monocytes were incubated with Con-A-stimulated lymphocyte supernatants, an increase in HLA-A, B, C, and DR staining was observed. No increase was noted when two other monoclonal antibodies against non-HLA-related monocyte antigens (63D3 and 61D3) were studied under the same culture conditions. These results indicate that soluble factor(s) present in Con-A-stimulated lymphocyte supernatants modulate the expression of the major histocompatibility antigens on the surface of human monocytes.

Antibodies, Monoclonal↗
PubMed1983

Characterization of B cell antibodies in kidney transplant recipients.

Antibodies against B lymphocytes were found in the serum of the majority of 59 kidney transplant recipients and of 22 eluates obtained from kidney allografts undergoing rejection. To characterize these B cell lymphocytotoxins we have used a mouse monoclonal anti-DR antibody (L227) that inhibits cytotoxicity of antibodies against HLA-DR antigens and a chicken serum against human Ia-like antigens that also inhibits antibodies against DR-related supertypic determinants and other Class II histocompatibility antigens. Three types of B cell cytotoxins were defined: antibodies against HLA-DR, antibodies against Ia-like antigens other than DR, and antibodies against non-Ia-related B cell antigens. Before transplantation, B cell antibodies were detected in about a third of the patients studied. They were inhibited by monoclonal anti-DR more often in recipients who ultimately rejected a kidney allograft (67%) than in those in whom the graft was successful (44%, P less than 0.03). After transplantation, antibodies inhibited by L227 were found in 56% of the patients with functioning grafts and in 94% of the recipients whose grafts had been removed because of rejection (P less than 0.001). B cell antibodies inhibited by monoclonal anti-DR were found in the majority of kidney eluates. However, although 85% of the B cell reactions of kidney eluates were blocked by this antibody, only 55% of the B cell reactions of sera obtained from the same recipients after nephrectomy were similarly inhibited. Thus it appears that antibodies against HLA-DR were bound and concentrated in the transplanted organ and other B cell antibodies were not. These results indicate that anti-DR antibodies blocked by the monoclonal antibody L227 are the most common type of B cell lymphocytotoxins formed in kidney transplant recipients. Their role in kidney allografts undergoing rejection, where they are bound in high concentration, needs to be determined.

Antigens, Surface↗
PubMed1983

Accessory cell function of human endothelial cells. I. A subpopulation of Ia positive cells is required for antigen presentation.

The expression of class I and class II HLA antigens on preparations of human endothelial cells, isolated from umbilical cord veins, was investigated by immunofluorescence. While virtually all endothelial cells expressed class I antigens, less than 1% were positive for class II antigens, as detected with a panel of 10 different monoclonal antibodies. Antigen specific T cell lines proliferated in response to mumps antigen in the presence of endothelial cells or blood monocytes from HLA-DR matched donors. However, these T cell lines failed to respond in the absence of accessory cells or when accessory cells from HLA-D-region mismatched cord donors were used. The ability of both monocytes and endothelial cells to present antigen was abolished by treatment of the cells with monoclonal antibodies specific for either class I or class II HLA antigens plus complement. Similar treatment with monoclonal antibodies specific for monocytes greatly reduced antigen presentation by endothelial cells. These results indicate that preparations of endothelial cells contain a subpopulation of Ia positive cells, distinct from monocytes, which are required for antigen presentation.

Animals↗
PubMed1982

Monoclonal antibodies against human monocytes. II. Recognition of two distinct cell surface molecules.

Three monoclonal antibodies (63D3, 63D2, and 61D3) with reactivity against human monocytes have been studied. They reacted with most adherent mononuclear cells but not with pure populations of peripheral blood B and T lymphocytes. Two of these antibodies, 63D3 and 63D2, competed in fluorescence inhibition experiments, recognized a monocyte surface antigen of about 200,000 daltons, and were idiotypically related. The third antibody, 61D3, did not compete with the others in fluorescence inhibition experiments, recognized a different surface molecule, and was idiotypically distinct from 63D3 and 63D2. Whereas 63D3 and 63D2 reacted very weakly with some granulocytes, 61D3 did not, suggesting that it is specific for monocytes alone.

Animals↗
PubMed1982

The human HLA-DR antigens are encoded by multiple beta-chain loci.

Monoclonal antibodies have been used to isolate and characterize human HLA-DR antigens from human B cell lines. Using sequential immunodepletion experiments, several subsets of DR antigens have been identified. Partial amino-terminal amino acid sequencing has identified these subsets as DR molecules with sequences homologous to the murine I-E alloantigens. In addition, sequence data provide evidence for primary structural differences in the DR beta-chains of two of the subsets. These results provide primary structural evidence for the presence of multiple DR beta-chain loci.

Amino Acid Sequence↗
PubMed1981

Characterization of B-cell and monocyte antibodies in recipient sera and in eluates from rejected kidney allografts.

The specificity of B-cell antibodies developing in kidney transplant recipients was investigated by blocking with monoclonal anti-DR and chicken anti-human IA antibody. Among 34 recipients who ultimately rejected their kidney allograft, 35% displayed antibodies against B cells before transplantation, most of which were blocked by the anti-DR reagents. Thirty-three of 34 recipients developed B-cell lymphocytotoxins after nephrectomy, and over half of these were not blocked by monoclonal anti-DR. B-cell antibodies were found also in the majority of the kidney eluates, and most of them were shown to be directed against HLA-DR antigens, Monocyte-specific antibodies, which were not blocked by chicken anti-human IA serum, were frequently found in eluates from kidney allografts undergoing rejection. The methods described appear to be useful for the characterization of B-cell and monocyte antibodies developing in kidney transplant recipients. The possibility of correlation with allograft outcome is currently being investigated.

Antibody Specificity↗
PubMed1980

Initial characterization of monoclonal antibodies against human monocytes.

Three monoclonal antibodies against human monocytes have been produced by somatic cell fusion. Extensive specificity analysis suggests that these antibodies react with most if not all human peripheral blood monocytes and not with highly purified T or B cells. Initial chemical characterization of the monocyte antigen recognized by two of these antibodies is presented. The molecule is a single polypeptide chain with an apparent molecular weight of 200,000. These reagents should prove useful in the clinical definition of disorders of monocyte differentiation, in studies of monocyte function, and in the elucidation of the genetics and structure of monocyte cell surface antigens.

Animals↗
PubMed1979

[Caval catheterization via the innominate vein (author's transl)].

Experience gained in 3500 supraclavicular innominate vein punctures for catheterization of the superior vena cava with the indirect technique is explained and discussed. The innominate vein is easily accessible in every state of blood circulation, even intraoperatively when the patient is covered by drapes. The thrombosis risk is reduced because of the wide lumen and the straight course of the vessel (vena anonyma dextra). The special advantages of the indirect technique are the small puncture trauma and absence of false positions. The only important complication observed during an average infusion time of 8 days was pneumothorax at a rate of 1.4%.

Blood Specimen Collection↗