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D N Howell

Publications and source records attributed to D N Howell.

71 records · Page 4Linked to original sources
PubMed1988

Viral infections in the acquired immunodeficiency syndrome.

The following communication is a tripartite synopsis of the role of viral infection in the acquired immunodeficiency syndrome (AIDS). The first section describes the impact of viral opportunistic infection in AIDS; for each virus, clinical presentation and diagnosis, laboratory diagnostic approaches (with emphasis on electron microscopy), and therapeutic interventions attempted to date are discussed. The second segment explores current theories on the pathogenesis of AIDS, and describes diagnostic and therapeutic approaches to the syndrome itself. The final section catalogues ultrastructural anomalies in the cells of AIDS patients, many of which have been mistakenly identified as etiologic agents.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Evidence that pretransplant donor blood transfusion prevents rat renal allograft dysfunction but not the in situ cellular alloimmune or morphologic manifestations of rejection.

The effects of preoperative donor-specific blood transfusion (DSBT) on the physiologic, morphologic, and immunologic aspects of allograft responsiveness were evaluated in a rat renal transplant model, using the ACI (RT1a) into PVG (RT1c) high-responder strain combination. Indefinite graft survival (mean greater than 63 days) could be induced by DSBT administration alone. In comparison, animals receiving autologous blood transfusion (ABT) all died within 7 days posttransplantation. As assessed by clearance of inulin and paraaminohippurate, renal allograft function in DSBT-pretreated recipients at 6 days was equivalent to that of isograft recipients, and in contrast to the significant reduction seen in ABT treated rats. Likewise, thromboxane B2 (TXB2) production by ex-vivo-perfused allografts from DSBT-treated recipients was comparable to that of isografts, and significantly lower than that of allografts from ABT-treated rats. A significant inverse correlation was found between renal TXB2 production and inulin clearance. Despite these substantial differences in renal function and eicosanoid metabolism, morphologic evaluation of renal allografts from DSBT-enhanced and ABT-rejecting recipients at comparable time points showed equivalent histologic manifestations of rejection. In addition, immunohistologic labeling of renal allograft sections and fluorescence-activated cell sorter analysis of cells eluted from allografts showed the same phenotype and pattern of infiltrating T cell subsets in both groups. Specific antidonor cytotoxic T lymphocyte precursor (pCTL) frequencies of cells eluted from kidney grafts were equivalent in DSBT and ABT-pretreated animals, and both groups expressed significantly higher (but equivalent) pCTL frequencies in the kidneys than spleens. Comparisons of the lysis of PVG.R1 (RT1.Aa on a PVG background) and ACI targets indicated that cytotoxic responses from effector cells freshly eluted from DSBT and ABT kidneys were primarily directed against allogeneic class I major histocompatibility complex (MHC) specificities, whereas several long term T cell lines generated from 6-day kidney transplants of both groups expressed a predominant W3/25+ (T helper) phenotype and cytotoxic activity against donor specificities other than RT1.Aa class I MHC. Specific antidonor proliferative T lymphocyte (pPTL) precursor frequencies of cells eluted from renal allografts were also equivalent for both DSBT- and ABT-treated recipients, and the range of pPTL frequencies for allograft cell eluates was similar to that in spleens, regardless of the source of the transfusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Expression of differentiation antigens by hybrids of human lymphoblastoid cells.

In previous communications, we have described the expression of class I and class II histocompatibility antigens by hybrids of human B and T lymphoblastoid cell lines (B- and T-LCL). In all cases, such hybrids were found to resemble their B-LCL parents, expressing high levels of class I and class II antigens encoded by both parent cell lines. In the current study, we have conducted a more extensive analysis of B-LCLxT-LCL hybrids with a panel of monoclonal antibodies recognizing a variety of B and T lymphocyte differentiation markers. Rather than exhibiting a B-LCL-dominant phenotype, most hybrids were found to express a majority of both T and B lymphocyte antigens expressed by their parent cell lines. Several hybrids of pairs of dissimilar T-LCL were also produced and analyzed. Again, a majority of parental antigens was expressed on the hybrids. However, eight of eight hybrids of the T-LCL CEM and HSB failed to express HNK-1, an antigen strongly expressed by HSB; and two hybrids of the T-LCL CEM and SKW3 expressed CD3, an antigen expressed by neither parent cell line.

Antibodies, Monoclonal↗
PubMed1985

Genes regulating HLA class I antigen expression in T-B lymphoblast hybrids.

Regulation of HLA class I and class II antigen expression was studied in hybrids of human T and B lymphoblastoid cell lines (LCL). The T-LCL CEMR.3 expresses no HLA class II antigens. It expresses little total HLA class I antigen and no HLA-B antigens. The B-LCL 721.174 is a radiation-induced variant immunoselected for loss of class II antigen expression. In addition to showing a deletion of all HLA-DR and DQ structural genes, 721.174 expresses no HLA-B antigens and a decreased level of HLA-A antigen compared with the parental cell line. A hybrid of 721.174 and CEMR.3 expresses class II antigens encoded by CEMR.3. Increased expression of HLA class I antigens encoded by both 721.174 and CEMR.3 was also observed. Specifically, the previously undetectable HLA-B5 and HLA-Bw6 antigens encoded by 721.174 and CEMR.3, respectively, were present on the hybrid. Increased expression of the HLA-A2 antigen encoded by 721.174 was also observed. An immunoselected variant of the hybrid lacking both CEMR.3-derived copies of chromosome 6 lost expression of the HLA-B5 antigen encoded by 721.174 and expressed a decreased amount of HLA-A2. From these data, we infer that two complementary trans-acting factors mediate enhanced expression of HLA class I antigens in the hybrid. One of these factors is provided by a gene located on chromosome 6 derived from CEMR.3. The second factor, introduced by 721.174, is the gene previously postulated to induce expression of CEMR.3-encoded class I antigens in hybrids of CEMR.3 with B-LCL.

B-Lymphocytes↗
PubMed1985

Natural killing target antigens as inducers of interferon: studies with an immunoselected, natural killing-resistant human T lymphoblastoid cell line.

The human T lymphoblastoid cell line CEM was subjected to immunoselection by co-culture with peripheral blood mononuclear cells (PBMC) for resistance to natural killer (NK) cell-mediated lysis. The NK susceptibility of the resulting subline, CEM.NKR, was 8.4 to 20.6% of that of CEM when PBMC or adherent cell-depleted PBMC were used as effector cells, and -7.1 to 12.1% of that of CEM when Percoll gradient-enriched large granular lymphocytes (LGL) were used. However, CEM and CEM.NKR exhibited comparable sensitivity to antibody-dependent cellular cytotoxicity. Unlabeled CEM was eight- to 32-fold more effective than unlabeled CEM.NKR in inhibiting the NK lysis of labeled CEM target cells, and CEM bound 1.9 to 3.9-fold more Percoll gradient-enriched LGL than CEM.NKR in single cell-binding assays, suggesting that the NK-resistant variant has lost the expression of NK target antigens. However, CEM.NKR was comparable to CEM in its ability to induce interferon (IFN)-alpha production by PBMC in vitro, and the NK-resistant variant maintained its susceptibility to the antiproliferative effects of IFN-alpha, indicating that these phenomena may be mediated by molecules other than NK target structures. Comparison of CEM and CEM.NKR by indirect immunofluorescence with monoclonal antibodies specific for leukocyte antigens and the transferrin receptor, and by microcytotoxicity typing for HLA-A and B specificities, revealed no major differences.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1984

Expression of class I histocompatibility antigens on human T-B lymphoblast hybrids.

Expression of class I histocompatibility antigens (HLA-A and B) on hybrids of human T and B lymphoblastoid cell lines (LCL) was examined. The T-LCL CEM expressed low levels of HLA-A and B antigens. CEMR and CEMR .3, two 8-azaguanine- and ouabain-resistant sublines of CEM used for fusion, expressed no detectable HLA-B antigens and expressed HLA-A antigens at a level below that of CEM. The three B-LCL studied expressed class I histocompatibility antigens at levels 50- to 80-fold in excess of that found on CEM as assessed by indirect immunofluorescence and flow cytometry. Total levels of class I histocompatibility antigens on hybrids of CEMR and CEMR .3 with B-LCL were similar to those found on the B-LCL. CEM-encoded HLA-A and B antigens were expressed on the hybrids at levels much greater than those seen on CEM itself; expression by the hybrids of CEM-encoded and B-LCL-encoded class I antigens was comparable. By RNA-DNA filter hybridization, CEMR .3 was found to have extremely low levels of class I heavy-chain mRNA compared with two B-LCL and with HSB, a T-LCL that expresses high levels of class I histocompatibility antigens. Thus, the paucity of HLA-A and B expression by CEMR .3 (and by inference, CEMR and CEM), as well as the enhancement of CEM-encoded HLA-A and B antigen expression on B-LCL X T-LCL hybrids, must be due, at least in part, to modulation of the level of transcripts encoding HLA class I heavy chains.

Antibodies, Monoclonal↗
PubMed1983

Expression of T-lymphoblast-encoded HLA-DR antigens on human T-B lymphoblast hybrids.

The mode of expression of novel HLA-DR antigens on hybrids of human T and B lymphoblastoid cell lines (LCL) was examined by several approaches. In each case, the results indicated that the novel antigens are T-LCL-encoded. First, hybrids of sublines of the T-LCL CEM with three different B-LCL express indistinguishable sets of novel HLA-DR antigens. Second, the novel HLA-DR and MT specificities of WI-L2 x HSB (a hybrid of a subline of the T-LCL HSB and the B-LCL WI-L2) match those of SB, a B-LCL derived from the same individual as HSB. Finally, an immunoselected variant of SB x CEM.1 (a hybrid of a subline of CEM and SB) lacking one copy of chromosome 6 and one of the hybrid's novel HLA-DR specificities also lacks a class I antigen known to be encoded by CEM.

Antibodies, Monoclonal↗
PubMed1983

Expression of T-lymphoblast-encoded HLA-DR, MT, and SB antigens on human T-B lymphoblast hybrids.

The Ia-like antigens of hybrids of the B-lymphoblastoid cell line (B-LCL) WI-L2 and a subline of the T-lymphoblastoid cell line (T-LCL) HSB were examined. Antigens of the HLA-DR and MT series were analyzed by indirect immunofluorescence with chimpanzee anti-DR sera and monoclonal antibodies, and antigens of the SB series were analyzed by primed lymphocyte typing (PLT). The WI-L2 X HSB hybrids expressed antigens of each series not found on either parent cell. In each case, the novel antigens were indistinguishable from those found on SB, a B-LCL established from the same individual as HSB, and are thus presumably HSB encoded.

Animals↗
PubMed1982

Elimination of mycoplasma from human B-lymphoblastoid cell lines.

Intraperitoneal passage of human B-lymphoblastoid cell lines in nude mice was examined as a means of mycoplasma eradication. Recovery of viable cells from the mice was facilitated by immediate plating on feeder layers of human foreskin fibroblasts. In all cases, nude mouse passage for as little as 5 days was totally effective in removing all contaminating mycoplasma.

Animals↗
PubMed1977

Studies of viral antibody responses among Amish families.

Serum antibodies to adenovirus (ADN), cytomegalovirus (CMV), herpes simplex virus (HSV), influenza (INF), para-influenza (PAR), mumps (MUM), coxsackie B4 (Cox B4) and B5 (Cox B5) viruses were measured from 584 individuals belonging to 21 Indiana Amish families. Sex and age effects on antibody responses to cytomegalovirus were observed. Age effect on CMV, HSV, INF, PAR, MUM responses were also found. The percentage of responders to some of the viruses was shown to be age dependent, but the levels of antibody response were not affected by the difference in age. A familial basis for the antibody response was demonstrated. Attempts at demonstrating association between HLA haplotypes and responses were not successful. The unlikelihood of predominantly HLA-associated control of viral antibody response was discussed.

Adenoviruses, Human↗
PubMedDate not supplied

Glomerulopathies with fibrillary deposits.

Renal diseases involving glomerular deposits of fibrillary material are an important diagnostic challenge for the ultrastructural pathologist. Two primary disorders of this type, termed "fibrillary glomerulonephritis" (characterized by fibrils measuring approximately 20 nm in diameter) and "immunotactoid glomerulopathy" (characterized by larger, microtubular deposits), have been described. The possible relatedness of these two disorders and their potential association with other systemic illnesses are subjects of current debate. Other multisystemic diseases, including amyloidosis and various forms of cryoglobulinemia, can also present with fibrillary or microtubular deposits in the kidney. Five cases are presented in which fibrillar or microtubular structures were identified in renal biopsies by ultrastructural examination. The distinction between fibrillary glomerulonephritis, immunotactoid glomerulopathy, and other processes that have similar ultrastructural features are discussed.

Actin Cytoskeleton↗
PubMedDate not supplied

Identification of focal viral infections by confocal microscopy for subsequent ultrastructural analysis.

A correlative microscopy method for the ultrastructural analysis of focal viral tissue infections is presented. Using a confocal scanning laser microscope, foci of infection are identified in tissue sections prior to embedment; a variety of techniques can be employed for viral detection, including staining with standard histochemical reagents and fluorescently labeled antibodies. Areas of infection identified using confocal microscopy are excised from the tissue sections, embedded, and examined by transmission electron microscopy. Applications of this technique in both diagnostic and basic research settings are described.

Animals↗
PubMedDate not supplied

Concerted use of immunologic and ultrastructural analyses in diagnostic medicine: immunoelectron microscopy and correlative microscopy.

Electron microscopy (EM) is a valuable tool in diagnostic medicine, and in some cases, can be enhanced by immunological methods. A major medical application of EM, diagnostic virology, can frequently be augmented by employment of immunological reagents. Three immunoelectron microscopy (IEM) methods, aggregation, coating, and gold labeling, provide means for serotyping viruses; aggregation by antibody can also be used to concentrate viruses in dilute suspension or to serotype them. As a research tool, IEM can be useful in studying the relationship of various pathogen proteins to the infected cells or tissues. Delineating the subcellular location of viral components can yield information about how virions are constructed, and hence, suggest methods and compounds for inhibiting that process. Conversely, labeling virus-infected cells with antibodies against various cell receptors and proteins can yield information about the association of the proteins with budding virions. Another research example is the identification by immunological staining of virus-infected cells for subsequent ultrastructural identification of the specific cell type involved. Electron microscopy and immunolabeling methods are also useful in the diagnosis of immune complex disorders, including various forms of postinfectious immune complex glomerulonephritis. Precise analysis of immune complex deposits can be accomplished by using EM to pinpoint their location and immunohistology to probe their composition. Finally, a variety of optical microscopic techniques, including some involving immunofluorescent labeling, can be used to identify areas of interest in inhomogeneous tissues for further study by EM.

Child↗