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Biomedical subjects

K Hopper

Publications and source records attributed to K Hopper.

At least 37 records · Page 2Linked to original sources

Phase I study of interleukin-2 and interferon alfa-2a as outpatient therapy for patients with advanced malignancy.

Twenty-six patients were treated in this phase I study with the combination of interleukin-2 (IL2) administered as a continuous infusion and interferon alfa-2a (IFN alpha-2a) administered intramuscularly to patients in an outpatient setting. The maximum-tolerated dose of both agents given as outpatient therapy was 2 x 10(6) U/m2 days 1 to 5 of IL2 and 9 x 10(6) U/m2 days 1, 3, and 5 of IFN alpha-2a for 4 consecutive weeks. A 2- to 4-week rest period was permitted after each 4 weeks of treatment. Fatigue was the treatment-limiting toxicity, and serious clinical or laboratory abnormalities occurred infrequently during this study. Patients with colon cancer metastatic to the liver tolerated treatment worse than patients with other tumors. Twelve of the 15 patients with renal cell cancer were assessable for response determinations. Of these 12 patients, three exhibited complete tumor regression, three have had partial objective regression, and three patients experienced stabilization of rapidly progressive disease. This therapy appears to be well tolerated in an outpatient treatment setting and shows significant activity against advanced renal cell cancer.

Adult↗

Direct detection of Neisseria gonorrhoeae with monoclonal antibodies characterized by serotyping reagents.

A panel of monoclonal antibodies (MAbs) directed to outer membrane protein I were generated with the ultimate aim of detecting Neisseria gonorrhoeae in patient samples by a direct immunofluorescence (IF) test. In an initial evaluation of the sensitivity of these reagents, a cocktail of six IF MAbs recognized 491 (91%) of 540 gonococci isolates from several centers in Sydney, Australia. IF MAbs designated 185 and 228 recognized serovars of WI serogroup and IF MAbs 208, 210, and 312 recognized serovars of WII/III serogroup. IF MAb 198 recognized serovars within both serogroups. Three additional IF MAbs, designated 322, 323, and 330, were then generated by using strains which failed to react with the original MAb cocktail and which belonged to particular serovars. The new cocktail of nine IF MAbs recognized 96% of the gonococcal isolates, which incidentally contained representatives of serovars shown to have a worldwide distribution in previous studies. Although subtle differences were apparent in the reaction patterns found with coagglutination (serotyping) and IF, there nonetheless seems to be merit in the approach of continually evaluating the sensitivity of diagnostic reagents such as MAbs. This is especially true with an organism such as N. gonorrhoeae, which has the capacity to regularly alter the antigenic structure of its outer membrane proteins.

Antibodies, Monoclonal↗

Windows and blinking: techniques for enhanced ocular computed tomographic imaging.

Computed tomography (CT) has become an important diagnostic modality in the evaluation of ocular and orbital disease. A weakness of CT, however, is its inability to show clearly intraocular lesions that do not contain calcium. These images can be improved by the careful selection of window width and window level and by the use of a technique known as "blinking." The use of these enhancement techniques is illustrated in two cases of leukocoria in children.

Eye↗

Release of galactosyltransferase from peritoneal macrophages during acute inflammation.

Peritoneal cells harvested from mice injected with Salmonella enteritidis or thioglycollate released large amounts of galactosyltransferase (GT), but not sialyltransferase, into their culture supernatants. Maximum release of GT (using ovalbumin as acceptor) occurred from cells harvested 2-4 days after primary injection, but little GT was released from cells elicited by a secondary injection of salmonella or ovalbumin in sensitised mice or during intraperitoneal allogeneic reactions. Enzyme release in culture did not parallel GT levels in serum. Most enzyme was released by large, poorly adherent, macrophage-enriched, Fc receptor-bearing peritoneal cells of low density. Normal monocytes, bone marrow cells, and platelets also produced large amounts, and normal spleen cells or polymorphonuclear leukocytes moderate amounts, of GT. Lymphocytes, dead cells, mast cells, red blood cells, or whole populations of lymph node and thymus cells released very low levels of enzyme. Very little GT was bound to the cell surface and was not passively absorbed from serum or platelets. Release of GT was prevented at 4 degrees C but was not markedly affected by a variety of metabolic inhibitors except pretreatment of the cells with thrombin, which increased release and trypsin which decreased release.

Animals↗

Brugia pahangi: serum-dependent cell-mediated reactions to sheathed and exsheathed microfilariae.

The immune mechanisms operating on the sheath and the cuticle of the Brugia pahangi microfilariae have been studied in vitro. The intact and exsheathed parasites were used for this purpose with serum from albino rats immunized with sonicated homogenates of the parasites as the source of antibodies. The IgG component of the serum was found to promote adherence of rat leucocytes and death of the sheathed and exsheathed parasites in presence of fresh normal serum. EDTA and EGTA abolished the adherence activity suggesting the involvement of complement components via the classical pathway. Both macrophages and neutrophils participate in this reaction. Eosinophils exhibit marginal activity only on exsheathed parasites. The intensity of adherence and killing by neutrophils in the presence of immune serum was greater with the exsheathed microfilariae than with the sheathed ones.

Animals↗

The ability of lymphokine and lipopolysaccharide to induce procoagulant activity in mouse macrophage cell lines.

A comparison was made of the abilities of mouse macrophage cell lines and cultured bone marrow-derived macrophages to respond to lymphokine and lipopolysaccharide (LPS) in the macrophage procoagulant assay (MPCA). Mouse macrophage cell lines PU5 and WEHI 265 responded to low concentrations of lymphokine and LPS by increased procoagulant activity; the activity of PU5 cells was comparable to that of TG-PEC. Approximately one-half of the MPCA induced by lymphokine after 20 hr culture was detectable after 2 hr with either cell line. J774 was unresponsive to LPS but responded weakly to lymphokine, and P388D1 and WEHI 274 were unresponsive to both stimuli as determined by the MPCA test. Addition of purified T cells (five T cells to one macrophage) to the unresponsive cell lines induced procoagulant activity in the presence of either stimulus, which suggests that cell contact is necessary in some cases. Only J774 cells responded to lymphocyte-derived chemotactic factor (LDCF) or endotoxin-activated mouse serum (EAMS) in chemotaxis assays. Immature bone marrow cells responded to chemotactic stimuli, and procoagulant activity was induced with lymphokine after 4 days in culture. Cells cultured for 7 days had about twice as much MPCA, but further culturing did not result in cells with enhanced activity. The procoagulant responsiveness of different macrophage cell lines to lymphokine or LPS may reflect differences in the maturation and differentiation states of these cells.

Animals↗

IgE-dependent cellular adhesion and cytotoxicity to Litomosoides carinii microfilariae--nature of effector cells.

Albino rats immunized with sonicated microfilarial antigen incorporated in Freund's complete adjuvant, produce antibodies that promote cell-mediated adhesion and killing of Litomosoides carinii microfilariae in vitro. Using highly purified cell populations, it has been shown that macrophages and neutrophils are most active in this phenomenon. Eosinophils, while adhering readily to parasites in the presence of the antibody, did not affect the viability of the parasites when observed after 24 hr incubation.

Animals↗

Antibody-dependent cell-mediated effects in bancroftian filariasis.

The nature of immunoglobulin and effector cells involved in the antibody-dependent cell-mediated adhesion and cytotoxicity to Wuchereria bancrofti larvae has been investigated. Human neutrophils and eosinophils purified from peripheral blood by metrizamide gradients readily adhered to the parasites in presence of IgG fraction of sera from majority of elephantiasis cases with amicrofilaraemia and many of the endemic normals. The cells from normal, microfilariae and elephantiasis cases were equally effective inthe adhesion reaction. While the adhered neutrophils killed the larvae, eosinophils were ineffective in this respect. DEC treatment of elephantiasis cases results in a significant reduction in the ability of their sera to promote cellular adhesion.

Antibody-Dependent Cell Cytotoxicity↗

Rethinking suicide: notes toward a critical epidemiology.

Where the genesis of "disease" owes much to causes that are social and economic in nature, epidemiology holds unrealized potential as a tool of social criticism. A particularly interesting example is provided by suicide and suicide research. Methodological difficulties are explored in detail, major findings reviewed, and the dominant interpretations of such findings criticized. Research has consistently pointed to the risks of marginal or minority status, unemployment, weak community supports, situational crises, and the pressures people are subjected to during periods of economic depression. It is argued that the sociostructural implications of such research have been systematically ignored, attention being devoted instead to more efficient management of the suicidal individual--this in spite of the lack of success of suicide prevention centers. Initial steps toward an alternative framework are outlined, with emphasis laid on the need to disaggregate the suicide act. It is further suggested that self-destruction is a far commoner--indeed, integral--part of our social environment than the bare rack of suicide statistics would suggest.

Adolescent↗

The differentiation of T lymphocytes. IV. Net increases in low theta cells, maintenance of biological activity and death of high theta cells during short-term culture of mouse thymocytes.

Dissociated mouse thymocytes were cultured under optimized conditions in Marbrook vessels in order to follow some aspects of T-cell differentiation. Under particular conditions it was possible to obtain a 50% net increase in the total number of the peripheral T-cell like, minor low theta thymocyte subpopulation over the first day of culture, although this increase was lost with further incubation. The increase arose from proliferation of preexistent low theta cells,and not from transformation of the major, high theta population. Under all conditions the high theta cells died rapidly in culture. These results are in accordance with the view that the high theta and low theta thymocytes represent separate streams of T-cell development. There was a striking increase in responsiveness to phytohemagglutinin and concanavalin A after culture of thymocytes under these conditions. However, this was ascribed, not to the development of new immunocompetent T cells, but to selective cell death in the cultures eliminating some inhibitory elements. No increase in progenitors of cytotoxic lymphocytes was obtained. The results demonstrate some potential artifacts in assessing the immunocompetence of cultured thymocytes.

Adrenal Glands↗