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Biomedical subjects

C Ernst

Publications and source records attributed to C Ernst.

At least 73 records · Page 4Linked to original sources
PubMed1984

Efficient selection of human tumor growth-inhibiting monoclonal antibodies.

A method is described for selection early after fusion for hybridomas that secrete IgG2a monoclonal antibodies (MAbs) with binding specificity for antigens on the human tumor cells used to immunize mice. By combining this preselection method with antibody-dependent macrophage-mediated cytotoxicity assays, it was possible to select those MAbs mediating a tumoricidal effect against tumor cells in culture and inhibiting the growth of tumor xenografts in nude mice. Two such MAbs, GA733 and CO441, inhibited the growth of colorectal carcinoma cells, and one of them (GA733) was effective even when administered 6 days after implantation of tumor cells. These results suggest the potential usefulness of the 2 MAbs in immunodiagnosis and immunotherapy of human tumors.

Animals↗
PubMed1984

Labeling monoclonal antibodies and F(ab')2 fragments with (111In) indium using cyclic DTPA anhydride and their in vivo behavior in mice bearing human tumor xenografts.

Monoclonal antibodies (MAb) and their F(ab')2 fragments to human colorectal carcinoma (CRC) and human melanoma-associated antigens were conjugated to diethylenetriaminepentaacetic acid (DTPA) via an acylation reaction using cyclic DTPA dianhydride. Relative immunoreactivity of the F(ab')2 fragments was as high as 70% when an average of only 0.7 DTPA molecules was conjugated per fragment, decreasing rapidly to less than 5% when 9.0 DTPA molecules were conjugated. The 111In-labeled whole MAb in mice bearing human tumor xenografts showed higher concentrations in tumor, liver, kidney, and spleen 7 days after injection of MAb when compared with the same MAb labeled with 131I. F(ab')2 labeled with 111In showed a marked persistence in the tumor-bearing mice with higher concentrations in all organs except blood, when compared with 131I-labeled F(ab')2. Radioactivity was particularly high in the kidneys. Although images of human tumor xenografts were easily visualized using 131I-labeled F(ab')2 3 days after injection, it was difficult to visualize tumor grafts with 111In-labeled F(ab')2 due to persistently high renal, liver, and background activity. Increased catabolism of the 131I-labeled MAb may be the cause of the difference; but antibodies with high immunological activity are a necessity for in vivo imaging studies before firm conclusions can be drawn.

Animals↗
PubMed1984

Production and characterization of monoclonal antibodies to peripheral and central nervous system myelin.

Monoclonal antibodies against P0, myelin basic protein, or myelin-associated glycoprotein were generated by fusing mouse myeloma cells with spleen cells from BALB/c mice immunized with central and peripheral nervous system myelin proteins. The antibodies secreted were either IgG, IgM, or IgA. Clone C6B5 (iso-type IgM) secreted antibody(ies) that bound to both myelin basic protein and myelin-associated glycoprotein, although binding of antibody to myelin basic protein as detected by the immunoblot technique appeared to be much less than to the myelin-associated glycoprotein. Antibodies were characterized in solid-phase radioimmunoassay for their species cross-reaction, and histologically for the specificity of binding to myelin in central and peripheral nervous system tissues. These monoclonal reagents should prove valuable in studying CSF and myelin-producing cells, since in both cases the concentration of myelin proteins is low.

Animals↗
PubMed1984

Monoclonal antibody localization of Lewis antigens in fixed tissue.

Monoclonal antibodies that bind specifically with Lewisa (Lea) and Lewisb (Leb) antigens were used in an immunoperoxidase assay to characterize Lewis (Le) antigenic profile of a variety of fixed tissues. Representative sections of normal and malignant tissue from the stomach, colon, pancreas, and kidney were examined and compared. Lea antigen was expressed more often in gastric adenocarcinomas (80%) than normal gastric mucosa (40%). In gastric tumors with concomitant expression of Le antigens, larger areas within an individual tumor expressed Lea antigen rather than Leb antigen. Expression of Leb antigen in normal colonic tissue was seen only in the proximal colon and not distal colon; colon carcinomas, on the other hand, expressed Leb antigen (64%) regardless of where the primary arose. Leb antigen was expressed in large pancreatic ducts (three of three) more often than Lea antigen (one of three); exclusive expression of Lea antigen was demonstrated in the proximal convoluted tubules of normal kidney (three of three) and in renal cell carcinomas (six of eight).

Animals↗
PubMed1984

Monoclonal antibody localization of A and B isoantigens in normal and malignant fixed human tissues.

The expression of human blood group A and B isoantigens in normal and malignant tissues from stomach, colon, and pancreas was analyzed in an immunoperoxidase assay using monoclonal antibodies specific for these isoantigens. Appropriate isoantigen expression was demonstrated in the normal epithelium from the stomach, pancreas, and proximal but not distal colon of blood group A, AB, or B patients. Half of all gastric carcinomas and of proximal colon carcinomas showed complete loss of isoantigen, whereas the adjacent mucosa in these cases continued to express appropriate isoantigen. Isoantigen expression was completely lost in only 13% of pancreatic carcinomas tested. Neither A nor B isoantigen was detected in normal epithelium from the distal colon. By contrast, 85% of carcinomas derived from this site showed reexpression of isoantigen. Inappropriate expression of A isoantigen was detected in pancreatic carcinomas (2/5) but not in gastric or colon carcinomas (0/21). Inappropriate expression of B substance was not detected in any tissue (0/38). Interestingly, differential binding of antibodies to Type 1 versus Type 2 and/or difucosyl versus monofucosyl blood group B substances was manifested by differences in intensity of staining for endothelium and red blood cells.

ABO Blood-Group System↗
PubMed1983

Radioimmunodetection of human tumor xenografts by monoclonal antibodies.

Mouse IgG2a monoclonal antibodies with specific binding reactivity in vitro to human tumors of the gastrointestinal tract were radioiodinated and injected into immunosuppressed mice xenografted with human colon carcinoma tumors. The antibodies preferentially localized in tumor tissue compared to normal mouse tissue, as determined by differential tissue counting of radioactivity. Preferential antibody localization in tumor tissue was greatly enhanced when F(ab')2 fragments of the antibodies were used, and the fragments localized specifically only in those tumors that bind the antibodies in vitro and not in unrelated tumors. Radiolabeled fragments of an anti-hepatitis virus monoclonal antibody of the same isotype as the specific antibody did not localize in tumors. Tumors could be located by whole-body gamma-scintigraphy with radiolabeled specific antibody F(ab')2 fragments without background subtraction.

Animals↗
PubMed1982

Phase-I clinical trial of monoclonal antibody in treatment of gastrointestinal tumours.

A phase-I clinical trial of a murine monoclonal antibody that specifically suppresses growth of human gastrointestinal tumours in athymic mice was conducted in four patients, who were given 15-200 mg purified antibody. The monoclonal antibody persisted in the circulation for more than a week when more than 15 mg was given. Antibodies against mouse immunoglobulin developed in three of the four patients. In one patient who received autologous mononuclear cells that had been mixed with monoclonal antibody by way of a hepatic-artery catheter, hepatic metastases became smaller and their echogenic characteristics changed, and there was heavier monocyte infiltration in the histological appearance of a resected metastasis.

Adenocarcinoma↗
PubMed1981

Preparation of psychiatric inpatients for group therapy.

Nurses have been acquiring the skills necessary for involvement as cotherapists in group therapy with increasing frequency and have been taking a more active role in the inpatient psychiatric treatment. Preparation of patients for group therapy is supported by the literature for outpatients and equivocally supported for inpatients by this study. Nurses, with their frequent and prolonged contact with inpatients, are in the unique position of being able to form a close, consistent relationship that allows them to assess expectations, plan individualized preparation for the patient, and reinforce the importance of group therapy within the total treatment program. Continued research is needed to assess further the effectiveness of preparation for inpatients prior to group therapy and the nurses' role in preparation.

Adult↗
PubMed1981

Single or multicellular origin of human T lymphocyte colonies in vitro: modification by 12-o-tetradecanoylphorbol 13-acetate (TPA).

The assumption that human T lymphocyte colonies have a unicellular origin has been directly tested with peripheral blood mononuclear cells from 2 women heterozygous for the common X-linked glucose-6-phosphate dehydrogenase (G-6-PD) gene (GdB) and the variant GdA. T cells were cultured in semisolid medium in the presence of phytohemagglutinin (PHA) and T lymphocyte growth factor with or without preincubation in suspension culture with PHA (2-stage and 1-stage assays, respectively). The enzyme type of individual T cell colonies was then determined electrophoretically at the lowest colony density with adequate growth (usually less than 100 colonies/dish). In the 2-stage system, 90 of 97 tested colonies had equal amounts of A and B enzyme activities suggesting multicellular origin of the colonies. Similarly, in the single-stage system, 21 of 31 colonies had both A and B enzymes. Increasing the density of the soft agar did not influence the frequency of A/B colonies. However, when 12-O-tetradecanoylphorbol 13-acetate (TPA), a promoter of T cell colony growth shown in other systems to inhibit metabolic cooperation, was added, a striking decrease in frequency of colonies with both G-6-PD types was found. In the 2-stage culture, 0 of 9 colonies had a double-enzyme type and in the single-stage system, the frequency of A/B colonies declined to 9 of 34 (p less than 0.025). The data suggest that despite the apparent multicellular origin of T cell colonies in cultures with TPA, most colonies do originate from single cells when cultured with TPA at low colony densities. Stimulation of cell growth or inhibition of metabolic cooperation between cells by TPA are possible explanations for these differences.

Cells, Cultured↗
PubMed1980

[Increasing suicides of psychiatric inpatients: reality or artefact? (author's transl)].

In several countries the suicide rate for psychiatric inpatients has increased more than that for admissions and suicides in the general population. This was also the case in our clinic. This hypothesis was tested: today, because of more liberal management, suicides are committed during hospitalization that in an earlier and more restrictive age would have taken place after discharge. All suicides taking place 1960-1979 in the clinic's main catchment area were examined for previous hospitalization. The hypothesis was not supported. Over twenty years neither the suicide cases nor all discharged patients changed significantly in distribution of age, sex, number of previous admissions, duration of hospitalization, or diagnosis. Therefore, none of these variables explain the increase. In both decades, on the other hand, patients that committed suicide during their stay at the clinic had been hospitalized longer; those that committed suicide within three months after discharge had been hospitalized for a shorter time than the sum of discharged patients. Among the suicides that occurred after discharge, the percentage of depressives and addicts was higher and the percentage of schizophrenic patients was smaller than among all discharged patients. A change in patient management (more time off, more working outside, more open wards) has preceded the increase in suicides; medical staff, however, has doubled over the decades considered here. Rising pressure for resocialization to avoid hospitalism may heighten suicidal behavior. Preventive measures are discussed.

Adult↗
PubMed1980

Polycythemia vera. Physical separation of normal and neoplastic committed granulocyte-macrophage progenitors.

In previous studies of two patients with polycythemia vera (PV) who were heterozygous at the X-linked locus for glucose-6-phosphate dehydrogenase (G6PD), only A type enzyme was found in nonlymphoid blood cells. However, some erythroid and granulocytic colonies grown in vitro were type B and therefore arose from presumably normal progenitors. One patient had enough type B colonies (8%) that studies of the physical characteristics of normal and PV clonal colony-forming cells could be undertaken. When marrow cells were separated by velocity sedimentation at unit gravity, most PV clonal granulocyte-macrophage progenitors (CFU-C) (type A G6PD) sedimented between 6.4 and 7.2 mm/h, whereas most residual normal, type B CFU-C sedimented less than or equal to 5.9 mm/h (P = 0.04)., When blood cells were separated over a discontinuous buoyant density gradient, PV clonal CFU-C equilibrated at densities < 1.065 g/ml, whereas residual normal CFU-C were found greater than or equal to 1.065 g/ml (P < 0.01). PV clonal and residual normal erythroid burst-forming progenitors were not separable by either method. Thus PV clonal CFU-C are larger and less dense cells than are residual normal CFU-C.

Erythrocytes↗
PubMed1980

Polycythemia vera. Further in vitro studies of hematopoietic regulation.

Further in vitro studies of hematopoietic regulation were carried out in two patients with polycythemia vera who were also heterozygotes (Gd(B)/Gd(A)) for glucose-6-phosphate-dehydrogenase (G-6-PD). While only G-6-PD type A was detectable in circulating erythrocytes, granulocytes and platelets, cultures of peripheral blood and marrow from one patient revealed a substantial number of G-6-PD type B erythroid burst-forming units (BFU-E) and granulocyte/macrophage colony-forming units. Detailed analysis demonstrated: (a) where detectable, normal BFU-E and granulocyte/macrophage colony-forming units were found with similar frequencies; (b) the same frequencies for normal progenitors characterized cultures of peripheral blood and marrow; (c) inhibition of normal erythroid differentiation between BFU-E and the more mature erythroid colony-forming unit; (d) a decline in the prevalence of normal colony-forming units with time, suggesting that disease progression is associated with further suppression of normal hematopoiesis by products of the abnormal clone.

Bone Marrow Cells↗
PubMed1979

[Interaction between an antifungal heptaene, amphotericin B and cholesterol in vitro, as detected by circular dichroism and absorption. Influence of temperature].

The polyene antibiotic "Amphotericin B" can interact with sterols, cholesterol or ergosterol in aqueous and hydroalcoholic media and a correlative striking spectral change appears between 300 and 420 nm in the CD and absorption spectra. Using these spectroscopic methods we have determined that the influence of temperature between 4 and 80 degrees C is very important. The higher the temperature the most rapid is the modification of the spectra. Thus, the "Amphotericin B"-sterol complex is more easily formed when heating. We have not found any reversibility at 80 degrees C.

Amphotericin B↗