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Biomedical subjects

J Schindler

Publications and source records attributed to J Schindler.

At least 91 records · Page 5Linked to original sources

Protein synthetic requirements for the outgrowth of trophoblast cells from mouse blastocysts.

Mouse blastocysts cultured under optimal conditions attach to the surface of the culture dish and subsequently give rise to outgrowths of trophoblast cells. The migration of trophoblast cells appears to be analogous to their behavior during the invasive phase of implantation in utero. In these studies, we have attempted to determine the time of synthesis and nature of the products required for trophoblast outgrowth. Fourth-day blastocysts were cultured in two different media: cNCTC, a nutrient medium supplemented with fetal calf serum, and PCMF, a simple preimplantation medium lacking amino acids and serum. Trophoblast outgrowth occurs in the former, but not in the latter, medium. Most blastocysts will give rise to outgrowths following as little as 12 hr of exposure to cNCTC at the appropriate time, even if they are subsequently placed in PCMF. Outgrowth fails to occur if blastocysts are treated with cycloheximide during the interval of exposure to cNCTC, whereas treatment with the antimetabolite after the period of culture in cNCTC does not block outgrowth. These observations are consistent with the view that protein(s) essential for trophoblast outgrowth are synthesized many hours prior to the actual event.

Amino Acids↗

[In vivo induction of antigenic modulation in man by an anti-T cell monoclonal antibody (author's transl)].

The anti-T cell monoclonal antibody OKT3 was administered to renal allograft recipients. A dramatic depletion of peripheral T cells was immediately observed followed, after 2-5 days, by the reappearance of a limited but significant number of or OKT3-4+ or OKT3-8+T cells showing antigenic modulation of the OKT3-defined antigen. These cells recovered the OKT3 receptor after overnight in vitro incubation.

Antibodies, Monoclonal↗

Human in vivo antigenic modulation induced by the anti-T cell OKT3 monoclonal antibody.

The anti-pan T cell monoclonal antibody OKT3 was administered daily for 2 weeks in four human renal allograft recipients. The antibody induced a dramatic and immediate depletion of peripheral T cells followed by an in vivo antigenic modulation of the OKT3-defined membrane antigen: after three injections, OKT3-treated patients showed a limited but significant number of OKT3- cells of T cell nature (as defined by OKT4 and OKT8) which recovered the OKT3 receptor after an overnight in vitro incubation in the absence of the monoclonal antibody.

Antibodies, Monoclonal↗

Numerical identification of bacteria with a hand-held calculator as an alternative to code books.

The Hewlett-Packard HP 41C hand-held calculator can be used for the numerical identification of bacteria. The dimensions of the identification matrix are limited to about 30 by 22; however, many groups of clinically important bacteria can be numerically identified by this method. Hand-held calculators can be used as an alternative to code books. At present, these calculators and additional tests can help solve identification problems in profiles not contained in code books.

Bacteria↗

[Clinical syndromes after subtotal resection of the small intestine (author's transl)].

After subtotal resection of the small gut intestinal function for a certain period of time is not sufficient to guarantee survival of the patient. Prognosis depends upon the length of the residual small gut but also upon its location and upon the ability of the intestine to adapt to the new situation. The use of elemental diets is most important in therapy. Resorption may be improved by applying surgical procedures, which will increase the time of passage of the chyle. If the remaining small intestine is less than 60 cm long in grown ups, or less than 40 cm long in children additional parenteral nutrition is usually necessary. Such nutrition can be given on a home care basis and will enable the patient to survive and lead a normal family and professional life.

Amino Acids↗

Studies on the mechanism of induction of embryonal carcinoma cell differentiation by retinoic acid.

On the basis of our studies, we conclude that RA is a potent promoter of differentiation of EC cells. We have demonstrated that the tumorigenicity of PCC4-azalR EC cultures can be effectively reduced following exposure of the cells to RA. This is presumably a result of differentiation of the EC cells to nontumorigenic derivatives. However, even after several weeks of exposure to RA, there remains in the culture a subpopulation of unresponsive EC cells. The reason why these cells do not differentiate in the presence of RA is currently under investigation. We have also derived by mutagen treatment and clonal selection EC cells that fail to respond to RA. Preliminary indications are that these cells have lost the capacity to differentiate when subjected to other manipulations which stimulate differentiation of the parental EC cells. This is an important observation since the mutants were selected only by their lack of response to RA. Unlike the parental cells, which have relatively large amounts of RABP, dif- cells appear either to lack RABP or to possess an altered binding protein which has a greatly reduced affinity for RA. These observations are consistent with the view that some function of the RA-RABP complex is critical in the sequence of events leading to differentiation of EC cells. However, further studies are required before we can establish the generality of this proposal. We are presently investigating whether the level and/or function of RA-RABP complexes in cells from the EC lines listed in TABLE 1 can explain their varying tendencies to differentiate.

Animals↗

Determination of T lymphocyte subpopulations by monoclonal antibodies in rheumatoid arthritis. Influence of immunomodulating agents.

The pathogenesis of rheumatoid arthritis is unknown, but clear abnormalities of the immune system are well documented in this disease. We therefore evaluated T cell subpopulations in patients with rheumatoid arthritis using monoclonal antibodies previously shown to react with all T cells (OKT3), with inducer/helper T cells (OKT4) and with suppressor/cytotoxic T cells (OKT8). These investigations disclosed evidence of a significant decrease in the number of OKT8+ cells/mm3 and a high inducer-helper/suppressor-cytotoxic (OKT4+/OKT8+) ratio in active rheumatoid arthritis. A modest number of patients with active arthritis were treated wit levamisole or with synthetic thymopoietin 32-36 (thymopoietin pentapeptide or TP-5). These individuals responded with ratio decreases to more normal levels. Our data support the hypothesis that monoclonal T cell antibodies may offer an important tool for the further evaluation of patients with rheumatoid arthritis and their individual response to treatment.

Adult↗

Isolation and characterization of mouse mutant embryonal carcinoma cells which fail to differentiate in response to retinoic acid.

Murine embryonal carcinoma cells from line PCC4.aza1R differentiate readily in response to retinoic acid. By treating PCC4.aza1R cells with the mutagen N-methyl-N' -nitro-N-nitrosoguanidine, we derived two embryonal carcinoma lines in which the cells failed to differentiate during exposure to retinoic acid. Although these dif(RA)- cells maintained the tumorigenic potential of the parental cells, they differentiated poorly in tumor form. Similarly, the tendency of dif(RA)- cells to differentiate when aggregated in vitro was diminished relative to that of PCC4.zaz1R cells. The rate of retinoic acid uptake in cells from the two mutant lines did not appear to be reduced compared with the rate in cells from the parental line; however, specific cytoplasmic retinoic acid-binding protein activity was virtually absent in both mutants. These results strengthen the view that differentiation of embryonal carcinoma cells in response to retinoic acid requires formation of retinoic acid-cytoplasmic retinoic acid-binding protein complexes.

Animals↗

Biochemical analysis of the p30's of N-, B-, and B leads to NB-tropic murine leukemia viruses of BALB/c origin.

Previous analysis of the virion proteins of an N- and a B-tropic type C virus of BALB/c mice, of 16 N-tropic recombinants (XLPN viruses) between these viruses, and of eight NB-tropic viruses derived from the B-tropic virus suggested that among these closely related viruses N-, B-, or NB-tropism was associated with the electrophoretic mobility of p30 on sodium dodecyl sulfate-polyacrylamide gels, and thus that p30 might determine this phenotype. To obtain further evidence for the association of structural markers of p30 with N-, B-, or NB-tropism, we have analyzed the p30's of these same viruses by using two-dimensional tryptic peptide mapping and slab gel isoelectric focusing. The results of these analyses suggest that (i) a single peptide unique to the N-tropic virus p30- is present in the p30 of all N-tropic recombinants; (ii) a single peptide unique to the B virus p30 is not present in p30's of the N-tropic recombinants, and this peptide is also absent in p30's of NB-tropic viruses derived from the B-tropic virus; and (iii) p30's of NB-tropic viruses possess a new tryptic peptide not found in the p30 of their B-tropic virus progenitors, and this new peptide is not found in the p30 of the N-tropic virus of BALB/c or the XLPN viruses. These results are consistent with the possibility that p30 may determine the N-, B-, or NB-tropism of murine leukemia viruses. In addition, these studies indicate that some of the N-tropic recombinants have experienced recombination within the p30 gene.

Animals↗

Fosfomycin therapy of experimental infections in mice.

Fosfomycin inhibits the development of severe pyogenic infection by Staphylococcus aureus in kidneys if administered during establishment of infection. It inhibits the development of lethal infection by Escherichia coli. It has a positive therapeutic effect on listeria infection in mice even with a fosfomycin resistant mutant.

Animals↗

Structural markers on core protein p30 of murine leukemia virus: functional correlation with Fv-1 tropism.

Tryptic peptide maps from more than 50 isolates of murine leukemia virus (MuLV) have shown that, in general, the structure of core protein p30 is highly conserved. However, a structurally variable region of p30 has been identified that is functionally associated with Fv-1 tropism. On the basis of this structural variability, MuLV strains can be classified as B-tropic, N-tropic, xenotropic, and/or as being derived from wild mice. Certain xenotropic viruses have a p30 like that of B-tropic MuLV and presumably would be subject to restriction in cells containing an Fv-In allele. Other p30 structural markers serve to distinguish the exogenous Friend, Moloney, and Rauscher viruses from endogenous MuLV. Furthermore, some MuLV strains have structural differences in their p30s that are useful as strain-specific markers. Finally, a possible sarcoma-associated alteration in the structure of p30 has been noted in the ml clone of Moloney murine sarcoma virus.

Amino Acid Sequence↗