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Biomedical subjects

K Falk

Publications and source records attributed to K Falk.

At least 109 records · Page 6Linked to original sources

Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma.

Expression of the Epstein-Barr virus (EBV) encoded nuclear antigens (EBNA 1 to 6) and membrane-associated protein (LMP) was investigated by immunoblotting in 83 nasopharyngeal carcinoma (NPC) biopsies and 25 other tumor and normal tissue specimens from the head and neck region. Fifty-eight of the 83 NPC biopsies were large enough to yield parallel data on virus DNA and viral expression. All 16 cases of clinically diagnosed and histologically confirmed NPCs from North Africa contained EBV DNA and expressed EBNA-1. Of 31 clinically diagnosed NPCs from China, 29 contained EBV DNA and 25 of these expressed EBNA-1. One control tissue biopsy from the oropharynx of NPC patients contained EBV DNA, but none expressed EBNA-1. The latent membrane protein (LMP) was detected in 22/31 of the Chinese and in 10/16 of the North African NPC biopsies. None of the NPC biopsies or control tissues expressed detectable amounts of EBNA 2 or any of the other 4 nuclear antigens which are invariably expressed in EBV-transformed B cells. A smaller number of tumors from Malaysia and East Africa exhibited a similar pattern of expression. EBV was rescued from a nude-mouse-passaged North African NPC tumor by co-cultivation of the tumor cells with umbilical cord blood lymphocytes. The tumor expressed EBNA 1 and LMP, but not EBNA 2 or the other 4 EBNAs. The resulting LCLs expressed all 6 nuclear antigens, EBNA 1 to 6 and LMP. Our data suggest that expression of the EBV genome is regulated in a tissue-specific fashion.

Animals↗

The effect of trauma to the leg on the first-pass uptake of bacteria by the lung.

Our previous studies have shown that the first-pass pulmonary uptake of lidocaine and serotonin were not impaired by bullet wounding of the leg. Since there is decreased resistance to bacterial infection with trauma, it was of interest to study the uptake of bacteria. First-pass pulmonary uptake of 51-chromium-labeled, killed Salmonella typhimurium bacteria was studied in 26 pigs. In 16 controls, four injections at hourly intervals revealed an initial uptake of 84.5% +/- 1.5 (Mean +/- S.E.M.) and a 95% first-pass uptake of 78.6% +/- 2.4, and no significant change with time. In the ten traumatized animals only the values at 5 hours were significantly lower than the controls. It is concluded that repeated injections of killed Salmonella typhimurium bacteria without trauma do not interfere with the ability of the lung to remove these bacteria during their first passage through the lung, but that with trauma to the leg do to a slight degree.

Animals↗

Progenitor and pre-B lymphocytes transformed by Epstein-Barr virus.

By rosetting with SRBC coupled to rabbit-anti-human IgM, the surface IgM-negative cells of human fetal bone marrow were enriched, and subsequently infected and transformed by Epstein-Barr virus (EBV). Single clones of the transformed cells were obtained. Ninety percent of the resulting cell clones were surface-immunoglobulin-negative, and of 8 clones which were further studied, 5 lacked intracellular, cytoplasmic Ig as measured by immunofluorescence. Control cell clones derived from the same material without pre-selection expressed surface Ig and also secreted Ig. Utilization of a panel of B-cell-specific monoclonal antibodies (MAbs) showed no difference between the cell clones expressing surface Ig and those that did not. The progenitor B-cell lines did not show a phenotype resembling that of cell lines derived from B-cell malignancies, such as high agarose clonability. In spite of their immature Ig-phenotype, these clones showed rearrangement of at least one heavy chain Ig-allele. Efforts to induce differentiation in these clones were unsuccessful. These clones may represent progenitor B cells, or B cells with faulty heavy-chain rearrangement. EBV can apparently be used as a tool to derive cell lines representing different levels of B-cell differentiation, and can also transform immature B cells, which may be useful in the analysis of B-cell differentiation.

Antibodies, Monoclonal↗

Lymphoblastoid cell lines and Burkitt-lymphoma-derived cell lines differ in the expression of a second Epstein-Barr virus encoded nuclear antigen.

Twenty-seven Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and 27 EBV-carrying Burkitt-lymphoma-derived lines were analyzed for expression of the second EBV-encoded nuclear antigen (EBNA-2) by immunoblotting and anticomplement immunofluorescence with EBNA-2-specific sera. While all lymphoblastoid cell lines expressed EBNA-2, only 10 of the 27 BL lines were EBNA-2-positive. Comparison of the EBNA-2 coding BamHI W-, Y- and H-fragments of EBV-DNA in the different cell lines by restriction enzyme analysis suggests that EBNA-2 negativity is due either to sequence diversity or to a deletion in the BamHI WYH region.

Antigens, Viral↗

Epstein-Barr virus transformation of human pre-B cells.

In vitro infection of human B lymphocytes with Epstein-Barr virus (EBV) results in establishment of B lymphoblastoid cell lines that reflect normal B cell phenotypes. In this study we have investigated whether immature B cells from fetal bone marrow and liver can serve as targets for EBV. The fetal bone marrow cells were readily transformed by EBV. Among the resulting cell lines, five were surface Ig (sIg)-negative. Three B cell-associated antigens defined by monoclonal antibodies were expressed to the same extent on the fetal cell lines, whether they belonged to the sIg- or sIg+ group. The various differentiation stages that these cell lines may represent are discussed.

Antibody-Producing Cells↗

[Human albumin or dextran 60 for the restoration of the blood volume, with special reference to the colloid osmotic pressure (author's transl)].

The high cost and limited availability of human albumin as a plasma substitute make it desirable to limit its use to special cases and to replace it by inexpensive and easily obtainable colloids. Patients about to undergo major abdominal surgery were given either human albumin or dextran 60 during the operation and for three days afterwards. Although both groups received the same quantity of colloidal plasma substitutes they differed significantly in respect to the serum albumin and protein concentrations. However, the osmotic pressure, for the maintenance of which the albumin fraction is mainly responsible, showed a marked fall in both groups, indicating that human albumin is not superior to dextran. All other parameters, particularly the clotting mechanism, remained within the normal range and did not differ between the two groups. The results of the study, in conjunction with the known facts regarding the metabolism and function of albumin, suggest that dextran 60 can adequately replace human albumin in a large number of cases. Great importance belongs to measurement of the colloid osmotic pressure.

Blood Proteins↗

[Measurement of colloid osmotic pressure. Experience with the IL 186 Weil-Oncometer system].

The crystalloid colloid fluid controversy has increased the interest in colloidoncotic pressure (COP) of plasma as a significant parameter in fluid exchange. Equipments for direct measurement of COP are now available and their value has to be determined now. Based on own experiences the handling, advantages and disadvantages of the WEIL-Oncometer are described and recommendations for improving the system are made.

Colloids↗

Relationship between Epstein-Barr virus (EBV)-production and the loss of the EBV receptor/complement receptor complex in a series of sublines derived from the same original Burkitt's lymphoma.

Virus production, EBV (P3HR-1 substrain) superinfectability, IdUrd inducibility, EBV receptor and complement (C3) receptor expression were assessed in two independently maintained jijoye lines, the derived P3HR-1 clone that releases a growth inhibitory and cytopathic, non-transforming viral mutant, and in non-producer sublines derived from the P3HR-1 line by the spontaneous cessation of virus production. Both jijoye lines were superinfectable, inducible, and carried EBV and C3 receptors. Virus-producing P3HR-1 cells and recently derived non-producer sublines lacked EBV-receptors and C3 receptors, could not be superinfected, but were IdUrd inducible. Two long-passaged, non-producer sublines of P3HR-1 reexpressed EBV and C3 receptors to an equal degree (different in the two sublines). EBV-superinfectability became partially reestablished in the subline with the higher expression of EBV and C3 receptors. These findings support the hypothesis that the EBV-receptor/C3 receptor negativity of the producer P3HR-1 sublines and their recent non-producer derivatives is due to negative selection by the growth-inhibitory, cytopathic P3HR-1 virus variant. The closely linked disappearance and reappearance of EBV-receptors and complement receptors gives further support to the idea that these two receptors are either identical or closely linked constituents of the cell membrane.

Antigens, Viral↗