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Biomedical subjects

E Hofer

Publications and source records attributed to E Hofer.

At least 19 recordsLinked to original sources

Candidate natural killer cell receptors.

Among the high points of immunological discovery has been the identification of antigen-recognizing receptors on B and T cells. Of the lymphocyte populations, only the NK cell receptor remains unknown. Consequently, any newly-recognized, cell-surface molecules expressed selectively on NK cells, especially ones that can transmit a signal to the cell upon appropriate ligand interaction, are possible candidates. This article describes such candidates.

Animals

Analysis of some virulence factors of Vibrio vulnificus isolated from Rio de Janeiro, Brazil.

Twenty strains of V. vulnificus isolated from the environment were investigated for characteristics related to their infectivity such as colonial morphology, enzymatic activity and animal assays. The presence of DNase, chitinase, amylase, lecithinase and gelatinase was observed in 100% of the strains, haemolytic activity was absent, and variable results were obtained in elastase, collagenase and chondroitinase. In the animal assays, 70% of the strains were lethal to adult mice, while 45% caused fluid accumulation in suckling mice. Although all strains had opaque colonies, only 3 of the 20 had the three enzymes elastase, collagenase and gelatinase, and only one of these was virulent in animal assays.

Animals

Cellular Vmax reflects both membrane properties and the load presented by adjoining cells.

This study was designed to test the hypothesis that the electrical load seen at a microelectrode impalement site is sensitive to the direction of propagation of the approaching wavefront as a reflection of an altered spatial relationship between the impalement site and the surrounding microscopic electrical boundaries located up- and downstream. These boundaries correspond to the different sizes and shapes of the impaled and surrounding cells as well as to the distribution of the associated electrical connections between the cells. The effects of changes in these geometric relationships on maximum rate of rise of transmembrane potential (Vmax) were investigated in canine ventricular muscle by measuring Vmax in different cells while the direction of propagation was changed from along the longitudinal axis to the transverse axis of the fibers or the direction of conduction was reversed along either of these axes. Comparison of the Vmax values for longitudinal propagation (LP) and transverse propagation (TP), each in one direction, showed that TP Vmax was significantly greater than LP Vmax (P < 0.001). However, the values of Vmax were different from cell to cell during LP (93-139 V/s) and TP (110-181 V/s). The absolute values of LP Vmax and TP Vmax at the same site varied independently of each other, e.g., some of the lowest LP Vmax values occurred at the same site as the highest TP Vmax values. Furthermore, at the same site, Vmax changed considerably when propagation was maintained along the longitudinal axis but the direction of conduction was reversed. Similar prominent changes in Vmax occurred when the direction was reversed along the transverse axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

A new superfamily of lymphoid and melanoma cell proteins with extensive homology to Schistosoma mansoni antigen Sm23.

A novel cDNA clone termed R2 was isolated by subtractive hybridization of a cDNA library of phytohemagglutinin (PHA)/phorbol myristate acetate-stimulated Jurkat cells and by rescreening a cDNA library of PHA-stimulated peripheral blood lymphocytes. It hybridizes to a single mRNA species of about 2.2 kb, which is inducible in lymphoid cells and codes for a protein of 267 amino acids which contains four potential transmembrane domains. A computer-aided comparison showed strong homology to four other membrane proteins, the pan B cell marker CD37, the pan leukocyte marker CD53, the melanoma antigen ME491 and, surprisingly, the Schistosoma mansoni antigen Sm23. The four human proteins share a number of additional similarities in their overall structure. These include identical spacing of the transmembrane domains, similar hydrophobicity plots, possible N-linked glycosylation sites of similar number and position as well as similar distribution of the cysteine residues. The majority of these characteristics are still conserved in the evolutionary most distant member of this family, the Schistosoma mansoni antigen Sm23. Here we introduce this new protein superfamily and characterize the inducible, lymphoid-specific member R2.

Amino Acid Sequence

Characterization of the human cyclophilin gene and of related processed pseudogenes.

The human cyclophilin gene was isolated from a genomic library derived from leucocyte DNA and sequenced. The gene contains five exons and four introns. The amino acid sequence deduced from the exons matches perfectly the one previously determined from the T-cell cyclophilin cDNA. A TATA box is visible in the promoter region and putative Sp1 binding sites are also found there as well as in the first intron. Six members of the middle repetitive Alu gene family are present in one or other orientation in the non-coding regions of the cyclophilin gene. Hybridisation of genomic DNA to probes derived from the promoter region or the first intron indicates that the cyclophilin gene is present as a single copy in the human haploid genome. Seven other cyclophilin-related DNA clones isolated from the same library were also characterized. They show a high degree of similarity to the cyclophilin cDNA and are colinear to it. However, multiple genetic lesions, often including deletion and/or insertion events which modify the reading frame, are found in these clones which are therefore likely to represent processed pseudogenes.

Amino Acid Sequence

Transcription and expression of transforming growth factor type beta in the skin of progressive systemic sclerosis: a mediator of fibrosis?

Progressive systemic sclerosis is characterized by extensive generalized fibrotic destruction associated with increased accumulation of collagen and other extracellular macromolecules in the skin and other involved organs. It has been suggested that mediators released from mononuclear or endothelial cells play a critical role in the initial activation of connective tissue metabolism. Transforming growth factors beta(TGF-beta 1, TGF-beta 2) mediate the inhibition of epithelial cell proliferation and the induction of fibronectin and collagen gene expression. Therefore, we investigated the distribution of both TGF-beta 1 and TGF-beta 2 mRNA and the final proteins in PSS skin in comparison with other inflammatory dermatoses and healthy controls by means of in situ hybridization and immunohistochemistry. Our studies revealed TGF-beta 1 and -beta 2 mRNA in dermal and subcutaneous infiltrating cells in both acute and chronic PSS, but also in the other inflammatory skin disorders. In the vicinity of this infiltrate single TGF-beta positive fibroblasts could be found in acute PSS. The cytoplasm of epithelial cells of all skin adnexa showed TGF-beta transcripts and no apparent differences were seen in the distribution and number of autoradiographic grains between diseased and healthy skin samples. Especially, we could demonstrate abundant expression of TGF-beta 1/2 in epithelial hair follicle cells of the outer root sheath. Generally, the expression of TGF-beta 2 was less abundant than TGF-beta 1. Immunohistochemical studies revealed the same distribution pattern of the final proteins. Our data indicate that TGF-beta expression in infiltrating cells is not a specific feature of fibrotic disease, but seems to be associated with highly proliferating cells in general, perhaps functioning as common mediator in regulation of cellular physiology with special importance for negative control of cell growth.

Adult

Transforming growth factor-beta inhibits the generation of cytotoxic T cells in virus-infected mice.

The immunoregulatory effects of human recombinant transforming growth factor (rTGF) beta 1 and human recombinant glioblastoma-derived T cell suppressor factor (rG-TsF)/TGF beta 2 was investigated in mice infected with lymphocytic choriomeningitis virus (LCMV) or vaccinia virus. Starting on the day of infection, i.p. injections of 1 microgram/day or rTGF-beta 1 or rG-TsF/TGF-beta 2 suppressed the generation of virus specific CTL. The effect of TGF-beta on CTL (day 8) was less pronounced when TGF-beta treatment was delayed for 3 days after LCMV infection. rG-TsF/TGF-beta 2 also has an inhibiting effect on CTL-mediated disease in LCMV-infected mice: it prolonged the survival time of mice infected with LCMV and reduced the local swelling reaction after infection into the footpad. These results indicate that rTGF-beta 1 and rG-TsF/TGF-beta 2 influence T cell immune reactivity in vivo.

Animals

Antimicrobial resistance among Salmonella serovars isolated from different sources in Brazil during 1978-1983.

A total of 748 Salmonella strains (97 serovars) isolated from human (291), animal (119), environmental (141), food (102) and animal feed (95) sources were examined for resistance to 9 antimicrobial agents. Most of the human isolates were from hospitalized patients (282). An overall resistance rate of 98.8% was determined with 100% for human and environmental isolates. Resistance to sulfadiazine (87.7%) was most common, followed by streptomycin (61.2%), ampicillin (39%) and trimethoprim-sulphamethoxazole (37.9%). Fifty one different resistance patterns were identified with Su (164 strains), Su-Sm (122) and Su-Sm-Tc-Cm-Km-Ap-Nx-Gm-Tm (95) predominating, the latter occurring only in human isolates. Multiple resistance was most frequently found among human isolates, particularly in S. derby and S. typhimurium strains. The relationship between antibiotic resistance, serovar and source of isolation of the Salmonella strains is discussed.

Animals

The glioblastoma-derived T cell suppressor factor/transforming growth factor-beta 2 inhibits T cell growth without affecting the interaction of interleukin 2 with its receptor.

Human glioblastoma cells secrete a peptide termed glioblastoma-derived T cell suppressor factor (G-TsF) which inhibits T cell activation. Recently, purification and cloning of G-TsF revealed that G-TsF is identical to transforming growth factor-beta 2. As shown here, G-TsF suppresses the growth of an ovalbumin-specific mouse T helper cell clone (OVA-7T) independently of the stimulus used being either (a) antigen in the presence of antigen-presenting cells, or (b) interleukin 2 (IL2) or (c) phorbol ester and calcium ionophore. Furthermore, in the presence of antibodies against IL2 receptors, G-TsF was able to suppress the residual proliferation still observed when OVA-7T were stimulated with phorbol ester/ionophore. G-TsF failed to inhibit the release of IL3 from OVA-7T activated with IL2. Taken together, the data provide evidence that G-TsF does not directly interfere with interactions of IL2 with its receptor but rather inhibits T cell activation by interfering with an as yet unidentified pathway used by both IL2 and phorbol ester/ionophore. When analyzing different monokines and lymphokines for its effect on G-TsF-induced suppression of T cell growth the only factor found to partially neutralize the effect of G-TsF was tumor necrosis factor-alpha.

Animals

The structure of procalcitonin of the salmon as deduced from its cDNA sequence.

Oligonucleotide probes based on the known amino acid sequence of salmon calcitonin were used to screen a cDNA library obtained from ultimobranchial glands of salmon for clones encoding salmon calcitonin. From the cDNA sequence of strongly hybridizing clones the complete primary structure of the calcitonin precursor could be deduced. Its overall structure is identical with the structures of procalcitonins from other vertebrates and has the highest homology with the chicken precursor.

Amino Acid Sequence

Complementary DNA for human glioblastoma-derived T cell suppressor factor, a novel member of the transforming growth factor-beta gene family.

Human glioblastoma cells secrete a peptide, termed glioblastoma-derived T cell suppressor factor (G-TsF), which has suppressive effects on interleukin-2-dependent T cell growth. As shown here, complementary DNA for G-TsF reveals that G-TsF shares 71% amino acid homology with transforming growth factor-beta (TGF-beta). In analogy to TGF-beta it is apparently synthesized as the carboxy-terminal end of a precursor polypeptide which undergoes proteolytic cleavage to yield the 112 amino-acid-long mature form of G-TsF. Comparison of the amino-terminal sequence of G-TsF with that of porcine TGF-beta 2 and bovine cartilage-inducing factor B shows complete homology, which indicates that we have cloned the human analogue of these factors. It is tempting to consider a role for G-TsF in tumor growth where it may enhance tumor cell proliferation in an autocrine way and/or reduce immunosurveillance of tumor development.

Amino Acid Sequence

T cell suppressor factor from human glioblastoma cells is a 12.5-kd protein closely related to transforming growth factor-beta.

T cell suppressor factor produced by human glioblastoma cells inhibits T cell proliferation in vitro and more specifically interferes with interleukin-2 (IL-2)-dependent T cell growth. Here we report the purification of this factor from conditioned medium of the human glioblastoma cell line 308. Amino-terminal sequence analysis of the 12.5-kd protein demonstrates that eight out of the first 20 amino acids are identical to human transforming growth factor-beta. Purified glioblastoma-derived T cell suppressor factor and transforming growth factor-beta from porcine platelets inhibit both IL-2-induced proliferation of ovalbumin-specific T helper cells and lectin-induced thymocyte proliferation with similar specific activities. If released by glioblastoma cells in vivo, the factor may contribute to impaired immunosurveillance and to the cellular immunodeficiency state detected in the patients.

Amino Acid Sequence

Complementary DNA for human T-cell cyclophilin.

Complementary DNA encoding human cyclophilin, a specific cyclosporin A-binding protein, has been isolated from the leukemic T-cell line Jurkat and sequenced. Comparison of the deduced amino acid sequence with the previously determined sequence of bovine thymus cyclophilin reveals only three differences: an additional amino acid at the carboxy terminus end and two internal changes. RNA transfer blot analysis indicates an mRNA size of approximately 1 kb for human T-cell cyclophilin. Phytohaemagglutinin and phorbol myristate acetate induction of T cells treated or not with cyclosporin A affects only marginally the level of cyclophilin mRNA. Southern blot analysis of human genomic DNA digested with different restriction enzymes strongly suggests the existence of a multigene family for cyclophilin.

Amino Acid Sequence

Analysis of single channel currents with a microprocessor based device.

Data evaluation of single channel currents obtained from artificial black lipid membranes and with the patch clamp method is an important part of every single channel study, but it is a time consuming part often exceeding the time for experimentation and recording by far. We describe here a microprocessor based device, which allows the experimentator to analyse in a simple way the distribution of current levels in a single channel trace (amplitude-histogram analysis of single channel currents) either online, or offline. Current levels are sampled at a constant frequency of 6 kHz and the relative frequencies of occurrence of these current levels are displayed as a histogram on the screen of an analog or digital storage oscilloscope. The data reducing algorithm of this analyser eliminates the requirement of large amounts of mass storage that normally is needed for digital amplitude-histogram analysis of single channel recordings. Examples of evaluation for both a voltage operated cation-channel and a blockage of a potassium channel by tetraethylammoniumchloride (TEA) are given.

Animals

Catheter jet ventilation, a favorable technique during resection of the central tracheobronchial system.

Experience with catheter jet ventilation as an optimal ventilation technique during the critical phase of resection in the region of the central tracheobronchial system (bifurcational resections, extended resections in the bifurcational region) in 9 patients is described. For this technique we use a simple and cheap system consisting of a pressure-reduction valve, an interruption valve manually worked with a pistol handle, 2 manometers and a thin plastic catheter as a jet. In 8 cases the anesthesiologic management during the jet ventilation phase, ranging between 35 and 150 minutes, was without any problem; the one complication and the possible way of solving similar accidents are discussed. In comparison with the conventional technique, catheter jet ventilation gives the surgeon the possibility of complete freedom of action during suturing of the airway anastomosis.

Bronchi