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Biomedical subjects

B Friedrich

Publications and source records attributed to B Friedrich.

At least 109 records · Page 6Linked to original sources
PubMed1989

Evidence that a kinase distinct from protein kinase C induces CD3 gamma-subunit phosphorylation without a concomitant down-regulation in CD3 antigen expression.

An immediate consequence of Ag-specific activation of T cells is phosphorylation of the gamma-subunit of the CD3 gamma-chain. There is good evidence that the kinase that mediates CD3 gamma-chain phosphorylation is protein kinase C (pkC). It has also been proposed that the interaction between pkC and CD3 gamma-chains controls the cell surface expression of the antigen receptor/CD3 Ag complex. In the present study we present data relevant to these two points. Thus we show that CD3 gamma-subunit phosphorylation can be triggered by the calcium ionophore ionomycin. However, as judged by several criteria, ionomycin does not stimulate cellular pkC. Accordingly, ionomycin must regulate phosphorylation of the CD3 Ag by a kinase distinct from pkC. The phosphorylation of CD3 Ag induced by ionomycin is not accompanied by a modulation of the cell surface expression of CD3 molecules which implies that CD3 gamma-chain phosphorylation is not a sufficient signal for the endocytosis of the CD3/Ag receptor complex.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Evidences for protein kinase C. Activation in T lymphocytes by stimulation of either the CD2 or CD3 antigens.

Phosphorylation of protein kinase C (PKC) substrates in T lymphocytes was analyzed after stimulation with specific pairs of anti-CD2 monoclonal antibodies (mAb) or an anti-CD3 mAb. The results show that the appropriate stimulation of both CD2 or CD3 antigens results in phosphorylation of a 80-kDa putative PKC substrate and that this phosphorylation event is sensitive to a PKC inhibitor, sphinganine. CD2- and CD3-dependent phosphorylation was found to be strongly dependent on an extensive cross-linking of surface antigens. The biological importance of cross-linking of CD2 and CD3 was also evident for other biological responses such as interleukin 2 production and induction of an autocrine growth response. Finally, we also present evidence for interaction between the CD2 and CD3 signal transducing pathways.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Increased cyclic AMP levels block interleukin 2-induced protein kinase C substrate phosphorylation but not the mitogenic response.

Protein kinase C (PKC) has been implicated in the signaling of a number of cellular responses including activation of T cells. In the present report we have evaluated the effect of increased cAMP levels on PKC activation after stimulation of two distinct receptor systems on normal human T cells. PKC substrate phosphorylation can be induced via either the CD3 complex or, to a limited extent, the high affinity interleukin 2 (IL 2) receptor. Substrate phosphorylation via both pathways is shown to be blocked by increased intracellular levels of cAMP. In accordance with previous reports, the CD3-dependent autocrine proliferative response could also be blocked by a cAMP-dependent mechanism. Since direct activation of PKC with a phorbol ester reversed this inhibition, a causal relationship between cAMP-dependent PKC blockage and inhibition of the CD3 response is suggested. In contrast, however, initiation of IL 2-induced proliferation was essentially unaltered by cAMP and could progress in the apparent absence of PKC activity. Thus, this study indicates that IL 2-induced proliferation can under such conditions be completely uncoupled from IL 2-induced PKC activation in normal T cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

A rapid separation procedure to analyse phosphorylation of two putative protein kinase C substrates in intact lymphocytes.

Activation of protein kinase C (PKC) has been implicated in the regulation of many biological processes including the regulation of T and B lymphocyte responses. A direct means of studying activation of this kinase is to analyse specific phosphorylation events of cellular substrates. In the present report we describe a fractionation method that allows quantitative analysis of phosphorylation of two distinct PKC substrates using normal human T cells and T-cell tumour lines. This method, which selectively visualizes PKC-dependent phosphorylation of both an 80- and a 19-kDa substrate, involves three simple fractionation steps and allows a large number of samples to be analysed simultaneously. Since specific antibodies to these cellular substrates are not commonly available, the present method provides an alternative approach which makes it feasible to use phosphorylation of the 19- and 80-kDa proteins as a sensitive marker for PKC activation. Finally, in a cellular system where PKC-mediated phosphorylation of these substrates can be studied without prior purification, the present method results in greatly improved resolution of these phosphorylation events.

Chromatography, Ion Exchange↗
PubMed1989

An rpoN-like gene of Alcaligenes eutrophus and Pseudomonas facilis controls expression of diverse metabolic pathways, including hydrogen oxidation.

Pleiotropic mutants of Alcaligenes eutrophus with the phenotype Hno- have been characterized previously. They are deficient in several diverse metabolic activities, including hydrogen oxidation, nitrate and urea assimilation, denitrification, and various substrate transport systems. Phenotypically similar mutants were identified among hydrogenase-deficient strains of Pseudomonas facilis. The Tn5-labeled hno gene was cloned from a genomic DNA library of A. eutrophus and used to identify the corresponding unimpaired wild-type DNA sequence. The recombinant plasmid pCH148 contained an insert of 12.3 kilobase pairs and was shown to restore the Hno+ phenotype to mutants of A. eutrophus and P. facilis. A cosmid isolated from a DNA library of P. facilis also exhibited intergeneric Hno-complementing activity. The cloned hno loci from both organisms showed DNA homology by Southern blot hybridization. A subclone of pCH148 which contained a 6.5-kilobase-pair insert was constructed. The resulting hybrid, pCH170, not only was able to complement Hno- mutants but also relieved glutamine auxotrophy in NtrA- mutants of enteric bacteria. This suggests that the hno gene product from A. eutrophus is functionally similar to the NtrA protein, which has been identified as a novel sigma factor (sigma 54) of RNA polymerase.

Alcaligenes↗
PubMed1989

Genetic determinants of a nickel-specific transport system are part of the plasmid-encoded hydrogenase gene cluster in Alcaligenes eutrophus.

Nickel-deficient (Nic-) mutants of Alcaligenes eutrophus requiring high levels of nickel ions for autotrophic growth with hydrogen were characterized. The Nic- mutants carried defined deletions in the hydrogenase gene cluster of the indigenous pHG megaplasmid. Nickel deficiency correlated with a low level of the nickel-containing hydrogenase activity, a slow rate of nickel transport, and reduced activity of urease. The Nic+ phenotype was restored by a cloned DNA sequence (hoxN) of a megaplasmid pHG1 DNA library of A. eutrophus H16. hoxN is part of the hydrogenase gene cluster. The nickel requirement of Nic- mutants was enhanced by increasing the concentration of magnesium. This suggests that the Nic- mutants are impaired in the nickel-specific transport system and thus depend on the second transport activity which normally mediates the uptake of magnesium.

Alcaligenes↗
PubMed1989

[Resorbable implants and their use exemplified by fracture of the head of the radius].

First a short survey of the variety of experiments concerning absorbable implants is given. The result of those experiments, especially with large implants are still quite unsatisfactory. For small osteosynthesis the development of Polydioxanon-Pins seems to open new perspectives of therapy. Also some selected indications in the field of hand surgery as well as maxillary surgery are mentioned. Promising characteristics of PDS-Pins, such as gentle application, complete absorbability, no late infections and no removal of metal plates, made us implant these pins in eight patients aged 35 to 58 suffering from radial head fractures (type Ib and Ic according to Vogt). Early functional treatment showed very good results. Two exemplary cases are illustrated.

Female↗
PubMed1989

[Damage to the arm plexus caused by atypical callus formation following clavicular fracture].

Secondary brachial plexus paralysis do not occur very often as a consequence of collar bone fractures. It is difficult to detect the cause, especially as there can be quite a long interval between the trauma and occurrence of the first symptoms. The problem is discussed with reference to a case observed by the authors: atypical callus formation 7 weeks after a clavicular fracture that was conservatively treated and had healed had led to brachial plexus damage. The patient was treated 11 months later by a trauma surgeon. Once the callus had been removed she was finally free of symptoms.

Adult↗
PubMed1988

The role of protein kinase C in early activation vs. growth of T lymphocytes.

Protein kinase C (PKC) has been implicated in the signaling of a number of cellular responses including activation of T cells. In an approach to study the role of PKC in both early activation and interleukin 2 (IL2)-dependent growth, we have used in vivo phosphorylation of endogenous substrates as a marker for PKC activation. In the present report the requirements for CD3-specific activation of PKC are defined, and it is shown that the conditions required for optimal activation coincide with the induction of a proliferative response. Moreover, it is also shown that IL2 receptor interactions induce only low levels of PKC substrate phosphorylation and that IL2 does not cooperate with CD3-specific signals on the level of PKC activation.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Activation-dependent phosphorylation of endogenous protein kinase C substrates in quiescent human T lymphocytes.

Activation of quiescent human T lymphocytes with phorbol ester, synthetic diacylglycerol, or an antibody specific for the antigen receptor associated CD3 antigen resulted in a rapid phosphorylation of a Mr 80,000 (termed 80K) and a Mr 19,000 (termed 19K) cellular protein. The 80K (pI 4.4-5.1) protein was evidently analogous to a previously described 80K protein, which is a putative in vivo substrate for the Ca2+-activated phospholipid-dependent protein kinase (PK.C), while the identity of the 19K protein is unknown. We present evidences that the 19K protein is variably phosphorylated on serine residues and that phosphorylation involves activation of the PK.C pathway. The biological significance of these phosphorylation events was suggested both by the ligand specificity and the correlation with subsequent induction of cellular proliferation.

Enzyme Activation↗
PubMed1988

Transfer and expression of lithoautotrophy and denitrification in a host lacking these metabolic activities.

The conjugative 450-kilobase-pair megaplasmid pHG1 from Alcaligenes eutrophus H16 was transferred to the herbicide-degrading soil bacterium A. eutrophus JMP134. This transfer was achieved by means of RP4 mobilization and a Tn5-Mob insertion provided in trans on the megaplasmid replicon. Although kanamycin-resistant transconjugants also occurred with other gram-negative species such as Rhizobium, Agrobacterium, and thiobacteria, A. eutrophus JMP134 was the only recipient which stably maintained the megaplasmid. pHG1-containing transconjugants derived from JMP134 expressed all metabolic functions associated with the plasmid: the ability to oxidize hydrogen through catalysis of two hydrogenases, to assimilate carbon dioxide via the Calvin cycle pathway, and to grow with nitrate anaerobically. All of these metabolic activities were absent in the original strain JMP134.

Journal Article↗
PubMed1988

[Results and assessment of computerized tomography in the initial diagnosis in polytrauma].

In a period from 1984 to 1986 (T-scan was used as acute diagnostic in 74 polytraumatized patients. The patients were brought by emergency car or helicopter during or shortly after shock treatment directly to the computerized tomography. In all patients several regions of the body (head, thorax, abdomen, extremities) were examined in the (T-scan. Nearly two third of the patients (n = 58) were examined because of an uncertain abdominal trauma. In 27 of these patients pathological results were found, which have been followed by immediate laparotomy. Besides the high efficiency one more advantage of the method is its non-invasivity.

Abdominal Injuries↗
PubMed1987

Cloning of plasmid genes encoding resistance to cadmium, zinc, and cobalt in Alcaligenes eutrophus CH34.

A 238-kilobase-pair plasmid, pMOL30, confers resistance to cadmium, zinc, and cobalt salts in Alcaligenes eutrophus CH34. After Tn5 mutagenesis, restriction nuclease analysis, and Southern DNA-DNA hybridization, a 9.1-kilobase-pair EcoRI fragment was found to harbor all of these resistance properties and was cloned into the broad-host-range hybrid plasmid pRK290. When transferred to a plasmid-free derivative of CH34, the hybrid plasmid conferred the same degree of resistance as the parent plasmid pMOL30. In two other Alcaligenes strains, the hybrid plasmid was expressed, but to a lower degree than in CH34 derivatives.

Alcaligenes↗
PubMed1986

Interleukin-2 versus phorbol-ester-induced cellular events in normal T-lymphocytes.

Activation of primary T-lymphocytes (T-cells) is dependent on interactions with the T3/T-cell antigen receptor complex which results in expression of cell surface receptors for the lymphocytotrophic growth factor interleukin-2 (IL-2). In the present communication we have compared the cellular responses to phorbol ester with IL-2-induced cellular responses. Thus, the effect of respective ligand on T-cell growth, the level of expression and composition of two distinct affinity classes of IL-2 receptors, and phosphorylation of an 80,000 mol. wt cellular substrate for the Ca2+-dependent, phospholipid-dependent protein kinase C (PK-C) was analysed. The results demonstrate that only the high affinity IL-2 receptor class is induced by phorbol esters and that both IL-2 and cell surface expression of its high affinity receptor is required for induction of low affinity IL-2 receptors. Moreover, IL-2 receptor signalling seems not to involve activation of PK-C and the results suggest that another intracellular pathway, distinct from the PK-C pathway which induces high affinity IL-2 receptors, is employed in the transmission of IL-2 growth promoting signals.

Cells, Cultured↗
PubMed1986

Genetics of hydrogenase from aerobic lithoautotrophic bacteria.

Aerobic facultatively autotrophic hydrogen bacteria are distinguished on the basis of their hydrogen-oxidizing enzyme system (Hox). The major group, represented by Paracoccus denitrificans and Pseudomonas facilis, contains a membrane-bound, electron transport-coupled protein. Species of Nocardia are characterized by the possession of a cytoplasmic NAD-dependent hydrogenase. Both enzymes are present in strains of Alcaligenes. All hydrogenases from lithoautotrophs are H2-consuming nickel-iron-sulfur proteins. Despite these common characteristics, hydrogenases differ in catalytic and molecular properties, in particular in the regulation of enzyme synthesis. Hydrogenase formation is either inducible by H2 (e.g. P. denitrificans strain F1, Alcaligenes hydrogenophilus) or subject to derepression in response to the supply of reductant, temperature, and oxygen (e.g. Alcaligenes eutrophus). The only plasmid-encoded Hox function has been conclusively identified in species of Alcaligenes. Structural and regulatory hox genes reside on megaplasmids, ranging in size between 400 and 500 kilobase pairs (kb). Most of the plasmids are self-transmissible by conjugation. Hox genes of A. eutrophus H16 have been localized by plasmid curing, genetic transfer, molecular cloning and analysis of plasmid deletions and insertions. They seem to be clustered in a DNA sequence of approximately 50 kb, representing several transcriptional units. In addition, a chromosomally encoded regulatory function is required for the expression of plasmid-linked hox genes. Plasmid pHGl of A. eutrophus H16 has been transferred to the non-lithoautotrophic soil bacterium JMP222. Both hydrogenases are expressed in the new host. The current state of hydrogenase genetics in Alcaligenes is discussed in reference to hydrogenase systems of other lithoautotrophic bacteria.

Alcaligenes↗
PubMed1986

Molecular cloning of structural and regulatory hydrogenase (hox) genes of Alcaligenes eutrophus H16.

A gene bank of the 450-kilobase (kb) megaplasmid pHG1 from the hydrogen-oxidizing bacterium Alcaligenes eutrophus H16 was constructed in the broad-host-range mobilizable vector pSUP202 and maintained in Escherichia coli. hox DNA was identified by screening the E. coli gene bank for restoration of hydrogenase activity in A. eutrophus Hox mutants. Hybrid plasmids that contained an 11.6-kb EcoRI fragment restored soluble NAD-dependent hydrogenase activity when transferred by conjugation into one class of Hos- mutants. An insertion mutant impaired in particulate hydrogenase was partially restored in Hop activity by an 11-kb EcoRI fragment. A contiguous sequence of two EcoRI fragments of 8.6 and 2.0 kb generated Hox+ recombinants from mutants that were devoid of both hydrogenase proteins. hox DNA was subcloned into the vector pVK101. The resulting recombinant plasmids were used in complementation studies. The results indicate that we have cloned parts of the structural genes coding for Hos and Hop activity and a complete regulatory hox DNA sequence which encodes the thermosensitive, energy-dependent derepression signal of hydrogenase synthesis in A. eutrophus H16.

Alcaligenes↗
PubMed1986

[Arterial occlusions following Ender nailing of proximal femoral fractures].

On assessing the 160 cases of nailing according to the method of Ender and Simon-Weidner ("Ender Nailing") during a five-year period we noticed three cases (1.8%) where arterial occlusion had occurred postoperatively on the operated side. The article describes the cases and discusses the possible aetiological factors and consequences which may result therefrom with regard to therapy. Particular attention is given to a discussion on the possible influence exercised by the form of thromboembolism prophylaxis.

Aged↗