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Biomedical subjects

M Raab

Publications and source records attributed to M Raab.

At least 55 records · Page 3Linked to original sources
PubMed1996

[Management of abdominal stab wounds].

In general, laparotomy is accepted as treatment of choice for abdominal shot wounds. However, the management of abdominal stab wounds is controversial. In order to study the concept of laparotomy for penetrating abdominal trauma our patient collective was analyzed retrospectively. From 1st January 1985 to 31st December 1993 we performed laparotomy in 30 cases of abdominal stab wounds. 24 patients were victims of violence. In 6 patients the cause of injury was a suicidal attempt. Laparotomy was negative in 27% of cases. In most cases explorative laparotomy showed injuries of the vessels (n = 12) and the intestines (n = 9). The mortality rate was 6.7%. None of the fatal cases was caused by negative laparotomy. During a mean follow-up time of 54 months none of the patients showed disorders of late onset after negative laparotomy. Because of the limited diagnostic possibilities to rule out intestine injury and minimal morbidity of negative laparotomies we continue to favour laparotomy in the management of penetrating abdominal trauma.

Abdominal Injuries↗
PubMed1996

[Geriatric surgery--stomach carcinoma in patients older than 70].

In a prospective study the results of surgery for gastric carcinoma were analysed comparing patients under 70 years of age (n = 384) and patients over 70 years of age. The surgical treatment for gastric cancer resulted in increased mortality in patients over 70 years of age due to severe risk factors. Optimization of anociassociation and stageoriented cancer treatment may further prolong survival of patients over 70 years of age with this malignancy.

Aged↗
PubMed1995

p56Lck and p59Fyn regulate CD28 binding to phosphatidylinositol 3-kinase, growth factor receptor-bound protein GRB-2, and T cell-specific protein-tyrosine kinase ITK: implications for T-cell costimulation.

T-cell activation requires cooperative signals generated by the T-cell antigen receptor zeta-chain complex (TCR zeta-CD3) and the costimulatory antigen CD28. CD28 interacts with three intracellular proteins-phosphatidylinositol 3-kinase (PI 3-kinase), T cell-specific protein-tyrosine kinase ITK (formerly TSK or EMT), and the complex between growth factor receptor-bound protein 2 and son of sevenless guanine nucleotide exchange protein (GRB-2-SOS). PI 3-kinase and GRB-2 bind to the CD28 phosphotyrosine-based Tyr-Met-Asn-Met motif by means of intrinsic Src-homology 2 (SH2) domains. The requirement for tyrosine phosphorylation of the Tyr-Met-Asn-Met motif for SH2 domain binding implicates an intervening protein-tyrosine kinase in the recruitment of PI 3-kinase and GRB-2 by CD28. Candidate kinases include p56Lck, p59Fyn, zeta-chain-associated 70-kDa protein (ZAP-70), and ITK. In this study, we demonstrate in coexpression studies that p56Lck and p59Fyn phosphorylate CD28 primarily at Tyr-191 of the Tyr-Met-Asn-Met motif, inducing a 3- to 8-fold increase in p85 (subunit of PI 3-kinase) and GRB-2 SH2 binding to CD28. Phosphatase digestion of CD28 eliminated binding. In contrast to Src kinases, ZAP-70 and ITK failed to induce these events. Further, ITK binding to CD28 was dependent on the presence of p56Lck and is thus likely to act downstream of p56Lck/p59Fyn in a signaling cascade. p56Lck is therefore likely to be a central switch in T-cell activation, with the dual function of regulating CD28-mediated costimulation as well as TCR-CD3-CD4 signaling.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Selective CD28pYMNM mutations implicate phosphatidylinositol 3-kinase in CD86-CD28-mediated costimulation.

CD28 costimulatory signals are required for lymphokine production and T cell proliferation. CD28 signaling recruits the intracellular proteins PI 3-kinase, ITK, and GRB-2/SOS. PI 3-kinase and GRB-2/SOS bind the CD28 cytoplasmic pYMNM motif via SH2 domains. We generated CD28 pYMNM mutants and found that Y191 mutation (Y191CD28F) disrupted both PI 3-kinase and GRB-2 binding, while M194 mutation (M194CD28C) disrupted only PI 3-kinase binding. Both mutants still bound ITK. We have assessed the ability of these selective mutants to support IL-2 production upon TCR zeta/CD3 ligation in the presence of CHO-CD86 (B7-2) cells. Both Y191CD28F and M194CD28C mutants failed to generate IL-2. These data directly implicate PI 3-kinase in CD28-mediated costimulation leading to IL-2 secretion. Wortmannin, an inhibitor of PI 3-kinase, induced cell apoptosis and as such was unsuitable for use in this study.

Animals↗
PubMed1995

[Special problems of benign stomach tumors].

Comparing with malignant lesions or peptic ulcers benign gastric tumors are rare. From 916 patients with gastric diseases, who underwent laparatomy between 1980 and 1993 in the Surgical Department at the University of Cologne, we found only 15 cases (1.6%) of benign gastric tumors. The most common benign tumor of the stomach are leiomyomas followed by adenomas. The majority of benign tumors are asymptomatic. Complaints as hemorrhage or pain are seen of large tumors. Gastroscopy is the most important examination in the diagnosis of benign gastric tumors. Endoscopic polypectomy should be carried out in those lesions still benign. Greater lesions or endoscopically incomplete excised polyps should be treated surgically. Mesenchymal tumors are difficult to estimate in their dignity. The treatment of choice is local surgical extirpation. The postoperative results are excellent.

Adenoma↗
PubMed1995

[Trans-sternal thymectomy in myasthenia gravis and thymoma].

In a retrospective study the role of thymectomy in the treatment of myasthenia gravis (n = 19) and of thymoma (n = 7) was analysed in 26 patients operated on between 1989 and 1994 in the Department of Surgery at the University of Cologne. The mean follow-up period was 28 months (follow-up rate: 96.2%). A transsternal incision was preferred in 24 cases (92.3%). Patients with myasthenia gravis were preoperatively classified according to Ossermann. Patients with thymoma were classified according to Masaoka. 17 patients (89.5%) with myasthenia gravis demonstrated a significant improvement. 4 patients (57.1%) with thymoma were free of recurrence. Stage II to IV thymoma should receive postoperative radiotherapy. Patients with stage IV lesions are usually offered postoperative radiation therapy plus cis-platinum based chemotherapy.

Adult↗
PubMed1994

T-cell antigen CD28 interacts with the lipid kinase phosphatidylinositol 3-kinase by a cytoplasmic Tyr(P)-Met-Xaa-Met motif.

The T-cell antigen CD28 provides a costimulatory signal that is required for T-cell proliferation. T-cell receptor zeta/CD3 engagement without CD28 ligation leads to a state of nonresponsiveness/anergy, thereby implicating CD28 in the control of peripheral tolerance to foreign antigens or tumors. A key unresolved question has concerned the mechanism by which CD28 generates intracellular signals. Phosphatidylinositol 3-kinase (PI 3-kinase) is a lipid kinase with Src-homology 2 (SH2) domain(s) that binds to the platelet-derived growth factor receptor (PDGF-R), an interaction that is essential for signaling by growth factor. In this study, we demonstrate that CD28 binds to PI 3-kinase by means of a Y(P)MXM motif within its cytoplasmic tail. CD28-associated PI 3-kinase was detected by lipid kinase and HPLC analysis as well as by reconstitution experiments with baculoviral-expressed p85 subunit of PI 3-kinase. CD28 bound directly to the p85 subunit without the need for the associated p110 subunit. Site-directed mutagenesis and peptide competition analysis using Y(P)-MXM-containing peptides showed that PI 3-kinase bound to a Y(P)MXM motif within the CD28 cytoplasmic tail (residues 191-194). Mutation of the Y191 within the motif resulted in a complete loss of binding, while mutation of M194 caused partial loss of binding. Binding analysis showed that the CD28 Y(P)-MXM motif bound to the p85 C- and N-terminal SH2 domains with an affinity comparable to that observed for PDGF-R and insulin receptor substrate 1. In terms of signaling, CD28 ligation induced a dramatic increase in the recruitment and association of PI 3-kinase with the receptor. CD28 is likely to use PI 3-kinase as the second signal leading to T-cell proliferation, an event with implications for anergy and peripheral T-cell tolerance.

Amino Acid Sequence↗
PubMed1994

Two-step TCR zeta/CD3-CD4 and CD28 signaling in T cells: SH2/SH3 domains, protein-tyrosine and lipid kinases.

A central question in T-cell immunity concerns the nature of intracellular signaling from the antigen receptor, the CD4/CD8 co-receptors and the CD28 antigen. Since the original discovery that T-cell receptors such as CD4 can interact with intracellular protein-tyrosine kinases such as p56lck, remarkable progress has been made in deciphering the signaling pathways that control T-cell growth and immune function. Here, Christopher Rudd and colleagues examine the role of protein-tyrosine kinases, SH2/SH3 domains and lipid kinases in the generation of signals from the TCR zeta/CD3 complex and the CD28 antigen.

Amino Acid Sequence↗
PubMed1994

The T-cell antigen CD5 acts as a receptor and substrate for the protein-tyrosine kinase p56lck.

CD5 is a T-cell-specific antigen which binds to the B-cell antigen CD72 and acts as a coreceptor in the stimulation of T-cell growth. CD5 associates with the T-cell receptor zeta chain (TcR zeta)/CD3 complex and is rapidly phosphosphorylated on tyrosine residues as a result of TcR zeta/CD3 ligation. However, despite this, the mechanism by which CD5 generates intracellular signals is unclear. In this study, we demonstrate that CD5 is coupled to the protein-tyrosine kinase p56lck and can act as a substrate for p56lck. Coexpression of CD5 with p56lck in the baculovirus expression system resulted in the phosphorylation of CD5 on tyrosine residues. Further, anti-CD5 and anti-p56lck coprecipitated each other in a variety of detergents, including Nonidet P-40 and Triton X-100. Anti-CD5 also precipitated the kinase from various T cells irrespective of the expression of TcR zeta/CD3 or CD4. No binding between p59fyn(T) and CD5 was detected in T cells. The binding of p56lck to CD5 induced a 10- to 15-fold increase in p56lck catalytic activity, as measured by in vitro kinase analysis. In vivo labelling with 32P(i) also showed a four- to fivefold increase in Y-394 occupancy in p56lck when associated with CD5. The use of glutathione S-transferase-Lck fusion proteins in precipitation analysis showed that the SH2 domain of p56lck could recognize CD5 as expressed in the baculovirus expression system. CD5 interaction with p56lck represents a novel variant of a receptor-kinase complex in which receptor can also serve as substrate. The CD5-p56lck interaction is likely to play roles in T-cell signalling and T-B collaboration.

Amino Acid Sequence↗
PubMed1993

src-related protein tyrosine kinases and their surface receptors.

The CD4-p56lck and CD8-p56lck complexes have served as a paradym for an expanding number of interactions between src-family members (p56lck, p59fyn, p56lyn, p55blk) and surface receptors. These interactions implicate src-related kinases in the regulation of a variety of intracellular events, from lymphokine production and cytotoxicity to the expression of specific nuclear binding proteins. Different molecular mechanisms appear to have evolved to facilitate the receptor-kinase interactions, including the use of N-terminal regions, SH2 regions and kinase domains. Variation exists in stoichiometry, affinity and the nature of signals generated by these complexes in cells. The CD4-p56lck complex differs from receptor-tyrosine kinases in a number of important ways, including mechanisms of kinase domain regulation and recruitment of substrates such as PI 3-kinase. Furthermore, they may have a special affinity for receptor-substrates such as the TcR zeta, MB1/B29 or CD5 receptors, and act to recruit other SH2-carrying proteins, such as ZAP-70 to the receptor complexes. Receptor-src kinase interactions represent the first step in a cascade of intracellular events within the protein-tyrosine kinase/phosphatase cascade.

Amino Acid Sequence↗
PubMed1993

Src-homology 3 domain of protein kinase p59fyn mediates binding to phosphatidylinositol 3-kinase in T cells.

The Src-related tyrosine kinase p59fyn(T) plays an important role in the generation of intracellular signals from the T-cell antigen receptor TCR zeta/CD3 complex. A key question concerns the nature and the binding sites of downstream components that interact with this Src-related kinase. p59fyn(T) contains Src-homology 2 and 3 domains (SH2 and SH3) with a capacity to bind to intracellular proteins. One potential downstream target is phosphatidylinositol 3-kinase (PI 3-kinase). In this study, we demonstrate that anti-CD3 and anti-Fyn immunoprecipitates possess PI 3-kinase activity as assessed by TLC and HPLC. Both free and receptor-bound p59fyn(T) were found to bind to the lipid kinase. Further, our results indicate that Src-related kinases have developed a novel mechanism to interact with PI 3-kinase. Precipitation using GST fusion proteins containing Fyn SH2, SH3, and SH2/SH3 domains revealed that PI 3-kinase bound principally to the SH3 domain of Fyn. Fyn SH3 bound directly to the p85 subunit of PI 3-kinase as expressed in a baculoviral system. Anti-CD3 crosslinking induced an increase in the detection of Fyn SH3-associated PI 3-kinase activity. Thus PI 3-kinase is a target of SH3 domains and is likely to play a major role in the signals derived from the TCR zeta/CD3-p59fyn complex.

Amino Acid Sequence↗
PubMed1993

Experimental basis of shockwave-induced renal trauma in the model of the canine kidney.

Using the new electromagnetic shockwave source of the Modulith SL 20 shockwave-induced renal trauma was evaluated by acute and chronic studies in the the canine kidney model. In a further study the electromagnetic shockwave source of the Lithostar Plus Overhead module was tested. Overall, 92 kidneys were exposed to shock waves coupled either by water bath (Modulith lab type) or by water cushion (Modulith prototype, Lithostar Overhead) under ultrasound localization. The generator voltage ranged between 11 and 21 kV, the number of impulses between 25 and 2500. After application of 1500/2500 shocks the extent of the renal lesion depended strictly on the applied generator voltage and was classified into 4 grades: Grade 0, no macroscopic trauma detectable (at 11-12 kV); grade 1, petechial medullary bleeding (at 13 kV); grade 2, cortical hematoma (at 14-16 kV); and grade 3, perirenal hematoma (17-20 kV). Whereas at low and medium energy levels the number of shocks played only a minor role, at maximal generator voltage (20 kV) even 25 impulses induced a grade 2 and 600 shocks a grade 3 lesion, emphasizing the importance of shockwave limitation in the upper energy range. In shockwave-induced renal trauma a vascular lesion was predominant and cellular necrosis was secondary. Coupling with a water cushion resulted in a 15%-20% decrease in the disintegrative and traumatic effect, which was compensated for by increasing the generator voltage by 2 kV. Long-term studies showed complete restitution following grade 1 and 2 trauma, whereas after a grade 3 lesion a small segmental and capsular fibrosis without hyperplasia of the juxtaglomerular apparatus was observed. Based on the characteristic ultrasound pattern found in the first study, the threshold for induction of grade 1 lesion was investigated. With both lithotripters a wide range for induction of a grade 1 lesion (Modulith 234-411, Lithostar Plus 220-740) and also a significant overlapping with grade 0 and 2 lesions was seen at low energy settings (levels 2-4). In contrast, the range of shocks (Modulith 96-150, Lithostar Plus 90-142) and overlapping was minimal when high energy was used (levels 7-9). Finally, the disintegration-trauma coefficient combining the results obtained in a standard stone model with those of the canine kidney model was introduced.

Animals↗
PubMed1992

A strong protein-tyrosine kinase activity is associated with a baculovirus-expressed chicken tkl gene.

We have previously described a gene named tkl (tyrosine kinase related to lck). It belongs to the src family of protein-tyrosine kinases and among these it has significant homology to the lck gene (lymphoide cell kinase). The tkl gene product may represent the avian homolog of Lck, which is believed to participate in a lymphocyte-specific signal transduction pathway by association with a membrane receptor. To study the biochemical properties of the protein, a nearly complete tkl gene (isolated from a cDNA library from chicken spleen cells) was expressed in a baculovirus system. Approximately 10% of the extracted protein consisted of the soluble 51-kDa Tkl protein (p51tkl) at 40 h post-infection. This protein was found to be phosphorylated on tyrosine and serine residues at a ratio of 5:1. As expected, glycosylation or myristoylation could not be detected. Immunocomplex kinase assays indicated strong autophosphorylation of p51tkl at tyrosine residues and phosphorylation of exogenous substrates such as D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH), histones H2b and H4, and casein. This protein-tyrosine kinase activity also exhibited a marked preference for Mn2+ compared to Mg2+. The high level expression of enzymatically active Tkl should provide an excellent tool to further study the biological functions of this class of enzymes.

Amino Acids↗
PubMed1991

Insufficiency of local approach regarding treatment of early gastric cancer.

Out of 1041 patients who underwent surgery for gastric cancer between 1968 and 1987, 120 patients suffered from early gastric cancer (11.5%). Until 1976, early gastric cancer was treated along the lines of surgical treatment of benign ulcer disease, i.e. by partial 2/3-gastric resection without lymphadenectomy, even though malignancy had been confirmed preoperatively in all cases. Since 1979 oncological criterias (subtotal or total gastrectomy with lymphadenectomy) have gained importance in treating early gastric carcinoma. In the case of mucosal carcinoma, the extent of surgical intervention does not have any influence on the 10-year survival rate. In treating submucosal carcinoma 10-year survival rates of 72.9 (+/- 7.2%) can only be achieved by performing total gastrectomy and lymphadenectomy whereas the 10-year survival rate after performing partial 2/3-gastric resection alone (p = 0.01) is only 17.6 (+/- 9.2%). Since mucosal and submucosal carcinoma cannot accurately be differentiated preoperatively, surgical intervention must be carried out in an oncological sense. The fact that 2/3 partial gastric resection does not generally ensure adequate therapy implies that local procedures are even less sufficient. Even in cases of mucosal infiltration only, local procedures such as laser therapy and local excision of the tumour cannot be considered being a curative approach, since hereby the probability of lymph node metastases (4%) is not taken into account.

Gastrectomy↗
PubMed1990

Evolution of a telomere associated satellite DNA sequence in the genome of Drosophila tristis and related species.

A highly repetitive satellite DNA sequence from the genome of Drosophila tristis with a length of 181 bp has been cloned in the pUC plasmid. The sequence hybridizes to the telomeres of all chromosomes but the Y of D. tristis and produces a ladderlike hybridization pattern with filterbound genomic DNA of D. tristis digested with Eco RI or Pst I with the hybridization bands at fragment lengths in multiples of 181 bp. A similar pattern is found when the genomic DNA comes from D. ambigua or, though less clear, from D. microlabis. Additional bands appear in the zones of high fragment lengths, too. In D. obscura and D. kitumensis, however, the 181 bp sequence is found in fragments with a length of a few kb only. The 181 bp sequence is tandemly arranged in the genome of D. tristis and has a copy number of about 82,000 per haploid genome (i.e. 10 per cent of the total DNA). A sequence comparison among four independently cloned copies of the family from D. tristis and another homologous sequence from D. obscura, found by chance, shows a one to six per cent variation in basepair composition. However, low divergence (only one per cent) between two copies of D. tristis and between the one of D. obscura and one of D. tristis was observed, and high divergence (six per cent) between these two pairs. This is discussed and explained as the evolutionary consequence of an existing homogenization process by unequal crossing over.

Animals↗
PubMed1989

Long-term results of highly selective vagotomy for the treatment of duodenal ulcer.

Between 1971 and 1987, highly selective vagotomy (HSV) was carried out in 984 patients suffering from duodenal ulcer disease. In 97.3% of these cases, the surgical intervention was uncomplicated, the related mortality being 0.3%. During the follow-up period the postoperative condition of the patients was checked once a year wherever possible; in 92.3%, follow-up was continued until december 1987, the maximum period of postoperative follow-up being 16 years. No prognostically reliable indication of the risk of ulcer recurrence was obtained from an analysis of gastric juice. In 79.1% of the cases who underwent surgery, the result was good to satisfactory, while 11.7% had functional complaints such as dumping or diarrhea. The probability of developing a recurrent ulcer within 16 years after the initial operation was 29.7%. This rate of recurrence is determined among other things, by the discovery of clinically quiescent ulcers during the yearly follow-up examinations, when these are performed carefully, and over a sufficiently long period.

Adult↗