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Biomedical subjects

C Stroh

Publications and source records attributed to C Stroh.

At least 19 recordsLinked to original sources
PubMed2006

The tyrosine kinase Lck is a positive regulator of the mitochondrial apoptosis pathway by controlling Bak expression.

Tyrosine kinases of the Src family have been implicated in key biological processes. Here, we provide evidence that p56(Lck), a lymphoid-specific Src kinase, is involved in the activation of the mitochondrial apoptosis pathway. Lck-deficient T cells were completely resistant to anticancer drugs. In contrast, apoptosis sensitivity to death receptors was not altered, indicating a specific interference of Lck with the mitochondrial pathway. Re-expression of Lck restored sensitivity to drug-induced apoptosis and triggered mitochondrial cytochrome c release and caspase activation. Further analysis identified that the sensitization by Lck was independent of classical mediators of T-cell signaling, but essentially involved the Bcl-2 protein Bak. Expression of Bak was completely absent in Lck-deficient cells, while re-expression of Lck transcriptionally triggered Bak expression and conferred sensitivity to apoptosis, associated with a proapoptotic conformational change of Bak. Furthermore, in vitro the truncated fragment of Bid specifically activated Bak and cytochrome c release only from mitochondria of Lck-expressing cells. These results do not only demonstrate a sentinel role of Lck in drug resistance but also delineate a hitherto unknown pathway of Src kinases in regulation of Bcl-2 proteins.

Antineoplastic Agents↗
PubMed2006

Unique and overlapping substrate specificities of caspase-8 and caspase-10.

Although caspase-8 has an established role as an initiator of death receptor-mediated apoptosis, the function of its closest homolog, caspase-10, is almost completely unknown. To gain a closer insight into the physiological function of caspase-10, we compared the cleavage of known caspase-8 substrates by both initiator caspases. We demonstrate that caspase-10 and -8 have overlapping cleavage preferences for several substrates such as the kinases RIP and PAK2. Interestingly, in other substrates, such as the Bcl-2 protein Bid, we found additional and distinct cleavage sites for both caspases, which might have important consequences for mitochondrial targeting and propagation of the death signal. Caspase-8 and -10 also caused different interchain cleavage patterns of their enzyme precursors. Together, these results suggest that caspase-8 and -10, despite having overlapping functions, also have selective substrate cleavage specificities and might thereby exert nonredundant roles in apoptosis signaling.

Amino Acid Sequence↗
PubMed2006

[Complications after adjustable gastric banding. Results of an inquiry in Germany].

BACKGROUND: Adjustable gastric banding is a popular bariatric operation in Europe. About 1500 patients per year undergo a such procedures in Germany. Clinical data on the rate of long-term complications such as pouch dilatation, slippage, and band migration are available in only a few long-term studies with small numbers of patients. Meta-analyses report on comordities and reduction in weight. The rate and management of long-term complications were examined at this inquiry. METHODS: Ninety hospitals were asked about rates of band implantation, follow-up, and complications. Thirty-eight hospitals (42.2%) participated in the study. The management of complications including slippage, pouch dilatation, and band migration was analyzed. RESULTS: At 35 hospitals, 4138 patients underwent gastric banding procedures in 25 hospitals over more than 5 years. The mean follow-up rate is presently 85.3%. Long-term complications were described in 8.6% of the patients. Pouch dilatation occurred in 5.0%, slippage in 2.6%, and band migration in 1.0%. CONCLUSIONS: Laparoscopic adjustable gastric banding can effectively achieve weight loss. However, band-related and functional complications influence late outcome. The rate of long-term complications was equivalent to that already in the literature.

Body Mass Index↗
PubMed2005

[Band migration. A late complication of gastric banding].

BACKGROUND: Adjustable silicone gastric banding is an effective and safe treatment for morbid obesity. Migration of the band through the stomach wall is a long-term complication. The causes, clinical symptoms, timing, and incidence of band migration have not yet been investigated. METHODS: We report our experience over 9 years. Between February 1995 and February 2004, we performed adjustable silicone gastric banding in 161 patients, with follow-up of about 90.5% of cases. Mean follow-up time was 60.4 months. Cases of erosion were studied retrospectively. RESULTS: Eight patients (4.9%) developed band migration. In seven, the migration occurred between 30 and 86 months after band implantation. In one case, the migration occurred 10 months after laparoscopic repositioning of the band to avoid pouch dilatation. In all cases, the bands were removed. CONCLUSION: Band migration is a late complication after gastric banding that requires band removal. Various symptoms and complications of band migration influence the kind of band removal. The causes of band migration and its treatment are discussed.

Female↗
PubMed2005

[Study of quality assurance "surgical treatment of morbid obesity" since 1.1.2005].

Since January 1st 2005, the situation of bariatric surgery has been examined in Germany. The data are registered in cooperation with the An-institute of quality control in surgery at the Otto-von-Guericke-Universität Magdeburg. The data registration occurs in an internet on-line data bank. Application for participation in this study is available on our correspondence address. All hospitals carrying out bariatric surgery are asked to take part in this study.

Bariatric Surgery↗
PubMed2005

[Long-term results after gastric banding].

BACKGROUND: Adjustable gastric banding is a popular bariatric operation in Europe. The rate of long-term complications like pouch dilatation, slippage and band migration and the long-term effect of weight loss are reported in meta-analysis and few studies for a period of more than five years. We report on experiences after gastric banding. METHODS: Over a period of 10 years 168 patients with morbid obesity were treated with gastric banding. Preoperative data, postoperative weight loss and long-term complications were prospectively obtained and retrospectively analyzed. RESULTS: Mean age of the patients was 41.7 years with a mean preoperative BMI of 49.6 kg/m2. No intraoperative or postoperative death occurred in the first 30 postoperative days. Intraoperative conversion rate was 7.1 %. 79.8 % of the patients (n = 134) were available for follow up (mean follow-up time 66.7 months). Long-term complications occurred in 22.5 % of the patients. 30 complications (17.8 %) were related to the band and 8 (4.7 %) to the access-port or to the tube. Mean excess weight loss was 39.6, 47.3, 44.2, 43.4 and 32 % after 1, 2, 4, 5 and 8 years. CONCLUSIONS: Laparoscopic gastric banding can achieve an effective weight loss. However band-related and functional complications will influence the late outcome. Pathways to choose the best surgical method for the individual patient are necessary to reduce failures after gastric banding.

Adult↗
PubMed2005

Rhabdomyolysis after biliopancreatic diversion with duodenal switch.

Rhabdomyolysis is an uncommon event in bariatric surgery. It can be caused by ischemia, crush injury, alcohol ingestion and drug intake, and as a consequence renal failure can develop. A few reports indicate that patients undergoing bariatric surgical intervention are at risk for rhabdomyolysis. A super-obese male (BMI 52 kg/m2) is reported, who underwent laparoscopic biliopancreatic diversion with duodenal switch (BPD/DS). Operative time was 265 minutes, and the BPD/DS operation was uneventful. Post-operatively, the patient complained of pain in both hips and the left shoulder, and suffered oliguria. He was treated with fluids (isotonic saline), bicarbonate, and mannitol. Despite this, he developed renal failure, which subsequently required hemodialysis. The patient died from arrhythmia and cardiac arrest on the 8th postoperative day. Obese patients undergoing bariatric surgery are at risk of rhabdomyolysis. Prolonged compression of the muscles during the surgical intervention, in long laparoscopic procedures, predisposes to this complication.

Adult↗
PubMed2004

Single-molecule recognition imaging microscopy.

Atomic force microscopy is a powerful and widely used imaging technique that can visualize single molecules and follow processes at the single-molecule level both in air and in solution. For maximum usefulness in biological applications, atomic force microscopy needs to be able to identify specific types of molecules in an image, much as fluorescent tags do for optical microscopy. The results presented here demonstrate that the highly specific antibody-antigen interaction can be used to generate single-molecule maps of specific types of molecules in a compositionally complex sample while simultaneously carrying out high-resolution topographic imaging. Because it can identify specific components, the technique can be used to map composition over an image and to detect compositional changes occurring during a process.

Animals↗
PubMed2004

Accuracy of endorectal ultrasonography in the preoperative staging of rectal cancer.

BACKGROUND: Preoperative staging of rectal tumours is considered essential to tailoring treatment for individual patients. The aim of the present study was to evaluate the accuracy of 3-D-endorectal ultrasonography for the preoperative staging of rectal cancer. METHODS: Three hundred and fifty-seven patients with rectal adenocarcinomas underwent an endorectal ultrasonography evaluation during a period of eight years. The evaluation was performed by four surgeons. We compared the endorectal ultrasonography staging with the pathology findings. Patients with preoperative chemoradiation were excluded from the study. RESULTS: Overall accuracy in assessing the level of rectal wall invasion was 77.3%, with 9.3% of the tumours overstaged and 8.1% understaged. Accuracy in assessing nodal involvement in 313 patients treated with radical surgery was 74.9%, with 8.9% overstaged and 8.9% understaged. CONCLUSIONS: The accuracy of 3-D-endorectal ultrasonography in assessing the depth of tumour infiltration is good, but it is lower than previously reported. The technique is precise in distinguishing between benign tumours and invasive cancer. The results depend on the experience of the surgeon.

Adenocarcinoma↗
PubMed2004

[Importance of endorectal 3-D-ultrasonography in diagnosis of rectum cancer].

BACKGROUND: Preoperative staging of rectal tumors is considered essential to tailor treatment for individual patients. The aim of the present study was to evaluate the accuracy of endorectal ultrasonography in preoperative staging of rectal cancer. METHODS: 357 patients with rectal adenocarcinoma underwent endorectal ultrasonography evaluation during an eight year period. The evaluation was performed by four surgeons. We compared the endorectal ultrasonography staging with the pathology findings. Patients with preoperative chemoradiation were excluded from the study. RESULTS: Overall accuracy in assessing the level of rectal wall invasion was 77.3 %, with 9.3 % of the tumors overstaged and 8.1 % understaged. Accuracy in assessing nodal involvement in 313 patients treated with radical surgery was 74.9 %, with 8.9 % overstaged and 8.9 % understaged. CONCLUSION: The accuracy of endorectal ultrasonography in assessing the deepth of tumor invasion is good, but lower than previosly reported. The technique is precise in distinguishing between benign tumors and invasive cancer. The results depend on the experience of the surgeon.

Adenocarcinoma↗
PubMed2003

[Ultrasound diagnosis of rare retrorectal tumors].

The diagnosis of perirectal masses can be accomplished by computer tomography and magnet resonance imaging if the rectum is contrasted. The accuracy of these methods is > 90 %. But often the assessment of the exact borders with respect to the rectum wall and to the genitalia is difficult. Therefore transrectal 3D-ultrasound is of major importance in the preoperative staging and postoperative follow-up of rectum cancer and allows the diagnosis of pararectal findings using the ultrasound-guided, transrectal aspiration. By ultrasound-guided aspiration biopsy we detected five cases of pararectal and especially presacral diseases including one case of endometriosis. The diagnostic algorithm is described.

Adult↗
PubMed2001

Magnetic and electronic properties in novel terpyridine-based nitroxide complexes: strong radical-metal interaction via a pyridyl ring.

Transition metal complexes of 2-[4'-(2,2':6',2' '-terpyridyl)]-(4,4,5,5-tetramethylimidazolinyl-3-oxide-1-oxyl) (terpy-NIT) and 2-[4'-(2,2':6',2' '-terpyridyl)]-(4,4,5,5-tetramethylimidazolinyl-1-oxyl) (terpy-IM) have been prepared. Whereas the pyridyl fragments of the free ligands are in an anti conformation, the complexes are obtained by coordination of two terpyridines in a syn conformation, forming a distorted octahedron around the metal center: [M(terpy-NIT)(2)](ClO(4))(2) (M = Ni(II) 1, Zn(II) 2, Cu(II) 3) and [M(terpy-IM)(2)](ClO(4))(2) (M = Ni(II) 4, Zn(II) 5). The ligands and their complexes have been characterized by FAB-MS, UV-vis, FT-IR spectroscopies, elemental analysis, and by EPR spectroscopy and susceptibility measurements. Single-crystal X-ray diffraction have been performed on the terpy-NIT ligand and on complexes 1, 4, and 5 giving following crystal data: terpy-NIT, monoclinic, P2(1)/c, Z = 4, a = 14.2186(5), b = 12.9129(6), c = 11.704(1) A, beta = 108.615(4) degrees; 1, orthorhombic, P(n a 2(1)), Z = 4, a = 23.6367(6), b = 8.7836(1), c = 24.2748(7) A; 4, monoclinic, P2(1), Z = 1, a = 8.738(1), b = 25.010(1), c = 11.704(1) A, beta = 102.849(3) degrees; 5, monoclinic, P2(1), Z = 1, a = 8.7463(2), b = 25.0833(5), c = 11.8168(3) A, beta = 102.757(3) degrees. For complexes 1 and 3, an antiferromagnetic behavior has been found and parametrized by considering a symmetric magnetic trimer, highlighting a strong intramolecular coupling between the metal and the radicals (average values 2J(M-NIT) = -19.6 K for M = Ni and -22.8 K for M = Cu). In the case of compound 4, an asymmetric magnetic trimer has been used to model the antiferromagnetic interactions (2J(Ni-IM1) = -13.0 K, 2J(Ni-IM2) = -5.6 K). The shape of the EPR spectra of complexes 2, 3, and 5 in solution indicates the intermediate exchange limit, of the order of a few mK, between the two nitroxide radicals through the pyridyl-metal-pyridyl fragment.

Journal Article↗
PubMed2001

Caspases: more than just killers?

Proteases of the caspase family constitute the central executioners of apoptosis. Several recent observations suggest that caspases and apoptosis-regulatory molecules exert important functions beyond that of cell death, including the control of T-cell proliferation and cell-cycle progression. Here, Los and colleagues propose a model that directly connects cell suicide mechanisms to the regulation of cell-cycle progression.

Animals↗
PubMed2000

Caspase-8/FLICE functions as an executioner caspase in anticancer drug-induced apoptosis.

Caspase-8 plays an essential role in apoptosis triggered by death receptors. Through the cleavage of Bid, a proapoptotic Bcl-2 member, it further activates the mitochondrial cytochrome c/Apaf-1 pathway. Because caspase-8 can be processed also by anticancer drugs independently of death receptors, we investigated its exact role and order in the caspase cascade. We show that in Jurkat cells either deficient for caspase-8 or overexpressing its inhibitor c-FLIP apoptosis mediated by CD95, but not by anticancer drugs was inhibited. In the absence of active caspase-8, anticancer drugs still induced the processing of caspase-9, -3 and Bid, indicating that Bid cleavage does not require caspase-8. Overexpression of Bcl-x(L) prevented the processing of caspase-8 as well as caspase-9, -6 and Bid in response to drugs, but was less effective in CD95-induced apoptosis. Similar responses were observed by overexpression of a dominant-negative caspase-9 mutant. To further determine the order of caspase-8 activation, we employed MCF7 cells lacking caspase-3. In contrast to caspase-9 that was cleaved in these cells, anticancer drugs induced caspase-8 activation only in caspase-3 transfected MCF7 cells. Thus, our data indicate that, unlike its proximal role in receptor signaling, in the mitochondrial pathway caspase-8 rather functions as an amplifying executioner caspase.

Adenocarcinoma↗
PubMed2000

[Postoperative follow-up and body weight after gastric banding].

BACKGROUND: Since 1983 gastric banding has become a proven operative method, which reduces effectively excess weight in morbid obesity. Gastric banding has been popularized as a minimally invasive, completely reversible surgical treatment for morbid obesity. We report here our 4 year experiences of gastric banding with special reference to complications. PATIENTS AND METHODS: There were 109 patients in total, of whom 92 were women. Median age was 41.5 years (range 17-62 years) and median body-mass-index (BMI) was 49.6 kg/m2 (range 36.7-82.6 kg/m2). From February 1995 to June 1997 39 patients were operated upon with the open technique. In June 1997 we started the laparoscopic gastric banding. 70 patients were treated with this method from June 1997 to February 1999. RESULTS: The weight loss 6 months postoperatively after gastric banding was 35.3% and 12 months after the operation 43.0% of the overweight. In 17 cases a re-operation was necessary. Indications for re-operations included pouch dilatation in 4 cases, slippage in 3 cases and complications connected with the port system. The operation technique and the kind of band fixation influenced the frequency of complications. CONCLUSIONS: A lot of complications especially after laparoscopic gastric banding can be prevented by a strong indication. Using the laparoscopic technique complications like pouch dilatation are diminished compared to the open technique. A standardized operation technique decreases the complication and re-operation rate. Conversions to the open technique were mostly necessary during the learning curve of LASGB (laparoscopic adjustable silicone gastric banding).

Adolescent↗
PubMed2000

[Protocol for lymph node dissection in stomach carcinoma. Possibility for quality assurance].

Since 1984 we have been using the opportunity to registrate the dissected lymph nodes at different locations of the lymph nodes and the carcinoma in case of D-2 dissection by means of a lymph node dissection protocol. The total rate of lymph nodes by the several patients is an indirect sign for the quality of the lymph node dissection and the preparation work of the pathologist. In about 17% of all cases the number of all found lymph nodes by the pathologist was lower than 15 and so an exactly classification in the N-category was not possible. In case of an exactly lymph node dissection on one hand side the prognosis for the patients life can be improved and on the other hand side an exactly pathological classification is an opportunity to estimate the prognosis better than.

Gastrectomy↗
PubMed1999

P2X7/P2Z purinoreceptor-mediated activation of transcription factor NFAT in microglial cells.

ATP is released from neurons and other cell types during several physiological and stress conditions under which it exerts various biological effects upon binding to purinoreceptors. A rather peculiar purinoreceptor called P2X7/P2Z is expressed on microglial and other myeloic cells. Although increasing evidence implicates an important role for P2Z in inflammatory processes, little information exists about underlying signaling pathways. Here, we report that in N9 microglial cells, extracellular ATP potently activates nuclear factor of activated T cells (NFAT), a central transcription factor involved in cytokine gene expression. ATP activated NFAT rapidly (within 1 min), whereas activation of nuclear factor kappaB was much delayed, with strikingly distinct kinetics. During ATP stimulation, both NFAT-1 and NFAT-2 were activated by a calcineurin-dependent pathway that required the influx of extracellular calcium ions. Based on the pharmacological profile, NFAT activation was specifically mediated by P2Z and not by other purinoreceptors. N9 cells that lacked P2Z but still expressed P2Y purinoreceptors failed to respond to NFAT activation. We conclude that P2Z-mediated NFAT activation may represent a novel mechanism by which extracellular ATP can modulate early inflammatory gene expression within the nervous and immune system.

Adenosine Triphosphate↗