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S Bauer

Publications and source records attributed to S Bauer.

At least 127 records · Page 7Linked to original sources
PubMed1995

Influence of hysterectomy on the fibrinolytic activity of plasma of women with intact ovarian function.

Hysterectomies are frequently required operations in gynecology. Several studies have reported an association between premenopausal hysterectomy and the risk of cardiovascular diseases. However, the pathophysiological linkages between these two conditions have not been elucidated. In recent years it has been shown that a decrease in plasma fibrinolytic activity is associated with increased risk of thrombosis. Furthermore, it has been known that the uterus is a very finbrinolytic active organ. In the present study we investigated the hypothesis that hysterectomy may lead to a decrease in plasma fibrinolytic activity, and thereby increase the risk for thromboembolic diseases. Fibrinolytic parameters of plasma were investigated in 26 women before and 6 weeks after premenopausal hysterectomy. Euglobulin lysis time (ELT), a global measure of plasma fibrinolytic activity, and the levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) were not different before and after hysterectomy. The ELT difference before and after venous occlusion, which is a good indicator for the risk of thrombosis, was also not significantly changed after hysterectomy. Estradiol-17 beta, progesterone, LH, FSH and sex hormone binding globulin displayed no significant changes after hysterectomy. Furthermore, the hormone measurements also indicated that the women were premenopausal. There were no correlations between the hormone values and fibrinolytic parameters. These data indicate that premenopausal hysterectomy does not lead to changes in plasma fibrinolytic activity.

Adult↗
PubMed1995

In vivo CTL induction with point-substituted ovalbumin peptides: immunogenicity correlates with peptide-induced MHC class I stability.

Class I molecules are conformationally sensitive to peptide binding, prolonging the complex's half-life on the surface of the cell. By making a series of H2-Kb anchor motif amino acid point substitutions in the ovalbumin 257-264 octamer, we were able to analyse subtle changes in peptide binding, Kb stabilization and in vivo immunogenicity. The cell line RMA-S was used to determine peptide-dependent Kb stabilization under equilibrium and non-equilibrium binding conditions. Sixteen conservative and non-conservative amino acid substitutions were made at positions 3, 5 or 8 of the peptide. At 37 degrees C, Kb stabilization was differentially affected by these substitutions, with several substitutions severely affecting Kb surface expression. When the substituted peptides were used as immunogens to prime cytotoxic T lymphocytes (CTL) in vivo, each peptide's ability to stabilize Kb directly correlated with the intensity of specific CTL activation. We conclude that peptide class I stabilization is an important influencing factor in determining cell surface steady-state expression of these peptides and thus the breadth of CTL recruitment. These concepts may relate the phenomenon of immunodominance to cell surface-presented peptide steady-state levels and may also aid in peptide vaccine design.

Amino Acid Sequence↗
PubMed1995

Formation of cytosine arabinoside-5'-triphosphate in different cultured lymphoblastic leukaemic cells with reference to their drug sensitivity.

The accumulation of intracellular cytosine arabinoside-5'-triphosphate (Ara-CTP) is determined in five lymphoblastic cell lines: Molt 4, H9 and three newly established cell lines from paediatric patients, KFB-1, KFB-2, KFT-1. The cell lines KFB-1 and KFB-2 are B-lymphoblastic (B-ALL), the others are T-lymphoblastic leukaemic cells (T-ALL). The Ara-CTP levels were compared with the sensitivity of the cells to Ara-C. The cells were incubated at different concentrations (100 nM-100 microM) of Ara-C for 4 h or incubated for variable times (30 min-11 h) at 0.1, 1 and 10 microM Ara-C to form Ara-CTP. The Ara-CTP-concentrations were measured by high pressure liquid chromatography (HPLC). To determine the sensitivity of the cells to Ara-C, the MTT colorimetric-assay was used. The studies indicate that different B- and T-lymphoblastic leukaemia cell lines accumulate Ara-CTP to a markedly different extent. Ara-CTP plateau levels and sensitivity of the cells to Ara-C correlated well in four of the five cells lines studied.

Arabinofuranosylcytosine Triphosphate↗
PubMed1995

Regression and progression in neuroblastoma. Does genetics predict tumour behaviour?

Neuroblastoma (NB) is a heterogeneous disease. The clinical course may range from spontaneous regression and maturation to very aggressive behaviour. Stage 4s is a unique subcategory of NB, generally associated with good prognosis, despite skin and/or liver involvement and the frequent presence of tumour cells in the bone marrow. Another type of NB is the locally invasive tumour without bone and bone marrow involvement which can also have a good prognosis, irrespective of lymph node involvement. Unfortunately, there is only limited biological information on such tumours which have not been treated with cytotoxic therapy despite lymph node involvement, residual tumour mass after surgery and/or bone marrow infiltration. In order to find specific genetic changes common to NBs with a benign clinical course, we studied the genetic abnormalities of these tumours and compared them with highly aggressive tumours. We analysed a series of 54 localised and stage 4s tumours by means of in situ hybridisation performed on fresh cells or on paraffin embedded tissues. In addition, we performed classical cytogenetics, Southern blotting and PCR analysis on fresh tumour tissue. The majority of patients had been treated with surgery alone, and in a number of patients tumour resection was incomplete. Deletions at 1p36 and amplifications of the MYCN oncogene were absent, and diploidy or tetraploidy were not seen in any case, with residual localised tumours possessing a favourable outcome. Unexpectedly, one patient with a tetraploid 4s tumour without any genetic structural changes not receiving any cytotoxic treatment, did well. Interestingly, this genetic spectrum contrasted with that of progressing tumours, in which most had genetic aberrations, the deletion at 1p36 being the most common event. These data, although limited, suggest that an intact 1p36 (recognised by D1Z2), the absence of MYCN amplification and near-triploidy (at least in localised tumours), represent prerequisites for spontaneous regression and/or maturation.

Adolescent↗
PubMed1995

Identification of H-2Kb binding and immunogenic peptides from human papilloma virus tumour antigens E6 and E7.

Peptides can be used to induce MHC class I restricted cytotoxic T cells (CTL) through in vivo immunization. This approach may enable the development of peptide vaccination schemes for immunization against viral infection in humans. Human papillomavirus (HPV) is one of a few viruses associated with human cancer and the development of an anti-cancer vaccine seems possible. As a model approach, we searched the E6 and E7 proteins of the human papillomavirus type 16 for possible murine MHC class I restricted peptide epitopes. We utilized the mouse H2-Kb peptide binding motif which consists of phenylalanine or tyrosine at position five and leucine at the carboxy-terminus with the modification that leucine could be replaced by other aliphatic but non-aromatic amino acids. Four peptide sequences from E6 and two from E7 were selected. These peptides were tested for their ability to bind and stabilize Kb and for their immunogenicity in vivo. It was shown that one peptide from E6, E6.1 (50-57), bound Kb, but was not able to prime mice in vivo. In contrast, the two selected E7 peptides E7.1 (21-28) and E7.2 (48-55) bound Kb and were immunogenic in vivo. The peptide induced CTL lysed syngeneic EL-4 cells transfected with the open reading frame of E7 but not vector only transfectants. This implies that both peptides were naturally processed and presented by Kb on the surface of target cells. MHC class I peptide binding motifs therefore appear to be an effective and useful tool to predict peptide epitopes of proteins associated with cancer.

Amino Acid Sequence↗
PubMed1995

Neurophysiologic assessment of urinary dysfunction in children with thoracic syringomyelia.

Isolated syringomyelia of the thoracic portion of the spinal cord is relatively uncommon. In children, signs and symptoms may involve only the urinary system. Five children who presented for evaluation of urinary tract dysfunction were found to have syringomyelia of the thoracic cord not associated with any other central nervous system abnormality on radiographic imaging. Each child underwent a complete neurologic examination and a complete electrophysiologic/urodynamic evaluation. One patient underwent surgical drainage of the syrinx due to progression of neurologic deficit, with slight improvement; three patients were treated pharmacologically to control the urinary dysfunction.

Child↗
PubMed1995

Hypothermic bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta.

BACKGROUND: Hypothermic cardiopulmonary bypass with intervals of circulatory arrest is a useful adjunct during operations on the descending thoracic aorta and distal aortic arch when severe aortic disease precludes placement of clamps on the aorta. Hypothermia also has a marked protective effect on spinal cord function during periods of aortic occlusion. METHODS: Fifty-one patients (age range, 22 to 79 years) with descending thoracic or thoracoabdominal aortic disease had resection and graft replacement of the diseased aortic segments using hypothermic cardiopulmonary bypass and intervals of circulatory arrest in situations where the location, extent, or severity of disease precluded placement of clamps on the proximal aorta (8 patients) or (in 43 patients) when extensive thoracic (11) or thoracoabdominal (32) aortic disease was present and the risk for development of spinal cord ischemic injury and renal failure was judged to be increased. Patent intercostal (below T-6) and upper lumbar arteries were attached to the graft whenever possible. RESULTS: Thirty-day mortality was 9.8% (5 patients). Paraplegia occurred in 2 and paraparesis in 1 of the 46 30-day survivors (6.5%). Among the 27 operative survivors with thoracoabdominal aneurysms, paraplegia occurred in 1 of 12 with Crawford type I (8%), 0 of 10 with type II, and 1 of 5 with type III aneurysms (20%). Paraplegia occurred in none of the 12 patients with aortic dissection and in 2 of the 15 patients with degenerative aneurysms. Renal failure requiring dialysis occurred in 1 (2.2%) of the 46 30-day survivors. CONCLUSIONS: Hypothermic circulatory arrest is a valuable adjunct for the treatment of complex aortic disease involving the aortic arch and thoracoabdominal aorta. In patients with thoracoabdominal aneurysms, its use has been associated with a low incidence of renal failure and an incidence of paraplegia/paraparesis in traditionally high-risk subsets (type I and II aneurysms, aortic dissection), which may be less than that observed with other surgical techniques.

Adult↗
PubMed1995

Peptide engineering allows cytotoxic T-cell vaccination against human papilloma virus tumour antigen, E6.

Major histocompatibility complex (MHC) class I allele-specific binding motifs have proved useful in predicting cytotoxic T-cell epitopes from immunogenic proteins. In a search of the E6 protein from human papilloma virus type 16 utilizing the Kb binding motif, we discovered four potential binding peptides. One peptide, E6.1 (sequence 50-57, YDFAFRDL), was poor in its ability to stabilize empty Kb on RMA-S cells, with a t1/2 = 33 min versus 30 min for empty Kb. This peptide subsequently proved to be non-immunogenic upon mouse in vivo vaccination. It was hypothesized that an isoleucine for aspartate substitution at position 2 would improve Kb stabilization kinetics and therefore immunogenic potential. The engineered peptide E6.1 I2 increased the Kb t1/2 to 100 min and was immunogenic upon in vivo vaccination. Cytolytic T lymphocytes (CTL) raised with the E6.1 I2 peptide responded to cells pulsed with either the wild-type peptide or the engineered peptide, implying a blindness to the substitution. More striking, these CTL also lysed a syngeneic cell line transfected with the E6 gene, implying that the E6.1 peptide was processed and presented. These data demonstrate that subimmunogenic peptides can be engineered to improve binding kinetics, which in turn improves immunogenicity. Provided that poor binding peptides are processed, the induction threshold for CTL activation can be achieved with engineered peptides, thus allowing for the kill of wild-type target cells. This approach may prove relevant to the design of subunit vaccines to virally induced tumours.

Animals↗
PubMed1994

[Prolonged course of an idiopathic hypereosinophilic syndrome with transition to eosinophilic gastroenteritis].

Idiopathic hypereosinophilic syndrome (IHES) is a multi-system disorder of unknown origin with eosinophilic infiltration of bone marrow and various organs, including the gastrointestinal tract. Involvement of the heart has a poor prognosis. The etiology of eosinophilic gastroenteritis (EGE) also is unclear. In this disease there is exclusive involvement of the gastrointestinal tract (including liver/bile ducts) and prognosis usually is good. Transition from one disease to the other has not yet been described. We report the 20 years' history of a male patient with an initial IHES without gastrointestinal symptoms and transition to a clinically pure EGE with resolution of any other involvement. At the age of 45 years the patient developed IHES with fever and constitutional symptoms. Fluctuating eosinophilia and symptoms necessitated continuous steroid therapy. After a 10 years' disease course watery diarrhea and malabsorption syndrome became more and more prominent. On the other hand, bone marrow eosinophilia regressed completely and blood eosinophilia partially. Biopsies showed a severe EGE of the mucosal type with involvement of the whole gastrointestinal tract. Besides the prominent eosinophilia there was a dense infiltration of the intestinal mucosa with T-lymphocytes invading the epithelium. We postulate that the destructive eosinophilic/lymphocytic inflammation is caused by a pathologic proliferation of T-lymphocytes with liberation of type 2 helper cell cytokines and consecutive stimulation of eosinophils.

Aged↗
PubMed1994

[Eradication of metronidazole-resistant Helicobacter pylori: is omeprazole/amoxicillin a therapeutic alternative?].

Recommended therapies with the highest eradication rates for Helicobacter pylori (HP) are triple therapies comprising bismuth salts, nitroimidazole and amoxicillin or tetracycline. Primary and secondary resistance of HP to nitroimidazole, however, represents a major problem of this treatment since it is the main cause of eradication failure. In these cases therapeutic regimes without nitroimidazole could prove more successful. High dose omeprazole/amoxicillin has been suggested as a simple and effective therapy with few side effects. The effectiveness of this combination in eradicating metronidazole resistant HP has not been established so far. The aim of this study was to evaluate high dose omeprazole/amoxicillin in eradicating metronidazole resistant HP in our population. 33 patients (6 women, 27 men, mean age 39 [range 21-68]) with recurrent duodenal ulcer and gastric colonization by metronidazole resistant HP were examined. Smokers were defined as patients currently smoking > 10 cigarettes/day. Exclusion criteria were: gastric surgery or intake of antibiotics, omeprazole bismuth salts and NSAIDs within four weeks before study entry endoscopy. Biopsy specimens were obtained in a standardized manner: 5 from the gastric antrum (1 CLO, 1 culture, 3 histology: H & E, Giemsa) and 2 from the gastric body (histology). Resistance testing for penicillin, amoxicillin and metronidazole was performed using a disk diffusion test (E-test, AB Biodisk, Sweden). Metronidazole resistance was defined as a minimal inhibitory concentration (MIC) of metronidazole of > 8 micrograms/ml. Eradication therapy consisted of oral omeprazole (40 mg bid) and amoxicillin solute (750 mg tid) for 10 days. Subsequently, for ulcer treatment, patients were given omeprazole (20 mg per day) for 20 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Chronic pancreatitis and primary hyperparathyroidism].

The frequency of acute or chronic pancreatitis in primary hyperparathyroidism has decreased from the former 5-10% to 1-2% thanks to earlier diagnosis and operative treatment. Chronic pancreatitis, which occurs only in prolonged primary hyperparathyroidism, should therefore virtually disappear. We investigated this topic in a prospective long term study of chronic pancreatitis (1963-1992). Over the last three decades 336 patients with chronic pancreatitis have been studied at regular intervals. 245 suffered from alcohol-induced (84% with calcifications) and 91 from non-alcohol-induced chronic pancreatitis (77% with calcifications). The average period of observation in the group with non-alcohol-induced chronic pancreatitis was 10.6 years. Primary hyperparathyroidism was found in 6 patients (4 male, 2 female), i.e. 6.6% of non-alcohol-induced chronic pancreatitis (100% with calcifications). They were evenly distributed over the 30 years' study period. 3 patients had acute attacks of pancreatitis prior to the diagnosis of chronic calcific pancreatitis (2 months, 3 + 8 years). In 3 patients with primary painless chronic calcific pancreatitis the condition was diagnosed twice incidentally and once because of diabetes mellitus. Chronic pancreatitis was diagnosed 3 times before primary hyperparathyroidism (8.3 +/- 2.1 years), once simultaneously and twice afterwards (2 + 14 years). In three patients chronic pancreatitis was initially misinterpreted as alcohol-induced. Severe exocrine pancreatic insufficiency was present in 4 of 5 patients (no data in one), and diabetes mellitus in 3 of 6 patients. At the time of diagnosis of primary hyperparathyroidism, mean serum calcium was 3.08 +/- 0.43 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗
PubMed1994

[Thoracic pain, shock-inducing gastrointestinal bleeding].

A 65-year-old patient was referred to hospital with suspected myocardial infarction because of left-sided thoracic pain. A paresis of the left recurrent nerve of unknown etiology has been known for three years. Because of shock with anemia, upper gastrointestinal endoscopy was performed. A diverticulum-like lesion in the proximal esophagus was found to be the source of the bleeding. A contrast X-ray examination showed a cavity of approximately 2 x 2 cm originating from the proximal esophagus. Computerized tomography revealed a large mediastinal mass reaching from the thyroid to the diaphragm. An ultrasound-guided fine-needle puncture of this tumor, together with the endoscopical snare biopsies of the esophageal lesion, allowed the diagnosis of an anaplastic thyroid carcinoma with erosion of the esophagus. The patient responded well to palliative radiotherapy. The defect in the proximal esophagus refilled quickly. Nine months after radiotherapy the patient is doing well.

Aged↗
PubMed1994

The immunodominant peptide from listeriolysin in Quil A liposomes vaccinates CD8+ cytolytic T cells and confers protection to infection.

Cytolytic T-cell vaccination with immunodominant MHC class I-restricted peptides contained within Quil A liposomes has been previously demonstrated. In recent years, Quil A has been under consideration for use as an adjuvant in humans. We assessed the possible use of peptide inoculation in the context of Quil A liposomes to be protective in a mouse model. Listeria monocytogenes was used as the challenge pathogen and the previously identified listeriolysin 91-99 peptide as the immunogen. The listeriolysin 91-99 Quil A liposome inoculum showed significant enhancement of survival after challenge with up to 10 times the L. monocytogenes LD50.

Adjuvants, Immunologic↗