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Biomedical subjects

E Schmidt

Publications and source records attributed to E Schmidt.

At least 91 records · Page 5Linked to original sources

Prognostic significance of molecular alterations in human pancreatic carcinoma--an immunohistological study.

BACKGROUND: During the last decade, many molecular alterations have been described for pancreatic carcinomas. However, the clinical and prognostic value of these alterations has been discussed and is controversial. METHODS: An immunohistochemical study was performed in 82 cases of adenocarcinoma of the pancreas. Using specific antibodies, expression of EGF, EGF-receptor, cERB-B2, p53, p21CIP1, cyclin-D1, BCL-2, CD95 and KI67 was evaluated. RESULTS: Overexpression of the different molecules was found in 44-69% of the pancreatic carcinomas. With regard to clinico-pathological features, p53 positivity was more frequently found in advanced and undifferentiated tumours (P<0.05), EGF overexpression was significantly more frequent in advanced tumours (P<0.05) and CD95 overexpression was observed to a greater extent in undifferentiated tumours (P<0.05). Besides cyclin-D1, none of the molecules tested was of prognostic significance. Patients whose tumours expressed cyclin-DI lived significantly shorter than patients with cyclin-D1-negative tumours. However, in subgroup analyses of patients with the same tumour stage or tumour grade, even cyclin-D1. expression had no prognostic significance. CONCLUSION: These results demonstrate that the prognostic significance of the molecules tested here is low. Nevertheless, with regard to tumorigenesis and tumour biology of pancreatic carcinoma, determination of molecular alterations could provide important information about pancreatic cancer.

Adenocarcinoma↗

[Thoracic diagnosis with electron-beam computed tomography].

The electron beam computed tomography (EBCT) is characterised by an up to 10-fold increased speed in comparison to a spiral CT scanner. Although originally designed for diagnosing the heart, some indications in the chest and for the vessels have also become well established. In the forefront exists the possibility to exam a large volume with a small slice thickness in a short time period without having to sacrifice on important features of spiral CT scanning. During one breathhold, the thorax can be continually examined with 1.5 mm slice thickness, which means that indications for high-resolution (HR-) CT, spiral-CT and for virtual bronchoscopy can be combined into one examination. Beyond the artefact-reduced images, the EBCT presents image data which, following image processing (sliding MIPs, coronal reconstructions), allow recognition of a new horizon in thoracic diagnostics.

Aged↗

Simultaneous degradation of chloro- and methyl-substituted aromatic compounds: competition between Pseudomonas strains using the ortho and meta pathway or the ortho pathway exclusively.

Pseudomonas sp. D7-4 and Pseudomonas sp. B13 FR1(pFRC20P) degraded mixtures of chloro- and methyl-substituted benzoates exclusively via an extended ortho pathway, whereas in Pseudomonas putida WR 201 both ortho and meta fission were induced by mixtures of 3-chloro- and 3-methylbenzoate or even by 3-chloro-benzoate alone. The competition behaviour of these strains was compared in batch and in chemostat cultures.. Despite misrouting of metabolites, strain WR201 was competitive, in a lot of the competition experiments, with mixtures of these substrates. Only in a narrow range of the mixing ratio of chloro- and methylbenzoate was the presence of both the meta and ortho pathways a disadvantage for competitiveness. Outside these ranges other attributes, such as high growth rates or short lag periods, or a respective strain were even more essential for one strain to outcompete another.

Benzoates↗

The antinuclear autoantibodies Sp100 and gp210 persist after orthotopic liver transplantation in patients with primary biliary cirrhosis.

BACKGROUND/AIMS: Primary biliary cirrhosis is an autoimmune liver disease which is characterized by the presence of autoantibodies directed against mitochondrial components which belong to the pyruvate dehydrogenase enzyme complex. Apart from antibodies against mitochondrial components, primary biliary cirrhosis patients often show antibodies against nuclear components, of which anti-Sp100 and anti-gp210 are considered to be disease specific. We investigated the incidence and course of antibodies against nuclear components in primary biliary cirrhosis patients before and after liver transplantation. METHODS: Sera from 42 primary biliary cirrhosis patients were studied using indirect immunofluorescence to detect antibodies against mitochondrial components and antibodies against nuclear components, ELISA to detect anti-Sp100, and immunoblot analysis to detect anti-gp210 and antibodies against nuclear components subtypes. RESULTS: Ninety-three percent of primary biliary cirrhosis patients in our study were antimitochondrial antibody positive. Forty-three percent of the patients were antinuclear antibody positive. Of these, 35% had antibodies against Sp100 and 36% were positive for anti-gp210. After transplantation, antimitochondrial antibody titers as well as antinuclear antibody titers decreased in all patients. Autoantibodies in low titer persisted for up to 13 years. The pattern of nuclear autoantigens recognized by patient sera was unchanged after liver transplantation. However, the antinuclear antibody pattern was very different between the individual patients. Anti-Sp100 and anti-gp210 were not detected in sera of patients with autoimmune hepatitis, hepatitis C infection, inflammatory bowel disease, connective tissue diseases, or primary sclerosing cholangitis. The serum alkaline phosphatase level was not different in antinuclear antibody negative or positive patients before or after transplantation. CONCLUSIONS: We conclude that the persistence of antibodies against mitochondrial components, and anti-Sp100 and anti-gp210 in primary biliary cirrhosis patients after liver transplantation is disease specific, but that this does not reflect recurrent disease activity in the graft.

Adult↗

Cloning and sequence analysis of four t(9;11) therapy-related leukemia breakpoints.

The t(9;11)(p22;q23) is the most common chromosomal translocation in topoisomerase II inhibitor therapy-related acute myeloid leukemia (tAML). This translocation fuses the MLL and AF9 proto-oncogenes producing a novel chimeric protein. In order to gain insight into the mechanism generating the t(9;11) and to clarify the role topoisomerase II inhibition may play in that mechanism we have cloned and sequenced the breakpoints from four tAML patients with the t(9;11). This sequence analysis identifies topoisomerase II consensus binding sequences near or at the chromosome 11 and chromosome 9 breakpoints in all four patients. One patient also had the consensus binding sequence for the TRANSLIN DNA-binding protein at the 9p22 and 11q23 breakpoints. Our results further support a direct role for topoisomerase II in the genesis of these tAML translocations.

Acute Disease↗

Validity of DSM-IV attention-deficit/hyperactivity disorder for younger children.

OBJECTIVE: Little is known about the validity of the diagnosis of attention-deficit/hyperactivity disorder (ADHD) in young children. Moreover, the results of the DSM-IV field trials raised concerns that inclusion of the new predominantly hyperactive-impulsive type of ADHD in DSM-IV might increase the likelihood of the diagnosis being given to active but unimpaired preschool and primary school children. METHOD: The validity of DSM-IV criteria for each subtype of ADHD was evaluated in 126 children, aged 4 through 6 years, and 126 matched comparison children. Probands and controls were classified by using structured diagnostic interviews of the parent and a DSM-IV checklist completed by the teacher. RESULTS: Children who met DSM-IV criteria for each subtype of ADHD according to parent and teacher reports differed consistently from controls on a wide range of measures of social and academic impairment, even when other types of psychopathology and other potential confounds were controlled. CONCLUSIONS: When diagnosed by means of a structured diagnostic protocol, all three DSM-IV subtypes of ADHD are valid for 4- through 6-year-old children in the sense of identifying children with lower mean scores on measures of adaptive functioning that are independently associated with ADHD.

Attention Deficit Disorder with Hyperactivity↗

Earlier positivity of central-venous- versus peripheral-blood cultures is highly predictive of catheter-related sepsis.

To diagnose catheter-related sepsis without removing the catheter, we evaluated the differential positivity times of cultures of blood drawn simultaneously from central venous catheter and peripheral sites. In a 450-bed cancer reference center, simultaneous central- and peripheral-blood cultures were prospectively performed for patients with suspicion of catheter-related sepsis over an 18-month period. Data for 64 patients for whom the same microorganisms were found when central- and peripheral-blood samples were cultured were retrospectively reviewed by two independent physicians blinded to the differential positivity time values in order to establish or refute the diagnosis of catheter-related sepsis. The diagnosis was established in 28 cases, refuted in 14, and indeterminate in the remaining 22. The differential positivity time was significantly greater for patients with catheter-related sepsis (P < 10(-4)). A cutoff limit of +120 min had 100% specificity and 96.4% sensitivity for the diagnosis of catheter-related sepsis. These results strongly suggest that measurement of the differential positivity time might be a reliable tool facilitating the diagnosis of catheter-related sepsis in patients with an indwelling catheter.

Catheterization, Central Venous↗

The tomato Hsf system: HsfA2 needs interaction with HsfA1 for efficient nuclear import and may be localized in cytoplasmic heat stress granules.

In heat-stressed (HS) tomato (Lycopersicon peruvianum) cell cultures, the constitutively expressed HS transcription factor HsfA1 is complemented by two HS-inducible forms, HsfA2 and HsfB1. Because of its stability, HsfA2 accumulates to fairly high levels in the course of a prolonged HS and recovery regimen. Using immunofluorescence and cell fractionation experiments, we identified three states of HsfA2: (i) a soluble, cytoplasmic form in preinduced cultures maintained at 25 degrees C, (ii) a salt-resistant, nuclear form found in HS cells, and (iii) a stored form of HsfA2 in cytoplasmic HS granules. The efficient nuclear transport of HsfA2 evidently requires interaction with HsfA1. When expressed in tobacco protoplasts by use of a transient-expression system, HsfA2 is mainly retained in the cytoplasm unless it is coexpressed with HsfA1. The essential parts for the interaction and nuclear cotransport of the two Hsfs are the homologous oligomerization domain (HR-A/B region of the A-type Hsfs) and functional nuclear localization signal motifs of both partners. Direct physical interaction of the two Hsfs with formation of relatively stabile hetero-oligomers was shown by a two-hybrid test in Saccharomyces cerevisiae as well as by coimmunoprecipitation using tomato and tobacco whole-cell lysates.

Amino Acid Sequence↗

[Effect of mast cell activation on microcirculation of intestinal mucosa in inflamed small intestine of the rat].

Intravital microscopy and FITC-labeled erythrocytes were used to investigate villous perfusion in the rat small intestine in a model of inflammatory bowel disease. Inflammation was induced with s.c. application of Indomethacin. It has previously been demonstrated that systemic Indomethacin leads to an increase in villous blood flow in the small intestine of the rat. In order to determine whether mast cell activation may contribute to the increase in villous perfusion, Ketotifen was used to inhibit mast cell degranulation. We found that Ketotifen significantly reduced villous perfusion in the inflamed intestine, but had no effect in the control group. We conclude that mast cell activation is one of the mechanisms leading to hyperemia in the mucosa of the small intestine in this animal model. Further studies are required to determine whether mast cell stabilizers may be beneficial in the treatment of inflammatory bowel disease in man.

Animals↗

[Reduction of local and systemic complications of acute pancreatitis by monoclonal antibody to ICAM-1].

The prognosis of acute necrotizing pancreatitis is dependent on systemic complications. The endothelial adhesion molecule ICAM-1 mediates both leukocyte adhesion and migration. Expression of ICAM-1 was investigated at various time points in mild and severe necrotizing pancreatitis in the pancreas, lungs and intestine. A possible therapeutic effect of monoclonal antibodies against ICAM-1 was evaluated in severe necrotizing disease. The expression of ICAM-1 preceded the fulminant leukocyte Infiltration of the organs. In contrast to mild pancreatitis, ICAM-1 expression was increased at an earlier time point and systemically in severe necrotizing disease. Treatment with antibodies against ICAM-1 improved microcirculation and reduced local and systemic organ damage in severe pancreatitis.

Animals↗

[Halicephalobus (Syn. Micronema) deletrix as a cause of granulomatous gingivitis and osteomyelitis in a horse].

Therapy resistant swellings of the maxillary region and unilateral nasal discharge in older horses are mainly thought to be consequences of neoplasias of the oral cavity, especially of the gingiva and the teeth, or to develop from tumours of the nasal cavity. We report an unilateral swelling of the left nasal and buccal region in a 13-year-old gelding, which was accompanied by an aggressive destruction of involved osseous tissue due to a severe proliferative granulomatous inflammation. The granuloma was caused by the nematode Halicephalobus (syn. Micronema) deletrix. This nematode infection is known for over 30 years, even though the here reported form is uncommon and rarely diagnosed. However, this report shows that even in cases of unilateral maxillary swellings in horses a granulomatous inflammation due to nematodiasis should be considered as an additional differential diagnosis.

Animals↗

[Lower bone density (osteopenia) in adolescent girls with oligomenorrhea and secondary amenorrhea].

Occurrence of reduced BMD among adolescent girls and young women due to certain specific oligomenorrhea or amenorrhea (anorexia nervosa, excessive sport or ballet, etc.) is well known. However the prevalence of osteopenia among 16-18 years old girls with the cycle disorders mentioned above--caused by "pure" hypothalamo-pituitary-ovarian insufficiency--is not yet sufficiently examined. The hormonal (FSH, LH, prolactin, LH/FSH, estradiol. testosterone, progesterone) and ion (Ca++,PO4(3-),Na+,K+,Cl-) parameters and the bone mineral density (BMD) of the lumbar spine of 19 girls age 16-18 with oligomenorrhea or secondary amenorrhea, due to hypothalamo-pituitary-ovarian axis insufficiency were investigated, and correlation were searched for among them. In 3 of the case significant BMD reduction was found with a value lower than the -2 SD. compared to the age, sex and race matched control values, showing definite osteoporosis. The BMD of 10 girls was between the -2.SD. and -1 SD.: they had osteopenia. Only 6 of them had normal BMD ranging from the -1 SD. to the +1 SD. Neither the ion or hormonal values, nor the clinical parameters (height, weight age, age at menarche, duration of amenorrheic period) showed correlation with the BMD values, except of the body mass index (BMI), which showed a loose positive linear correlation. The measured low BMD values have a significance, referring to a possible reduction in the peak BMD. Patients having low peak BMD have an inclination for earlier, and more sever osteoporosis and fractures in the climacteric decades. These results emphasize the need of effective and early treatment of adolescent bleeding disorders from the point of view of prevention of osteoporosis as well.

Adolescent↗

[Comparative study of verapamil and bisoprolol in the secondary prevention of myocardial infarction].

The effect of Ca-antagonist, long-acting verapamil and the selective beta-1 blocking bisoprolol were investigated and compared in the secondary prevention after myocardial infarction. Eighty-seven patients were enrolled, 27 patients were not included because of the exclusion criteria, 30 patients were treated with verapamil and 30 patients with bisoprolol. During the 540 days of follow up period treadmill ergometry and dobutamine stress-test with SPECT investigation were performed two times. Both clinically and the data of our investigations the effect of the two drugs in the secondary prevention was good, and even at the 540th day the protective effect was still excellent.

Adrenergic beta-Antagonists↗

Expression of natural and synthetic genes encoding herpes simplex virus 1 protease in Escherichia coli and purification of the protein.

An attractive target for anti-herpes chemotherapy is the herpes simplex virus 1 (HSV-1) protease encoded by the UL26 gene. Studies with HSV-1 strains that harbour mutations in the protease gene have demonstrated that the protease is essential for DNA packaging and virus maturation. The UL26 translation product is 635 amino acids long and undergoes autoproteolytic processing between residues Ala247/Ser248 and Ala610/Ser611. The N-terminal processing product (amino acids 1-247) contains the protease domain. To perform crystallization studies and high throughput screening for potent inhibitors, large amounts of the HSV-1 protease are required. However, expression of the natural HSV-1 protease gene in Escherichia coli using a T7-promoter-regulated system is low and does not allow for the efficient production of larger amounts of highly purified enzyme. In this report, we describe the use of a synthetic protease gene with optimized E. coli codon usage. The level of protease expression was at least 20 times higher with the synthetic gene as compared to the natural UL26 gene. The HSV-1 protease was purified to homogeneity in three steps using mixed-bed ion-exchange chromatography, affinity chromatography, and hydroxyapatite chromatography.

Amino Acid Sequence↗

Discrete determinants in transfer RNA for editing and aminoacylation.

During translation errors of aminoacylation are corrected in editing reactions which ensure that an amino acid is stably attached to its corresponding transfer RNA (tRNA). Previous studies have not shown whether the tRNA nucleotides needed for effecting translational editing are the same as or distinct from those required for aminoacylation, but several considerations have suggested that they are the same. Here, designed tRNAs that are highly active for aminoacylation but are not active in translational editing are presented. The editing reaction can be controlled by manipulation of nucleotides at the corner of the L-shaped tRNA. In contrast, these manipulations do not affect aminoacylation. These results demonstrate the segregation of nucleotide determinants for the editing and aminoacylation functions of tRNA.

Acetylation↗

Use of preoperative vascular embolisation in spinal metastasis resection.

Preoperative selective embolisation was carried out on 17 patients with spinal metastases from various primary tumours. There was a significant reduction in the blood loss (2088 ml) and infusion volume requirement (3500 ml) and more favourable postoperative haemoglobin (Hb) development compared with the non-embolised but otherwise identical control group. The reduced intraoperative bleeding manifested itself in the form of greater clarity and a less complicated intraoperative course. Particularly with a dorsal approach, the reduced bleeding permitted more exact preparation and more extensive tumour resection. Preoperative embolisation is thus a valuable aid in spinal metastasis resection. Given suitable indications and exact positioning of the embolising material, no significant complications should arise. The method as a whole calls for close collaboration between interventional radiologists and spinal orthopaedists.

Blood Loss, Surgical↗