Biomedical subjects
Publications and source records attributed to A Weber.
We report a case of a neonate with sectional narrowing of the spinal cord on the level of T12 to L2 and a deformed vertebral body on a different level, L4. In previously described cases of sectional spinal dysgenesis, the vertebral and spinal cord malformations are usually found on the same level. Our case may represent a new variant of spinal dysgenesis.
UNLABELLED: While breast milk appears to be superior to formula for the development of very low birthweight (VLBW) infants, it is supplemented to meet the metabolic demands of the rapidly growing premature infant. To estimate the nutritional variability of breast milk from mothers of VLBW infants, protein (bicinchoninic acid method) and fat content (creamatocrit) were measured in breast-milk spot samples from mothers of 20 VLBW infants, collected 4 times a day during the first 4 wk of lactation. Protein content (median 1.9 g dl(-1), range 1.1-3.5 g dl(-1)) and fat content (3.8/1.0-14.6 g dl(-1)) were highly variable and lacked a normal distribution over all samples and in individual women's milk. There was only a weak correlation between fat and protein (rs=0.416, p < 0.001). Fat but not protein was lower in morning samples than in samples collected later in the day (p < 0.001). Protein but not fat content decreased during the weeks of lactation (rs =-0.446, p < 0.001). No impact of the baby's gestational age was observed. CONCLUSION: The fat and protein content of breast milk from mothers of VLBW infants is highly variable, calling into question the clinical feasibility of individualized supplementation of breast milk for VLBW infants based on spot sample measurements.
We report on the case of a 35 year-old woman who was initially admitted for acute pancreatitis in october 1995. The patient was suffering from asthma (since childhood) and diffuse abdominal pain (since adolescence). The diagnosis of cystic fibrosis was made fortuitously during a sterility evaluation. After extensive etiological screening the acute pancreatitis was considered to be a manifestation of the cystic fibrosis. Despite therapy with pancreatic enzymes, the patient continued to suffer from chronic abdominal pain. High intake of analgesics was required. Until December 1995, the patient was repeatedly admitted for episodes of acute pancreatitis. In January 1996, we initiated a preventive treatment with subcutaneous octreotide between 100 and 200 microgram, three time a day. Thereafter, there were fewer episodes of pancreatitis and the consumption of analgesics decreased. Side effects of octreotide were intermittent diarrhea and development of cholelithiasis that was complicated by biliary migration in November 1998. In June 1999, the prolonged-release form of the molecule was given without modification of the efficacy.
We are developing cell therapy approaches on non-human primates as a preclinical model for the treatment of hepatic metabolic diseases. In foetuses, the tissues, including liver, are in expansion, which should facilitate hepatocytes engraftment, and the immune system becomes fully mature only after birth. We have set out conditions for isolation of fetal hepatocytes from macaca mulatta at the end of the 2nd trimester of gestation (90-100 days), their cryopreservation and retroviral transduction. Two different routes of administration of hepatocytes were evaluated: the umbilical vein which was deleterious for the foetuses, and the intraparenchymatous injection which was well tolerated by the animals. Administration of hepatocytes into the hepatic parenchyma resulted in microchimerism and allogenic cells were visualized 9 days after transplantation. Another approach has been to immortalize simian foetal hepatocytes using a retroviral vector expressing SV40 Large T flanked by lox sites. A cell line has been established for 2 years, which is not tumorigenic when injected subcutaneously into nude mice and display characteristics of bipotent hepatoblasts, precursors of hepatocytes and biliary cells. After orthotopic transplantation into nude mice via the portal vein, these cells expressed albumin until the sacrifice of the animals (17 days). The next steps will be to define conditions for transplantation of retrovirally transduced fetal primary and/or immortalized hepatocytes into young foetuses (60 days of gestation) and post-natally.
BACKGROUND AND OBJECTIVES: The aim of this study was to gather, against the background of a long-discussed deficit in academic teaching, data on the current activities of medical faculties with regard to teaching, and to analyse these findings. Another aim was to obtain suggestions for establishing a consensus on indicators that could be used to assess the quality of teaching. MATERIAL AND METHODS: In March 2000, a written inquiry was addressed to the deans of all 37 medical faculties in Germany. The questionnaire, arranged so that responses could be entered into a data-base, consisted of ten items in three parts. Part 1 concerned the evaluation of teaching, parts 2 and 3 dealt with the place of specific assessment of teaching in the process of choosing lecturers ("habilitation") and appointing senior professors. In addition to providing alternative answers (in some instances, allowing a choice of several alternatives) there was also space for written comments. The answers were analysed by descriptive statistics. RESULTS: All questionnaires were returned in a usable form (response rate 100%). 36 faculties had, at the time of receiving the questionnaire, already instituted teaching assessments, of clinical teaching sessions more often than preclinical ones (97% vs 89%). The most widespread method of assessment consisted of obtaining students' opinion and of using the centralized written examinations of the institute for Medical and Pharmaceutical Examination Questions. In more than half of the faculties (57%) an above-average teaching performance by teachers was acknowledged in special ways (honours/prizes). In 31 faculties (84%) teaching experience counted as an absolute prerequisite for obtaining a lectureship, but as a rule without employing any defined standards. With regard to the selection of senior professors, 27 faculties (73%) explicitly took teaching competence into account. Defined criteria for assessing teaching ability were largely absent. CONCLUSIONS: The assessment of teaching quality can be considered as well established at medical faculties in Germany. However, the methods and models used are highly heterogeneous. Furthermore, numerous activities exist in the various faculties to increase the importance attached to academic teaching. However, despite using diverse indicators of quality, the central problems for assessing teaching ability remain unsolved.
FUSE binding protein (FBP) binds in vivo and in vitro with the single-stranded far upstream element (FUSE) upstream of the c-myc gene. In addition to its transcriptional role, FBP and its closely related siblings FBP2 (KSRP) and FBP3 have been reported to bind RNA and participate in various steps of RNA processing, transport or catabolism. To perform these diverse functions, FBP must traffic to different nuclear sites. To identify determinants of nuclear localization, full-length FBP or fragments thereof were fused to green fluorescent protein. Fluorescent-FBP localized in the nucleus in three patterns, diffuse, dots and spots. Each pattern was conferred by a distinct nuclear localization signal (NLS): a classical bipartite NLS in the N-terminal and two non-canonical signals, an alpha-helix in the third KH-motif of the nucleic acid binding domain and a tyrosine-rich motif in the C-terminal transcription activation domain. Upon treatment with the transcription inhibitor actinomycin D, FBP completely re-localized into dots, but did not exit from the nucleus. This is in contrast to many general RNA-binding proteins, which shuttle from the nucleus upon treatment with actinomycin D. Furthermore, FBP co-localized with transcription sites and with the general transcription factor TFIIH, but not with the splicing factor SC-35. Taken together, these data reveal complex intranuclear trafficking of FBP and support a transcriptional role for this protein.
Tiam1 activates the Rho-like GTPase Rac1, and studies indicate that Tiam1-Rac1 signaling affects invasion in different ways depending on the cell type studied. However, no investigations on Tiam1 in human tumors have been reported. Here, we show that for 4 of 5 human renal-cell carcinoma (RCC) cell lines the expression levels of Tiam1 tended to be inversely correlated with in vitro invasiveness, whereas no obvious correlation could be found between the expression levels of Rac1 and invasion. Subsequent mutation analysis of these cell lines revealed no mutations in Rac1 but up to 5 different point mutations in the Tiam1 gene. Of these, 1 mutation (A441G) was located in the NH2-terminal pleckstrin homology domain, which is essential for membrane localization and functional activity of Tiam1. By analysis of an additional 30 primary human RCCs, mutation A441G was found in 4 of 35 tumors and tumor cell lines (11.5%) but not in the respective normal kidney tissues. By enzymatic digestion, mutation A441G proved to be heterozygous, suggesting a dominant active function. This was supported by showing that stable over-expression of mutated A441G-Tiam1 induced transformation of NIH3T3 cells, as determined in a colony formation assay, whereas empty vector and wild-type Tiam1 failed to do so. In conclusion, a distinct Tiam1 mutation (A441G) was identified in several human RCCs. This mutation induced transformation of NIH3T3 cells and, hence, might play a major role in the progression of human RCCs. Further analyses on Tiam1 mutations in human tumors might give new clues to their role in tumor progression.
BACKGROUND: The actual value of medical dissertations is under current discussion. Studies concerning medical dissertation focused on successful candidates only. Therefore, data about physicians without "MD" are still lacking. PERSONS AND METHODS: We therefore performed a representative study of both, physicians with and without the "Dr. med." degree. Using an anonymous questionnaire we asked for reasons to perform a doctoral thesis. RESULTS: A total of 321 questionnaires could be evaluated (successful candidates n = 181; unsuccessful candidates n = 140). Nearly 96% have attempted to perform a medical dissertation at the beginning of their studies. Only 4% never had this intention. However, 67% answered that writing a medical dissertation has no relevance in clinical practice. For 80% of the successful physicians, it was the first attempted dissertation, they judged the supervision as very good or good. Physicians who did not write a medical dissertation stated that deficits in planning and supervising were the main reason for prematurely breaking off. 90% of the successful dissertationists thought that it had been personally meaningful and recommended the procedure to younger physicians. However, two-thirds of the practicing physicians without "MD" still intend to write a thesis. CONCLUSION: We conclude that the medical dissertation is highly rated in terms of personal and scientific value and should therefore remain a part of medical studies and science.
Glucocorticoids exert their regulatory effects on the hypothalamic-pituitary-adrenocortical axis via two types of corticosteroid receptors: the glucocorticoid receptor and the mineralocorticoid receptor. Whereas the glucocorticoid receptor has a broad distribution in the brain, highest levels of mineralocorticoid receptor are found in the hippocampus. Based on the differential occupancy profile by endogenous glucocorticoids, glucocorticoid receptors are thought to mediate negative feedback signals of elevated glucocorticoid levels, whereas mineralocorticoid receptors control the inhibitory tone of the hippocampus on hypothalamic-pituitary-adrenocortical axis activity. Dysfunction of mineralocorticoid receptors and glucocorticoid receptors are thought to be implicated in stress-related psychiatric diseases such as major depression. Because of its intriguing features, we focus in this review on the mineralocorticoid receptor and provide data which reveal novel aspects of the pharmacology and physiology of mineralocorticoid receptors. Newly obtained results are presented, which help to solve the paradox of why dexamethasone binds with high affinity to mineralocorticoid receptors in vitro, yet binds poorly in vivo. Until recently, mineralocorticoid receptor protein and mRNA levels could only be routinely studied with in vitro cytosol binding assays, in vitro and in vivo receptor autoradiography, Northern blot analysis, and in situ hybridization. These methods are unfortunately hampered by several flaws, such as the necessity of adrenalectomy, no or poor neuroanatomical resolution, the fact that mRNA does not provide the same information as protein, or combinations of these factors. We present immunohistochemical data on mineralocorticoid receptors in the brain obtained by using commercially available antibodies, which alleviate many of these shortcomings. Furthermore, an in vivo microdialysis method is presented which allows the assessment of free corticosterone levels in the brain, which is critical for the study of the pharmacological basis of mineralocorticoid receptor (and glucocorticoid receptor) function. Finally, a novel aspect of the regulation of mineralocorticoid receptors is described which provides evidence that this receptor system is dynamically regulated. In conjunction with previously reported effects of antidepressants, these results have initiated a new concept on the cause of the hypothalamic-pituitary-adrenocortical axis disturbances often seen in stress-related psychiatric disorders such as major depression.
A recent report suggested that platelet-derived growth factor (PDGF) activates nuclear factor-kappa B (NF-kappa B) by phosphorylation of the protein kinase Akt [Romashkova and Makarov, Nature 401 (1999) 86-90]. The present study investigates the role of Akt in the activation of NF-kappa B by tumor necrosis factor-alpha (TNF alpha, 10 ng/ml) and PDGF-BB (20 ng/ml) in human vascular smooth muscle cells (SMC), skin and foreskin fibroblasts. TNF alpha stimulated serine phosphorylation and degradation of the inhibitory protein I kappa B alpha and strongly induced nuclear NF-kappa B translocation and binding activity. PDGF did not induce serine phosphorylation or degradation of I kappa B alpha and did not enhance binding activity of NF-kappa B. In contrast, stimulation with PDGF resulted in a marked phosphorylation of Akt, but no Akt phosphorylation occurred after stimulation with TNF alpha. These data suggest that Akt phosphorylation is not involved in NF-kappa B activation in human SMC and fibroblasts.
This study investigates the role of platelet-derived microparticles for vascular smooth muscle cell (SMC) proliferation. Microparticles concentration dependently stimulated p42/p44 MAP kinase phosphorylation, c-fos induction, DNA synthesis, and proliferation of cultured bovine coronary artery SMC. The maximum mitogenic effects of microparticles were significantly higher than those of platelet-derived growth factor (PDGF)-BB. Microparticle-induced SMC mitogenesis was heat sensitive, whereas the effects of PDGF were not. In addition, neutralizing anti-PDGF antibodies prevented PDGF-induced DNA synthesis but did not inhibit the effects of microparticles. In contrast to PDGF, which potently stimulated SMC migration, microparticles had only minor migratory activity. These results demonstrate a novel mechanism of SMC mitogenesis by platelet-derived microparticles that is probably independent of PDGF.
This study investigates the possible modulation of platelet-derived growth factor-(PDGF, 20 ng/ml)-induced DNA synthesis in bovine coronary artery smooth muscle cells by the protein kinase A inhibitors Rp-adenosine-3',5'-cyclic phosphorothioate (Rp-cAMPS, 0. 03-10 microM) and ¿N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, HCl¿ (H-89, 0.01-1 microM). Rp-cAMPS concentration dependently enhanced PDGF-induced DNA synthesis. In contrast, no potentiation of PDGF-induced DNA synthesis was seen with H-89. However, H-89 but not Rp-cAMPS, inhibited p42/p44 mitogen-activated protein kinase phosphorylation. Thus, Rp-cAMPS, but not H-89, unmasks inhibitory actions of protein kinase A on PDGF-induced mitogenesis of vascular smooth muscle cells. Low specificity may limit the use of H-89 as protein kinase A inhibitor.
BACKGROUND: With the changes in the structure of education and society, in recent years also the medical habilitation (German postdoctoral lecturing qualification) has been called into question as an academic qualification. With this in mind, the aim of our study was to discover the current opinion of those who had successfully completed a habilitation on the prerequisites for a habilitation, the habilitation procedure and the status of a habilitation, and to document potential wishes for reform. COLLECTIVE AND METHODS: The target group of our survey were the 616 persons (female: 77, male 539) who successfully completed their habilitation in 1997 at one of the 36 German medical faculties. The database was formed by an anonymous questionnaire (23 items), which included questions on sociodemographic factors and occupational history (general part), and subjective opinions (specific part). Recruitment of the participants in the survey and passing on of the questionnaire were carried out by the office of the medical dean of the various universities, as the names of those who had completed a habilitation were not available to the investigators for reasons of protecting the individual's rights and identity. Evaluation of the returned questionnaires was carried out using descriptive statistics. Subgroups were formed according to sex, age and subject groups. RESULTS: The questionnaire was answered in a useable form by 389 persons (female: 46, male 343) from 35 medical faculties (return quota 63%). 95% of those who took part in the survey were registered doctors; 79% of these came from clinics, 16% from the field of theoretical medicine. 81% were specialist physicians. 5% had studied the natural sciences or humanities. The median age at the time of completing the habilitation was 38 years (minimum 30, maximum 54 years old). At present 93% were assistant professors, 5% were professors. The median interval between the doctoral thesis and habilitation was 10 years. 58% had carried out a period of research abroad. In 90% of cases the persons had written a postdoctoral thesis for their habilitation, 10% qualified cumulatively. 47% had improved their occupational rank within a period of 2 years after completing the habilitation, about 2/3 of these reached senior positions. Among the prerequisites for habilitation, "Humboldt's trias" (research, teaching and caring for patients) was accepted by the great majority. Other prerequisites regarded as important for habilitation were publications, holding talks, specialist status and experience abroad. Impact factors, however, should be regarded as important conditions for habilitation only in combination with other criteria. The value of a habilitation was not called into question; 89% would recommend completing one. 80% of those questioned, however, thought the procedure for completing a habilitation should be optimized. The general abolition of the medical habilitation was, however, not desired by the vast majority. CONCLUSION: The value of completing a medical habilitation is not a point for debate for most of those who successfully completed one. It remains the springboard for occupational advancement. The vast majority do not wish to see it abolished. Also the usual prerequisites for habilitation are accepted by the majority of persons. The procedure for completing a habilitation is, however, regarded as in need of improvement. There is a wide consensus of opinion regarding potential aims for reform.
Explore the source record for details and available documents.
The aryl-propionic acid derivative, ketoprofen, has been shown to inhibit fibroblast growth by a cylooxygenase-dependent mechanism [Sánchez, T., Moreno, J.J., 1999. S(+) enantiomer inhibits prostaglandin production and cell growth in 3T6 fibroblast cultures. Eur. J. Pharmacol. 370, 63-67]. The present study demonstrates that ibuprofen, another aryl-propionic acid derivative, inhibited platelet-derived growth factor-BB (20 ng/ml)-induced mitogenesis of cultured bovine coronary artery smooth muscle cells in a stereo-independent manner. In addition, pretreatment of the cells with indomethacin (3 microM) did not affect the inhibitory effects of ibuprofen enantiomers on smooth muscle cell mitogenesis. Thus, aryl-propionic acid-type cyclooxygenase inhibitors can inhibit cell proliferation by both, cyclooxygenase-dependent and -independent ways.
Screening of transposon-associated mutants of Arabidopsis thaliana for altered starch metabolism resulted in the isolation of a mutant that did not accumulate starch in any tissue or at any developmental stage (starch-free mutant, stf1). Allelism tests with known mutants showed that stf1 represents a new mutant allele of the plastid isoform of the enzyme phosphoglucomutase (PGMp). The mutation was mapped to chromosome 5. An Arabidopsis EST that showed significant homology to the cytosolic isoform of phosphoglucomutase (PGM) from maize was able to complement the mutant phenotype. The Arabidopsis EST was transcribed and translated in vitro and the protein product was efficiently imported into isolated chloroplasts and processed to its mature form. The lack of starch biosynthesis in stf1 is accompanied by the accumulation of soluble sugars. The rate of CO2 assimilation measured in individual leaves was substantially diminished only under conditions of high CO2 and low O2. Remarkably, stf1 exhibits an increase rather than a decrease in total leaf PGM activity, suggesting an induction of the cytosolic isoform(s) in the mutant. The substrate for PGM, glucose 6-phosphate, accumulated in stf1 during the day, resulting in 10-fold higher content than in the wild type at the end of the photoperiod.
The high prevalence of aspirin intolerance in asthmatics and patients with nasal polyps as well as reports of familial clustering suggest a genetic disposition of this disease. Our study aimed at obtaining further evidence of hereditary factors in this disease. We included 33 unselected patients from 28 families with aspirin intolerance and rhinosinusitis in this study. Controls were recruited from individuals treated in our ENT clinic for diseases other than aspirin intolerance (n = 52). A questionnaire focused on family histories as well as reports on diseases of the upper respiratory tract or allergies. ASS intolerance was verified either by bronchial or nasal provocation tests. We found cases of aspirin intolerance among parents, siblings, and children of ASS intolerant probands. The children of probands had nasal polyps and rhinosinusitis more often than the children of controls. We propose that ASS intolerance with nasal polyps and asthma represents a complex phenotype, with genetic and environmental factors contributing to its manifestation.
The present study gives a survey of radiological findings after surgical treatment of laryngeal and pharyngeal carcinomas, whereby the surgical procedures and the localisation of tumours found special consideration. One important point of view of modern surgery is the improvement of quality of life. By reason of this point the role of reconstructive surgery will become increasingly important. Representative radiographs between 1997 and 1999 are discussed to show the difficulties to distinguish between normal and pathological postoperative findings after operations of hypopharyngeal diverticula, after partial and total laryngectomy as well as after different methods of surgical reconstructions of pharynx. The examinations which are shown were realized with the conventional radioscopy. Hereby the normal radiological findings and their comparison to the particular postoperative specials rank first. Furthermore the early and late postoperative complications are mentioned. A variety of surgical procedures in treatment of laryngeal and pharyngeal carcinoma make new demands on the postoperative diagnostic possibilities especially on the postoperative pharyngography. The variability of the postoperative radiographs complicates the differentiation between normal and pathological radiological findings and only the exact knowledge of the performed surgical procedure allows their differentiation.