Regulation of functional steroid receptors and ligand-induced responses in telomerase-immortalized human endometrial epithelial cells.

Information on the regulation of steroid hormone receptors and their distinct functions within the human endometrial epithelium is largely unavailable. We have immortalized human primary endometrial epithelial cells (EECs) isolated from a normal proliferative phase endometrium by stably transfecting the catalytic subunit (hTERT) of the human telomerase complex and cultured these hTERT-EECs now for over 350 population doublings. Active hTERT was detected in hTERT-EECs employing the telomerase repeat amplification assay protocol. hTERT-EECs revealed a polarized, non-invasive epithelial phenotype with apical microvilli and production of a basal lamina when grown on a three-dimensional collagen-fibroblast lattice. Employing atomic force microscopy, living hTERT-EECs were shown to produce extracellular matrix (ECM) components and ECM secretion was modified by estrogen and progesterone (P4). hTERT-EECs expressed inducible and functional endogenous estrogen receptor-alpha (ER-alpha) as demonstrated by estrogen response element reporter assays and induction of P4 receptor (PR). P4 treatment down-regulated PR expression, induced MUC-1 gene activity and resulted in increased ER-beta transcriptional activity. Gene activities of cytokines and their receptors interleukin (IL)-6, leukemia inhibitory factor (LIF), IL-11 and IL-6 receptor (IL6-R), LIF receptor and gp130 relevant to implantation revealed a 17 beta-estradiol (E2)-mediated up-regulation of IL-6 and an E2- and P4-mediated up-regulation of IL6-R in hTERT-EECs. Thus, hTERT-EECs may be regarded as a novel in vitro model to investigate the role of human EECs in steroid hormone-dependent normal physiology and pathologies, including implantation failure, endometriosis and endometrial cancer.

Dramatic development of quadriplegia in a young man while engaged in heavy manual labour: a post-traumatic spinal cord injury?

A healthy 16-year-old male suddenly developed paraesthesiae in his hands during heavy manual labour. He was able to walk to the nearest doctor's practice himself. The symptoms worsened dramatically, and within a short period of time cardiac arrest occurred. After resuscitation and intensive care, quadriplegia due to a high cervical cord lesion was diagnosed. The patient died 70 days later without any changes in the neurological symptoms. Post mortem revealed severe focal ischaemic lesions in the cervical spinal cord in a mixed arterial/venous distribution, but no evidence of direct traumatic changes in the spinal cord, the spine or the soft tissues. All other possible causes than trauma were excluded. The clinical development of the symptoms suggest that this spinal cord lesion should be classified as a secondary traumatic spinal cord injury caused by a subluxation of the cervical spine. The pathogenesis of post-traumatic ischaemic damage to the spinal cord appears to be related to localized hypercoagulability resulting in the formation of microthrombi. Impaired microcirculation in a limited area and for a limited period of time may have caused the irregularly distributed ischaemic necrosis.

Severe hemoptysis requiring lobectomy in an 11-year-old patient with Kartagener's syndrome.

The case of a young girl with severe hemoptysis in a Kartagener's syndrome is described. Because bronchoscopy failed to locate the origin of the bleeding, preoperative angiography was performed. The patient was treated by resection of the middle lobe. The bronchus wall was located as the origin of bleeding.

Lipoma of the larynx. Report of 2 cases and review of the literature.

Among the primary mesenchymal tumors of the hypopharynx and larynx lipomas are very rare, as they often look macroscopically like retention cysts. Up today approximately 112 cases have been described in literature. We present two further cases of laryngeal lipomas, which were removed endoscopically and by an external approach. Both patients were free of local recurrence.

[Brain drain in stem cell research? The views and attitudes of stem cell researchers in Germany]. / Brain Drain in der Stammzellforschung? Erste Ergebnisse einer Befragung von Wissenschaftlern zur Lage der Stammzellforschung in Deutschland.

The legal status of stem cell research in Germany has most recently been debated at the highest political level. Stakeholders have argued referring to the situation of stem cell researchers in past debates; however, a survey of the views and attitudes of German stem cell researchers is currently being performed by the University of Marburg also involving a team at Exeter University. Here, we present some of the first findings from this study on the basis of 14 qualitative interviews and 117 responses to the quantitative survey. The data suggest that the motives for engaging in particular areas of research are multilayered. Respondents take a critical view towards the way in which research on human embryonic stem cells has been regulated. The majority of interviewees rejected a change in legislation involving the amendment of the cut-off date for the import of human embryonic stem cells lines. Also, the recent changes in the German regulation of stem cell research that, among other changes, include a change of the cut off date for the production of lines which could become used in the country from January 2002 to May 2007 appear not to be received as a satisfactory solution of the constraints experienced by science through the law in Germany.

[2 cases of Whipple's disease with different outcomes]. / Zwei Fälle von Morbus Whipple mit unterschiedlichem Ausgang.

A 45-year-old man developed migratory arthritis and fever, at first believed to be caused by rheumatoid arthritis. Whipple's disease was eventually diagnosed after a malabsorption syndrome had occurred and biopsies been taken from the distal duodenum and jejunum. The patient was cured after several months on tetracycline. In a second case, a 73-year-old woman, malabsorption of six months' duration resulting from Whipple's disease had brought about such deterioration that after hospitalisation she died despite a correct diagnosis and an appropriate treatment.

[Analysis of FIM-values during the hospital treatment of patients with acute spinal cord injury]. / Analyse von FIM-Werten während der stationären Behandlung nach akuter Querschnittlähmung.

The cost pressures in the German health care system continue to rise. In the context of the introduction of the DRG system, adequate treatment of paraplegic and tetraplegic patients within the financial limits will become even more difficult. In dispute with health care insurance companies, scientifically sound studies have been lacking to justify a treatment lasting up to six months as an in-patient of individuals with acute spinal cord injury or disease. The FIM (Functional Independence Measurement), established as a reliable tool in the evaluation of the functional development of patients presenting with acute spinal cord lesions, has been used as the basic tool in our study. Under the conditions of a specialized spinal cord injury centre the FIM showed a statistically highly significant increase of functional independence during the entire course of treatment. No therapeutic standstill could be detected in order to determine a point of discharge. Even in the last six weeks of treatment significant progress in functional independence can be observed.

A case of rapidly progressive multiple system degeneration: morphological findings and pathogenetic implications.

A 62-year-old woman was referred to our psychiatric hospital by the municipal health office, because she was in such a neglected condition that she was a danger to herself. Initially, it was suspected that she was suffering from dementia or psychosis. X-rays led to the suspicion of bronchial carcinoma. Consequently, the mental changes were interpreted as probable effects of metastases to the brain. There was not enough time, however, to check the patient thoroughly to find the actual cause of her altered personality. The patient developed a high fever (up to 42 degrees C). A few days later, she died of cardiorespiratory failure with severe abscess-forming obstructive pneumonia. An autopsy confirmed the bronchial carcinoma. However, metastases were only found in the hilar lymph nodes. No metastases were detectable in the CNS, either macroscopically or microscopically. The neuropathological examination of the brain revealed multiple system degeneration. The striking microscopic findings (a large number of typical apoptotic figures visible with the light microscope in ganglion cells, lack of cytoplasmic inclusion bodies in the oligodendroglia and an unusually strong monocytic reaction (so-called reactive satellitosis) indicated that the disease course had been very rapid. Perhaps these were early steps in the evolution of a multisystem atrophy. A kind of time-lapse effect, as it were, revealed simultaneously individual details of the pathogenetic course, which would have disappeared in the usual long course of the disease and thus could not have been observed, even with the most up-to-date molecular methods. It is very likely that this was a paraneoplastic syndrome.

The immunological significance of cellular infiltrates in chronic rejection of human kidney transplants.

Fifteen transplanted human kidneys with clinical and histological signs of chronic rejection were examined microscopically for cellular infiltration. Three normal kidneys were used as a reference. All infiltrating cells were classified and counted. The average number of cells per 10 microscopic fields was called the relative density of cellular infiltrates. Differences in the densities of different cell classes and changes in the cellular infiltration of the grafts were regarded as cellular expressions of the immune response. Summarizing our results, we conclude that: 1) the chronic immunological rejection of transplanted human kidneys is essentially caused by immunocompetent cells; 2) plasma cells develop in the graft itself; 3) the immunocompetent cell population tends to be purely and simply made up of plasma cells; 4) therefore, the true "effector cell" among the immunocompetent cells may be the plasma cell--at least in the chronic rejection of transplanted human kidneys. Cleaved lymphocytes were the most frequent of the infiltrating cells found in the transplants. However, their role is not yet clear.

[Propofol for anesthesia and short-term sedation. The final word on use in children under three years]. / Propofol zur Narkose und Kurzzeitsedierung. Plädoyer für die Anwendung auch bei Kindern unter drei Jahren.

Since its introduction in clinical use more than ten years ago, propofol is well appreciated for sedation and supplemental hypnosis in anaesthesia. However the substance is approved only for anaesthesia in children elder than three years. As can be substantiated by many data reported in literature, there are no pharmacokinetic or pharmacodynamic reasons whatsoever to withhold propofol from the younger children; this applies both to the use as a narcotic supplement and as a short term hypnotic for diagnostic and therapeutic interventions.

A potential role of the cytoskeleton of Saccharomyces cerevisiae in a functional organization of glycolytic enzymes.

Numerous individual enzymes participate in a given synthetic or degradative pathway in which the product of one reaction becomes the substrate for the subsequent enzyme. This raises the question of whether the product of one 'soluble' enzyme diffuses freely through the available cell volume, where it accidentally collides with the subsequent 'soluble' enzyme. Alternatively, enzymes acting in a given pathway may be organized in ordered structures, metabolons. Certain glycolytic enzymes have been shown to co-localize with the cytoskeleton in mammalian cells. We deleted genes coding for proteins associated with the cytoskeleton of Saccharomyces cerevisiae: TPM1 coding for tropomyosin, SAC6 for fimbrin and CIN1 for a microtubule-associated protein. Single deletions or deletions of two such genes had no effect on the specific activities of glycolytic enzymes, or on the rates of glucose consumption and ethanol production. However, the concentrations of glycolytic metabolites during a switch from a gluconeogenic mode of metabolism, growth on an ethanol medium, to glycolysis after glucose addition showed transient deviations from the normal change in metabolite concentrations, as observed in wild type cells. However, all metabolites in mutant strains reached wild-type levels within 2-4 h after the shift. Only ATP levels remained low in all but the tmp1-Delta-sac6-Delta double mutant strains. These observations can be interpreted to mean that metabolic reorganization from a gluconeogenic to a glycolytic metabolism is facilitated by an intact cytoskeleton in yeast.

[On the etiology of spindle-shaped acid-fast bodies in the human spleen (author's transl)]. / Säurefeste Spindlekörper in der menschlichen Milz. Ein Beitrag zu ihrer Atiologie

Spindle-shaped acid-fast bodies have been identified only in lymph nodes till now. Their nature and their origin remained unclear. We have also found these bodies in the human spleen. Their staining reactions and their correlations to age, sex, weight of spleen, and to hemosiderin deposits were examined. They have been encountered in 50% of cases of hereditary spherocytosis and in 41.7% of cases of traumatic rupture of the spleen--but only in 2.3% of all other cases of groups of various other disorders. We conclude from our results that: 1. The spindle-shaped acid-fast bodies are made of ceroid. 2. They are not causative organisms and therefore cannot be of importance in the etiology of sarcoidosis. 3. They derive from increased destruction of erythrocytes. 4. They originate due to oxidative polymerization of membrane lipids. 5. They may also be found in absence of any fat-metabolism disturbance.

[Adenoid cystic carcinoma of the trachea. Case report and review of the literature on malignant tracheal tumors]. / Das adenoidzystische Karzinom der Trachea. Fallbericht und Literaturübersicht zu den malignen Trachealtumoren.

Primary tumours of the trachea are rare. In most cases one finds squamous cell carcinoma or adenoid cystic carcinoma. At the Department of Otolaryngology, Head and Neck Surgery at the Christian-Albrechts-Universität of Kiel only 19 malignant tumours of the trachea were diagnosed between 1949 and 1992 among a total of 6000 malignancies. In most cases the patients suffered from invasive thyroid carcinoma. Only five patients had a primary malignancy of the trachea (2 squamous cell carcinomas, 1 adenoid cystic carcinoma, 1 undifferentiated carcinoma, 1 solid, otherwise not classifiable carcinoma). Of these patients we report on the case of a 57-year old female patient who was diagnosed with an adenoid cystic carcinoma of the trachea and is free of disease eight years after open resection. Since initial symptoms are nonspecific emphasis is on the diagnostic process. The latest publications on therapeutic measures are reported.

Aortic annular enlargement with the use of a homograft valve.

A technique of annular enlargement for use in homograft aortic valve surgery is described. Potential advantages of this technique, that allows convenient valve sizes in small aortic annuli, lie in the pediatric group of patients requiring aortic valve replacement.

[Mucoepidermoid cancer of the larynx. Case report and review of the literature]. / Mukoepidermoides Karzinom des Larynx. Fallbericht und Literaturübersicht.

Mucoepidermoid carcinoma (MEC) is classified among the salivary gland tumours and is most commonly found in the parotid gland. It rarely occurs in the larynx. There have been only 87 cases of laryngeal MEC reported in the literature. We report on an MEC of the vocal cord in a 75-year-old man, with a thickened right vocal cord without any loss of movement. The initial diagnosis was squamous cell carcinoma. One year after radiotherapy a tumour recurrence developed. Because the patient refused to laryngectomise, a tumour resection with the CO2 laser was performed twice. To date, the patient has been free from disease for more than five years. The true incidence of this type of neoplasm could be higher than is believed because of its frequent misdiagnosis as squamous cell carcinoma.

Investigation of two yeast genes encoding putative isoenzymes of phosphoglycerate mutase.

Our previous data indicated that GPM1 encodes the only functional phosphoglycerate mutase in yeast. However, in the course of the yeast genome sequencing project, two homologous sequences, designated GPM2 and GPM3, were detected. They have been further investigated in this work. Key residues in the deduced amino acid sequence, shown to be involved in catalysis for Gpm1 (i.e. His8, Arg59, His181) are conserved in both enzymes. Overexpression of the genes under control of their own promoters in a gpm1 deletion mutant did not complement for any of the phenotypes. This could in part be attributed to a lack of expression due to their weak promoters. Higher level expression under the control of the yeast PFK2 promoter partially complemented the gpm1 defects, without restoring detectable enzymatic activity. Nevertheless, deletion of either GPM2 or GPM3, or the two deletions in concert, did not produce any obvious lesions for growth on a variety of different carbon sources, nor did they change the levels of key intermediary metabolites. We conclude that both genes evolved from duplication events and that they probably constitute non-functional homologues in yeast.

Leiomyosarcoma of the larynx.

Leiomyosarcomas account for approximately 7% of all soft-tissue sarcomas and occur most frequently in the gastrointestinal tract and uterus. Leiomyosarcomas of the larynx are extremely rare with only about 27 cases reported in the available literature. We present a leiomyosarcoma of the left vocal cord that was treated by transoral CO2 laser surgery. To date, the patient has been free of disease for more than 25 months. Since these tumors may be difficult to diagnose, immunohistochemical studies may be necessary for making an unambiguous diagnosis. Primary treatment should be surgical resection, with small tumors suitable for partial laryngectomy or transoral laser surgery.

[Psammomamatoid ossifying fibroma of the frontal sinus with intracranial extension]. / Psammomatoides ossifizierendes Fibrom des Sinus frontalis mit intrakranieller Ausbreitung.

Case report of a 29-year-old woman with an psammomatoid ossifying fibroma of the left frontal sinus. Headache was the presenting clinical symptom. The tumor and its intracranial extension were identified by computed tomography and magnetic resonance tomography. Through a two-step combined neuro-rhinosurgical operation the tumor could be completely removed. Ossifying fibroma is a benign tumor mostly affecting the mandible and maxilla. A more aggressive approach may be more beneficial than expectant observation or curettage in the initial management of this benign neoplasm. Because of the unusual location of this rare entity the case history is published and differential diagnostic and therapeutical implications are discussed.

[Benign fibro-osseous tumors of the frontal skull base with intracranial extension. Report of 2 cases]. / Gutartige fibroossäre Tumoren der frontalen Schädelbasis mit intrakranieller Ausbreitung. Bericht über 2 Fälle.

We report on two patients with ossifying fibroma of the anterior skull base with intracranial extension. A psammomatoid ossifying fibroma was removed from a 29 year old female patient, and in a 37 year old female patient a cemento ossifying fibroma was removed. The main clinical symptom in both cases was headache. Surgery took place after diagnosis and therapy in an interdisciplinary operation with ENT colleagues. The ossifying fibroma is a benign neoplasm mainly affecting the maxilla and mandible. Complete removal is better than a curettage of the tumor.

Characterization of a glucose-repressed pyruvate kinase (Pyk2p) in Saccharomyces cerevisiae that is catalytically insensitive to fructose-1,6-bisphosphate.

We have characterized the gene YOR347c of Saccharomyces cerevisiae and shown that it encodes a second functional pyruvate kinase isoenzyme, Pyk2p. Overexpression of the YOR347c/PYK2 gene on a multicopy vector restored growth on glucose of a yeast pyruvate kinase 1 (pyk1) mutant strain and could completely substitute for the PYK1-encoded enzymatic activity. PYK2 gene expression is subject to glucose repression. A pyk2 deletion mutant had no obvious growth phenotypes under various conditions, but the growth defects of a pyk1 pyk2 double-deletion strain were even more pronounced than those of a pyk1 single-mutation strain. Pyk2p is active without fructose-1,6-bisphosphate. However, overexpression of PYK2 during growth on ethanol did not cause any of the deleterious effects expected from a futile cycling between pyruvate and phosphoenolpyruvate. The results indicate that the PYK2-encoded pyruvate kinase may be used under conditions of very low glycolytic flux.