Homocysteine concentration in coronary artery disease: Influence of three common single nucleotide polymorphisms.

BACKGROUND AND AIMS: Whether single nucleotide polymorphisms (SNPs) of homocysteine metabolism enzymes influence the rate of cardiovascular (CV) events in coronary artery disease (CAD) patients remains controversial. METHODS AND RESULTS: In this analysis, 1126 subjects from the AtheroGene study with CAD and 332 control subjects without known CAD were included. The following SNPs were investigated: methylentetrahydrofolate reductase (MTHFR-C667T), methionin synthetase (MS-D919G), and cystathionin beta synthetase (CBS-I278T). The endpoint was the combination of cardiovascular death, stroke, and non-fatal myocardial infarction (N = 286). The median follow-up time was 6.4 years. Kaplan-Meier curve analysis showed an increasing event rate with rising homocysteine levels (p < 0.001) in CAD patients. Further, in Cox-Regression analysis homocysteine was a predictor of the endpoint with a hazard ratio (HR) of 6.5 (95% CI: 2.9-14.6, p < 0.001) in the adjusted model including cardiovascular risk factors. Of the three SNPs, homozygous MTHFR SNP increased homocysteine levels significantly in patients with CAD and individuals without CAD (both p < 0.001). The SNPs in MS and CBS were not related to relevant changes in homocysteine levels in CAD patients or controls. The different SNPs of MTHFR, MS, and CBS were not related to an increased event rate. CONCLUSION: Homocysteine level is a strong predictor of CV events. Subjects with and without CAD and SNPs in the enzyme MTHFR had increased homocysteine levels. This was not observed for MS and CBS SNPs. Although MTHFR SNPs alter homocysteine levels in patients and controls, these polymorphisms had no impact on prognosis in CAD patients.

The predictive value of different equations for estimation of glomerular filtration rate in patients with coronary artery disease - Results from the AtheroGene study.

BACKGROUND: Impaired renal function leads to dramatically increased risk for the development and progression of coronary artery disease (CAD). Therefore we aimed to assess the predictive value of different equations for estimated glomerular filtration rate (eGFR) in CAD-patients. METHODS: From the AtheroGene study 2135 patients were included. eGFR was calculated using the 4-variable Modification of Diet in Renal Disease (4MDRD) equation for serum creatinine (sCr), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for sCr and cystatin C (CysC) each alone, and in combination (CysC/sCr). eGFR was assessed regarding the combined outcome of cardiovascular death and non-fatal myocardial infarction and regarding complex CAD represented by a SYNTAX score ≥23. Median follow-up was 4.3years. RESULTS: Only the CKD-EPI equation using CysC could differentiate between eGFR >90ml/min/1.73m(2) vs. eGFR 60-90ml/min/1.73m(2) according to the occurrence of an endpoint event (log-rank test p=0.009). In the Cox regression analysis only eGFR calculated by CKD-EPI equation for CysC (Hazard ratio per 1 standard deviation (HR) 1.27 (95% CI 1.07-1.50); p=0.007) and for CysC/sCr (HR 1.22 (95% CI 1.02-1.46); p=0.026) were predictive regarding the outcome after adjustment for cardiovascular risk factors and Nt-proBNP. Furthermore, only eGFR calculated by CKD-EPI equation for CysC (odds ratio (OR) 1.57 (95% CI 1.36-1.78); p<0.001) and for CysC/sCr (OR 1.32 (95% CI 1.13-1.53); p<0.001) were significantly associated with a SYNTAX score ≥23. CONCLUSION: In patients with CAD the CKD-EPI equation for CysC and for CysC/sCr provided the best predictive value regarding the prognosis and the severity of CAD.

Next-generation sequencing of the basal cell carcinoma miRNome and a description of novel microRNA candidates under neoadjuvant vismodegib therapy: an integrative molecular and surgical case study.

BACKGROUND: MicroRNAs (miRNAs) have been identified as key players in posttranscriptional gene regulation and have a significant impact on basal cell carcinoma (BCC) development. The Sonic hedgehog pathway inhibitor vismodegib has been approved for oral therapy of metastatic or advanced BCC. Here, a high-throughput miRNA sequencing analysis was carried out to identify differentially expressed miRNAs and possible novel miRNA candidates in vismodegib-treated BCC tissue. Additionally, we described our surgical experience with neoadjuvant oral vismodegib therapy. PATIENTS AND METHODS: A punch biopsy (4 mm) from a patient with an extensive cranial BCC under oral vismodegib therapy and a corresponding nonlesional epithelial skin biopsy were harvested. Total RNA was isolated, after which a sequencing cDNA library was prepared, and cluster generation was carried out, which was followed by an ultra-high-throughput miRNA sequencing analysis to indicate the read number of miRNA expression based on miRBase 21. In addition to the identification of differentially expressed miRNAs from RNA sequencing data, additional novel miRNA candidates were determined with a tool for identifying new miRNA sequences (miRDeep2). RESULTS: We identified 33 up-regulated miRNAs (fold change ≥2) and 39 potentially new miRNA candidates (miRDeep scores 0-43.6). A manual sequence analysis of the miRNA candidates on the genomic locus of chromosome 1 with provisional IDs of chr1_1913 and chr1_421 was further carried out and rated as promising (chr1_1913) and borderline (chr1_421). Histopathology revealed skip lesions in clinically healthy appearing skin at the tumor margins, which were the cause of seven re-excisions by micrographic controlled surgery to achieve tumor-free margins. CONCLUSION: miRNA sequencing revealed novel miRNA candidates that need to be further confirmed in functional Dicer knockout studies. Clinically, on the basis of our surgical experience described here, neoadjuvant vismodegib therapy in BCC appears to impede histopathologic evaluations with effects on surgical therapy. Thus, larger studies are necessary, but are not preferable at this time if other options are available.

Clinical course and complications following diagnostic bronchoalveolar lavage in critically ill mechanically ventilated patients.

BACKGROUND: Flexible, fibreoptic bronchoscopy (FFB) and bronchoalveolar lavage (BAL) have been used for diagnostic purposes in critically ill ventilated patients. The additional diagnostic value compared to tracheal aspirations in ventilator-associated pneumonia (VAP) has been questioned. Nevertheless, BAL can provide extra information for the differential diagnosis of respiratory disease and good antibiotic stewardship. These benefits should outweigh potential hazards caused by the invasiveness of this diagnostic technique. The focus of the present study was on the clinical course and complications of patients following BAL procedures up to 24 h. METHODS: Hundred sixty-four FFB guided BAL procedures for suspected pneumonia were analysed in an observational study. The clinical course of patients was monitored by respiratory and haemodynamic data before BAL, 1 and 24 h after BAL. Complications were defined and registered. Factors associated with complications were analysed by logistic regression. CLINICAL COURSE: a decrease in average pO2/FiO2 ratio 1 h after BAL from 29 kPa (218 mmHg) to 25 kPa (189 mmHg) (p < 0.05) was observed which fully recovered within 24 h. Respiratory complications: the incidence of procedure related hypo-oxygenation (SaO2 ≤ 88 %) and/or bronchospasm was 9 %; a decrease of >25 % PaO2/FiO2 ratio 1 h after BAL was found in 29 % of patients; no bleeding or pneumothorax were registered. Haemodynamic complications: there were no cases of hypertension and cardiac rhythm disturbances; haemodynamic instability within the first 24 h after BAL was recorded in 22 %; this was correlated with a cardiovascular diagnosis at admission (OR 2.9; 95 % CI 1.2 - 6.7) and the presence of cardiovascular co-morbidity (OR 3.5; 95 % CI 1.5 - 8.3). The incidence of bacteraemia was 7 %. There was no case of procedure related death. DISCUSSION: Frequently occurring haemodynamic and respiratory instability but no cases of cardiac rhythm disturbances, bleeding, pneumothorax or procedure related death were attributable to diagnostic FFB and BAL. The procedures should be conducted under careful supervision by experienced physicians. Only a randomized controlled trial that compares diagnostic FFB and BAL with a non-invasive strategy could ultimately establish the safety profile and clinical utility of these procedures in critically ill ventilated patients.

Mimivirus is not a frequent cause of ventilator-associated pneumonia in critically ill patients.

Acanthamoeba polyphaga mimivirus (APMV) belongs to the amoebae-associated microorganisms. Antibodies to APMV have been found in patients with pneumonia suggesting a potential role as a respiratory pathogen. In addition, positive serology for APMV was associated with an increased duration of mechanical ventilation and intensive care unit stay in patients with ventilator-associated pneumonia. The aim of the present study was to assess the presence of APMV in bronchoalveolar lavage fluid samples of critically ill patients suspected of ventilator-associated pneumonia. The study was conducted in the intensive care unit of the Maastricht University Medical Centre. All consecutive bronchoalveolar lavage fluid samples obtained between January 2005 and October 2009 from patients suspected of ventilator-associated pneumonia were eligible for inclusion. All samples were analyzed by real-time PCR targeting the APMV. A total of 260 bronchoalveolar lavage fluid samples from 214 patients (139 male, 75 female) were included. Bacterial ventilator-associated pneumonia was confirmed microbiologically in 105 out of 260 (40%) suspected episodes of ventilator-associated pneumonia (86 patients). The presence of APMV DNA could not be demonstrated in the bacterial ventilator-associated pneumonia positive or in the bacterial ventilator-associated pneumonia negative bronchoalveolar lavage fluid samples. Although suspected, APMV appeared not to be present in critically ill patients suspected of ventilator-associated pneumonia, and APMV does not seem to be a frequent cause of ventilator-associated pneumonia.

Transcriptional upregulation of both egl-1 BH3-only and ced-3 caspase is required for the death of the male-specific CEM neurons.

Most of the 131 cells that die during the development of a Caenorhabditis elegans hermaphrodite do so approximately 30 min after being generated. Furthermore, in these cells, the pro-caspase proCED-3 is inherited from progenitors and the transcriptional upregulation of the BH3-only gene egl-1 is thought to be sufficient for apoptosis induction. In contrast, the four CEM neurons, which die in hermaphrodites, but not males, die approximately 150 min after being generated. We found that in the CEMs, the transcriptional activation of both the egl-1 and ced-3 gene is necessary for apoptosis induction. In addition, we show that the Bar homeodomain transcription factor CEH-30 represses egl-1 and ced-3 transcription in the CEMs, thereby permitting their survival. Furthermore, we identified three genes, unc-86, lrs-1, and unc-132, which encode a POU homeodomain transcription factor, a leucyl-tRNA synthetase, and a novel protein with limited sequence similarity to the mammalian proto-oncoprotein and kinase PIM-1, respectively, that promote the expression of the ceh-30 gene in the CEMs. On the basis of these results, we propose that egl-1 and ced-3 transcription are coregulated in the CEMs to compensate for limiting proCED-3 levels, which most probably are a result of proCED-3 turn over. Similar coregulatory mechanisms for BH3-only proteins and pro-caspases may function in higher organisms to allow efficient apoptosis induction. Finally, we present evidence that the timing of the death of the CEMs is controlled by TRA-1 Gli, the terminal global regulator of somatic sexual fate in C. elegans.

Construction of bovine whole-genome radiation hybrid and linkage maps using high-throughput genotyping.

High-density whole-genome maps are essential for ordering genes or markers and aid in the assembly of genome sequence. To increase the density of markers on the bovine radiation hybrid map, and hence contribute to the assembly of the bovine genome sequence, an Illumina BeadStation was used to simultaneously type large numbers of markers on the Roslin-Cambridge 3000 rad bovine-hamster whole-genome radiation hybrid panel (WGRH3000). In five multiplex reactions, 6738 sequence tagged site (STS) markers were successfully typed on the WGRH3000 panel DNA. These STSs harboured SNPs that were developed as a result of the bovine genome sequencing initiative. Typically, the most time consuming and expensive part of creating high-density radiation hybrid (RH) maps is genotyping the markers on the RH panel with conventional approaches. Using the method described in this article, we have developed a high-density whole-genome RH map with 4690 loci and a linkage map with 2701 loci, with direct comparison to the bovine whole-genome sequence assembly (Btau_2.0) in a fraction of the time it would have taken with conventional typing and genotyping methods.

[Primary adenocarcinoma of the left atrium mimicking benign myxoma]. / Primäres Adenokarzinom des linken Herzvorhofes. Erst die Histologie führt zur Diagnose Adenokarzinom des Herzens.

Primary tumors of the heart are rare, whereas cardiac metastases, most frequently from adenocarcinomas, occur in up to 20% of malignant tumors. We report about a 61-year-old female patient who was admitted with recurrent stress-induced dizziness, intermittent tachycardia and a fall due to a pre-syncope. Echocardiography showed a left atrial tumor with the typical features of a pediculated myxoma, leading to open heart surgery. However, histopathology revealed a 2.2 x 1.5 cm adenocarcinoma. The subsequent search for a primary tumor, including tumor markers and (18)F-FDG-PET, was unsuccessful, as was a second thorough diagnostic workup half a year later. The tumor was therefore classified as a primary cardiac adenocarcinoma.

Effect of nitric oxide in ischemia/reperfusion of the pancreas.

BACKGROUND: Ischemia/reperfusion injury, and thus graft pancreatitis, remains a major problem in pancreas transplantation. Contradictory results about the role of nitric oxide (NO) in pancreatic ischemia/reperfusion have been reported; however, in none of the reports has a detailed comparison between inhibition of NO synthase and NO supplementation been carried out. METHODS: Vascular isolation of the pancreatic tail was performed in landrace pigs. After splenectomy catheters placed in the distal part of the splenic vessels allowed collection of the venous effluent and perfusion of the pancreatic tail. Three hours of complete warm ischemia was followed by 6 h of reperfusion. The effect of the NO donor sodium nitroprusside (SNP) and L-arginine was compared to a control group and NO synthase inhibition with L-NAME. RESULTS: Lipase in the venous effluent of the pancreas was significantly decreased in the SNP and the L-arginine groups. Vascular resistance was markedly elevated in the L-NAME group and reduced in the NO donor groups. Tissue pO2 after reperfusion was only significantly elevated in the SNP group. Granulocyte infiltration and also overall histological tissue injury were most severe in the control group followed by the L-NAME group, the SNP group, and the L-ARG group. CONCLUSION: The data show that supplementation of nitric oxide is clearly protective in pancreatic ischemia/reperfusion. However, inhibition of NO synthesis does not lead to an equally clear aggravation of tissue injury.

Protein phosphatase inhibitors facilitate DHPG-induced LTD in the CA1 region of the hippocampus.

We have shown earlier that activation of metabotropic glutamate (mGlu) receptors using a group I-specific mGlu receptor agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG), can induce long-term depression (LTD) in the CA1 region of the hippocampus. In an attempt to determine the signal transduction mechanisms involved in this form of synaptic plasticity, we have tested the effects of a range of inhibitors on DHPG-induced LTD. In vitro grease-gap electrophysiological recordings were performed in the rat hippocampal CA1 region. We have found that DHPG-induced LTD is resistant to the two potent protein kinase C (PKC) inhibitors, Gö 6976 (10 microM) and Gö 6983 (10 microM), the potent and selective protein kinase A (PKA) inhibitor, KT 5720 (10 microM), and the potent broad spectrum kinase inhibitor, staurosporine (10 microM). In contrast, non-selective inhibitors of protein phosphatases (PP1 and PP2A), okadaic acid (1 microM) or calyculin A (1 microM), facilitated DHPG-induced LTD. However, an inhibitor of protein phosphatase 2B, FK 506 (1 microM), did not influence this process. The PP1/PP2A protein phosphatase inhibitors, but none of the other agents tested, also inhibited (S)-alpha-methyl-4-carboxyphenylglycine (MCPG)-induced reversal of DHPG-induced LTD. These data suggest that activation of neither PKC nor PKA is involved in DHPG-induced LTD. They do, however, suggest that the process is under regulation by protein phosphorylation and dephosphorylation.

Effect of social experience on dopamine-stimulated adenylyl cyclase activity and G protein composition in chick forebrain.

The stimulation of adenylyl cyclase (AC) by dopamine was investigated in membrane fractions of the forebrain areas mediorostral neostriatum/hyperstriatum ventrale (MNH) and lobus parolfactorius (LPO) of 8-day-old domestic chicks that had been raised under different social conditions: group A, socially isolated; group B, imprinted on an acoustic stimulus; group C, trained but nonimprinted; and group D, reared in small groups. Only in the brain of the socially experienced groups could cyclic AMP (cAMP) synthesis be stimulated by dopamine, but not in the socially isolated animals (group A). Ligand binding studies of dopamine D1- and D2-type receptors in membrane fractions did not reveal differences between socially experienced and isolated animals. Forskolin stimulation of total AC in MNH and LPO membrane fractions revealed a significantly enhanced AC stimulation in the socially reared but not in the imprinted group compared with isolated controls. Stimulation of AC by the G protein activator guanylylimidodiphosphate was significantly increased in the MNH and the LPO of socially reared chicks compared with isolated control animals. These results suggest that early postnatal social experience modulates the rate of cAMP synthesis and that these lasting changes are not due to changes of dopamine receptors but are related to increased AC activities and to increased sensitivity of Gs protein.

[Amalgam deposit in a gastric leiomyosarcoma. Case report of an unusual amalgam constellation]. / Amalgamdepositionen in einem gastralen Leiomyosarkom. Fallbeschreibung einer ungewöhnlichen Amalgamkonstellation.

We report an a 57-year-old man with gastric leiomyosarcoma containing depositions of amalgam that possibly originate from a swallowed filling. The significance of this finding remains unclear. This case does not permit any conclusions as to whether this is a coincidence or not. The worldwide use of amalgam without an increase of oral sarcomas/leiomyosarcomas speaks against the supposition that amalgam induces sarcomas.

Successful treatment of decompensated chronic viral hepatitis by bursal disease virus vaccine.

Three cases of women with chronic liver inflammation caused by hepatitis B (two) and C (one) viral infections, were followed up to twelve years after diagnosis. As conventional therapy was ineffective and the patients progressed into decompensated liver disease, they were superinfected with massive doses of an attenuated variant (MTH-68/B) of the apathogenic avian Bursal Disease virus (a double-stranded RNA virus from the Birnaviridae family). Clinical symptoms and biochemical abnormalities were resolved in two patients following few months of virus treatment. Cirrhosis was stabilized and significant clinical improvement was achieved in the third patient--who before the virus therapy was moribund with recurring, diuretic-resistant ascites, variceal bleedings, portal encephalopathy and renal failure. To our knowledge, these are the first recorded cases of decompensated chronic viral hepatitis which went to long-lasting remission or were stabilized by superinfection with an apathogenic virus.

The nitric oxide donor sodium nitroprusside is protective in ischemia/reperfusion injury of the pancreas.

BACKGROUND: The role of nitric oxide in the ischemia/reperfusion injury of the pancreas is still unclear. In other organs, protective as well as aggravating effects have been described. We have, therefore, investigated the effect of the nitric oxide donor sodium nitroprusside on pancreatic ischemia/reperfusion injury. METHODS: In Landrace pigs, after transsection of the pancreas, complete vascular isolation of the pancreatic tail was performed. The tail was subjected to 3 hr of warm ischemia and thereafter reperfusion (6 hr). The animals were divided into a control group (n=7) and a treatment group (n=7) that received 15 mg of sodium nitroprusside after reperfusion intra-arterially into the splenic artery. RESULTS: The morphological tissue damage and lipase activity in the venous effluent of the pancreas were significantly lower in the treatment group. Partial oxygen tension in the tissue after reperfusion was markedly reduced in the control group, indicating an impairment of microcirculation. In the treatment group, however, partial oxygen tension in the tissue was significantly higher (43 vs. 20 mmHg; P<0.014). Furthermore, total blood flow through the pancreatic tail in the treatment group was found to be significantly higher in the late reperfusion period (14 vs. 9.5 ml/min at 5 hr after reperfusion; P<0.05). CONCLUSION: There is a marked impairment of pancreatic microcirculation after reperfusion. Sodium nitroprusside counteracts this impairment and has a protective effect on ischemia/reperfusion injury of the pancreas.

Ischemia/reperfusion injury of the pancreas: a new animal model.

BACKGROUND: Ischemia/reperfusion is thought to play an important role in the development of postimplantation pancreatitis after pancreas transplantation and also in the transition of edematous pancreatitis into necrotizing pancreatitis. Previous studies have suggested that impairment of microcirculation and hence tissue oxygenation and energy metabolism may be critical steps in this process. MATERIALS AND METHODS: In landrace pigs vascular isolation of the pancreatic tail was performed. Morphological alterations, tissue oxygenation, and energy metabolism were assessed in response to 3 h of global warm ischemia and the following reperfusion. RESULTS: A rapid onset of morphological alterations immediately after reperfusion was noted. Oxygen consumption and ATP levels were markedly decreased, and tissue oxygenation was severely impaired especially during the first hour after reperfusion. ATP tissue levels and oxygen consumption 10 min after reperfusion correlated significantly with the morphological changes at the end of the experiment. CONCLUSION: These findings can be explained by a failure of nutritive capillary perfusion and concomitant shunt perfusion. Therefore an impaired microcirculation rather than an impaired oxygen utilization shortly after reperfusion is of major relevance in the development of the ischemia/reperfusion injury of the pancreas.

[XY gonadal dysgenesis (Swyer syndrome) with gonadoblastoma]. / Androgenproduzierendes Gonadoblastom bei reiner XY-Gonadendysgenesie (Swyer-Syndrom).

This is a case report of 46 xy gonadal dysgenesis (Swyer-syndrome) with bilateral androgen producing gonadoblastoma in streak gonads in a 15-year-old patient. The presenting features were: hypergonadotrophic hypogonadism, male pseudohermaphroditism and virilisation. A hypoplastic uterus with normal looking Fallopian tubes and bilateral adnexal tumors were detected through laparoscopy. A laparotomy was performed and the streak gonads with bilateral gonadoblastoma were removed. This led to a normalisation of serum testosterone and serum beta-HCG levels and an amelioration of signs of virilisation. Uterus and fallopian tubes were conserved during the operation. A second look laparoscopy 6 months later showed no evidence of recurrent tumor. No mutation were found in the sex-determining gene (SRY) on DNA-screening using SSCP assay.

Localization of dopamine D1 receptors and dopaminoceptive neurons in the chick forebrain.

The distributions of dopamine D1 receptors, dopaminoceptive neurons, and catecholaminergic fibers were investigated in the forebrain of the domestic chick by using D1 receptor autoradiography and immunohistochemical detection of D1 receptor protein (D1rp), the dopamine- and cAMP-regulated phosphoprotein DARPP-32, and tyrosine hydroxylase (TH). Particular attention was paid to two forebrain regions, the mediorostral neostriatum/ hyperstriatum ventrale (MNH) and neostriatum dorsocaudale (Ndc), which have been shown to be crucially involved in filial imprinting. In general, there was a good, but not complete, correlation between the immunohistochemical pattern of DARPP-32 positive perikarya and the distribution of D1 receptors. Both, DARPP-32 positive neurons as well as D1 receptors were highly enriched in the striatal part of the basal ganglia including the lobus parolfactorius (LPO) and paleostriatum augmentatum. High to moderate densities were observed in the outer rind of the pallium. Low to moderate densities were found in the belt regions of primary sensory areas, whereas densities in the respective core regions were generally low. Labeling in the MNH and Ndc was heterogeneous. Whereas the neostriatal part of MNH displayed both, moderate DARPP-32 immunostaining and moderate D1 receptor densities, the hyperstriatal part showed also moderate D1 receptor densities but was only weakly labeled by DARPP-32. The rostral part of the Ndc was among the most intensely DARPP-32 labeled areas of the pallium, its caudal part revealed only moderate DARPP-32 immunostaining. By using D1 receptor autoradiography, a homogeneous labeling throughout the rostrocaudal extension of the Ndc was found. Double-labeling experiments with antibodies to DARPP-32 and TH revealed that TH positive fibers in the MNH, Ndc, and LPO were often closely related to DARPP-32 positive perikarya. At the ultrastructural level, both immunoreaction for D1rp and DARPP-32 in the MNH and Ndc were primarily found to be associated with postsynaptic elements. Whereas D1rp immunoreactivity was enriched at postsynaptic densities or in their vicinity, reaction product for DARPP-32 was present throughout the perikaryal cytoplasm, dendrites, and dendritic spines. These results indicate that DARPP-32 as well as D1 receptors in the avian forebrain reveal a distribution that is substantially similar to that of mammals.

Cell autonomous expression of perlecan and plasticity of cell shape in embryonic muscle of Caenorhabditis elegans.

Perlecan, a component of the extracellular matrix (ECM), is essential for myofilament formation and muscle attachment in Caenorhabditis elegans. We show here that perlecan is a product of muscle and that it behaves in a cell autonomous fashion. That is, perlecan expressed in an individual muscle cell does not spread beyond the borders of the ECM underlying that cell. Using a polyclonal antibody that recognizes all isoforms of perlecan, we demonstrate that this protein first appears extracellularly at the comma stage (approx. 350 min) of development. We also show that during morphogenesis muscle cells have a heretofore undescribed plasticity of shape. This ability to regulate cell shape allows cells within a muscle quadrant to compensate for missing cells and to form a functional quadrant. A dramatic example of this morphological flexibility can be observed in animals in which the D blastomere has been removed by laser ablation. Such animals, lacking 20 of the 81 embryonic body wall muscle cells, can survive to become viable adult animals indistinguishable from wildtype animals. This demonstrates that the assembly of an embryo via a stereotypic lineage does not preclude a more general regulation during morphogenesis. It appears that embryos are flexible enough to immediately compensate for drastic alterations in tissue composition, a feature of development that may be of general importance during evolution.

[Diagnosis and therapy of primary malignant fibrous histiocytoma of the kidney]. / Diagnose und Therapie eines primären malignen fibrösen Histiozytoms der Niere.

Malignant Fibrous Histiocytoma (MFH) is an unfrequent mesenchymal tumor first described by O'Brian in 1964 [1, 16]. The most common site of this malignancy is the limbs area and the retroperitoneum. Primary involvement of the kidney is extremely rare. Only thirteen cases are well documented in the literature. We report an additional case of such primary renal tumor.