RhoC is dispensable for embryogenesis and tumor initiation but essential for metastasis

The Rho proteins are Ras-related guanosine triphosphatases (GTPases) that function in cytoskeletal reorganization, cell migration, and stress fiber and focal adhesion formation. Overexpression of RhoC enhances the ability of melanoma cells to exit the blood and colonize the lungs. However, in vivo confirmation of RhoC's role in metastasis has awaited a RhoC-deficient mouse model. Here we report the generation of RhoC-deficient mice and show that RhoC is dispensable for embryonic and post-natal development. We demonstrate that loss of RhoC does not affect tumor development but decreases tumor cell motility and metastatic cell survival leading to a drastic inhibition of metastasis.     

Autistic-spectrum disorders in Down syndrome: further delineation and distinction from other behavioral abnormalities.

The present study extends our previous work characterizing the behavioral features of autistic-spectrum disorder (ASD) in Down syndrome (DS) using the Aberrant Behavior Checklist (ABC) and Autism Behavior Checklist (AutBehav). We examined which specific behaviors distinguished the behavioral phenotype of DS + ASD from other aberrant behavior disorders in DS, by determining the relative contribution of ABC and AutBehav subscales and items to the diagnosis of ASD. A total of 127 subjects (aged 2-24 years; mean age: 8.4 years; approximately 70% male), comprising: a cohort of 64 children and adolescents with DS and co-morbid ASD (DS + ASD), 19 with DS and stereotypic movement disorder (DS + SMD), 18 with DS and disruptive behaviors (DS + DB), and 26 with DS and no co-morbid behavior disorders (DS + none) were examined using the aforementioned measures of aberrant behavior. We found that subjects with DS + ASD showed the most severe aberrant behavior, especially stereotypy compared to DS + none and lethargy/social withdrawal and relating problems compared to DS + SMD. Specifically, relatively simple stereotypic behavior differentiated DS + ASD from DS + DB, whereas odd/bizarre stereotypic and anxious behavior characterized DS + ASD relative to DS + SMD and DS + none. Additionally, in a subset of subjects with DS + ASD and anxiety, social withdrawal was particularly pronounced. Overall, our findings indicate that a diagnosis of DS + ASD represents a distinctive set of aberrant behaviors marked by characteristic odd/bizarre stereotypic behavior, anxiety, and social withdrawal.     

Melanotic paraganglioma of the posterior mediastinum

A melanotic paraganglioma occurred in a 57-year-old woman, located in the left paravertebral space of the upper mediastinum. It was totally resected. During a 5 year follow up period neither tumour reccurrence nor metastasis were observed. Histological examination of the tumour revealed a paraganglioma with monomorphous chief cell like elements which were arranged in a zellballen pattern. Immunohistochemical results also were in accordance with the diagnosis since neuron-specific enolase, chromogranin and synaptophysin were found in tumour cells whereas keratin was not. Additionally, neurosecretory granules were found in tumour cells during electron microscopy. A peculiar feature of the tumour was its strong pigmentation due to melanin located within the tumour cells and tumour associated melanophages. The simultaneous expression of functional properties of two different neural crest derived cells in one tumour stresses the close relationship between all neural crest elements and is in accordance with the observation of other melanotic, non-melanomatous tumours.Dedicated to Prof. Dr. Dr. mult. h.c. W. Doerr on the occasion of his 80th birthday     

Interepithelial cells of the oral mucosa in mice

Summary Non-epithelial mesenchymal and neuroectodermal cells occur between the keratinocytes in the stratified squamous epithelium of the oral mucosa. These cells cannot be classified adequately by light microscopy. In the present study the oral mucosa of the lip, cheek and tongue of 50 mice were studied by light and electron microscopy. 3,025 mononuclear interepithelial cells were documented and analysed.Monocytogenic macrophages, plasma cells and mast cells were not found interepithelially and cannot be regarded as a regular constituent of the epithelium. Only a few neuroectodermal cells — in mice these are exclusively Merkel cells, with no melanocytes — were localized in the epithelium. The majority of the interepithelial cell population is made up of lymphocytes (22.8%) and Langerhans cells (56.8%). They are an integral constituent of the epithelium. Lymphocytes with rounded and indented nuclei can be identified. The larger and dendritic Langerhans cells are a specific cell of squamous epithelium and also occur in the oral mucosa. Not all cells which feature the cytological characteristics of Langerhans cells contain Langerhans or Birbeck granules. Accordingly these granules cannot be considered an exclusive identification characteristic. Two types of Langerhans cells can be differentiated. 80.9% have the more or less typical appearance known from the epidermis and were termed macrophagocytoid Langerhans cells. The nuclei are irregularly indented and moderately heterochromatic. 19.1% possessed conspicuous large, spherical, euchromatic nuclei and an electron-lucent cytoplasm. These were termed reticuloid Langerhans cells. About 20% of the interepithelial cell population could not be identified, neither as typical lymphocytes nor as Langerhans cells. These were small to medium sized cells with deeply indented cerebriform strongly heterochromatic nuclei. They are similar to the Sézary cells or mycosis fungoides cells of epidermotropic human T-cell lymphomas. The lymphocytic nature of these cells has been confirmed. It seems likely that differentiation of lymphocytes to cerebriform cells occurs within the epithelium. It is further discussed whether cerebriform cells are precursors of Langerhans cells, a conclusion suggested morphologically by transitional forms. This would imply that Langerhans cells originate from lymphocytes, and that the cerebriform cell is an intermediate step of differentiation. The microenvironment of the squamous epithelium may play a role in the process of differentiation, which could explain the epitheliotropy of lymphocytes. The possibility is considered that Langerhans cells and interdigitating reticulum cells of the T-cell area of lymph nodes are identical. The close functional cooperation of Langerhans cells, lymphocytes, and interdigitating reticulum cells in immunological defenses against external antigens is discussed.The authors wish to express their sincere appreciation to Miss P. Starck and Miss I. Brandt for invaluable technical assistance in this project.     

Prognostic value of MMP-2, -9 and TIMP-1,-2 immunoreactive protein at the invasive front in advanced head and neck squamous cell carcinomas

In head and neck cancer as well as in other carcinomas, tumor expansion and spread to distant sites require the secretion of destructive enzymes that degrade the extracellular matrix. A variety of proteases contribute to matrix destruction. Characteristics of the invasive tumor front may reflect tumor prognosis better than do other parts of the tumor. Therefore, it was the aim of the present study to (i) compare central and peripheral tumor zones for differences in the expression of matrix-metalloproteinases (MMP) -2 and -9 and their naturally occurring inhibitors (tissue inhibitor of matrix-metalloproteinases (TIMP) -1 and -2), (ii) examine the morphological potential of malignancy, and (iii) correlate these findings with clinicopathological parameters. The study population consisted of 106 surgical specimens of advanced head and neck squamous cell carcinomas. The invasive front was graded for malignancy, and immunohistochemical staining with MMP-2, MMP-9, TIMP-1 and TIMP-2 antibodies was performed. Both MMP-2 and MMP-9 were found to be significantly overexpressed at the tumor front. The MMP-2-positive invasive front exhibited diminished overall survival times. In multivariate analysis, MMP-2 expression retained its correlation with overall survival in addition to nodal status and total malignancy score. Expression of TIMP-2 correlated with local tumor invasion. We conclude that the expression of MMP-2 at the invasive front is a marker of poor survival and appears to be associated with early recurrence in initially lymph node-negative patients.     

A chromosome No. 2 abnormality in a child with a few congenital defects*

An abnormal chromosome No. 2 was found in the case of a child with an imperforate anus, a recto-vaginal fistula, unilateral atresia of the inner canal, and deformity of the external ear. G-banding studies revealed an insertion of a segment of the short arm into the long arm in one of the chromosomes No. 2 of the proband, the apparent result of a de novo phenomenon of chromosome rearrangement.     

American Associatin of Anatomists. Eighty Sixth Annual Session,Cornell University Medical College,New York,New York,April 9, 10, 11, 12, 1973. Officers,abstracts, demonstrations

A method for producing flexible silicone rubber casts of the airways of the lungs in-situ is described. Casts are made to correspond to lung volumes occurring during normal breathing. The lung is prepared for casting by replacing the air within with CO₂ followed by filling with degassed physiological saline. The saline dissolves the CO₂ gas within the airways allowing for a bubble-free finished cast. Casting compound is then slowly injected through the trachea. The saline diffuses out of the lung and passes out of the thorax through several small slits in the thoracic wall. After the injection is completed, the cast lung is allowed to cure in-situ before it is removed and the tissue digested away. Finished casts have an overall shape corresponding closely to the shape of the thorax. Casts produced by this in-situ method appear to have more realistic geometrical relationships than those produced from excised lungs.     

Zur Bestimmung des Kaliumspiegels im Blutplasma

Zusammenfassung Die Kaliumkonzentration im Blutserum nach der Gerinnung ist höher als im Blutplasma, dessen Gerinnung durch Heparin, Äthylendiamintetraessigsäure (EDTA) oder Citrat verhindert wurde. Die Differenz beträgt beim Hund 15–20%, beim Menschen 12–16% und beim Rind 8–10%.Der Unterschied wird durch den bei der Gerinnung des Blutes auftretenden Zerfall der Thrombocyten hervorgerufen, deren Kaliumgehalt überraschend hoch ist (mindestens das 10–20fache der Konzentration im Plasma).Aus diesem Grund geben Kaliumbestimmungen im Serum, bei denen das Blut während der Präparation der Proben gerinnt, zu hohe Werte gegenüber der tatsächlich in vivo herrschenden Konzentration im Plasma. Messungen der Kaliumkonzentration sollten immer im Plasma erfolgen, wobei als gerinnungshemmende Substanzen Heparin oder EDTA geeignet sind.