Uptake of inert microparticles in normal and immune deficient mice.

Intestinal microparticle uptake is important for drug delivery, environmental pollution and multiple organ dysfunction syndrome. This paper explores further whether uptake occurs at mucosa associated lymphoid tissue (MALT) via the microfold (M) cells of Peyer's patch domes or through villous epithelium. It does this by comparing the results of exposure of either severe combined immunodeficient (SCID) mice (lacking MALT) or normal BALBc mice, to oral gavage with 2 microm fluorescent latex microparticles. At 5 and 30 min after gavage, full circumference samples along the small intestine were processed for fluorescence microscopy and microparticle numbers were collected for surface and tissue sites. Uptake occurred in both BALBc and SCID mice within 5 min of particle administration and increased further in the following 25 min. In BALBc mice, almost all particles (96%) are in non-MALT sites in MALT circumference samples, with very few at the domes: uptake was also substantial in entirely villous samples. In SCID mice, particle numbers were only slightly lower than those of the BALBc mice, and occurred exclusively by the villous route. These findings confirm that the villous uptake route must be considered when assessing the extent of the dose delivered following pharmaceutical or toxicological oral exposure to microparticles.

The short-term effect of hippotherapy on spasticity in patients with spinal cord injury.

STUDY DESIGN: Assessment of spasticity before and after hippotherapy treatment. OBJECTIVE: To evaluate the short-term effect of hippotherapy on spasticity of spinal cord injured patients (SCIs). SETTING: Swiss Paraplegic Centre, Nottwil. METHODS: 32 patients with spinal cord injury with various degrees of spasticity had repeated sessions (mean 11) of Hippotherapy-K. Spasticity of the lower extremities was scored according to the Ashworth Scale. RESULTS: In primary rehabilitation patients Ashworth values after hippotherapy were significantly lower than before (Wilcoxon's signed-rank test: P<0.001). Highest improvements were observed in SCIs with very high spasticity. No significant difference between short-term effect in paraplegic and short-term effect in tetraplegic subjects was found. CONCLUSIONS: Hippotherapy significantly reduces spasticity of lower extremities in SCIs.

Cell differentiation and chemotherapy influence p53 and Mdm2 immunoreactivity in human HT29 colon cancer cells grown in scid mice.

Absence of a functional p53 gene product can lead to increased p53 accumulation in cancer cells. In this contribution, the association between cell differentiation, chemotherapy and p53 immunoreactivity in human HT29 colon cancer cells grown in scid mice as undifferentiated cells and as mucin containing signet-ring cells was investigated. Mutated p53 was more frequently expressed in the undifferentiated tumour cells than in the signet-ring cells. 5-fluorouracil (5FU) treatment resulted in a substantial increase in the p53-positive signet-ring cell population (from 17% to 45%) and in an increased Mdm2 immunoreactivity. These findings indicate that mutated p53 expression is related to the differentiation pattern and that tumour cells devoid of mutated p53 immunoreactivity are preferentially eliminated by 5FU treatment.

Lectin histochemistry of the spleen: a new lectin visualizes the stromal architecture of white pulp and the sinuses of red pulp.

The subcompartmentalization of the white pulp in the spleen is the result of interactions of specific resident stromal cells and migrating subtypes of lymphocytes. Because carbohydrate residues of cell membranes and extracellular matrices are involved in cell-cell and cell-matrix interactions, they were investigated in rat spleen by a broad panel of lectins. Splenic macrophages, which were also demonstrated by Perls' Prussian blue reaction, were labeled selectively by most mannose-specific lectins and gave the characteristic distribution patterns in all splenic (sub)compartments. One recently isolated lectin, Chelidonium majus agglutinin (CMA), visualized predominantly central arterioles, the reticular meshwork (RM) in the periarteriolar lymphatic sheaths (PALS), the circumferential reticulum cells limiting PALS and follicles, and some follicular dendritic cells (FDCs) in white pulp. The endothelial cells of venous sinuses in red pulp were also labeled by CMA and, if frozen sections were used, CMA also labeled the macrophages of the red pulp. Compared to CMA, the monoclonal antibody CD11, which can be used only in frozen sections, stained almost solely the fibrous (extracellular) component of the RM. Because CMA stains the reticulum cells in particular, it is better suited to visualize the stromal architecture of splenic white pulp than the monoclonal antibody. Because CMA can be applied to paraffin-embedded material, it is a particularly useful tool to study the splenic stromal architecture in archival material.

Recombinant mistletoe lectin (rML) is successful in treating human ovarian cancer cells transplanted into severe combined immunodeficient (SCID) mice.

The main active constituents carrying the anti-cancer activities of aqueous mistletoe extracts have recently been identified as the mistletoe lectins (MLs). Although three different isolectins have been isolated from plant extracts, molecular biological techniques have revealed the presence of one gene only. Subsequently, recombinant mistletoe lectin (rML) has become available and the aim of the present study was to analyse its anti-cancer potential. SoTü 3 human ovarian cancer cells (2x10(7)) were injected intraperitoneally into SCID mice, while rML treatment was started on the following day. Three experimental groups (n=20 SCID mice) each received every working day an intraperitoneal injection of 30, 150, 500 ng rML per kg body weight, respectively, while 20 SCID mice in the control group received the vehicle solution only. The survival of the animals was taken as the principal outcome measure. In addition, the peritoneal cavity was searched for the presence of tumour cells. Animals were sacrificed when the weight increase due to the development of ascites exceeded 120% of the initial body weight. The treatment continued until day 83 and the surviving animals were sacrificed 84 days after inoculation. In the control group, only two animals survived and were free of tumour at the end of the experiment at 84 days. In contrast, thirteen animals in the 500 ng/kg rML group were still alive and no evidence for the presence of tumour cells in the peritoneum was found. Both, number of animals surviving and survival time were larger in this treatment group. The 30 ng/kg rML group showed an increased number of survivors, whilst the 150 ng rML per kg body weight group revealed the worst survival rates. The results of the present study indicate that rML has potent anti-tumour activity, if administered locally into the peritoneum of a human ovarian cancer harbouring SCID mouse. RML is a macromolecule and its instillation into the peritoneal cavity seems to be particularly effective to inhibit intraperitoneal growth of cancer cells. One explanation might be that altered glycosylation of the cancer cells leads to an increased affinity of rML towards tumour cells. Clinical studies with post-operative instillation of rML in ovarian cancer patients should, therefore, be encouraged to provide clinical evidence for the effectiveness of rML treatment.

Diagnostic features and treatment of the Askin tumor--malignant small cell tumor of the thoraco-pulmonary region: a case report.

The Askin tumor is one of a group of small round cell tumors and is found mainly in the thoraco-pulmonary region of children and young adults. The treatment of the patient and the differentiation of this tumor from other small round cell tumors, especially Ewing's sarcoma and neuroblastoma by light microscopy, immunohistochemical methods, and electron microscopy is discussed.

[Veterinary relations between Germany and Turkey on the military level at the beginning of the 20th century]. / Tierärztliche Beziehungen zwischen Deutschland und der Türkei auf militärischer Ebene am Anfang des 20. Jahrhunderts.

At the beginning of the 20th century the veterinary relations between Turkey and Germany intensified at the military level. After the Balkan Wars there were urgent attempts to reorganize the army, which lead to the visit of a German military mission under General L. von Sanders, who was appointed to review the army. Along with other members of the German military mission A. Thieme (1881-1949) belonged to the staff of the Turkish Army's Supreme Command as orderly officer and as advisory army veterinarian. During the First World War (1914-1918) there were 44 German veterinary officers, 23 in Turkish and 21 in German uniform. The veterinary officers in Turkish formations were assigned to the military mission, where the veterinary major Dr. K. Dreyer served as official adviser. Moreover mixed German-Turkish special units were formed under German leadership in Turkey, which included German veterinary officers in German uniform. The higher salaries were paid to the German veterinary officers than their Turkish colleagues by the Turkish government. As far as can gathered three German officers perished in Turkey.

Influence of hydroxylation and conjugation of bile salts on their membrane-damaging properties--studies on isolated hepatocytes and lipid membrane vesicles.

To characterize the relative toxicity of different bile salts, isolated hepatocytes were incubated with different concentrations of one bile salt or with identical concentrations of different bile salts and their conjugates. Incubation lasted for 1 hr; samples were taken at intervals and studied for enzyme release, urea synthesis and stimulation by glucagon, and by electron microscopy. While the trihydroxylated bile salt, taurocholate, did not produce alterations at concentrations up to 1,500 microM, the dihydroxylated salts, chenodeoxy- and deoxycholate, caused enzyme release and membrane lysis, and inhibited urea synthesis at concentrations above 500 microM. In contrast, ursodeoxycholate was ineffective at concentrations up to 1,500 microM. Conjugation of these bile salts did not result in significant differences with the exception of deoxycholate conjugates which induced enzyme leakage more rapidly. Studies of lipid membrane vesicles revealed corresponding alterations. The monohydroxylated salt, taurolithocholate, caused cellular damage as indicated by enzyme loss and impairment of hormonal sensitivity of cells at low concentrations (30 to 100 microM). Dihydroxylated salts produced a different time course of membrane leakage, ultrastructural changes and release of volume marker and lipid in liposomes, suggesting a possible different mechanism of damage induced by this bile salt. Both systems can readily be used to study bile salt membrane interactions.

Prenatal differentiation of colliculus superior in the rat.

Up till emybryonic day (ED) the 13 the prenatal histogenesis of rat mesencephalic roof is characterized by an exclusive proliferation of ventricular cells. Then the first differentiating postmitotic cells are found above the ventricular layer, so that proliferation and differentiation occur simultaneously. On ED 15 a lamination typical for embyronic CNS with ventricular, subventricular, intermediate layers and stratum zonale can be observed in the area of presumptive colliculus superior. A definite demarcation between ventricular and subventricular layers, however, is only possible by means of autoradiograpahic methods. At the end of gestation the lamination of adult colliculus superior is already noticeable. During early prenatal development, cells which originate on one single day can autoradiographically be demonstrated in different cell layers and particularly over the whole width of the intermediate layer, while towards the end of gestation time of cell origin and location inside the mesencephalic roofs are closely correlated: cells that originate on ED 13 can be found predominantly in deeper cell layers (stratum griseum profundum, lower stratum griseum intermedium), while cells originating on EDs 15 and 17 are on ED 21 situated in the upper cell layers (upper stratum griseum intermedium, stratum griseum superficiale). This results in an inside-outside gradient of cell origin, which corresponds to an inside-outside gradient of cell differentiation. Besides, a rostro-caudal and a lateromedial gradient can be observed. On ED 13 a median ventriculaar formation (MVF) can be distinguished displaying a significantly lower mitotic activity than the cells of the neighbouring ventricular layer as could be demonstrated by autoradiographic investigation. This difference is even more pronounced in latter embryonic stages. From ED 17 on the cells of this particular structure are arranged in a typical onion-like pattern. Towards the end of gestation the MVF expands considerably as compared with the surrounding ventricular layer. As long-time experiments with 3H-thymidine reveala this increase in area is brought about by the immigration of numerous ventricular cells which originated on earlier embryonic days. The apical processes of the cells of the MVF form a thick fibre bundle which can be followed upwards to the stratum zonale. Ulstructurally these strictly parallel arranged fibers mainly resembly astroglial processes, but possess, in contrast to the latter, numerous microtubules. Because of their morphological characteristics a classification of these cells as tanycytes appears justified. The MVF is compared with similar structures in other regions of the CNS and its possible function as a guide for migrating preneurons is discussed.

Varying expressions of lectin receptors within embryonic cell layers of murine cerebral cortex.

The ability of prenatal cerebral tissue to bind different lectins was analyzed using cryostat sections of mouse brains. It was shown that the immature cells within the embryonic cell layers possess receptors for different lectins in varying amounts. Of all lectins tested, only PNL, RCL and LPL were bound on the outer cell membranes to a considerable degree. Although the labeling patterns of PNL and RCL are similar, the latter is additionally well detectable on the wall of cerebral blood vessels. Cells of the ventricular layer are moderately labeled by PNL, which recognizes beta-D-galactosyl (1-3)-N-acetyl-D-galactosamine, but heavily labeled by LPL which binds to terminal sialic acid residues. Cells of the intermediate layer, on the other hand, are heavily stained PNL and only faintly by LPL. Hence it is suggested that the process of migration might be correlated to the removal of terminal sialic acid moieties from cell surface glycoconjugates, resulting in an exposure of the penultimate galactosyl residues.