alpha(v)beta(3) Integrin in central nervous system tumors

alpha(v)beta(3) Is an integrin specifically expressed in endothelial cells of newly forming blood vessels. Integrin-mediated angiogenesis is hypothesized to play a central role in the development and the progression of central nervous system neoplasms. Accordingly, it is considered a potential target for antiangiogenic therapy. In the current study, we compare the expression of alpha(v)beta(3) in ependymomas, oligodendrogliomas, pilocytic astrocytomas, medulloblastomas, and vestibular schwannomas (acoustic neuromas). Samples of 5 tumors of each of the 5 tumor types were harvested surgically and frozen. After the pathological diagnosis was confirmed, immunohistochemistry was performed using an anti- alpha(v)beta(3) monoclonal antibody (LM609). The expression of alpha(v)beta(3) was assessed using a 4-tiered (0-3) grading scheme reflecting the percentage of positively staining vessels. All vestibular schwannomas demonstrated strong (grade 3) alpha(v)beta(3) expression. The expression was uniformly prominent in Antoni B regions of the tumors. Of 5 ependymomas, 4 demonstrated uniformly strong alpha(v)beta(3). Oligodendrogliomas, medulloblastomas, and pilocytic astrocytomas demonstrated more variable alpha(v)beta(3). alpha(v)beta(3) may contribute significantly to angiogenesis in vestibular schwannomas and ependymomas. Despite the high vascular density of oligodendrogliomas, pilocytic astrocytomas, and medulloblastomas, these tumors had variable moderate alpha(v)beta(3) expression. This discrepancy suggests temporal and/or regional variability in the angiogenesis in these types of tumor. This study provides the first demonstration of alpha(v)beta(3) expression in vestibular schwannomas, medulloblastomas, and pilocytic astrocytomas.     

Stimulus specificity in the habituation of the startle response in the rat

A series of experiments evaluated whether the habituation of the startle response of the rat to tactile and auditory cues is stimulus specific. Experiment 1 showed stimulus specificity of a short-term habituation effect, whereby the startle to the second of a pair of stimuli was significantly less when the initial stimulus involved the same rather than the different modality. Experiments 2 and 3 focused on the more persistent decrement in startle that is a result of repeated stimulation, and demonstrated that such long-term habituation to the tactile and auditory stimuli contained a stimulus specific component in addition to a generalized component. The generalized habituation observed between the tactile and auditory stimuli in the three experiments may be due to an auditory accompaniment of the tactile stimulus employed. Discussion emphasized the utility of investigating habituation in a preparation with robust specificity.     

Psychological factors associated with the uptake of measles immunization: findings and implications for prevention

A cross-sectional study of 8204 children was performed to investigate the prevalence of immunization against measles, mumps and rubella and possible determinants of immunization uptake. The study was approached from a Lewinian perspective on preventive behaviour. Seventy-one questions referring to the guardian of the child, his or her partner, the household and the child, as well as to immunization-related experiences and situational topics were asked. Two psychological variables were studied: health locus of control and subjective relevance concerning measles. The immunization rate was 77.7 percent [95 percent confidence interval 76.8-78.6]. Multiple logistic regression yielded the following odds ratios for non- uptake of measles immunization: natural health orientation 8.74 [6.72-11.37]; advice of paediatrician 6.02 [4.67-7.75]; dangerousness of measles 2.00 [1.53-2.60]; marital status 1.87 [1.31-2.51]; assessed reliability of vaccination 1.57 [1.23-2.01]; smoking 1.55 [1.21-1.98]; and number of siblings 1.55 [1.21- 1.98]. Parents or guardians of immunized children were more internal and assessed measles as more relevant than those of non- immunized children.     

Characterization of the promastigote surface protease of Leishmania as a membrane-bound zinc endopeptidase

The effects of a variety of inhibitors suggested that the promastigote surface protease (PSP) of Leishmania might be a zinc metalloprotease. To investigate this possibility, we conducted atomic emission and absorption spectroscopic analyses, which show that PSP contains 1 atom of zinc per 63-kDa monomer. Further studies showed that the enzyme can be biosynthetically labeled with 65ZnCl2. The comparison of the amino acid sequence of Leishmania major PSP with nine other zinc metalloproteinases revealed significant similarity in the area of their zinc-binding sites. These data show clearly that the promastigote surface protease of Leishmania is a zinc metalloproteinase. Secondary structure analysis by circular dichroism spectroscopy indicates that PSP contains over 40% beta-strand and less than 20% alpha-helical structure. The molecular masses of amphiphilic PSP (152 kDa) and of hydrophilic PSP (142 kDa), determined by quantitative electron scattering, suggest that the purified enzyme occurs in solution, and presumably at the cell surface, as a non-covalent homodimer.     

Clinical consequences of heterozygosity for autosomal-recessive diseases*,**

Heterozygotes of autosomal-recessive diseases can often be recognized by special heterozygote tests, since enzyme activities are normally reduced in comparison with the normal homozygote state. In Drosophila, the majority of recessive lethal mutations shows a reduction of fitness in heterozygotes, whereas in a strong minority fitness of heterozygotes is increased. This review will be devoted to a consideration of the extent to which heterozygotes for a wide variety of nominally recessive diseases are subject either to an increased liability for common diseases or slight shifts of behavioral characteristics. The available evidence has been collected and will be discussed in three steps: Most studies are available for phenylketonuria. For this group of diseases, a slight reduction of average--especially verbal--I.Q. in heterozygotes has been reported together with signs of a slightly increased cerebral irritability, a possible slight increase of risk for mental disease, and an increase of blood phenylalanine levels in stress situations. The PKU example is used to discuss methodological problems involved in such studies. Other conditions for which relevant deviations in heterozygotes are possible or even likely include among others lipid storage diseases, microcephaly, myoclonus epilepsy, Wilson's disease, galaktokinase deficiency, homocystinuria, recessive myotonia and ataxia- teleangiectasia (increased cancer risk). Since heterozygotes for autosomal recessive diseases are common, it is possible that an appreciable fraction of "multifactorial" genetic liabilities for common, "constitutional" or mental disease might simply be due to heterozygosity for genes whose homozygous affects are already well known. By the same token, much of the "normal" genetic variability influencing cognitive performance (I.Q.)--especially in the lower range--and personality characteristics could also be caused by recessive genes in the heterozygous state.     

European vestibular experiments on the Spacelab-1 mission: 7. Ocular counterrolling measurements pre- and post-flight

Summary The static ocular counterrolling (OCR) of the four scientific crew members in the first Spacelab mission was measured during baseline-data-collection before and after the flight of SL-1. It was presumed that the modification of otolithic responses during spaceflight will be reflected in specific changes of the OCR-gain on the first days after recovery. The magnitude of OCR was determined analysing colour-transparencies of subjects right eyes that were produced in different positions of lateral body tilt. In general, one subject did not show any changes at all; three subjects exhibited a significant decrease of OCR-gain after exposure to weightlessness, whereby differences could be found between the responses for small and large angles of lateral body tilt. Moreover, asymmetrical effects of OCR-gain were found between body tilt to the left and tilt to the right side. Two subjects already demonstrated such an asymmetry before the flight with the higher gain on left-tilt (or right eye up), and three subjects exhibited left-right asymmetries after the spaceflight with the higher gain tilting to the right (or right eye down). A possible correlation between these vestibular asymmetries and space-sickness susceptibility is discussed.     

Effects of transforming growth factor beta1 on bonelike tissue formation in three-dimensional cell culture. I. Culture conditions and tissue formation

Bone tissue engineering based on growing bone marrow stromal cells on poly(L-lactic-co-glycolic acid) fiber meshes suffers from limited matrix production and mineralization when the cells are cultured with the standard differentiation supplements (dexamethasone, beta-glycerophosphate, and ascorbic acid). To overcome this problem we included transforming growth factor beta1 (TGF-beta1), which is described as playing a key role in collagen type I formation, although its effect on mineralization is controversially discussed. The investigations focused on establishing culture conditions for the application of TGF-beta1 in three-dimensional cell culture and on the effects of different doses of TGF-beta1 (1-20 ng/mL) on bonelike extracellular matrix formation. Immunohistochemical staining showed that TGF-beta1 enhanced the formation of procollagen type I, collagen type I, and collagen type V, especially under dynamic culture conditions (orbital shaker). A long-term study confirmed positive effects on the formation of extracellular matrix, which penetrated the scaffold to a depth of 250 to 300 microm. Mineralization, qualified by scanning electron microscopy in combination with energy-dispersive X-ray analysis and evaluated by determination of the Ca2+ content per scaffold, was up to 1.7-fold increased by TGF-beta1 compared with the control. In conclusion, the growth factor TGF-beta1 seems to be effective in improving extracellular bonelike matrix formation in vitro.