Alterations of the levels of glycoproteins Ib-IX and IIb-IIIa in platelets stored at 22°C

Platelets stored in CLX™ blood bags, under normal blood banking conditions, were studied for up to 7 days to determine if changes ocurred in the levels of membrane glycoproteins (GP) Ib-IX and IIb-IIIa. Radiolabeled monoclonal antibodies (MAB) were used to estimate the number of glycoprotein molecules on the surface membrane of intact platelets. GP IX and GP IIb-IIIa levels remained essentially unaltered during storage. In contrast, the content of GP Ib at day 7 decreased by 45% of the total when fresh. The aggregation response to ristocetin, which requires GP Ib, was also diminished after 7 days. Addition of protease inhibitors, leupeptin and/or aprotinin did not appear to influence the degradation of this glycoprotein. We conclude that storage at 22°C has deleterious effects on the GP Ib content of platelets.     

Unilateral nephrectomy in the rat: effects on mercury handling and renal cortical subcellular distribution

As unilateral nephrectomy (UNX) is associated with enhanced mercuric chloride nephrotoxicity, studies were undertaken to characterize the effects of UNX on the tissue content, urinary excretion, and renal cortical subcellular distribution of mercury in the rat. Animals were studied immediately, 2 days or 14 days following UNX, during separate phases of compensatory renal hypertrophy. As compared to sham surgery controls, mercury content in renal cortex was higher in all UNX groups at 24 hr following injection and in the immediate and 2-day groups at 1 or 3 hr. However, UNX was not associated with any alteration in mercury content within outer or inner medulla, liver, plasma, or red blood cells. Subcellular distribution studies demonstrated that cytosolic mercury was uniformly elevated in all UNX groups at 1, 3, and 24 hr following injection while mercury bound to "metallothionein-like" proteins or free in the cytosol was increased only at 1 or 3 hr. Nuclear, mitochondrial, or microsomal mercury content was elevated in the animals studied immediately or 14 days after UNX at 3 or 24 hr following injection, while animals studied 2 days after UNX demonstrated a nearly uniform increase at 1, 3, and 24 hr. Single-kidney urinary mercury excretion was elevated in all UNX groups while excretion per gram kidney weight was increased only in the animals studied immediately or 2 days after surgery. These studies suggest that all phases of compensatory renal hypertrophy are associated with an enhanced content of mercury within the cell cytoplasm and in critical cellular organelles, which may explain the enhanced nephrotoxicity seen following UNX.     

Targeted gene disruption of murine CD7

CD7 is a 40 kDa type I transmembrane glycoprotein member of the Ig superfamily. CD7 is a marker of mature human T cells and NK cells, and is expressed early in their development. Cross-linking CD7 positively modulates T cell and NK cell activity as measured by calcium fluxes, expression of adhesion molecules, cytokine secretion and proliferation. CD7 associates directly with phosphoinositol 3'-kinase, and CD7 ligation induces production of D-3 phosphoinositides and tyrosine phosphorylation. Severe combined immunodeficiency has been associated with a lack of lymphocyte surface CD7. The CD7 ligand is unknown. The murine CD7 homolog is encoded by a single gene on chromosome 11. In order to characterize the role of CD7 in lymphocyte development and function we have eliminated the CD7 gene by targeted disruption. CD7- deficient mice display normal histology of thymus and spleen, normal lymphocyte populations in primary and secondary lymphoid tissues, and normal serum Ig levels. Specific antibody responses after immunization with T-dependent and T-independent antigens are equivalent in wild-type and CD7 knockout mice. CD7-deficient lymphocytes respond normally to T cell mitogenic and allogeneic stimuli, and display normal NK cell cytotoxicity.      

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Histopathological diagnosis of Barrett's mucosa and associated neoplasias. Results of a consensus conference of the Working Group for "Gastroenterological Pathology of the German Society for Pathology" on 22 September 2001

There are a number of difficulties regarding the diagnosis of Barrett's mucosa and the varying grades of neoplasia that may be associated with it. It was therefore the aim of a consensus conference of the "Working Group for Gastroenterological Pathology within the German Society of Pathology" to achieve standardization regarding the following issues: definition and diagnostic criteria for Barrett's mucosa and its discrimination from intestinal metaplasia of the cardia, diagnostic criteria for intraepithelial neoplasia, number of biopsies necessary to establish the diagnosis, significance of additional immunohistochemical and/or molecular biological methods as well as importance of a second opinion in the diagnosis of intraepithelial neoplasia.     

Interaction of peripheral and central respiratory drives in cats I. Effects of sodium cyanide as a peripheral chemoreceptor stimulus at different levels of CSF pH

In cats anesthetized with chloralose-urethane, the central respiratory chemoreceptors were exposed to mock CSF of pH 7.02, 7.20, or 7.57. The right carotid body was simultaneously stimulated by intracarotid injections of 40, 80, or 160 μg sodium cyanide in 200 μl Ringer solution. The left carotid nerve and, in some animals, both vagosympathetic truncs were dissected. It could be demonstrated the the increase in ventilation produced by application of NaCN to the peripheral chemoreceptors is significantly larger at high than at low mock CSF pH (i.e. at low than at high central stimulus intensity). In vagotomized cats the responses of V_T and gelai to NaCN similarly depend upon CSF pH; they are somewhat larger, though, than in intact animals. These results are discussed as compared with results reported by different authors. Supported by the Deutsche Forschungsgemeinschaft (Be 477)     

Relationship between slow-wave EEG bursts and heart rate changes in preterm infants

The objective of the study is to explore interactions between cortical and autonomic functions in the first weeks of postnatal life. We investigated the behaviour of one-channel electroencephalogram (EEG) patterns and heart rate (HR) dynamics in preterm infants. In a group of 15 healthy preterm infants with a mean conceptional age (CA) of 36 weeks and a mean postnatal age of 17.5 days simultaneous registration of amplitude integrated EEG (aEEG) and HR pattern was performed during interfeeding intervals. Periods with a discontinuous EEG activity and a low heart-rate variability (HRV) were selected for further processing and averaging. It was found that spontaneous activity transients (SATs) or slow wave EEG bursts during "Tracé alternant" (TA) can be accompanied by an HR acceleration of 1-2% (mean: 1.9, range: 0.6-3.5 beats/min) lasting approximately 5s (mean, range: 3.6-7.1s). The aim of the study is to give evidence of a coherent behaviour of EEG bursts and HR in the developing nervous system of preterm infants.