Calretinin expression in human normal and neoplastic tissues: a tissue microarray analysis on 5233 tissue samples

Calretinin is a calcium-binding protein expressed in different normal and neoplastic tissues. Early studies suggested that calretinin is a useful marker to differentiate adenocarcinomas from malignant mesotheliomas of the lung, but subsequent work has shown that calretinin can be expressed in several other tumor types. To systematically investigate the epidemiology of calretinin expression in normal and neoplastic tissues, we used tissue microarrays (TMAs) to analyze the immunohistochemically detectable expression of calretinin in 5233 tissue samples from 128 different tumor categories and 76 different normal tissue types. At least 1 case with weak expression could be found in 74 of 128 (58%) different tumor types and 46 entities (36%) had at least 1 tumor with strong positivity. In normal tissues, a particularly strong expression was found in Leydig cells of the testis, neurons of the brain, theca-lutein and theca interna cells of the ovary, and mesothelium. In tumors, strong calretinin expression was most frequently found in malignant mesotheliomas (6 of 7), Leydig cell tumors of the testis (5 of 5), adenomas of adrenal gland (5 of 9), and adenomatoid tumors (4 of 9). In summary, calretinin is frequently expressed in many different tumor types. Metastases of various different origins must be included in the differential diagnosis of calretinin-positive pleura tumors.     

Rapid acquisition of two-way active avoidance in inbred Roman Low Avoidance rats

Two inbred strains of rats, derived from the Roman High Avoidance and Roman Low Avoidance selection lines, were tested for performance on the two-way active avoidance task which had been used during selection. Both inbred strains rapidly acquired the avoidance response and showed nearly perfect avoidance from trial 40 through trial 50. Probably, genes responsible for the low avoidance performance in the RLA strain disappeared during inbreeding.     

Human defensins

Antimicrobial peptides are small, cationic, amphiphilic peptides of 12–50 amino acids with microbicidal activity against both bacteria and fungi. The eukaryotic antimicrobial peptides may be divided into four distinct groups according to their structural features: cysteine-free -helices, extended cysteine-free -helices with a predominance of one or two amino acids, loop structures with one intramolecular disulfide bond, and -sheet structures which are stabilised by two or three intramolecular disulfide bonds. Mammalian defensins are part of the last-mentioned group. The mammalian defensins can be subdivided into three main classes according to their structural differences: the -defensins, -defensins and the recently described -defensins. Mammalian -defensins are predominantly found in neutrophils and in small intestinal Paneth cells, whereas mammalian -defensins have been isolated from both leukocytes and epithelial cells. Recently, two novel human -defensins, human beta-defensin-3 (HBD-3), and human beta-defensin-4 (HBD-4) have been discovered. Similar to HBD-1 and HBD-2, HBD-3 has microbicidal activity towards the Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli) and the yeasts Candida albicans and Malassezia furfur. In addition, HBD-3 kills Gram-positive bacteria such as Streptococcus pyogenes or Staphylococcus aureus, including multi-resistant S. aureus strains, and even vancomycin-resistant Enterococcus faecium. In contrast to HBD-1 and HBD-2, significant expression of HBD-3 has been demonstrated in non-epithelial tissues, such as leukocytes, heart and skeletal muscle. HBD-4 is expressed in certain epithelia and in neutrophils. Its bactericidal activity against P. aeruginosa is stronger than that of the other known -defensins. Here we present an overview of human antimicrobial peptides with some emphasis on their antifungal properties.J.J. Schneider and A. Unholzer contributed equally to this work     

Activation kinetics of Glutamate receptor channels from wild-type Drosophila muscle

Outside-out patches from wild-type Drosophila larval muscle were exposed briefly to L-Glutamate (Glu) using a piezo-driven application system. Glu in concentrations of 0.1 to 30 mM was applied and the responses to repeated applications of a given concentration were averaged. The peak current, î, and the current rise time, t_r, from 0.1 î to 0.9 î were determined from the averages. Half-maximum activation of the channels was reached with ≈ 2 mM Glu. î increased proportional to the power n = 3.5 to n = 5.8 (average of four experiments, n = 4.4) for Glu concentrations between 0.3 and 0.5 mM. t_r increased from ≈ 0.2 ms at 10 mM Glu to a value of ≈ 3.5 ms at 0.2 mM Glu. A linear reaction scheme with five binding steps preceding the channel-opening conformational change is proposed as the kinetic mechanism of channel activation and investigated in computer simulations. A set of rate constants assuming the same affinity for each binding site is found to describe the data better than one assuming positive cooperativity. The results are very similar to those for Glu-gated channels of crayfish and locust muscle, which is evidence for a common kinetic mechanism of these channels.     

Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid

1. Download : Download high-res image (177KB)
2. Download : Download full-size image

     

The time course of cross-talk during the simultaneous specification of bimanual movement amplitudes

 We investigated the time course of the amplitude specification of rapid bimanual reversal movements (lateral displacements on two digitizers). To this end we used the timed-response paradigm in which the response has to be initiated synchronously with an auditory signal. Information about the required amplitudes was presented at various times before the synchronization signal. Consistent with previous results, the progression of amplitude specification was reflected in the dependence of the amplitudes of the reversal movements on the time interval between amplitude information and synchronization signal. Same or different amplitudes for the hands were used to examine cross-talk at the programming level of the two-level model of intermanual interference. The results indicate the existence of cross-talk in particular at short intervals between information about amplitude and movement initiation. This is consistent with the notion that cross-talk between concurrent processes of amplitude specification is transient and vanishes as the time available for motor programming increases. Received: 28 August 1996 / Accepted: 10 July 1997     

Detection of perforin and granzyme A mRNA in infiltrating cells during infection of mice with lymphocytic choriomeningitis virus

The analysis of gene expression in cytotoxic T cells by in situ hybridization of serial liver and brain sections from mice infected with lymphocytic choriomeningitis virus (LCMV) and immunostaining with T cell marker- and virus-specific antibodies revealed a close histological association of infiltrating lymphocytes expressing the perforin and granzyme A genes with virally infected cells. Maximal frequency of perforin and granzyme A mRNA-containing cells on liver sections preceded by about 2 days maximal LCMV-specific cytotoxicity of the lymphoid liver infiltrating cells. These results are most consistent with an involvement of perforin and granzyme A in cell-mediated cytotoxicity in vivo.