Expression of CD44V2 in transitional cell carcinoma of the urinary bladder and in urine

CD44 is the principal cell surface receptor for hyaluronate. Variant forms of the receptor, produced by alternative splicing, have been found to be associated with tumor progression in a variety of cancers. Based on investigations at the RNA level, it has recently been proposed that expression of CD44 variant V2 was present in urothelial cancer but not in normal urothelium. Since a distinctive marker for urothelial cancer would be extremely useful, frozen sections of normal urothelium and urothelial cancer were examined for expression of standard CD44 and CD44V2. Frozen sections of specimens of 35 patients with transitional cell carcinoma of the bladder, 16 specimens of normal bladder and 5 ureters were examined. Immunohistochemical staining was performed using a polyclonal antibody to CD44V2 (PAB CD44V2), a monoclonal antibody to CD44V2 (MAB CD44V2) and a monoclonal antibody to CD44S (MAB CD44S). CD44V2 and CD44S were also measured in lysates of urine sediments from 21 patients by enzyme-linked immunoabsorbent assay (ELISA). All investigated transitional cell carcinomas expressed CD44V2. There was no differentiation between invasive and noninvasive carcinoma. CD44V2 was also expressed in normal urothelium. Standard CD44 was expressed by the transitional cell carcinoma, normal urothelium, musculature and interstitial tissue. The amount of CD44V2 and CD44S in lysates of urine sediments is not correlated to diagnosis. In contrast to investigations at the RNA level, CD44V2 on the protein level seems not to be a distinctive marker for urothelial cancer. Therefore, CD44V2 will not be a useful diagnostic marker for detection of transitional cell carcinoma.     

Fulminant subacute sclerosing panencephalitis in association with pregnancy

Subacute sclerosing panencephalitis developed during pregnancy in a 27-year-old woman and immediately after delivery in an 18-year-old woman. In both, disease took an acute and fulminant course culminating in a vegetative state within several weeks. It is suggested that the relative older age of disease presentation and the unusually rapid neurologic deterioration were partially due to immunologic and hormonal alterations of pregnancy.     

Audiotaped versus written administration of the Situational Competency Test

The Situational Competency Test (SCT) is an audiotaped, verbal role-play measure of coping responses to eight drinking and eight non-drinking situations. The present investigation evaluated the comparability of response scores to audiotaped versus written administrations of the SCT in two samples of alcohol clients. The written administration of the SCT yielded significantly shorter durations of response in both clinical samples, but there were no other significant differences between the administration methods on the other scoring dimensions. Correlations of the audiotaped and written summary scores revealed no consistently significant or meaningful associations. Given the differences in duration, the generally poor correlations between summary scores, and the loss of the latency measure in the written format, we recommend retention of the audiotaped administration for use in research.     

The quality of acute stroke units on a nation-wide level: the Austrian Stroke Registry for acute stroke units

Concepts for stroke units that cover the acute phase vary. Therefore, the network of acute stroke units that is being set up in Austria in a uniform way is of general interest. This nationwide network has been established in accordance to evidence-based recommendations and prespecified criteria for available resources. The location for such a unit follows a maximum of 90-min isochrones (transport time) to the hospital. The quality of the network is currently documented and the results are reported. A nationwide stroke registry was prospectively performed on 15 stroke units that were already functional in this network. The aim was to document the quality performance of Austrian stroke units, focusing on rapid admissions, ready availability of investigations and therapies performed. Outcome measures were Barthel scale, Rankin score and percentages of complications. Between August 1998 and December 2000, 2,313 patients with ischemic stroke or with primary intracerebral hemorrhage admitted to an Austrian stroke unit within 24 h after onset of symptoms were prospectively included. Forty-three percent of the patients had a moderate or severe stroke. Fifty-seven percent of all patients were admitted to the stroke unit within 3 h after the onset of symptoms. Twenty-seven percent of these patients were brought in by ambulance accompanied by an emergency physician. Two percent of patients were admitted by helicopter. Fifty-four percent of patients had their first brain imaging within 30 min after admission, another 26% within 3 h. Intravenous thrombolysis was performed in 4.1% of patients. The overall stroke-unit mortality was about 6.8% and mortality at 3 months was 12.9%. The outcome at 3 months showed a modified Rankin Scale score of 0 or 1 in 47% of patients, denoting none or mild impairment. This network of acute stroke units is highly efficient in terms of rapid admissions, short intrahospital delays, as well as rapid use of readily available investigations. Stroke units seem to be well accepted by the general public and the medical community because our data show that all types of strokes are treated in Austrian stroke units, including severe strokes. The total number of concurrently treated acute strokes in other institutions across Austria is not known and no formal comparison with other systems of hospitalized care was undertaken, therefore further research is necessary.     

Proteolytic Processing Mechanisms in the Biosynthesis of Neuroendocrine Peptides: The Subtilisin-like Proprotein Convertases

The recent discovery of a novel family of precursor processing endoproteases has greatly accelerated progress in understanding the complex mechanisms underlying the maturation of prohormones, neuropeptides, and many other precursor-derived proteins. At least six members of this family have been found thus far in mammalian species, several having alternatively spliced isoforms, and related enzymes have been identified in many invertebrates, including molluscs, insects, nematodes, and coelenterates. The proprotein convertases are all dependent on calcium for activity and all possess highly conserved subtilisin-like domains with the characteristic catalytic triad of this serine protease (ordered Asp, His, and Ser along the polypeptide chain). Two members of this family, PC2(SPC2) and PC1/PC3(SPC3), appear to play a preeminent role in neuroendocrine precursor processing. Both convertases are expressed only in the brain and in the extended neuroendocrine system, while another important family member—furin/PACE (SPC1)—is expressed more ubiquitously, in almost all tissues, and at high levels in liver. SPC2 and SPC3 exhibit acidic pH optima and other properties which enhance their activity in the acidic, calcium-enriched environment of the dense-core secretory granules of the regulated pathway in neuroendocrine cells, while furin has a neutral pH optimum and is localized predominantly to the trans Golgi network where it is retained by a C-terminal transmembrane domain. Furin processes a wide variety of precursors in the constitutive pathway, such as those of growth factors, receptors, coagulation factors, and viral glycoproteins. Recent findings on the processing of proopiomelanocortin, proinsulin, proglucagon, and several other neuroendocrine precursors by SPC2 and SPC3 are discussed, along with information on the structure, properties, evolution, developmental expression, and regulation or the convertases. An inherited defect in the fat/fat mouse which affects the processing of proinsulin, and probably also many other prohormones, due to a point mutation in carboxypeptidase E has recently been identified and has begun to provide new insights into the functional integration of the individual processing steps.     

Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase

It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed AC superactivation (or supersensitization). More recently, we showed that acute G_i/o-coupled receptor activation inhibits the activity of several AC isozymes, including Ca²⁺/calmodulin-stimulated AC-I and -VIII, whereas chronic receptor activation induces their superactivation. Here, we report that both acute μ-opioid receptor-induced inhibition and chronic induced superactivation of AC-I and -VIII are pertussis toxin sensitive. In addition, we show that proteins that interfere with the activity of {ie195-2} subunits ({ie195-3} scavengers) strongly attenuate the acute inhibition of AC-I and -VIII and the superactivation of AC-I, and abolish the superactivation of AC-VIII. Based on these results, we suggest that {ie195-4} is involved in the acute inhibition and chronic agonist-induced superactivation of AC types I and VIII.