Novel KChIP2 isoforms increase functional diversity of transient outward potassium currents

Kv4.3 channels conduct transient outward K⁺ currents in the human heart and brain where they mediate the early phase of action potential repolarization. KChIP2 proteins are members of a new class of calcium sensors that modulate the surface expression and biophysical properties of Kv4 K⁺ channels. Here we describe three novel isoforms of KChIP2 with an alternatively spliced C-terminus (KChIP2e, KChIP2f) or N-terminus (KChIP2g). KChIP2e and KChIP2f are expressed in the human atrium, whereas KChIP2g is predominantly expressed in the brain. The KChIP2 isoforms were coexpressed with Kv4.3 channels in Xenopus oocytes and currents recorded with two-microelectrode voltage-clamp techniques. KChIP2e caused a reduction in current amplitude, an acceleration of inactivation and a slowing of the recovery from inactivation of Kv4.3 currents. KChIP2f increased the current amplitude and slowed the rate of inactivation, but did not alter the recovery from inactivation or the voltage of half-maximal inactivation of Kv4.3 channels. KChIP2g increased current amplitudes, slowed the rate of inactivation and shifted the voltage of half-maximal inactivation to more negative potentials. The biophysical changes induced by these alternatively spliced KChIP2 proteins differ markedly from previously described KChIP2 proteins and would be expected to increase the diversity of native transient outward K⁺ currents.     

Histopathological aspects of Dengue-2 virus infected mice tissues and complementary virus isolation

The difficulty in studying dengue virus (DENV) infection in humans and in developing a virus vaccine is the absence of a suitable animal model which develops the full spectra of the Dengue haemorrhagic fever (DHF) and Dengue shock syndrome (DSS). Despite the fact that viruses have been found in various animal tissues, we isolated DENV from tissues of adult BALB/c mice, inoculated with DENV serotype 2 (DENV-2) obtained from human serum. Viruses were ultrastructurally identified and immunolocalized by immunofluorescence techniques in C6/36 mosquito cell cultures, inoculated with tissues (liver, lung, kidney and cerebellum) macerate supernatant from mice, 48 h post-infection (p.i.). These organs, collected at the same stage of infection, were examined histologically. The histopathological analysis revealed focal alterations in all tissues examined. Liver contained focal ballooned hepatocytes, but without modifying the average diameter of the majority of hepatocytes. Sinusoidal lumen was significantly diminished at this stage but portal and centrolobular veins became congested. Lungs exhibited hemorrhagic foci in the alveolar space, vascular congestion and focal alveolitis. Cerebellar tissue showed rare foci of neuronal compactation (Purkinje cells) and perivascular oedema. In kidneys it was observed an increase in glomerular volume with augmented endocapillary and mesangial cellularity, with reactivity to anti-IgM in all glomeruli of infected mice. In conclusion, DENV-2 was found in all tissues examined early in the evolution of infection. Presence of viruses in tissues has mainly led to hemodynamic alterations with generalized vascular congestion and increased permeability, and mast cell recruitment in lungs. The latter could participate in the vascular modifications in tissues.     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

A prospective study of the accuracy of preoperative computed tomographic staging of patients with biopsy-proven rectal carcinoma

From June 1983 to January 1986, 91 patients with biopsy-proven adenocarcinoma of the rectum had computed tomographic scans of the pelvis performed before treatment as part of a "sandwich" radiotherapy-surgery regimen. Two experienced diagnostic radiologists performed locoregional staging of all scans according to the University of California at San Francisco criteria; one of these radiologists repeated this staging at a later time to test the reproducibility of a single observer. Staging was performed without the use of any other radiographic studies or of any clinical information except the patients' age, sex, and the diagnosis of rectal carcinoma, to test the value of computed tomographic scans alone for staging. Agreement between the two stagings performed by the first observer was 51 percent, and interobserver agreement was only 37 percent. Agreement with Dukes' staging was only 33 percent. Therefore, preoperative pelvic computed tomographic scanning of primary rectal adenocarcinoma should not be relied upon for staging or for the selection of patients for treatment options.     

Ultraviolet exposure in the environment of welding work sites

It has been checked if the "limits of the acceptable doses of ultraviolet radiation of monochromatic radiation at the workplace" (NIOSH-standard of USA) are adhered to in the vicinity of welders' work stations in a factory hall. For recording of UV-doses polysulphon films have been used. According to these investigations non-welders are exposed to doses of UV-radiation which exceed the limits recommended by about eight times. Clinical examinations of these persons showed chronic damage of the external parts of the eyes in a higher percentage than in a control group. It is pointed to the necessity of taking protective measures to shield persons working in the vicinity of welding job sites from ultraviolet radiation.     

Non-responsiveness to hepatitis B vaccination in haemodialysis patients: association with impaired TCR/CD3 antigen receptor expression regulating co-stimulatory processes in antigen presentation and recognition

The study was undertaken to evaluate the relationship betweennon-responsiveness to hepatitis B (HBV) vaccination in haemodialysedpatients and HBs antigen (Ag) presentation and recognition dependingon TCR/CD3 receptors expression. We have found that the causeof the blunted response to HBV vaccination is multifactorialand seems to be associated with the following: (1) A reducednumber of TCR/CD3 antigen receptor complexes on freshly isolateduraemic CD4 T cells, especially in non-responders. (2) The bluntedproliferative response of uraemic CD4 T cells isolated fromnon-responders and stimulated for 6 days by autologous monocytespresenting HBsAg was associated with the decreased density ofthe TCR/CD3 receptors. (3) Moreover, in uraemic non-respondersthe expression of adhesion and accessory molecules on monocytes(intercellular adhesion molecule-1/ ICAM-1, HLA-DR/Ia/) wassignificantly decreased following the culture with autologousmonocytes serving as HBsAg-presenting cells. CD4 molecules andlymphocyte function antigen-1ß /LFA-1ß/on helper-inducer T cells were increased before and after theculture. (4) These findings were also associated with a diminishedbinding capacity of IL-1ß and IL-6 to their receptorson helper-inducer T cells. (5) IL-2, IFN- and IL-4 productionwas decreased in uraemic non-responders, especially after 72h of the culture. (6) Inhibited proliferation of helper-inducerT cells in uraemic non-responders was only partially reversiblein the presence of exogenous IL-1ß, IL-6, IL-2 andIFN-. (7) HLA typing of uraemic non-responders was associatedwith extended haplotype: HLA A1, B8, DR3, DR7, DQ2.     

Congenital muscular dystrophy and severe central nervous system atrophy in two siblings

Severe degenerative features of the nervous system of a hitherto unknown kind, associated with a neuromuscular disorder with histopathological features of congenital muscular dystrophy, are reported in two female siblings. The clinical profile was characterized by generalized hypotonia followed by spastic tetraplegia, contractures, polyneuropathy, lack of cognitive development and progressive microcephaly. There was no involvement of the eyes. Neuropathological examination of the brain of one sibling, who died at the age of 30 months, revealed subtotal loss of neurons in the cerebral and cerebellar cortex and in the ventral pons, and secondary loss of myelin in the cerebral and cerebellar subcortical white matter. Sural nerve biopsy in the other sibling, who had a similar neurological affection, showed a lack of large myelinated fibers.This investigation is part of the research program Disorders of the Neuromuscular System of the University of Nijmegen     

Evaluation of abstracts submitted for the annual meeting of the German Neurosurgical Society 1999--unravelling a mystery

The evaluation for the abstracts submitted for the annual meeting of the German Neurosurgical Society together with the Swiss Neurosurgical Society in Munich 1999, is presented as it has developed during the meetings of the last years. 597 abstracts were reviewed by the 30 members of the review committee according to a 5 point grading system. Cut off for acceptance was a mean grading of 2.7 points. Abstracts better than 2.4 were accepted, abstracts worse than 2.7 were rejected. Experimental studies were judged slightly better than clinical studies: the mean grading of clinical and experimental studies was 2.55 +/- 0.5 vs. 2.72 +/- 0.6 (p < 0.02). All abstracts with a mean grading of 2.4-2.7 and a standard deviation > 1.0 were discussed in a meeting of the review committee. 353 abstracts were accepted. Some of the abstracts submitted for oral presentation had to be converted to poster presentations. Among others the decision was based on the grading of the abstract.