The role of auxiliary dihydropyridine receptor subunits in muscle

The skeletal muscle dihydropyridine receptor is a slowly-activating calcium channel that functions as the voltage sensor in excitation-contraction coupling. In addition to the pore-forming α_1S subunit it contains the transmembrane α₂δ-1 and γ₁ subunits and the cytoplasmic β_1a subunit. Although the roles of the auxiliary subunits in calcium channel function have been intensively studied in heterologous expression systems, their functions in excitation-contraction coupling has only recently been elucidated in muscle cells of various null-mutant animal models. In this article we will briefly outline the current state of these investigations. * To whom correspondence should be addressed: Tel.: +43-512-507-3787; Fax: +43-512-507-2836; E-mail: bernhard.e.flucher@uibk.ac.at     

Impact of Dual Chamber Pacing on the Incidence of Atrial and Ventricular Tachyarrhythmias in Recipients of Implantable Cardioverter Defibrillators

Recent observations suggest that frequent dual-chamber pacing in recipients of implantable cardioverter defibrillators (ICD) may adversely influence clinical outcomes. This prospective, multicenter study examined the relationship between the frequency of atrial (%AP) and ventricular pacing (%VP) and the incidence of atrial (AT) and/or ventricular tachyarrhythmias (VT) in a standard ICD population. A total of 141 consecutive patients with primary and secondary ICD indications were studied. Continuous arrhythmia detection with a dual-chamber ICD revealed paroxysmal AT in 60 (43%) and VT in 72 (51%) patients within 6 months of device implantation. Far-field oversensing of ventricular signals occurred in 13% of all "atrial tachy response" mode switches. Without adjustment for covariates, a higher %AP was associated with an increased incidence of AT (P < 0.05). However, this association remained only weakly significant after adjustment for covariates using a multivariate model. High New York heart failure functional classes correlated significantly with AT (P = 0.02) and VT (P = 0.007). Rate-modulated pacing, programmed in 1/3 of patients, correlated with occurrence of AT (P = 0.006), but not with occurrence of VT. With respect to dual-chamber pacing, a %AP ≥ 48% combined with a %VP > 40% was associated with an increased probability for VT. In conclusion, AT and VT occurred frequently within 6 months after dual-chamber ICD implantation. High rates of DDD/R stimulation were associated with a trend toward higher incidence of AT, VT, or both.     

Primary structures of proteins characterized by proteinase K digestion and matrix-assisted laser desorption/ionization mass spectrometry

To improve the sequence ions of a protein in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), proteinase K was used to digest the protein followed by MALDI-MS characterization of the peptide fragments. The primary structures of three proteins, insulin B chain, cytochrome c and lysozyme, were determined by this method. A series of peptide fragments including those differentiated by one residue can be produced from the protein by using proteinase K digestion, thus providing support to the protein sequence. The peptide fragments liberated from proteinase K proteolysis of the insulin B chain allow the protein to be partially sequenced. Furthermore, some of the residues are double or triple checked by generating a variety of fragments. The same method was used to investigate cytochrome c and lysozyme denaturated in 3 M guanidine hydrochloride. The success of the method relies on the intrinsic properties of proteinase K and accurate determination of the peptide fragments by MALDI-MS.     

Morphometric study of the equine navicular bone: variations with breeds and types of horse and influence of exercise

Navicular bones from the 4 limbs of 95 horses, classified in 9 categories, were studied. The anatomical bases were established for the morphometry of the navicular bone and its variations according to the category of horse, after corrections were made for front or rear limb, sex, weight, size and age. In ponies, navicular bone measurements were smallest for light ponies and regularly increased with body size, but in horses, navicular bone dimensions were smallest for the athletic halfbred, intermediate for draft horse, thoroughbreds and sedentary halfbreds and largest for heavy halfbreds. The athletic halfbred thus showed reduced bone dimensions when compared with other horse types. Navicular bones from 61 horses were studied histomorphometrically. Light horses and ponies possessed larger amounts of cancellous bone and less cortical bone. Draft horses and heavy ponies showed marked thickening of cortical bone with minimum intracortical porosity, and a decrease in marrow spaces associated with more trabecular bone. Two distinct zones were observed for the flexor surface cortex: an external zone composed mainly of poorly remodelled lamellar bone, disposed in a distoproximal oblique direction, and an internal zone composed mainly of secondary bone, with a lateromedial direction for haversian canals. Flexor cortex external zone tended to be smaller for heavy ponies than for the light ponies. It was the opposite for horses, with the largest amount of external zone registered for draft horses. In athletic horses, we observed an increase in the amount of cortical bone at the expense of cancellous bone which could be the result of reduced resorption and increased formation at the corticoendosteal junction. Cancellous bone was reduced for the athletic horses but the number of trabeculae and their specific surfaces were larger. Increased bone formation and reduced resorption could also account for these differences.     

A Novel Glycine Mutation in the Col7a1 Gene Leading to Dominant Dystrophic Epidermolysis Bullosa with Intra-Familial Phenotypical Heterogeneity

Abstract:   Dystrophic epidermolysis bullosa (DEB) represents a group of inherited skin disorders characterized by sublamina densa blister formation. We resent the case of a 16-year old girl with DEB, who had a 10-year-history of recurrent pruritic skin lesions. Despite misleading biopsy results, the correct diagnosis was suspected by examination of other family members. Finally, mutational analysis revealed a novel glycine substitution mutation in the COL7A1 gene in three affected family members.     

Cellular proliferation markers in peripheral and central fibromas: a comparative study

Objective:

To perform a comparative study of the cellular proliferation in the peripheral and central fibromas.

Material and Methods:

Immunohistochemistry for PCNA and the AgNOR technique were performed in 9 cases of peripheral odontogenic fibroma (POF), in 4 cases of odontogenic fibroma (OdF), in 8 cases of peripheral ossifying fibroma (PEOF) and 7 cases of ossifying fibroma (OsF). The Kruskal-Wallis and Mann-Whitney tests were used for the statistical analyses.

Results:

Mesenchymal component of the central lesions presented a higher mean number of AgNOR per nucleus and PCNA index than did the peripheral lesions (P≤0.05). The mean number of AgNOR per nucleus in the epithelial component proved to be higher in the OdF than in the POF (P≤0.05). The mesenchymal and epithelial components presented similar mean numbers of AgNOR per nucleus and PCNA index in the OdF, as well as a similar mean number of AgNOR per nucleus in the POF.

Conclusions:

The mesenchymal component may well play a role in the differences between the biological behaviour of the central lesions as compared to the peripheral lesions. Moreover, considering that the epithelial and mesenchymal components in odontogenic fibromas presented a similar proliferation index, more research is warranted to understand the true role of the epithelial components, which are believed to be inactive in nature, as well as in the development and biological behaviour of these lesions.     

Improvement of Quality of Life by Means of Antitachy Pacing: From PainFREE to the ADVANCE-D Trial

Background: Implantable cardioverter-defibrillators (ICD) can terminate ventricular tachyarrhythmias with shocks (painful) or antitachycardia pacing (painless). According to the results of the Pacing Fast VT Reduces Shock ThErapies Trials, antitachycardia pacing (ATP) can avoid painful shocks and also increase device longevity. The purpose of the ADVANCE-D (Atp DeliVery for PAiNless ICD ThErapy) study is to determine the most appropriate ventricular tachycardia (VT) therapy, so as to optimize painless therapy for life-threatening arrhythmias.
Methods and Results: The ADVANCE-D is a prospective, multicenter, parallel, two-arm randomized study designed to evaluate the efficacy of two different sequences of ATP therapies (burst 15 pulses, 88%, vs burst 8 pulses, 88%), during an episode of spontaneous arrhythmia classified as fast VT (FVT) in patients with a Class I or IIA indication for ICD implantation (single and dual chamber devices). The primary endpoint is to compare the efficacy of two ATP therapies for FVT episodes. The study will enroll a minimum of 900 patients within 2 years, followed-up for 12 months. The investigation is expected to be completed in 2007.
Conclusions: The ADVANCE-D trial is the first large randomized clinical investigation aimed to evaluate optimal programming and efficacy of ATP.     

Erythropoietin and Renin Substrate in Cerebellar Haemangioblastoma

ABSTRACT. We examined eight cerebellar haemangioblastoma tumours from eight patients, aged 16–63 years, 5 females and 3 males. Preoperative haemoglobin values exceeded 180 g/1 in four patients, and 150 g/1 in four. All high Hb values were normalized upon surgical removal of the tumours. All tumours contained scattered cells which stained positively with antisera against pure human urinary erythropoietin and plasma renin substrate. We conclude that cerebellar haemangioblastomas produce immunoreactive erythropoietin, which shares common antigenic determinants with renin substrate.     

Recurrent Coronary In-Stent Restenosis: Potential of Membrane-Covered Stents

We report a 64-year-old patient with single vessel coronary disease who initially underwent PTCA and stent implantation for a complex RCA lesion. The patient was subsequently readmitted for unstable angina pectoris after 2 and 6 months. Coronary angiograms each time revealed subtotal reocclusions of the target vessel due to in-stent restenosis. At 2 months, the patient underwent rotational atherectomy and additional stent implantation, During the second reintervention at 6 months rotational atherectomy was followed by implantation of two membrane-covered stent deployed within the conventional stents (stent-indent). Subsequently, the patient remained asymptomatic. Control angiography after 5 months revealed only minor stent lumen loss not requiring reintervention. Membrane-covered stents appear to be a promising alternative to reduce the incidence and degree of in-stent restenosis in selected lesions.     

DETECTION OF HEPATITIS C VIRUS ANTIBODIES AND HEPATITIS C VIRUS RNA IN PATIENTS WITH ALCOHOLIC LIVER DISEASE

The prevalence of hepatitis C virus (HCV) antibody was determinedin 130 patients with alcoholic liver disease using a second-generationanti-HCV enzyme immunoassay (ELISA 2) and confirmed by a sensitivepolymerase chain reaction procedure measuring HCV RNA. Hepaticdisease was evaluated by clinical and biochemical studies and,whenever possible, by liver biopsy. Seventy-one patients werediagnosed as having cirrhosis, and 59 alcoholic hepatitis (n= 33) or fatty liver (n = 26). The prevalence of anti-HCV inthe total group was 9.2% and did not differ significantly inthe cirrhotics (11.3%) as compared with the non-cirrhotics (6.8%).HCV RNA was detected in six out of eight cirrhotics and threeOut of four non-cirrhotics who were ELISA 2 positive. A positivetest for antibodies to hepatitis core antigen (anti-HBc) wasmore frequent in anti-HCV-positive patients (75%) than in theanti-HCV-negative group (14%, P<0.001). Anti-HBc was alsofound more frequently in the cirrhotics (25.4%) than in thealcoholics without cirrhosis (11.9%). However, the prevalenceof hepatitis B surface antigen was equally low in both groups(cirrhotics 1.4%, non-cirrhotics 1.7%). No correlation was observedbetween the prevalence of anti-HCV antibodies and the severityof liver dysfunction. These results indicate that HCV, and especiallyHCV-viraemia, is less frequent in alcoholics in southern Germanythan suspected in previous studies, and that the prevalenceof HCV markers in alcoholics has been overestimated by ELISA1 used alone.