Prolonged exercise potentiates sarcoplasmic reticulum Ca<Superscript>2+</Superscript> uptake in rat diaphragm

The effects of a single bout of prolonged treadmill exercise [mean=81 (13) min] on sarcoplasmic reticulum (SR) Ca²⁺ release, uptake and ATPase activity were determined in the costal region of rat diaphragm (D) and red gastrocnemius (RG). Glycogen depletion measurements made immediately following exercise suggested that treadmill running substantially recruited the fibers throughout both muscles. SR Ca²⁺ ATPase activity, measured in isolated SR vesicles, decreased in the RG by 33% but remained unchanged in D in response to the exercise bout. This effect in RG was matched by a 37% decline in Ca²⁺ uptake and a 28% depression in Ca²⁺ release when measured in muscle homogenates. Conversely, Ca²⁺ uptake increased between 157% and 263% in the D in the absence of any change in Ca²⁺ release. These data show that the attenuation of SR function that has been consistently observed in limb muscle over the last several decades is absent in diaphragm despite the fact that its fibers appear to experience sufficient activity to deplete their glycogen. In fact, the large increase in Ca²⁺ uptake in D shows that prolonged activity actually potentiates the ability of SR vesicles to sequester Ca²⁺ in the absence of any increase in energy cost. Thus, it appears necessary to re-evaluate the role of exercise in regulating Ca²⁺ sequestration by the SR as different muscles may respond in ways that are dictated by their function. Electronic Publication     

Comparative allograft histology after liver transplantation for cryptogenic cirrhosis, alcohol, hepatitis C, and cholestatic liver diseases

BACKGROUND: End-stage liver disease for which no cause can be identified, cryptogenic cirrhosis, is a common indication for liver transplantation. Allograft inflammation and fibrosis have been reported to recur with similar frequencies after liver transplantation for cryptogenic cirrhosis and hepatitis C (HCV). METHODS: We determined sequential posttransplant allograft histology in four groups of recipients: 31 transplanted for cryptogenic cirrhosis, 70 for cholestatic etiologies, 40 for alcoholic liver disease, and 56 for HCV. Modified hepatitis activity index (HAI) and fibrosis stage were determined at 4 months, 1 year, and at most recent biopsy posttransplantation. RESULTS: The prevalence of HAI > or = 2 among cryptogenic recipients was similar to that of cholestatic and alcoholic recipients at 4 months, 1 year, and at most recent evaluation (mean 45+/-17 months posttransplantation). For HCV-infected recipients, the frequency of HAI > or = 2 was more than for cryptogenic recipients at 1 year (52 vs. 29%, P=0.04) and at most recent evaluation (64 vs. 15%, P=0.003). Fibrosis scores for cryptogenic, cholestatic, and alcoholic recipients were similar at all timepoints. The proportion of HCV-infected recipients with fibrosis stage >2 was more than that of cryptogenic recipients at 4 months (29 vs. 12%, P=0.05), 1 years (46 vs. 7%, P=0.0002), and at most recent evaluation (42 vs. 15%, P=0.06). None of the cryptogenic recipients developed cirrhosis. RESULTS: The frequency of elevated HAI and fibrosis stage in recipients who undergo transplantation for cryptogenic cirrhosis is similar to that of recipients who undergo transplantation for cholestatic etiologies and significantly less than that of HCV-infected recipients. Fibrosis stage and HAI are generally stable after transplantation for cryptogenic cirrhosis. These data do not suggest a viral etiology of liver disease in the majority of patients with cryptogenic cirrhosis.     

An essential role of Bmp4 in the atrioventricular septation of the mouse heart

Proper septation and valvulogenesis during cardiogenesis depend on interactions between the myocardium and the endocardium. By combining use of a hypomorphic Bone morphogenetic protein 4 (Bmp4) allele with conditional gene inactivation, we here identify Bmp4 as a signal from the myocardium directly mediating atrioventricular septation. Defects in this process cause one of the most common human congenital heart abnormalities, atrioventricular canal defect (AVCD). The spectrum of defects obtained through altering Bmp4 expression in the myocardium recapitulates the range of AVCDs diagnosed in patients, thus providing a useful genetic model with AVCD as the primary defect.     

Protein-Losing Enteropathy with Collagenous Colitis

Collagenous colitis is a distinct cause of chronic watery diarrhea characterized by abnormal deposition of collagen in the subepithelial region of the colonic mucosa. Typically, laboratory tests of blood, urine, and stool are normal. A few patients have laboratory evidence of small bowel dysfunction and malabsorption, but excessive enteric protein loss is not a commonly recognized manifestation of collagenous colitis. We report a 62-yr-old woman who had collagenous colitis associated with a marked protein-losing enteropathy in the absence of obvious small intestinal disease or colonic ulceration. Biopsies of endoscopically normal-appearing colonic mucosa should be performed in patients with protein-losing enteropathy in whom no cause is apparent after initial evaluation.     

Adjuvant intravesical therapy for superficial bladder cancer.

OBJECTIVE: To review the results of clinical trials and adverse drug effects of thiotepa, BCG vaccine, mitomycin, and doxorubicin, which are used as adjuvant intravesical therapy for superficial bladder cancer. DATA SOURCE: Information was retrieved from a MEDLINE search, of the English-language literature. Indexing terms included adjuvant pharmaceutics, bladder neoplasms, thiotepa, mitomycin, BCG vaccine, and doxorubicin. DATA EXTRACTION: Data from several human and in vitro studies were assessed and evaluated, according to the strength of comparative data and therapeutic response. STUDY SELECTION: Emphasis was placed on clinical trials that assessed and evaluated dosage, therapeutic regimens, and therapeutic response of adjuvant intravesical therapy for superficial bladder cancer. DATA SYNTHESIS: Adjuvant intravesical therapy and long-term prophylaxis are effective for superficial bladder cancer. Studies have shown that doxorubicin, thiotepa, BCG, and mitomycin, when used as adjuvant therapy, provide better protection than transurethral resection alone against tumor recurrence and prolong the time to when cystectomy is required. CONCLUSIONS: Several randomized clinical trials suggest that BCG is superior to thiotepa, doxorubicin, and mitomycin in preventing bladder tumor recurrence and tumor progression. Local cystitis is an adverse effect produced by all four agents; however, BCG vaccine has been reported to cause a higher incidence of adverse reactions (e.g., dysuria, hematuria). BCG may also cause an influenza-like syndrome, arthralgias, and fever, but most of these reactions have resulted in few severe adverse effects when the drug is given in the relatively modest recommended doses.     

Digital subtraction angiography system evaluation with phantoms

Advances in digital subtraction angiography imaging demonstrate the need for critical evaluation of the performance of digital subtraction equipment. The design of a phantom set for noninvasive assessment of the imaging quality of digital subtraction equipment is described; components include a remotely controlled transport system and individual patterns to evaluate the contrast and detail properties of the image intensifier, low-contrast sensitivity and resolution of the system, geometric distortion of image, linearity, mechanical and electronic stability of equipment, and effects of bone and bowel gas on iodine perception. The performance of an add-on digital radiographic system is presented, along with radiation exposure levels at the image intensifier for a range of radiographic techniques.     

A founder mutation in the gamma-sarcoglycan gene of gypsies possibly predating their migration out of India

We investigated the molecular basis of a severe form of early onset autosomal recessive muscular dystrophy with sarcoglycan (SG) deficiency in seven large Gypsy families living in different parts of Western Europe and apparently not closely related. They were linked to the LGMD2C locus (13q12) suggesting a primary defect in the gamma-SG gene coding for the 35 kDa dystrophin-associated glycoprotein. All of the 18 investigated patients were homozygous for the same G-->A transition in codon 283 producing the replacement of a conserved cysteine of the extra-cellular domain of the protein by a tyrosine. All affected chromosomes in homozygous and heterozygous relatives carried the same allele 5 of the intragenic marker D13S232. Flanking markers were studied to delineate a common ancestral haplotype, the size of which was used to compute the date of the founding mutation. We found evidence that the mutation occurred between 60 and 200 generations ago, therefore possibly predating the commonly accepted date of migration of the Gypsy ancestors out of India.