Cardiac autophagic vacuolation in severe X-linked myopathy with excessive autophagy.

X-linked myopathy with excessive autophagy (XMEA), caused by mutations of the VMA21 gene, is a strictly skeletal muscle disease. Extensive studies in yeast established VMA21 as the master assembly chaperone of V-ATPase, the complex multisubunit proton pump that acidifies organelles and that is vital to all mammalian tissues. As such, skeletal muscle disease exclusivity in XMEA is highly surprising.

MANAGEMENT OF TRAUMATIC LIVER LESIONS.

Aim: To determine the correct therapeutic approach to the different grades of liver trauma.

Material And Methods: The study is based on a retrospective analysis of treatment outcomes in 56 patients with abdominal trauma admitted over a 9-year period to in the IIIrd Surgical Clinic of the Iasi "Sf. Spiridon" Hospital.

A diagnostic dilemma in a family with cystinuria type B resolved by muscle magnetic resonance.

Background: Congenital myopathies are inherited primary disorders of the muscle caused by mutations affecting structural, contractile, or regulatory proteins. In the more than 20 genes associated to these conditions, ryanodine receptor type 1 gene (RYR1) is responsible for the most common forms and is associated with a wide range of clinical phenotypes and pathological findings. Magnetic resonance imaging of muscle has been used increasingly to direct genetic testing in myopathies.

No cardiomyopathy in X-linked myopathy with excessive autophagy.

In X-linked myopathy with excessive autophagy (XMEA) progressive sarcoplasmic accumulation of autolysosomes filled with undegraded debris leads to atrophy and weakness of skeletal muscles. XMEA is caused by compromised acidification of lysosomes resulting from hypofunction of the proton pump vacuolar ATPase (V-ATPase), due to hypomorphic mutations in VMA21, whose protein product assembles V-ATPase. To what extent the cardiac muscle is affected is unknown.

Loss-of-function mutations in MICU1 cause a brain and muscle disorder linked to primary alterations in mitochondrial calcium signaling.

Mitochondrial Ca(2+) uptake has key roles in cell life and death. Physiological Ca(2+) signaling regulates aerobic metabolism, whereas pathological Ca(2+) overload triggers cell death. Mitochondrial Ca(2+) uptake is mediated by the Ca(2+) uniporter complex in the inner mitochondrial membrane, which comprises MCU, a Ca(2+)-selective ion channel, and its regulator, MICU1.

Malignant tumors of digestive organs and liver metastases at the time of diagnosis.

Aim: Malignant tumors localized in the digestive tract have a tendency to local growth and invasion with lymph node metastasis. Distant metastases through blood with prevalent liver location are detected late in disease progression, in an advanced stage, when therapeutic possibilities are often limited to palliative therapy.

Material And Methods: The study included a series of 139 patients with liver metastases admitted to the Center of Gastroenterology and Hepatology lasi between January 1 and October 10, 2011 for the identification of primitive tumor.

RyR1 deficiency in congenital myopathies disrupts excitation-contraction coupling.

In skeletal muscle, excitation-contraction (EC) coupling is the process whereby the voltage-gated dihydropyridine receptor (DHPR) located on the transverse tubules activates calcium release from the sarcoplasmic reticulum by activating ryanodine receptor (RyR1) Ca(2+) channels located on the terminal cisternae. This subcellular membrane specialization is necessary for proper intracellular signaling and any alterations in its architecture may lead to neuromuscular disorders. In this study, we present evidence that patients with recessive RYR1-related congenital myopathies due to primary RyR1 deficiency also exhibit downregulation of the alfa 1 subunit of the DHPR and show disruption of the spatial organization of the EC coupling machinery.

VMA21 deficiency prevents vacuolar ATPase assembly and causes autophagic vacuolar myopathy.

X-linked Myopathy with Excessive Autophagy (XMEA) is a childhood onset disease characterized by progressive vacuolation and atrophy of skeletal muscle. We show that XMEA is caused by hypomorphic alleles of the VMA21 gene, that VMA21 is the diverged human ortholog of the yeast Vma21p protein, and that like Vma21p, VMA21 is an essential assembly chaperone of the vacuolar ATPase (V-ATPase), the principal mammalian proton pump complex. Decreased VMA21 raises lysosomal pH which reduces lysosomal degradative ability and blocks autophagy.

Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies.

Ryanodine receptor 1 (RYR1) mutations are a common cause of congenital myopathies associated with both dominant and recessive inheritance. Histopathological findings frequently feature central cores or multi-minicores, more rarely, type 1 predominance/uniformity, fiber-type disproportion, increased internal nucleation, and fatty and connective tissue. We describe 71 families, 35 associated with dominant RYR1 mutations and 36 with recessive inheritance.

VMA21 deficiency causes an autophagic myopathy by compromising V-ATPase activity and lysosomal acidification.

X-linked myopathy with excessive autophagy (XMEA) is a childhood-onset disease characterized by progressive vacuolation and atrophy of skeletal muscle. We show that XMEA is caused by hypomorphic alleles of the VMA21 gene, that VMA21 is the diverged human ortholog of the yeast Vma21p protein, and that like Vma21p it is an essential assembly chaperone of the V-ATPase, the principal mammalian proton pump complex. Decreased VMA21 raises lysosomal pH, which reduces lysosomal degradative ability and blocks autophagy.

[Postoperative digestive fistulas. Etiopathogenic considerations].

The digestive fistula is one of the most serious complications that might appear following different types of resectional digestive surgery. This condition still carries a considerable morbidity and mortality rate and therefore all surgical and ICU staff pay a great deal of attention and intensify their care to avoid the fatalities. The postoperative digestive fistulas, through their physiopathological and clinical complexity induce the disturbance of the biological equilibrium with vital consequences.

[Surgical therapeutic strategy in vital risk polytrauma with multiple organ injuries, case report].

The medical interest for trauma pathology is incresing, due to the gravity of the given injuries. The surgical therapeutic strategy used is directly related to the localization and to the type of the trauma. The supplementary lesions and their vital risk also matter.

[Intraoperative injuries of the biliary tract].

Statistically speaking, the intraoperative lesions of common bile duct are rare clinical cases, but they have a high gravity potential. Our study was made on a lot of 11 operated pacients during 1995-2007 in our Clinic and it shows the tactical and technical approach used in solving these complications. The study also shows the high level of difficulty of these cases, as immediate recognition of this type of intraoperative lesions is needed.

[General principles of clinical and therapeutic management in postoperative external enteral fistulas].

Postoperative enterocutaneous fistulas represent a frequent complication in the emergency or cancerous digestive surgery. As to the high level of mortality and morbidity caused by this type of postoperative complication (4%), efforts are made to establish the principles of therapeutic management, on the purpose of decreasing these indicators and thus lowering the prolonged hospitalisation afferent costs.

[Internal hernia--a rare cause of intestinal obstruction].

Internal hernia is rare its frequency ranging between 0.6 and 5.8%.

A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome.

Rett syndrome is caused by mutations in the gene MECP2 in approximately 80% of affected individuals. We describe a previously unknown MeCP2 isoform. Mutations unique to this isoform and the absence, until now, of identified mutations specific to the previously recognized protein indicate an important role for the newly discovered molecule in the pathogenesis of Rett syndrome.

Mutations in NHLRC1 cause progressive myoclonus epilepsy.

Lafora progressive myoclonus epilepsy is characterized by pathognomonic endoplasmic reticulum (ER)-associated polyglucosan accumulations. We previously discovered that mutations in EPM2A cause Lafora disease. Here, we identify a second gene associated with this disease, NHLRC1 (also called EPM2B), which encodes malin, a putative E3 ubiquitin ligase with a RING finger domain and six NHL motifs.