Quantification of the zymogenicity and the substrate-induced activity enhancement of complement factor D.

Complement factor D (FD) is a serine protease present predominantly in the active form in circulation. It is synthesized as a zymogen (pro-FD), but it is continuously converted to FD by circulating active MASP-3. FD is a unique, self-inhibited protease.

Proprotein Convertase Is the Highest-Level Activator of the Alternative Complement Pathway in the Blood.

Factor D (FD) is an essential element of the alternative pathway of the complement system, and it circulates predominantly in cleaved, activated form in the blood. In resting blood, mannose-binding lectin-associated serine protease 3 (MASP-3) is the exclusive activator of pro-FD. Similarly to FD, MASP-3 also circulates mainly in the active form.

Ecotin, a microbial inhibitor of serine proteases, blocks multiple complement dependent and independent microbicidal activities of human serum.

Ecotin is a serine protease inhibitor produced by hundreds of microbial species, including pathogens. Here we show, that ecotin orthologs from Escherichia coli, Yersinia pestis, Pseudomonas aeruginosa and Leishmania major are potent inhibitors of MASP-1 and MASP-2, the two key activator proteases of the complement lectin pathway. Factor D is the key activator protease of another complement activation route, the alternative pathway.

Genetic investigation confirmed the clinical phenotype of congenital chloride diarrhea in a Hungarian patient: a case report.

Background: Congenital chloride diarrhea (CCD, OMIM 214700) is a rare autosomal recessively inherited condition characterized by watery diarrhea, hypochloremia and metabolic alkalosis. Mutations of the solute carrier family 26, member 3 (SLC26A3, OMIM 126650) gene are responsible for the disease. The gene encodes a transmembrane protein, which is essential for intestinal chloride absorption.

Cutting Edge: A New Player in the Alternative Complement Pathway, MASP-1 Is Essential for LPS-Induced, but Not for Zymosan-Induced, Alternative Pathway Activation.

The complement system is a sophisticated network of proteases. In this article, we describe an unexpected link between two linear activation routes of the complement system: the lectin pathway (LP) and the alternative pathway (AP). Mannose-lectin binding-associated serine protease (MASP)-1 is known to be the initiator protease of the LP.

Extensive Basal Level Activation of Complement Mannose-Binding Lectin-Associated Serine Protease-3: Kinetic Modeling of Lectin Pathway Activation Provides Possible Mechanism.

Serine proteases (SPs) are typically synthesized as precursors, termed proenzymes or zymogens, and the fully active form is produced limited proteolysis by another protease or by autoactivation. The lectin pathway of the complement system is initiated by mannose-binding lectin (MBL)-associated SPs (MASP)-1, and MASP-2, which are known to be present as proenzymes in blood. The third SP of the lectin pathway, MASP-3, was recently shown to be the major activator, and the exclusive "resting blood" activator of profactor D, producing factor D, the initiator protease of the alternative pathway.

MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are fundamentally linked.

MASP-3 was discovered 15 years ago as the third mannan-binding lectin (MBL)-associated serine protease of the complement lectin pathway. Lacking any verified substrate its role remained ambiguous. MASP-3 was shown to compete with a key lectin pathway enzyme MASP-2 for MBL binding, and was therefore considered to be a negative complement regulator.

MASP-1 and MASP-2 Do Not Activate Pro-Factor D in Resting Human Blood, whereas MASP-3 Is a Potential Activator: Kinetic Analysis Involving Specific MASP-1 and MASP-2 Inhibitors.

It had been thought that complement factor D (FD) is activated at the site of synthesis, and only FD lacking a propeptide is present in blood. The serum of mannose-binding lectin-associated serine protease (MASP)-1/3(-/-) mice contains pro-FD and has markedly reduced alternative pathway activity. It was suggested that MASP-1 and MASP-3 directly activate pro-FD; however, other experiments contradicted this view.

Hormonal and biochemical parameters correlated with bone densitometric markers in prepubertal Hungarian children.

Background: The conditions that define bone development in prepuberty profoundly influence bone health later in life. We aimed to reveal important determinants of bone mass in Tanner stage I.

Methods: We studied 84 healthy children (43 girls and 41 boys) aged 7 to 11 years.

Association of lean and fat body mass, bone biomarkers and gonadal steroids with bone mass during pre- and midpuberty.

Background/aims: The association of bone mass with body composition, bone turnover markers and gonadal steroids was examined in Hungarian children during pre- and midpuberty.

Methods: Two hundred and thirty-seven 7- to 16-year-old subjects (56% girls) were investigated. Bone mineral density (BMD), fat mass and total and appendicular lean mass were estimated with dual-energy X-ray absorptiometry (Lunar Prodigy).

Randomized trial: immunogenicity and safety of coadministered human papillomavirus-16/18 AS04-adjuvanted vaccine and combined hepatitis A and B vaccine in girls.

Purpose: This randomized, open, controlled, multicenter study (110886/NCT00578227) evaluated human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (HPV-16/18 vaccine) coadministered with inactivated hepatitis A and B (HAB) vaccine. Coprimary objectives were to demonstrate noninferiority of hepatitis A, hepatitis B, and HPV-16/18 immune responses at month 7 when vaccines were coadministered, compared with the same vaccines administered alone.

Methods: Healthy girls (9-15 years) were age-stratified (9, 10-12, and 13-15 years) and randomized to receive HPV (n = 270), HAB (n = 271), or HPV + HAB (n = 272).

[Investigation of adolescents' bone metabolism in the western part of Transdanubia].

Unlabelled: Childhood reference range based on the age is not available in Hungary, therefore the diagnosis and therapy of bone metabolic diseases of childhood are subject to difficulties. The aim of this work is to provide information about the adolescents' results of bone mineral density and bone biomarkers.

Subjects And Methods: Measurements were performed in 169 healthy adolescents (98 girls, 71 boys, age: 17.

Tick-born encephalitis (TBE) vaccination in children: advantage of the rapid immunization schedule (i.e., days 0, 7, 21).

Tick-borne encephalitis (TBE) is an important, vaccine-preventable arthropod-borne disease, causing severe illness in children too. In order to evaluate the immune response to different licensed primary immunization schedules, a total of 294 children aged 1 to 11 years of age were enrolled in a randomized, controlled, multi-center trial. The subjects were vaccinated with the pediatric formulation of a TBE vaccine (Encepur children) according to the conventional schedule (Group C; N = 73, vaccination on days 0, 28 and 300), the modified conventional schedule (Group M; N = 139, vaccination on days 0, 21 and 300), or the rapid schedule (Group R; N = 82, vaccination on Days 0, 7 and 21).

Severe Shwachman-Diamond syndrome phenotype caused by compound heterozygous missense mutations in the SBDS gene.

Objective: A 5-month-old male infant presenting with recurrent respiratory tract infections, chronic diarrhea, and failure to thrive was found to be pancytopenic. Bone marrow and x-ray examinations were consistent with Shwachman-Diamond syndrome (SDS). Genomic DNA sequencing, restriction fragment analysis, and studies of the mutant proteins were performed to gain further knowledge on the molecular pathology of SDS.

[Chronic recurrent multifocal osteomyelitis].

The chronic recurrent multifocal osteomyelitis has been reported very rarely in the literature. However, its significance must be emphasized, because it is a spontaneously healing, benign disease, as compared to the classical forms of osteomyelitis. It leaves behind almost no residual symptoms, and many operations, long antimicrobial therapy may be avoided by diagnosing it.

Complications of frontal sinusitis and their management.

Because of the anatomic location and venous drainage pattern of the frontal sinus, complications commonly involve intracranial structures but can involve the orbit and adjacent bony and soft tissue structures also. Evaluation of patients by a thorough history and physical examination, culture of purulent discharge or infected bone, and axial and coronal CT scanning with contrast is important for diagnosis and treatment planning. Treatment of complications uniformly involves the use of intravenous antibiotics and appropriate drainage procedures to arrest the infection and allow for resolution of the inflammatory complication.

[Vertical transmission causing hepatitis C in a newborn infant].

There is a case report of an intrauterine growth retarded infant who was suffering of sepsis caused by Klebsiella pneumoniae. An exchange transfusion was carried out because of hyperbilirubinaemia on the 5th day of life. 10 days later high bilirubin concentration was observed again parallel to the liver enzyme abnormalities.

D-penicillamine inhibits the action of reactive oxygen species in the pig pulmonary circulation.

Oxygen radicals produced by the hypoxanthine-xanthine oxidase (Hyp-XO) system potently constrict the pulmonary circulation of pigs. D-penicillamine (DPA) is thought to be a free radical scavenger. In the present work we have studied if DPA may influence the vasoactive action of Hyp-XO in pig lungs.

[D-penicillamine: old drug, new indication? D-penicillamine reduced pulmonary hypertension induced by free radicals].

Pulmonary hypertension is one of the major problems in the neonatal period. Free oxygen radicals play important role in the activation of pulmonary vasoconstriction. Since D-penicillamine has proved to be a strong antioxidant in newborns it was of interest to investigate the effect of the drug in the oxygen radical induced pulmonary hypertension.

[Hemorrhagic shock and encephalopathy].

Levin et al. described a new syndrome called haemorrhagic shock and encephalopathy in 1983. The authors present a case report and give an overview about the disease.

Ultrastructural investigations in late infantile type of ceroid lipofuscinosis (Jansky-Bielschowsky).

Ultrastructural findings of biopsy materials of four gipsy first cousin infants suffering from late infantile type of ceroid lipofuscinosis (Jansky-Bielschowsky) were investigated. The diagnostic significance of the conjunctival biopsy is emphasized. The pericytes and the vascular smooth muscle cells of the arterioles proved to be the main inclusion storing cells.