ABSTRACT
Tick-borne encephalitis (TBE) is recognized as the most important viral tick-borne zoonosis in 27 countries in Europe. In this study, ticks were collected in Germany from two non-risk areas in the states of Saxony-Anhalt and Mecklenburg-Western Pomerania, where several single human TBE cases have occurred in recent years. Ticks were also collected from a region in Thuringia, known to be a former risk area for TBE virus (TBEV), where numerous human cases were reported between 1960 and 1975. Detection of TBEV RNA was conducted by real-time RT-PCR. No TBEV was detected in any field-collected ticks. However, ticks were also collected from volunteers living in Bavaria. Three of 239 ticks from this collection were positive for TBEV genome and two genetically distinct TBEV strains were detected and characterized.
Subject(s)
Encephalitis Viruses, Tick-Borne/genetics , Encephalitis Viruses, Tick-Borne/isolation & purification , Ixodes/virology , RNA, Viral/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Child , Child, Preschool , Female , Germany , Human Experimentation , Humans , Male , Middle Aged , Molecular Sequence Data , Prevalence , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Young AdultABSTRACT
BACKGROUND: Multiple-endocrine-neoplasia-type-1 (MEN1) is an autosomal-dominant inherited disorder characterized by the combined occurrence of primary hyperparathyroidism (pHPT), gastroenteropancreatic neuroendocrine tumors (GEP), adenomas of the pituitary gland (APA), adrenal cortical tumors (ADR) and other tumors. As the tumors appear in an unpredictable schedule, uncertainty about screening programs is persisting. OBJECTIVE: To optimize screening and to analyze possible differences in sporadic versus familial cases. METHODS: We analyzed data of 419 individuals including 306 MEN-1 patients (138 isolated and168 familial cases out of 102 unrelated families). RESULTS: A total of 683 tumors occurred consisting of 273 pHPT, 138 APA, 166 GEP, 57 ADR, 24 thymic- and bronchial-carcinoids as well as 25 neoplasms of other tissues. The age-related penetrance was determined as 10%, 35%, 67%, 81% and 100% at 20, 30, 40, 50 and 65 years respectively. Although pHPT being the most frequent first manifestation (41%), also GEP (22%) or APA (21%) were found to be the first presentation. APA occurred significantly more frequent (p<0,05) in isolated (n=138) than in familial (n=168) cases, whereas GEP showed a tendency to occur more often in familial cases. Genotype/phenotype correlation in 140 clinically affected MEN-1 cases showed a tendency for truncating mutations, especially nonsense mutations to be associated to GEP and carcinoids of the lungs and thymus. CONCLUSION: In view of the morbidity and frequency in familial cases an effective screening programme should aim at an early diagnosis of GEP particularly when truncating, especially nonsense mutations are found.
Subject(s)
Mass Screening/methods , Multiple Endocrine Neoplasia Type 1/epidemiology , Adolescent , Adult , Age of Onset , Aged , Aged, 80 and over , Child , DNA/blood , DNA/genetics , Female , Genotype , Germany/epidemiology , Humans , Male , Middle Aged , Multiple Endocrine Neoplasia Type 1/genetics , Nuclear Family , Phenotype , Polymerase Chain ReactionABSTRACT
Annexin V belongs to a class of Ca2+-binding proteins for which different functions in the cell are discussed, e.g., involvement in exocytosis, inhibition of protein kinase C, and calcium channel activity in cartilage matrix vesicles. All these functions are related to the ability of the annexins to bind to acidic phospholipids. In this study, the interaction of annexin V with large unilamellar vesicles (LUV) prepared from phosphatidylserine (PS) at low pH was compared to that at neutral pH. Annexin V strongly binds to PS LUV at low pH, whereas at neutral pH 20-100 microM Ca2+ are required to induce binding. This is caused by the different electric charge of the protein. The binding ability of the PS LUV for annexin V is higher at low pH. Binding of annexin V induces dehydration of the vesicle surface and a decrease of the lateral diffusion within the bilayer. While this dehydration is due to vesicle contact at pH 4, at pH 7.4 it is due to surface covering by annexin V. Annexin V promotes the phospholipid intermixing between LUVs at pH 5 and below but inhibits it at pH 7.4. A substitution of up to 80% of the PS by the uncharged phosphatidylcholine does not impair the extent of phospholipid intermixing at pH 4. The high binding capacity of PS LUV, the disappearance of the inhibiting action, and a calculated increase of the annexin V hydrophobicity make it likely that annexin V is able to penetrate into the membrane at low pH. At neutral pH, annexin V molecules act as steric barriers, preventing close apposition of two vesicles. At pH 5, annexin V lowers the threshold concentration of the Ca2+-induced phospholipid intermixing. Such a promotion is well-known for annexin VII (synexin). The effect may be related to the isoelectric points of the two annexins which have been reported as 4.8 (annexin V) and 7.0 (annexin VII), respectively.
