Resistance to activated protein C caused by a factor V gene mutation.

Each year, approximately one in 1000 individuals suffers from venous thromboembolism. The pathogenesis of the disease is multifactorial and a thrombotic event is the result of a combination of genetic and circumstantial risk factors. Until recently, genetic defects could only be identified in a minority of thrombosis patients.

Evaluation of the relationship between protein S and C4b-binding protein isoforms in hereditary protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of the same genetic disease.

Type III protein S deficiency is characterized by a low plasma level of free protein S, whereas the total concentration of protein S is normal. In contrast, both free and total protein S levels are low in type I deficiency. To elucidate the molecular mechanism behind the selective deficiency of free protein S in type III deficiency, the relationship between the plasma concentrations of beta-chain containing isoforms of C4b-binding protein (C4BP beta+) and different forms of protein S (free, bound, and total) was evaluated in 327 members of 18 protein S-deficient families.

Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S.

Inherited resistance to activated protein C (APC), which is caused by a single point mutation in the gene for factor V, is a common risk factor for thrombosis. In this study, the prevalence of APC resistance in 18 unrelated thrombosis-prone families with inherited protein S deficiency was investigated to determine its role as additional genetic risk factor for thrombosis. In addition, a detailed evaluation of the clinical manifestations in these families was performed.

Homozygous APC-resistance combined with inherited type I protein S deficiency in a young boy with severe thrombotic disease.

Inherited resistance to activated protein C (APC) is a frequent cause of familial thrombosis. It is associated with a factor V gene point mutation replacing arginine506 in the APC-cleavage site with a glutamine. Thrombotic events are rare during childhood even in patients with homozygous APC-resistance.

Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C.

Resistance to activated protein C (APC) is the most prevalent inherited cause of venous thrombosis. The APC resistance phenotype is associated with a single point mutation in the factor V gene, changing Arg506 in the APC cleavage site to a Gln. We have investigated 50 Swedish families with inherited APC resistance for this mutation and found it to be present in 47 of them.

Differential regulation of alpha and beta chains of C4b-binding protein during acute-phase response resulting in stable plasma levels of free anticoagulant protein S.

Regulation of C4b-binding protein (C4BP) isoforms during acute phase and its relationship to the plasma concentration of free protein S was elucidated. An assay for beta chain containing C4BP (C4BP beta+) was developed and the concentrations of total C4BP, C4BP beta+, total, free, and bound protein S were measured in patients with acute-phase response. Even though total C4BP was increased to 162% (mean value) of controls, the corresponding value of C4BP beta+ was only 122%.

Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis.

Resistance to activated protein C (APC) is a major cause of familial thrombophilia, and can be corrected by an anticoagulant activity expressed by purified factor V. We investigated linkage between APC resistance and the factor V gene in a large kindred with familial thrombophilia. Restriction fragment length polymorphisms in exon 13 of the factor V gene were informative in 14 family members.

Interferon induction of chicken MHC class I gene expression: phylogenetic conservation of the interferon-responsive element.

The 5' upstream region of a chicken MHC class I gene BF-IV contains sequence motifs similar to the interferon consensus sequences (ICS) contained in promoters of many mammalian interferon-regulated genes. To study a possible functional role of this putative chicken ICS, an oligonucleotide spanning the upstream sequences of the BF-IV gene (-174/-194) was cloned singly or in multiple copies before the herpes TK promoter controlling the chloramphenicol acetyl transferase (CAT) gene (pBLCAT2). Transient expression studies performed with primary chicken fibroblasts (CEF) showed that the chicken ICS represses constitutive promoter activity.

[The use of different conscious sedation procedures in ambulatory dental surgery].

Conditions and selections of patients undergoing oral surgery under intravenous conscious sedation are reviewed. The practicability of several medicaments and combinations are discussed. Intravenous conscious sedation in combination with local anesthesia is an alternative during unpleasant surgical and dental procedures, and in several cases, can replace general anesthesia.

[Comparison of two methods for conscious sedation in maxillofacial surgery with local anesthesia].

A randomised, prospective study was conducted to compare the efficiency and safety of methods for intravenous conscious sedation in patients undergoing oral surgery under local analgesia. 150 systemically healthy patients (ASA Class I and II) participated. Three groups were formed: group 1 received 0.

Increased turnover of vaccinia virus-specific immediate early RNAs in interferon-treated chick embryo fibroblasts.

The synthesis and steady state level of immediate early vaccinia virus-specific RNAs in interferon-treated chick embryo fibroblasts were determined by blot hybridization analysis using the cloned restriction endonuclease fragment pEJ 18 containing the gene of vaccinia virus WR-specific DNA polymerase as a probe. Even though early vaccinia virus WR RNA was still synthesized, accumulation of immediate early viral RNAs was strongly inhibited. Accumulation of beta-actin RNA was not affected.

Reduced steady-state levels of vaccinia virus-specific early mRNAs in interferon-treated chick embryo fibroblasts.

The molecular mechanism of interferon action on vaccinia virus-specific immediate early protein synthesis was studied in interferon-treated chick cells. In line with previous observations, the synthesis of total vaccinia WR virus-specific mRNA, thymidine kinase (TK) mRNA, and several other early mRNAs was detectable by short [3H]uridine pulses. Under conditions of over 90% inhibition of poxvirus-specific TK induction, accumulation of TK mRNA was strongly inhibited.

[Demonstration of increased influenza-A-antibody levels in the serum of patients with chronic polyarthritis].

Patients with rheumatoid arthritis show increased levels of anti-influenza-A antibodies in their sera compared to healthy controls and patients with other inflammatory rheumatic diseases (systemic lupus erythematosus, ankylosing spondylitis and psoriatic arthritis). These antibody levels are dependent on the activity of rheumatoid arthritis.

Synthesis of early vaccinia-virus-specific enzymes under conditions of immediate early gene expression.

Cycloheximide reversal experiments in chick embryo fibroblasts and mouse L-929 cells indicate that the poxvirus-induced enzymes DNA polymerase and 'alkaline' DNase are immediate early gene products of the virus. In contrast to the vaccinia-WR-coded enzyme under conditions of immediate early gene expression the cowpox-virus-induced DNA polymerase is made only in very small amounts. The studies are consistent with the notion that all poxvirus-specific early proteins may be immediate early viral gene products.

[Interaction of isoxicam and digoxin].

The influence of maintenance therapy with Isoxicam, 200 mg daily, on digoxin steady-state plasma levels was studied on 12 healthy volunteers. One person dropped out from the investigation program on account of cardiac sensations following the invasion phase with digoxin. No statistically significant differences could be shown during concomitant therapy or after withdrawal of Isoxicam.

[Indomethacin kinetics in synovia and plasma following administration of indomethacin Gits 7/85 in patients with chronic polyarthritis].

Patients suffering from rheumatoid arthritis received a single dose of the new therapeutic system of indomethacin (Gits 7/85). Samples of plasma and synovial fluid were taken after 1, 2, 4, 6, 8, 10, 12, and 24 h. Concentration peaks could not be observed.

An interaction study between benoxaprofen and digoxin.

The influence of maintenance therapy with benoxaprofen, 600 mg daily, on digoxin steady-state plasma levels was studied in 12 patients with rheumatic disease. No difference could be shown during concomitant therapy or after withdrawal of benoxaprofen (p greater than 0.10 and p greater than 0.

[Spread of hepatitis B virus infection among family contacts of asymptomatic HBsAg carriers (author's transl)].

Family members of 34 asymptomatic HBsAg carriers were tested for different hepatitis B virus (HBV) markers. Among 67 family members tested 24 (36%) presented signs of a past or ongoing HBV-infection. Spread of HBV-infection was particularly high in those families in which the HBsAg carrier was positive for HBeAg and Dane particle-associated DNA polymerase activity.

Two survivors of severe paraquat intoxication by "continuous hemoperfusion".

"Continuous hemoperfusion" (8 h/day for 2--3 weeks) was performed in two patients suffering from severe paraquat intoxication. On account of paraquat plasma concentrations a fatal outcome due to pulmonary fibrosis would have been expected in both cases. However, both patients survived following "continuous hemoperfusion" therapy.

Hepatitis B virus markers among family contacts of asymptomatic HBsAg carriers.

A study was undertaken to establish the risk of family contacts of HBsAg carriers acquiring a hepatitis B virus (HBV) infection. About one-third of all household contacts of asymptomatic HBsAg carriers had signs of past or ongoing HBV infection. Family contacts of HBsAg carriers with high numbers of circulating Dane particles were shown to have a higher risk of developing HBV infection than family contacts of HBsAg carriers without serological evidence of HBV synthesis.