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B Zöller

Publications and source records attributed to B Zöller.

At least 19 recordsLinked to original sources
PubMed1995

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. Venous thrombotic events had occurred in 47% of the protein S-deficient patients (64/136) and in 7% of relatives without protein S deficiency (14/191). As estimated from Kaplan-Meier analysis, 50% of protein S-deficient family members and 12% of those without protein S deficiency had had manifestation of venous thromboembolism at the age of 45 years. The age at the first thrombotic event ranged from 10 to 81 years (mean, 32.5 years) and a large intrafamilial and interfamilial variability in expression of thrombotic symptoms was seen. The factor V gene mutation related to APC resistance was present in 6 (38%) of 16 probands available for testing; in total, the mutation was found in 7 (39%) of the 18 families. In family members with combined defects, 72% (13/18) had had thrombosis as compared with 19% (4/21) of those with only protein S deficiency and 19% (4/21) of those with only the factor V mutation. In conclusion, APC resistance was found to be highly prevalent in thrombosis-prone families with protein S deficiency and was an additional genetic risk factor for thrombosis in these families. The results suggest thrombosis-prone families with protein S deficiency often to be affected by yet another genetic defect.

Adolescent↗
PubMed1995

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. In normal relatives (n = 190), protein S correlated well with C4BP beta+, with free protein S (96 +/- 23 nmol/L) being equal to the molar excess of protein S (355 +/- 65 nmol/L) over C4BP beta+ (275 +/- 47 nmol/L). In protein S-deficient family members (n = 117), the equimolar relationship between protein S (215 +/- 50 nmol/L) and C4BP beta+ (228 +/- 51 nmol/L), together with the high affinity of the interaction, resulted in low levels of free protein S (16 +/- 10 nmol/L). Free protein S levels were distinctly low in protein S-deficient members, whereas in 47 of the protein S-deficient individuals, the concentration of total protein S was within the normal range, which fulfils the criteria for type III deficiency. The remaining 70 had low levels of both total and free protein S and, accordingly, would be type I deficient. Coexistence of type I and type III deficiency was found in 14 families, suggesting the two types of protein S deficiency to be phenotypic variants of the same genetic disease. Interestingly, not only protein S but also C4BP beta+ levels were decreased in orally anticoagulated controls and even more so in anticoagulated protein S-deficient members, suggesting that the concentration of C4BP beta+ is influenced by that of protein S. In conclusion, our results indicate that type I and type III deficiencies are phenotypic variants of the same genetic disease and that the low plasma concentrations of free protein S in both types are the result of an equimolar relationship between protein S and C4BP beta+.

Adolescent↗
PubMed1995

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. We now wish to report on a case of severe venous thrombosis, in a 10-year-old boy. He was found to have pronounced APC-resistance due to homozygous factor V gene mutation in combination with inherited type I protein S deficiency. The two traits were independently inherited in the family. The APC-resistance was partially corrected by adding factor V, whereas added protein S was without effect. This is the first reported case of homozygous APC-resistance combined with another inherited prothrombotic disorder. It illustrates how multiple genetic defects may provoke thrombosis at young age and emphasizes the need of complete evaluation of thrombotic patients in order to determine whether multiple risk factors exist.

Adult↗
PubMed1994

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%. In the acute-phase group, total protein S was increased to the same extent as C4BP beta+ (mean value of 124%), whereas free protein S was not decreased. In controls, total and bound protein S correlated with total C4BP and C4BP beta+. However, in the acute-phase group, the correlation between bound protein S and total C4BP was lost, although the correlation between C4BP beta+ and protein S remained. The present results suggest stable levels of free protein S during acute phase to be the result of differential regulation of C4BP alpha- and beta-chain expression, and the concentration of free protein S to be the resulting molar excess of protein S over C4BP beta+. This mechanism ensures functional levels of free anticoagulant protein S despite high levels of C4BP.

Acute-Phase Proteins↗
PubMed1994

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. The 100% linkage between factor V gene polymorphism and APC resistance strongly suggested a factor V gene mutation as a cause of APC resistance. A point mutation changing Arg506 in the APC cleavage site to a Gln was found in APC resistant individuals. These results suggest factor V gene mutation to be the most common genetic cause of thrombophilia.

Alleles↗
PubMed1994

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. Perfect cosegregation between a low APC ratio and the presence of mutation was seen in 40 families. In seven families, the co-segregation was not perfect as 12 out of 57 APC-resistant family members were found to lack the mutation. Moreover, in three families with APC resistance, the factor V gene mutation was not found, suggesting another still unidentified cause of inherited APC resistance. Of 308 investigated families members, 146 were normal, 144 heterozygotes, and 18 homozygotes for the factor V gene mutation and there were significant differences in thrombosis-free survival curves between these groups. By age 33 yr, 8% of normals, 20% of heterozygotes, and 40% of homozygotes had had manifestation of venous thrombosis.

Arginine↗
PubMed1992

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 chicken ICS, however, enhanced CAT activity up to 20-fold following treatment with chicken interferon (IFN). Deletion analysis of the BF-IV promoter also confirms that the upstream DNA sequences (-174/-194) contain a functional ICS recognized by chicken interferon. The murine ICS of the H2-Ld gene was also activated by chicken interferon when introduced into CEF. IFN activation of chicken ICS containing reporters was also observed in transformed chicken fibroblast lines. We show that the chicken ICS binds two specific nuclear factors present in chicken fibroblasts which are induced by interferon. These factors were also capable of recognizing the mouse ICS, suggesting the conservation of a relevant DNA-binding protein. Taken together, these data indicate that the chicken ICS motif contained in a sequence from -174 to -194 of the BF-IV gene acts as a strong interferon-response element, which has been functionally conserved during about 270 million years of separate evolution of mammals and birds.

Animals↗
PubMed1992

[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 0.05 mg/kg midazolam; group 2 0.05 mg/kg midazolam, 1.5 mg/kg tramadol, 50 mg alizaprid; group 3 0.05 mg/kg midazolam, 0.2 mg/kg nalbuphine, 50 mg alizaprid. Blood pressure, heart rate and oxygen saturation were measured throughout the procedure. The results confirmed that the use of nalbuphine (group 3) allows a reduction in the mean dosage of midazolam required to produce satisfactory sedation and effected a more rapid recovery time compared to group 12 and 2. With the combination nalbuphine and alizaprid nausea and vomiting could be reduced for the most part compared to group 2.

Procedural Sedation↗
PubMed1992

[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. A sufficient monitoring as well as a good trained staff makes the methods safe and allows to reduce complications.

Ambulatory Surgical Procedures↗
PubMed1987

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. Northern blot analysis revealed strong degradation of residual TK mRNA prepared from interferon-treated chick embryo fibroblasts (CEF). Blot hybridization analysis using total vaccinia DNA and restriction fragment N as probes demonstrated a generally reduced steady-state amount of vaccinia virus-specific early mRNAs in interferon-treated CEF. When CEF were infected with a recombinant vaccinia virus strain into the TK gene of which the chloramphenicol acetyltransferase gene had been inserted, CAT activity was far lower in interferon-treated than in untreated CEF. We conclude that signals that specify rapid breakdown of viral TK mRNA in interferon-treated CEF are located in the regions flanking the coding sequences of the viral TK gene.

Acetyltransferases↗
PubMed1987

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. This indicated an enhanced degradation of vaccinia virus WR-specific early RNAs in interferon-treated chick embryo fibroblasts. This notion was supported by Northern blot analysis which revealed degradation of residual RNA of vaccinia virus WR-specific DNA polymerase. In contrast to interferon-treated mouse L 929 cells, ribosomal RNA is not degraded in interferon-treated vaccinia WR-infected chick embryo fibroblasts.

Animals↗
PubMed1984

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.

Animals↗
PubMed1982

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 0.90, respectively). Toxic concentrations were not observed. There were no changes in renal function values.

Anti-Inflammatory Agents↗
PubMed1979

[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. Non-parenteral "horizontal" transmission of HBV among spouses and brothers and sisters and probably parenteral vertical transmission of HBV from carrier mothers to their infants occurred in approximately the same frequency. Fathers transmitted HBV unfrequently to their offsprings. The results show that the risk to acquire a HBV-infection from an asymptomatic HBsAg carrier is closely linked to the serological findings in the HBe/anti-HBe-system of the index HBsAg carrier and not to the family relationship to the HBsAg carrier.

Adolescent↗