Biomedicine. Congress investigates fetal tissue sales.
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Biomedical subjects
Publications and source records attributed to G Vogel.
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The A allele of a G/A dimorphism at position nt20210 in the 3'-untranslated region of the prothrombin gene has been recently identified as a common risk factor for venous thrombosis. It is detected mostly by PCR amplification using a mutagenic primer and subsequent restriction analysis. We have applied two alternative methods--DGGE and SSCP-to analyse the nt20210 dimorphism in a series of 383 consecutive patients with deep venous thrombosis and in 144 controls. Both screening methods resulted in the unambiguous identification of carriers of the nt20210 A allele not only in heterozygotes but in two cases as well in homozygous state. The frequency of the A allele was 0.7% in the control group but 3.7% in the patient group, demonstrating a substantial increase in risk for venous thrombosis in carriers of the 20210 A allele. Both methods have the potential to detect other DNA sequence variations in the vicinity of the 20210 G/A dimorphism. This was demonstrated by the identification of a new mutation T20122G in the 3'-untranslated region of the prothrombin gene in a single patient.
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Influenza viruses type A and B can cause a wide spectrum of illness, and they are responsible for considerable mortality and morbidity. With the new neuraminidase inhibitors, of which zanamivir was the first drug to be licensed, the physician has antivirals at his disposal which are safe and effective against both influenza virus type A and type B. Available data from clinical Phase III studies indicate benefits in terms of a reduction in the median time to alleviation of major symptoms by 1.5 to 3 days when treatment is started within 36 to 48 h after onset of influenza. Similar results have been obtained with oseltamivir. Neuraminidase inhibitors provide a valuable treatment option, particularly for individuals not protected by vaccination, and those at high risk of influenza-related complications. The study results obtained so far indicate that patients with pre-existing diseases and those with severe influenza symptoms profit most from the treatment. This is confimed by our own experience in treating severe influenza conditions.
Cytomegalovirus (CMV) remains a major cause of morbidity in solid organ transplant patients. In order to reduce CMV morbidity, we designed a program of routine virological monitoring that included throat and urine CMV shell vial culture, along with peripheral blood leukocyte (PBL) shell vial quantitative culture for 12 weeks post-transplantation, as well as 8 weeks after treatment for acute rejection. The program also included preemptive ganciclovir treatment for those patients with the highest risk of developing CMV disease, i.e., with either high-level viremia (>10 infectious units [IU]/106 PBL) or low-level viremia (<10 IU/106 PBL) and either D+/R- CMV serostatus or treatment for graft rejection. During 1995-96, 90 solid organ transplant recipients (39 kidneys, 28 livers, and 23 hearts) were followed up. A total of 60 CMV infection episodes occurred in 45 patients. Seventeen episodes were symptomatic. Of 26 episodes managed according to the program, only 4 presented with CMV disease and none died. No patient treated preemptively for asymptomatic infection developed disease. In contrast, among 21 episodes managed in non-compliance with the program (i.e., the monitoring was not performed or preemptive treatment was not initiated despite a high risk of developing CMV disease), 12 episodes turned into symptomatic infection (P=0.0048 compared to patients treated preemptively), and 2 deaths possibly related to CMV were recorded. This difference could not be explained by an increased proportion of D+/R- patients or an increased incidence of rejection among patients with episodes treated in non-compliance with the program. Our data identify compliance with guidelines as an important factor in effectively reducing CMV morbidity through preemptive treatment, and suggest that the complexity of the preemptive approach may represent an important obstacle to the successful prevention of CMV morbidity by this approach in the regular healthcare setting.
The authors compared bone resorption of autogenous bone grafts and revascularized free flaps used for the reconstruction of mandibular continuity defects following resection for tumors, before and after the placement of endosseous implants. Ten patients (group 1) were treated with autogenous bone grafts taken from the fibula or the anterior iliac crest; 8 patients (group 2) were treated with iliac or fibula revascularized flaps. Four to 8 months later, 72 endosseous implants were placed in the reconstructed areas. After a further healing period of 4-6 months, patients were rehabilitated with implant-borne prostheses. The following parameters were evaluated and compared between the two groups: 1) bone resorption of grafts and free flaps before and after implant placement; 2) peri-implant bone resorption mesial and distal to each implant, immediately after prosthetic rehabilitation and then during yearly follow-ups. Bone resorption before implant placement showed mean values of 3.53 mm in group 1, and 0.96 mm in group 2. Peri-implant bone resorption was: 0.49 mm (39 implants) in group 1, and 0.45 mm (30 implants) in group 2, at time of prosthetic rehabilitation; 0.78 mm (39 implants) in group 1, and 0.89 mm (30 implants) in group 2, 12 months after prosthetic load; 1.16 mm (24 implants) in group 1, and 1.02 mm (13 implants) in group 2, 24 months after the prosthetic load. A significant difference in bone resorption before implant placement was found between the two groups, whereas it was not found after implant placement and prosthetic load. The failure rate according to Albrektsson criteria was 4.9% (2/41 implants) in group 1, and was 3.2% (1/31) in group 2.
The intracellular amounts of diphospho-myo-inositol phosphates and InsP6 were determined in Dictyostelium discoideum AX2 throughout the life cycle, including exponential growth, starvation, differentiation, sporulation and spore germination. Similar experiments were performed with the closely related species Polysphondylium pallidum under conditions resulting in microcyst formation. A distinct accumulation of these compounds is observed during the early starvation phase of the cell population before the onset of the actual differentiation program. When exponentially growing D. discoideum cells were shifted to starvation conditions, a 25-fold accumulation of 5,6-bis-PP-InsP4 within 3 h was observed. In P. pallidum, the 5,6-bis-PP-InsP4 pool rises around 20-fold within 8 h during the formation of microcysts from vegetative cells. Finally, the diphosphoinositol phosphates are deposited in spores or microcysts and are degraded when spores or microcysts germinate at low cell density.
Inherited factor VII (FVII) deficiency is a rare autosomal recessive disorder. Mutations and polymorphisms of the FVII gene were characterized in more than 40 unrelated patients with FVII deficiency. Among the 29 different mutations, the most frequent were Ala294 Val, Ala294Val;404delC, IVS7+7, and Val281 Phe. Four novel mutations (IVS2+1G>C, Arg247 Cys, Glu265 Lys, Asp343 His) were detected. The relationships between genotypes of mutations and polymorphisms of the FVII gene, FVII deficiency, and clinical phenotype were investigated. Homozygosity of the Phe4 Leu, IVS4+1G>A, Cys135 Arg, Ala244 Val, and Ala294 Val;404delC and the double heterozygosity of Tyr68 Cys / IVS3-1G>A, Val252 Met / IVS2+5G>T, Val281 Phe / Cys135 Arg, Ala294 Val / Val281 Phe, Ala294 Val;404delC / Val281Phe, Ala294 Val;404delC / Arg152 stop, Ala294Val;404delC / Gln(-35) stop, Ala294 Val / Val252 Met, Ala294 Val / Gly156 Asp, and Thr359 Met / Asp242 His were related to clinical symptoms. Double heterozygotes for Arg247 Cys / IVS2+1G>C, Ala206 Thr / Pro303 Arg, Leu(-20) Pro / Val252 Met as well as IVS7+7 /Ala294 Val, IVS7+7 /Ala206 Thr, and IVS7+7 / Met298 Ile were asymptomatic. The clinical symptomatology is rather poor in correlation with the FVII activity. Concerning the clinical phanotype, a correlation seems to exist between specific mutations and clinical symptoms.
Enzymes of grasses involved in fructan synthesis are of interest since they play a major role in assimilate partitioning and allocation, for instance in the leaf growth zone. Several fructosyltransferases from tall fescue (Festuca arundinacea) have previously been purified (Lüscher and Nelson, 1995). It is surprising that all of these enzyme preparations appeared to act both as sucrose (Suc):Suc 1-fructosyl transferases (1-SST) and as fructan:fructan 6(G)-fructosyl transferases. Here we report the cloning of a cDNA corresponding to the predominant protein in one of the fructosyl transferase preparations, its transient expression in tobacco protoplasts, and its functional analysis in the methylotrophic yeast, Pichia pastoris. When the cDNA was transiently expressed in tobacco protoplasts, the corresponding enzyme preparations produced 1-kestose from Suc, showing that the cDNA encodes a 1-SST. When the cDNA was expressed in P. pastoris, the recombinant protein had all the properties of known 1-SSTs, namely 1-kestose production, moderate nystose production, lack of 6-kestose production, and fructan exohydrolase activity with 1-kestose as the substrate. The physical properties were similar to those of the previously purified enzyme, except for its apparent lack of fructan:fructan 6(G)-fructosyl transferase activity. The expression pattern of the corresponding mRNA was studied in different zones of the growing leaves, and it was shown that transcript levels matched the 1-SST activity and fructan content.
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