Biomedical subjects

I Zorn

Publications and source records attributed to I Zorn.

6 recordsLinked to original sources

PubMed1992

Major growth reduction and minor decrease in mitochondrial enzyme activity in cultured human muscle cells after exposure to zidovudine.

Zidovudine-induced mitochondrial myopathy in AIDS patients reported recently might be due to inhibition of mitochondrial DNA polymerase gamma. We investigated the effect of zidovudine on proliferation, differentiation, activity of mitochondrial- and nuclear-encoded enzymes, and mitochondrial DNA (mtDNA), in cultured human muscle cells. Marked inhibition of cell proliferation was found, even in the presence of low (10 mumol/L) zidovudine concentrations. Enzyme activity of the nuclear-encoded mitochondrial citrate synthase was not affected, and the partially mitochondrial-encoded cytochrome c oxidase was not decreased, except only after exposure to high concentrations (5 mmol/L) zidovudine. No decrease of mtDNA content and no mtDNA deletions were found in zidovudine-exposed muscle cells. We propose that the effect of zidovudine on muscle, seen in zidovudine-treated AIDS patients, results mainly from decrease in proliferation of muscle cells rather than inhibition of mtDNA replication.

Acquired Immunodeficiency Syndrome↗

PubMed1992

The peripheral myelin gene PMP-22/GAS-3 is duplicated in Charcot-Marie-Tooth disease type 1A.

Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with a DNA duplication at chromosome 17p11.2. In view of the point mutation in the gene for peripheral myelin protein pmp-22/gas-3 in Trembler mice, a murine model for CMT1A, we have analysed whether this gene is altered in CMT1A. Here we show that the human homologue of the murine pmp-22 gene is located within the CMT1A DNA duplication, which is a direct repeat and does not interrupt the coding region of PMP-22. Expression of PMP-22 in CMT1A fibroblasts is similar to expression in control fibroblasts. Increased gene dosage or altered PMP-22 expression in the peripheral nervous system are therefore possible mechanisms by which PMP-22 is involved in CMT1A.

Base Sequence↗

PubMed1992

Identical point mutations of PMP-22 in Trembler-J mouse and Charcot-Marie-Tooth disease type 1A.

We have investigated the peripheral myelin protein gene, PMP-22, in a family with Charcot-Marie-Tooth disease type 1A (CMT1A). The DNA duplication commonly found in CMT1A was absent in this family, but strong linkage existed between the disease and the CMT1A marker VAW409R3 on chromosome 17p11.2. We found a point mutation in PMP-22 which was completely linked with the disease. The mutation, a proline for leucine substitution in the first putative transmembrane domain, is identical to that recently found in the Trembler-J mouse. The presence of this PMP-22 defect in this CMT1A family and the location of PMP-22 within the DNA duplication associated with CMT1A suggest that both structural alteration and overexpression of PMP-22 may lead to the disease.

Amino Acid Sequence↗

PubMed1991

The duplication in Charcot-Marie-Tooth disease type 1a spans at least 1100 kb on chromosome 17p11.2.

Recently, it has been shown that Charcot-Marie-Tooth disease type 1a (CMT1a) is linked with a duplication of a DNA segment that is detected by probe VAW409R3, and that is located on chromosome 17p11.2. Here, we show that this duplication also contains VAW412R3a, but not A10-41 and EW503. Accounting for the duplication in recombination analysis, we found recombinants between CMT1a and EW301 and EW502, but not with A10-41, VAW409R3, and VAW412R3. Using pulsed-field gel electrophoresis analysis, we estimated the minimal size of the duplicated region in CMT1a patients to be 1100 kb.

Blotting, Southern↗

PubMed1990

Usefulness of digital angiography in the assessment of left ventricular ejection fraction.

With modern digital cardiac systems the image data are digitized on-line and in real-time, allowing the replay and subsequent interpretation and analysis during or directly after the cardiac catheterization procedure. In this study we have evaluated the advantages and limitations of a manual tracing technique for left ventricular digital angiograms on the Phillips DCI system. Thirty-three patients who were catheterized for suspected coronary artery disease were studied. The manual tracings were performed by a senior cardiologist and an experienced function-analyst. It was found that the short- and long-term intraobserver variabilities in the assessment of the global ejection fraction were very small; short-term mean difference +/- standard deviation (correlation coefficient): 0.5 +/- 2.7 (r = 0.97) global EF%-units; long term; 0.7 +/- 2.7 (r = 0.96) EF%-units. The interobserver variabilities (5.1 +/- 4.8 (r = 0.93) EF%-units) were slightly higher than the intraobserver variabilities. A decrease by 25% in the amount of contrast medium administered did not significantly influence the variabilities in the contour tracings, which would suggest the use of smaller doses. At the average, the cardiologist and the function-analyst required 6 and 11 min of analysis time for a left ventricular study, respectively, emphasizing the need for further developments towards automated contour detection. Finally, an excellent correlation was found with a standard off-line cinefilm analysis procedure. Thus, it may be concluded that quantitative digital left ventricular angiography based on manual tracing of the outlines performed immediately following the cardiac catheterization (post-processing) is feasible as a routine procedure for the assessment of left ventricular function.

Aged↗

PubMed1989

A new method for the estimation of C3d. Affinity clearance of C-determinant-bearing C3 molecules and fragments followed by estimation of C3d by ELISA.

A method is described to quantitate human complement fragment C3d. Test samples were treated with a predetermined excess of anti-C3c-Sepharose beads in the presence of EDTA to remove all the C-determinant-bearing C3 molecules or fragments. C3d left in the supernatant was then estimated by ELISA. Using this method, C3d could be estimated accurately in normal plasma samples. A good correlation (r = 0.93) was observed between C3d values obtained by this method and values obtained by the widely used method of Perrin and coworkers. The average C3d plasma concentration was 2.8 mg/l (SD = 0.7 mg/l, n = 21). The interassay coefficient of variation using a normal plasma pool (C3d 2.7 mg/l) was 8.3% and using normal plasma pools in which the C3d concentrations were raised to 10.3 and 17.4 mg/l by the addition of aged normal serum the levels were 8.0 and 7.5% respectively. Intra-assay coefficients of variation with these samples were 4.6, 3.0 and 2.8%, respectively. 16 patients with renal dysfunction had C3d levels in the range of 4.3-10.0 mg/l and 15 patients undergoing continued ambulant peritoneal dialysis had levels of 3.3-12.2 mg/l. The C3d content in peritoneal dialysate of patients undergoing dialysis varied from 9.3 to 383 micrograms/l.

Antibody Specificity↗