Muscle strength, muscle cross-sectional area, fiber size, fiber type distribution, capillarity, and mitochondrial volume were estimated before and after 6 weeks of heavy-resistance exercise. Isokinetic torque production of the knee extensor muscles increased by a total of 17.6%, mainly during the first half of the training period. The cross-sectional area of the vastus lateralis muscle increased by 8.4%, mainly during the second half of the training period. Morphometrically determined fiber size, fiber type distribution, and capillarity from biopsies of vastus lateralis did not change significantly with training. Likewise, the surface densities of inner and outer mitochondrial membranes as well as the volume density of myofibrils remained unchanged. In contrast, the volume density of mitochondria decreased by 9.6%. However, due to the increase in total muscle volume, the calculated absolute volume of mitochondria remained constant, whereas the absolute volume of myofibrils increased by 10%. It is concluded that strength training of short duration in previously untrained young male subjects does not change the ultrastructural composition of mitochondria and that the apparent dilution of mitochondria can quantitatively be accounted for by the increase in myofibrillar volume.

SUMMARY1. Six weeks of a dynamic heavy-resistance training of the quadriceps muscle in healthy young men resulted in a continuous increase in muscle strength, in an increase in muscle cross-sectional area (significant only in the second half of the training period) and in an increase in radiological density of the muscle tissue of 3 1 % (2P < 0 001) in the first three weeks and 1-6 % (2P < 0 01) in the second three weeks.2. The linear distance between myosin filaments (38-7 + 0-3 nm before, 38-7 + 0 4 nm after training; mean + S.E.M.) as well as the ratio of actin to myosin filaments (3 94 + 0-03 before, 3-86 + 0-06 after training) did not change with training.3. These results refute the concept that the increases in muscle strength or radiological density during short-term heavy-resistance training are caused by changes in myofilament spacing.

We investigated molecular and cellular parameters which set metabolic and mechanical functioning of knee extensor muscles in the operated and contralateral control leg of 9 patients with a chronically insufficient anterior cruciate ligament (ACL; 26.6 ± 8.3 years, 8 males, 1 female) after open reconstructive surgery (week 0), after ambulant physiotherapy under cast immobilization (week 9), succeeding rehabilitation training (up to week 26), and subsequent voluntary physical activity (week 260). Clinical indices of knee function in the operated leg were improved at 52 weeks and remained at a comparable level at week 260. CSA of the quadriceps (-18%), MCSA of muscle fibers (-24%), and capillary-to-fiber ratio (-24%) in m. vastus lateralis from the ACL insufficient leg were lower at week 0 than reference values in the contralateral leg at week 260. Slow type fiber percentage (-35%) and mitochondrial volume density (-39%) were reduced in m. vastus lateralis from the operated leg at weeks 9 and 26. Composition alterations in the operated leg exceeded those in the contralateral leg and, with the exception of the volume density of subsarcolemmal mitochondria, returned to the reference levels at week 260. Leg-specific deterioration of metabolic characteristics in the vasti from the operated leg was reflected by the down-regulation of mitochondrial respiration complex I-III markers (-41–57%) at week 9. After rehabilitation training at week 26, the specific Y397 phosphorylation of focal adhesion kinase (FAK), which is a proxy for mechano-regulation, was elevated by 71% in the operated leg but not in the contralateral leg, which had performed strengthening type exercise during ambulant physiotherapy. Total FAK protein and Y397 phosphorylation levels were lowered in both legs at week 26 resulting in positive correlations with mitochondrial volume densities and mitochondrial protein levels. The findings emphasize that a loss of mechanical and metabolic characteristics in knee extensor muscle remains detectable years after untreated ACL rupture, which may be aggravated in the post-operative phase by the deterioration of slow-oxidative characteristics after reconstruction due to insufficient load-bearing muscle activity. The reestablishment of muscle composition subsequent to years of voluntary physical activity reinforces that slow-to-fast fiber transformation is reversible in humans.

The most frequent chromosomal aberrations in B-cell chronic lymphocytic leukemia (B-CLL) are deletions on 13q, 11q, and 17p, and trisomy 12, all of which are of prognostic significance. Conventional cytogenetic analysis and fluorescence in situ hybridization (FISH) are used for their detection, but cytogenetic analysis is hampered by the low mitotic index of B-CLL cells, and FISH depends on accurate information about candidate regions. We used a set of 400 highly informative microsatellite markers covering all chromosomal arms (allelotyping) and automated polymerase chain reaction (PCR) protocols to screen 46 patients with typical B-CLL for chromosomal aberrations. For validation, we compared data with our conventional karyotype results and fine mapping with conventional single-site PCR. All clonal cytogenetic abnormalities potentially detectable by our microsatellite PCR (eg, del13q14 and trisomy 12) were picked up. Allelotyping revealed additional complex aberrations in patients with both normal and abnormal B-CLL karyotypes. Aberrations detectable in the samples with our microsatellite panel were found on almost all chromosomal arms. We detected new aberrant loci in typical B-CLL, such as allelic losses on 1q, 9q, and 22q in up to 25% of our patients, and allelic imbalances mirroring chromosomal duplications, amplifications, or aneuploidies on 2q, 10p, and 22q in up to 27% of our patients. We conclude that allelotyping with our battery of informative microsatellites is suitable for molecular screening of B-CLL. The technique is well suited for analyses in clinical trials, it provides a comprehensive view of genetic alterations, and it may identify new loci with candidate genes relevant in the molecular biology of B-CLL.