The diagnostic accuracy of exercise electrocardiography in asymptomatic recreational and competitive athletes.

The goals of this study were to determine the prevalence and determinants of false-positive exercise tests in athletes. Data from all athletes who visited the Department of Sport Medicine for assessment of sports eligibility during a 1.5-year period were reviewed retrospectively. Potential determinants of (false) positive test results that were evaluated included demographics, cardiovascular risk factors, sports characteristics, resting electrocardiogram (ECG) abnormalities, and exercise capacity. Data from 1298 athletes were included. In 53 athletes (4.1%), the exercise ECG was classified as positive. Among 38 athletes who were referred to a sports cardiologist for further diagnostic evaluation, 36 (95%) were classified as having a false-positive test result and 2 athletes (5%) required coronary revascularization. Athletes with a false-positive test were older than athletes with a negative test (53 ± 8 vs 45 ± 13 years, P = 0.03). In conclusion, exercise electrocardiography has a low positive predictive value in asymptomatic recreational and competitive athletes, with a false-positive test result being associated with higher age. Given the relatively high prevalence of false-positive test results in this population, efforts should be made to develop strategies aimed at identifying false-positive test results in a simple noninvasive manner.

[Athletes with exercise-related pain at the medial side of the lower leg]. / Sporters met inspanningsgerelateerde pijn aan de mediale zijde van het onderbeen.

Two patients were diagnosed with exercise-related pain at the medial side of the lower leg. The first patient, an 18-year-old woman who had expanded her athletic activities extensively, had developed pain at the inner side of the distal third portion of the left lower leg. She showed over-pronation of the ankle during running. A 3-phase bone scintigram revealed diffuse uptake of the tracer covering a large portion of the medial tibia margin. Based on this evidence, a diagnosis of periostalgia was made. She recovered after a period of relative calf massages and used insoles. The second patient was a 28-year-old male endurance runner who developed pain at the medial shin after intensifying his training regimen. The periods without pain during running became increasingly shorter, and the medial side of the lower leg became sore and tense. Intracompartmental pressure measurements indicated exercise-related posterior deep compartment syndrome of the calf. The patient recovered after fasciotomy. In athletes, exercise-related symptoms of the medial side of the lower leg can be usually attributed to the tibial periosteum or tendons of the deep calfmusculature, tibial stress reaction or fracture, or a compartment syndrome of the deep calf. Surgery is indicated for chronic compartment syndrome, but conservative therapy provides favourable outcomes in the other types of disorders. The optimal conservative therapeutic approach is unknown, but it is advisable to temporary reduce symptom-provoking athletic activity and modify any risk factors present. Ankle over-pronation during running is considered a very relevant intrinsic risk factor.

Chronic deep posterior compartment syndrome of the leg in athletes: postoperative results of fasciotomy.

The present study evaluates the efficacy of two treatment regimens in individuals possibly suffering from chronic exercise induced compartment syndrome (CECS) of the deep posterior compartment of the leg. We hypothesised that the current method of fasciotomy of the deep posterior compartment of the leg is a procedure with a limited success rate. Dynamic intra-compartmental pressure measurements were applied to 46 patients that had symptomatology of a posterior CECS. Only those patients that met predefined pressure criteria, the "high-pressure group" (27 patients), were offered surgical treatment in the form of fasciotomy. The other 19 patients, "low-pressure group", received conservative treatment, consisting of inlays and physiotherapy. In addition, these patients were examined more closely in order to exclude different pathology. Efficacy of both approaches was evaluated by a questionnaire after a mean three-year follow-up. Fifty-two percent of the high-pressure group judged their operation successful, whereas 48 % did not. The majority of the low-pressure group (84 %) was free of symptoms, after conservative treatment as well as following treatment of other pathology. The present study shows that the success rate of patients surgically treated for posterior CECS is relatively low (52 %). The established cut-off points for the compartment pressure to deselect patients for an operation are justified based on the long-term success rate of the low-pressure group.

Myocardial adaptation in different endurance sports: an echocardiographic study.

OBJECTIVE: Of this study was to investigate three groups of highly trained competitive endurance athletes consisting of marathon runners, triathletes and cyclists for differences in left ventricular adaptation. METHODS: 25 marathon athletes, 21 triathlon athletes and 38 cyclists underwent a standard echocardiographic and Doppler study. RESULTS: The left ventricular internal diameter in diastole divided by body surface area was significantly larger in cyclists than in marathon runners (31.6+/-3.0 vs. 30.0+/-2.0 mm/ m2, p < 0.05) but did not differ of that of triathletes. Left ventricular mass was significantly different between marathon runners and triathletes (253.6+/-63.7 vs. 322.0+/-62.1 g, p < 0.005) and between marathon runners and cyclists (253.6+/-63.7 vs. 314.2+/-79.2 g, p < 0.005). Systolic wall stress was significantly different between the marathon runners and the triathletes (88.4+/-11.7 vs. 78.9+/-11.0 g/cm2 p < 0.05). Only a minority of the endurance athletes showed concentric remodeling (7%), whereas a majority showed eccentric remodeling (65%) of the left ventricle. The prevalence of eccentric remodeling was more apparent in cyclists. There were some specific differences in left ventricular diastolic function between the three different endurance sports, but no left ventricular diastolic dysfunction could be detected. CONCLUSION: There is a sport-specific left ventricular adaptation in endurance athletes. The triathlon heart and the heart of a cyclist differ significantly from a marathon heart.

Left atrial and ventricular dimensions in highly trained cyclists.

OBJECTIVES: This study sought to investigate the development of left ventricular remodeling during active cycling. METHODS: A group of 17-year-old (+/- 0.2 years) highly trained competitive cyclists (group I, n = 66) and a group of 29-year old (+/- 2.6 years) professional cyclists (group II, n = 35) underwent two-dimensional (2D) echocardiography. Data from groups I and II were compared with values of normal untrained subjects based on the literature. RESULTS: Left atrial dimensions were significantly increased in group II as compared to group I (44 +/- 5 vs. 36 +/- 4 mm, p < 0.005). Left ventricular end diastolic diameter was significantly increased in group II as compared to group I (61 +/- 5 vs. 54 +/- 6 mm, p < 0.005). Left ventricular mass was also significantly increased in group II as compared to group I (321 +/- 77 vs. 246 +/- 59 g, p < 0.005). Wall stress showed a significant inverse relation: 104 +/- 42 mmHg in group I vs. 83 +/- 14 mmHg in group II (p < 0.005). The early filling phase of the left ventricular inflow was significantly larger in both athlete groups in relation to the normal value. The E-wave in the athletes compared to the E-wave in normal subjects was 0.87 +/- 0.17 vs. 0.71 +/- 0.14 m/s in group I, p < 0.005, 0.82 +/- 0.17 vs. 0.71 +/- 0.14 m/s in group II, p < 0.05. Late filling phase and the ratio of the diastolic filling pattern did not show significant differences between the two groups. CONCLUSIONS: Left atrial and left ventricular remodeling starts early in the athlete's career. Athletes of 17 years of age already show significant left atrial and left ventricular dilatation compared to data of untrained subjects described in literature. The process of dilatation continues during the athlete's career. Also left ventricular mass is increased at a young age which continues for several years. More than 60% of the athletes in both groups demonstrated an intermediate form of left ventricular hypertrophy. Diastolic function of the left ventricle remains normal during a long period of athletic career performance.

Arrhythmogenic right ventricular dysplasia and sudden cardiac death in endurance athletes.

Arrhythmogenic right ventricular dysplasia (ARVD) is a cardiomyopathy with several time-dependent clinical presentations. The clinical characteristics depend on the penetration grade of the disease. There are two different histological patterns consisting of a lipomatous and a fibrolipomatous form. The presence of arrhythmias in the ARVD syndrome constitutes an important risk factor for sudden cardiac death in athletes. In this article, we describe two professional endurance athletes who died suddenly. One of these athletes had asymptomatic ARVD, the other had symptomatic polymorphic ventricular tachycardias. Both athletes showed fatty penetration of the disease in both the right and left ventricle; one of them also showed fatty involvement at the atrial level and in the other there were signs of myocarditis consistent with ARVD. In the last few years magnetic resonance imaging has become an important diagnostic tool in patients with ARVD.

[Long-term intensive athletic training; few adverse effects on later physical health]. / Langdurige intensieve fysieke sportbeoefening: weinig nadelige late gevolgen voor de gezondheid.

In general, physical activity benefits health. However, long-term intensive physical training may have detrimental effects on the health of some individuals. In cyclists, changes in the femoral arteries may occur leading to stenoses that are manifested in claudication type symptoms. Some endurance athletes may experience atrial fibrillations that are possibly related to long-term physical training. Older athletes only have an increased risk of osteoarthritis in joints that have suffered injuries. Menstrual disturbances and premature osteoporosis may occur in women as a consequence of intensive physical training. However, the risk for these adverse consequences of long-term physical training is small.

Mutation-dependent aggregation of tau protein and its selective depletion from the soluble fraction in brain of P301L FTDP-17 patients.

Mutations in the gene for the microtubule-associated protein tau are associated with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). In this study we compared the presence of the P301L mutated tau protein from brain material of patients with that of the normal 4-repeat, using polyclonal antibodies specific for the P301L point mutation and its normal counterpart. We determined the relative ratio of mutated versus normal tau protein in the sarkosyl-soluble and -insoluble protein fractions from several brain regions. Although mutated and normal tau proteins are both present in the sarkosyl-insoluble deposits, quantitative analysis showed that the mutated protein is the major component. In the sarkosyl-soluble fraction of frontal and temporal cortex the overall ratio of 3-repeat versus 4-repeat tau isoforms is unchanged but there is a dramatic depletion of mutant tau protein. Furthermore, we observed an increase in tau-immunoreactive cleavage products with the P301L antibody, suggesting that the mutant protein is partly resistant to degradation and this is confirmed by pulse-chase experiments. This is the first direct evidence using patient material that shows a selective aggregation of mutant tau protein resulting in sarkosyl-insoluble deposits and the specific depletion of mutated tau protein in the soluble fraction.

The effect of endurance training on the ventilatory response to exercise in elite cyclists.

The purpose of this study was to investigate the effects of endurance training on the ventilatory response to acute incremental exercise in elite cyclists. Fifteen male elite cyclists [mean (SD) age 24.3 (3.3) years, height 179 (6) cm, body mass 71.1 (7.6) kg, maximal oxygen consumption (VO2max) 69 (7) ml x min(-1) x kg(-1)] underwent two exercise tests on a cycle ergometer. The first test was assessed in December, 6 weeks before the beginning of the cycling season. The second test was performed in June, in the middle of the season. During this period the subjects were expected to be in a highly endurance-trained state. The ventilatory response was assessed during an incremental exercise test (20 W x min(-1)). Oxygen consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE), and heart rate (HR) were assessed at the following points during the test: at workloads of 200 W, 250 W, 300 W, 350 W, 400 W and at the subject's maximal workload, at a respiratory exchange ratio (R) of 1, and at the ventilatory threshold (Th(vent)) determined using the V-slope-method. Post-training, the mean (SD) VO2max was increased from the pre-training level of 69 (7) ml x min(-1) x kg(-1) (range 61.4-78.6) to 78 (6) ml x min(-1) x kg(-1) (range 70.5-86.3). The mean post-training VO2 was significantly higher than the pre training value (P < 0.01) at all work rates, at Th(vent) and at R = 1. VO2 was also higher at all work rates except for 200 W and 250 W. VE was significantly higher at Th(vent) and R = 1. Training had no effect on HR at all workloads examined. An explanation for the higher VO2 cost for the same work rate may be that in the endurance-trained state, the adaptation to an exercise stimulus with higher intensity is faster than for the less-trained state. Another explanation may be that at the same work rate, in the less-endurance-trained state power is generated using a significantly higher anaerobic input. The results of this study suggest the following practical recommendations for training management in elite cyclists: (1) the VO2 for a subject at the same work rate may be an indicator of the endurance-trained state (i.e., the higher the VO2, the higher the endurance-trained capacity), and (2) the need for multiple exercise tests for determining the HR at Th(vent) during a cycling season is doubtful since at Th(vent) this parameter does not differ much following endurance training.

The fragile X-related proteins FXR1P and FXR2P contain a functional nucleolar-targeting signal equivalent to the HIV-1 regulatory proteins.

Fragile X syndrome is caused by the absence of the fragile X mental-retardation protein (FMRP). FMRP and the fragile X-related proteins 1 and 2 (FXR1P and FXR2P) form a gene family with functional similarities, such as RNA binding, polyribosomal association and nucleocytoplasmic shuttling. In a previous study, we found that FMRP and FXR1P shuttle between cytoplasm and nucleoplasm, while FXR2P shuttles between cytoplasm and nucleolus. The nuclear and nucleolar-targeting properties of these proteins were investigated further. Here, we show that FXR2P contains in its C-terminal part, a stretch of basic amino acids 'RPQRRNRSRRRRFR' that resemble the nucleolar-targeting signal (NoS) of the viral protein Rev. This particular sequence is also present within exon 15 of the FXR1 gene. This exon undergoes alternative splicing and is therefore only present in some of the FXR1P isoforms. We investigated the intracellular distribution of various FXR1P isoforms with (iso-e and iso-f) and without (iso-d) the potential NoS in transfected COS cells treated with the nuclear export inhibitor leptomycin-B. Both iso-e and iso-f showed a nucleolar localization, as observed for FXR2P; iso-d was detected in the nucleo-plasm outside the nucleoli. Further, when a labelled 16-residue synthetic peptide corresponding to the NoS of FXR1P was added to human fibroblast cultures a clear nucleolar signal was observed. Based on these data we argue that the intranuclear distribution of FXR2P and FXR1P isoforms is very likely to be mediated by a similar NoS localized in their C-terminal region. This domain is absent in some FXR1P isoforms as well as in all FMRP isoforms, suggesting functional differences for this family of proteins, possibly related to RNA metabolism in different tissues.

Immunocytochemical and biochemical characterization of FMRP, FXR1P, and FXR2P in the mouse.

Fragile X syndrome is caused by the absence of expression of the FMR1 gene. Both FXR1 and FXR2 are autosomal gene homologues of FMR1. The products of the three genes are belonging to a family of RNA-binding proteins, called FMRP, FXR1P, and FXR2P, respectively, and are associated with polyribosomes as cytoplasmic mRNP particles. The aim of the present study is to obtain more knowledge about the cellular function of the three proteins (Fxr proteins) and their interrelationships in vivo. We have utilized monospecific antibodies raised against each of these proteins and performed Western blotting and immunolabeling at the light-microscopic level on tissues of wild-type and Fmr1 knockout adult mice. In addition, we have performed immunoelectron microscopy on hippocampal neurons of wild-type mice to study the subcellular distribution of the Fxr proteins. A high expression was found in brain and gonads for all three proteins. Skeletal muscle tissue showed only a high expression for Fxr1p. In the brain the three proteins were colocalized in the cytoplasm of the neurons; however, in specific neurons Fxr1p was also found in the nucleolus. Immunoelectronmicrsocopy on hippocampal neurons demonstrated the majority of the three proteins in association with ribosomes and a minority in the nucleus. The colocalization of the Fxr proteins in neurons is consistent with similar cellular functions in those specific cells. The presence of the three proteins in the nucleus of hippocampal neurons suggests a nucleocytoplasmic shuttling for the Fxr proteins. In maturing and adult testis a differential expression was observed for the three proteins in the spermatogenic cells. The similarities and differences between the distribution of the Fxr proteins have implications with respect to their normal function and the pathogenesis of the fragile X syndrome.

Immunological detection of polycystin-1 in human kidney.

Polycystin-1 is the protein product of the PKD1 gene. Mutations in this gene are responsible for most cases of polycystic kidney disease, but little is known about how these mutations lead to the development of cysts. Indeed, even less is known about the normal role of polycystin-1 in the kidney. The cellular localization of polycystin-1 has been the subject of intense investigation by many groups, including ours. In this report we describe our results and compare our data with those of others. We generated 14 different polyclonal antisera against fragments of the predicted 462-kDa polycystin-1 molecule to enable us to investigate the expression of polycystin-1 in cells and tissues by immunocytochemistry, western blotting, and immunoprecipitation. Our antibodies readily recognized a 134-kDa polycystin-1 fragment overexpressed in COS cells and stained the epithelial cells of fetal, adult, and cystic kidney sections with the same pattern as reported by others. However, further investigations revealed that this pattern was not specific for polycystin-1. We could not unequivocally detect polycystin-1 in vivo, either by immunoblotting or immunocytochemistry. Therefore our studies do not support the reported pattern of polycystin-1 expression in the kidney.

Oligomerization properties of fragile-X mental-retardation protein (FMRP) and the fragile-X-related proteins FXR1P and FXR2P.

The absence of fragile-X mental-retardation protein (FMRP) results in fragile-X syndrome. Two other fragile-X-related (FXR) proteins have been described, FXR1P and FXR2P, which are both very similar in amino acid sequence to FMRP. Interaction between the three proteins as well as with themselves has been demonstrated. The FXR proteins are believed to play a role in RNA metabolism. To characterize a possible functional role of the interacting proteins the complex formation of the FXR proteins was studied in mammalian cells. Double immunofluorescence analysis in COS cells over-expressing either FMRP ISO12/FXR1P or FMRP ISO12/FXR2P confirmed heterotypic interactions. However, Western-blotting studies on cellular homogenates containing physiological amounts of the three proteins gave different indications. Gel-filtration experiments under physiological as well as EDTA conditions showed that the FXR proteins were in complexes of >600 kDa, as parts of messenger ribonuclear protein (mRNP) particles associated with polyribosomes. Salt treatment shifted FMRP, FXR1P and FXR2P into distinct intermediate complexes, with molecular masses between 200 and 300 kDa. Immunoprecipitations of FMRP as well as FXR1P from the dissociated complexes revealed that the vast majority of the FXR proteins do not form heteromeric complexes. Further analysis by [(35)S]methionine labelling in vivo followed by immunoprecipitation indicated that no proteins other than the FXR proteins were present in these complexes. These results suggest that the FXR proteins form homo-multimers preferentially under physiological conditions in mammalian cells, and might participate in mRNP particles with separate functions.

Different targets for the fragile X-related proteins revealed by their distinct nuclear localizations.

Fragile X syndrome is caused by the absence of the fragile X mental retardation protein (FMRP). FMRP and its structural homologues FXR1P and FXR2P form a family of RNA-binding proteins (FXR proteins). The three proteins associate with polyribosomes as cytoplasmic mRNP particles. Here we show that small amounts of FMRP, FXR1P and FXR2P shuttle between cytoplasm and nucleus. Mutant FMRP of a severely affected fragile X patient (FMRPI304N) does not associate with polyribosomes and shuttles more frequently than normal FMRP, indicating that the association with polyribosomes regulates the shuttling process. Using leptomycin B we demonstrate that transport of the FXR proteins out of the nucleus is mediated by the export receptor exportin1. Finally, inactivation of the nuclear export signal in two FXR proteins shows that FMRP shuttles between cytoplasm and nucleoplasm, while FXR2P shuttles between cytoplasm and nucleolus. Therefore, molecular dissection of the shuttling routes used by the FXR proteins suggests that they transport different RNAs.

The ventilatory threshold, heart rate, and endurance performance: relationships in elite cyclists.

The purpose of this study was to investigate the validity of the ventilatory response during incremental exercise as indication of endurance performance during prolonged high-intensity exercise under field test conditions in elite cyclists. The ventilatory threshold (VT) was assessed in 14 male elite cyclists (age 22.4+/-3.4 years, height 181+/-6 cm, weight 69.2+/-6.8 kg, VO2max 69+/-7 ml x min(-1) x kg(-1)) during an incremental exercise test (20 W x min(-1)). Heart rate and oxygen uptake were assessed at the following ventilatory parameters: 1. Steeper increase of VCO2 as compared to VO2 (V-slope-method); 2. Respiratory exchange ratio (RQ)=0.95 and 1.00; 3. VE/VO2 increase without a concomitant VE/VCO2 (VE/VO2 method). Three weeks following the laboratory tests, the ability to maintain high-intensity exercise was determined during a 40 km time trial on a bicycle. During this time trial the mean heart rate (HR(TT)) and the road racing time (TT) were assessed. The V-slope-method and the VE/VO2 method showed significant correlations with TT (V-slope: r = -0.82; p<0.001; 90% interval of confidence = +/-82 sec; VE/VO2: r=-0.81; p<0.01; 90% interval of confidence = +/-81 sec). Heart rate at the ventilatory parameters and at the maximum heart rate (HRmax) showed significant correlations with HR(TT). The V-slope-method is the preferred method to predict heart rate during prolonged high-intensity exercise (r=0.93; p<0.0001; 90% interval of confidence: +/-4.8 beats x min(-1)). For predicting heart rate during prolonged high-intensity exercise using an incremental exercise test (20 W x min(-1)), without the knowledge of ventilatory parameters, we recommend using the regression formula: H(TT)=0.84 x Hmax + 14.3 beats x min(-1) (r=0.85; p<0.001).

FMR1 gene expression in olfactory neuroblasts from two males with fragile X syndrome.

The fragile X mental retardation 1 gene (FMR1) mutation is strongly correlated with specific and marked neurobehavioral and neuroanatomical abnormalities. The protein product, FMRP, is highly expressed in neurons of the normal mammalian brain, and absent or in low levels in leukocytes from individuals with fragile X (FraX)-associated mental impairment. Inferences which arise from these findings are that FMRP has a critical role in the development and functioning of the brain, and that leukocyte-derived molecular assessments provide a good indicator of FMR1 expression in that organ. This latter conclusion appears true in most cases even though the typical FMR1 mutation is an unstable triplet repeat expansion which demonstrates somatic heterogeneity within and across tissues. Blood to brain correspondence in FraX patients has only rarely been confirmed by the direct study of human brain specimens and, to our knowledge, it has never been studied in living individuals with the FMR1 mutation. In this report, we describe the FMR1 patterns in olfactory neuroblasts (ON) from two living brothers with expansion mutations in their leukocytes who are mentally retarded and autistic. ON were chosen for study because they are accessible neurons closely linked to the brain. In both subjects, the ON genotype was highly, but not perfectly, consistent with that observed in leukocytes. Protein phenotypes across tissues were completely consistent showing the absence of FMRP-immunoreactivity (-ir). These results augment the limited amount of direct evidence which indicates that FMR1 mutation patterns in leukocytes are a good, albeit potentially fallible, reflection of such patterns in the brain. This report further demonstrates the feasibility of using ON samples to evaluate the FMR1 mutation in humans in vivo.

Subcellular localization of the oncoprotein MTG8 (CDR/ETO) in neural cells.

The t(8;21) translocation associated with acute myeloid leukemia (AML) disrupts two genes, the AML1 gene also known as the core binding factor A2 (CBFA2) on chromosome 21, and a gene on chromosome 8, hereafter referred to as MTG8, but also known as CDR and ETO. Extensive information is available on AML1, a member of the CBF family of transcription factors, containing a highly conserved domain, the runt box, of the Drosophila segmentation gene runt. This gene is essential for the hematopoietic development and is found disrupted in several leukemias. In contrast, the function of the MTG8 gene is poorly understood. The predicted protein sequence shows two unusual, putative zinc-fingers, three proline-rich regions, a PEST domain and several phosphorylation sites. In addition, we found a region encompassing aa 443-514 predicted to have a significant propensity to form coiled coil structures. MTG8 displays a high degree of similarity with nervy, a homeotic target gene of Drosophila, expressed in the nervous system. Human and mouse wild-type MTG8 are also highly expressed in brain relative to other tissues. For these reasons, we set out to investigate the expression and subcellular localization of the MTG8 protein in neural cells. Immunohistochemical experiments in a 12.5-day-old mouse embryo clearly showed that the protein was expressed in the neural cells of the developing brain and the spinal cord. In primary cultures of hippocampal neurons of 2-3 day-old mice, MTG8 was found in the nucleus, in the cytoplasm and as fine granules in the neurites. Cytoplasmic localization of the protein was observed in Purkinje cells of both human and mouse cerebellum. The molecular mass of MTG8 in total human and mouse brain was analysed by immunoblotting and determined to be between 70 and 90 kDa. Isoforms with the same molecular mass were demonstrated in synaptosomes isolated from mouse forebrain. The evidence of MTG8 in the nucleus and cytoplasm of neural cells suggests a specific mechanism regulating the subcellular localization of the protein.

The plasma lactate response to exercise and endurance performance: relationships in elite triathletes.

The lactate response to exercise has been studied thoroughly during the last decades and it has been described using a variety of terms and definitions. Numerous investigations observed close relationships between the lactate response and endurance performance. The main question in this study was which of the various lactate responses during incremental exercise described in the literature was the best indicator of endurance performance. The plasma lactate response (PLR) was assessed during an incremental exercise test on 13 male elite triathletes (age 25.5+/-5.8 yrs; HT 179.7+/-5.4 cm; WT 71.3+/-4.7 kg) on a bicycle ergometer. The load was started at 2.5 W/kg and increased by 40 W every 4 min. We evaluated the following PLR-parameters: the workloads at the fixed lactate levels of 2, 3, 4, 5, 6, 7, and 8 mmol/l which were assessed by extrapolation from a workload-lactate-heart rate curve (P2, P3, P4, P5, P6, P7, P8 respectively), the lactate threshold which was defined as the workload at the point at which a non-linear increase of blood lactate occurred (Plt), and the workload at the lactate level that was 1 mmol/l above the baseline (P + 1). Four to seven weeks after the laboratory test, heart rate and lactate levels were assessed during a 40-km long time trial on a bicycle. Two parameters were considered as indicative of athletic performance: the road racing time (Tt), and the workload extrapolated from the workload-lactate-heart rate curve at the heart rate and lactate levels observed during the time trial (Pt). Only P2 showed a significant correlation with Tt (r=-0.65; p < 0.05; se = 72.5 s). Multiple regression analysis with the anthropometric parameters height and weight as additional independent parameters did not change the predictive value. We concluded that for predicting the cycling performance of similarly well-trained subjects the predictive value of PLR is negligible.

Differential expression of FMR1, FXR1 and FXR2 proteins in human brain and testis.

Lack of expression of the fragile X mental retardation protein (FMRP) results in mental retardation and macroorchidism, seen as the major pathological symptoms in fragile X patients. FMRP is a cytoplasmic RNA-binding protein which cosediments with the 60S ribosomal subunit. Recently, two proteins homologous to FMRP were discovered: FXR1 and FXR2. These novel proteins interact with FMRP and with each other and they are also associated with the 60S ribosomal subunit. Here, we studied the expression pattern of the three proteins in brain and testis by immunohistochemistry. In adult brain, FMR1, FXR1 and FXR2 proteins are coexpressed in the cytoplasm of specific differentiated neurons only. However, we observed a different expression pattern in fetal brain as well as in adult and fetal testis, suggesting independent functions for the three proteins in those tissues during embryonic development and adult life.

The Han:SPRD rat is not a genetic model of human autosomal dominant polycystic kidney disease type 1.

Human autosomal dominant polycystic kidney disease (ADPKD) is a high incidence disorder leading to renal failure in many patients. The majority of cases results from a mutation in the PKD1 gene. The only well documented animal model of ADPKD is the Han:SPRD-Pkd strain. Its genetic basis is unknown as yet. In the current study we determined whether the disease in these rats is genetically linked to the rat homologue of the PKD1 gene. We used the protamine gene as a polymorphic marker (Prm1) of the PKD1 region. Matings of Han:SPRD-Pkd with BB rats and backcross of the offspring with BB yielded animals informative for linkage analysis. This analysis revealed random segregation of the defect and the Prm1 marker, indicating that the model is not caused by a mutation in the PKD1 gene. We conclude that the Han:SPRD-Pkd rat strain is not a genetic model of PKD1.