Effect of intensive swimming training on lung volumes, airway resistances and on the maximal expiratory flow-volume relationship in prepubertal girls

The aim of the present study was to analyse the effect of 1 year of intensive swimming training on lung volumes, airway resistance and on the flow-volume relationship in prepubertal girls. Five girls [9.3 (0.5) years old] performing vigorous swimming training for 12?h a week were compared with a control group of 11 girls [9.3 (0.5) years old] who participated in various sport activities for 2 h per week. Static lung volumes, maximal expiratory flows (MEF) at 75, 50 and 25% of vital capacity, 1-s forced expiratory volume (FEV_1.0) and airway resistance (R _aw) were measured by means of conventional body plethysmograph techniques. Prior to the training period there were no significant differences between the two groups for any of the parameters studied. Moreover, for both groups, all parameters were within the normal range for children of the corresponding age. After 1 year of training, vital capacity (VC), total lung capacity (TLC) and functional residual capacity (FRC) were larger (P<0.05) in the girl swimmers than in the control group, while physical development in terms of height and weight was similar. FEV_1.0 (P<0.01), MEF₂₅, MEF₅₀ (P<0.05) and MEF₇₅ as well as the ratio MEF₅₀ / TLC (P<0.05) had increased in the girl swimmers but were unchanged in the control group. R _aw tended to be lower in the girl swimmers and higher in the control group. The results indicate that intensive swimming training prepuberty enhances static and dynamic lung volumes and improves the conductive properties of both the large and the small airways. As to the causative mechanism, it can be speculated that at prepuberty intensive swimming training promotes isotropic lung growth by harmonizing the development of the airways and of alveolar lung spaces.     

Identification of iduronate sulfatase gene alterations in 70 unrelated Hunter patients

We studied 70 unrelated Hunter patients and found a gene alteration in every patient. The molecular heterogeneity was very important. Large gene rearrangements were identified in 14 patients. Forty-three different mutations were identified in the 56 other patients and 31 were not previously described. Deletions and insertions, splice site mutations were associated with a severe phenotype as nonsense mutations except Q531X. Only a few mutations were present in several patients making difficult genotype-phenotype correlations. Mutation identification allows accurate carrier detection improving prenatal diagnosis. The mother was not found to be a carrier in five cases among the 44 sporadic cases. Haplotype analysis demonstrated a higher frequency of mutations in male meiosis.     

Hitting moving objects: is target speed used in guiding the hand?

We investigated what information subjects use when trying to hit moving targets. In particular, whether only visual information about the target's position is used to guide the hand to the place of interception or also information about its speed. Subjects hit targets that moved at different constant speeds and disappeared from view after varying amounts of time. This prevented the subjects from updating position information during the time that the target was invisible. Subjects hit further ahead of the disappearing point when the target moved faster, but not as much as they should have on the basis of the target's speed. This could be because more time is needed to perceive and use the correct speed than was available before the target disappeared. It could also be due to a speed-related misperception of the target's final position. The results of a second experiment were more consistent with the latter hypothesis. In a third experiment we moved the background to manipulate the perceived speed. This did not affect the hitting positions. We conclude that subjects respond only to the changing target position. Target speed influences the direction in which the hand moves indirectly, possibly via a speed-related misperception of position.     

Complex CGH alterations on chromosome arm 8p at candidate tumor suppressor gene loci in breast cancer cell lines

Loss of genetic material from chromosome arm 8p occurs frequently in human breast carcinomas, consistent with this region of the genome harboring one or more tumor suppressor genes (TSGs). We used the complementary techniques of microsatellite-based LOH, high-density FISH, and conventional CGH on 6 breast cancer cell lines (MCF7, SKBR3, T47D, MDA MB453, BT549, and BT474) to investigate the molecular cytogenetic changes occurring on chromosome 8 during tumorigenesis, with particular emphasis on 6 potential TSGs on 8p. We identified multiple alterations of chromosome 8, including partial or complete deletion of 8p or 8q, duplication of 8q, and isochromosome 8q. The detailed FISH analysis showed several complex rearrangements of 8p with differing breakpoints of varying proximity to the genes of interest. High rates of LOH were observed at markers adjacent to or within PCM1, DUSP4/MKP2, NKX3A, and DLC1, supporting their status as candidate TSGs. Due to the complex ploidy status of these cell lines, relative loss of 8p material detected by CGH did not always correlate with microsatellite-based LOH results. These results extend our understanding of the mechanisms accompanying the dysregulation of candidate tumor suppressor loci on chromosome arm 8p, and identify appropriate cellular systems for further investigation of their biological properties.     

Two-center collaborative evaluation of the performance of the BD Phoenix automated microbiology system for identification and antimicrobial susceptibility testing of Enterococcus spp. and Staphylococcus spp

The performance of the BD Phoenix Automated Microbiology System (BD Diagnostic Systems, Sparks, Md.) was assessed for identification (ID) and antimicrobial susceptibility testing (AST) for the majority of clinically encountered bacterial isolates in a European collaborative two-center trial. A total of 469 bacterial isolates of the genera Staphylococcus (275 isolates), Enterococcus (179 isolates), and Streptococcus (15 isolates, for ID only) were investigated; of these, 367 were single patient isolates, and 102 were challenge strains tested at one center. Sixty-four antimicrobial drugs were tested, including the following drug classes: aminoglycosides, beta-lactam antibiotics, beta-lactam-beta-lactamase inhibitors, carbapenems, cephems, folate antagonists, quinolones, glycopeptides, macrolides-lincosamides-streptogramin B (MLS), and others. Phoenix ID results were compared to those of the laboratories' routine ID systems (API 32 Staph, API 32 Strep, and VITEK 2 [bioMérieux, Marcy l'Etoile, France]); Phoenix AST results were compared to those of frozen standard broth microdilution (SBM) panels according to NCCLS guidelines (NCCLS document M 100-S 9, approved standard M 7-A 4). Discrepant results were repeated in duplicate. Concordant IDs of 97.1, 98.9, and 100% were observed for staphylococci, enterococci, and streptococci, respectively. For AST results the overall essential agreement was 93.3%; the category agreement was 97.3%; and the very major error rate, major error rate, and minor error rate were 1.2, 1.9, and 1.3%, respectively. In conclusion, the Phoenix ID results showed high agreement with results of the systems to which they were being compared; the AST performance was highly equivalent to that of the SBM reference method.     

A contig of non-chimaeric YACs containing the spinal muscular atrophy gene in 5q13

We have constructed a contig of non-chimaeric yeast artificialchromosomes (YACs) across the candidate region for childhoodautosomal recessive spinal muscular atrophy (SMA) In 5q13. Anovel microsatellite reduces the candidate region to approximately400kb of DNA distal to D5S435. The candidate region containsblocks of chromosome 5 specific repeats which have copies on5p as well as elsewhere on 5q. Restriction mapping of the YACsreveals at least one CpG island In the SMA gene region. TheYAC maps indicate that the contig contains minimal rearrangementsor deletions. The data show the value of screening several YAClibraries simultaneously in order to construct a set of overlappingsequences suitable for candidate gene searches and direct genomicsequencing.     

Potentiation by deprenyl of the autoreceptor-mediated inhibition of [3H]-5-hydroxytryptamine release by 5-methoxytryptamine

Summary The 5-hydroxytryptamine (5HT) receptor agonist, 5-methoxytryptamine, inhibited in a concentration-dependent manner the electrically-evoked release of ³H-5HT from superfused rat hypothalamic slices, with an IC₅₀ of 560 nmol/l, without affecting the spontaneous outflow of radioactivity. In the presence of the selective monoamine oxidase B (MAO B) inhibitor, (–)-deprenyl (1 mol/l), the concentration-effect curve for 5-methoxytryptamine was shifted significantly to the left, and the IC₅₀ was decreased to 25 nmol/l. Under the same experimental conditions, the potency of the 5HT receptor agonist lysergic acid diethylamide (LSD) at inhibiting the electrically-evoked release of ³H-5HT was the same in the presence as well as in the absence of (–)-deprenyl. The IC₅₀ values for LSD were 34 nmol/l in the absence of deprenyl, and 31 nmol/l in the presence of the MAO B inhibitor. It is concluded that deprenyl potentiates the inhibition by 5-methoxytryptamine of ³H-5HT release, by preventing its inactivation through MAO B. Since 5-methoxytryptamine may be present in the pineal gland of some species, the potent effects of this 5-HT receptor agonist on seretoninergic neutrotransmission may be of physiological relevance.     

The neu-protein and breast cancer

The neu-protein is overexpressed in about 20% of invasive duct cell carcinomas of the breast. The only reliable sign for neu-overexpression by immunohistochemistry is membrane staining. Its overexpression is correlated with decreased overall survival and disease free survival due to increased metastatic activity of neu-overexpressing tumour cells. This increased metastatic potential is a consequence of the motility enhancing activity of the neu-protein, which is exclusively expressed on pseudopodia, and to a lesser extent of its growth stimulating effect. From a clinical point of view, the assessment of neu-overexpression in breast cancer might become a useful tool in the future treatment of patients by chemotherapy, since patients whose tumour shows neu-overexpression benefit from higher doses of chemotherapy. The molecule plays a key role in the pathogenesis of Paget's disease of the breast. A chemotactic factor which is secreted by epidermal keratinocytes attracts the Paget cells to spread into the epidermis and acts via the neu-protein. In ductal carcinoma in situ, the combination of neu-overexpression and large cell type is highly correlated with extent of disease and therefore neu-overexpression might be a predictive marker for recurrence of disease after tumour resection.     

Renal functional reserve in children with reduced renal mass: study by two dietary periods

It has been suggested that the renal functional reserve (RFR) defined by the rise in glomerular filtration rate (GFR) after a protein load could disappear in patients with severe nephron loss but with a normal GFR. This study compared, in 17 children, inulin clearance (C _in) measured by the plasma inulin plateau at the end of two 14-day randomized periods differing in protein intake: 100% (low protein, LP), or 200% (high protein, HP) of recommended dictary allowances (RDA). Diets were aimed at maintaining food habits and energy intake. Compliance was assessed by records of the last 3–4 days, an interview with the dietician and by urinary nitrogen measurements. Mean actual protein intake was 109% (56%–139%) RDA for the LP period and 220% (163%–319%) RDA for the HP period.C _in did not change in 14 children with GFR below (n=7) or within (n=7) the normal range.C _in was higher in the HP period than in the LP period (+32, 50, 63%) in 3 children who had a 50% (single kidneys) or a 25% (sclerosed glomeruli) nephron loss. Non-responding children had a GFR below 105 ml/min per 1.73 m². Nephron loss (70% sclerosed glomeruli) was estimated in only 1 child with no RFR. The results suggest that GFR measurement after prolonged dietary stimulation could help in evaluating the severity of nephron loss in children with normal or borderline GFR. The prognostic value of this test has to be confirmed by long-term follow-up.     

Differential effects of zidovudine and zidovudine triphosphate on mitochondrial permeability transition and oxidative phosphorylation

1. The effects of zidovudine (ZDV) and zidovudine triphosphate (ZDV-3P) on Ca²⁺-induced mitochondrial permeability transition (MPT), respiratory control ratio (RCR) and ATP synthesis have been investigated on isolated rat liver mitochondria.
2. ZDV slightly but significantly decreased RCR and ATP synthesis but was ineffective in inhibiting MPT. In contrast, ZDV-3P did not alter RCR and ATP synthesis but strongly inhibited MPT (IC₅₀=3.0±0.9 μM).
3. The effect of ZDV-3P on mitochondrial swelling required a preincubation time. When incubated 10 min with mitochondria, ZDV-3P (8 μM) totally inhibited the rate of swelling.
4. ADP, ATP and atractyloside, which are agents known to interact with the mitochondrial adenine nucleotide carrier (ANC), antagonized the effect of ZDV-3P on mitochondrial swelling. Indeed, the IC₅₀ value of ZDV-3P increased from 3.0 to 17.4, 93.6 and 66.5 μM, in the presence of 20 μM, ADP, ATP or atractyloside, respectively.
5. ZDV-3P did not displace [³H]-ATP from its mitochondrial binding site(s) whereas ADP and atractyloside did, suggesting that ZDV-3P and [³H]-ATP do not share the same binding sites.
6. ZDV-3P did not affect either mitochondrial respiration or ATP synthesis but inhibited Ca²⁺-dependent mitochondrial swelling. It was concluded that mitochondrial toxic effects observed during the chronic administration of ZDV cannot be related to its active metabolite (ZDV-3P).