In vivo human muscle structure and function: adaptations to resistance training in old age

This study investigated changes in elderly muscle joint angle-torque relation induced by resistance training. Older adults were assigned to either training (n = 9, age 74.3 +/- 3.5 years; mean +/-s.d.) or to control groups (n = 9, age 67.1 +/- 2 years). Leg-extension and leg-press exercises were performed three times per week for 14 weeks. Maximal isometric knee extension torque was measured across the knee joint angle range of movement. Vastus lateralis muscle architecture was examined in vivo using ultrasonography. The vastus lateralis muscle fascicle force was estimated from the measured joint torque, enabling construction of the fascicle length-force relation. Electromyographic (EMG) activity was measured from representative agonist and antagonist muscles. Training altered the angle-torque relation: (a) displacing it by 9-31% towards higher torque values (P < 0.05); and (b) shifting the optimal angle from 70 deg (corresponding torque: 121.4 +/- 61 N m) before to 60 deg (134.2 +/- 57.2 N m; P < 0.05) after training. Training also altered the fascicle length-force relation: (a) displacing it by 11-35% towards higher force values; and (b) shifting the optimal fascicle length from 83.7 +/- 8 mm (corresponding force: 847.9 +/- 365.3 N) before to 93.2 +/- 12.5 mm (939.3 +/- 347.8 N; P < 0.01) after training. The upward displacement of the angle-torque relation was mainly due to a training-induced increase in agonist activation, whilst the shift in the optimal angle was associated with changes in muscle-tendon properties.     

Molecular evolutionary relationships of enteroinvasive Escherichia coli and Shigella spp

Enteroinvasive Escherichia coli (EIEC), a distinctive pathogenic form of E. coli causing dysentery, is similar in many properties to bacteria placed in the four species of Shigella. Shigella has been separated as a genus but in fact comprises several clones of E. coli. The evolutionary relationships of 32 EIEC strains of 12 serotypes have been determined by sequencing of four housekeeping genes and two plasmid genes which were used previously to determine the relationships of Shigella strains. The EIEC strains were grouped in four clusters with one outlier strain, indicating independent derivation of EIEC several times. Three of the four clusters contain more than one O antigen type. One EIEC strain (an O112ac:H- strain) was found in Shigella cluster 3 but is not identical to the Shigella cluster 3 D2 and B15 strains with the same O antigen. Two forms of the virulence plasmid pINV have been identified in Shigella strains by using the sequences of ipgD and mxiA genes, and all but two of our EIEC strains have pINV A. The EIEC strains were grouped in two subclusters with a very low level of variation, generally not intermingled with Shigella pINV A strains. The EIEC clusters based on housekeeping genes were reflected in the plasmid gene sequences, with some exceptions. Two strains were found in the pINV B form by using the ipgD sequence, with one strain having an mxiA sequence similar to the divergent sequence of D1. Clearly, EIEC and Shigella spp. form a pathovar of E. coli.     

Complementary and alternative medical therapy utilization by people with chronic fatiguing illnesses in the United States

Background  

Chronic fatiguing illnesses, including chronic fatigue syndrome (CFS), pose a diagnostic and therapeutic challenge. Previous clinical reports addressed the utilization of health care provided to patients with CFS by a variety of practitioners with other than allopathic training, but did not examine the spectrum of complementary and alternative medicine (CAM) therapies used. This study was designed to measure CAM therapy use by persons with fatiguing illnesses in the United States population.     

The post-baccalaureate premedical certification program at the University of North Texas Health Science Center strengthens admission qualifications for entrance into medical school.

The Post-Baccalaureate (postbac) Premedical Certification Program at the University of North Texas Health Science Center provides an opportunity for individuals to enhance their credentials for entry into medical school by offering a challenging biomedical science core curriculum in graduate biochemistry, cell biology, physiology, and pharmacology. In addition, students (called postbacs) receive instruction in human gross anatomy, histology, and embryology with first-year medical students. More than 90% of the students accepted into the postbac program have applied to medical school previously but have been rejected by admission committees at least once, primarily because of low cognitive scores. In spring 2001, seven postbacs completed the program, of which only one was admitted into the Texas College of Osteopathic Medicine (TCOM), the medical school affiliated with the University of North Texas Health Science Center. Three postbacs went to other medical schools. Thirty-one completed the program by spring 2006, of whom 13 were admitted to TCOM, and eight to other medical schools. After six years, 101 postbacs have completed the program, and 70 have been accepted into medical schools. Postbacs admitted into TCOM have performed well compared with their medical school classmates. Overall, average scores for postbacs are above those of their medical school classmates. In addition, postbacs have taken class leadership positions, served as tutors and mentors, and have served as school ambassadors for new applicants. The postbac premedical program has proven to be very successful in preparing students for the rigors of a medical school curriculum by allowing these students to develop the skills and confidence necessary to compete.     

Confirmation of multiple sulfonamide residues in bovine milk by gas chromatography-positive chemical ionization mass spectrometry

Gas chromatography-mass spectrometry (GC-MS) using positive chemical ionization was utilized to confirm the presence of 10 ng ml(-1) of nine sulfonamides (SFAs) in bovine milk (50 ml). After the addition of a surrogate and hydroxylamine hydrochloride, the SFAs are extracted with ethyl acetate followed by cyclohexyl solid-phase extraction clean-up. The methylamidotrifluoroacetyl derivatives are prepared and analyzed in selected ion monitoring mode. For regulatory confirmation, the required specificity was achieved by monitoring the molecular ion plus three to five fragment ions for each SFA. Retention times for all SFAs were within 0.1 min of their respective standard. The relative ion abundances were within 10% of those obtained with standards diluted to the same concentration, analyzed on the same day. Concentration was critical, especially for the early eluting SFAs, as the enhancement of the relative abundance of the parent was more pronounced in extracted samples then in the standards. The sensitivity of the mass spectrometer for the different SFAs varied greatly. The amount of SFA necessary to obtain spectra that would meet the confirmation criteria varied from 25 ng on column for the least sensitive to less than 3 ng for the more robust.     

Differential effects of trisomy on brain shape and volume in related aneuploid mouse models

Down syndrome (DS) results from inheritance of three copies of human chromosome 21 (Hsa21). Individuals with DS have a significantly smaller brain size overall and a disproportionately small cerebellum. The small cerebellum is seen in Ts65Dn mice, which have segmental trisomy for orthologs of about half the genes on Hsa21 and provide a genetic model for DS. While small cerebellar size is well-established in mouse and humans, much less is known about the shape of the brain in trisomy. Here we conduct a morphometric analysis of the whole brain and cerebellum in Ts65Dn mice and show that the differences with euploid littermates are largely a function of volume and not of shape. This is not the case in two aneuploid mouse models that have fewer genes orthologous to Hsa21 than Ts65Dn. Ts1Rhr is trisomic for genes corresponding to the so-called Down syndrome critical region (DSCR), which was purported to contain a dosage sensitive gene or genes responsible for many phenotypes of DS. Ms1Rhr is monosomic for the same segment. These models show effects on cerebellum and overall brain that are different from each other and from Ts65Dn. These models can help to identify the contributions of genes from different regions of the chromosome on this and other aspects of brain development in trisomy.     

Discovery and genetic localization of Down syndrome cerebellar phenotypes using the Ts65Dn mouse

Down syndrome (DS) is the most common genetic cause of mental retardation and affects many aspects of brain development. DS individuals exhibit an overall reduction in brain size with a disproportionately greater reduction in cerebellar volume. The Ts65Dn mouse is segmentally trisomic for the distal 12-15 Mb of mouse chromosome 16, a region that shows perfect conserved linkage with human chromosome 21, and therefore provides a genetic model for DS. In this study, high resolution magnetic resonance imaging and histological analysis demonstrate precise neuro- anatomical parallels between the DS and the Ts65Dn cerebellum. Cerebellar volume is significantly reduced in Ts65Dn mice due to reduction of both the internal granule layer and the molecular layer of the cerebellum. Granule cell number is further reduced by a decrease in cell density in the internal granule layer. Despite these changes in Ts65Dn cerebellar structure, motor deficits have not been detected in several tests. Reduction in granule cell density in Ts65Dn mice correctly predicts an analogous pathology in humans; a significant reduction in granule cell density in the DS cerebellum is reported here for the first time. The candidate region of genes on chromosome 21 affecting cerebellar development in DS is therefore delimited to the subset of genes whose orthologs are at dosage imbalance in Ts65Dn mice, providing the first localization of genes affecting a neuroanatomical phenotype in DS. The application of this model for analysis of developmental perturbations is extended by the accurate prediction of DS cerebellar phenotypes.     

Netrin-1 Overexpression Protects Kidney from Ischemia Reperfusion Injury by Suppressing Apoptosis

Netrin-1, a diffusible laminin-related protein, is highly expressed in the kidney. However, the pathophysiological roles of netrin-1 in the kidney are unknown. To address this question directly, we used transgenic mice that overexpress chicken netrin-1 in the kidney. Netrin-1 overexpression was confirmed by real-time RT-PCR and Western blot analysis. Eight-week-old wild-type and transgenic mice were subjected to 26 minutes of renal ischemia followed by reperfusion for 72 hours. Wild-type mice developed more severe renal dysfunction by 24 hours than netrin-1 transgenic mice. Functional improvement was associated with better preservation of morphology, reduced cytokine expression, and reduced oxidative stress in the kidney of transgenic mice as compared with wild-type mice. In addition, both basal and reperfusion-induced cell proliferation were dramatically increased in transgenic kidneys as determined by Ki-67 staining. Interestingly, ischemia reperfusion induced a large increase in apoptosis in wild-type mice but not in netrin-1 transgenic mice that was associated with reduced caspase-3 activation in the transgenic kidney. These results suggest that netrin-1 protects renal tubular epithelial cells against ischemia reperfusion-induced injury by increasing proliferation and suppressing apoptosis.Netrin-1, a diffusible laminin-related protein, is highly expressed outside the nervous system; its most abundant expression is found in the kidney. However, the function of netrin-1 in tissues outside the nervous system is not clear. In recent studies using both in vitro and in vivo systems, netrin-1 was shown to play a role in angiogenesis,^1,2,3 cell migration,⁴ tissue morphogenesis,^5,6 tumor progression and growth,^7,8 and regulation of inflammation.⁹ Our most recent studies showed that administration of recombinant netrin-1 before renal ischemia reperfusion (I/R) injury prevented renal dysfunction and inflammation.¹⁰ Our studies also showed that netrin-1 protein was rapidly upregulated in renal tubular epithelial cells and could be detected in urine. However, the function of netrin-1 in tubular epithelial cells and how netrin-1 reduces renal dysfunction is not known.Netrin-1 has a major role during the development of the nervous system by mediating chemo-attraction and chemo-repulsion. However, netrin-1 has also been described as a survival factor. Indeed, netrin-1 prevents cell death by acting as a ligand of the dependence receptors DCC and UNC5H.^11,12,13 Netrin-1 binds to two families of receptors: DCC (DCC and neogenin) and UNC5H (UNC5A, UNC5B, UNC5C, and UNC5D). Netrin receptors are referred to as dependence receptors because these receptors have been shown to induce apoptosis in the absence of ligand (netrin).¹⁴ DCC, UNC5A, UNC5B, and UNC5C are all cleaved by caspase-3 in vitro, and mutation of the cleavage site strongly inhibits cell death in vitro and in vivo.¹² However, the mechanism for DCC or UNC5-induced apoptotic signaling is still largely unknown. Recently, the administration of netrin-1 to mice before I/R of the kidney and the brain was shown to suppress tissue injury.^10,15To determine the role of netrin-1 in renal tubular epithelial cell function and the mechanism of netrin-1 mediated protection against I/R injury of the kidney, we used mice that overexpress netrin-1 in the proximal tubular epithelial cells. Our results show that netrin-1 transgenic mice are resistant to I/R injury. This resistance was associated with reduced cytokine production, increased cell proliferation, and the suppression of apoptosis in tubular epithelial cells.     

An evaluation of exclusionary medical/psychiatric conditions in the definition of chronic fatigue syndrome

Background  

The diagnosis of chronic fatigue syndrome (CFS) in research studies requires the exclusion of subjects with medical and psychiatric conditions that could confound the analysis and interpretation of results. This study compares illness parameters between individuals with CFS who have and those who do not have exclusionary conditions.     

Criteria to define interruption of transmission of human cytomegalovirus from organ donor to recipient

In this review article, we consider results suggesting that transmission of human cytomegalovirus (HCMV) from a donor of a solid organ to an immunologically naive individual can be reduced. Two randomized controlled trials have been conducted recently, one of active immunization of recipients pretransplant and another of passive immunization with monoclonal antibodies specific for HCMV given at the time of transplant. Although the available data are encouraging—providing evidence of a reduction in the incidence of HCMV viraemia—they fall short of what would be required to prove definitively that transmission has been completely prevented. Here, we reflect on these studies and propose a set of 5 criteria, which, if satisfied in the future, could be taken as proof that active and/or passive immunization against HCMV effectively interrupts transmission of virus from the donor. We suggest that these criteria are considered when designing future randomized controlled trials.