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Biomedical subjects

S Bass

Publications and source records attributed to S Bass.

At least 19 recordsLinked to original sources
PubMed2006

Typical and atypical trafficking pathways of Ad5 penton base recombinant protein: implications for gene transfer.

The adenovirus (Ad) penton base protein facilitates viral infection by binding cell surface integrins, triggering receptor-mediated endocytosis and mediating endosomal penetration. Given these multiple functions, recombinant penton base proteins have been utilized as non-viral vehicles for gene transfer by our lab and others. Although we have previously demonstrated that penton base-derived vectors undergo integrin-specific binding and cell entry, less than desirable levels of gene expression have led us to re-evaluate the recombinant penton base as an agent for gene delivery. To do so, we have examined here the intracellular trafficking of an Ad serotype 5 (Ad5) recombinant penton base protein (PB). Here, we not only observed that PB utilizes a similar, typical trafficking pathway of whole Ad, but also found that PB entered HeLa cells through pathways not yet identified as contributing to cell entry by the whole virus. We show by high-resolution confocal microscopy and biochemical methods that binding to alphav-integrins is a requirement for cell entry, but that early internalization stages did not substantially pass through clathrin-positive and early endosomal compartments. Moreover, a subpopulation of internalized protein localized with caveolin-positive compartments and Golgi markers, suggesting that a certain percentage of proteins pass through non-clathrin-mediated pathways. Similar to the virus, trafficking toward the nucleus was affected by disruption of microtubules and dynein. The majority of penton base molecules avoided the lysosome while facilitating early vesicle release of low molecular weight dextran molecules. In further support of a vesicle escape capacity, a subpopulation of internalized penton base appeared to enter the nucleus, as observed by high-resolution confocal microscopy and cell fractionation. As a confirmation of these findings, we demonstrate that a recombinant penton base facilitated cytosolic entry of an siRNA molecule as observed by RNA interference of a marker gene. Based on our findings here, we suggest that whereas soluble penton base proteins may enter cells through clathrin- and non-clathrin-mediated pathways, vesicle escape and nuclear delivery appear to be supported by a clathrin-mediated pathway. As our previous efforts have focused on utilizing recombinant penton base proteins as delivery agents for therapeutics, these findings allow us to evaluate the use of the penton base as a cell entry and intracellular trafficking agent, and may be of interest concerning the development of vectors for efficient delivery of therapeutics to cells.

Capsid Proteins↗
PubMed2001

The oculocardiac reflex in a congenitally anophthalmic child.

We report a case of reflex bradycardia due to ophthalmic surgical stimulus in a congenitally anophthalmic child. Although the oculocardiac reflex has been previously reported from the empty orbit following enucleation, we are unaware of other cases involving a congenital absence of the globe.

Anophthalmos↗
PubMed2001

Anaesthetic management of a patient with myotonic dystrophy.

A 13-year-old boy with myotonic dystrophy underwent insertion of a percutaneous gastrostomy feeding tube under general anaesthesia. We used a laryngeal mask airway and a spontaneously breathing technique with propofol total intravenous anaesthesia. Postoperative vomiting and aspiration, 12 h after the procedure, subsequently required intubation and ventilation. We discuss the anaesthetic management of this case and review the features of the disease to be considered when contemplating anaesthesia in such patients.

Adolescent↗
PubMed2001

The evidence that exercise during growth or adulthood reduces the risk of fragility fractures is weak.

There has never been, and will never be, a randomized double-blind placebo-controlled trial demonstrating that exercise in youth, adulthood or old age reduces fragility or osteoporosis-related fractures in old age. The next level of evidence, a randomized, controlled but unblinded study with fractures as an end-point is feasible but has never been done. The basis for the belief that exercise reduces fractures is derived from lower levels of 'evidence', namely, retrospective and prospective observation cohort studies and case-control studies. These studies are at best hypothesis generating, never hypothesis testing. They are all subject to many systematic biases and should be interpreted with extreme scepticism. Surrogate measures of anti-fracture efficacy are the next level of evidence, such as the demonstration of a reduction in risk factors for falls, a reduction in falls, a reduction in fractures due to falls, an increase in peak bone size and mass, prevention of bone loss in midlife and restoration of bone mass and structure in old age.

Adolescent↗
PubMed2001

Does gymnastics training inhibit growth of females?

OBJECTIVE: The increasingly dominant performance of smaller-sized female gymnasts and increased magnitude of training beginning at an early age have prompted public and medical concerns, especially from an auxological perspective. The objective of this review is to determine if gymnastics training inhibits growth of females. DATA SOURCES: An extensive research of MedLine (PubMed interface) along with cross-referencing was conducted using the Text and MeSH words "gymnastics" in combination with "growth," "maturation," "body height," "body weight," and "growth plate." Our analysis is limited to English articles only. STUDY SELECTION: All published studies that included data related to the research questions were included. MAIN RESULTS: Although data from three historical cohort studies indicate that female gymnasts are short even before they begin training, clinical reports and cohort studies do suggest that some female gymnasts experience attenuated growth during training followed by catch-up growth during periods of reduced training or retirement. There is conflicting evidence whether the "catch-up" is complete. There were no studies reporting prevalence or incidence of inadequate growth. Three cohort studies provide evidence of reduced growth but training was not partitioned from other confounding factors in the gymnastics environment. Although there is a paucity of studies examining the link of dietary practices with diminished growth in female gymnasts, a review of related dietary literature indicates the potential for insufficient energy and nutrient intake among female gymnasts. CONCLUSIONS: Elite level or heavily involved female gymnasts may experience attenuated growth during their years of training and competition followed by catch-up growth during reduced training schedules or the months following retirement. However, a cause-effect relation between gymnastics training and inadequate growth of females has not been demonstrated.

Adolescent↗
PubMed2000

DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae.

Here we determine the complete genomic sequence of the gram negative, gamma-Proteobacterium Vibrio cholerae El Tor N16961 to be 4,033,460 base pairs (bp). The genome consists of two circular chromosomes of 2,961,146 bp and 1,072,314 bp that together encode 3,885 open reading frames. The vast majority of recognizable genes for essential cell functions (such as DNA replication, transcription, translation and cell-wall biosynthesis) and pathogenicity (for example, toxins, surface antigens and adhesins) are located on the large chromosome. In contrast, the small chromosome contains a larger fraction (59%) of hypothetical genes compared with the large chromosome (42%), and also contains many more genes that appear to have origins other than the gamma-Proteobacteria. The small chromosome also carries a gene capture system (the integron island) and host 'addiction' genes that are typically found on plasmids; thus, the small chromosome may have originally been a megaplasmid that was captured by an ancestral Vibrio species. The V. cholerae genomic sequence provides a starting point for understanding how a free-living, environmental organism emerged to become a significant human bacterial pathogen.

Base Sequence↗
PubMed2000

Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39.

The genome sequences of Chlamydia trachomatis mouse pneumonitis (MoPn) strain Nigg (1 069 412 nt) and Chlamydia pneumoniae strain AR39 (1 229 853 nt) were determined using a random shotgun strategy. The MoPn genome exhibited a general conservation of gene order and content with the previously sequenced C.trachomatis serovar D. Differences between C.trachomatis strains were focused on an approximately 50 kb 'plasticity zone' near the termination origins. In this region MoPn contained three copies of a novel gene encoding a >3000 amino acid toxin homologous to a predicted toxin from Escherichia coli O157:H7 but had apparently lost the tryptophan biosyntheis genes found in serovar D in this region. The C. pneumoniae AR39 chromosome was >99.9% identical to the previously sequenced C.pneumoniae CWL029 genome, however, comparative analysis identified an invertible DNA segment upstream of the uridine kinase gene which was in different orientations in the two genomes. AR39 also contained a novel 4524 nt circular single-stranded (ss)DNA bacteriophage, the first time a virus has been reported infecting C. pneumoniae. Although the chlamydial genomes were highly conserved, there were intriguing differences in key nucleotide salvage pathways: C.pneumoniae has a uridine kinase gene for dUTP production, MoPn has a uracil phosphororibosyl transferase, while C.trachomatis serovar D contains neither gene. Chromosomal comparison revealed that there had been multiple large inversion events since the species divergence of C.trachomatis and C.pneumoniae, apparently oriented around the axis of the origin of replication and the termination region. The striking synteny of the Chlamydia genomes and prevalence of tandemly duplicated genes are evidence of minimal chromosome rearrangement and foreign gene uptake, presumably owing to the ecological isolation of the obligate intracellular parasites. In the absence of genetic analysis, comparative genomics will continue to provide insight into the virulence mechanisms of these important human pathogens.

Animals↗
PubMed2000

Short stature and delayed puberty in gymnasts: influence of selection bias on leg length and the duration of training on trunk length.

BACKGROUND: Delays in bone age, the onset of puberty, and skeletal growth in gymnasts could be, in part, the reason for an interest in gymnastics, rather than being the result of vigorous exercise. We hypothesized that short stature and delayed bone age are present at the start of gymnastics, and training delays growth, producing short stature, even after retirement. METHODS: Sitting height and leg length were measured in 83 active female gymnasts, 42 retired gymnasts, and 154 healthy control subjects. Results were expressed as age-specific SD scores (mean +/- SEM). RESULTS: In the cross-sectional data, active gymnasts had delayed bone age (1.3 +/- 0.1 years), reduced height -1.32 +/- 0.08 SD, sitting height -1.24 +/- 0.09 SD, and leg length, -1.25 +/- 0.08 SD (all P <.001). However, in those training for less than 2 years, the deficit was confined to leg length (-0.8 +/- 0.2 SD). During 2 years of follow-up of 21 gymnasts, only the deficit in sitting height worsened (by 0.4 +/- 0.1 SD). In 13 gymnasts followed up in the immediate 12 months after retirement, sitting height accelerated, resulting in a lessening of the deficit in sitting height by 0.46 +/- 0.14 SD (P <.01). Adult gymnasts who had been retired for 8 years had no deficit in sitting height, leg length, or menstrual dysfunction. CONCLUSIONS: Short stature in active gymnasts is partly due to selection of individuals with reduced leg length. Reduced sitting height is likely to be acquired but is reversible with cessation of gymnastics. A history of gymnastic training does not appear to result in reduced stature or menstrual dysfunction in adulthood.

Adolescent↗
PubMed2000

Heterogeneity in the growth of the axial and appendicular skeleton in boys: implications for the pathogenesis of bone fragility in men.

Men with spine fractures have reduced vertebral body (VB) volume and volumetric bone mineral density (vBMD). Men with hip fractures have reduced femoral neck (FN) volume and vBMD, site-specific deficits that may have their origins in growth. To describe the tempo of growth in regional bone size, bone mineral content (BMC), and vBMD, we measured bone length, periosteal and endocortical diameters, BMC, and vBMD using dual-energy X-ray absorptiometry in 184 boys aged between 7 and 17 years. Before puberty, growth was more rapid in the legs than in the trunk. During puberty, leg growth slowed while trunk length accelerated. Bone size was more advanced than BMC in all regions, being approximately 70% and approximately 35% of their predicted peaks at 7 years of age, respectively. At 16 years of age, bone size had reached its adult peak while BMC was still 10% below its predicted peak. The legs accounted for 48%, whereas the spine accounted for 10%, of the 1878 g BMC accrued between 7 and 17 years. Peripubertal growth contributed (i) 55 % of the increase in leg length but 78% of the mineral accrued and (ii) 69% of the increase in spine length but 87% of the mineral accrued. Increased metacarpal and midfemoral cortical thickness was caused by respective periosteal expansion with minimal change in the endocortical diameter. Total femur and VB vBMD increased by 30-40% while size and BMC increased by 200-300%. Thus, growth builds a bigger but only slightly denser skeleton. We speculate that effect of disease or a risk factor during growth depends on the regions maturational stage at the time of exposure. The earlier growth of a regions size than mass, and the differing growth patterns from region to region, predispose to site-specific deficits in bone size, vBMD, or both. Regions further from their peak may be more severely affected by illness than those nearer completion of growth. Bone fragility in old age is likely to have its foundations partly established during growth.

Absorptiometry, Photon↗
PubMed1999

Mepivacaine: its pharmacological effects and their relationship to analytical findings in the horse.

Mepivacaine is a local anaesthetic drug that is widely used in equine medicine and is classified by the Association of Racing Commissioners International (ARCI) as a Class 2 foreign substance that may cause regulators to impose significant penalties if residues are identified in post-race urine samples. Therefore, an analytical/pharmacological database was developed for this agent and its metabolites. Using an abaxial sesamoid local anaesthetic model, it was determined that the highest no-effect dose (HNED) for its local anaesthetic effect was 2 mg. Using enzyme-linked immunosorbent assay (ELISA) screening, it was determined that subcutaneous (s.c.) administration of the HNED of mepivacaine to eight horses yielded a peak urinary concentration of apparent mepivacaine of 63 ng/mL 2 h after injection. The major identified metabolite recovered from equine urine after dosing with mepivacaine is 3-hydroxymepivacaine. Therefore, 3-hydroxymepivacaine was synthesized, purified and characterized, and a quantitative mass spectrometric method was developed for this metabolite as isolated from horse urine. Following subcutaneous injection of the HNED of mepivacaine, the concentration of 3-hydroxymepivacaine recovered from horse urine reached a peak of about 64.6 ng/mL at 4 h after administration as measured by GC/MS. The concentration of mepivacaine or its metabolites after administration of a HNED dose are detectable by mass spectral techniques. Within the limits of this research, the study suggests that recovery of concentrations less than about 65 ng/mL of 3-hydroxymepivacaine from post-race urine samples may not be associated with a recent LA effect of mepivacaine.

Anesthetics, Local↗
PubMed1999

Solitary spinal intramedullary abscess caused by Nocardia asteroides.

Nocardial spinal cord abscesses are extremely rare. Only three have been reported, one each from Austria, Thailand, and the United States. All three patients also had extraneurologic nocardiosis. We present the first case of an intramedullary abscess caused by Nocardia asteroides and without concomitant extraneurologic nocardiosis. It is also the first such abscess in a living human being to be diagnosed by both magnetic resonance imaging and tissue culture. Resolution was complete after treatment.

Abscess↗
PubMed1999

The differing tempo of growth in bone size, mass, and density in girls is region-specific.

The differing tempo and direction of growth of the periosteal and endocortical surfaces, and the differing tempo of growth of the axial and appendicular skeleton, may predispose to regional deficits in bone size, bone mineral content (BMC), and volumetric bone mineral density (vBMD). These traits were measured during 2 years by dual x-ray absorptiometry in 109 girls. By 7 years of age, bone size was approximately 80% of its maturational peak, and BMC was approximately 40% of its peak. Before puberty, the legs grew more rapidly than the trunk. During puberty, the growth spurt was truncal. Between 7 and 17 years, femoral and lumbar spine BMC increased by 50-150% because bone size increased. vBMD increased by 10-30%. Thus, growth builds a bigger, but only moderately denser, skeleton. Regions growing rapidly, or distant from their peak, may be more severely affected by illness than those growing slowly or nearer completion of growth. Depending on the age of exposure to disease, deficits may occur in limb dimensions (prepuberty), spine dimensions (early puberty), or vBMD by interference with mineral accrual (late puberty). As vBMD is independent of age before puberty, the position of an individual's vBMD in the population distribution is established early in life. Bone fragility in old age may have its foundations in growth.

Adolescent↗
PubMed1999

Effects of high-impact exercise on ultrasonic and biochemical indices of skeletal status: A prospective study in young male gymnasts.

Physical activity has been proposed as one strategy to enhance bone mineral acquisition during growth. The aim of this study was to determine whether frequent impact loading associated with gymnastics training confers a skeletal benefit on pre- and peripubertal male gymnasts. We measured broadband ultrasonic attenuation (BUA, dB/MHz) at the calcaneus (CBUA); ultrasound velocity (m/s) at the calcaneus (CVOS), distal radius (RVOS) and phalanx (PVOS); serum osteocalcin (OC); total alkaline phosphatase (ALP) and insulin-like growth factor-I (IGF-I) every 3-4 months over an 18-month period in elite male gymnasts and matched normoactive controls (pubertal stage </=2). Ground reaction forces of common gymnastics maneuvers were determined using a force platform and loading histories of the upper and lower extremities approximated from video recordings. Ultrasound results were expressed as a standardized score (Z score) adjusted for age, height, and weight. At baseline, no differences were detected between the gymnasts (n = 31) and controls (n = 50) for CBUA, although ultrasound velocity at each site was higher in the gymnasts (0.6-1.5 SD) than the predicted mean in controls (p </= 0. 001). Over 18 months, CBUA Z scores increased significantly in the gymnasts from baseline (0.3 vs. 1.0, p < 0.05, n = 18). In contrast, ultrasound velocity did not increase in either group, although CVOS and RVOS remained significantly higher in gymnasts compared with controls (range p < 0.01 and < 0.001). No differences between groups were found for OC, ALP, or IGF-I at any time. Gymnastics training was associated with on average 102 and 217 impacts per session on the upper and lower extremities, respectively, with peak magnitudes of 3.6 and 10.4 times body weight. These results suggest that frequent high-impact, weight-bearing exercise during the pre and peripubertal period may enhance the mechanical competence of the skeleton, perhaps offering an important strategy for osteoporosis prevention if the benefits are maintained.

Body Constitution↗
PubMed1999

Sports participation, sports injuries and osteoarthritis: implications for prevention.

There is increasing concern that too much physical activity may lead to osteoarthritis. The continuous stress that physical activity places on the joints can result in microtrauma and degeneration of the articular cartilage. However, the onset of osteoarthritis appears to depend on the frequency, intensity and duration of physical activity. Research has shown that individuals of all ages can tolerate moderate amounts of exercise without adverse consequences or accelerated development of osteoarthritis. However, excessive participation in high impact sports, particularly over a long period of time and at an elite level, can increase the risk of developing osteoarthritis. Participants may also be at risk if they have abnormal joint anatomy or alignment, joint instability, underlying muscle weakness or imbalance, or if they are overweight and engage in significant amounts of exercise. Individuals who have experienced sports injuries to joints, or macrotrauma, may also be at risk of accelerated development of osteoarthritis. Certain types of surgery for the treatment of severe sports injuries, particularly to the knee, also appear to be associated with an increased risk. If surgery to the knee is required, continuous passive motion is an ideal form of rehabilitative treatment, as it promotes healing of the articular cartilage, ligaments and tendons. Moreover, athletes who have undergone surgery should return slowly to sporting activities to ensure they do not place too much stress on their injured joint(s). Further research into the causes of osteoarthritis is required; in particular, prospective and retrospective cohort studies are needed to confirm the association between exposure to risk factors and the development of osteoarthritis.

Animals↗
PubMed1998

Structure-function study of the extracellular domain of the human IFN-alpha receptor (hIFNAR1) using blocking monoclonal antibodies: the role of domains 1 and 2.

We have performed a structure-function analysis of extracellular domain regions of the human IFN-alpha receptor (hIFNAR1) using mAbs generated by immunizing mice with a soluble hIFNAR1-IgG. Five mAbs described in this study recognize different epitopes as determined by a competitive binding ELISA and by alanine substitution mutant analyses of the hIFNAR1-IgG. Two mAbs, 2E1 and 4A7, are able to block IFN-stimulated gene factor 3 (ISGF3) formation and inhibit the antiviral cytopathic effect induced by several IFN-alpha (IFN-alpha 2/1, -alpha 1, -alpha 2, -alpha 5, and -alpha 8). None of these anti-IFNAR1 mAbs were able to block activity of IFN-beta. mAb 4A7 binds to a domain 1-hIFNAR1-IgG but not to a domain 2-hIFNAR1-IgG, which suggests that its binding region is located in domain 1. The binding of the most potent blocking mAb, 2E1, requires the presence of domain 1 and domain 2. The most critical residue for 2E1 binding is a lysine residue at position 249, which is in domain 2. These findings suggest that both domain 1 and domain 2 are necessary to form a functional receptor and that a region in domain 2 is important. IFN-beta recognizes regions of the hIFNAR complex that are distinct from those important for the IFN-alpha.

Alanine↗