Voltage-gated Ca2+ channel Ca(V)1.3 subunit expressed in the hair cell epithelium of the sacculus of the trout Oncorhynchus mykiss: cloning and comparison across vertebrate classes

Full-length sequence (>6.5 kb) has been determined for the Ca(V)1.3 pore-forming subunit of the voltage-gated Ca(2+) channel from the saccular hair cells of the rainbow trout (Oncorhynchus mykiss). Primary structure was obtained from overlapping PCR and cloned fragments, amplified by primers based on teleost, avian, and mammalian sources. Trout saccular Ca(V)1.3 was localized to hair cells, as evidenced by its isolation from an epithelial layer in which the hair cell is the only intact cell type. The predicted amino acid sequence of the trout hair cell Ca(V)1.3 is approximately 70% identical to the sequences of avian and mammalian Ca(V)1.3 subunits and shows L-type characteristics. The trout hair cell Ca(V)1.3 expresses a 26-aa insert in the I-II cytoplasmic loop (exon 9a) and a 10-aa insert in the IVS2-IVS3 cytoplasmic loop (exon 30a), neither of which is appreciably represented in trout brain. The exon 9a insert also occurs in hair cell organs of chick and rat, and appears as an exon in human genomic Ca(V)1.3 sequence (but not in the Ca(V)1.3 coding sequence expressed in human brain or pancreas). The exon 30a insert, although expressed in hair cells of chick as well as trout, does not appear in comparable rat or human tissues. Further, the IIIS2 region shows a splice choice (exon 22a) that is associated with the hair cell organs of trout, chick, and rat, but is not found in human genomic sequence. The elucidation of the primary structure of the voltage-gated Ca(2+) channel Ca(V)1.3 subunit from hair cells of the teleost, representing the lowest of the vertebrate classes, suggests a generality of sensory mechanism for Ca(V)1.3 across hair cell systems. In particular, the exon 9a insert of this channel appears to be the molecular feature most consistently associated with hair cells from fish to mammal, consonant with the hypothesis that the latter region may be a signature for the hair cell.     

Stem cells and neuropoiesis in the adult human brain

Stem cells in adult tissues have attracted a great deal of interest. These cells are self-renewing and can give rise to diverse progeny. An extraordinary finding was the presence of stem cells in the mature human brain. This tissue was previously believed incapable of generating new neurons, but neuropoiesis is now an established phenomenon in the adult brains of mammals, including human beings. This persistent neurogenesis has potential therapeutic applications for various neurological disorders as a source for tissue engraftment and as self-repair by a person's own indigenous population of pluripotent cells or biogenic by-products of their proliferation and differentiation.     

Reevaluating the role of phosphodiesterase inhibitors in the treatment of cardiovascular disease

First developed for clinical use in the late 1980s, the phosphodiesterase inhibitors were found to increase the levels of the ubiquitous second messenger cyclic adenosine monophosphate and could effect changes in vascular tone, cardiac function, and other cellular events. After several early studies using high doses of phosphodiesterase inhibitors in patients with severe heart failure suggested adverse consequences, they fell out of favor. However, recent investigations of phosphodiesterase inhibitors in patients with intermittent claudication have demonstrated profound benefits. Furthermore, these agents have proven useful in prevention of cerebral infarction and coronary restenosis, and their use in the treatment of heart failure is being reevaluated. The reemergence of phosphodiesterase inhibitors can be attributed to a better understanding of dosing and drug-specific pharmacology, the use of concomitant medications, and a recognition of unique ancillary properties; however, their use still requires caution.     

Acquired gastrointestinal fistulas: classification,etiologies, and imaging evaluation

Fistulas are abnormal communications between two epithelial-lined surfaces. Gastrointestinal fistulas encompass all such connections that involve the alimentary tract, and they can be congenital or acquired in nature. This review focuses on acquired gastrointestinal fistulas. Development of an acquired gastrointestinal fistula can greatly affect patient outcome, yet the clinical manifestations are often protean in nature and the etiology, elusive. Imaging plays an important role in the detection and management of acquired gastrointestinal fistulas. The more routine use of cross-sectional imaging (especially computed tomography and magnetic resonance imaging) has altered the standard sequence of radiologic evaluation for possible fistulas, but fluoroscopic studies remain a valuable complement, especially for confirming and defining the anomalous communications. In this review, a classification scheme for gastrointestinal fistulas is provided, major causes are discussed, and individual fistula types are elaborated with an emphasis on contemporary imaging approaches.     

Age-related total gray matter and white matter changes in normal adult brain. Part I: volumetric MR imaging analysis

BACKGROUND AND PURPOSE: A technique of segmenting total gray matter (GM) and total white matter (WM) in human brain is now available. We investigated the effects of age and sex on total fractional GM (%GM) and total fractional WM (%WM) volumes by using volumetric MR imaging in healthy adults. METHODS: Fifty-four healthy volunteers (22 men, 32 women) aged 20-86 years underwent dual-echo fast spin-echo MR imaging. Total GM, total WM, and intracranial space volumes were segmented by using MR image-based computerized semiautomated software. Volumes were normalized as a percentage of intracranial volume (%GM and %WM) to adjust for variations in head size. Age and sex effects were then assessed. RESULTS: Both %GM and %WM in the intracranial space were significantly less in older subjects (> or =50 years) than in younger subjects (<50 years) (P <.0001 and P =.02, respectively). Consistently, %GM decreased linearly with age, beginning in the youngest subjects. %WM decreased in a quadratic fashion, with a greater rate beginning only in adult midlife. Although larger GM volumes were observed in men before adjustments for cranium size, no significant differences in %GM or %WM were observed between the sexes. CONCLUSION: GM volume loss appears to be a constant, linear function of age throughout adult life, whereas WM volume loss seems to be delayed until middle adult life. Both appear to be independent of sex. Quantitative analysis of %GM and %WM volumes can improve our understanding of brain atrophy due to normal aging; this knowledge may be valuable in distinguishing atrophy of disease patterns from characteristics of the normal aging process.     

Training techniques to improve endurance exercise performances

In previously untrained individuals, endurance training improves peak oxygen uptake (VO2peak), increases capillary density of working muscle, raises blood volume and decreases heart rate during exercise at the same absolute intensity. In contrast, sprint training has a greater effect on muscle glyco(geno)lytic capacity than on muscle mitochondrial content. Sprint training invariably raises the activity of one or more of the muscle glyco(geno)lytic or related enzymes and enhances sarcolemmal lactate transport capacity. Some groups have also reported that sprint training transforms muscle fibre types, but these data are conflicting and not supported by any consistent alteration in sarcoplasmic reticulum Ca2+ ATPase activity or muscle physicochemical H+ buffering capacity. While the adaptations to training have been studied extensively in previously sedentary individuals, far less is known about the responses to high-intensity interval training (HIT) in already highly trained athletes. Only one group has systematically studied the reported benefits of HIT before competition. They found that >or=6 HIT sessions, was sufficient to maximally increase peak work rate (W(peak)) values and simulated 40 km time-trial (TT(40)) speeds of competitive cyclists by 4 to 5% and 3.0 to 3.5%, respectively. Maximum 3.0 to 3.5% improvements in TT(40) cycle rides at 75 to 80% of W(peak) after HIT consisting of 4- to 5-minute rides at 80 to 85% of W(peak) supported the idea that athletes should train for competition at exercise intensities specific to their event. The optimum reduction or 'taper' in intense training to recover from exhaustive exercise before a competition is poorly understood. Most studies have shown that 20 to 80% single-step reductions in training volume over 1 to 4 weeks have little effect on exercise performance, and that it is more important to maintain training intensity than training volume. Progressive 30 to 75% reductions in pool training volume over 2 to 4 weeks have been shown to improve swimming performances by 2 to 3%. Equally rapid exponential tapers improved 5 km running times by up to 6%. We found that a 50% single-step reduction in HIT at 70% of W(peak) produced peak approximately 6% improvements in simulated 100 km time-trial performances after 2 weeks. It is possible that the optimum taper depends on the intensity of the athletes' preceding training and their need to recover from exhaustive exercise to compete. How the optimum duration of a taper is influenced by preceding training intensity and percentage reduction in training volume warrants investigation.     

Advantages of real-time spatial compound sonography of the musculoskeletal system versus conventional sonography

OBJECTIVE: Spatial compound sonography is a method that obtains sonographic information from several different angles of insonation and combines them to produce a single image. By reducing speckle and improving definition of tissue planes, this method can potentially improve image quality in musculoskeletal sonography. The purpose of our study was to compare real-time spatial compound sonography with conventional high-resolution musculoskeletal sonography. MATERIALS AND METHODS: Thirty-four patients underwent sonography of the musculoskeletal system for a variety of indications. All patients were evaluated using conventional high-resolution sonography and real-time spatial compound sonography performed with a 12-5-MHz multifrequency linear array transducer. Conventional images and compound images depicting the same musculoskeletal structure were obtained in pairs. A total of 118 images (59 image pairs) were randomly assorted and reviewed on a computer monitor by three experienced sonologists working independently. The reviewers were unaware of the type of images they were evaluating. Image quality was rated using a 5-point scale. The image parameters evaluated were definition of tissue planes, speckle, other noise, and image detail. RESULTS: Analysis of variance revealed that real-time spatial compound sonography significantly improved definition of soft-tissue planes, reduced speckle and other noise, and improved image detail when compared with conventional high-resolution sonography (p < 0.0001 for all evaluated parameters). CONCLUSION: Real-time spatial compound sonography significantly improved sonographic image quality in the musculoskeletal system when compared with conventional high-resolution sonography. Because musculoskeletal sonography is highly dependent on image quality and tissue-plane definition, spatial compound sonography represents an important development.