A point mutation in the glycerol kinase gene associated with a deletion in the dystrophin gene in a familial X-linked muscular dystrophy: non-contiguous gene syndrome involving Becker muscular dystrophy and glycerol kinase loci

We report a family with an X-linked recessive muscular dystrophy characterised by exercise-induced myalgia, recurrent pigmenturia and mild proximal muscle involvement. Immunocytochemical and immunoblotting analysis in muscle, using the antibody directed against the rod domain of dystrophin, revealed a loss of immunoreactivity, but the immunolabelling using the antibodies directed against the COOH and NH2 domains of dystrophin were almost normal. The immunoreactions for alpha-sarcoglycan, gamma-sarcoglycan and beta-dystroglycan were normal. In the five male patients of this family with increased serum creatine kinase levels (from x8 to x50), mass spectrometry screening of the urine revealed a large increase in glycerol elimination which was quantified by enzymatic assay (from x14 to x39). An in-frame deletion of the dystrophin gene (exons 13-29) was found in the same five males and in three carrier females. All the deleted chromosomes also carried a missense mutation at nucleotide 947 of the Xp glycerol kinase (GK) gene resulting in a Thr to Met substitution at codon 278. These findings indicate that the two mutations cosegregate on the same chromosome in this family. This is the first reported case of two physically independent mutations, within the DMD and GK genes, which are contiguous but several hundred kilobases apart.     

The construction of M-ary (d,∞) codes that achieve capacityand have the fewest number of encoder states

The existence of 100% efficient (i.e., capacity-achieving) fixed-rate codes for input-constrained, noiseless channels is guaranteed provided the channel has rational capacity. A class of M-ary runlength-limited (M,d,∞) constraints was shown in previous work to have rational capacity. In this correspondence we present a code construction procedure for obtaining 100% efficient codes with the fewest number of encoder states for all (M,d,∞) constraints with rational capacity. The decoders are sliding-block decoders with sliding window size d+1     

Effect of Substructure on the Thermoelectric Power of aβ-Quenched ZrCrFe Alloy

β-quenching a Zr-1.15 wt％Cr-0.10 wt％Fe alloy produces a martensitic or a Widmanst(a|¨)tten transforma-tion morphology,or a mixture of the two,depending on the cooling rate.For the Widmanst(a|¨)tten structure,orthe mixed martensitic-Widmanst(a|¨)itten structure,a grain boundary phase is observed at most prior-β grainboundaries.X-ray line broadening analysis and the thermoelectric power(TEP)measurements of thesequenched samples show that not only the solubility of alloying elements in α-Zr matrix,but also substructure(microstrain,crystallite size and dislocation density)have an effect on TEP.Thus,TEP measurements are verywell suited for following the structural transformations taking place in Zr alloys during fabrication.     

Treatment of osteoporosis with bisphosphonates

Several bisphosphonates are effective for preventing bone loss associated with estrogen deficiency, glucocorticoid treatment, and immobilization, and for at least partially reversing bone loss in patients with postmenopausal osteoporosis and steroid-induced osteoporosis. The most promising of these agents are etidronate, alendronate, risedronate, and ibandronate. These drugs should have an important role in the prevention and treatment of osteoporosis; however, more research is needed regarding optimal doses and regimens (continuous versus intermittent, oral versus parenteral), comparisons with other agents, and their use in combination with other agents.     

Contribution of retinoic acid receptor beta isoforms to the formation of the conotruncal septum of the embryonic heart

To investigate the relative contribution of retinoic acid receptor (RAR)beta isoforms in conotruncal septation, RAR beta 1 and beta 3 were inactivated in the mouse. Mice lacking RAR beta 1 and beta 3 appear normal. Disruption of these isoforms in RAR alpha or RAR gamma null genetic backgrounds results in a high postpartum lethality. However, except for ocular defects found in RAR beta 1-3/RAR gamma compound mutants, the double null mutants display only abnormalities seen in single null mutants. This probably reflects a functional redundancy with other RARs, most notably with RAR beta 2 which is five- to sixfold more abundant than RAR beta 1 and beta 3 and whose domain of expression is largely overlapping. The conotruncal ridges form normally in retinoid X receptor (RXR)alpha/RAR beta compound mutants but fail to fuse, apparently as a result of excessive apoptosis of mesenchymal cells. Additionally, many cardiomyocytes in the conotruncal wall of these mutants appear necrotic. Although RAR beta 1 and beta 3 are expressed specifically in the conotruncal ridges, failure of fusion of these structures is not more frequent in RXR alpha/RAR beta 1-3 double null mutants than in RXR alpha single null mutants. Similarly, the disruption of the sole RAR beta 2 isoform in a RXR alpha null genetic background does not result in an increase of the frequency of conotruncal septum agenesis. However, this agenesis is fully penetrant in RXR alpha/RAR beta +/- mutants, which reflects distinct role of RXR alpha:RAR beta 1 (and beta 3) and RXR alpha:RAR beta 2 heterodimers in promoting the survival of conotruncal mesenchymal cells. Unexpectedly, we discovered that, in wild-type embryos, the conotruncal mesenchyme is a major site of morphogenetic cell death and that conotruncal myocytes are occasionally necrotic. Thus, excessive cell death in the conotruncus is a potential cause of ventricular septal defects in humans.     

Two new species of nematodes (Rhabditida: Diplogasteridae and Rhabditidae) parasites of Gryllodes laplatae (Orthoptera: Gryllidae) in Argentina

Cephalobium magdalensis n. sp. (Rhabditida: Diplogasteridae) found in Magdalena, Buenos Aires, and Cruznema lincolnensis n. sp. (Rhabditida: Rhabditidae) found in Lincoln, Buenos Aires, parasitizing the cricket Gryllodes laplatae (Orthoptera: Gryllidae) are described and illustrated. C. magdalensis n. sp. is characterized by having the excretory pore between the pseudobulb and the basal bulb and seven pairs of postanal papillae in the male. C. lincolnensis n. sp. can be distiguished by having meanly two pairs of preanal papillae, one pair of adanal papillae and six pairs of postanal papillae in the male.     

Entry of US medical school graduates into family practice residencies: 1997-1998 and 3-year summary

This is the 17th report prepared by the American Academy of Family Physicians (AAFP) on the percentage of each US medical school's graduates entering family practice residency programs. Approximately 16.6% of the 15,894 graduates of US medical schools between July 1996 and June 1997 were first-year family practice residents in October 1997, compared with 15.9% in 1996 and 14.6% in 1995. This is the highest percentage since this series of studies began in 1980-1981 (12.8%). Medical school graduates from publicly funded medical schools were almost twice as likely to be first-year family practice residents in October 1997 than were residents from privately funded schools, 19.8% compared with 11.8%. The Mountain region reported the highest percentage of medical school graduates who were first-year residents in family practice programs in October 1997 at 25.8%; the Middle Atlantic and New England regions reported the lowest percentages at 11.7% and 10.7%, respectively. Nearly half of the medical school graduates (48.1%) entering a family practice residency program as first-year residents in October 1997 entered a program in the same state where they graduated from medical school. The percentages for each medical school have varied substantially from year to year since the AAFP began reporting this information. This article reports the average percentage for each medical school for the last 3 years. Also reported are the number and percentage of graduates of colleges of osteopathic medicine who entered Accreditation Council for Graduate Medical Education-accredited family practice residency programs, based on estimates provided by the American Association of Colleges of Osteopathic Medicine.     

Phonetic profiles of toddlers with specific expressive language impairment (SLI-E)

Spontaneous language samples of 30 24-month-old toddlers diagnosed with Specific Expressive Language Impairment (SLI-E) were compared with samples produced by an age-matched group of 30 typically developing toddlers. Vocalization patterns, phonetic inventories, and syllable formation patterns were compared. Toddlers with SLI-E vocalized significantly less often than their typically developing peers, had proportionately smaller consonantal and vowel inventories, and used a more restricted and less mature array of syllable shapes. Although the mean incidence of phoneme usage varied significantly in all comparisons, profiles of consonant usage were similar between the two groups for initial phoneme usage, but considerably different for final consonant closure. Such patterns of vocal and phonetic behavior confirm earlier reports of phonetic delay in SLI-E, and suggest that nongrammatical factors contribute to the development of expressive language deficits in toddlers. We further propose a bidirectional model for the expressive deficits in SLI-E, in which the child's limited phonetic capacity interacts with propensities in caretaker interaction to further reduce opportunities for expressive language learning and practice.