Reduced performance of male and female athletes at 580 m altitude

Patients with craniocervical mandibular (TMD) disorders can present with tinnitus as a primary or secondary complaint. The embryology and functional anatomy of the middle ear, temporomandibular joint, muscles of mastication and associated tendons, ligaments, blood vessels, nerves and lymphatics was found to be helpful in establishing etiologic concepts which relate tinnitus to these temporomandibular disorders. In addition to etiologic concepts, treatment modalities are described. The authors relate their experiences as well as those of others with different patient populations.     

Influence of maternal bodyweight on size, conformation and survival of newborn lambs

Although body condition score was not significantly different between light (<55 kg, n = 6) and heavy (> or =60 kg, n = 7) ewes at mating, it declined between Day 30 and Day 90 of gestation in light but not heavy ewes, and remained lower up to term. All ewes bore twins, delivered near term (Days 144-146) by Caesarean section. One lamb was immediately placed into a warm (30 degrees C; WD) and its twin into a cool (15 degrees C; CD) ambient temperature, and tissues were sampled at 0.5 h or 6 h. All CD lambs born to light ewes exhibited hypothermia and/or respiratory failure and did not survive longer than 30 min; these symptoms were not observed in their WD twins or any lamb born to heavy ewes. Total lamb birth weight, placental weight and fetal cotyledonary weight were lower with light than with heavy ewes. Lambs born to light ewes had less perirenal adipose tissue and smaller liver, heart, kidneys, brain, adrenals and thyroid, although their heart, brain and pancreas represented a larger proportion of total bodyweight; pancreas weight was similar to that in lambs born to heavy ewes. Hence, maternal bodyweight critically influences placental weight and lamb size and survival after birth.     

The natural history of great toe amputations

The purpose of this study is to report the prevalence of reamputation following resection of the great toe and first ray in adults with diabetes. We abstracted the medical records of 90 diabetic great-toe and first-ray amputees admitted between 1981 and 1991. The most common etiologies of initial amputations were ulcer with soft tissue infection (39%), ulcer with osteomyelitis (32%), and puncture wounds (12%). Sixty percent of all patients had a second amputation, 21% had a third, and 7% had a fourth. Fifteen percent of the patients who had a second amputation had it contralaterally. Seventeen percent subsequently underwent a below-knee amputation and 11% had a Transmetatarsal amputation on the same extremity, 3% had a below-knee amputation, and 2% a transmetatarsal amputation contralaterally. The mean time from the first to the second amputation was approximately 10 months. The results of this study suggest that a large proportion of patients undergoing an amputation at the level of the great toe or first ray have subsequent amputations in the first year following the initial procedure. Additionally, it appears that the contralateral foot may be at significant risk for distal amputation following resection of the hallux or first day.     

The six N-linked carbohydrates of the lutropin/choriogonadotropin receptor are not absolutely required for correct folding, cell surface expression, hormone binding, or signal transduction

Using two separate methods, we have determined that all six potential sites for N-linked glycosylation on the rat lutropin/choriogonadotropin receptor (rLHR) contain carbohydrates. The functional roles of the carbohydrates were analyzed initially through the use of two nonglycosylated receptor mutants rLHR(N(77,152,173,269,277,291)Q) and rLHR(N(77,152,269,277,291)Q;T(175)A). Although Western blot analyses demonstrated both mutant receptors to be stably expressed, little or no hCG binding activity could be detected in detergent solubilized extracts of 293 cells expressing either nonglycosylated LHR mutant. Although this loss of hCG binding was concluded to be due to misfolding, it was unknown whether this misfolding was due to the absence of carbohydrates or to the multiple amino acid substitutions that had been introduced into the polypeptide. To differentiate between these possibilities, hCG binding assays were performed with nonglycosylated receptors obtained after tunicamycin treatment of cells expressing the wild-type rLHR. Even though these wild-type receptors were confirmed to be devoid of all N-linked carbohydrates by Western blots, they were found to bind hCG with a normal high affinity. In addition, tunicamycin-derived, nonglycosylated LHRs were present at the cell surface and exhibited a phenotype consistent with mature receptors due to their capability to mediate hCG-stimulated cAMP production as well as bind oLH with high affinity. These results indicate that the loss of high affinity hormone binding by rLHR(N(77,152,173,269,277,291)Q) and rLHR(N(77,152,269,277,291)Q;T(175)A) is simply due to the collective amino acid substitutions rather than to the absence of carbohydrates. Therefore, N-linked carbohydrates are not absolutely required for the proper folding of the rLHR into a mature receptor capable of binding hormone and signaling. These results are in marked contrast to the follitropin receptor (FSHR), a very similar receptor which has been shown to strictly require N-linked carbohydrates for folding of the nascent protein.     

A gene for autosomal recessive symmetrical spastic cerebral palsy maps to chromosome 2q24-25

Cerebral palsy has an incidence of approximately 1/500 births, although this varies between different ethnic groups. Genetic forms of the disease account for approximately 1%-2% of cases in most countries but contribute a larger proportion in populations with extensive inbreeding. We have clinically characterized consanguineous families with multiple children affected by symmetrical spastic cerebral palsy, to locate recessive genes responsible for this condition. The eight families studied were identified from databases of patients in different regions of the United Kingdom. After ascertainment and clinical assessment, we performed a genomewide search for linkage, using 290 polymorphic DNA markers. In three families, a region of homozygosity at chromosome 2q24-q25 was identified between the markers D2S124 and D2S148. The largest family gave a maximum LOD score of 3.0, by multipoint analysis (HOMOZ). The maximum combined multipoint LOD score for the three families was 5.75. The minimum region of homozygosity is approximately 5 cM between the markers D2S124 and D2S2284. We have shown that a proportion of autosomal recessive symmetrical spastic cerebral palsy maps to chromosome 2q24-25. The identification of genes involved in the etiology of cerebral palsy may lead to improved management of this clinically intractable condition.     

Genomic organization, fine-mapping, and expression of the human islet-brain 1 (IB1)/c-Jun-amino-terminal kinase interacting protein-1 (JIP-1) gene

Islet-brain 1 (IB1), a regulator of the pancreatic beta-cell function in the rat, is homologous to JIP-1, a murine inhibitor of c-Jun amino-terminal kinase (JNK). Whether IB1 and JIP-1 are present in humans was not known. We report the sequence of the 2133-bp human IB1 cDNA, the expression, structure, and fine-mapping of the human IB1 gene, and the characterization of an IB1 pseudogene. Human IB1 is 94% identical to rat IB1. The tissue-specific expression of IB1 in human is similar to that observed in rodent. The IB1 gene contains 12 exons and maps to chromosome 11 (11p11.2-p12), a region that is deleted in DEFECT-11 syndrome. Apart from an IB1 pseudogene on chromosome 17 (17q21), no additional IB1-related gene was found in the human genome. Our data indicate that the sequence and expression pattern of IB1 are highly conserved between rodent and human and provide the necessary tools to investigate whether IB1 is involved in human diseases.