Emergence and scattering of multiple neurofibromatosis (NF1)-related sequences during hominoid evolution suggest a process of pericentromeric interchromosomal transposition

Type 1 neurofibromatosis (NF1) gene encodes for a member of the GTPase activating protein family and is considered to be a tumor suppressor gene. Its very high rate of de novo mutation in humans led us to study a specific feature of this gene: the presence of numerous NF1-related sequences. According to our results, the human genome contains at least 11 NF1-related sequences, nine of which are scattered near centromeric sequences of seven different chromosomes. These NF1-related sequences, whose extent is quite varied according to loci, are unprocessed copies of the NF1 gene, and bear numerous mutations. A phylogenetic analysis of the six largest sequences indicates that they are all derived from a common ancestor, which would have appeared 22-33 million years ago, and was subsequently duplicated several times during hominoid evolution. The most recent duplication and interchromosomal transposition occurred in the last million years suggesting that the process could still be ongoing. Intriguing similarities between the evolution of alpha- satellite DNA and NF1-related sequences suggest the involvement of a common genetic mechanism for the generation and pericentric spreading of these NF1 partial copies.      

Mechanical behavior of articular cartilage in shear is altered by transection of the anterior cruciate ligament

The flow-independent viscoelastic and equilibrium behaviors of canine articular cartilage were examined with time after transection of the anterior cruciate ligament. The equilibrium, transient, and dynamic shear behaviors of cartilage were studied in biaxial compression-torsion testing at two time periods after transection of the anterior cruciate ligament and at two sites on the femoral condyle, in order to test for differences between sites of frequent and less frequent contact. Water content also was measured in cartilage at sites corresponding to the areas of mechanical testing. Transection of the anterior cruciate ligament produced significant decreases in all measured moduli of articular cartilage tested in equilibrium and dynamic shear and in equilibrium compression; the values for these moduli were 61, 56, and 77% of the control values, respectively, beginning at 6 weeks following transection of the anterior cruciate ligament. There was evidence of increased energy dissipation of cartilage in shear, with a 13 and 35% increase in tan δ at 6 and 12 weeks after transection of the anterior cruciate ligament, respectively. Changes in the viscoelastic relaxation function of cartilage in shear also were evident at 12 weeks after surgery. In all tissue, there was a significant increase in hydration of approximately 4% at 6 or 12 weeks after surgery. There was little difference between the material parameters for areas considered to be in frequent and less frequent contact, with the exception of hydration, which was greater for areas of less frequent contact. The observed changes in material properties demonstrate that relatively short periods of joint instability result in significant changes in the flow-independent viscoelastic behavior of articular cartilage, as well as in the intrinsic stiffnesses in compression and shear.     

Alterations in the mechanical behavior of the human lumbar nucleus pulposus with degeneration and aging

This study tested the hypothesis that changes in the morphology and composition of the nucleus pulposus with age and degeneration have associated changes in its mechanical properties. A torsional shear experiment was used to determine viscoelastic shear properties of cylindrical samples of human nucleus pulposus with large ranges of grades of morphological degeneration (normal to severely degenerated) and ages (range: 16–88 years; average: 57 ± 21.5 years). Viscoclastic shear properties were determined from stress-relaxation and dynamic sinusoidal tests. A linear viscoelastic law with a variable-amplitude relaxation spectrum was used to model experimental behaviors of nucleus pulposus specimens. A statistically significant increase in the instantaneous and dynamic shear moduli was found with increasing age and grade of degeneration; the values for moduli ranged from 5.0 to 60 kPa. A significant decrease in tanδ was also detected; the values ranged from 0.43 to 0.33, indicating a decreased capacity for the nucleus pulposus to dissipate energy. The dynamic modulus and tanδ were also significantly affected by frequency. It was generally concluded that the nucleus pulposus undergoes a transition from “fluid-like” behavior to more “solid-like” behavior with aging and degeneration.     

Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.      

Medico-legal aspects of malignant mesothelioma

The object of this investigation was to discuss medico-legal aspects of malignant mesothelioma in relation to social insurance legislation for occupational injuries and diseases in Norway. During the period 1960-79 the Cancer Registry of Norway recorded a total of 155 men and 35 women with malignant mesothelioma. However, only 21 men and no women were notified to the National Insurance Institution as occupational disease cases before 31 December 1979, in spite of the well established causal association between occupational asbestos exposure and the disease. The investigation is based on these 21 patients. The long latency period from first asbestos exposure until appearance of the disease and the short survival were evident in this study. Furthermore, the legislation and provisions for occupational injuries and diseases in Norway are obviously intended for occupational accidents, and consequently the legal assessment of patients with malignant mesothelioma was complicated. For those notified, the delay in notification was considerable, and only 50% were notified before death. Delay in the claim procedure was also substantial, and few patients survived the claim procedure period. The decisions were not consistent, particularly decisions regarding "the year of injury" and appeared to have been more restrictive during recent years. One of the 21 cases was not accepted as occupational disease, because domestic exposure was considered more probable than occupational exposure.     

Osteoarthritic changes in the biochemical composition of thumb carpometacarpal joint cartilage and correlation with biomechanical properties

The biochemical composition and biomechanical properties of articular cartilage from 53 human thumb carpometacarpal (CMC) joints from cadavers aged 20 to 79 years were measured and studied in normal, mildly fibrillated, and advanced osteoarthritic (OA) joints. Statistical analyses were performed to determine the correlations between the compositional measures and biomechanical properties. For these CMC joint tissues we found that water content increased, proteoglycan content decreased, and collagen content per dry weight remained unaltered with progression of OA degeneration. We also found that with disease progression, as defined by an OA staging score, the aggregate modulus (ie, compressive stiffness) decreased, along with an unexpected moderate decrease in permeability. This latter finding appears to be specific to CMC cartilage degeneration since articular cartilage from knees and hips generally demonstrates an increase in permeability with water content and OA score. Correlations between biochemical composition and biomechanical properties were found to be stronger in joints with OA than in joints without OA. This finding suggests that OA changes in biochemical composition, relative to baseline normal values, directly affect the biomechanical properties of cartilage, even though the baseline compositional values themselves do not directly determine the magnitude of the biomechanical properties in normal tissue.     

ANTIBIOTIC RESISTANCE PATTERN OF ISOLATES FROM WOUND AND SOFT TISSUE INFECTIONS

Two-hundred and eighty bacterial isolates from wound and soft tissue infections were studied for species identification and antibiotic resistance pattern. Amongst them 122 isolates were from community acquired infection and 158 were from nosocomial infections. The common community acquired pathogens were Staphylococcus aureus (67.8%) and Streptococcus pyogenes (10.7%), whereas Staphylococcus aureus (60.1%) and E. Coli (8.9%) were common in nosocomial infection. Only two anaerobes (Cl perfringens) were isolated. Penicillin resistance was found to be 87% and 92% for Staphylococccus aureus in community acquired and noscomial infections respectively. 85% of Proteus isolates were resistant to ampicillin. There was relatively lower level of resistance by all isolates to cefotaxime. Gentamicin showed higher rate of resistance than netilmicin and amikacin. Resistance of E. coli isolates to fluoroquinolones being 79% for norfloxacin, 81% for ciprofloxacin and 60% for ofloxacin. The study showed a higher resistance of methicillin resistant Staphylococcus aureus (MRSA) to other antibiotics. Amikacin and ofloxacin were the best recommended drugs for empirical therapy for all organisms, the susceptibility rate being 80.7% and 80.4%.KEY WORDS: Antibiotic resistance, Soft tissue infections, Wound infections     

再发性低血糖对幼鼠脑内GLUT1及GLUT3表达的影响

目的观察再发性低血糖后脑内葡萄糖转运蛋白1(glucose transporter 1,GLUT1)及葡萄糖转运蛋白3(GLUT3)表达的变化,从而探讨无症状低血糖的发生机制。方法将80只15日龄野生型小鼠随机分为正常对照组及低血糖组,每组40只。低血糖组给予正规胰岛素腹腔注射3次,每次剂量为5U/kg,对照组注射等体积生理盐水。两组分别在最后1次注射后12、24、48及72 h处死小鼠取脑组织(每组每时间点10只),应用免疫组化方法观察小鼠脑内GLUT1及GLUT3表达的变化。结果低血糖后脑内微血管上GLUT1表达有增加趋势,皮质增加高于海马,72 h皮质GLUT1表达显著高于对照组;低血糖后48、72 h皮质及海马GLUT3表达均显著高于相应对照组。结论再发性低血糖后脑内GLUT1及GLUT3适应性增高,这种适应既能节省神经元的能量代谢,但也能削减神经元对低血糖的反应。