Mapping of hereditary neuralgic amyotrophy (familial brachial plexus neuropathy) to distal chromosome 17q

Hereditary neuralgic amyotrophy with predilection for the brachial plexus (HNA) is an autosomal dominant disorder associated with recurrent, episodic, painful brachial neuropathies. Mildly dysmorphic facial features, including hypotelorism, long nasal bridge, and upslanting palpebral fissures, are present in affected persons in some pedigrees with HNA. To determine the chromosomal location of the HNA gene, we carried out genetic linkage studies with polymerase chain reaction-based DNA markers in two large pedigrees. Linkage to markers from the distal long arm of chromosome 17 was established.     

Interaction of the recombinant human methylpurine-DNA glycosylase (MPG protein) with oligodeoxyribonucleotides containing either hypoxanthine or abasic sites

Methylpurine-DNA glycosylases (MPG proteins, 3-methyladenine-DNA glycosylases) excise numerous damaged bases from DNA during the first step of base excision repair. The damaged bases removed by these proteins include those induced by both alkylating agents and/or oxidizing agents. The intrinsic kinetic parameters (k(cat) and K(m)) for the excision of hypoxanthine by the recombinant human MPG protein from a 39 bp oligodeoxyribonucleotide harboring a unique hypoxanthine were determined. Comparison with other reactions catalyzed by the human MPG protein suggests that the differences in specificity are primarily in product release and not binding. Analysis of MPG protein binding to the 39 bp oligodeoxyribonucleotide revealed that the apparent dissociation constant is of the same order of magnitude as the K(m) and that a 1:1 complex is formed. The MPG protein also forms a strong complex with the product of excision, an abasic site, as well as with a reduced abasic site. DNase I footprinting experiments with the MPG protein on an oligodeoxyribonucleotide with a unique hypoxanthine at a defined position indicate that the protein protects 11 bases on the strand with the hypoxanthine and 12 bases on the complementary strand. Competition experiments with different length, double-stranded, hypoxanthine-containing oligodeoxyribonucleotides show that the footprinted region is relatively small. Despite the small footprint, however, oligodeoxyribonucleotides comprising <15 bp with a hypoxanthine have a 10-fold reduced binding capacity compared with hypoxanthine-containing oligodeoxyribonucleotides >20 bp in length. These results provide a basis for other structural studies of the MPG protein with its targets.     

Outcomes of recipients of both bone marrow and solid organ transplants. A review

In this review we examine the clinical outcomes of patients who have received both bone marrow transplantation (BMT) and solid organ transplantation (SOT) and discuss the possible immunologic consequences of the dual transplants. We collected cases through a comprehensive literature search (MEDLINE database, English literature only) covering the years 1990 through 1997 and correspondence with the International Bone Marrow Transplant Registry. Our study selected case reports of patients who have undergone both bone marrow and solid organ transplants; cases in which bone marrow transplantation was undertaken as an adjunct ot induce or augment donor-specific tolerance in a recipient to the transplanted organ were excluded. Clinical characteristics included patient's demographic information, underlying disorders for each transplant, source of donor organ or tissue, time between transplants, and immunosuppressive regimens used to prevent graft-versus-host disease (GVHD) or graft rejection. Clinical outcomes included patient survival, complications of transplantation, and donor-specific tolerance that was experienced in many cases. Twenty-one cases of SOT after BMT and 7 cases of BMT after SOT were reviewed. Solid organ transplantations included lung, liver, cardiac, and kidney for a variety of BMT-related complications including GVHD, hepatic veno-occlusive disease, chronic renal failure, end-stage pulmonary disease, and severe cardiomyopathy. Bone marrow transplants were performed following SOT for aplastic anemia and hematologic malignancies. Clinical outcomes for patients who received both BMT and SOT were variable and depended on transplant indication and degree of histocompatibility. Prior bone marrow transplantation may tolerize for a subsequent organ transplant from the same donor. Conversely, severe GVHD may follow BMT from human leukocyte antigen (HLA)-matched donors following SOT. The favorable survival in this high-risk group of patients may represent a literature review bias (that is, an undetermined number of unsuccessful cases may not have been reported). Nonetheless, dual transplantation is clearly feasible in selected cases.     

Three-dimensional ultrasonography of the fetal distal lower extremity: normal and abnormal

The objective of this study was to compare two-dimensional and three-dimensional ultrasonographic evaluation of fetal distal lower extremities. Data from two-dimensional and three-dimensional ultrasonographic examinations from 40 distal lower extremities in 33 fetuses from a predominantly high-risk patient population were compared. Three-dimensional ultrasonography routinely provided three orthogonal planes (coronal, sagittal, and axial) for distal lower extremity evaluation. Specific features of distal lower extremity evaluation were not different using two-dimensional and three-dimensional ultrasonography. Rotation of the rendered volume provided assistance in assessing all but one of 40 distal lower extremities. Time from image acquisition to assessment for two views (coronal and sagittal) was longer with three-dimensional ultrasonography (8.2 min) than with two-dimensional ultrasonography (3.2 min). Confidence in the diagnosis of abnormal distal lower extremities was slightly improved using three-dimensional ultrasonography compared to two-dimensional ultrasonography. Pregnancy management was assisted in three of the four cases with isolated limb anomalies. In conclusion, three-dimensional ultrasonography improves the ability to evaluate the fetal distal lower extremity because of the multiplanar nature of volume assessment and the ability to rotate volume data sets. In addition, it provides assistance in counseling families, particularly for cases involving isolated limb anomalies.     

Increased epidermal growth factor-receptor protein in a human mesothelial cell line in response to long asbestos fibers

The burden of violence is born disproportionately by the youngest of our country. In this article, three important aspects of violence are discussed: premature death, violence recidivism, and violent criminality. The author emphasizes the role of the pediatrician in preventing these consequences.     

DNA damage triggers DRB-resistant phosphorylation of human p53 at the CK2 site

OBJECTIVE: To describe the comparative impact of current and preventive treatments on incidence of choroidal neovascularization (CNV) and severe vision loss in patients with bilateral soft drusen (BSD). DESIGN: Stochastic model. SETTING: US population. PATIENTS: Prevalence cohort of white patients 43 years or older with BSD. INTERVENTIONS: Application of prophylaxis of 10% to 50% efficacy to 1 or both eyes of patients with BSD, application of laser photocoagulation to eligible CNV lesions, or both. MAIN OUTCOME MEASURES: Proportion of patients with BSD after 10 years with unilateral and bilateral CNV and resultant unilateral and bilateral vision loss to visual acuity of 20/200 or worse. RESULTS: The natural history of patients with BSD generated by the model shows that 12.40% of these patients develop either unilateral or bilateral CNV within 10 years of their entry into the BSD prevalence cohort. Bilateral disease occurs in 3.86% of patients with BSD within 10 years. The proportion of patients with BSD becoming legally blind from CNV within 10 years is 2.54% if no treatment is performed. Current laser treatment for CNV decreases the proportion with legal blindness within 10 years to 2.24%. The addition of a preventive treatment of 10% efficacy applied bilaterally to the current laser treatment regimen decreases the proportion with legal blindness to 1.86%; a 25% effective preventive treatment decreases it to 1.34%. Comparatively, preventive treatment of 10% and 25% efficacy given to the fellow eye only after the first eye has developed CNV decreases the proportion of legally blind patients at 10 years only to 2.06% and 1.77%, respectively. All outcomes vary with sex and age at entry into the BSD cohort. CONCLUSIONS: Patients with BSD face a 12.40% risk of developing CNV within 10 years. The addition of even a modest (10% effective) bilateral preventive treatment to the current regimen for CNV would more than double the prevention of legal blindness in the BSD population relative to current laser treatment; a preventive treatment of 33% efficacy more than halves the rate of legal blindness caused by CNV. Preventive treatment given to the fellow eye only after the first develops CNV has substantially less impact.     

Colour Doppler ultrasound in the diagnosis, management and follow-up of a digital flexor pulley injury

We present the case of a rock climber with a rupture of the A3 flexor sheath pulley. The diagnosis was confirmed with Colour Doppler Imaging (CDI) and with B-mode ultrasound imaging, and the surgical repair was evaluated in the same way. Vertical displacement of the flexor tendon meant that using CDI measurements of the longitudinal movements was not possible. However, using computer analysis of digitized B-mode images from texture patterns identified in the tendons, the vertical and longitudinal components of movement during flexion were calculated. The repair of the pulley was shown to produce tendon movement ratios nearer those of the control digit of the opposite hand.     

Differential effects of nonselective nitric oxide synthase (NOS) and selective inducible NOS inhibition on hepatic necrosis, apoptosis, ICAM-1 expression, and neutrophil accumulation during endotoxemia

The roles of nitric oxide derived from either the constitutive endothelial NO synthase (eNOS or NOS3) or the inducible NOS (iNOS or NOS2) in hepatic injury during endotoxemia remain controversial. To investigate this further, rats received a bolus of lipopolysaccharide (LPS) following implantation of osmotic pumps containing one of two nonselective NOS inhibitors (NMA or NAME), one of two inducible NOS inhibitors (NIL or AG), or saline. The inhibitors were infused continuously into the liver via the portal vein. Treatment of LPS-injected rats with NMA and NAME resulted in 106 and 227% increases, respectively, in circulating hepatic enzyme levels compared to LPS-treated control rats. In contrast, infusion of the iNOS-selective inhibitors had no effect on the LPS-induced hepatic necrosis. In rats receiving NAME, LPS induced greater neutrophil infiltration and ICAM-1 expression than in the LPS + saline group, whereas NIL infusion did not. The increased hepatic necrosis and PMN infiltration in the LPS + NAME group was partially prevented by a simultaneous infusion of a liver-selective NO donor. Inhibition of PMN accumulation using an anti-ICAM-1 antibody or by PMN depletion using vinblastine pretreatment, however, did not reverse the increased necrosis with NAME infusion during endotoxemia. In contrast to the assessment for necrosis, increased apoptosis was observed in the livers of LPS-treated rats receiving infusions of either NAME or NIL, but not with LPS alone. These data indicate that NO produced by eNOS may be adequate to prevent necrosis by a mechanism independent of PMN, while induced NO appears to prevent apoptosis.     

Effects of dietary supplementation on nutrient digestion and the milk yield of intensively grazed lactating dairy cows

Fourteen midlactation Holstein cows were used in an 80-d study to examine supplementation strategies during intensive rotational grazing. Factors examined were the concentration of protein in the supplement [12 or 16% crude protein (CP) on a dry matter basis] and the amount of supplement offered (6.4 or 9.6 kg/d per cow). The supplement was offered in equal portions three times daily after milking. Pasture, composed of alfalfa (Medicago sativa) and orchardgrass (Dactylis glomerata), was divided into 27 0.16-ha paddocks that were grazed for 12 to 24 h. Intake of forage tended to increase as CP in the supplement increased but was unaffected by the amount of supplement offered. Intakes of organic matter and dry matter and the digestion of these nutrients in the total tract increased as CP in the supplement increased and as the amount of supplement increased. Ruminal pH and concentrations of volatile fatty acids were unaffected by treatments, but concentrations of NH3 N increased as CP in the supplement increased. An increase in CP resulted in a greater intake and flow of total N to the duodenum. The flow of microbial N to the duodenum and the efficiency of microbial protein synthesis were unaffected by treatment. Flows of total amino acids and essential amino acids to the duodenum tended to increase as CP in the supplement increased. Yield of fat-corrected milk and concentrations of fat and protein in milk were unaffected by treatment. These results suggested that the supply and digestion of nutrients in grazing dairy cows may be improved through an increase in the CP concentration of the supplement or the amount of supplement offered. However, effects on the yield of milk and milk components may be small.