Isolation and partial characterization of a phospholipase A2 from the venom of Crotalus scutulatus salvini

A phospholipase A₂ (EC 3.1.1.4) has been isolated and purified from the venom of Crotalus scutulatus salvini in 33% yield. The enzyme was homogeneous on polyacrylamide gel electrophoresis. The molecular weight of the enzyme was in the same range (30,000) whether determined by gel filtration or ultracentrifugation. On polyacrylamide gel electrophoresis, in the presence of sodium dodecyl sulphate and β-mercaptoethanol, the enzyme migrated into a single protein band with a mobility corresponding to about 14,000 molecular weight, indicating that the native enzyme was a dimer. Amino acid composition of the enzyme is reported. Two NH₂-amino acid terminals were found which indicates that the dissociable monomers of the native enzyme were non-identical. Antiserum against the purified enzyme completely inhibited the phospholipase A₂ activity and immunodiffusion of the antiserum against both purified phospholipase A₂ and crude venom of Crotalus scutulatus salvini gave single precipitin lines indicating a lack of contaminating antigens.     

Maternal fish consumption, hair mercury, and infant cognition in a U.S. Cohort

Fish and other seafood may contain organic mercury but also beneficial nutrients such as n-3 polyunsaturated fatty acids. We endeavored to study whether maternal fish consumption during pregnancy harms or benefits fetal brain development. We examined associations of maternal fish intake during pregnancy and maternal hair mercury at delivery with infant cognition among 135 mother-infant pairs in Project Viva, a prospective U.S. pregnancy and child cohort study. We assessed infant cognition by the percent novelty preference on visual recognition memory (VRM) testing at 6 months of age. Mothers consumed an average of 1.2 fish servings per week during the second trimester. Mean maternal hair mercury was 0.55 ppm, with 10% of samples > 1.2 ppm. Mean VRM score was 59.8 (range, 10.9-92.5). After adjusting for participant characteristics using linear regression, higher fish intake was associated with higher infant cognition. This association strengthened after adjustment for hair mercury level: For each additional weekly fish serving, offspring VRM score was 4.0 points higher [95% confidence interval (CI), 1.3 to 6.7]. However, an increase of 1 ppm in mercury was associated with a decrement in VRM score of 7.5 (95% CI, -13.7 to -1.2) points. VRM scores were highest among infants of women who consumed > 2 weekly fish servings but had mercury levels 相似文献   

IL-6 induces regionally selective spinal cord injury in patients with the neuroinflammatory disorder transverse myelitis

Transverse myelitis (TM) is an immune-mediated spinal cord disorder associated with inflammation, demyelination, and axonal damage. We investigated the soluble immune derangements present in TM patients and found that IL-6 levels were selectively and dramatically elevated in the cerebrospinal fluid and directly correlated with markers of tissue injury and sustained clinical disability. IL-6 was necessary and sufficient to mediate cellular injury in spinal cord organotypic tissue culture sections through activation of the JAK/STAT pathway, resulting in increased activity of iNOS and poly(ADP-ribose) polymerase (PARP). Rats intrathecally infused with IL-6 developed progressive weakness and spinal cord inflammation, demyelination, and axonal damage, which were blocked by PARP inhibition. Addition of IL-6 to brain organotypic cultures or into the cerebral ventricles of adult rats did not activate the JAK/STAT pathway, which is potentially due to increased expression of soluble IL-6 receptor in the brain relative to the spinal cord that may antagonize IL-6 signaling in this context. The spatially distinct responses to IL-6 may underlie regional vulnerability of different parts of the CNS to inflammatory injury. The elucidation of this pathway identifies specific therapeutic targets in the management of CNS autoimmune conditions.     

Amplatzer Angled Duct Occluder for Closure of Patent Ductus Arteriosus Larger than the Aorta in an Infant

Transcatheter closure of patent ductus arteriosus (PDA) by Amplatzer duct occluder is the treatment of choice. However, closure of very large ducts in infants with low weight is a challenge for the interventionalist because a large device may obstruct the aorta or left pulmonary artery. Difficulty is also encountered in advancing the device around the curve of the right ventricular outflow tract toward the pulmonary artery; this curve is tight, more or less at a right angle in infants, leading to kinking of the sheath, which increases fluoroscopic time. This is the first reported case of a very large PDA (8.7 mm), larger than the aorta (8.2 mm), successfully closed by an Amplatzer angled duct occluder in an infant weighing 5 kg.     

Neuropathological spectrum of Rasmussen encephalitis

BACKGROUND: Rasmussen encephalitis (RE) is a chronic epileptic disorder of unknown etiology, and is clinically characterized by progressive neurological deterioration, focal seizures often progressing to intractable epilepsy, cognitive decline and hemispheric atrophy. AIMS: We report the spectrum of neuropathological changes seen in RE, and discuss the evolutionary mechanisms of this disease. MATERIALS AND METHODS: Surgically obtained specimens from RE patients diagnosed during 2002-2004 at this institute were evaluated for the presence and extent of different histopathological features of RE. The H&E and immunohistochemistry stained slides were also evaluated for the type and distribution pattern of inflammatory infiltrates, along with a semiquantitative evaluation for the severity of inflammation. RESULTS: Four cases of RE were admitted during the study period, all of which presented with partial seizures with successive deterioration to intractable epilepsy. The age at onset varied between 5 and 10 years (mean 7.8 years), with three male and one female patients. Subsequently, all four patients underwent hemispherotomy. Histopathological features of perivascular lymphocytic infiltrate, neuronal loss, microglial nodules, and reactive astrocytosis, with or without evidence of neuronophagia confirmed a diagnosis of RE. These cases also had varying degrees of T-cell-rich (CD3-positive) inflammatory infiltrates and CD68-immunopositive microglial proliferation. It was observed that the severity of inflammation had a trend to inversely correlate with the duration of symptoms. CONCLUSION: It is proposed that an accurate evaluation and histopathological grading of these lesions may possibly have a role in patient prognostication.     

The importance of gut motility in the metabolic control of propionic acidemia

We hypothesized that gut motility likely plays a critical role in the metabolic stability in propionic acidemia (PA). Therefore, 4 known patients with PA (aged 47 months to 185 months) were prospectively studied over 7 days in the Clinical Research Center at Children's Hospital, Boston. Determinations of ammonia, bicarbonate, and amino acids in blood; organic acids and propionylglycine in urine; and a lactulose breath test were conducted under two study conditions: on regular therapy (for 4 days) and on regular therapy plus Senekot (Purdue Frederick Company, Norwalk, Conn), an intestinal motility agent (for 3 days). The total gastrointestinal transit time was calculated using 20 nonabsorbable, inert, radio-opaque markers. The addition of an intestinal motility agent resulted in a significant decrease in blood ammonia, urinary excretion of propionylglycine, and a rise in the ratio of free to total carnitine over baseline. We concluded that enhancement of gut motility can improve metabolic stability in patients with PA.     

Allergen immunotherapy in the prevention of asthma

PURPOSE OF REVIEW: Asthma is a disease causing significant morbidity and mortality. In the recent past, there has been an explosion of pharmacotherapeutic options attempting to control the disease. Unfortunately, none of the current options offers the promise of prevention or a permanent cure. However, there appear to be exciting, new data emerging to support the hypothesis that the prevention or early treatment of allergic rhinitis, such as with the use of allergen immunotherapy, may help mitigate the severity of bronchial symptoms and even prevent the development of asthma. In this paper, we review recent research published proposing immunotherapy as a means of preventing the development of, or at least ameliorating, allergic asthma. RECENT FINDINGS: There is evidence that the upper and lower airways may be considered a single unit, with the nasal and bronchial mucosa having features in common. Epidemiological, pathophysiological and clinical studies have shown that they can be affected by similar inflammatory triggers, with interconnected mechanisms amplifying the inflammatory cascade. Allergic rhinitis is interrelated to, and is a risk factor for, the development of asthma. An evidence-based review validates the successful use of allergen immunotherapy in treating allergic rhinitis and asthma. There is promising evidence advocating its use in the prevention of clinical asthma. SUMMARY: This article explores current research pertaining to the use of immunomodulation, such as by using allergen immunotherapy, to ameliorate and prevent the development of allergic asthma.