First mutation in the voltage-gated NaV1.1 subunit gene SCN1A with co-occurring familial hemiplegic migraine and epilepsy

Almost all mutations in the SCN1A gene, encoding the α₁ subunit of neuronal voltage-gated Na_V1.1 sodium channels, are associated with severe childhood epilepsy. Recently, two mutations were identified in patients with pure familial hemiplegic migraine (FHM). Here, we identified a novel SCN1A L263V mutation in a Portuguese family with partly co-segregating hemiplegic migraine and epilepsy. The L263V mutation segregated in five FHM patients, three of whom also had epileptic attacks, occurring independently from their hemiplegic migraine attacks. L263V is the first SCN1A mutation associated with FHM and co-occurring epilepsy in multiple mutation carriers, and is the clearest molecular link between migraine and epilepsy thus far. The results extend the clinical spectrum associated with SCN1A mutations and further strengthen the molecular evidence that FHM and epilepsy share, at least in part, similar molecular pathways.     

THE NATURE AND TREATMENT OF CONGESTIVE HEART FAILURE. II. PREVENTION AND TREATMENT

In the West, in countries where many serious infectious diseases have been eliminated or brought under control, cardiovascular disease has become the most frequent cause of death among adults(I). Illness from heart failure causes an enormous loss of time and money, so that the economic aspects of heart djsease loom la.rge(2). Its prevention is, therefore, a most important problem of public health, taking rank next after tuberculosis (3) Realization of this need is growing rapidly, as is shown by the formation of national associations with the principal pur- pose of attacking the.problem. State public health, administrations have hardly entered the field as yet, but they must soon do so. .     

Characterization of four N-3-thymidine adducts formed in vitro by the reaction of thymidine and butadiene monoxide

Four products were characterized from the reaction of thymidine with butadiene monoxide (BM), a known human mutagen and possible human carcinogen. These products were purified by HPLC and characterized as diastereomeric pairs of N-3-(1-hydroxy-3-buten-2-yl)thymidine and N-3- (2-hydroxy-3-buten-1-yl)thymidine based upon their UV spectra, 1H NMR and fast atom bombardment mass spectra. Incubation of thymidine with an excess of BM at pH 7.4 and 37 degrees C allowed calculation of the pseudo-first-order kinetic rate constants for the adduct formation, but when these rate constants were compared with the rates we previously determined with guanosine, adenosine and deoxycytidine, the results suggested a lower reactivity with thymidine in comparison with the other nucleosides. When incubations were carried out at lower BM concentrations, the formation of adducts appeared to be linearly dependent on BM concentration. The four thymidine adducts were completely stable for 1 week when incubated at 37 degrees C in pH 7.4 phosphate buffer. These results suggest that the interactions of BM with thymidine may play a role in the molecular mechanisms of mutagenesis and carcinogenesis of BM.      

Surface coil MR imaging of abdominal viscera. Part III. The pancreas

Eight healthy volunteers and 11 patients with pancreatic abnormalities were studied using a conventional body coil and a prototype magnetic resonance (MR) surface coil. Final pathologic diagnoses included carcinoma of the head (six), body (one), and tail of the pancreas (two) and chronic pancreatitis (two). In surface coil images of the volunteers, the body and tail of the pancreas was visualized in all cases but one, and the pancreatic duct was seen in five of eight cases. In-plane spatial resolution of 0.9 X 0.9 mm and 5-mm section thickness was obtained. At the same time, pancreatic surface coil images had a twofold improvement in the signal-to-noise ratio (SNR) compared with body coil images. T1-weighted spin-echo images gave greater SNR, reduced motion artifacts, provided superior anatomic detail, and offered more diagnostic information than comparable T2-weighted images. Significant abnormalities detected only by surface coil imaging included a small tumor surrounded by reactive edema and periglandular tumor invasion. This study demonstrates that surface coil imaging of the pancreas not only is feasible but provides an improved method for examining the pancreas by MR.     

Localization and quantitation of the vitamin D binding protein (Gc- globulin) in human neutrophils

Plasma-derived vitamin D binding protein (DBP) is an important physiologic regulator of the neutrophil chemotactic response to activated complement. A cell-associated form of DBP has been observed in numerous cell types. We now report that mature, circulating human neutrophils also contain cell-associated DBP. Immunofluorescence studies of normal untreated neutrophils showed the presence of DBP on the cell surface. Western blotting of detergent-soluble neutrophil lysates with a polyclonal anti-DBP showed two major immunoreactive bands, one with an apparent molecular weight of 56 Kd (identical to purified plasma-derived DBP) and a second less prominent band at 12 to 14 Kd. Quantitation of the immunoreactive bands by video densitometry indicated that normal human neutrophils contain 1.5 +/- 0.8 ng DBP/10(6) cells (n = 9). Immunoprecipitation of detergent-soluble lysates with the polyclonal anti-DBP showed only the 56-Kd form by Western blotting. In contrast, a monoclonal anti-DBP immunoprecipitated the 12 to 14 Kd form of DBP from lysates of surface-radioiodinated cells. Western blots of subcellular fractions showed that immunoreactive bands were found in the specific (secondary) granule and plasma-membrane fractions. In addition, pretreatment of neutrophils with 10 nmol/L phorbol myristate acetate (PMA) resulted in approximately a 50% reduction in the amount of DBP in both the specific granule and plasma-membrane fractions. Finally, analysis of the cell- free supernates showed that DBP was spontaneously released into the extracellular milieu: moreover, this release was enhanced if the cells were first stimulated with C5a, formyl-norleucyl-leucyl-phenylalanine (fNLP) or PMA.     

Expandable intraluminal graft: a preliminary study. Work in progress

To overcome the problem of recurrence of stenosis after vascular balloon dilatations, we developed an expandable, intraluminal graft that allows dilatation of the lesion and simultaneous placement of a supportive endoprosthesis to prevent recoil of the arterial wall. The graft is made of continuous, woven, stainless steel wire. The resulting tubular mesh has a wall thickness of 200-450 micron and 80% open surface. The grafts, mounted on angioplasty catheters, are introduced through 8-12-F Teflon sheaths. Eleven grafts of 6, 8, and 10 mm in diameter by 20 mm long were placed in the aorta, common carotid, superior mesenteric, iliac, and renal arteries of dogs. Six grafts showed no stenosis in follow-up studies of up to 8 weeks. Two grafts had moderate stenosis as a result of neointimal hyperplasia. Two partial and one complete graft thrombosis occurred in nonheparinized animals in which the graft outflow was restricted. Anticoagulant was not used on a long-term basis. Light and electron microscopy studies showed complete covering of the graft's inner surface by endothelium at 3 weeks.     

Adrenal abscess in the neonate

Adrenal abscess in the neonate is a rare complication of adrenal hemorrhage. The radiographic and clinical findings of 12 previously published cases and two new cases of adrenal abscess in the newborn are presented. Sonography was the most helpful examination in distinguishing a suprarenal lesion from an intrarenal lesion and in demonstrating the morphology of the abscess.