Rapid development of massive pleural effusion in Legionnaires' disease

The rapid development of a massive exudative pleural effusion was documented in a case of Legionnaires' disease. This clinical event can be considered an established though unusual feature of the widening clinical spectrum of infection by Legionella pneumophila.     

Distinct and overlapping expression patterns of ligands for Eph-related receptor tyrosine kinases during mouse embryogenesis

Recent studies have implicated Eph-related receptor tyrosine kinases and their membrane-bound ligands in restricting or stimulating the movement of cells and axons. Members of these large families of receptors and ligands fall into two major binding specificity classes, in which the GPI-anchored subgroup of ligands can each bind to all members of a subgroup of receptors, whereas the transmembrane ligands interact with a distinct subgroup of receptors. Analysis of expression patterns is therefore important in order to understand which receptor-ligand interactions occur in vivo. We have cloned mouse orthologues of five members of the ligand family and analysed in detail their developmental expression, in comparison with each other, and with the receptor specificity class they can interact with. We find that B61, AL-1/RAGS, LERK4, and ELF-1, members of the GPI-anchored subgroup of ligands, have both distinct and overlapping aspects to their expression in early mesoderm, somites, and branchial arches; in complex, dynamic patterns in the limb; and in spatial domains and specific neurons in the CNS. Similarly, Elk-L is expressed in hindbrain segments, the roof plate, and floor plate, which overlaps with that of other transmembrane ligands, but has distinct expression in somites. The expression domains of ligands are complementary to those of the corresponding receptors in a number of tissues, including the midbrain, hindbrain, and differentiating limbs, consistent with potential roles in restricting cell movement. In addition, we find that there are some overlaps in expression of receptors and ligands, for example in somites and the early limb. Taken together with previous studies showing that Eph-related receptors also have distinct but overlapping expression patterns, these data indicate that each ligand may have stage- and tissue-specific interactions with an individual member or multiple members of the receptor family.     

Improvement of plasma lipoprotein profiles during high-flux dialysis

Patients undergoing maintenance hemodialysis therapy have increased mortality due to cardiovascular disease. One possible etiologic factor for this increased mortality is the lipid abnormalities associated with chronic renal failure. These include elevated triglyceride (TG) and decreased high-density lipoprotein (HDL) concentrations. Lipoprotein profiles of patients undergoing chronic hemodialysis with either saponified cellulose ester (CE) (N = 9) or polysulfone (PS) high-flux dialysis membranes (N = 10) were compared. Patients in each group received similar amounts of heparin during the dialysis. CE-dialyzed patients showed no alteration in serum TG, HDL, low-density lipoprotein, or total cholesterol when predialysis and postdialysis values were compared. PS patients, on the other hand, had a significant decrease in TG concentrations (P < 0.01) as well as a significant rise in HDL (P < 0.01). These changes might signify activation of lipoprotein lipase (LPL) during dialysis. LPL activity in PS sera was significantly greater than LPL in CE sera. Moreover, sera from PS patients inhibited LPL much less than did sera from CE patients. These findings suggest that a circulating substance not dialyzable with cellulosic membranes inhibits LPL in uremic subjects and is removed during dialysis with a PS membrane. Alternatively, the greater biocompatibility of PS may produce less LPL inhibitory cytokines during dialysis. The improvement of lipoprotein profiles in patients receiving dialysis with PS membranes may, in the long term, lead to less morbidity and mortality from atherosclerotic disease.     

A histological and ultrastructural study of the cells of the mantle edge of a marine bivalve, Cerastoderma edule

The cells of the mantle edge of Cerastoderma edule are described after light and electron microscopical observations. Histochemical tests for calcium in the mantle edge and digestive gland (Dahl, 1952; McGee-Russell, 1958) and analytical electron microscopy of mantle edge of C. edule both failed to show calcium. Similar results were obtained for Mytilus edulis and Chlamys opercularis. However, calcium was detected in the digestive gland of the terrestrial gastropod Helix aspersa. The outer secretory fold of the mantle edge is composed of tall columnar cells. These cells have highly convoluted lateral cell membranes with which many mitochondria are closely associated. These features are indicative of an ion pump which could move calcium from the mantle space to the extrapallial cavity (compare with Bubel's findings, 1973b). There are many features of the cells lining the periostracal groove of C. edule that have not been reported previously (e.g. Bubel, 1973b) and which are now discussed. The periostracal sheet arises within a line of basal cells in the fundus of the periostracal groove. Within these cells the periostracum in section has a spiral form. It is suggested that the newly formed periostracum adheres to the microvillous border through secretions produced from the middle fold cells lining the groove. During its passage along the groove the periostracum is gradually thickened by secretions from the outer fold cells.     

A frequent activated smoothened mutation in sporadic basal cell carcinomas

Basal-cell carcinomas (BCCs) are the most common cancer in Caucasians. It has been reported that the patched gene is inactivated in 30-40% sporadic BCCs and 20% sporadic medulloblastomas via loss of heterozygosity and nonsense mutations. Recently, two activating smoothened mutations have been found in the sporadic basal cell carcinomas. One, at base pair 1604 (G-to-T transversion) of exon 9, changes codon 535 from tryptophan to leucine, and the other, at base pair 1685 (G-to-A transition) of exon 10, changes codon 562 from arginine to glutamine (Xie et al., 1998). In our study, 1604G-->T was found in 20 out of 97 (20.6%) sporadic BCCs. The high prevalence indicates that 1604G is the mutation hot spot in our tumor samples. This mutation was detected in all three histological subtypes of BCCs, suggesting that smoothened mutation is an early event during the development of the tumor. Our finding of a high smoothened mutation rate, together with high frequent patched gene mutations reported recently, indicates that activation of the hedgehog signal transduction pathway is the most common and early event in the development of sporadic BCCs. Additionally, to determine whether smoothened, like patched, is also involved in the carcinogenesis of medulloblastomas, we screened medulloblastoma samples for these two mutations by restriction analysis. We have found the 1604G-->T mutation in 1 out of 21 medulloblastomas. This result confirmed smoothened gene involvement in the carcinogenesis of medulloblastoma.     

Dynamic equilibrium unfolding pathway of human tumor necrosis factor-alpha induced by guanidine hydrochloride

The dynamic equilibrium unfolding pathway of human tumor necrosis factor-alpha (TNF-alpha) during denaturation at different guanidine hydrochloride (GdnHCl) concentrations (0-4.2 M) was investigated by steady-state fluorescence spectroscopy, potassium iodide (KI) fluorescence quenching, far-UV circular dichroism (CD), picosecond time-resolved fluorescence lifetime, and anisotropy decay measurements. We utilized the intrinsic fluorescence of Trp-28 and Trp-114 to characterize the conformational changes involved in the equilibrium unfolding pathway. The detailed unfolding pathway under equilibrium conditions was discussed with respect to motional dynamics and partially folded structures. At 0-0.9 M [GdnHCl], the rotational correlation times of 22-25 ns were obtained from fluorescence anisotropy decay measurements and assigned to those of trimeric states by hydrodynamic calculation. In this range, the solvent accessibility of Trp residues increased with increasing [GdnHCl], suggesting the slight expansion of the trimeric structure. At 1.2-2.1 M [GdnHCl], the enhanced solvent accessibility and the rotational degree of freedom of Trp residues were observed, implying the loosening of the internal structure. In this [GdnHCl] region, TNF-alpha was thought to be in soluble aggregates having distinct conformational characteristics from a native (N) or fully unfolded state (U). At 4.2 M [GdnHCl], TNF-alpha unfolded to a U-state. From these results, the equilibrium unfolding pathway of TNF-alpha, trimeric and all beta-sheet protein, could not be viewed from the simple two state model (N-->U).     

In vivo verification of an automatic noninvasive system for real time Kt evaluation

It is generally accepted that morbidity and mortality of hemodialysis patients is related to dialysis quantitation. Currently available methods for the quantitation of dialysis require blood sampling or a continuous measurement of changes in urea concentration during treatment. These maneuvers are time consuming and expensive, and are generally performed, at most, once per month. The authors introduce an on-line, automated method for measurement of dialyzer electrolyte clearance comparable to urea clearance by using dialysate conductivity sensors placed pre and post dialyzer, and measuring conductivity at three different pre dialyzer levels. Conditions that reduce clearance, such as recirculation or fiber clotting, are automatically taken into account so that the method measures effective clearance rather than dialyzer clearance. In vitro and in vivo studies validate the method. Results are immediately available and can be used to address problems such as improper needle placement and access recirculation. In addition, repetitive electrolyte clearance data can serve to enhance quality assurance programs with respect to verifying the function of reused or new dialyzers. Appropriate algorithms can be used to calculate delivered Kt/V.     

Anterolateral soft-tissue impingement in the ankle: diagnosis using MR imaging

OBJECTIVE: This study was performed to elucidate the MR imaging findings and pitfalls for the diagnosis of anterolateral soft-tissue impingement in the ankle, a cause of chronic ankle pain that can be relieved by arthroscopic resection. MATERIALS AND METHODS: We retrospectively reviewed MR imaging examinations of 18 patients with arthroscopically confirmed anterolateral ankle impingement. The MR images of 18 additional subjects with symptoms that could mimic anterolateral impingement, but who had a surgically confirmed alternate diagnosis (instability, peroneal tendon injury, osteochondral defect, normal arthroscopy) and no evidence of impingement at arthroscopy, served as controls. RESULTS: On the MR imaging studies, nine patients had an ankle effusion, eight of whom showed an abnormal soft-tissue structure in the anterolateral gutter, 2-15 mm in maximal diameter. No soft-tissue mass was seen in the patients without joint fluid. Four control subjects with instability had a similar soft-tissue structure in the anterolateral gutter, but in the control subjects the finding represented a portion of the torn anterior talofibular ligament. CONCLUSION: Anterolateral soft-tissue impingement of the ankle can be suggested by MR imaging when fluid in the lateral gutter outlines an abnormal soft-tissue structure separate from the anterior talofibular ligament.     

Determinants of premenopausal bone mineral density: the interplay of genetic and lifestyle factors

Bone mineral density (BMD) is a reflection of both genetic and lifestyle factors. The interplay of genetic (vitamin D receptor [VDR] gene polymorphisms) and lifestyle factors on BMD at the lumbar spine and proximal femur was examined in 470 healthy premenopausal women, aged 44-50 years, using a Hologic QDR 2000 densitometer. The objective of this study was to examine the genetic and lifestyle determinants of premenopausal BMD. Each participant was genotyped for BsmI polymorphism at the VDR gene locus. The presence of a restriction site within VDR, specified as bb (189, 40.2%) (n, %) was associated with reduced spinal BMD, whereas absence of this site in BB (97, 20.6%) conferred greater spinal BMD, as did the genotype Bb (184, 39.1%). Associations between smoking, alcohol use, oral contraceptives, education level, multivitamins, number of children, degree of obesity, body weight, physical activity, dietary calcium intake, and VDR genotype to BMDs were examined. VDR genotype, body weight, degree of obesity, physical activity, and dietary calcium intake were all significant determinants of BMD. The association of VDR genotype with BMD at the femoral neck appeared to be modified by calcium intake (BB and Bb: 0.797 +/- 0.11 g/cm2 vs. 0.844 +/- 0.11 g/cm2, interaction term, p = 0.06) for low (< 1036 mg/day) and high (> or = 1036 mg/day; upper quartile) calcium intakes, respectively. A similar trend was demonstrated for physical activity. These findings suggest that prophylactic interventions aimed at achieving and maintaining optimal BMD, such as greater calcium intake or physical activity, may be important in maximizing one's genetic potential for BMD.