Motor neuron disease presenting as acute respiratory failure: electrophysiological studies.
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Aged↗
Biomedical subjects
J D Brown
Publications and source records attributed to J D Brown.
WNTs modulate cell fate and behavior during vertebrate development.
Wnt genes encode a family of secreted glycoproteins that modulate cell fate and behavior in embryos through activation of receptor-mediated signaling pathways. Wnt sequences, patterns of expression and activities are highly conserved in evolution, so it has been possible to gain insights into the functions, and mechanisms of action, of the Wnt genes through a synthesis of genetic and cell biological approaches in different organisms. These studies suggest that there are functionally distinct WNT proteins as assayed by the ability to transform cells and by differences in embryonic responses to ectopic WNT signals. Moreover, gain-of-function and loss-of-function studies both support the involvement of Wnt proteins in modulating cell fate and cell behavior during vertebrate development, often through combinatorial interactions with other signaling pathways to regulate gene expression.
Animals↗
The potential for catheter microbial contamination from a needleless connector.
Needleless connectors have been widely introduced into clinical practice to allow the connection of syringes and luers to peripheral and central vascular catheters. The potential for microbial contamination of catheters via these devices is currently unclear. A recently introduced connector, the 'Connecta Clave', was assessed by various in-vitro methods. The 'Connecta Clave' is specifically devised to separate external components from the fluid pathway. The compression seals of 50 devices were contaminated with 1 x 10(4) cfu Staphylococcus epidermidis, disinfected with isopropanol, and fluid passed through. Only one device allowed organisms to pass through, despite this challenge, representing a contamination rate of 2%. In comparison, when 50 connectors were challenged with 20 cfu of S. epidermidis, no organisms passed through the device during use. In the clinical situation, after manipulation, < 16 cfu of skin organisms were found associated with the compression seal of the devices. It is, therefore, likely that the contamination rates in clinical practice will be extremely low. Three methods of disinfecting the compression seals and associated rims were also evaluated. A combination of alcohol chlorhexidine spray, followed by a 70% isopropanol swab, resulted in the most efficacious disinfection. The isopropanol swabs produced an adequate disinfection rate. The overall results suggest that by use of specially designed connectors, not only are needlestick injuries reduced, but the likelihood of microbial contamination of catheters via the internal route may also be diminished.
Catheters, Indwelling↗
Outcome of subarachnoid haemorrhage. An analysis of surgical variables, cognitive and emotional sequelae related to SPECT scanning.
A group of 48 patients, consecutive apart from exclusions, from a 1-year series of 60 cases of aneurysmal subarachnoid haemorrhage (SAH), was reviewed, in respect of clinical and radiological features, surgical management, clinical outcome, psychological distress and psychometric status, the neuropsychological assessment being compared with a closely-matched group of controls, the postoperative assessment being accompanied by a single positron emission computed tomogram (SPECT) scan. A review of those features which might have been expected to have a bearing on cognitive outcome (CT abnormalities at the outset, angiographic vasospasm, operative aneurysmal leakage, temporary vessel occlusion) failed to show a significant difference on cognitive tests. There was, however, a cognitive deficit shown by the patient group as a whole, when compared with the controls. Thus, SAH itself, the initial insult, would appear to be the essential factor in the production of persistent cognitive deficits.
Activities of Daily Living↗
Use of prototype automated blood culture system and gas-liquid chromatography for the analysis of continuous ambulatory peritoneal dialysis associated infection.
AIMS: (1) To compare the recovery of organisms from continuous ambulatory peritoneal dialysis (CAPD) effluent fluid obtained from patients with clinical evidence of peritonitis, with an automated system (AS) and the Septichek blood culture system; (2) to evaluate the times to detection of organisms with the two systems; (3) to identify anaerobes from CAPD samples by extended anaerobic culture and gas-liquid chromatography (GLC). METHODS: 168 CAPD effluent fluid samples were studied, representing 157 episodes of peritonitis in 97 patients. CAPD samples were inoculated into two AS bottles-one anaerobic, one aerobic-and a Septichek bottle; samples were also examined for cell count, Gram stain, and direct culture. Culture bottles were then subcultured onto various media, and any organisms isolated were identified. After routine culture, GLC was performed on culture fluid in the anaerobic AS and Septichek bottles. When volatile fatty acids were detected, the broths were cultured anaerobically on specialised medium for a further five days. RESULTS: 147 organisms were isolated from the 168 samples: 96 (57%) yielded growth of significant organisms by direct culture, as compared to 129 (76.8%) by both AS and Septichek. There was no significant difference in isolation rates between AS and Septichek, but time to detection was more rapid with the AS system (p < 0.002). GLC showed volatile fatty acid in 15 specimens; of these, 14 subsequently grew anaerobic organisms. CONCLUSIONS: AS was comparable to Septichek for numbers of isolations. Speed to detection was faster with the AS, which may be an advantage in management of patients with CAPD peritonitis. GLC showed anaerobes in several cases which would not have been detected without prolonged anaerobic culture; thus anaerobic cultures are recommended for patients who are unresponsive to antimicrobials or who have evidence of bowel perforation.
Bacteria↗
Expression of a dominant-negative Wnt blocks induction of MyoD in Xenopus embryos.
During gastrulation of Xenopus embryos the prospective mesoderm is induced initially with domains of dorsal and ventral fate, then further patterned to generate somitic mesoderm by signals from the gastrula organizer. Although Xwnt-8 is expressed in future ventrolateral mesoderm and induces prospective epidermis to differentiate in vitro as ventral mesoderm, no loss-of-function studies have demonstrated a requirement for Wnt signaling for the normal expression of mesodermal genes in the gastrula. We report development of a dominant-negative Wnt (dnXwnt-8) that inhibits embryonic responses to Wnt signaling in a cell-nonautonomous fashion. By expressing dnXwnt-8 in Xenopus embryos, we uncover a requirement of Wnt signaling for localized expression in prospective mesoderm of XMyoDa and Xenopus-posterior (Xpo). Because ectopic expression of functional Xwnt-8 in the dorsal marginal zone of the gastrula induces ectopic XMyoDa and Xpo, both gain-of-function and loss-of-function experiments support a model in which endogenous Xwnt-8 functions to induce expression of genes involved in specification of ventral and somitic mesoderm.
Amino Acid Sequence↗
A frizzled homolog functions in a vertebrate Wnt signaling pathway.
BACKGROUND: Wnts are secreted proteins implicated in cell-cell interactions during embryogenesis and tumorigenesis, but receptors involved in transducing Wnt signals have not yet been definitively identified. Members of a large family of putative transmembrane receptors homologous to the frizzled protein in Drosophila have been identified recently in both vertebrates and invertebrates, raising the question of whether they are involved in transducing signals for any known signaling factors. RESULTS: To test the potential involvement of frizzled homologs in Wnt signaling, we examined the effects of overexpressing rat frizzled-1 (Rfz-1) on the subcellular distribution of Wnts and of dishevelled, a cytoplasmic component of the Wnt signalling pathway. We demonstrate that ectopic expression of Rfz-1 recruits the dishevelled proten-as well as Xenopus Wnt-8 (Xwnt-8), but not the functionally distinct Xwnt-5A-to the plasma membrane. Moreover, Rfz-1 is sufficient to induce the expression of two Xwnt-8-responsive genes, siamois and Xnr-3, in Xenopus explants in a manner which is antagonized by glycogen synthase kinase-3, which also antagonizes Wnt signaling. When Rfz-1 and Xwnt-8 are expressed together in this assay, we observe greater induction of these genes, indicating that Rfz-1 can synergize with a Wnt. CONCLUSIONS: The results demonstrate that a vertebrate frizzled homolog is involved in Wnt signaling in a manner which discriminates between functionally distinct Wnts, which involves translocation of the dishevelled protein to the plasma membrane, and which works in a synergistic manner with Wnts to induce gene expression. These data support the likely function of frizzled homologs as Wnt receptors, or as components of a receptor complex.
Adaptor Proteins, Signal Transducing↗
Characterisation of the specific binding of the histamine H3 receptor antagonist radioligand [3H]GR168320.
We have examined the specific binding of the tritiated derivative of the potent histamine H3 receptor antagonist, [3,4-3H2]-cyclohex-yl-¿[4-(3H-imidazol-4-yl)-piperidin-l-yl] iminomethyl¿- amine ([3H]GR168320), to homogenates of rat cerebral cortex. Specific binding of [3H]GR168320 at 37 degrees C associated and dissociated rapidly. Binding was saturable (Bmax 412 +/- 89 fmol/mg protein) and of high affinity (Kd 0.12 +/- 0.11 nM). Saturation studies suggested the involvement of a single site. Histamine H3 receptor agonists and antagonists inhibited [3H]GR168320 binding with high affinity. Agonist and antagonist affinities correlated when compared with affinities obtained using the tritiated histamine H3 agonist radioligand N alpha-methylhistamine.
Animals↗
Noninvasive ankle distraction: relationship between force, magnitude of distraction, and nerve conduction abnormalities.
Seven healthy volunteers (14 ankles; four males, 3 females) with no history of ankle or foot pathology were placed in a modified beach chair position on an operating table for ankle distraction using a noninvasive ankle distractor. In-line traction of 0 to 225 N (50 lb) in 22.5-N (5-lb) increments was applied to the ankle. A direct lateral radiograph was obtained at each distraction force. The joint space was measured on the lateral radiographs using electronic microcalipers. Surface recordings of the superficial peroneal, deep peroneal dorsal digital cutaneous, and sural nerves were obtained. The ankle joint space increased progressively from an average 3.1 mm with no force applied to an average 4.2 mm with 225 N (50 lb) distraction force applied. The maximum joint distraction averaged 1.3 mm (range, 0.35 to 2.35 mm). The sensory amplitudes were diminished or absent with increasing time and force of distraction. The decreased amplitudes were most marked after 1 hour of distraction with 135 N (30 lb) or greater distraction force. This correlated with symptoms of paresthesias. The superficial and deep peroneal cutaneous nerves were affected to a much greater extent than the sural nerve. The amplitudes quickly returned to normal values with the weight being released from the ankle. The noninvasive ankle distractor safely increased ankle joint space by more than 1 mm. Distraction with 135 N (30 lb) or more for 1 hour is associated with reversible nerve conduction changes. Based on these findings, we recommend using the noninvasive ankle distraction apparatus for ankle arthroscopy, with up to 135 N (30 lb) of traction applied to the foot for up to 1 hour. Greater force, applied for longer periods, is associated with increasing nerve conduction abnormalities.
Adolescent↗
Signal sequences specify the targeting route to the endoplasmic reticulum membrane.
In the yeast Saccharomyces cerevisiae, only a subset of preproteins that are translocated across the ER membrane require the function of the signal recognition particle (SRP), suggesting that an alternative, SRP-independent pathway must exist (Hann, B.C., and P. Walter. 1991. Cell. 67:131-144). We have established that the two targeting pathways function in parallel. Mutant alleles of SEC62 and SEC63 were isolated that specifically impaired the translocation of SRP-independent preproteins in vivo and in vitro, whereas SRP-dependent preproteins were unaffected. Based on this analysis, preproteins fall into three distinct classes: SRP dependent, SRP independent, and those that can use both pathways. Pathway specificity is conferred by the hydrophobic core of signal sequences. Our studies show a previously unrecognized diversity in ER-directed signal sequences, that carry structural information that serves to identify the route taken.
Base Sequence↗
The value of skeletal scintigraphy in predicting the need for revision surgery in total knee replacement.
We have reviewed the results of 99mtech-netium-methylene diphosphonate (Tc-MDP) bone scintigrams performed on patients following total knee arthroplasty. In addition, 67gallium (Ga) citrate scintigrams were carried out sequentially on 29 patients. Three groups of patients were identified: those with asymptomatic knees (undergoing scans for other reasons); those with aseptic or septic loosening; and those with pain without radiologic evidence of loosening. There was good correlation between the results of the scans and the final outcome. We conclude that sequential 99mTc-MDP and 67Ga citrate scintigrams are useful for demonstrating the presence of aseptic and septic loosening in knee prostheses, and pain with a normal scan appearance is probably not due to loosening or infection.
Aged↗
Using computer systems to enhance case management.
This article describes how an on-line computer system can enhance case management by improving communication within internal departments and adding consistency and objectivity to the referral process. At PacifiCare, the computer system has supported case management's efforts to provide members with cost-effective medical care and has improved satisfaction with the health plan.
California↗
Extraordinary sequence conservation of the PRP8 splicing factor.
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Amino Acid Sequence↗
The thrill of victory, the complexity of defeat: self-esteem and people's emotional reactions to success and failure.
Low self-esteem people are assumed to have more severe emotional reactions to failure than are high self-esteem people, but this assumption has not received consistent empirical support. In this article the authors report 2 investigations that found that self-esteem differences of this sort emerge for emotions that directly implicate the self (e.g., pride, humiliation) but not for emotions that do not directly implicate the self (e.g., happiness, unhappiness). Additional evidence suggested that this occurs, in part, because low self-esteem people overgeneralize the negative implications of failure. The relevance of these findings for understanding the nature and functions of self-esteem is considered.
Adult↗
Targeting pathways to the endoplasmic reticulum membrane.
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Biological Transport, Active↗
Xwnt-8b: a maternally expressed Xenopus Wnt gene with a potential role in establishing the dorsoventral axis.
In amphibian embryos, establishment of dorsal-ventral asymmetry is believed to involve dorsal-ventral differences in vegetally derived mesoderm-inducing signals and/or differences in the competence of animal hemisphere (ectodermal) cells to respond to these signals. Previous studies have shown that certain Wnt proteins can generate an ectopic dorsal axis when misexpressed, and that they do so by modifying the response of ectodermal cells to inducers. None of these Wnt proteins are expressed at an appropriate time to do so in vivo. In this study, we describe the isolation and characterization of a full length cDNA for the Xenopus Wnt gene, Xwnt-8b, whose biological activity and expression pattern suggest that it may be involved in establishment of the dorsoventral axis. Both maternal and zygotic Xwnt-8b transcripts undergo alternative splicing to generate mRNAs which encode two different forms of Xwnt-8b protein. During early cleavage stages Xwnt-8b transcripts are confined primarily to animal hemisphere blastomeres, while zygotically derived Xwnt-8b transcripts are restricted almost exclusively to a band of cells in the prospective forebrain of neurula and tailbud stage embryos. Ectopically expressed Xwnt-8b can completely rescue dorsal development of embryos ventralized by exposure to ultraviolet light, and can induce a complete secondary axis in wild-type embryos. Axis induction is observed only if Xwnt-8b is supplied prior to the onset of zygotic gene transcription. This biological activity, together with the presence of maternal Xwnt-8b transcripts in cells that will be induced to form the dorsal mesoderm, is consistent with the possibility that Xwnt-8b may be the endogenous agent that establishes asymmetry in the response of ectodermal cells to mesoderm-inducing signals, thereby initiating dorsal development.
Alternative Splicing↗
'Doc Quixote' in health care reform.
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Ethics, Medical↗
Subunits of the Saccharomyces cerevisiae signal recognition particle required for its functional expression.
The signal recognition particle (SRP) is an evolutionarily conserved ribonucleoprotein (RNP) complex that functions in protein targeting to the endoplasmic reticulum (ER) membrane. Only two protein subunits of the SRP, Srp54p and Sec65p, and the RNA subunit, scR1, were previously known in the yeast Saccharomyces cerevisiae. Purification of yeast SRP by immunoaffinity chromatography revealed five additional proteins. Amino acid sequencing and cloning of the genes encoding four of these proteins demonstrated that the yeast SRP contains homologs (termed Srp14p, Srp68p and Srp72p) of the SRP14, SRP68 and SRP72 subunits found in mammalian SRP. The yeast SRP also contains a 21 kDa protein (termed Srp21p) that is not homologous to any protein in mammalian SRP. An additional 7 kDa protein may correspond to the mammalian SRP9. Disruption of any one of the four genes encoding the newly identified SRP proteins results in slow cell growth and inefficient protein translocation across the ER membrane. These phenotypes are indistinguishable from those resulting from the disruption of genes encoding SRP components identified previously. These data indicate that a lack of any of the analyzed SRP components results in loss of SRP function. ScR1 RNA and SRP proteins are at reduced levels in cells lacking any one of the newly identified proteins. In contrast, SRP components are present at near wild type levels and SRP subparticles are present in cells lacking either Srp54p or Sec65p. Thus Srp14p, Srp21p, Srp68p and Srp72p, but not Sec65p or Srp54p, are required for stable expression of the yeast SRP.
Amino Acid Sequence↗