Biomedical subjects
Publications and source records attributed to S C Smith.
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Degeneration of neurons in Alzheimer's disease is mediated by beta-amyloid peptide by diverse mechanisms, which include a putative apoptotic component stimulated by unidentified signaling events. This report describes a novel beta-amyloid peptide-binding protein (denoted BBP) containing a G protein-coupling module. BBP is one member of a family of three proteins containing this conserved structure. The BBP subtype bound human beta-amyloid peptide in vitro with high affinity and specificity. Expression of BBP in cell culture induced caspase-dependent vulnerability to beta-amyloid peptide toxicity. Expression of a signaling-deficient dominant negative BBP mutant suppressed sensitivity of human Ntera-2 neurons to beta-amyloid peptide mediated toxicity. These findings suggest that BBP is a target of neurotoxic beta-amyloid peptide and provide new insight into the molecular pathophysiology of Alzheimer's disease.
The reductive biotransformation of a Ni(2+)-substituted (5 mol %) hydrous ferric oxide (NiHFO) by Shewanella putrefaciens, strain CN32, was investigated under anoxic conditions at circumneutral pH. Our objectives were to define the influence of Ni2+ substitution on the bioreducibility of the HFO and the biomineralization products formed and to identify biogeochemical factors controlling the phase distribution of Ni2+ during bioreduction. Incubations with CN32 and NiHFO were sampled after 14 and 32 d, and both aqueous chemistry and solid phases were characterized. By comparison of these results with a previous study (Fredrickson, J. K.; Zachara, J. M.; Kennedy, D. W.; Dong, H.; Onstott, T. C.; Hinman, N. W.; Li, S. W. Geochim. Cosmochim. Acta 1998, 62, 3239-3257), it was concluded that coprecipitated/sorbed Ni2+ inhibited the bioreduction of HFO through an undefined chemical mechanism. Mössbauer spectroscopy allowed analysis of the residual HFO phase and the identity and approximate mass percent of biogenic mineral phases. The presence of AQDS, a soluble electron shuttle that obviates need for cell--oxide contact, was found to counteract the inhibiting effect of Ni2+. Nickel was generally mobilized during bioreduction in a trend that correlated with final pH, except in cases where PO4(3-) was present and vivianite precipitation occurred. CN32 promoted the formation of Ni(2+)-substituted magnetite (Fe2IIIFe(1-x)IINixIIO4) in media with AQDS but without PO4(3-). The formation of this biogenic coprecipitate, however, had little discernible impact on final aqueous Ni2+ concentrations. These results demonstrate that coprecipitated Ni can inhibit dissimilatory microbial reduction of amorphous iron oxide, but the presence of humic acids may facilitate the immobilization of Ni within the crystal structure of biogenic magnetite.
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Computational simulations of the title reaction are presented, covering a temperature range from 300 to 2000 K. At lower temperatures we find that initial formation of the cyclopropene complex by addition of methylene to acetylene is irreversible, as is the stabilisation process via collisional energy transfer. Product branching between propargyl and the stable isomers is predicted at 300 K as a function of pressure for the first time. At intermediate temperatures (1200 K), complex temporal evolution involving multiple steady states begins to emerge. At high temperatures (2000 K) the timescale for subsequent unimolecular decay of thermalized intermediates begins to impinge on the timescale for reaction of methylene, such that the rate of formation of propargyl product does not admit a simple analysis in terms of a single time-independent rate constant until the methylene supply becomes depleted. Likewise, at the elevated temperatures the thermalized intermediates cannot be regarded as irreversible product channels. Our solution algorithm involves spectral propagation of a symmetrized version of the discretized master equation matrix, and is implemented in a high precision environment which makes hitherto unachievable low-temperature modelling a reality.
Patients with advanced, recurrent, or metastatic gynaecological malignancies constitute a heterogenous population with diverse symptomatology. Progressive abdominopelvic disease can result in vaginal or diffuse pelvic bleeding, pain, and visceral or lymphovascular obstruction. Gynaecological cancer can also develop debilitating metastases, in particular to bone, central nervous system, or chest. Radiation therapy is a local-regional treatment modality, that, when applied judiciously, can lead to substantial symptomatic relief and tumour response. Individualized application is necessary, balancing efficacy and patient convenience versus treatment intensity, expected duration of palliation and potential toxicity. Important factors to consider are a patient's performance status, extent and sites of tumour, specific symptoms, and life expectancy. The optimal incorporation of radiotherapy is best achieved in the context of a multidisciplinary approach that addresses all facets of palliative care in patients with incurable gynaecological malignancies, to maximize their quality of life and functional level.
Placentas were obtained at delivery from 34 pregnancies complicated by preeclampsia and from 34 uncomplicated pregnancies. The incidence of apoptotic nuclei was significantly greater (P <.01) in the placentas from the pregnancies complicated by preeclampsia.
Understanding the dry eye would be a great deal easier if we thoroughly understood normal tear function. To date, many aspects of tear function remain poorly understood. Only when normal tear characteristics and function are fully illuminated will the treatment of tear abnormalities and ocular surface disease be remedied. This instructional article aims to provide the reader with basic information regarding tear production, abnormalities, and current therapies in order to permit ophthalmic health care providers to intervene and teach patients who suffer from the frustrating and often chronic maladies associated with a dry eye.
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A novel developmental mutant in the Mexican axolotl is described. Designated redneck (rn), the mutant gene is inherited as a simple Mendelian recessive. In homozygotes, rn causes massive haemorrhage in the posterior head, rostrocaudal compression of the craniovisceral skeleton, abnormal differentiation of vertebral cartilage, micrognathia, aglossia, microphthalmia and abnormal hepatic development. Affected larvae become evident at the onset of feeding, and eventually die of starvation. Based on the tissues affected, we propose that rn affects later developmental events in the differentiation and morphogenesis of a subset of cranial neural crest cells. Thus, rn may prove a valuable model system for examining the role of neural crest cells in the development of cranial and endodermal derivatives.
Technical aspects of computer-aided sperm analysis and the influence of semen preparation were investigated for their effect on the measured motility characteristics of dog spermatozoa. Altering the internal image settings significantly influenced the measured motility by changing the ability of the computer to recognize spermatozoa. Similarly, the use of a longer minimum track point (the minimum length of sperm track detected before analysis) resulted in failure to detect some of the faster moving spermatozoa. There was a clear interaction between the search radius (the threshold distance below which objects are linked together) and the minimum track point. A 1 min analysis period was required to eliminate reduced motility as a result of sample deterioration upon the microscope stage. The dilution of semen to between 1:10 and 1:20 was necessary to allow accurate detection of sperm motility; however, such dilution significantly altered the motility characteristics of spermatozoa. The influence of viscosity and ionic composition of the media was confirmed by comparing dilution in seminal plasma with dilution in iso-viscous methylcellulose and iso-osmotic saline, respectively. Analysis temperature had a significant influence on sperm motility, although values were most constant within the range of 25-45 degrees C. Extremes of temperature had marked deleterious effects. Careful selection of internal image settings, the minimal track point and search radius, and the analysis time are essential for accurate detection of sperm motility. Moreover, dilution of spermatozoa per se, and dilution with media of different viscosities and ionic compositions can alter the sperm motility. Once these aspects of computer image analysis are determined for each system, the method can achieve a high degree of repeatability with interanalysis coefficients of variation of < 12%, and intra-analysis coefficients of variation of < 3% for most parameters.
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Studies have found that most dyslipidemic coronary artery disease and postsurgical cardiac patients are not monitored for serum lipids, especially high-density lipoprotein cholesterol (HDL-C). These patients are not prescribed lipid-altering therapy and are not treated to National Cholesterol Education Program (NCEP) target levels. When prescribed, the most commonly administered drugs are statins, followed by fibrates and niacin. Resins are the least commonly prescribed treatment for dyslipidemia. Unfortunately, drugs chosen are often not the best for each patient. To compound matters, compliance with lipid-modification therapy is poor. Nurse case-management programs, supportive regular contact with healthcare professionals, and immediate postinterventional initiation of therapy significantly improves compliance.