Biomedical subjects

R Schnur

Publications and source records attributed to R Schnur.

7 recordsLinked to original sources

PubMed2001

Detection of anthropogenic climate change in the world's oceans.

Large-scale increases in the heat content of the world's oceans have been observed to occur over the last 45 years. The horizontal and temporal character of these changes has been closely replicated by the state-of-the-art Parallel Climate Model (PCM) forced by observed and estimated anthropogenic gases. Application of optimal detection methodology shows that the model-produced signals are indistinguishable from the observations at the 0.05 confidence level. Further, the chances of either the anthropogenic or observed signals being produced by the PCM as a result of natural, internal forcing alone are less than 5%. This suggests that the observed ocean heat-content changes are consistent with those expected from anthropogenic forcing, which broadens the basis for claims that an anthropogenic signal has been detected in the global climate system. Additionally, the requirement that modeled ocean heat uptakes match observations puts a strong, new constraint on anthropogenically forced climate models. It is unknown if the current generation of climate models, other than the PCM, meet this constraint.

Journal Article↗

PubMed2000

Quantifying the uncertainty in forecasts of anthropogenic climate change

Forecasts of climate change are inevitably uncertain. It is therefore essential to quantify the risk of significant departures from the predicted response to a given emission scenario. Previous analyses of this risk have been based either on expert opinion, perturbation analysis of simplified climate models or the comparison of predictions from general circulation models. Recent observed changes that appear to be attributable to human influence provide a powerful constraint on the uncertainties in multi-decadal forecasts. Here we assess the range of warming rates over the coming 50 years that are consistent with the observed near-surface temperature record as well as with the overall patterns of response predicted by several general circulation models. We expect global mean temperatures in the decade 2036-46 to be 1-2.5 K warmer than in pre-industrial times under a 'business as usual' emission scenario. This range is relatively robust to errors in the models' climate sensitivity, rate of oceanic heat uptake or global response to sulphate aerosols as long as these errors are persistent over time. Substantial changes in the current balance of greenhouse warming and sulphate aerosol cooling would, however, increase the uncertainty. Unlike 50-year warming rates, the final equilibrium warming after the atmospheric composition stabilizes remains very uncertain, despite the evidence provided by the emerging signal.

Journal Article↗

PubMed1997

Neuropathological findings in eight children with cerebro-oculo-facio-skeletal (COFS) syndrome.

Cerebro-oculo-facial-skeletal (COFS) syndrome is a rare autosomal recessive disorder with microcephaly, severe mental retardation, and death in childhood. The pathogenesis is unknown. Neuropathological features of 8 children with COFS syndrome are presented. Seven of the children, ranging in age from 36 weeks gestation to 5 years 8 months, are of North American aboriginal background from Manitoba, Canada. The eight child is a 3-year-old Caucasian male. In all children there was severe microencephaly and mild ventriculomegaly. Cerebral myelination appeared to be delayed in one infantile case. Swollen ubiquitinated granular cells appeared in the white matter shortly after birth. Older children displayed cortical neuron loss, patchy or diffuse absence of myelin and gliosis in the white matter, and pericapillary and parenchymal mineralization in the globus pallidus and to a lesser extent the putamen and cerebral cortex. The cerebellum of older children exhibited severe degenerative changes involving the internal granular layer and Purkinje cell layer. The neuropathological changes, previously not well documented, suggest that COFS syndrome is associated with a degenerative process that begins in utero and affects many brain cell types. Similarities to Cockayne syndrome are discussed.

Brain↗

PubMed1996

p185erbB2 binds to GRP94 in vivo. Dissociation of the p185erbB2/GRP94 heterocomplex by benzoquinone ansamycins precedes depletion of p185erbB2.

Treatment of SKBr3 cells with benzoquinone ansamycins, such as geldanamycin (GA), depletes p185erbB2, the receptor tyrosine kinase encoded by the erbB2 gene. In the same cells, a biologically active benzoquinone photoaffinity label specifically binds a protein of about 100 kDa, and the ability of various GA derivatives to reduce the intracellular level of p185erbB2 correlates with their ability to compete with the photoaffinity label for binding to this protein. In this report, we present evidence that the approximately 100-kDa ansamycin-binding protein is GRP94. Membrane-associated p185erbB2 exists in a stable complex with GRP94. GA binding to GRP94 disrupts this complex, leading to degradation of pre-existing p185erbB2 protein, and resulting in an altered subcellular distribution of newly synthesized p185erbB2.

Benzoquinones↗

PubMed1996

A repeated element in the regulatory region of the MNK gene and its deletion in a patient with occipital horn syndrome.

Occipital horn syndrome (OHS), an X-linked connective tissue disorder, has recently been shown to result from mutations in the Menkes disease gene (MNK), which encodes a copper-transporting ATPase. By Southern analysis we detected a small deletion in a region 5' to the MNK gene in one patient with OHS. Genomic clones from an unaffected individual were isolated and sequenced, revealing three tandem 98 bp repeats situated upstream of the reported transcription start site, and analysis of the patient's DNA showed a deletion of one of the repeats. The deletion is likely to be responsible for the disease in this patient, as it was not observed in 110 unaffected individuals analyzed, and no other mutation in the patient was detected by RT-PCR and chemical cleavage mismatch analysis or by cDNA sequence analysis. The deletion is associated with a dramatic decrease in expression of a chloramphenicol acetyltransferase reporter gene, implicating the repeat sequences in regulation of MNK expression, although a quantitative analysis of MNK mRNA from a cell line derived from the patient shows no detectable reduction. Other experiments revealed no effect on the site of transcription initiation, termination or on splicing.

Adenosine Triphosphatases↗

PubMed1988

Aglossia with congenital absence of the mandibular rami and other craniofacial abnormalities.

We describe a severe first branchial arch abnormality including nearly complete absence of mandible, hypoplasia of the maxilla and the zygomatic arches, and complete gingival fusion in a chromosomally normal child born to a nonconsanguineous couple who deny prenatal exposures. A tight orbicularis oris muscle caused the lips to be constantly pursed. Intraoral contents could only be defined after the fused gingiva were separated. The infant had hypoplasia of the buccal cavity with a persistent membrane separating it from the pharynx; palate structures and tongue were absent. The orbits and midface were severely hypoplastic. However, the ears were normal in shape and only slightly low in position. There was unilateral optic nerve coloboma and coronal craniosynostosis. The only noncraniofacial malformation was an atrial septal defect. Embryologically, there is severe malformation of structures arising from the cephalic neural crest cells of both the maxillary and mandibular prominences of the first branchial arch. However, the first branchial cleft region was spared.

Facial Bones↗

PubMed1983

Statistical "biases" in respiratory disability determinations.

The manner in which pulmonary function test results are employed in the assessment of respiratory disability may be affected by 4 statistical choices: (1) choice of prediction equation(s), (2) adjustment factors (such as sex and race), (3) criterion values, and (4) method of comparison of observed to predicted normal test values. The records of 900 respiratory disability applicants were employed to estimate the direction and magnitude of the effect of these choices on the overall number of persons who would be declared "disabled" and upon the manner in which personal characteristics (e.g., sex, race, height, age) affect the likelihood of being declared "disabled." Choice of prediction equation had minor effects, and adjustment for race and sex had more significant effects. Choice of criterion value affected the overall number and, in certain instances (e.g., Social Security Disability Insurance), the distribution of "disability" declarations. Method of comparison (percent of predicted, difference of predicted minus observed or minimal value criterion) had major effects upon the distribution of "disability" declarations between population subgroups. Preliminary analysis therefore suggests that these statistical choices should be carefully manipulated in the design of a disability system to facilitate achievement of the system's goals.

Age Factors↗