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Biomedical subjects

A Dobbs

Publications and source records attributed to A Dobbs.

7 recordsLinked to original sources
PubMed2001

Complexation of two proteic insect inhibitors to the active site of chymotrypsin suggests decoupled roles for binding and selectivity.

The crystal structures of two homologous inhibitors (PMP-C and PMP-D2v) from the insect Locusta migratoria have been determined in complex with bovine alpha-chymotrypsin at 2.1- and 3.0-A resolution, respectively. PMP-C is a potent bovine alpha-chymotrypsin inhibitor whereas native PMP-D2 is a weak inhibitor of bovine trypsin. One unique mutation at the P1 position converts PMP-D2 into a potent bovine alpha-chymotrypsin inhibitor. The two peptides have a similar overall conformation, which consists of a triple-stranded antiparallel beta-sheet connected by three disulfide bridges, thus defining a novel family of serine protease inhibitors. They have in common the protease interaction site, which is composed of the classical protease binding loop (position P5 to P'4, corresponding to residues 26-34) and of an internal segment (residues 15-18), held together by two disulfide bridges. Structural divergences between the two inhibitors result in an additional interaction site between PMP-D2v (position P10 to P6, residues 21-25) and the residues 172-175 of alpha-chymotrypsin. This unusual interaction may be responsible for species selectivity. A careful comparison of data on bound and free inhibitors (from this study and previous NMR studies, respectively) suggests that complexation to the protease stabilizes the flexible binding loop (from P5 to P'4).

Animals↗
PubMed1997

A generic method for the production of cell lines expressing high levels of 7-transmembrane receptors.

G-protein-coupled or 7-transmembrane receptors (7TMRs) are often studied after heterologous expression in mammalian cells such as COS-7, CHO-K1, or HEK-293s. In this paper, we describe the development of a rapid and generic method for producing stable Chinese hamster ovary cell lines expressing high levels of recombinant 7TMRs by N-terminal tagging these proteins with the hemagglutinin (HA) sequence. To illustrate the broad applicability of this technique, we have presented data from cell lines expressing a glycoprotein hormone receptor for follicle-stimulating hormone (FSHR), CXC- (CXCR-2), and CC-chemokine (CCR-1) receptors and peptide receptors from the somatostatin (SSTR1, 2, 5) and neuropeptide Y (NPY-Y2, -Y4 Rs) families. Typically, cell lines with a receptor density of 1 to 15 pmol/mg protein are produced with this method. The presence of the HA tag does not adversely affect the binding or functional activity of the receptors.

Amino Acid Sequence↗
PubMed1994

Artificial neural networks that use single-photon emission tomography to identify patients with probable Alzheimer's disease.

Single-photon emission tomographic (SPET) images using technetium-99m labelled hexamethyl-propylene amine oxime were obtained from 97 patients diagnosed as having Alzheimer's disease, as well as from a comparison group of 64 normal subjects. Multiple linear regression was used to predict subject type (Alzheimer's vs comparison) using scintillation counts from 14 different brain regions as predictors. These results were disappointing: the regression equation accounted for only 33.5% of the variance between subjects. However, the same data were also used to train parallel distributed processing (PDP) networks of different sizes to classify subjects. In general, the PDP networks accounted for substantially more (up to 95%) of the variance in the data, and in many instances were able to distinguish perfectly between the two subjects. These results suggest two conclusions. First, SPET images do provide sufficient information to distinguish patients with Alzheimer's disease from a normal comparison group. Second, to access this diagnostic information, it appears that one must take advantage of the ability of PDP networks to detect higher-order nonlinear relationships among the predictor variables.

Aged↗
PubMed1986

Accumulation of polymorphonuclear leukocytes during 3-h experimental myocardial ischemia.

Recent evidence indicates that mechanical obstruction of capillaries by leukocytes plays an important role in the "no-reflow" phenomenon in the heart. This entrapment of leukocytes in the microcirculation precedes their recognized role in an inflammatory reaction following ischemia. It is a fundamental rheological mechanism that may be associated with ischemic injury and reflow injury and it has not been elucidated. To explore the accumulation of granulocytes during myocardial ischemia we studied the accumulation of 111Inlabeled autologous granulocytes in acutely ischemic myocardium during 3 h of flow reduction with and without a subsequent period of reflow in open-chest dogs. Granulocytes accumulated in the ischemic endocardium of all animals and, for the majority of dogs, also in the epicardium. Accumulation in the endocardium was enhanced by reperfusion. The entrapped leukocytes may have an influence on the increase in resistance, since regional accumulation of leukocytes in the endocardium inversely correlated with ischemic blood flow during 3 h of ischemia. The tissue water content measured from the wet and dry weights of biopsies showed a significant positive correlation with the number of entrapped granulocytes. These results suggest that collateral flow is an important mechanism of leukocyte arrival early in ischemic myocardium and that reperfusion enhances granulocyte accumulation.

Animals↗
PubMed1980

The relationship between cerebral blood flow and the EEG in normals.

Using the Xe133 inhalation technique, measurements of the blood flow to the left and right parietal and temporal regions of the cerebrum were obtained in 5 healthy individuals while simultaneously recording their EEGs. Up to 3 measurements were obtained from each of the subjects the first while they were mentally at rest and the others while they were engaged in prescribed forms of mental activity. Relationships between the measured blood flow through grey matter, initial slope index, relative grey weight, percent grey flow and power in the delta, delta-theta, alpha, beta and gamma rhythms of the EEG were examined. The results showed that for the subject group as a whole there was a strong correlation between the power present in the low frequency components of EEG and the grey flow and relative grey weight parameters of blood flow. On an individual basis, the observed relationships were highly variable particularly at high flow rates and at low relative grey weights, but became much more definitive at low flows and high weights. The results as they relate to previous work of this kind are discussed.

Adult↗