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Biomedical subjects

S Mathews

Publications and source records attributed to S Mathews.

At least 37 records · Page 2Linked to original sources

Spatiotemporal transfer function of human accommodation.

We have investigated the spatiotemporal transfer function of human "reflex" accommodation. An accommodative mechanism that is sensitive to an intermediate temporal rate of retinal image contrast change is proposed as the basis of the fine focus control hypothesis. To test the proposed mechanism accommodative responses were monitored by a dynamic infrared optometer while the subject focused on sinusoidal gratings (0.98-10.5 c/deg) which were moving sinusoidally at temporal frequencies in the range of 0.05-0.80 Hz over a 0.50 or 2.00 D peak-to-peak amplitude. The accommodative responses were best at 3 and 5 c/deg at both amplitudes of target motion. This result does not support the proposed mechanism or the fine focus control hypothesis for "reflex" accommodation. Fitting the data with first-order response functions showed little evidence of prediction. In addition, a second experiment found that the profile of the accommodative gain function is not altered by instruction at spatial frequencies above 5 c/deg in this type of dynamic accommodation experiment. The use of sinusoidally moving accommodative blur targets, particularly with careful instruction, seems to discourage voluntary accommodation in investigations of "reflex" control mechanisms of accommodation.

Accommodation, Ocular

Ciprokiren (Ro 44-9375). A renin inhibitor with increasing effects on chronic treatment.

The present study characterizes the new transition-state renin inhibitor ciprokiren (Ro 44-9375) in squirrel monkeys. Arterial blood pressure was monitored by telemetry in freely moving, chronically instrumented conscious animals. In vitro at pH 7.4, ciprokiren inhibited human renin in buffer and human plasma with an IC50 of 0.07 and 0.65 nmol/L, respectively. It was equipotent against primate plasma renin and also inhibited plasma renin from dog and guinea pig in the nanomolar range (IC50, 29 and 65 nmol/L, respectively). After acute oral administration it reduced arterial blood pressure dose dependently in normotensive sodium-depleted and cyclosporin-induced hypertensive squirrel monkeys, starting with the minimal oral dose of 3 micrograms/kg. Daily oral doses of 1 microgram/kg showed a progressive blood pressure decrease, with a maximal response reached after 1 week. The drug could also be applied transdermally with similar hemodynamic effects without any decrease of plasma renin activity or plasma immunoreactive angiotensin II. Thus, ciprokiren is characterized in squirrel monkeys as a renin inhibitor with high in vivo potency that might act mainly in the tissular compartment.

Animals

Chromatic aberration and ocular focus: Fincham revisited.

Longitudinal chromatic aberration of the eye (LCA) produces "color fringes" at edges that specify focus. Fincham [(1951) British Journal of Ophthalmology, 35, 381-393] concluded that these chromatic effects were important for accommodation, but most investigators disagree. We monitored accommodation in 25 subjects while they viewed a sinusoidally moving target (1.5-2.5 D at 0.2 Hz) in a Badal optometer. The target was monochromatic (590 nm with 10 nm bandwidth), or white (3000 K) with LCA normal, neutralized or reversed. Sensitivity to the effects of LCA is profound and widespread. Gain decreases substantially and phase-lag increases when LCA is eliminated, and reversing the aberration severely disrupts accommodation. The ordered arrangement of spectral foci produced by LCA seems to be a fundamental aspect of the stimulus for "reflex" accommodation.

Accommodation, Ocular

Symptomatic spondylolysis: correlation of CT and SPECT with clinical outcome.

Twenty-seven patients with spondylolysis and back pain were considered for spinal fusion. All patients underwent clinical evaluation, multiplanar computed tomography (CT) and single photon emission computed tomography (SPECT). After clinical evaluation 12 patients were not considered suitable for fusion on clinical grounds. SPECT was normal in these patients. Fifteen underwent a trial of lumbar immobilization and nine of those rendered pain free subsequently underwent spinal fusion. The results of clinical examination, lumbar immobilization, imaging and final outcome were compared in these patients. Those patients rendered pain free by surgery all had positive SPECT scans. Those with persistent pain after surgery had negative scans. This small series suggests a positive relationship between SPECT scanning and patient outcome following fusion. These findings need to be confirmed by larger studies with longer periods of follow-up.

Adolescent

Accommodation and chromatic aberration: effect of spatial frequency.

When subjects view an edge in white light, a colour fringe, produced by longitudinal chromatic aberration (LCA) of the eye, is formed at the edge. The colour fringe changes with changes in focus, and serves as a complex colour-coded cue for reflex accommodation. Fincham found that 60% of his subjects failed to accommodate appropriately when the colour fringe was removed with an achromatizing lens or by the use of monochromatic light. Our experiment sought to determine the spatial frequencies at which LCA is most effective. We monitored accommodation in 10 subjects while they viewed sinusoidally moving sine-wave gratings (1-3 D at 0.2 Hz; 1-10.5 c/deg) in a Badal optometer. The targets were 'white' gratings with LCA normal, doubled, neutralized or reversed. Doubling the aberration has minimal effect, removing the aberration reduces gain and increases phase-lag, and reversing the aberration severely disrupts accommodation. Sensitivity to these chromatic cues exists at all spatial frequencies tested, but is most prominent between 3 and 5 c/deg. These results support the view that the system monitors focus by comparing contrast in red-green and perhaps blue-yellow colour-opponent mechanisms.

Accommodation, Ocular

A trial of desmopressin to reduce blood loss in patients undergoing spinal fusion for idiopathic scoliosis.

Desmopressin (DDAVP) has been reported to reduce bleeding in patients undergoing spinal fusion. To evaluate its efficacy in normal patients, 30 healthy young patients (ASA physical status I or II) undergoing spinal fusion for idiopathic scoliosis were randomly allocated to receive either 100 mL of physiologic saline solution (placebo group) or DDAVP (10 micrograms/m2 of body surface area) (DDAVP group) in a prospective, double-blind trial. Intraoperative blood loss was measured by weighing sponges and suction drainage and postoperative bleeding by wound drainage. The amount of blood loss expressed as a percent of the estimated blood volume was similar in both groups during the intraoperative period (67.0% +/- 28.8% [mean +/- SD] placebo group vs 57.4% +/- 26.5% DDAVP group), the postoperative period up to 24 h (32.5% +/- 6.4% placebo group vs 31.1% +/- 10.6% DDAVP group), and both periods (94.3% +/- 29.4% placebo group vs 88.2% +/- 30.7% DDAVP group). With the dose used in our study, we conclude that DDAVP does not reduce surgical bleeding in patients undergoing spinal fusion for idiopathic scoliosis.

Adolescent

The differentiation pathway of HL60 cells is a model system for studying the specific regulation of some myeloid genes.

During granulopoiesis, certain myeloid genes encoding products of azurophilic granules are specifically down-regulated. The myeloid specific enzyme myeloperoxidase belongs to this group of genes. It is responsible for the production of hypochlorous acid, a potent microbicidal agent which is involved in host defense. During induced differentiation of promyelocytic leukemic HL60 cells to granulocyte- or monocyte-like cells, myeloperoxidase RNA is depressed. We studied this depression process in more detail by limiting the exposure to the inducer phorbol 12-myristate 13-acetate to 24 h. During this time period, no significant decrease in cell number and cell viability could be observed. Analysis of these in vitro differentiated HL60 cells on the protein and RNA levels showed that they can be used under defined conditions as a cell system to study the specific depression of myeloid genes. Under the described conditions, both the transcriptional rate of the myeloperoxidase gene as well as the stability of its transcript was reduced.

Actins

What is the utility of the psychophysical 'light scattering factor'?

It has been suggested by Sjöstrand and his colleagues that an index of scatter by the ocular media may be derived from contrast sensitivity measured with and without a glare source. This index was tested under different conditions of stimulus luminance and found not to be constant and thus to not reflect a property of the media.

Adult

Arterial catheter-related infections in children. A 1-year cohort analysis.

To determine the incidence of infection secondary to arterial catheterization in children as well as the risk markers, we prospectively evaluated, during a 1-year period, all arterial catheters installed in children admitted to the pediatric intensive care unit. A total of 340 cannulas were placed in 310 children aged 80 +/- 4 months (mean +/- SEM) for a period of 64 +/- 4 hours. Most catheters were inserted percutaneously (99%) in the radial artery (86.5%). Ninety-two percent (313/340) of the catheters were sterile (group 1), 5% (17/340) were contaminated (less than 10 colony-forming units on semiquantitative culture) (group 2), and 3% (10/340) were considered either locally infected (ie, greater than or equal to 10 colony-forming units) (eight of 10) or associated with a possible catheter-related sepsis (two of 10) (group 3, or infected group). The incidence of local inflammation at the insertion site was higher in group 2 than in group 1 (18% vs 2.9%) but not statistically different between groups 3 and 1 (10% vs 2.9%). The duration of arterial catheterization was longer in group 3 than in group 1 (125 +/- 31 vs 61 +/- 4 hours). The risk of infection was nonexistent in the first 48 hours of catheterization. Thereafter it was calculated as being 6.2% (10/161), but it correlated poorly with the duration of arterial catheterization. These results confirm the very low incidence of infection related to arterial catheterization in children. Thus, routine catheter reinsertion is, in our opinion, unjustified.

Adolescent

Multiple divergent mRNAs code for a single human calmodulin.

The isolation of a novel complementary DNA (cDNA) clone coding for human calmodulin (CaM) is reported. Although it encodes a protein indistinguishable from the only known higher vertebrate calmodulin, its nucleotide sequence varies extensively from that of two previously reported human CaM cDNAs (Wawrzynczak and Perham, 1984; SenGupta et al., 1987). Only 82 and 81% identity, respectively, is found between the newly isolated and the two known human mRNAs in their coding regions. No striking homology is present in their noncoding regions. Codon usage in the three CaM mRNAs is also surprisingly divergent. A 2.3-kilobase mRNA corresponding to the newly isolated clone is expressed to varying extents in several human tissues, together with an approximately 0.8-kilobase mRNA species presumably arising from alternative polyadenylation of the same primary transcript. The results indicate that the human genome contains at least three divergent CaM genes that are under selective pressure to encode an identical protein while maintaining maximally divergent nucleotide sequences. Partial characterization of a genomic clone specifying the 3' portion of the newly identified CaM mRNA shows that this gene contains introns at identical positions as the previously characterized bona fide vertebrate CaM genes. Evolutionary implications of the presence of a CaM multigene family are discussed.

Amino Acid Sequence

Complete primary structure of a human plasma membrane Ca2+ pump.

cDNAs coding for a plasma membrane Ca2+ pump were isolated from a human teratoma library and sequenced. The translated sequence contained 1,220 amino acids with a calculated molecular weight of 134,683. All regions of functional importance known from other ion-transporting ATPases could be identified. The translated sequence also contained, near the carboxyl terminus, the calmodulin-binding domain and two domains which are very rich in glutamic acid and aspartic acid. These two domains resemble calmodulin somewhat and one of them may play a role in the binding of Ca2+. The enzyme also contains domains rich in serine and threonine, one of which has a sequence matching those of good cAMP-dependent protein kinase substrates. The carboxyl-terminal region is important for regulation by calmodulin, proteolysis, and phosphorylation. Near the amino terminus are two domains which are very rich in lysine and glutamic acid, as well as two domains resembling EF hands, one of which also has some resemblance to calmodulin. Comparison of the cloned sequence with peptide sequences from the erythrocyte Ca2+ pump showed that the two proteins have a very high proportion of identical residues but are not 100% identical, indicating that they represent different isozymes.

Amino Acid Sequence

Mapping of brain areas containing RNA homologous to cDNAs encoding the alpha and beta subunits of the rat GABAA gamma-aminobutyrate receptor.

An in situ hybridization technique was used to determine the distribution in rat brain of RNA homologous to cDNA clones encoding the alpha and beta subunits of the rat brain GABAA gamma-aminobutyrate receptor. The subunit proteins were mapped in adjacent sections autoradiographically and immunohistochemically. Many brain areas containing high densities of GABAA receptors showed strong hybridization signals with both the alpha- and the beta-subunit antisense RNA probe--e.g., cerebral cortex, hippocampus, and cerebellum. On a cellular level, a dense dendritic localization of GABAA receptors was correlated with a strong hybridization in the corresponding somata--e.g., in mitral cells of the olfactory bulb, pyramidal cells of hippocampus, granule cells of the dentate gyrus, and Purkinje and granule cells of the cerebellum. In some brain areas--e.g., substantia nigra--the intensity of the hybridization signal with the beta-subunit probe was much weaker than that with the alpha-subunit probe, whereas the inverse ratio of hybridization intensity was found in others--e.g., in bed nucleus. This regional heterogeneity in the hybridization pattern may reflect regional differences in RNA stability, transcription rate, or subunit composition. The results open the way for studies on the regulation of GABAA-receptor gene expression in normal and pathological brain in situ.

Animals

Cloning of the K+-ATPase of Streptococcus faecalis. Structural and evolutionary implications of its homology to the KdpB-protein of Escherichia coli.

The K+-ATPase of Streptococcus faecalis consists of a single polypeptide component of relative Mr = 78,000 and serves as an ATP-driven pump for the accumulation of potassium by the bacterial cell. The gene encoding this ATPase was isolated by immunological screening of an S. faecalis genomic library in the Escherichia coli/pUC8 host/vector system. Two independently derived clones express the full-size ATPase polypeptide. Transcription and translation of the cloned DNA apparently proceed by means of the respective S. faecalis signals. DNA sequencing revealed a gene encoding a protein of 583 amino acids and a calculated Mr of 63,070. This protein exhibits in its primary structure regions of homology with the KdpB-subunit of the K+-ATPase of E. coli and, to a lesser extent, with eukaryotic ion-motive ATPases. The hydropathy profiles and secondary structure predictions, respectively, for the S. faecalis ATPase and the E. coli KdpB-protein show striking similarity. Even regions with low homology in the amino acid sequence exhibit structural features that have clearly been conserved in the two proteins. This points to a fundamental role of these domains in the structure and/or function of these transport ATPases.

Adenosine Triphosphatases

Expression of the "split gene" COB in yeast mtDNA. Translation of intervening sequences in mutant strains.

This study deals with the effects that mutations in the COB region of yeast mtDNA have on the expression of mitochondrially made polypeptides. Based on the detection of two series of polypeptide chain-terminating mutations, we conclude that two proteins are specified by this region, apocytochrome b (Mr = 30,000) and a polypeptide of Mr = 42,000. One series of mutations generates new polypeptides ranging in size from 8,000 to 29,000 daltons; all of them are precipitated by serum direct against apocytochrome b. These mutations are located in five distinct segments of the COB region, the sequences alpha to epsilon coding for apocytochrome b. The second series of mutations, generating new polypeptides ranging in size from 17,000 to 41,000 daltons, is located within the first intervening sequence (alpha/beta) of the split gene for apocytochrome b. These mutations cause premature chain termination in the COOH-terminal part of a 42,000-dalton polypeptide. Its NH2-terminal part is likely to be specified by sequence alpha and thus to be homologous to that of apocytochrome b. We conclude that the 42,000-dalton polypeptide is translated on a processing intermediate of th COB transcript by reading through sequence alpha into sequence alpha/beta. We discuss the hypothesis that this polypeptide has a function in the expression of the COB region, possibly at the level of transcript processing.

DNA, Mitochondrial