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Biomedical subjects

P Guzman

Publications and source records attributed to P Guzman.

10 recordsLinked to original sources

RESPONSIVE-TO-ANTAGONIST1, a Menkes/Wilson disease-related copper transporter, is required for ethylene signaling in Arabidopsis.

Ethylene is an important regulator of plant growth. We identified an Arabidopsis mutant, responsive-to-antagonist1 (ran1), that shows ethylene phenotypes in response to treatment with trans-cyclooctene, a potent receptor antagonist. Genetic epistasis studies revealed an early requirement for RAN1 in the ethylene pathway. RAN1 was cloned and found to encode a protein with similarity to copper-transporting P-type ATPases, including the human Menkes/Wilson proteins and yeast Ccc2p. Expression of RAN1 complemented the defects of a ccc2delta mutant, demonstrating its function as a copper transporter. Transgenic CaMV 35S::RAN1 plants showed constitutive expression of ethylene responses, due to cosuppression of RAN1. These results provide an in planta demonstration that ethylene signaling requires copper and reveal that RAN1 acts by delivering copper to create functional hormone receptors.

Alkenes↗

Subtle neurological deficits and psychopathological findings in substance-abusing homeless and non-homeless veterans.

This study evaluated the hypothesis that homeless individuals would display higher levels of neurological deficits than non-homeless individuals, particularly in frontal lobe or executive functions. Eighteen acutely homeless, 15 chronically homeless, and 20 non-homeless individuals admitted to an inpatient psychiatric service received a battery of neurological and psychosocial measures. In comparison to non-homeless subjects with comparable levels of psychopathology, homeless individuals showed higher levels of hostility, prior criminal activity, and family history of psychiatric illness, but lower levels of depression. A positive relationship between hostility and neurological soft signs was observed among chronically homeless subjects. These results suggest that a substantial subset of nonpsychotic homeless veterans suffers from "occult" neurological deficits.

Adult↗

Localization of alpha 7 nicotinic receptor subunit mRNA and alpha-bungarotoxin binding sites in developing mouse somatosensory thalamocortical system.

Previous studies in rat, showing a transient pattern of expression of the alpha 7 nicotinic acetylcholine receptor in the ventrobasal thalamus and barrel cortex during the first 2 postnatal weeks, suggest that these receptors may play a role in development of the thalamocortical system. In the present study, in situ hybridization and radiolabeled ligand binding were employed to examine the spatiotemporal distribution of alpha 7 mRNA and alpha-bungarotoxin binding sites in the thalamocortical pathway of mouse during early postnatal development. As in the rat, high levels of alpha 7 mRNA and alpha-bungarotoxin binding sites are present in the barrel cortex of mouse during the first postnatal week. Both alpha 7 mRNA and its receptor protein are observed in all cortical laminae, with the highest levels seen in the compact cortical plate, layer IV, and layer VI. When viewed in a tangential plane, alpha 7 mRNA and alpha-bungarotoxin binding sites delineate a whisker-related barrel pattern in layer IV by P3-5. Quantitative analysis reveals a dramatic decrease in the levels of expression of alpha 7 mRNA and alpha-bungarotoxin binding sites in the cortex by the end of the second postnatal week. Unlike in the rat, only low levels of alpha 7 mRNA or alpha-bungarotoxin binding sites are present in the ventrobasal complex of the mouse thalamus. The broad similarities between the thalamocortical development of rat and mouse taken together with the present results suggest that alpha 7 receptors located on cortical neurons, rather than on thalamic neurons, play a role in mediating aspects of thalamocortical development.

Animals↗

Transcription of a bacteriophage lambda DNA site blocks growth of Escherichia coli.

The rap mutation in Escherichia coli prevents the growth of bacteriophage lambda. Phage mutations that overcome rap inhibition (bar) have been mapped to loci in the pL operon. We cloned and sequenced three mutations in two of these loci: barIa to the left arm of the lambda attachment site (attP) and barII in the ssb (ea10) gene. The mutations represent single base-pair changes within nearly identical 16-base-pair DNA segments. Each mutation disrupts a sequence of dyad symmetry within the segment. Plasmids carrying a bar+ sequence downstream to an active promoter are lethal to rap, but not rap+, bacteria. The bar sequences isolated from the lambda bar mutants are not lethal. We synthesized a minimal lambda barIa+ sequence, 5'-TATATTGATATTTATATCATT, and cloned it downstream to an inducible promoter. When transcribed, this sequence is sufficient to kill a rap strain.

Alleles↗

Radiosensitization by derivatives of isoindole-4,7-dione.

New derivatives of isoindole -4,7-dione have been synthesized and their radiation sensitization and chemical behavior have been studied. One-electron reduction potentials have been determined by pulse radiolysis and found to be in the range of -0.45 to -0.36 V vs NHE . Radiosensitization effects were tested in vivo using soft tissue sarcoma transplanted in mice. All the isoindole -4,7-diones tested were found to exert considerable radiosensitization, approaching that of misonidazole tested under comparable conditions. The derivatives which contain a carbethoxy group on the pyrrolic ring were found to have more positive reduction potentials and to act as more efficient sensitizers. Further development of this class of radiosensitizers is underway.

Animals↗

Effects of coronary arterial pressure on left ventricular end-systolic pressure-volume relation of isolated canine heart.

In the excised canine left ventricle, the end-systolic pressure-volume relationship (ESPVR) has been shown to be approximately linear over the working range of loading conditions when coronary arterial pressure (CAP) is maintained constant, independent of loading conditions. To investigate the ESPVR under the more intact physiological condition in which the CAP varies with loading on the left ventricle, we studied the effect of changes in CAP on the ESPVR in 10 excised cross-circulated canine ventricles which were contracting isovolumically. The ESPVR, determined from isovolumic contractions at four different volumes, was reasonably independent of CAP as long as CAP remained above a critical pressure (67.0 +/- 22.1 mm Hg). Below this pressure, the slope of ESPVR decreased although the volume axis intercept (V0) remained unaltered. These findings indicate that under physiological conditions, where there is a close coupling of CAP to systolic left ventricular pressure, the ESPVR should become nonlinear in the low preload or afterload regions. When CAP was varied with the left ventricular pressure in five ventricles, the ESPVR indeed became nonlinear in the low-load region. We conclude that the ESPVR in intact conditions is reasonably linear in the physiological load range, but it can be nonlinear in the low-load range.

Animals↗

Ventricular size and shape by two-dimensional echocardiography.

The evaluation of cardiac size and shape has been aided by the recent development of high resolution real-time two-dimensional echocardiography, which permits dynamic cross-sectional evaluation of all or a large portion of the left ventricle throughout the cardiac cycle. This review addresses itself to the determination of left ventricular size and shape by two-dimensional echocardiography. A method is described for accurate volume determination in the intact, isolated, ejecting canine heart. By combining the two-dimensional echocardiogram with knowledge of transducer position and orientation with respect to the heart, it is possible to reconstruct a three-dimensional representation of a chamber and thereby measure volume without reliance on major geometric assumptions. Because of the unique ability of two-dimensional echocardiography to produce a cross-sectional image of the beating heart in a large number of planes, it is suitable for the determination of cardiac shape and architecture. The recognition of early regional cardiac dilatation in acute myocardial infarction is described. Changes in ventricular shape brought about by the dynamic alterations lend themselves well to two-dimensional echocardiographic study. The pivotal nature of the interventricular septum renders it susceptible to changes in the functional state of both ventricles. That the interventricular septum may mediate ventricular interaction acutely is suggested by the acute effects of right ventricular loading in man using the Mueller maneuver. Leftward septal displacement and flattening of the septum during the early maximal Mueller maneuver is evidenced by a substantial increase in the radius of curvature of the septal segment, without a change in the left ventricular free wall. This septal flattening occurs in diastole and persists during systole. Diastolic events thus appear to influence systolic shape. Changed septal shape may be an important mechanism of, and evidence for, ventricular interdependence in normal man.

Animals↗