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Biomedical subjects

M Price

Publications and source records attributed to M Price.

At least 127 records · Page 7Linked to original sources

Drug reviews.

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Aged↗

Regional distribution of muscarinic receptors preferring gallamine in the rat brain.

The regional distribution of muscarinic receptors recognized by the antagonist gallamine was determined autoradiographically by the ability of gallamine to reduce the binding of [3H]quinuclidinyl benzilate in rat brain slices. The inhibition data obtained from indirect binding assays on whole slices indicated that gallamine distinguished at least two sites with differing affinities. Analysis using a two-site model gave Kh = 0.6 microM, K1 = 10 microM. The regions of highest and lowest affinity for gallamine were apparent qualitatively by visual inspection of the autoradiograms. A number of regions in coronal sections at three different levels were compared by microdensitometry. Gallamine possessed greater overall affinity for the diencephalon and brainstem than for the forebrain. Within the forebrain, the septal nucleus was unique in that it displayed high affinity for gallamine. Within the brainstem, the superior colliculus had the greatest proportion of sites with high affinity for gallamine. In general, the binding profile of gallamine was opposite to that of the antagonist pirenzepine and similar to that of the agonist carbachol, suggesting that gallamine is selective for M2 muscarinic receptors.

Animals↗

The correlation of functional and structural measurements in glaucoma patients and normal subjects.

We measured a number of structural characteristics of the optic nerve head and retina in 52 glaucoma suspects, 51 glaucoma patients, and 28 normal eyes. In all of the patients, a number of psychophysical functions were recorded and evoked cortical potentials and pattern electroretinography were obtained. The correlations between these structural and functional parameters were established by multiple regression. Diffuse structural changes in the optic nerve head and retina were related to differential light threshold and color that measure diffuse psychophysical disturbances. Localized changes in the retinal nerve fibers and the vertical cup/disk ratio related to the "corrected loss variance," which is an index measuring localized psychophysical changes.

Glaucoma↗

The mouse myoglobin gene. Characterisation and sequence comparison with other mammalian myoglobin genes.

Seal myoglobin (Mb) exons 1 and 3 were used as probes to isolate the functional mouse Mb gene. This gene has a very low level of Mb expression in skeletal muscle. Although it is shorter, the mouse Mb gene displays the common organisation found in human and seal Mb genes. In addition, we have defined blocks of conserved sequences in the 5' flanking region by comparison with other mammalian Mb genes. Moreover, about 10(3) bases upstream of the cap site we identified a repetitive B1 element directly associated with two overlapping open reading frames, containing a putative polyadenylation signal. A polypyrimidine-rich region has also been located upstream from the gene.

Animals↗

N-methylaspartate: an effective tool for lesioning basal forebrain cholinergic neurons of the rat.

The ability of the excitotoxin, N-methyl-D,L-aspartic acid (NMA), to destroy basal forebrain cholinergic (BFC) neurons was evaluated. NMA (100 nmol) was directly injected into the peripallidum, a region containing a proportionately large number of cortically-projecting BFC neurons. Cholineacetyltransferase (ChAT) activity 10 days later was markedly and significantly reduced (up to 62%) in the cortex ipsilateral to the lesion. NMA induced a focal lesion affecting BFC neurons without damaging axons of passage or causing lesions distant from the site of injection. ChAT immunohistochemistry (IHC) was used to directly demonstrate loss of ChAT-positive neurons from the lesion site. This loss persisted at all survival times examined, from 2 days to 7.5 months post-injection.

Animals↗

Color vision and retinal nerve fiber layer in early glaucoma.

We tested 47 eyes in 47 patients (ten normal subjects, 15 with suspected glaucoma, and 22 with glaucoma) with the Pickford-Nicholson anomaloscope to assess the retinal nerve fiber layer and measure color vision. The 47 subjects were randomly selected from a group of 132 for whom Farnsworth-Munsell 100-hue color error scores were known. The yellow-blue and green-blue anomaloscopic matching ranges correlated significantly with diffuse retinal nerve fiber loss. There was no correlation with localized retinal nerve fiber loss.

Adult↗

Increased potassium permeability in erythrocytes from patients with hyperparathyroidism.

Parathyroid hormone (PTH) has been shown to modify Ca2+ and Na+ transport in several epithelia. The molecular mechanisms of these effects are poorly understood. We investigated here whether PTH may modify Na+ and K+ transport across the human red blood cell membrane in vitro and ex vivo. Fourteen patients with severe primary or secondary hyperparathyroidism and hypercalcemia were studied before and 5-7 days after surgical parathyroidectomy. Erythrocyte ouabain-sensitive as well as furosemide-sensitive Na+ efflux rates of the patients were comparable to that of healthy volunteers and remained unchanged after parathyroidectomy. Moreover, erythrocyte Na+ fluxes of control subjects remained unchanged when red blood cells were incubated in the presence of 1.0 IU/ml of bovine PTH (1-85). However, erythrocytes from hyperparathyroid patients showed a significant increase in passive K+ permeability when compared to that of healthy controls (p less than 0.05). This abnormality could be corrected in vivo after parathyroidectomy and in vitro using quinine, respectively. It is concluded that hyperparathyroidism induces a moderate increase in Ca2+ dependent K+ permeability of erythrocytes ("Gardos effect") which is reversible after parathyroidectomy.

Adult↗

Myoglobin expression: early induction and subsequent modulation of myoglobin and myoglobin mRNA during myogenesis.

We showed that myoglobin gene transcription and the appearance of myoglobin occur very early in myogenesis, in both humans and mice. In contrast to the contractile protein genes, there is a subsequent increase of 50- to 100-fold in myoglobin mRNA and protein levels during later muscle development. Myoglobin and myoglobin mRNA are present at elevated levels in fetal heart and are also detectable at low levels in adult smooth muscle. The absolute level of myoglobin mRNA in highly myoglobinized seal muscle is very high [2.8% of the total population of poly(A)+ RNAs]. Levels of myoglobin in seal skeletal muscle and in various human muscle types appear to be determined by the size of the myoglobin mRNA pool. In contrast, low levels of myoglobin in mouse skeletal muscle are not apparently correlated with low levels of myoglobin mRNA. As expected from the early appearance of myoglobin mRNA in embryonic skeletal muscle, both rat and mouse embryonic myoblasts accumulate myoglobin mRNA on fusion and differentiation in vitro.

Actins↗

Effect of diuretic therapy on ventricular arrhythmias in hypertensive patients with or without left ventricular hypertrophy.

Recent studies have suggested that hypertensive patients with ECG evidence of left ventricular hypertrophy (LVH) may have increased risk of sudden death when treated with diuretics. In the present study echocardiography was used as a more sensitive index for the presence of LVH. Thirty-one patients with uncomplicated hypertension underwent 48-hour ambulatory ECG monitoring both before any treatment and after 4 weeks of hydrochlorothiazide, (HCTZ), 100 mg daily. In 18 patients with left ventricular posterior wall thickness (LVPWT) greater than or equal to 13 mm (average = 14.4 +/- 0.2 mm) on echocardiogram, plasma potassium decreased from 4.1 +/- 0.3 to 3.3 +/- 0.4 mEq/L with HCTZ (p less than 0.01). Premature ventricular contractions (PVCs) averaged 5.7 +/- 9.9/hr at baseline and 7.1 +/- 16.6/hr following HCTZ (p = NS). The total number of couplets was 29 before and 13 after HCTZ, while four brief runs of ventricular tachycardia occurred only before treatment. In the remaining 13 patients with LVPWT less than or equal to 12 mm (average = 11.2 +/- 0.1 mm), plasma potassium decreased from 4.1 +/- 0.3 to 3.4 +/- 0.5 mEq/L with HCTZ (p less than 0.01). The average number of PVCs was 4.3 +/- 8.0/hr after HCTZ (p = NS). One couplet and one 3-beat run of ventricular tachycardia occurred before and one 3-beat run of ventricular tachycardia after HCTZ. Although more complex arrhythmias were noted in the LVH group, the differences were not statistically significant. These results indicate that thiazide therapy does not increase ventricular arrhythmias either in patients with or without LVH.

Adult↗

Depot fluphenazine and plasma prolactin.

In 14 schizophrenic patients, prolactin levels are studied in relation to dosage of depot fluphenazine and gender of patient. Prolactin levels in individual patients are similar across injection cycles. For males, the association between fluphenazine dosage and prolactin level was found to be significant (Spearman rho = .925, p less than .05).

Drug Tolerance↗

A classification of essential hypertensive patients according to the erythrocyte Na transport abnormalities: an application for monitoring the antihypertensive response to cicletanide.

We have studied the kinetic properties of the interaction of internal Na with four different Na transport pathways (ouabain-sensitive Na, K pump, bumetanide-sensitive Na,K cotransport, Li:Na countertransport and passive Na permeability) in erythrocytes from 197 essential hypertensive patients. This study permitted us to classify 168 of the 197 hypertensives studied into the following groups: Pump - hypertensives-six patients showing low pump affinity for internal Na and high maximal pump rate; Co - hypertensives -95 patients characterized by low cotransport affinity for internal Na and low or normal maximal outward cotransport rate. Counter + hypertensives - 35 patients characterized by low countertransport affinity for internal Na and high maximal countertransport rate; and Leak + hypertensives - 32 patients showing increased passive Na permeability. Having studied the apparent affinity of the Na,K cotransport system for external K we divided the co - hypertensives into three subgroups (symmetric, asymmetric or antisymmetric) according to the presence of low, normal or high K affinity. Forty-five hypertensive patients were submitted to antihypertensive treatment with a new diuretic and antihypertensive drug, cicletanide. Preliminary results indicate that one of the factors involved in the antihypertensive efficiency of the compound is the subgroup to which the hypertensive belongs.

Adult↗

External catheters: hazards and benefits of their use by men with spinal cord lesions.

Urinary tract status was reviewed in 60 men with spinal cord injury who had external bladder drainage from 1 to 159 months. Before use, 34 (57%) patients were free of roentgenographic abnormalities, and 27 (79%) of these developed changes. Twenty-six (43%) patients of the total group initially had morphologic defects; 5 (19%) of these became free of abnormalities, while 21 (81%) did not improve or showed progression. Glomerular filtration rate improved in 2 (3%) of the total study group, deteriorated in 12 (20%), and remained stable in 46 (77%). Infection persisted in 32 (53%); 10 (31%) of the positive cultures grew multiple isolates. In 18 (56%) of those patients with positive urine cultures, tissue invasion was indicated by the presence of antibody-coated bacteria. After external drainage 5 (8%) required sphincterotomy, 3 (5%) supravesical diversion, and 2 (2%) suprapubic cystotomy. Patient histories and examinations revealed tendencies toward poor hygiene and inattention to adequate bladder emptying. Equipment obstruction was common because of twisting or improper placement of drainage apparatus. It was concluded that although carefully monitored external catheters may accomplish adequate drainage and sterile urine, the hazards of infection and overdistention are great and must be countered by medical monitoring and ongoing patient education.

Catheters, Indwelling↗

Early changes in plasma and urinary potassium in diuretic-treated patients with systemic hypertension.

Two groups of patients with uncomplicated systemic hypertension were studied. Group 1 included 11 patients who had overt hypokalemia with diuretic drug treatment, and group 2 included 11 patients who remained normokalemic. After baseline studies without treatment were performed, both groups received hydrochlorothiazide, 50 mg twice daily. Plasma potassium (PK) was significantly reduced within the first day of treatment and stabilized by day 7 in both groups. The average decrease in PK was 1.0 +/- 0.1 mEq/liter (p less than 0.01) in the first group and 0.6 +/- 0.2 mEq/liter (p less than 0.01) in the second group. Cumulative losses of K were approximately 200 mEq in the hypokalemic group and were minimal in the normokalemic group as assessed by 24-hour urinary collections. Patients in the hypokalemic group also had a greater reduction in body weight and blood pressure. Supplementation with KCl, 96 mEq/day, or triamterene, 200 mg/day, in 9 hypokalemic patients resulted in an increase of PK to approximately 3.5 mEq/liter leveling off by day 7, and a cumulative K retention of approximately 200 mEq. Thus, overt thiazide-induced hypokalemia was associated with small and biologically unimportant losses of K from body stores. With replacement therapy the estimated amount of retained K was also small.

Blood Pressure↗

pH homeostasis in human lymphocytes: modulation by ions and mitogen.

Quiescent human peripheral blood lymphocytes have been shown to maintain a relatively constant intracellular pH of 7.0-7.2 over an extracellular pH range of 6.9-7.4. Two methods of measuring intracellular pH were used in these studies, 19F nuclear magnetic resonance and [14C]5,5-dimethyloxazolidine-2,4-dione (DMO) equilibrium distributions. When ATP levels were decreased in these cells, actively maintained pH regulation was abolished and cells exhibited a constant pH gradient of 0.2 pH unit (acid inside relative to outside). Possible mechanisms for pH regulation are discussed. The effects of the Na+ and K+ composition of the medium on pH regulation showed no correlation with their effects on mitogen-induced proliferative response, which we have previously determined (Deutsch, C., and M. Price, 1982, J. Cell. Physiol., 111:73-79). In low-Na+ mannitol medium, pH regulation was similar to that observed for lymphocytes in normal medium, whereas mitogen-induced proliferation was severely inhibited in low-Na+ mannitol. In contrast, high-K+, low Na+ medium caused loss of pH homeostasis, whereas it restored the proliferative response. Loss of pH homeostasis was also observed on prolonged exposure of lymphocytes to mitogen (greater than 6 h in culture). However, mitogen stimulation led to little or no change in intracellular pH in the first few hours of cell culture. Therefore, a shift in intracellular pH is not a necessary or general event in mitogen-stimulated proliferation of lymphocytes.

Adenosine Triphosphate↗

Genetic characterization and molecular cloning of the tripeptide permease (tpp) genes of Salmonella typhimurium.

Of the three bacterial peptide transport systems only one, the oligopeptide permease, has been characterized in any detail. We have now isolated Salmonella typhimurium mutants deficient in a second transport system, the tripeptide permease (Tpp), using the toxic peptide alafosfalin. Alafosfalin resistance mutations map at three loci, the gene encoding peptidase A (pepA) and two transport-defective loci, tppA and tppB. Locus tppA has been mapped to 74 min on the S. typhimurium chromosome, cotransducible with aroB, and is a positive regulator of tppB. Locus tppB maps at 27 min in the cotransduction gap between purB and pyrF. We cloned tppB, the structural locus for the tripeptide permease. Two simple methods are described for mapping the location of cloned DNA fragments on the chromosome of S. typhimurium.

Alanine↗