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Biomedical subjects

M Go

Publications and source records attributed to M Go.

At least 91 records · Page 5Linked to original sources
PubMed1985

Bovine surfactant (surfactant TA) therapy in immature baboons with hyaline membrane disease.

As a prelude to clinical trials with a bovine surfactant (surfactant TA), in human infants with hyaline membrane disease, pulmonary and hemodynamic changes following its instillation in premature baboons were investigated. Baboons, delivered by cesarean section at 141 +/- 3.5 days (mean +/- SD, 77% gestation), were provided with intensive care. At 2 hours of age in one group (n = 10), 100 mg/kg of surfactant TA (reconstituted bovine surfactant, Tokyo Tanabe Co., Tokyo) was instilled into the lungs. Sequential measurements and monitoring of pulmonary and hemodynamic variables were carried out in these ten baboons and in a control group of five baboons for 16 hours, at which time the experiments were electively terminated. At birth, the pulmonary compliance, findings of chest radiographs, ratio of arterial PO2 to alveolar PO2, and respirator variables needed to maintain normal blood gas and acid base status were identical in both groups and indicative of severe hyaline membrane disease. Following surfactant instillation, the treated group demonstrated a rapid increase in PO2 with significantly improved ratio of arterial PO2 to alveolar PO2 (from a mean +/- SD pretreatment value of 0.21 +/- 0.11 to 0.45 +/- 0.11 by 16 hours). Pulmonary compliance improved similarly (from pretreatment value of 0.18 +/- 0.06 mL/cm H2O/kg to 0.27 +/- 0.09 mL/cm H2O/kg). Significant reduction in respirator support variables could be achieved in all treated animals; however, in the control animals, the pulmonary status worsened as evidenced by increasing mean airway pressure and respirator variables to keep normal blood gas and acid base status, thus worsening compliance. At autopsy, pulmonary pressure-volume curves were significantly different with large hysteresis obtained in the surfactant-treated group. Although no deleterious effect on hemodynamics was noted in surfactant TA-treated animals, a large patent ductus arteriosus was demonstrated by aortography. Increased lung blood flow, probably due to a large patent ductus arteriosus flow, was demonstrated by radiolabeled microsphere technique. The physiologic significance and clinical relevance of these findings in premature baboons treated with surfactant TA are discussed.

Animals↗
PubMed1984

Improved efficacy of high-dose versus medium- and low-dose diltiazem therapy for chronic stable angina pectoris.

The efficacy of therapy with diltiazem, 360 mg/day, was studied in 11 men with chronic, stable angina pectoris. An initial dose-titration schedule in which diltiazem was increased weekly from placebo to 120, 240 and 360 mg/day (Period I) was followed by a randomized, double-blind, 1-month crossover trial of placebo vs diltiazem at 360 mg/day (Period II). A computer-assisted treadmill exercise test was performed at the end of each dose and each 2-week crossover period. Diltiazem at 360 mg/day, compared with placebo (Period II), significantly improved exercise performance. Exercise duration to onset of chest pain increased 40% from 5.3 +/- 2.1 to 7.4 +/- 2.7 minutes (p less than 0.01). Time to reach 1 mm of ST-segment depression increased 33%, from 5.1 +/- 2.0 to 6.8 +/- 1.8 minutes (p less than 0.01). Total exercise duration increased 16%, from 7.5 +/- 2.0 to 8.7 +/- 2.0 minutes (p less than 0.005). A computer-derived quantitative treadmill exercise score improved 27%, from -13.1 +/- 9.4 to -9.5 +/- 7.6 units (p less than 0.005), and the ST-segment depression at peak exercise improved from -1.9 +/- 1.1 to -1.6 +/- 1.2 mm (p less than 0.05). Progressive improvement in these variables was seen during the single-blind dose-titration period between 120 and 240 mg/day and between 240 and 360 mg/day (Period I). Baseline heart rate (HR) and diastolic blood pressure (BP) in the supine and upright position were significantly lower with diltiazem than with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1984

Clinical studies with transdermal nitroglycerin.

The short- and long-term effects of various Nitro-Dur formulations on performance and hemodynamics were studied in 15 men with stable angina pectoris who also had a positive treadmill exercise test. A treadmill exercise score (TES) was used that quantified the "ischemic" ST segment response to exercise. The score incorporated information that reflected the rapidity of evolution of ST segment depression during exercise and the time required for it to resolve after cessation of exercise. In early tests (n = 10) Nitro-Dur improved both the TES (by 31%: p less than 0.0001) and the time required for 1 mm ST segment depression (by 33%: p less than 0.0001). At all dosage levels, Nitro-Dur also decreased resting systolic blood pressure and increased resting heart rate. No dose-response patterns emerged. Changes in TES and time to ST segment depression were greater with sublingual nitroglycerin than they were with Nitro-Dur. In tests conducted after prolonged dosage (n = 5), the effects of Nitro-Dur on blood pressure and heart rate became attenuated at weeks 2 and 4, although cardiac responsiveness was preserved, as reflected in the increased time required before the occurrence of 1 mm ST segment depression. The latter effect was also observed with sublingual nitroglycerin. The clinical relevance of these data to the design of individual patient therapy is discussed.

Angina Pectoris↗
PubMed1983

Modular structural units, exons, and function in chicken lysozyme.

By the application of the same algorithm for finding compact structural units encoded by exons as applied previously to hemoglobin, five units, M1-M5, were identified in chicken egg white lysozyme. They consist of residues 1-30, 31-55, 56-84, 85-108, and 109-129, respectively. I call these compact structural units "modules." As in hemoglobin, modules thus identified correspond well to exons--i.e., modules M1, M2 plus M3, M4, and M5 correspond to exons 1, 2, 3, and 4 of the lysozyme gene, respectively. Localization of the catalytic sites glutamic acid-35 and aspartic acid-52 on the module M2 suggests that this module might have worked as a functional unit in a primitive lysozyme. The good correspondence between exons and modules reinforces the idea of "proteins in pieces," which was derived from the fact of "genes in pieces." The evolutionary origin of the introns in globins and lysozyme is discussed.

Animals↗
PubMed1983

Pharmacological study of the antitussive and respiratory-analeptic properties of N-(2'-ethylpyrrolidino)diphenylacetamide hydrochloride (F 1459).

The antitussive and respiratory stimulant properties of N-(2'-ethylpyrrolidino)diphenylacetamide hydrochloride (F 1459) in animals are reported. In the mechanical stimulation of the trachea in guinea pigs and after intraperitoneal administration of the product, F 1459 showed a better antitussive action as compared to oxeladin, zipeprol, codeine and clobutinol. Low intraduodenal doses of F 1459 also reduced in cats the cough induced by the electrical stimulation of the superior laryngeal nerve. In anesthetized dogs whose respiratory functions had been depressed by morphine, F 1459 significantly increased the volume inspired per minute, an effect not due to any uncoupling effect on oxidative phosphorylation. F 1459 has local anesthetic and broncholytic properties that may play a role in the mechanism of its antitussive action. Contrarily to codeine, the test compound did not induce a decrease in the intestinal transit.

Anesthetics, Local↗
PubMed1981

Correlation of DNA exonic regions with protein structural units in haemoglobin.

The discovery of intervening sequences (introns) in DNA led Gilbert and Tonegawa to suggest that a new protein could have been produced by bringing together certain segments of pre-existing ones. However, Blake argued that if DNA was so organized that coding sequences (exons) correspond to structural as well as functional units of proteins, then combinations would be much more likely to yield a stable globular conformation through being 'sums of parts'. In immunoglobulin heavy chain, four separate exons encode four different units, all with distinct functions and three of which have clear domain structures. However, in haemoglobin, which has no obvious domain structure, no clear conformational characteristics have so far been recognized for the segments encoded by exons. From a close inspection of their conformations by drawing various stereodiagrams and the Calpha-Calpha distance map, I now propose a conformational characterization of the segments as structural units.

Animals↗
PubMed1980

Relationship between mutability, polarity and exteriority of amino acid residues in protein evolution.

A systematic study was carried out on mutability of amino acid residues in evolving proteins in relation to their polarity and location within three-dimensional structure of proteins. Exteriority of residue sites is quantitatively defined as accessibility based on their static accessible surface area to solvent water molecule. Residue sites are classified into interior and exterior depending on their accessibility. More frequent substitution on exterior sites is confirmed to be general in eight sets of homologous protein families regardless of their biological functions and of presence or absence of a prosthetic group. Virtually all types of amino acid residues are found to have higher mutabilities on the exterior than in the interior. No correlation between mutability and polarity was observed of amino acid residues in the interior and on the exterior, respectively. Amino acid residues are classified into three depending on their polarity, polar (Arg, Lys, His, Gln, Asn, Asp and Glu), weak polar (Ala, Pro, Gly, Thr and Ser) and nonpolar (Cys, Val, Met, Ile, Leu, Phe, Tyr and Trp). Amino acid replacements during protein evolution are very conservative; 88% and 76% of them in the interior and on the exterior, respectively, are within the same group of the three. Inter-group replacements are such that weak polar residues are replaced more often by nonpolar residues in the interior and more often by polar residues on the exterior.

Amino Acids↗
PubMed1978

Volume and polarity changes accompanied by amino acid substitutions in protein evolution.

We evaluated the volume and polarity changes accompanied by amino acid substitutions along branches of the phylogenetic trees of cytochrome c, myoglobin and hemoglobin alpha and beta chains. In most cases the volume changes accompanied by the substitutions were found to be much larger than the volume of cavities existing in the interior of X-ray-analysed proteins. This implies that the interior of the proteins is very flexible and the necessary space for a larger amino acid residue substitution can be provided by adjusting nearby structures. Also, the volume and polarity changes are not particularly dependent on whether the substituted site is located in the exterior or interior of the proteins. This result supports the concept of the covarions by Fitch and Markowitz, when combined with the known fact that the exterior sites are more variable than the interior ones during protein evolution.

Amino Acids↗