Biomedical subjects

M S Paul

Publications and source records attributed to M S Paul.

12 recordsLinked to original sources

PubMed1993

Estrogen-induced left ventricular chamber enlargement in ewes.

We studied the chronic effect of administration of a single large intramuscular dose of 17 beta-estradiol on left ventricular chamber size and output in the ewe. Fourteen oophorectomized ewes were successfully instrumented and studied, with measurements made of left ventricular, aortic, right and left atrial pressures, left ventricular stroke volume, and left ventricular minor axis dimension. Unanesthetized ewes were studied before and 1, 2, and 3 wk after intramuscular administration of 0.6 mg/kg 17 beta-estradiol (7 ewes) or 1.5 ml sesame oil placebo (7 ewes). Left ventricular end-diastolic pressure-end-diastolic dimension (LVEDP-EDD) and left ventricular end-diastolic pressure-stroke volume (LVEDP-SV) relationships were quantified during graded inferior vena caval occlusion and volume infusion. Left ventricular end-diastolic diameter was larger after estrogen but not after placebo administration. The LVEDP-EDD relationship shifted progressively rightward, indicating left ventricular chamber enlargement in the estrogen group but was unchanged in the placebo group. The plateau limb of the LVEDP-SV relationship in the estrogen group shifted up from a mean stroke volume of 77.1-89.5 ml/beat and did not change in the placebo group. We conclude that administration of a single large intramuscular dose of 17 beta-estradiol resulted in left ventricular chamber enlargement and increased stroke volume in the ewe.

Animals↗

PubMed1991

Maternal left ventricular dimension in pregnancies complicated by fetal growth retardation.

Previous studies using two-dimensional chest radiographs have found a significant correlation between prematurity, fetal growth retardation, and the size of the maternal heart. Accordingly, we evaluated maternal left ventricular size and function by M-mode echocardiography near the end of gestation in 42 women with suspected fetal growth retardation and in 79 women whose pregnancies were normal. No significant differences were found between the two groups, implying that maternal left ventricular size and function is adequate in pregnancies complicated by "idiopathic" fetal growth retardation.

Echocardiography↗

PubMed1990

The murine complement receptor gene family. III. The genomic and transcriptional complexity of the Crry and Crry-ps genes.

The murine CR genes Crry (previously termed mCRY) and Crry-ps (previously termed mCRX) are two distinct, but related, sequences which are the evolutionary homologs to sequences contained within the human CR1 gene. Screening a BALB/c genomic DNA library with the Crry/Crry-ps specific cDNA resulted in the isolation of two clusters of genomic sequences: those specific for Crry and those specific for Crry-ps. The coding sequences of the Crry gene encompass over 25 kb of DNA, whereas the Crry-ps sequences are included within a single 5.6-kb Eco-R1 fragment. The Crry gene consists of 10 separate exons. The first of these contains both the signal sequence and an alternatively spliced 129 bp present in approximately 10% of the Crry transcripts. Of the remaining exons, two encode a single sixty amino acid repeat domain each (A and E), two encode a split sixty amino acid repeat (B), and another encodes two 60 amino acid domains (C and D) fused as one exon. The transmembrane and cytoplasmic regions are both split into two exons each. RNA protection analysis indicates that although there is alternative splicing in the 5' region of the gene, the 3' exons encoding the terminal 60 amino acid repeat, the transmembrane region and cytoplasmic exons are used in the same order in all Crry transcripts. This suggests that the Crry gene product is not found as a secreted protein, but only as a cell surface bound protein. DNA sequence analysis of the Crry-ps gene indicates that this sequence most likely represents a pseudogene resulting from a processed mRNA transcript from the Crry gene. This conclusion is based on the lack of intervening sequences in the Crry-ps gene and the observation that the Crry-ps gene sequence contains both an 11-bp deletion within the "coding" region and a degenerate poly A tail at the 3' end of the homologous sequence. Additionally, RNA protection analysis indicates that mRNA cannot be detected which matches the Crry-ps sequence.

Amino Acid Sequence↗

PubMed1989

Murine complement receptor gene family. II. Identification and characterization of the murine homolog (Cr2) to human CR2 and its molecular linkage to Crry.

CR2, a 145,000 to 150,000 Mr protein which binds specific breakdown products of C3, has been identified on the surface of both human and murine B cells. In order to understand the evolutionary relatedness of the human and murine proteins, we have used the coding sequences from the human CR2 gene to investigate those homologous sequences of murine Cr2. Human CR2 cDNA sequences were used as probes on a cDNA library derived from BALB/c spleen mRNA to identify cross-reacting cDNA sequences. A number of putative cDNA clones encoding murine Cr2 have been isolated and examined. DNA sequence analysis of these Cr2 cDNA clones indicates that they represent the murine homolog to human CR2. mRNA analysis with these Cr2 cDNA clones has revealed a transcription pattern similar to, but distinct from that seen for CR2. Whereas human CR2 coding sequences identify a single mRNA species of approximately 5 kb from human tonsillar mRNA, the murine counterpart identifies four transcripts from murine spleen of approximately 3, 5, 9 and 11 kb in size. The Cr2 cDNA clones which detect the four forms of spleen mRNA overlap in coding sequences and contain exons mapping to three colinear fragments as defined by EcoRI digestion. This suggests that the 3- 5-, 9-, and 11-kb mRNA forms arise by alternative splicing from a single gene. Use of these murine Cr2-specific cDNA clones to isolate their respective genomic sequences has allowed for the linkage of the 3' end of the Cr2 gene to the 5' end of the Crry gene, the evolutionary homolog to human CR1.

Amino Acid Sequence↗

PubMed1989

The murine complement receptor gene family. Analysis of mCRY gene products and their homology to human CR1.

The mouse genome contains two sets of gene sequences which are highly homologous to the gene encoding the human C3b/C4b receptor (CR1). These genes, termed murine CRY (mCRY) and murine CRX (mCRX) reside on murine chromosomes 1 and 8, respectively. Analysis of cDNA isolated by using these sequences as probes indicates that there are two related but distinct mRNA which are expressed in a wide variety of murine tissues including spleen, liver, lung, and brain. Both of these transcripts encode proteins which should contain a signal sequence for membrane insertion, a transmembrane/cytoplasmic tail region for membrane anchoring, and five extracellular domains made up of 60 amino acid consensus repeat sequences. The difference between the two is the presence of an additional exon of 129 bp immediately 3' of the signal sequence. This additional exon does not encode a 60 amino acid repeat. The sizes of the mature proteins predicted from the cDNA sequences are 43,998 Mr and 48,680 Mr; however, antisera raised against carboxy-terminal sequences detects a 70,000 Mr protein from murine fibroblasts suggesting a high degree of post-translational modification of the mature protein. A comparison of these murine gene sequences with a partial human CR1 sequence suggests that the human CR1 gene evolved by direct duplication of the ancestral coding sequences contained within these murine genes including those sequences important for membrane anchoring and cytoplasmic protein attachment.

Amino Acid Sequence↗

PubMed1989

Vascular pressure-volume relationships in pregnant and estrogen-treated guinea pigs.

We investigated the relationship between mean circulatory filling pressure (MCFP) and blood volume in nonpregnant (NP), estrogen-treated (E), and pregnant (P) guinea pigs. Reversible circulatory arrest was produced by rapid ventricular pacing or acetylcholine in unanesthetized animals remote from surgery. MCFP (mmHg) was higher for E (7.1 +/- 0.3) than for NP (5.8 +/- 0.5) or P (5.3 +/- 0.4). The gradient for venous return, the difference between MCFP and right atrial pressure (mmHg), did not differ in NP- (6.0 +/- 0.5), P- (5.8 +/- 0.5), or E- (5.8 +/- 0.4) treated animals. Capacitance, the blood volume (ml/kg) at an MCFP of 6 mmHg, was increased in P (84 +/- 6) and E (89 +/- 7), compared with NP (64 +/- 5) animals. Compliance, the ratio of the change in volume to change in pressure in the range of 6-12 mmHg (ml.kg-1.mmHg-1), was greater in P (4.4 +/- 0.3) than NP (3.5 +/- 0.3) animals. Hexamethonium blockade did not affect MCFP, capacitance, or compliance. We conclude that the effect of blood volume expansion on the circulation in pregnancy cannot be predicted from knowledge of MCFP-blood volume relationships in the nonpregnant animal, because capacitance and compliance are altered. Estrogen administration to nonpregnant animals reproduces some of these effects.

Animals↗

PubMed1985

Exercise dynamics in late gestation: effects of physical training.

Heart rate and stroke volume were measured serially in subjects at rest in the sitting position and at the onset and end of a 6-minute period of upright bicycle exercise. Twenty-three subjects with normal pregnancy were studied in late gestation and again post partum. Rest and exercise cardiac outputs in late gestation were not different from those in the postpartum period. Heart rate was higher at rest and stroke volume lower during exercise in late gestation than post partum. At the end of exercise, stroke volume fell dramatically in late gestation but not post partum. Ten women prospectively identified as physically fit had responses that were not different from those of the nonfit cohort in late gestation. Post partum, the physically fit women had exercise responses typical of trained persons and different from those of the nonfit cohort. In late gestation, rest and exercise hemodynamics in subjects in the sitting position appeared to be dominated by factors influencing venous return, independent of physical fitness.

Birth Weight↗

PubMed1985

Exercise during pregnancy.

Theoretical arguments suggest that cardiovascular fitness would be desirable during pregnancy but that high-intensity exercise should be avoided; both notions require rigorous testing. Moderate exercise, by normal women with uncomplicated pregnancy, does not appear to affect fetal health. Coexisting maternal medical or obstetrical complications may contraindicate exercise.

Animals↗

PubMed1985

Experimental autoimmune myocarditis in the guinea pig.

Male and female guinea pigs underwent immunisation with heterologous heart protein (rat heart), complete Freund's adjuvant and pertussis vaccine (immunised) or normal saline (control) at weekly intervals for 6 weeks, and were subsequently studied. In vivo intracardiac pressures, cardiac outputs, blood volumes, in vitro pressure-volume relations, left ventricular collagen contents, light microscopy, direct immunofluorescence, lymphocyte stimulation studies, and serology for circulating anti heart antibody (haemagglutination and radioimmunoassay) were performed. Immunised guinea pigs studied between 5 and 8 weeks following the immunisation protocol demonstrated a 44% increase in LVEDP (p less than 0.005), an increase in right atrial pressure (p less than 0.001), although no change in aortic pressure or cardiac output when compared with controls. Left ventricular weight was increased 20% (p less than 0.001), and in vitro left ventricular volume by 34% (at 8 mmHg distending pressure, p less than 0.001). Lung wet weight was increased 44% (p less than 0.005), and left ventricular collagen content increased 60% (p less than 0.001). Cultured lymphocytes from treated guinea pigs demonstrated a 1.5- to 4.5-fold (dependent upon proximity to last immunisation) increase in radiolabelled thymidine uptake when incubated with guinea pig heart protein compared to controls (p less than 0.001), and circulating anti guinea pig heart antibodies were detected by haemagglutination and radioimmunoassay. Histological examination of the left ventricles revealed inflammatory cell infiltration and myocyte increase to varying degrees in 15 of the 18 treated animals. We conclude that inflammatory, probably immune-mediated, chronic myocarditis can be produced in the guinea pig.

Animals↗

PubMed1981

Accelerated respiratory response to moderate exercise in late pregnancy.

We studied the rates of change of expired ventilation (VE, BTPS), O2 consumption (VO2, STPD) and CO2 production (VCO2, STPD) at the start and stop of 6 min of 50-W bicycle exercise, comparing 20 healthy young women at 38 weeks of pregnancy (G) and 3 months postpartum (NG). VO2, VCO2 and VE were significantly greater at rest for G than for NG. The absolute increases of VO2 and VCO2 from steady-state rest (SSR) to steady-state exercise (SSE) were the same for G and NG. The absolute increase of VE from SSR to SSE was significantly greater for G than NG. VCO2 and VE increased more rapidly in G than NG, but only during the first 90 sec of exercise. Recovery rates after exercise were equal for G and NG. We believe that lower extremity muscles of G contract on more distended veins at the onset of exercise, forcing increased volumes of venous blood through the lungs, increasing VO2 and VCO2. VE follows VCO2 closely.

Adult↗

PubMed1980

Effect of oxygen and of carbon dioxide tension on the incidence of apnea in fetal lambs.

Fetal breathing movements (FBM) in unanesthetized lambs in utero were correlated with measurements of arterial blood gases. One hundred and eighty-seven observations, consisting of the incidence of FBM during the hour preceding and the hour after the blood gas determinations, were made on 125 separate days in 30 fetuses of 117 to 146 days' gestational age. Fifty-eight percent of the observations with fetal apnea (FBM 0 to 9% in 2 hours) showed hypoxia (PaO2 less than or equal to 16 torr), whereas only 4% of the observations with FBM greater than 10% were associated with hypoxia. Sevety-eight percent of the hypoxic and normocarbic (PaCO2 42 to 53 torr) observations demonstrated apnea. However, only 44% of hypoxic plus hypercarbic (PaCO2 57 to 63 torr) fetuses were apneic, and with an elevated PaCO2, apnea tended to develop at a lower level of PaO2. We conclude that FBM may persist in the presence of hypercarbia with hypoxia.

Animals↗

PubMed1979

Effect of beta-adrenergic suppression by propranolol on coronary collateral development in response to chronic coronary ischemia in dogs.

Acute left circumflex coronary artery (LC) occlusion in conscious dogs caused marked ischemia in the myocardium supplied by the occluded artery, as judged by the radioactive microsphere technique for determining blood flow distribution. With the chest open, LC pressure distal to the occlusion fell to 21 +/- 1.9% of aortic pressure. By 8 weeks after gradual LC occlusion with an ameroid constrictor, collateral development had restored coronary blood flow distribution to near-normal under basal conditions and during pacing, at a heart rate of 200 beats/min. The only evidence for ischemia was in the subepicardium within the distribution of the unoccluded left anterior descending artery, which provided the extra collateral blood flow. Distal LC pressure was 70 +/- 1.7% of aortic pressure. Propranolol 160 mg orally every 6 hours for 8 weeks had no detectable effect on coronary collateral development, as judged by blood flow distribution or distal LC pressure. The only significant difference for the propranolol dogs was a slight transmural shift away from the subendocardium in the left anterior descending region.

Animals↗