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Biomedical subjects

S E Lewis

Publications and source records attributed to S E Lewis.

At least 109 records · Page 6Linked to original sources
PubMed1985

A mutation in the beta-globin gene detected in the progeny of a female mouse treated with ethylnitrosourea.

A mouse with a variant hemoglobin was discovered during electrophoretic screening of (C57BL/6J X DBA/2J)F1 progeny of females treated with ethylnitrosourea. The variant trait was transmitted as a simple Mendelian alternate at the Hbb locus in all crosses except those involving the original carrier of the mutation. The proband mouse which received the mutation directly from the mutagen-treated parent was a germinal mosaic for the mutant and normal Hbbs alleles. The mutant allele was designated Hbbs2. The mutant haplotype specifies both an electrophoretically fast hemoglobin band and a hemoglobin band in the normal beta single hemoglobin position. Thus, the mutation has altered one of the tandemly duplicated genes at the Hbbs locus. A comparison of the relative concentrations of the two hemoglobins in Hbbs2 mice demonstrates preferential expression of the mutant gene, possibly analogous to the enhanced expression of Hbbdmaj in the Hbbd haplotype. Analysis of the amino acid sequence of the variant beta-globin revealed that the valine at position 60 was changed to glutamic acid. The simplest mutation mechanism for such an alteration is an A X T----T X A transversion.

Animals↗
PubMed1985

Hematology of a murine beta-thalassemia: a longitudinal study.

Mice homozygous for a spontaneous mutation, in which the beta-major globin gene is deleted, have clinical symptoms of beta-thalassemia. These mice have a hypocellular, hypochromic, microcytic anemia that becomes more severe with increasing age. The defective red cell morphology, decreased osmotic fragility of erythrocytes and shortened red cell life span found in beta-thalassemic mice are similar to those observed in human beta-thalassemia. Synthesis of beta-globin is depressed but not as much as might be expected because the expression of the beta-minor globin gene is enhanced to encode two to three times more globin than in normal mice. Splenomegaly, an enlarged pool of stem cells for erythropoiesis, and iron overloading occur in older mice. The fact that these mice remain moderately healthy makes them a very suitable animal model in which to develop and test alternative techniques of gene therapy that could be successfully applied to the treatment of human thalassemia. Homozygous beta-thalassemic mice have large deposits of iron in their tissues, which might make these mice also useful for in vivo tests of the effectiveness and possible long-term side effects of newly developed iron chelators.

Animals↗
PubMed1985

Quantification of myocardial infarction: a comparison of single photon-emission computed tomography with pyrophosphate to serial plasma MB-creatine kinase measurements.

Single photon-emission computed tomography (SPECT) with 99mTc-pyrophosphate (PPi) has been shown to estimate size of myocardial infarction accurately in animals. We tested the hypothesis that SPECT with 99mTc-PPi and blood pool subtraction can provide prompt and accurate estimates of size of myocardial infarction in patients. SPECT estimates are potentially available early after the onset of infarction and should correlate with estimates of infarct size calculated from serial measurements of plasma MB-creatine kinase (CK) activity. Thirty-three patients with acute myocardial infarction and 16 control patients without acute myocardial infarction were studied. Eleven of the patients had transmural anterior myocardial infarction, 16 had transmural inferior myocardial infarction, and six had nontransmural myocardial infarction. SPECT was performed with a commercially available rotating gamma camera. Identical projection images of the distribution of 99mTc-PPi and the ungated cardiac blood pool were acquired sequentially over 180 degrees. Reconstructed sections were color coded and superimposed for purposes of localization of infarct. Areas of increased PPi uptake within myocardial infarcts were thresholded at 65% of peak activity. The blood pool was thresholded at 50% and subtracted to determine the endocardial border for the left ventricle. Myocardial infarcts ranged in size from 1 to 126 gram equivalents (geq) MB-CK. The correlation of MB-CK estimates of size of infarct with size determined by SPECT (both in geq) was good (r = .89 with a regression line of y = 13.1 + 1.5x).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Differential expression of murine adult hemoglobins in early ontogeny.

Mice with a mutation at the Hbbs, beta-globin locus, were used to study the relative levels of beta-s2major (mutant) and beta-sminor globins specified by the mutant Hbbs2 haplotype during development. At 11.5 days of gestation, beta-sminor comprised over 80 percent and beta-s2major under 20 percent of the adult beta-globin. The relative level of beta-sminor decreased through fetal development; at birth beta-sminor represented 33.7 percent of the beta-globin. The adult values of 29.0 percent beta-sminor and 71.0 percent beta-s2major globin are expressed in mice six days after birth. Because the two beta-globin genes are expressed in mice of the Hbbs2 haplotype, both the beta-smajor and beta-sminor genes are presumably expressed in mice of the Hbbs haplotype. Expression of the beta-sminor gene is elevated to 35.6 percent in adult Hbbs2/Hbbs2 mice that have been bled repeatedly. Thus, the 5' beta-s2major and 3' beta-sminor genes of the Hbbs2 haplotype and, presumably the 5' beta-smajor and 3' beta-sminor genes of the Hbbs haplotype, are regulated independently and are homologous to the 5' beta-dmajor and 3' beta-dminor genes of the Hbbd haplotype. Mice of the Hbbs2 haplotype are better suited than mice of the Hbbd haplotype for studying the mechanisms of hemoglobin switching because with Hbbs2 each of the three embryonic and two adult hemoglobins can be separated by electrophoresis.

Animals↗
PubMed1984

Measurement of myocardial infarct size by technetium pyrophosphate single-photon tomography.

The primary determinant of prognosis after acute myocardial infarction (AMI) is the size of the acute infarct. The present study evaluates 46 patients with different infarct distributions and sizes to test the hypothesis that single photon emission computed tomography with technetium-99m pyrophosphate (Tc-99m-PPi) and blood pool overlay allows measurements of AMI size that provide insight into prognosis irrespective of infarct location. Identical Tc-99m-PPi and ungated blood pool projections were acquired over 180 degrees with a rotating gamma camera. Reconstructed sections were color-coded and superimposed for purposes of infarct localization. Areas of increased pyrophosphate uptake within myocardial infarcts were thresholded at 65% of peak activity. The blood pool was thresholded at 50% and subtracted so as to determine an endocardial border for the left ventricle. Using this method, myocardial infarcts weighed 2.5 to 81.2 g. The correlation of infarct mass with prognosis showed that patients without previous AMI and with acute infarcts that weighed more than 40 g had an increased frequency of death and congestive heart failure (p less than 0.001). The correlation of measured infarct mass with peak serum creatine kinase level was significant (r = 0.83, p less than 0.001; y = 0.015x + 13.20). The correlation coefficients for anterior, inferior and nontransmural AMI were not significantly different from those for the entire group. In conclusion, tomographically determined infarct mass data correlate with subsequent clinical prognosis, and Tc-99m-PPi tomography with blood pool overlay is a safe and effective means of sizing infarcts in patients with AMI.

Adult↗
PubMed1984

Measurement of infarct size in acute canine myocardial infarction by single-photon emission computed tomography with technetium-99m pyrophosphate.

The location and extent of myocardial infarction (MI) are important predictors of patient course. The current study tests the hypothesis that MI size could be measured accurately using rotating gamma camera single-photon emission computed tomography ( SPECT ) and technetium-99m pyrophosphate (PPi) and that the accuracy of these measurements was independent of MI location and transmural or nontransmural distribution. SPECT was performed in 38 dogs 48 hours after ligation of the left anterior descending coronary artery (14 dogs) or left circumflex coronary artery (LC) (24 dogs) at the mid-level or below. Projection images were corrected for center-of-rotation and field nonuniformity and processed with a 1-dimensional low-pass filter to diminish rib activity. Sixteen 0.5-cm-thick transverse sections, including the entire left ventricle, were reconstructed by filtered backprojection , low-pass filtered, contrast enhanced and processed with a 3-dimensional boundary enhancement operator. The boundary of PPi uptake in each slice was marked automatically using an algorithm that combined a directional derivative and a threshold, and required continuity of the boundary in 3 dimensions. The total number of volume elements that showed abnormal tracer uptake were summed, corrected to absolute volume, and multiplied by the specific weight of cardiac muscle. Scintigraphic MI weight was compared with pathologic MI weight. There was an excellent correlation between scintigraphic and pathologic MI weight. The poorer correlation for nontransmural compared with transmural MIs is most likely a function of size alone, since MIs that weighed less than 10 g (n = 12, range 1.3 to 9.5 g), both transmural and nontransmural, showed a similar correlation: S = 1.07 X P + 0.56 (r = 0.81, standard error of the slope = 0.245).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Characteristics of alpha-aminoisobutyric acid transport in rat skeletal muscles.

alpha-Aminoisobutyric acid (AIB) transport into the intracellular compartment of extensor digitorum longus and soleus muscles was measured (in vitro) after allowance for the equilibration of the amino acid in the extracellular space. The latter was determined with three markers, [14C]inulin, 60Co-EDTA and [3H]mannitol. Net transport of AIB was subsequently divided into its two components, i.e. influx and efflux. Rates of influx were measured as the intracellular accumulation of [14C]AIB after a short incubation (5 min), and efflux was measured as the release of AIB with time (up to maximum of 50 min) from muscles that had previously been preloaded with AIB. This intracellular efflux was resolved into two phases, which probably represent two separate components of exit. The influence of extracellular Na+ on the transport of this neutral amino acid (representing the A system) was investigated. Na+ depletion resulted in lower accumulations of AIB, the effects becoming more pronounced with progressive depletions of external Na+. These changes arose from an inhibition of AIB influx, concomitant with an enhancement of its efflux. In contrast, all components of tyrosine transport (representing the L system) were unaffected by lowering external Na+ concentrations. The net accumulation of AIB was also suppressed by cortisol. This inhibitory effect was, however, Na+-dependent and resulted solely from the steroid's enhancement of AIB efflux, the hormone being without effect on AIB influx.

Aminoisobutyric Acids↗
PubMed1984

Determination of left ventricular mass by single-photon emission computed tomography with thallium-201.

To test the hypothesis that single-photon emission computed tomography (SPECT) might permit accurate, noninvasive measurement of LV mass, SPECT measurements of LV mass to LV weight were compared in 20 mongrel dogs. Projection images of the left ventricle were acquired after intravenous injection of thallium-201 (TI-201). Transverse sections were reconstructed using filtered backprojection. Coronal sections were extracted from the reconstructed volume. The boundary of LV uptake of TI-201 in each coronal section was defined automatically using a threshold detector. Scintigraphic LV mass [total number of volume elements (voxels) showing TI-201 uptake X voxel volume X specific gravity of myocardium] was compared to actual LV weight. There was good correlation between scintigraphic LV mass and LV weight. Mean LV weight was 68 +/- 20 g (+/- standard deviation) (range 27 to 94). Mean SPECT LV mass was 66 +/- 19 g (range 28 to 100). Linear regression analysis yielded the following relation: SPECT LV mass = 0.87 X LV weight + 6.79 (r = 0.91, root-mean-square deviation from regression = 7.5). SPECT measurements were reproducible, with a coefficient of variation of 0.24%. Thus, SPECT of LV TI-201 distribution can be used to measure LV mass in canine myocardium.

Animals↗
PubMed1984

Comparison of left ventricular function and infarct size in patients with and without persistently positive technetium-99m pyrophosphate myocardial scintigrams after myocardial infarction: analysis of 357 patients.

One hundred nine patients with persistently positive technetium-99m pyrophosphate (Tc-99m-PPi) myocardial scintigrams 6 months after acute myocardial infarction (MI) (Group A) and 185 patients without such persistently positive scintigrams (Group B) were compared with regard to enzymatically determined infarct size, early and late measurements of left ventricular (LV) function determined by radionuclide ventriculography, and preceding clinical course during the 6 months after MI. The CK-MB-determined infarct size index in Group A (17.4 +/- 10.6 g-Eq/m2) did not differ significantly from that in Group B (16.0 +/- 14.6 g-Eq/m2). Similarly, myocardial infarct areas in the 2 groups, determined by planimetry of acute Tc-99m-PPi scintigrams in those patients with well-localized 3+ or 4+ anterior pyrophosphate uptake, were not significantly different (35.7 +/- 13.4 vs 34.4 +/- 13.1 cm2, respectively). However, patients in Group A had significantly lower LV ejection fractions than those in Group B, both within 18 hours of the onset of MI (0.42 +/- 0.14 vs 0.49 +/- 0.14, p less than 0.01) and at 3 months after MI, both at rest (0.42 +/- 0.14 vs 0.51 +/- 0.14, p less than 0.01) and at maximal symptom-limited supine bicycle exercise (0.44 +/- 0.17 vs 0.51 +/- 0.17, p less than 0.01). Peak exercise levels achieved in the 2 groups were not significantly different. Furthermore, patients in Group A demonstrated a greater incidence of congestive heart failure during the initial hospital admission (41 vs 24%; p less than 0.01) and a greater requirement for digoxin (p less than 0.05) and furosemide (p less than 0.01) after discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care↗
PubMed1984

Pre- and post-natal growth and protein turnover in smooth muscle, heart and slow- and fast-twitch skeletal muscles of the rat.

The growth of one smooth and three individual striated muscles was studied from birth to old age (105 weeks), and where possible during the later stages of foetal life also. Developmental changes in protein turnover (measured in vivo) were related to the changing patterns of growth within each muscle, and the body as a whole. Developmental growth (i.e. protein accumulation) in all muscles involved an increasing proportion of protein per unit wet weight, as well as cellular hypertrophy. The contribution of the heart towards whole-body protein and nucleic acid contents progressively decreased from 18 days of gestation to senility. In contrast, post-natal changes in both slow-twitch (soleus) and fast-twitch (tibialis anterior) skeletal muscles remained reasonably constant with respect to whole-body values. Such age-related growth in all four muscle types was accompanied by a progressive decline in both the fractional rates of protein synthesis and breakdown, the changes in synthesis being more pronounced. Age for age, the fractional rates of synthesis were highest in the oesophageal smooth muscle, similar in both cardiac and the slow-twitch muscles, and lowest in the fast-twitch tibialis muscle. Despite these differences, the developmental fall in synthetic rates was remarkably similar in all four muscles, e.g. the rates at 105 weeks were 30-35% of their values at weaning. Such developmental changes in synthesis were largely related to diminishing ribosomal capacities within each muscle. When measured under near-steady-state conditions (i.e. 105 weeks of age), the half-lives of mixed muscle proteins were 5.1, 10.4, 12.1 and 18.3 days for the smooth, cardiac, soleus and tibialis muscles respectively. Old-age atrophy was evident in the senile animals, this being more marked in each of the four muscle types than in the animal as a whole. In each muscle of the senile rats the protein content and composition per unit wet weight, and both the fractional and total rates of synthesis, were significantly lower than in the muscles of younger, mature, animals (i.e. 44 weeks). In the soleus the decreased synthesis rate appeared to be related to a further fall in the ribosomal capacity. In contrast, the changes in synthesis in the three remaining muscles correlated with significant decreases in the synthetic rate per ribosome.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1984

Protein synthesis during the developmental growth of the small and large intestine of the rat.

The developmental growth and associated changes in protein synthesis were measured (in vivo) in the combined small and large intestine from 18 days in utero to 105 weeks post partum. Similar post-natal (3-105 weeks) changes were also studied in the separated large and small intestine, and in the mucosal and muscularis externa + serosal layers of the small intestine. Although the protein and nucleic acid contents of the whole intestine increased throughout both pre- and post-natal life, the maximal (11%) intestinal contribution to whole-body growth occurred 3 weeks after birth; this value declined to only 2.5-3.5% at both extremes of the age range studied. Between the 18-day foetus and old age the fractional rate of protein synthesis decreased from 107 to 61% per day. This developmental decline (43%) was, however, much smaller than that found in most other body tissues over the same period. Similar developmental trends (between weaning and senility) were found in both the small and the large intestine when studied separately, the small intestine in all respects contributing proportionately more than the large intestine to both the combined intestinal and whole-body values. At each age the large intestine possessed significantly lower fractional rates of synthesis and associated ribosomal activities. For the most part, the fractional synthesis rates in the mucosa and serosa of the small intestine were very similar, with each declining slightly with increasing age. These developmental changes are discussed with respect to functional aspects within the gastrointestinal tract.

Aging↗
PubMed1984

Radionuclide ventriculography: usefulness in evaluating alterations in ventricular function.

Radionuclide ventriculography allows the visualization of the right and left ventricles, the objective quantitation of right and left ventricular function at rest and during stress, and an evaluation of the influence of a variety of different physiologic, pharmacologic, and surgical interventions on global and regional ventricular function. The further development of tomographic imaging devices and sophisticated associated computer systems should allow sensitive three-dimensional analysis of global and segmental ventricular function and evaluations of the interrelationships between myocardial perfusion, metabolism, and function.

Angina Pectoris↗
PubMed1984

Prospective evaluation of renal allograft dysfunction with 99mtechnetium-diethylenetriaminepentaacetic acid renal scans.

A prospective, single-blinded study was done to determine the ability of serial 99mtechnetium-diethylenetriaminepentaacetic acid scans to diagnose renal allograft rejection. Among 28 transplant recipients 111 renal scans were obtained 1 day postoperatively and every 3 to 4 days thereafter for 3 weeks in all patients retaining an allograft. Computer-generated time-activity blood flow curves were analyzed semiquantitatively for the 1) interval between curve peaks of the allograft and iliac artery, 2) renal transit time and 3) renal washout of radionuclide. Excretory function was assessed by degree and interval to appearance of radionuclide in the calices and bladder. Deterioration of renal blood flow and excretion compared to the initial scan was considered rejection. Of 52 scans performed during clinical rejection 47 (90.4 per cent) were interpreted as showing rejection (sensitivity). Of 53 scans interpreted as showing rejection 47 (88.7 per cent) were positive for clinical rejection. The remaining 6 patients (initial false positive results) suffered clinical rejection within 24 to 72 hours. We conclude that 99mtechnetium-diethylenetriaminepentaacetic acid renal scans are useful in the differential diagnosis of renal allograft dysfunction.

Clinical Trials as Topic↗
PubMed1984

Is anterior ST depression with acute transmural inferior infarction due to posterior infarction? A vectorcardiographic and scintigraphic study.

The hypothesis that anterior ST segment depression represents concomitant posterior infarction was tested in 49 patients admitted with a first transmural inferior myocardial infarction. Anterior ST depression was defined as 0.1 mV or more ST depression in leads V1, V2 or V3 on an electrocardiogram recorded within 18 hours of infarction. Serial vectorcardiograms and technetium pyrophosphate scans were obtained. Eighty percent of the patients (39 of 49) had anterior ST depression. Of these 39 patients, 34% fulfilled vectorcardiographic criteria for posterior infarction, and 60% had pyrophosphate scanning evidence of posterior infarction. Early anterior ST depression was neither highly sensitive (84%) nor specific (20%) for the detection of posterior infarction as defined by pyrophosphate imaging. Of patients with persistent anterior ST depression (greater than 72 hours), 87% had posterior infarction detected by pyrophosphate scan. In patients with inferior myocardial infarction, vectorcardiographic evidence of posterior infarction correlated poorly with pyrophosphate imaging data. Right ventricular infarction was present on pyrophosphate imaging in 40% of patients with pyrophosphate changes of posterior infarction but without vectorcardiographic evidence of posterior infarction. It is concluded that: 1) the majority of patients with acute inferior myocardial infarction have anterior ST segment depression; 2) early anterior ST segment depression in such patients is not a specific marker for posterior infarction; and 3) standard vectorcardiographic criteria for transmural posterior infarction may be inaccurate in patients with concomitant transmural inferior myocardial infarction or right ventricular infarction, or both.

Diphosphates↗
PubMed1983

Iodine-123 phenylpentadecanoic acid: detection of acute myocardial infarction and injury in dogs using an iodinated fatty acid and single-photon emission tomography.

The ability of an iodinated fatty acid, iodine-123 phenylpentadecanoic acid (1-123 PPA), and single-photon emission computed tomography (SPECT) to detect myocardium injured by temporary or permanent coronary arterial occlusion was evaluated. In 5 control dogs, 11 dogs that underwent 90 to 120 minutes of fixed left anterior descending coronary artery (LAD) occlusion, and 8 dogs that underwent 90 minutes of temporary LAD occlusion and up to 90 minutes of reflow, 2 to 6 mCi of I-123 PPA were injected and the dogs were imaged with SPECT. Control dogs showed relatively uniform uptake and clearance of I-123 PPA in similar left ventricular (LV) regions. Dogs with permanent LAD occlusion were identified by computer algorithm as having regions of decreased I-123 PPA uptake in the infarct-related area and a reduced rate of I-123 PPA clearance (-9.4% in infarct sectors [washin], +3.7% in sectors adjacent to the area of infarction, and +15.4% in control LV sectors [p less than 0.01]). Dogs with temporary LAD occlusion and reperfusion had decreased clearance of I-123 PPA from the regions with infarction; I-123 PPA clearance was -5.2 +/- 16.4% in infarct sectors, 12.7 +/- 7.4% in periinfarct zones, and 30.4 +/- 12% in control LV regions. These data demonstrate that tomographic analysis of I-123 PPA uptake and clearance permits the relatively noninvasive detection of LV myocardium injured by permanent or temporary LAD occlusion and reperfusion.

Animals↗
PubMed1983

Prognostic value of submaximal exercise radionuclide ventriculography after myocardial infarction.

Submaximal exercise testing with radionuclide ventriculography (RVG) was performed in 117 patients before hospital discharge 17 +/- 7 days (+/- standard deviation) after an acute myocardial infarction (MI). The hypothesis tested in these studies was that submaximal exercise testing coupled to RVG allows the identification of patients at risk for future ischemic events in the subsequent 6 months, irrespective of MI location and type. The sites of MI were characterized as anterior transmural in 33, inferior transmural in 39, limited nontransmural in 18, extensive nontransmural in 24 and indeterminant in 3. During 6 months of follow-up, 9 patients died, 14 had recurrent MI, 18 had refractory angina pectoris, 16 had limiting angina and 17 had congestive heart failure. Discriminant function analysis ranked exercise changes in left ventricular (LV) ejection fraction and end-systolic volume the most important of all clinical, exercise and scintigraphic variables for predicting future cardiac events. The predictive accuracy of changes in LV ejection fraction and end-systolic volume were 93 and 91%, respectively, for the entire group, and were significantly more sensitive than any degree of ST-segment depression or elevation (p less than 0.001). These findings were generally independent of MI location and type. Thus, submaximal exercise RVG after MI is an accurate means of identifying patients at risk for major cardiac events in the 6 months after hospital discharge.

Angina Pectoris↗