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Biomedical subjects

W F Shen

Publications and source records attributed to W F Shen.

At least 55 records · Page 3Linked to original sources

Beneficial effect of residual flow to the infarct region on left ventricular volume changes after acute myocardial infarction.

To determine the relationship between alterations in left ventricular (LV) volumes and residual flow to the infarct region after myocardial infarction (MI), 57 patients with a first acute transmural MI underwent two-dimensional echocardiography within 48 hours of infarction and after 1 month. A reduction in ST segment elevation by greater than or equal to 35% of the peak value of ST segment elevation within the initial 6 hours was used as an indirect indicator for early reperfusion of the infarct-related artery (IRA). IRA patency and collateral circulation were assessed by coronary arteriography performed at 1 month. LV volumes increased in patients with a persistent ST segment elevation within the initial 6 hours of infarction and in those with a totally occluded IRA without collaterals. However, LV volumes were unchanged in patients with early reperfusion and in those who had subtotally occluded IRA or who had collateral circulation. LV dilation (greater than or equal to 20% increase in end-diastolic volume) occurred less often when early reperfusion and angiographically patent IRA or collateral supply to the infarct zone were present. This prospective study indicates that residual flow to the infarct region may exert a beneficial effect on LV volume changes after acute MI.

Cardiac Catheterization↗

Spontaneous alterations in left ventricular regional wall motion after acute myocardial infarction.

For assessing the relationship between the left ventricular (LV) wall motion abnormalities and the status of residual flow to the infarcted region, the extent of coronary artery disease and one-year outcome, 60 patients with a first transmural, Q-wave myocardial infarction (MI) underwent serial echocardiographic examinations. The abnormal wall motion (AWM) score was calculated, and the cardiac events (death, reinfarction, severe ventricular arrhythmia or congestive heart failure) after discharge were recorded. The AWM score of the infarcted area was higher in patients with total occlusion than in those with subtotal occlusion (anterior MI: 14.6 +/- 2.4 vs 7.2 +/- 2.1; inferior MI: 9.7 +/- 2.1 vs 5.1 +/-1.2, all P less than 0.01). Regional wall motion of the noninfarcted area was preserved in patients with single vessel disease but decreased in those with multivessel disease. In patients who developed cardiac events in follow-up period a higher AWM (16.4 +/- 3.7) was found than in those who did not (8.9 +/- 3.1, P less than 0.05). A score of greater than 13 had a strong prediction of cardiac events after acute MI, with a sensitivity of 81%, specificity of 94% and positive predictive accuracy of 88%.

Echocardiography↗

Expression of homeobox genes in human erythroleukemia cells.

Because homeobox-containing genes play a major role in embryogenesis and tissue identity in Drosophila and because similar genes encode tissue-specific transcription factors in mammalian cells, we hypothesized that homeobox genes might plan a role in hematopoietic differentiation and lineage commitment. We therefore surveyed a number of human leukemic cell lines for expression of homeobox-containing genes by Northern gel analysis with probes from the Hox 2 cluster of homeobox genes on chromosome 17. We observed transcripts for Hox 2.1, 2.2, 2.3 and 2.6 in the erythroid line HEL and for Hox 2.3 and 2.6 in the erythroid line K562. Using homeobox-specific probes we confirmed that the transcripts visualized contained the homeodomains for each gene as well as the flanking sequences. The myeloid lines HL60, KG1 and U937 did not express specific transcripts for any of the 4 genes studied. However, all these cell lines demonstrated bands when probed at low stringency with certain Hox 2 probes, indicating the expression of other homologous but as yet unidentified homeobox genes. Expression of Hox 2.3 and 2.6 was seen in some T and B lymphoid cell lines. Induction of differentiation in HEL cells resulted in complex modulation of expression of the Hox 2 genes. We have therefore observed erythroid-restricted expression of certain Hox 2 homeobox containing genes in human erythroid cell lines and modulation of that expression with differentiation, suggesting a role for these genes in the regulation of hematopoiesis. Different homeobox genes appear to be expressed in non-erythroid leukemic cell lines.

Cell Differentiation↗

Lineage-restricted expression of homeobox-containing genes in human hematopoietic cell lines.

We investigated the role of homeobox-containing genes in human hematopoiesis because homeobox genes (i) control cell fate in the Drosophila embryo, (ii) are expressed in specific patterns in human embryos, and (iii) appear to function as transcription factors that control cell phenotype in other mammalian organs. Using four homeobox probes from the HOX2 locus and a previously undescribed homeobox cDNA (PL1), we screened mRNAs from 18 human leukemic cell lines representing erythroid, myeloid, and T- and B-cell lineages. Complex patterns of lineage-restricted expression are observed: some are restricted to a single lineage, while others are expressed in multiple lineages. No single homeobox gene is expressed in all types of hematopoietic cells, but each cell type exhibits homeobox gene expression. HOX2.2 and -2.3 homeobox-containing cDNAs were cloned from an erythroleukemia cell (HEL) cDNA library, while the homeobox cDNA PL1 was isolated from a monocytic cell (U-937) library. Differentiation of HEL and K-562 cells with various inducers results in modulation of specific homeobox transcripts. In addition, HOX2.2 is expressed in normal bone marrow cells. We have demonstrated (i) lineage-restricted expression of five homeobox genes in erythroid and monocytic cell lines; (ii) expression of additional homeobox genes in other cell lineages (HL-60 and lymphoid cells); (iii) expression of one homeobox gene in normal marrow cells; and (iv) modulation of expression during differentiation. These data suggest that these genes play a role in human hematopoietic development and lineage commitment.

Amino Acid Sequence↗

Comparison of the effects of nifedipine and nitroglycerin on hemodynamic determinants of myocardial oxygen consumption and supply during exertional angina.

To investigate the antianginal action of nitroglycerin and nifedipine, systemic and right heart pressures, cardiac output, oxygen consumption, and radionuclide left ventricular ejection fraction and volume were measured in 14 men with stable effort angina and a positive exercise electrocardiogram. Exercise tests were performed on a semiupright bicycle ergometer on no therapy and after intravenous nitroglycerin and sublingual nifedipine, which lowered mean arterial pressure by 20 mm Hg. Exercise tolerance improved from 50 +/- 4 to 61 +/- 5 W on nifedipine and to 79 +/- 4 W on nitroglycerin (p less than 0.01, nitroglycerin vs. nifedipine). At submaximal workloads, both drugs decreased arterial pressure and ventricular volumes, but heart rate was higher on nifedipine. At peak exercise on nitroglycerin (79 W), oxygen consumption, cardiac index, heart rate, and rate-pressure product were significantly increased over peak control and nifedipine values, while systolic pressure and end-diastolic volume were unchanged. Nitroglycerin reduced pulmonary wedge pressure more and systemic diastolic pressure less than nifedipine, so the coronary perfusion gradient was reduced by nifedipine and maintained by nitroglycerin. Also, there was less angina and ST-segment depression after nitroglycerin compared to control or nifedipine, and the left ventricular diastolic pressure-volume relationship was improved only by nitroglycerin. This suggests that the action of nitroglycerin in reducing ischemia is not only due to reduced myocardial oxygen demand, but that myocardial oxygen delivery may also be increased.

Adult↗

Relationship between clinical manifestations and coronary angiographic morphology in patients with coronary artery disease.

To study the relationship between clinical manifestations and coronary anatomy and morphology, coronary angiography was performed in 20 patients with chronic stable angina (Group I), in 18 patients with unstable angina (Group II), and in 20 patients with previous myocardial infarction (Group III). Although the site and extent of coronary artery disease were similar among the three groups, coronary morphology differed considerably, with a concentric lesion occurring in 70% of Group I patients and an eccentric lesion in 62% and 63% of Group II and Group III patients, respectively. The study suggests that coronary lesion morphology may form an anatomic basis in determining clinical manifestations for patients with coronary artery disease. An eccentric coronary stenosis may be useful in identifying high-risk patients.

Aged↗

Value of angina pectoris after myocardial infarction in predicting extent of coronary artery disease.

Clinical, hemodynamic, and angiographic data were examined in 53 patients who underwent catheterization within 6 months of documented acute transmural myocardial infarction (MI). The patients were divided into two groups on the basis of presence (23 patients, group I) or absence (30 patients, group II) of angina pectoris 1 month after MI. Group I patients had more severe coronary artery disease and a greater prevalence of multivessel disease than group II patients. Partial preservation of segmental left ventricular wall function in group I was related to the presence of collateral vessels. In patients with single vessel disease, incidence of spontaneous recanalization of the infarct-related artery was more common in group I as compared with those in group II. It is concluded that angina pectoris after MI suggests multivessel disease or infarct-related artery recanalization. Coronary angiography may be advised in these patients in order to select adequate therapeutic interventions and improve prognosis.

Aged↗

[Value of angina pectoris after myocardial infarction in predicting the extent of coronary artery disease].

Clinical, hemodynamic, and angiographic data were examined in 53 patients who underwent catheterization within 6 months of a documented first acute transmural myocardial infarction. The patients were divided according to the presence (23 patients) or absence (30 patients) of angina pectoris 1 month after infarction (group I and group II). Group I patients had more severe coronary artery disease and a greater prevalence of multivessel disease than group II patients. Partial preservation of segmental wall function in group I was related to the presence of collateral vessels. In patients with single vessel disease, the incidence of spontaneous recanalization of the infarct-related artery was higher in group I as compared with that in group II. It is concluded that angina pectoris after myocardial infarction suggests multivessel disease or infarct-related artery recanalization. Coronary arteriography may be advised in order to select adequate therapeutic interventions and improve prognosis in these patients.

Aged↗

[A correlative study of ECG and coronary arteriogram findings after acute myocardial infarction].

To evaluate the electrocardiographic value in the prediction of reperfusion state of the infarct-related artery (IRA), serial changes in ST segment elevation were assessed in 38 patients with acute myocardial infarction (AMI). ST segment elevation decreased by 35% or more within 8 hours of peak sigma ST in 16 of the 20 patients with subtotal occlusion, but in none of the patients with total occlusion of the IRA (P less than 0.01). Myocardial infarct size estimated by peak serum CK-MB, sigma Q and QRS score was smaller and left ventricular function was better in patients with rapid resolution of ST segment elevation than in those with persistent ST elevation. The study indicates that a fall of ST segment elevation by 35% or more of the peak sigma ST within 8 hours of infarction may be a useful indicator of early reperfusion of the IRA in patients with AMI.

Adult↗

Primary structure of human pancreatic elastase 2 determined by sequence analysis of the cloned mRNA.

A cDNA encoding elastase 2 has been cloned from a human pancreatic cDNA library. The cDNA contains a translation initiation site and a poly(A) recognition site and encodes a protein of 269 amino acids, including a proposed 16-residue signal peptide. The amino acid sequence of the deduced mature protein contains a 12-residue activation peptide containing a cysteine at residue 1 similar to that of chymotrypsin. The proposed active enzyme contains all of the characteristic active-site amino acids, including His-57, Asp-102, and Ser-195. The S1 binding pocket is bounded by Gly-216 and Ser-226, making this pocket intermediate in size between chymotrypsins and elastase 1 or protease E, consistent with the substrate specificity of elastase 2 for long-chain aliphatic or aromatic amino acids. Computer modeling studies using the amino acid sequence of elastase 2 superimposed on the X-ray structure of porcine elastase 1 suggest that a change of Gln-192 in elastase 1 to Asn-192 in elastase 2 may account for the lower catalytic efficiency of the latter enzyme. In addition, modeling studies have been conducted to attempt to identify basic amino acids in elastases which are absent in chymotrypsins, and which could account for the specific property of elastolysis. Several basic residues appear to be near the ends of the extended binding pocket of elastases which might serve to anchor the enzyme to the elastin substrate. These studies indicate that elastases 2 and elastase 1 both contain an Arg-65A as well as a basic dipeptide at 223/224 which is not present in chymotrypsins.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Usefulness of ejection fraction response to exercise one month after acute myocardial infarction in predicting coronary anatomy and prognosis.

The prognostic value of left ventricular (LV) ejection fraction (EF) measured during maximal exercise testing early after acute myocardial infarction (AMI) was assessed in 75 patients, aged 65 years or younger, a mean of 36 days after AMI. At follow-up for a mean 12 months (range 6 to 26), medical complications developed in 15 patients: cardiac death in 5, ventricular fibrillation in 1, reinfarction in 2, unstable angina in 5, and severe cardiac failure in 2. Seven other patients underwent coronary artery bypass grafting for severe angina. When LVEF less than 50% at rest was compared with LVEF of 50% or more, the 2-year life-table survival free of complications was 54 +/- 21% compared with 84 +/- 19% (p less than 0.05). When exercise LVEF less than 50% was compared with LVEF of 50% or more, the 2-year survival rate free of medical complication was 42 +/- 32% compared with 83 +/- 20% (p less than 0.05). LVEF change from rest to exercise was not related to prognosis. Patients with combined medical and surgical events tended to have lower rest and exercise LVEFs, but changes in LVEF during exercise were again unrelated to prognosis. Sixty-five patients underwent coronary arteriography. After inferior AMI the mean LVEF was lower in those with multivessel than in those with 1-vessel coronary artery disease at rest (47 +/- 13% vs 59 +/- 7%, p less than 0.005) and during exercise (47 +/- 13% vs 59 +/- 9%, p less than 0.005); however, the change in LVEF during exercise was not related to coronary anatomy anatomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Primary structure of human pancreatic protease E determined by sequence analysis of the cloned mRNA.

Although protease E was isolated from human pancreas over 10 years ago [Mallory, P. A., & Travis, J. (1975) Biochemistry 14, 722-729], its amino acid sequence and relationship to the elastases have not been established. We report the isolation of a cDNA clone for human pancreatic protease E and determination of the nucleic acid sequence coding for the protein. The deduced amino acid sequence contains all of the features common to serine proteases. The substrate binding region is highly homologous to those of porcine and rat elastases 1, explaining the similar specificity for alanine reported for protease E and these elastases. However, the amino acid sequence outside the substrate binding region is less than 50% conserved, and there is a striking difference in the overall net charge for protease E (6-) and elastases 1 (8+). These findings confirm that protease E is a new member of the serine protease family. We have attempted to identify amino acid residues important for the interaction between elastases and elastin by examining the amino acid sequence differences between elastases and protease E. In addition to the large number of surface charge changes which are outside the substrate binding region, there are several changes which might be crucial for elastolysis: Leu-73/Arg-73; Arg-217A/Ala-217A; Arg-65A/Gln-65A; and the presence of two new cysteine residues (Cys-98 and Cys-99B) which computer modeling studies predict could form a new disulfide bond, not previously observed for serine proteases. We also present evidence which suggests that human pancreas does not synthesize a basic, alanine-specific elastase similar to porcine elastase 1.

Amino Acid Sequence↗