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S M Factor

Publications and source records attributed to S M Factor.

At least 19 recordsLinked to original sources
PubMed1992

High expression of human beta S- and alpha-globins in transgenic mice: erythrocyte abnormalities, organ damage, and the effect of hypoxia.

A line of transgenic mice with two cointegrated transgenes, the human beta S- and alpha 2-globin genes, linked to the beta-globin locus control region was produced and bred with mice carrying a deletion of the mouse beta major-globin gene. In transgenic mice homozygous for the beta major deletion (alpha H beta S[beta MDD]; where alpha H is human alpha-globin and MD is mouse deletion), 72.5 +/- 2.4% (mean +/- SD) of the beta-chains are beta S and the ratio of alpha H- to beta S-globin was 0.73. Introduction of a heterozygous mouse alpha-globin deletion into mice homozygous for the beta major deletion (alpha H beta S[alpha MD beta MDD]) resulted in 65.1 +/- 8.5% beta S and a human alpha/beta ratio of 0.89 +/- 0.2. Sickling occurs in 95% of erythrocytes from alpha H beta S[beta MDD] mice after slow deoxygenation. Transmission electron microscopy revealed polymer fiber formation but not fascicles of fiber. Increased organ weight was noted in lung, spleen, and kidney of transgenic mice vs. controls that may be due to hypertrophy or increased blood volume in the lungs and/or increased tissue water content. The hemoglobin content of lung, spleen, and kidney was also elevated in transgenic animals due to trapped hemoglobin and/or increased blood volume. When transgenic and control mice were examined by magnetic resonance imaging at 9.4 tesla, some transgenic animals had enlarged kidneys with prolonged relaxation time, consistent with increased organ weight and water content. The glomerular filtration rate was elevated in transgenic animals, which is characteristic of young sickle cell patients. Furthermore, exposure to hypoxia resulted in significantly decreased hematocrit, increased erythrocyte density, and induced a urine-concentrating defect. We conclude that the transgenic mouse line reported here has chronic organ damage and further hematological and organ dysfunction can be induced by hypoxia.

Anemia, Sickle Cell↗
PubMed1992

Demonstration of endothelial adhesion of sickle cells in vivo: a distinct role for deformable sickle cell discocytes.

Different morphologic and density classes of sickle cells (SS) may play distinct roles in the generation of vasoocclusion, explaining the complexity of this phenomena. The densest SS red blood cells (RBCs) (SS4) can induce vasoocculsion in ex vivo microcirculatory preparations as well as in an intact animal model. Previous studies of the interaction of SS deformable discocytes with endothelial monolayers or the rat ex vivo mesocecum preparation have shown adhesion that is desmopressin (dDAVP)-stimulated, von Willebrand factor (vWF)-mediated, and limited to the small venules. However, in vivo adhesion of SS RBCs to the endothelium has neither been demonstrated nor characterized; and, in particular, the relation of adhesion to vasoocclusion is unknown. Using an intact animal model that involves injecting saline-washed, density-defined SS RBCs into the femoral artery of a rat, we find that: (1) Quantitative studies of RBCs retained in the rat thigh using 99mTc-labeled RBCs and gamma camera imaging showed that dDAVP induces a threefold increase in retention of normal (AA) cells and deformable SS discocytes (SS2). (2) electron microscopy and Microfil injection show that the retention of SS2 cells is due to adhesion to the vascular endothelium with no evidence of obstruction. (3) H-1 magnetic resonance imaging showed that retention of SS4 cells induced a dose-dependent increase in tissue edema (presumable secondary to tissue hypoxia), while retention of AA or SS2 cells produced no change. We conclude that endothelial adhesion of deformable SS discocytes can be demonstrated in an in vivo animal model, that this adhesion is enhanced by dDAVP (presumably related to, but not necessarily limited to the release of vWF), and that this phenomenon per se does not lead to vasoocclusion. Nevertheless, adhesion of deformable SS discocytes may have consequences. We hypothesize that adhesion of SS discocytes could narrow the lumen of postcapillary venules and facilitate secondary trapping of SS4 cells and lead to subsequent vasoocclusion.

Anemia, Sickle Cell↗
PubMed1992

Diphenylhydantoin inhibits calcification of bovine pericardial implants and myocardium: a preliminary study.

Calcification is a major cause of glutaraldehyde-fixed bioprosthetic valve failure. Recent studies have shown that dystrophic calcification shares basic features with normal bone mineralization, including crystal initiation through the mediation of cell membranes, usually in the form of extracellular vesicles. In this study, we observed that calcification of the myocardium of DBA/2J mice was inhibited or reversed by diets supplemented with 100 mg/kg diet diphenylhydantoin (dilantin) for 70 days, with a calcification incidence of 25% in the dilantin group versus 58% in control. We further studied the effects of dilantin on bioprosthetic valve calcification. Three groups of young male Sprague-Dawley rats (100 g, 9/group) were implanted subcutaneously with 1-cm2 pieces of glutaraldehyde-fixed bovine pericardium. Controls were fed a ground chow for 45 or 90 days postimplantation; experimentals received the same chow for the first 45 days postimplantation and then were fed the same diet supplemented with 1000 mg dilantin/kg for the succeeding 45 days. Calcium content (microgram/mg dry weight) of the implants in the dilantin group was 137 +/- 18.6 versus 214 +/- 34.3 in 90 days control and 79.9 +/- 41.5 in 45 days control (mean +/- SD, P < 0.01 and P < 0.05 respectively, t test). The tibia calcium content of the dilantin group was not significantly different from 90 days control. We conclude that orally administered dilantin inhibits calcification of glutaraldehyde-fixed bovine pericardial implants preferentially. It does not cause decalcification either of implants that have already calcified or of the bones. The anti-calcification effect of dilantin may be associated with its anti-vitamin D effect.

Animals↗
PubMed1992

Histological evaluation of the inferior epigastric artery in patients with known atherosclerosis.

Comparative histological studies have been performed on the various arterial conduits available for myocardial revascularization including the inferior epigastric artery which has recently become the focus of intense investigation. In this study, 10 patients with known risk factors for atherosclerotic disease had their inferior epigastric artery harvested and the entire specimen examined for the microscopical presence of atherosclerosis or its precursors. Histopathological findings that have been shown to be theoretically protective against the progression of atherosclerosis were observed. These include the paucity of fenestrae in the internal elastic lamina, no medical calcification, the absence of foam cells and the absence of intimal smooth muscle cells. No specimen had atherosclerotic disease and only 3 specimens showed changes consistent with minimal intimal hyperplasia. Morphometric analysis of the 3 diseased specimens revealed only minimal luminal narrowing. These findings suggest that the inferior epigastric artery may not be prone to atherosclerosis. Thus, the inferior epigastric artery appears to be a safe myocardial conduit and long-term patency can be anticipated.

Abdominal Muscles↗
PubMed1992

Cytokine gene expression of endothelial cells infected with Trypanosoma cruzi.

Coronary microvascular spasm and platelet hyperreactivity have been implicated in the pathogenesis of Chagas' cardiomyopathy. To clarify further the role of the microvasculature in this disease, alterations in cytokine gene expression due to Trypanosoma cruzi infection of human umbilical vein endothelial cells were examined. Northern blot analysis of total RNA from endothelial cells demonstrated that interleukin (IL)-1 beta, IL-6, and colony-stimulating factor 1 (CSF-1) mRNA expression was absent or minimal in uninfected cells but significantly increased in infected cells. c-sis mRNA levels diminished with increased time of infection. In situ hybridization studies also demonstrated high levels of IL-6 mRNA in individual infected cells. Significant levels of IL-6 and IL-1 beta protein were detected in the supernatants of infected endothelial cells. The serum of an acutely infected individual contained high levels of IL-6 protein, suggesting the potential importance of cytokines secreted by the vascular endothelium in the pathogenesis of Chagas' cardiomyopathy.

Animals↗
PubMed1991

Beneficial effects of diltiazem on the natural history of hypertensive diabetic cardiomyopathy in rats.

Hypertensive diabetic rats develop a cardiomyopathy characterized by systolic and diastolic ventricular dysfunction, myocardial hypertrophy and fibrosis, pulmonary congestion and a very high mortality rate. Alterations in contractile proteins and sarcoplasmic reticular calcium (Ca2+) transport in diabetic myocardium and their partial reversal with verapamil suggest that calcium channel blockade may prevent death from congestive heart failure in hypertensive diabetic rats. A large group of rats with renovascular hypertension and streptozotocin diabetes were divided into four groups: untreated animals (Group 1) and animals treated with 100 (Group 2), 300 (Group 3) or 600 (Group 4) mg/kg per day of sustained release diltiazem mixed in their food. Treatment was begun shortly after the onset of hypertension and diabetes. Mortality rates after 4 months were 59% (19 of 32), 53% (17 of 32), 27% (7 of 26) and 35% (12 of 34) in Groups 1, 2, 3 and 4, respectively; the mortality rate in age-matched control rats was 5% (1 of 19). The reductions in mortality rates in Groups 3 and 4 were statistically significant. Diltiazem did not change systolic blood pressure, serum glucose concentration, heart rate or left ventricular mass. There was a trend to decreased left ventricular interstitial fibrosis and perivascular fibrosis in diltiazem-treated animals. Ventricular collagen concentration was similar in untreated hypertensive diabetic and control rats; levels were higher in hypertensive diabetic rats that died than in those that survived. There was a trend to decreased collagen concentration as diltiazem dose increased. Myosin isoenzyme distribution was not changed in Groups 3 and 4 (in comparison with Group 1). In all hypertensive diabetic groups, rats that died had a higher blood pressure, heart rate, relative left ventricular mass, lung weight and lung water than did survivors. The mortality rate was two to three times higher among rats with an initial blood pressure greater than or equal to 180 mm Hg. The beneficial effects of diltiazem on survival were most significant among rats with severe hypertension.

Animals↗
PubMed1991

Murine adenovirus infection of SCID mice induces hepatic lesions that resemble human Reye syndrome.

Murine adenovirus type 1 (MAV-1) infection of CB-17 SCID mice (which are homozygous for the severe combined immunodeficiency mutation) induces hepatic histopathologic and ultrastructural features that are strikingly similar to human Reye syndrome. Gross pathologic examination of MAV-1-infected mice revealed only pale yellow liver tissue. Histopathologic studies of tissue from MAV-1-infected mice revealed diffuse hepatic injury manifested by microvesicular fatty degenerative changes of hepatocytes and electron microscopic evidence of focal mitochondrial swelling with disruption of cristae and depletion of glycogen. Serum aminotransferase activities increased markedly in the infected animals; however, plasma ammonia levels were not elevated at the times assayed. Although all mice infected with MAV-1 died, neutralizing anti-MAV-1 monoclonal antibodies provided a dose-dependent delay in the appearance of clinical disease and hepatic histopathologic findings. Other findings included rare viral inclusions with only minimal inflammation in spleen, adrenal, and liver of infected mice. Our findings indicate that MAV-1 infection of SCID mice may provide important insights into the pathogenesis of the hepatic lesions of Reye syndrome.

Adenoviridae↗
PubMed1991

Aldehyde tanning: the villain in bioprosthetic calcification.

Preservation of bioprosthetic valves may play a role in valvular calcification. Subcutaneous implants in rats were used to test the effect of different preservation solutions. Fifty male Sprague-Dawley rats were divided into five groups. Fresh bovine pericardium was treated in one of five ways: group A: 99.5% glycerol for 1 week; group B: as group A, then normal saline wash and 0.25% formaldehyde storage for 24 h; group C: as group A, then normal saline wash and 4% formaldehyde storage for 24 h; group D: as group A, then normal saline wash and 0.625% glutaraldehyde storage for 24 h; group E: 0.625% glutaraldehyde and 4% buffered formaldehyde storage. Treated bovine pericardium was cut into 1-cm2 pieces and washed for 30 min with normal saline before implantation. In each animal, three pieces were implanted in the subcutaneous tissue of the back. After 70 days, retrieved specimens were examined grossly, and X-ray densitometry, calcium analysis, and histological examinations were carried out. The results showed that glycerol-treated tissue (group A) had less calcification (calcium 6.92 +/- 4.46 micrograms/mg dry weight) than other groups: group B (calcium 323.12 + 63.56 micrograms/mg dry weight); group C (calcium 240.65 + 13.47 micrograms/mg dry weight); group D (calcium 232.29 + 13.01 micrograms/mg dry weight). These differences were markedly significant (p less than 0.0001). It appears that aldehydes play an important role in the calcification of bioprosthetic valves. Experience with glutaraldehyde- and glycerol-treated pericardium in valvular applications in sheep support these observations.

Animals↗
PubMed1991

Pathologic fibrosis and matrix connective tissue in the subaortic myocardium of patients with hypertrophic cardiomyopathy.

To evaluate scar-type and matrix connective tissue and to assess their role in the diastolic dysfunction of hypertrophic cardiomyopathy, surgically resected subaortic myectomy specimens and several autopsy hearts from patients with hypertrophic cardiomyopathy were studied. Eighteen specimens were differentially stained by a newly developed method that precisely determines relative collagen content; these tissues were compared with postmortem hypertrophied and normal control subaortic specimens. Quantitation revealed a 72% higher level (36.5 vs. 22.1 micrograms collagen/mg protein) of stainable collagen in the hearts with hypertrophic cardiomyopathy than in hypertrophied control hearts. The endocardial plaque was quantitated morphometrically, and it constituted only 4.6 +/- 1.7% of the total increased collagen content in the cardiomyopathy specimens. For the matrix studies, the cardiomyopathy specimens were stained by a silver impregnation technique that identifies connective tissue elements not normally visible with routine histologic methods. There was a marked increase in content of all matrix components, both in areas of pathologic scarring and in "normal" zones. Whorls of matrix connective tissue were noted in regions of myocyte whorls, as well as independent of them. Thus, these studies revealed a striking increase of both scar-type and matrix connective tissue in hypertrophic cardiomyopathy. The extensive scarring and the pronounced interstitial and intercellular matrix connective tissue may contribute to the increased ventricular chamber stiffness and impaired relaxation in this disease.

Cardiomyopathy, Hypertrophic↗
PubMed1991

The diabetic heart: clinical, experimental and pathological features.

Patients with diabetes mellitus are particularly vulnerable to cardiovascular disease. Although both the macrovascular and microvascular complications are present in patients with diabetes alone, they are particularly severe in patients with both diabetes and hypertension. While there is no doubt that a primary diabetic cardiomyopathy occurs with functional consequences, considerable evidence--both in humans and in experimental animal models--points to hypertension as of critical importance in the pathogenesis of severe pathological and symptomatic diabetic heart disease. In hypertensive-diabetic cardiomyopathy, the histopathologic myocardial damage has been attributed to hypertension, while the myocellular dysfunction has been attributed to diabetes. Together, the consequences to the myocardium are devastating. Strict control of the hypertension and diabetes mellitus, along with prevention of the microvascular consequences of both conditions, may have an ameliorative effect on the subsequent development of diabetic heart disease.

Animals↗
PubMed1990

Autopsy-documented cure of multiple myeloma 14 years after M2 chemotherapy.

Multiple myeloma was diagnosed in a 65-year-old woman in 1974 who thereafter received five-drug M2 chemotherapy. All protein abnormalities subsequently returned to normal and serial bone marrow studies documented complete bone marrow remission. Destructive bone lesions persisted radiographically, but did not progress. In 1987, a localized sigmoid adenocarcinoma was resected. In 1988, the patient presented with multiple brain metastases associated with a primary pulmonary adenocarcinoma that proved rapidly fatal. At autopsy, no evidence of multiple myeloma was found. This report describes the first tissue-documented cure of multiple myeloma 14 years after diagnosis and initiation of M2 chemotherapy. The possible association of multiple myeloma with other malignancies is also discussed.

Aged↗
PubMed1990

Collagen degradation in ischaemic rat hearts.

Myocardial extracellular matrix is organized into a complex arrangement of intercellular and pericellular fibres and fibrils that serves as a supporting framework for contracting cells. Recent evidence suggests that changes in ventricular shape and function occurring after ischaemic injury may be related to alterations of this matrix. In this report we describe the rapid and extensive loss of collagen in myocardial infarction produced by ligating the left anterior descending coronary artery of the rat for 1-3 h. The total collagen content in the myocardial infarct zones after 1, 2 and 3 h of ligation was 75 +/- 8%, 65 +/- 7% and 50 +/- 10% respectively (mean +/- S.D.) of that of either the non-infarcted tissue controls or of the same regions in sex- and age-matched normal left ventricles. A marked decrease also occurred in the residual collagens which were not extractable with 6 M-guanidine hydrochloride, suggesting that rapid degradation of insoluble collagen fibres may also occur. The decreased collagen content in the 3 h myocardial infarct coincided with the appearance of several enzyme activities. Collagenase, other neutral proteinase and presumed lysosomal serine proteinase activities were increased by 3, 3 and 2 times the control values respectively. These results suggest that the increased activities of collagenase and other neutral proteinases may be responsible for the rapid degradation of extracellular matrix collagen in myocardial infarct.

Animals↗
PubMed1990

Endomyocardial biopsy diagnosis of small vessel disease: a clinicopathologic study.

We reviewed the clinical history of 191 patients undergoing endomyocardial biopsy and correlated signs and symptoms of heart disease with the presence or absence of small vessel disease. Idiopathic congestive heart failure (78%), arrhythmia (35%), and chest pain (25%) were the most frequent indications for biopsy. Small vessel disease was noted in 61% of the biopsies (67% female, 56% male): 10% severe, 36% moderate, and 15% mild small vessel disease. Patients with hypertension were twice as likely to have small vessel disease than those without hypertension. Of the 27 females with hypertension, 85% had small vessel disease, 67% with either severe or moderate small vessel disease. Small vessel disease was almost twice as frequent in patients with chest pain compared to patients without chest pain. Chest pain was significantly more common in patients with severe small vessel disease than in those with normal small vessels. Of all patients with chest pain, 18% had severe small vessel disease; however, of 20 patients with severe small vessel disease, 45% had chest pain. This analysis suggests that small vessel disease seen in endomyocardial biopsy is more common in women and is related to hypertension. When severe, it is likely to be associated with atypical chest pain.

Adult↗
PubMed1990

AIDS cardiomyopathy: first rule out other myocardial risk factors.

Consecutive autopsies of 59 male AIDS patients revealed that 21 had other myocardial risk factors: 17 were alcohol abusers and 6 had hypertension or coronary artery disease. AIDS patients with these myocardial risk factors were older (mean age 45 versus 35 years, P less than 0.01), and were more likely to have cardiomegaly (mean heart weight 397 grams versus 350 grams, P = 0.06) than patients with AIDS alone. When evaluating patients for AIDS cardiomyopathy, other myocardial risk factors must be considered.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Hypertensive-diabetic cardiomyopathy in rats.

Left ventricular papillary muscle function, transmembrane action potentials, myosin adenosinetriphosphatase (ATPase) and isoenzyme distribution, and myocardial pathology were studied in hypertensive (H), diabetic (D), hypertensive-diabetic (HD), and control (C) rats. There was approximately 50% relative left ventricular hypertrophy in H and HD rats. Relative lung and liver weights were greater in HD rats. Peak velocity of shortening tended to decrease progressively in H, D, and HD rats. The duration of contraction and relaxation was markedly prolonged in Ds and HDs. The length-developed tension relation was blunted in HDs. The negative inotropic effect of verapamil was similar in all groups. Resting membrane potential and amplitude were decreased in D and HD rats. Action potential duration was increased in H, D, and especially HD rats. The shortening of action potential duration with increased stimulus frequency was greater in H, D, and especially HD rats than in Cs. Left ventricular myosin ATPase and V1 isoenzyme content decreased progressively in H, D, and HD rats. Right ventricular V1 isoenzyme content was not affected in H rats but was markedly decreased in D and HD rats. Left (and right) ventricular pathology was unchanged in rats with diabetes but was increased in rats with hypertension. These data suggest that the combination of myocardial pathology (due to hypertension) and cellular dysfunction (caused mainly by diabetes) may result in cardiomyopathy and congestive heart failure in the HD rat.

Analysis of Variance↗
PubMed1990

A comparison of the pathological spectrum of hypertensive, diabetic, and hypertensive-diabetic heart disease.

The hearts obtained at autopsy of 67 patients with hypertension, diabetes mellitus, or both were examined microscopically and histochemically, and the amount of fibrosis was determined. Significant differences in heart weight, interstitial fibrosis, replacement fibrosis, and perivascular fibrosis were found among the groups. The mean heart weight of the hypertensive-diabetic patients was significantly greater than that of the hypertensive patients and the diabetic patients. The amount of microscopic fibrosis increased between the groups, the lowest in hypertensive hearts, midrange in diabetic hearts, and highest in hypertensive-diabetic hearts. Total fibrosis correlated with heart weight among diabetic and hypertensive-diabetic patients and was significantly greater among patients with congestive heart failure, most of whom had histories of both hypertension and diabetes. The microscopic grade of fibrosis correlated significantly (p less than 0.01) with a quantitative, histochemical determination of the amount of collagen per milligram of total noncollagenous protein in the heart tissue. Myocardial fibrosis may contribute to the diastolic dysfunction typical of hypertensive-diabetic cardiomyopathy, in which congestive heart failure is a common sequela. The importance of hypertension in the pathogenesis of severe diabetic heart disease is discussed.

Adult↗
PubMed1990

Swimming causes myosin adaptations in the rat cardiac isograft.

To investigate the contributions of humoral and hemodynamic factors to cardiac adaptations associated with chronic exercise, female Fischer 344 rats were subjected to chronic swimming, infrarenal cardiac transplantation, or both. Swimming resulted in hypertrophy (11-12%) of the in situ hearts in both the unoperated and operated animals compared with the matched sedentary controls. The cardiac isograft exhibited atrophy (32-35%), which was not attenuated by swimming. The cardiac isograft was also associated with a decrease in the percent of V1 myosin isoenzyme, which was attenuated by swimming (45 +/- 5% versus 66 +/- 6%). Swimming also increased the percent of this isomyosin in the in situ hearts of operated rats. These data suggest that hemodynamic load and/or neural innervation are necessary for hypertrophy associated with chronic conditioning by swimming, whereas myosin isoenzyme control is significantly mediated by humoral factors.

Adaptation, Physiological↗