Biomedical subjects
Publications and source records attributed to S Cho.
Only at cell concentrations of less than 10(7)/ml are E. coli in steady state as defined by three intrinsic properties: mean cell diameter, cellular specific gravity and the concentration of beta-galactosidase per cell. Such concentrations are below the range of turbidimetry.
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A 35-year-old homosexual man with acquired immune deficiency syndrome developed progressive dementia and spastic quadriparesis over a two-month period. Severe symmetrical, bilateral degeneration of the corticospinal and frontopontine fibers and cerebellar white matter were found postmortem. Several glial nodules in the brainstem and cerebellum suggested "smoldering" brainstem encephalitis. The possible association of the adenovirus that was isolated from the patient's cerebrospinal fluid to these obscure changes in the central nervous system is discussed.
Myocardial function, electrophysiologic characteristics, and structure were studied in rats with both renovascular hypertension and streptozotocin-induced diabetes (HD). Ventricular papillary muscles from untreated rats with HD showed a marked slowing of isometric and isotonic contractions. Peak developed tension and peak shortening were preserved, except in one animal with findings of congestive heart failure. Transmembrane action potentials increased fivefold in duration. Myocardial interstitial fibrosis was frequently observed. Physiologic parameters of rats with HD treated by left nephrectomy, captopril, and insulin were very similar to those of age-matched controls. The mortality rate of rats with HD was 43% over 5 to 6 months in the first study. In a second study, spontaneously dying rats with HD were compared with those deliberately killed. A 55% mortality was observed over 7 months. Myocardial structural damage and histologic evidence of congestive heart failure were more frequent in spontaneously dying rats with HD. Combined renovascular hypertension and diabetes in rats appears to be a new preparation of congestive cardiomyopathy.
Microspheres approximately 25 or 50 micrometers in diameter were systemically embolized from the left ventricular cavity. The number of microspheres given was empirically chosen to minimize the possibility of more than one microsphere lodging in an arteriole (3 mg/kg), yet was sufficient to allow for adequate histological assessment. The dogs were sacrificed after 24 hours, and focal areas of myocytolytic necrosis were noted in the myocardium. Groups of dogs were given pretreatment with drugs 10 minutes before embolization. Dogs pretreated with phentolamine (n = 8) and prazosin (n = 2) did not reveal any areas of myocardial necrosis after embolization with 25-micrometers microspheres. Cardiac lesions were also prevented in four of five dogs pretreated with verapamil. In contrast, cardiac lesions were not prevented by pretreatment with yohimbine (n = 2), dipyridamole (n = 3), propranolol (n = 2), or atropine (n = 2). Drug pretreatment with phentolamine or verapamil was not able to prevent cardiac lesions after embolization with 50-micrometers microspheres. Furthermore, despite a greater number of microspheres physically present in the subendocardial layer, the necrotic lesions were more frequent in the mid-wall and epicardial layers. Lesions produced by 25- or 50-micrometers emboli were also significantly smaller in the endocardium. Systemic embolization with microspheres excluding the coronary circulation did not produce cardiac lesions. We conclude that mechanical interruption of the coronary circulation with a 25-micrometers microsphere may be a necessary but not sufficient condition to produce cardiac necrosis. An alpha 1-adrenergic mechanism is also involved in the production of these lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
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The authors have continued their investigation of the hypertensive-diabetic (HD) rat by evaluating changes in the myocardial microvasculature in this model. Perfusion of HD animals in vivo with a silicone rubber solution revealed numerous areas of microvascular tortuosity, focal constrictions, and microaneurysm formation. These alterations were present to a lesser extent in normoglycemic hypertensive (H) rats, and were distinctly rare in normotensive diabetic rats and unaffected control animals. Quantitation of these vascular lesions revealed highly significant differences between HD animals and the other three groups, with hypertensive rats intermediate between HD rats and diabetic control rats. Areas of pronounced arteriolar constriction were also identified in the HD and H animals with the use of serial sections of Epon-embedded myocardium. It is believed that these lesions represent dynamic changes in the microcirculation, which may cause segmental reperfusion injury to the myocardium, leading to focal replacement fibrosis. Interstitial scarring may result from increased leakiness of small vessels exacerbated by the combined disease. The authors propose that the additive effects of hypertension and diabetes mellitus on the myocardial microcirculation may be a primary cause of cardiomyopathy in this model of human disease.
Accurate interpretation of chromosomal variants is essential in prenatal diagnosis in order to distinguish polymorphisms from potential pathology in the fetus. This paper reports intra-uterine diagnosis of a satellited Yq in two unrelated families. The 29-year-old consultant in Case A sought prenatal diagnosis because of a maternal family history of Down syndrome. Case B was studied because of maternal age of 37. GTG banded chromosome analysis of cultured amniotic fluid cells from both cases revealed a 46,XY chromosome constitution with extra material present on the Yqter. This was interpreted to be satellite material. QFQ, CBG and AgNOR staining were performed. The material in question proved to be AgNOR positive, indicating that it was transcriptionally active for ribosomal RNA production during the last cell cycle. In addition, frequent satellite association between the Yqter and other acrocentric chromosomes was noted. These findings confirmed the initial interpretation. Other family members were studied and an AgNOR positive Yqs chromosome was confirmed in normal males in three generations of both families. The Yqs chromosome observed in the fetal cells was therefore considered a normal variant. The outcome of pregnancy in Case A was a phenotypically normal male. Case B had not delivered at the time of this writing. The origin of this satellite material on the Y chromosome is considered.
In this study we quantitated the region of preserved myocardium between a subendocardial myocardial infarct (SEMI) and the endocardium in dogs and determined whether this preserved zone was within the region at risk and whether infarct extension could occur in this region. We also evaluated whether a similar subendocardial region exists in patients with SEMI. A 40-minute temporary occlusion of the left anterior descending coronary artery (LAD) in eight dogs resulted in a 35 +/- 5% transmural infarct with 8 +/- 1% subendocardial preservation as assessed by point-counting of the histologic specimens. In vivo perfusion of coronary vessels with Microfil showed that this preserved subendocardial zone was within the region at risk. The preserved subendocardial zone had significantly fewer cell layers in the dogs ventilated with room air than in dogs ventilated with 100% oxygen (8 +/- 4 vs 19 +/- 4, p less than 0.001), which suggests that diffusion from the ventricular cavity was the mechanism of cell preservation. In contrast, the inspired oxygen concentration did not influence the size of the SEMI. Reocclusion of the LAD for 24 hours in an additional eight dogs, 1 week after a SEMI had been created by a 40-minute temporary occlusion, resulted in both subendocardial and subepicardial extension involving 5 +/- % and 29 +/- 9%, respectively, of the transmural myocardium at the infarct center. Subendocardial infarct extension of a similar dimension to that in dogs ventilated on 100% oxygen was observed in postmortem material from eight patients with infarct extension. The preserved layers of subendocardium presumably receive sufficient nutrients from the ventricular cavity to maintain the viability of this region during temporary, but not permanent, reduction of blood supply from the coronary arteries.
The pathogenesis of the cardiomyopathy associated with diabetes mellitus is unknown. Among several suggested mechanisms, myocardial necrosis induced by endogenous catecholamines may play a role. Therefore, the sensitivity of the heart to the effect of varying doses of isoproterenol hydrochloride and norepinephrine bitartrate was examined in diabetic and control rats given streptozocin. The dose of isoproterenol hydrochloride ranged from 0.008 to 30 mg/kg of body weight. Norepinephrine bitartrate was given in doses from 0.2 to 1.0 mg/kg of body weight. Each dose was given twice, 24 hours apart. Animals were killed 48 hours after the first dose, and their hearts were examined pathologically. Diabetes did not significantly alter the pathological response of the heart to either drug. We conclude that the diabetic heart is not intrinsically hypersensitive to catecholamines.
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Though myocardial alterations are well recognized in haemochromatosis, little attention has been paid to the cardiac changes in Wilson's disease. To define the extent of myocardial degeneration in newly diagnosed or chronically treated Wilson's disease, we reviewed the autopsy findings in 9 cases with this condition. We compared our observations with those in 3 control cases, selected for comparable age and with liver disease having no known association with cardiac degeneration. Our results revealed cardiac hypertrophy in 5 out of 9 cases of Wilson's disease. There was evidence of interstitial and replacement fibrosis, intramyocardial small vessel sclerosis and focal inflammatory cell inflammation to a variable degree in all cases. One case had AV nodal degeneration, and a 15 year old boy had severe atherosclerosis of the left main coronary artery. Two patients died suddenly, presumably secondary to an arrhythmia; one of these patients had the most marked myocardial alterations. We could not correlate these changes specifically with the tissue levels of copper, treatment with D-penicillamine, or the presence of cirrhosis. We conclude that there are definite morphological abnormalities in the hearts of patients with Wilson's disease consistent with a cardiomyopathy. Though the myocardial changes were non-specific, the fact that 2 patients died suddenly, suggests the need for a prospective study of cardiac function in these patients in the future.
Nine new patients with de novo membranous nephropathy (MN) are reported. The onset of MN, as defined by onset of nephrotic-range proteinuria, ranged from 11 to 30 months after transplantation. Five of the nine patients returned to hemodialysis within 4 to 26 months after the onset of nephrotic syndrome. No known exogenous (for example, ALS or HBsAg) or endogenous antigens could be demonstrated as the cause in any of the nine patients. The possibility that excellent tissue compatibility might increase the risk of subsequent de novo MN is suggested by the finding of four patients with "full house" HLA-A,B mismatch. This phenomenon occurs in approximately one in 100 to 200 transplants. It is suggested that de novo MN is not as unusual as heretofore believed and that its prognosis is poor.
The cardiomyopathic Syrian hamster develops focal myocardial necrosis beginning at 1 month of age, which leads to eventual ventricular failure within 1 year. The pathogenesis of this myocytolytic necrosis is unknown. Based on the nature of the cell necrosis, cytochemical evidence of vascular alterations, and the sensitivity of the hamsters to catecholamines and other vasoactive substances, we believe that the cardiomyopathy may be mediated by abnormalities of the microcirculation. Nonetheless, until the present study, no significant changes have been observed in these vessels. To elucidate the pathogenesis of this disease, we perfused living cardiomyopathic hamsters with silicone rubber solutions, which revealed numerous areas of microvascular constriction, diffuse vessel narrowing and luminal irregularity. Fixed structural lesions in these vessels could not be demonstrated. Pretreatment of young hamsters with verapamil during the period when they normally develop myocardial necrosis prevented myocytolytic lesions and abolished microvascular hyperreactivity. We believe that focal, transient spasm of small blood vessels, probably secondary to vasoactive substances, may cause myocytolytic necrosis (a form of reperfusion injury) in this model. This may also be a multifactorial disease with myocellular as well as vascular abnormalities leading to myocardial degeneration. The similarity of this disease to human and experimental cardiomyopathy suggests that microvascular spasm may be a common denominator of many different cardiomyopathic syndromes.
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