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Biomedical subjects

M D Tilson

Publications and source records attributed to M D Tilson.

At least 19 recordsLinked to original sources
PubMed1992

Characterization of an elastase from aneurysmal aorta which degrades intact aortic elastin.

Accumulating evidence suggests that abdominal aortic aneurysms (AAA) are due to a pathologic process which results in the destruction of aortic elastin and other matrix components. In this study, protein extractions were performed on both aneurysmal and normal aorta. Extracts were applied to frozen section of normal aorta either alone or in combination with 10 mM ethylenediaminetetraacetic acid, recombinant tissue inhibitor of metalloproteases, 10 mM zinc, and 5 mM phenylmethylsulfonyl fluoride, under conditions where calcium was removed from the buffer. After incubation, the sections were stained for elastin and evaluated by computerized morphometry. Aneurysm extracts, only in the presence of calcium, showed significant elastolytic activity characterized by destruction of intact elastic lamellae that was inhibited by ethylenediaminetetraacetic acid, the recombinant metalloprotease inhibitor, and zinc. Phenylmethylsulfonyl fluoride showed no inhibitory activity. Healthy aortic extract showed no elastolytic activity. This inhibitory profile is consistent with a metalloenzyme. We conclude that aneurysmal aorta contains elastolytic activity that is secondary to a metalloenzyme which is not present in normal aorta. This activity may play a role in the destruction of the elastin matrix that is seen in AAA's.

Aorta, Abdominal↗
PubMed1991

The role of inflammation in nonspecific abdominal aortic aneurysm disease.

The predominant pathologic feature of abdominal aortic aneurysm is elastin destruction, and elastin destruction may be mediated by inflammation. In this investigation serial sections of abdominal aortic aneurysm specimens were selectively stained to study the relationship between inflammation and elastin degradation. In addition, soluble aortic extracts were examined for the presence of immunoglobulins. An inflammatory infiltrate was present in 8 of 10 of the abdominal aortic aneurysm specimens examined. The infiltrate was mononuclear, commonly located at the junction of the media and adventitia; it did not codistribute with loss of elastin. The presence of an inflammatory component in abdominal aortic aneurysm was associated with a large amount of immunoglobulin in soluble extracts from aneurysmal tissue compared to atherosclerotic and normal control extracts. This study further characterizes the microscopic pathology of abdominal aortic aneurysm and describes the presence of immunoglobulin in soluble tissue extracts. In addition, the possible role of inflammation in abdominal aortic aneurysm as it relates to protease expression is detailed.

Aorta, Abdominal↗
PubMed1991

Decreased tissue inhibitor of metalloproteinases (TIMP) in abdominal aortic aneurysm tissue: a preliminary report.

Important concepts underlying the pathophysiology of abdominal aortic aneurysm (AAA) disease include a genetic predisposition, male predominance, and increased proteolysis. Proteolytic activity is carefully controlled by an abundance of protease inhibitors and the increased proteolysis may reflect a decrease in inhibitory activity. The recent assignment for the major tissue inhibitor of metalloproteinases (TIMP) to the X chromosome provides a potential link between the male predominance and increased proteolysis noted in AAA. The purpose of this investigation was to measure the amount of TIMP in normal and diseased aorta. A polyclonal antibody to recombinant human TIMP was produced in rabbit and used to establish an immunoassay. Immunoreactive TIMP in normal and diseased aorta was then measured. There was more TIMP in the matrix-associated fraction than in the soluble fraction. There was significantly less immunoreactive TIMP in aortic extracts from AAA than from control as measured both by Western blot and radioimmunoassay. These results suggest that a diminished amount of TIMP in the aortic matrix in AAA patients may contribute to the increased proteolysis observed in AAA.

Aorta, Abdominal↗
PubMed1991

Suggested standards for reporting on arterial aneurysms. Subcommittee on Reporting Standards for Arterial Aneurysms, Ad Hoc Committee on Reporting Standards, Society for Vascular Surgery and North American Chapter, International Society for Cardiovascular Surgery.

The literature on arterial aneurysms is subject to potential misinterpretation because of inconsistencies in reporting standards. The joint councils of the Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery appointed an ad hoc committee to address this issue. This communication, prepared in response to the need for standardized reporting, defines and classifies arterial aneurysms and recommends standards for describing the causes, manifestations, treatment, and outcome criteria that are important when publishing data on aneurysmal disease.

Aneurysm↗
PubMed1990

Tissue inhibitor of metalloproteases (TIMP) is matrix associated in aortic tissue: report of a radioimmunoassay.

Tissue inhibitor of metalloproteinases (TIMP) is the major inhibitor of collagenase, gelatinase, proteoglycanase, stromelysin, and metalloelastases. An imbalance between proteases and inhibitors has been implicated in numerous disease processes including tumor invasion, rheumatoid arthritis, emphysema, and aortic aneurysm disease. The purpose of this investigation was to develop a polyclonal antibody to recombinant TIMP and establish an immunoassay to measure immunoreactive protein in normal and diseased tissues. A polyclonal antibody was produced in rabbit against recombinant human TIMP which was characterized and used to establish a radioimmunoassay. The assay was used to measure immunoreactive protein in fibroblast conditioned medium, human serum, and aortic extracts. There was more immunoreactive TIMP in matrix associated urea extracts than soluble salt extracts from human aorta, suggesting that TIMP is matrix associated. The sensitivity of the assay enables the specific measurement of this inhibitor in serum, fibroblast culture medium, and tissue extracts.

Aorta, Abdominal↗
PubMed1990

Hydrocortisone rapidly induces aortic rupture in a genetically susceptible mouse.

The Blotchy mouse has an X-linked trait that leads to aortic aneurysms and subsequent fatal rupture in nearly all affected male mice. Heterozygous female mice occasionally develop aneurysms, but they rarely rupture. Ten heterozygous female mice received 0.45 mg/mL of hydrocortisone acetate in drinking water. Within 2 weeks, 9 of 10 mice were dead (6 with proved aortic rupture, 3 with presumed rupture). The 10th mouse was documented to have an aortic aneurysm. A dose-response curve was generated. Hydrocortisone's effect was shown to be dose-dependent. In another experiment, normal female mice received 0.10 mg/mL of hydrocortisone acetate for 14 days. Two mice developed aneurysms, and the others developed aortic ectasia. These experiments establish the role of hydrocortisone in the induction of aortic rupture in a mouse with genetic susceptibility and the induction of aneurysms and ectasia in normal mice.

Animals↗
PubMed1990

Morphometric analysis of reticular and elastin fibers in the cerebral arteries of patients with intracranial aneurysms.

Elastin and reticular fibers were identified using standard histological strains in middle cerebral arteries taken from patients who had died from aneurysmal subarachnoid hemorrhage and control patients who did not have cerebral aneurysms. Examination of cerebral arteries from normal individuals revealed a dense network of fine reticular fibers in the arterial media that were uniformly distributed. Computerized morphometric analysis indicated that reticular fibers in the arterial media of cerebral arteries were significantly decreased in patients with aneurysms. In addition, these fibers were irregularly distributed and shortened when compared to those seen in control arteries. In both patients with aneurysms and control patients, elastin fibers were limited almost exclusively to the internal elastin lamina. No differences were observed in the appearance or content of elastin fibers in control patients and patients with aneurysm. Although other explanations cannot be excluded, these observations are consistent with the hypothesis that "intrinsic" abnormalities in the walls of cerebral arteries lead to conditions that favor the formation and rupture of cerebral aneurysms.

Aged↗
PubMed1989

Propranolol stimulates the crosslinking of matrix components in skin from the aneurysm-prone blotchy mouse.

Propranolol prevents or delays the formation of aortic aneurysms in both the lathyritic turkey and the Blotchy mouse models. This finding in the turkey is reported to be a direct effect on crosslinking of aortic collagen and elastin, independent of effects on pulse and blood pressure. The present work was performed to evaluate this hypothesis in the mouse model by studying the effect of propranolol on the insolubility of matrix proteins of skin, which would isolate the phenomenon from direct hemodynamic effects. Eight 6- to 8-week-old Blotchy mice were fed a diet containing 0.10% (w/w) propranolol for 12 weeks, and six Blotchy controls ate regular chow. At sacrifice the skins were extracted with 8 M urea, and the soluble and insoluble fractions were analyzed for hydroxyproline to determine the collagen contents. The elastin was estimated by subtracting the collagen from the insoluble fraction. There was a 147% increase in insoluble elastin with propranolol and a lesser increase of 54% in insoluble collagen. These results suggest that propranolol has a direct effect on crosslinking of matrix components.

Animals↗
PubMed1989

Incidence and etiology of abdominal aortic aneurysms.

Unlike coronary artery disease and cerebrovascular disease, the incidence of abdominal aortic aneurysms has increased dramatically over the past three decades. There appears to be a correlation between both hypertension and smoking and the development of aneurysms, and there is a substantial predominance of white men among the patients. Recent studies have also documented a strong genetic component to this disease. Several biochemical abnormalities have been noted in those with aortic aneurysms, including increased proteolysis (elastolysis and collagenolysis). At present, the precise etiology of aneurysmal disease remains unclear, but it will most likely turn out to be a heterogenous disease with several molecular forms.

Aorta, Abdominal↗
PubMed1988

Histochemistry of aortic elastin in patients with nonspecific abdominal aortic aneurysmal disease.

Histochemical studies of nine aneurysmal aortas revealed a conspicuous deficiency of iron hematoxylin-reactive elastin in four specimens, in comparison with eight atherosclerotic control specimens. A fibrillar matrix that morphologically resembled elastin was demonstrated in these same specimens under ultraviolet light. The phenomenon of substantial preservation of features of medial architecture suggests that, if the pathogenetic mechanism is enzymatic destruction, the process is highly selective. Comparisons with differences in human fetal vs newborn aortas and in Blotchy mouse vs normal mouse aortas suggest superficial similarities. These latter observations suggest that a hypothesis of maturation arrest might be considered as an alternative to enzymatic destruction. Definitive experiments to test the relative importance of maturation arrest vs enzymatic destruction in the pathogenesis of aneurysmal disease will require further studies.

Adult↗
PubMed1988

Effect of beta-adrenergic blockade on the growth rate of abdominal aortic aneurysms.

We retrospectively identified 136 patients with abdominal aortic aneurysms (AAAs) who were initially evaluated as outpatients. Twenty-seven of these patients met the following criteria for eligibility in the study: (1) roentgenographic documentation of an AAA larger than 3 cm, (2) at least two serial ultrasound size determinations over a minimum six-month interval, and (3) a documented medication history. Of these 27 patients, 12 received long-term beta-blockade, while 15 received no beta-blockade. The two groups were comparable with respect to age, sex, initial aneurysm size, mean systolic and diastolic blood pressure, and duration of follow-up (mean, 34 months). Among patients with beta-blockade, the mean growth rate was 0.17 cm/y. The rate for the controls was 0.44 cm/y. One patient of 12 (8%) in the beta-blocker group had a rate that exceeded the mean for the overall group compared with eight patients of 15 (53%) in the group with no beta-blockade. This difference was statistically significant. Thus, beta-blockade may be associated with a decreased AAA growth rate in this small, retrospective study.

Adrenergic beta-Antagonists↗
PubMed1988

Molecular diversity in the abdominal aortic aneurysm phenotype.

Abnormalities of collagenous peptides were detected among a group of 20 patients with abdominal aortic aneurysms, studied by high-performance liquid chromatography/NaDodSO4-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) analysis of the cyanogen bromide (CB) cleavage products of insoluble skin protein. Three abnormal patterns were identified as follows: (1) relative deficiency of a peptide with a relative molecular mass of approximately 58 kilodaltons (four patients); (2) relative decrease in the ratio of alpha-2 to alpha-1 (I) CB peptides (seven patients); and (3) decreased detection of all collagenous CB and pepsin cleavage products (one patient, who was also heterozygous for the Z allele of alpha 1-antitrypsin). The "minimal hypothesis" to explain these findings is that most of the observed abnormalities can be explained by collagenolysis in vitro, although a mutation in the primary structure of collagen has not been ruled out in all patients. Molecular heterogeneity appears to occur within the aneurysm phenotype, and the findings in the patient in group 3 allow identification of one possible risk factor in abdominal aortic aneurysmal disease that has a genomic assignment.

Amino Acids↗
PubMed1988

Propranolol delays the formation of aneurysms in the male blotchy mouse.

Propranolol has been reported to prevent aortic aneurysms in the beta-aminoproprionitrile-fed broad-breasted white turkey model. The purpose of this investigation was to determine the effect of propranolol in another animal model of aortic aneurysms, the spontaneously aneurysm-prone Blotchy (BLO) mouse. One hundred fourteen male BLO mice were fed control chow or a diet supplemented with 0.10% (w/w) propranolol. Groups were sacrificed at monthly intervals and the presence of aneurysms was determined after latex injection into the left ventricle. Aortic diameter was also measured at the widest point in a subset of mice from each group sacrificed at 4-5 months of age. At 4 months 86% of control and 32% of propranolol-fed animals had aneurysms (P less than 0.001). The difference in mean aortic diameter was also decreased by 33% in the propranolol-fed group (P less than 0.01). This study suggests that propranolol delays the formation of aneurysms in this spontaneous, genetically determined animal model.

Animals↗