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Biomedical subjects

G W Moore

Publications and source records attributed to G W Moore.

At least 19 recordsLinked to original sources
PubMed1992

Liver cell dysplasia: a DNA aneuploid lesion with distinct morphologic features.

Liver cell dysplasia is characterized by hepatocellular foci with nuclear atypia. It is often seen in cirrhosis and may be a precursor of hepatocellular carcinoma (HCC). To determine whether liver cell dysplasia is DNA aneuploid, 72 sections of 33 cirrhotic livers from the autopsy files of The Johns Hopkins Hospital were studied, and 14 foci of dysplasia from 13 cirrhotic livers were selected. Patients ranged in age from 32 to 70 years. Histologically, there were 10 foci of low-grade dysplasia and four foci of high-grade dysplasia. Nine HCCs served as positive controls; seven autopsy livers with no morphologic or clinical evidence of primary liver disease served as negative controls. One focus of HCC and one focus of dysplasia were unsatisfactory for analysis. Flow cytometric examination demonstrated subpopulations with DNA abnormality in four of nine (44%) foci of low-grade dysplasia, of which three were aneuploid. Three of four (75%) foci of high-grade dysplasia were aneuploid. Six of eight (75%) HCCs showed DNA abnormality, of which five were aneuploid. DNA aneuploidy was not present in the seven control livers; however, one showed DNA abnormality. We conclude that liver cell dysplasia is a morphologic entity that contains DNA aneuploid cells, a feature that supports the role of liver cell dysplasia in the evolution of HCC.

Adult↗
PubMed1992

Automated review of blood donor screening test patterns at a regional blood center.

Regional blood centers recently increased the number of tests used to protect transfusion recipients from infectious disease. The Food and Drug Administration has noted that computer systems for managing these data have lost donor data or failed to recognize all deferrals. Of 118,396 consecutive donations, including 4,859 records with at least one positive test result, records were analyzed to determine the number and frequency of distinct combinations of test data. A modular precedence-logic expert system assigned donor deferrals and unit dispositions. Ten combinations of data accounted for 4,334 records (89%); the remaining 525 records (11%) were distributed among 85 combinations of test data. The expert system correctly assigned all records. Regional blood centers must interpret a growing number of test results, including donations with a complicated pattern of multiple positive screening test results. The distribution of these data is described and the expert system's ability to monitor deferrals and ensure database completeness is demonstrated.

Blood Banks↗
PubMed1992

The role of cell death in the growth of preneoplastic lesions: a Monte Carlo simulation model.

A variety of experimental and clinical examples of preneoplasia demonstrate that regression of early lesions is common. This paper examines the hypothesis that early lesions operate under the identical growth kinetics of 'late' lesions (neoplasms), but that kinetic features favouring continuous growth in established lesions tend to favour extinction of lesions composed of small numbers of cells. Growth simulations of early lesions were produced using the Monte Carlo method, a technique demanding intensive computations. With the advent of powerful personal computers, this technique is now widely available to biologists. Simulating growth under conditions of cell loss similar to those observed in established tumours, the model predicts that the great majority of initiated cell clusters are expected to reach extinction within a few cell doubling times, and most early (promoted) lesions would not likely progress to the size of a clinically detectable lesion within the life span of the host organism. These Monte Carlo simulations provide a model of initiated cell growth consistent with the recently demonstrated role of early lesion cell death in the development of human lymphomas and in transgenic mice expressing the bcl-2 oncogene. The model demonstrates that small increments in the intrinsic cell loss probability in even the earliest progenitors of malignancy can strongly influence the subsequent development of neoplasia from initiated foci.

Apoptosis↗
PubMed1992

Research by pathologists not funded by external grant agencies: a success story.

The paradigm of pathology research as an endeavor among grant-funded principal investigators resulting in first-author publications is unsupported by quantitative examination of author profiles extracted from the scientific literature. Publications in six pathology journals (Modern Pathology, American Journal of Surgical Pathology, Human Pathology, Acta Cytologica, Archives of Pathology and Laboratory Medicine, and American Journal of Clinical Pathology) and three general science journals (Science, New England Journal of Medicine, and Proceedings of the U.S. National Academy of Sciences) were reviewed. Twenty articles per journal from each of three years (1987, 1989, and 1991) were examined (a total of 520 articles). Of these, 295 articles were first-authored by a member of a department of pathology. Of the 295 articles first-authored by a member of a pathology department, 47 (16%) articles listed competitive grant support. Of the grant-supported articles, 20 articles listed NIH support, but only four had an NIH-supported principle investigator as the first author of the article. Unfunded research represented the vast majority (84%) of work produced by pathologists. A review of the ISI Citation Index showed that those articles written by funded pathologists averaged 8.7 (S.D. 7.8) citations per article, compared to 10.4 (S.D. 12.1) citations per article for unfunded pathologists. Results suggest that unfunded research accounts for the majority of pathology research activity as well as their resulting literature citations.

Authorship↗
PubMed1992

Spontaneous regression of residual tumour burden: prediction by Monte Carlo simulation.

Current cancer treatment protocols are designed to release the tumour burden down to a small number of cells. In this study, we use Monte Carlo simulations to show that small populations of cells with intrinsic cell loss rates comparable to the cell loss rates observed clinically in human tumours, may regress spontaneously. Large populations of cells tend to grow under the same conditions of cell loss that result in extinction of small clones. Furthermore, minor variations in the intrinsic cell death probability near 0.50 result in large differences in the number of surviving cells calculated at the 100th generation. When Monte Carlo simulations of clonal growth resulted in clones with large populations (> 50 cells), the population as a whole behaved in a deterministic fashion (logarithmic growth) similar to those observed in clinically observed neoplasms and consistent with other published models of tumour growth. These findings provide a plausible explanation for the clinically observed failure of tumours to recur in instances where tumour burden remains following cancer therapy. The findings also demonstrate the usefulness of the Monte Carlo method to simulate biologic events in populations where the fate of each member of a population can be modeled probabilistically.

Cell Death↗
PubMed1992

Multiparameter DNA flow cytometry of keratoacanthoma.

Keratoacanthomas (KAs) are rapidly growing cutaneous lesions that frequently look much like well-differentiated squamous cell carcinomas (SCCs) but spontaneously regress. It is uncertain whether KA is a reactive hyperplastic lesion that mimics a neoplasm or a true (but defective) neoplasm that cannot sustain progressive growth. To address this question, we performed DNA flow cytometric analysis on 14 KAs and 10 cutaneous SCCs for comparison. By multiparameter DNA flow cytometry using forward scatter and orthogonal scatter, 10 KAs and 4 SCCs had peridiploid DNA aneuploid populations (DNA indices of 1.03-1.14), and 2 SCCs had grossly aneuploid populations (DNA index, 1.69 and 2.33). Our data thus support aneuploidy in KAs. It is argued that KA is a true neoplasm.

Aneuploidy↗
PubMed1979

Role of the left interventricular sulcus in formation of interventricular septum and crista supraventricularis in normal human cardiogenesis.

Serial sections of normal human embryos were studied and three-dimensional images reconstructed to determine the early development of the interventricular septum. The position of the interventricular septum is determined in stage 9 of normal development by the formation of the left interventricular sulcus. As a result of unknown properties of the cells of the myocardial layer, the left interventricular sulcus persists while the right disappears, producing the initial lateral asymmetry of the primary heart tube. By stage 14, the left interventricular sulcus forms a spiral which is continuous with the developing interventricular septum. The dorsal limb of the spiral passes to the right between the atrioventricular canal and the origin of the outflow tract, and is lost in the wall of the trabeculated right ventricle. It appears that this dorsal limb of the spiral is the precursor of part of the cirsta supraventricularis. The midportion of the sulcus, the bulboventricular groove, becomes the so-called fibrous continuity between the aortic and mitral valves. The ventral limb of the spiral passes caudally in the anterior interventricular groove and then dorsally and cranially toward the dorsal cushion of the atrioventricular canal. The ventral limb of the spiral is continuous with the crest of the muscular interventricular septum, which develops by apposition of tissue from the expanding right and left ventricles. From stage 14 to stage 19, the muscular interventricular septum, the atrioventricular endocardial cushions, and the ventricular end of the spiral ridges of the outflow tract appose and fuse. Subsequent formation of the membranous interventricular septum completes the physical separation of the right and left ventricles.

Endocardium↗
PubMed1979

Reversed septal curvature. Association with primary pulmonary hypertension and Shone syndrome.

In the normal heart the interventricular septum is curved concave to the left and functions as a component of the left ventricular wall. We have studied the hearts of five patients at autopsy, after postmortem angiography and fixation in distention, in which the septum was concave to the right ventricle. These patients ranged in age from eight months to 25 years (average, 16 years); three had primary pulmonary hypertension, and two had coarctation of the aorta and congenital aortic stenosis. Catheterization studies in the latter two patients had demonstrated subaortic stenosis. At autopsy there was no evidence of asymmetric septal hypertrophy or of abnormal septal myocardial fiber disarray. The right ventricles were markedly hypertrophied. In each, the septal curvature was reversed leading to protrusion of septal muscle into the left ventricular outflow tract with marked narrowing of the outflow tract. Since the septal configuration is determined early in life, this abnormality of ventricular topography may develop primarilary or it may develop in hearts subject to early as well as long-standing right ventricular overload.

Adolescent↗
PubMed1979

Reduction of serum cholesterol in two patients with homozygous familial hypercholesterolemia by dichloroacetate.

Dichloroacetate is known to reduce plasma cholesterol and triglyceride in patients with Fredrickson Types IIb or IV hyperlipoproteinemia. We now report the effects of chronic, oral dichloroacetate administration (as the sodium salt) in two patients with severe homozygous familial hypercholesterolemia. Dichloroacetate markedly reduced serum total and low density lipoprotein cholesterol levels and lowered the low density lipoprotein to high density lipoprotein cholesterol ratio. One patient developed a polyneuropathy while receiving dichloroacetate which resolved following discontinuation of the drug. Because of its apparent toxicity, dichloroacetate cannot be recommended for chronic oral use. Investigation of the mechanism of its lipid-lowering effect, however, may provide insight into the pathogenesis and treatment of hypercholesterolemic disorders.

Acetates↗
PubMed1979

Atrioventricular canal malformation interpreted as secondary to reduced compression upon the developing heart.

This study was undertaken to evaluate the nature and pathogenesis of malformations of the atrioventricular canal in relation to normal cardiogenesis. Serial histologic sections of normal human embryos and fetuses were made, from which three-dimensional images were reconstructed to show the relationship between the developing heart and its surrounding structures, and the course of development of the atrial septum and atrioventricular valves. Based on these reconstructions and on examination of the hearts of 59 patients with atrioventricular canal malformations, it is suggested that the spectrum of atrioventricular malformations may arise as a result of reduced compression of the developing atria by surrounding structures during embryonic Stages 13 through 18. Comparison of hearts with atrioventricular canal defects with normal embryos indicated that the malformations may be classified as primitive canals, complete canals, or partial canals, corresponding to failure of completion of normal development in Stages 14 through 18. In primitive canal the atrial septum was absent or had only a portion of septum primum. In complete canal both atrial septums were present, but the atrioventricular valve material was not subdivided and the four chambers were in communication. In partial canal, the atrioventricular valve was divided, but atrial and ventricular septal defects and valve clefts were present in varying degrees of severity. It is proposed that the spectrum of cardiac abnormalities which constitutes atrioventricular canal malformations may be understood as arising from varying degrees of lack of normal compression of the developing heart by surrounding structures. (Am J Pathol 95.579-598, 1979)

Adolescent↗
PubMed1978

On investigating the statistical properties of the populous path algorithm by computer simulation. Counterconclusions to those of Tateno and Nei.

Goodman et al.'s (1974) populous path algorithm for estimating hidden mutational change in protein evolution is designed to be used as an adjunct to the maximum parsimony method. When the algorithm is so used, the augmented maximum parsimony distances, far from being overestimates, are underestimates of the actual number of nucleotide substitutions which occur in Tateno and Nei's (1978) computer simulation by the Poisson process model, even when the simulation is carried out at two and a half times the sequence density. Although underestimates, our evidence shows that they are nevertheless more accurate than estimates obtained by a Poisson correction. In the maximum parsimony reconstruction, there is a bias towards overrepresenting the number of shared nucleotide identities between adjacent ancestral and descendant nodal sequences with the bias being stronger in those portions of the evolutionary tree sparser in sequence data. Because of this particular property of maximum parsimony reconstructed sequences, the conclusions of Tateno and Nei concerning the statistical properties of the populous path algorithm are invalid. We conclude that estimates of protein evolutionary rates by the maximum parsimony--populous path approach will become more accurate rather than less as larger numbers of closely related species are included in the analysis.

Biological Evolution↗
PubMed1978

Metabolic effects of dichloroacetate in patients with diabetes mellitus and hyperlipoproteinemia.

Dichloroacetate is known to reduce plasma glucose and triglycerides in diabetic and starved animals and to lower plasma lactate under various experimental conditions. To investigate its metabolic effects in man, we administered oral doses (3 to 4 g) of dichloroacetate as the sodium salt to patients with diabetes mellitus or hyperlipoproteinemia or both for six to seven days. Dichloroacetate significantly reduced fasting hyperglycemia an average of 24 per cent (P less than 0.01) from base line and produced marked, concomitant falls in plasma lactate (73 per cent; P less than 0.05 to less than 0.01) and alanine (82 per cent; P less than 0.01 to less than 0.001). In addition, it significantly decreased plasma cholesterol (22 per cent; P less than 0.01 to less than 0.001) and triglyceride (61 per cent; P less than 0.01) levels while increasing (71 per cent; P less than 0.01) plasma ketone-body concentrations. Plasma insulin, free fatty acid and glycerol levels were not affected. Serum uric acid rose, whereas excretion and renal clearance fell. Some patients experienced mild sedation, but no other laboratory or clinical evidence of adverse effects was noted during or immediately after the treatment phase.

Acetates↗
PubMed1978

Association of interrupted aortic arch with malformations producing reduced blood flow to the fourth aortic arches.

Interrupted aortic arch is a rare congenital malformation of the great arteries with loss of continuity between the proximal portion of the aortic arch and the descending aorta, which is usually supplied by a patent ductus arteriosus. The hearts of 12 patients with interrupted aortic arch listed in the autopsy files of The Johns Hopkins Hospital were evaluated. Four categories were identified. Seven hearts with normal outflow tract relations had significant pulmonary arterial override of a ventricular septal defect and thus recevived part of left ventricular and all of right ventricular ejection flow; flow into the aorta was correspondingly reduced. Two hearts had mitral valve obstruction with decreased left heart flow. Two hearts had double inlet left ventricle and transposed great arteries with the aorta originating from a small anterior conal chamber. One heart had a truncus malformation with a disproportionately large flow entering the pulmonary arterial division. In each of these hearts, the pattern of the outflow tracts and associated malformations suggested that there was a preferential flow of blood into the sixth arches and correspondingly a reduced flow into the fourth arches at the time of normal disappearance of components of the embryonic aortic arch system. Thus, interrupted aortic arch may simply be disappearance of the normally persisting connection between the left fourth and sixth arches as a result of flow imbalance in early cardiogenesis.

Aorta, Thoracic↗