Studies on thymic involution: growth potential and DNA repair of the stromal cells.
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Aging↗
Biomedical subjects
M Aronson
Publications and source records attributed to M Aronson.
Instability of leukocyte aggregation: lack of evidence for leukoembolization during various states of inflammation.
This study centers on the question of whether the phenomenon of leukocyte aggregation, which is typical to inflammatory conditions, is pathogenic per se. We examined patients and laboratory animals in whom the presence of aggregated leukocytes in the peripheral blood was documented by direct visualization and where, despite the presence of aggregated leukocytes, neither the patients nor the laboratory animals showed clinical or pathological evidence for leukoembolization. Our in vitro findings about the reversibility of the phenomenon of leukocyte aggregation help to explain the above-mentioned observations as well as the well-known daily clinical experience that, despite complement activation and other aggregatory stimuli, there is no clinical or pathological evidence for leukoembolization.
Aged↗
Endotoxin-induced shedding of viable uroepithelial cells is an antimicrobial defense mechanism.
ICR mice were infected intravesically with a virulent (7343) or a nonvirulent (U+) Escherichia coli strain. The U+ strain induced considerably more shedding of uroepithelial cells than did the 7343 strain. The stimulus for this shedding was shown to be associated with lipopolysaccharide and was abrogated by pretreatment with aprotinin. Desquamation commenced within 1 h postinjection, and the cells that were shed proved to be viable. Comparison of C3H/HeJ and C3H mice revealed that only the latter responded to shedding inducers. However, C3H/HeJ mice succumbed to a systemic infection on injection of 10(6) U+ cells intravesically, whereas other mouse strains required a 100-fold dose of bacteria for this effect. Since the first stage of a bacterial infection entails adherence of the microbes to epithelial cells, inducible shedding is an antimicrobial defense mechanism.
Animals↗
Evaluation of disease activity in rheumatic patients by leucocyte adhesiveness/aggregation.
Previous work has shown that leucocyte adhesiveness/aggregation (LAA), as measured by the leukergy test, correlates well with disease severity in rheumatic patients. As LAA is probably a manifestation of the acute phase reaction various components of the acute phase reaction were measured in order to identify the best marker of disease activity. In addition to LAA, the following variables were measured in 79 patients with various rheumatic diseases and in 10 controls: white blood cell and platelet counts, erythrocyte sedimentation rate, haptoglobin, fibrinogen, C reactive protein, albumin, globulin, caeruloplasmin, alpha 1, alpha 2, beta, and gamma globulin, and haemoglobin concentrations. Patients were graded according to the state of their disease as mild, moderate, or severe. The extent of leucocyte adhesiveness/aggregation in peripheral blood proved to be the best laboratory variable for the grading of disease activity. Correct grading was obtained in 63% of the patients by means of the LAA, compared with 48% with C reactive protein, 41% with caeruloplasmin, 40% with haptoglobin, and 32% with haemoglobin. It is suggested that LAA of the peripheral blood during inflammation may be used as a reliable marker of disease severity.
Adolescent↗
Clinico-pathologic studies in dementia: nondemented subjects with pathologically confirmed Alzheimer's disease.
We compared neuropsychological findings in 28 longitudinally evaluated elderly subjects with their postmortem neuropathology, including senile plaque and neurofibrillary tangle counts from standardized sections. Nine of the subjects were not demented when evaluated just prior to their death. Numerous cortical senile plaques and other changes of Alzheimer's disease (AD) occurred in six of nine nondemented old-old subjects. Five of these six subjects had shown decline on yearly neuropsychological tests but their cognitive impairment was too mild to meet clinical criteria for dementia. Whereas cortical senile plaque count did not distinguish well between demented and nondemented subjects, every subject with numerous cortical neurofibrillary tangles was demented. The nondemented subjects with Alzheimer pathology may have had "preclinical" AD, or numerous cortical plaques may occur in some elderly subjects who would never develop clinical dementia.
Aged↗
Traits of the 'ideal physician' as perceived by medical students and faculty.
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Attitude of Health Personnel↗
Synergism between zymosan-activated serum and heparin in the induction of polymorphonuclear leukocyte aggregation.
During the course of extracorporeal circulation, leukocyte aggregation is known to occur in some patients. This is attributed to complement activation and release of the chemotactic factor C5a. We investigated the effect of heparin on in vitro complement induced aggregation of polymorphonuclear leukocytes (PMNAGG), since most patients undergo heparinization during the extracorporeal circulation. Our results indicate that sub-aggregating concentrations of zymosan-activated serum (ZAS) enhance heparin-induced PMNAGG and that sub-aggregating amounts of heparin increase the aggregation induced by ZAS. Heat inactivation of the serum prior to zymosan activation abrogated the aggregating activity of the ZAS. Furthermore, the combined ZAS and heparin-induced PMNAGG was partially inhibited by specific antibodies to C5a but not to C3a. Therefore, we suggest that heparin and C5a may have a synergistic effect on the aggregation of polymorphonuclear leukocytes. These data might be relevant to situations in which patients are subjected to extracorporeal circulation.
Cell Aggregation↗
Possible role of fibrinogen in the aggregation of white blood cells.
In order to verify whether leukocyte aggregation correlated with aggregation of other cellular elements during inflammation, we examined the state of leukocyte adhesiveness/aggregation (LAA) in the peripheral blood and red cell aggregation. Correlation was found to be significant as was the correlation between LAA and fibrinogen, and with the fibrin/fibrinogen degradation products concentration during various inflammatory states. In vitro leukocyte aggregation was decreased when the cells were suspended in autologous heat defibrinogenated plasma as compared to cells suspended in autologous native plasma. Heat aggregated fibrinogen but not native fibrinogen caused leukocyte aggregation in vitro. Finally, Arvin defibrinogenation in rabbits reduced the state of LAA in endotoxinemic rabbits. Integrating all this information, we assume that fibrinogen participates not only in the aggregation phenomena of red cells and platelets, but also in those of leukocytes.
Animals↗
Deletion of 2p: a cytogenetic and clinical update.
The locus for acid phosphatase (ACP1) had been alternately assigned to two conflicting regions on the short arm of chromosome 2. We present a clinical and cytogenetic report of one patient who has an interstitial deletion of 2, del(2) (p23p25.1), and a cytogenetic study of another cell line with an interstitial deletion of 2p (p23.1p25.1). Because both patients are heterozygotes for ACP1, the assignment of ACP1 to 2p25.1----pter is supported.
Abnormalities, Multiple↗
Cytogenetic evaluation of human endothelial cell cultures.
Cytogenetic evaluation of serially subcultivated human endothelial cells revealed significant differences between cultures derived from fetal umbilical cords and cultures derived from various vessel sites in adults. A rapid increase in the prevalence of polyploid cells, to levels of 100% in many cases, was detected in human umbilical vein endothelial cell cultures but not in endothelial cell cultures from adult vessels. Because the development of polyploidy has been viewed as one signpost of in vitro senescence, it may be that these in vitro observations of high levels of polyploidy are a reflection of the fact that umbilical tissue is at the end of its in vivo developmental lifespan when studied. Consistent karyotypic alterations also were observed in two clones from adult human abdominal aorta, even though these cultures exhibited low percentages of polyploid cells. Cultures of one clone exhibited a trisomy of chromosome 11, on which there are at least three onc gene loci, and a deletion of chromosome 13 through band q14. A loss of band 13q14 is a prezygotic chromosomal lesion known to predispose to retinoblastoma. In the other clone, two cell populations were observed, and each displayed a chromosomal abnormality. A trisomy of the long arm of chromosome 2 was noted in one cell population via a marker chromosome involving 2 and 14. The other cell population exhibited an abnormality of chromosome 2. Neither of these karyotypic alterations was detected in the parent culture from which the clones were derived. The results reported in this study have both practical and theoretical implications. The high incidence of polyploidy in serially cultivated umbilical cultures as well as the occurrence of chromosomal changes in umbilical and aortic cultures testify to the need for cytogenetic monitoring of cell cultures even though they are derived from presumably normal tissue. Cytogenetic changes in the endothelium may be important in atherogenesis and other pathologic states. The conversion of diploid endothelial cells into polyploid endothelial cells may provide a convenient model cell system for studying mechanisms of the development of polyploidy in cells and their relationship to in vitro senescence.
Adult↗
Residents' attitudes, knowledge, and behavior regarding diagnosis and treatment of alcoholism.
Few studies have addressed the variables that affect physicians' practice behavior in treating alcoholism. In the study reported here, the authors hypothesized that alcohol-related training and experience would influence practice behavior more significantly than attitudes or knowledge. In order to assess the most important predictors of practice behavior, the authors conducted a survey of 163 junior and senior medical residents at five training hospitals affiliated with Harvard Medical School. Of these residents, 123 responded (75 percent). Negative attitudes toward alcoholics and knowledge of alcoholism were not significantly related to the residents' estimates of the prevalence of alcoholism among their patients, to their rate of treating alcoholic patients, or to their rate of referring patients for alcoholism therapy. There was a significant relationship between having supervised clinical experience in alcoholism and these three behaviors. These results are consistent with the authors' hypothesis that changing physicians' practice in treating alcoholics may be best achieved by providing relevant clinical experience in alcoholism.
Adult↗
Aggregation of white cells and C-reactive protein: relation between these two indices in acute phase reaction.
The association between aggregates of leucocytes in blood drawn from patients with various inflammatory conditions and the serum concentration of C-reactive protein (CRP) was examined: serum concentration of CRP might contribute to the development of cellular aggregations. A total of 213 patients with various inflammatory or necrotic conditions were examined (including 31 women with normal pregnancy and 59 controls). A significant correlation between the degree of leucocyte aggregation and CRP concentration was noted in patients with bacterial infections and in a group of patients with various inflammatory conditions. In contrast, there was no correlation between the extent of leucocyte aggregation and CRP concentrations in patients with viral infections, malignancies, or pregnancy. The presence or absence of aggregated leucocytes can help in differentiating between the respective bacterial or viral infections. The serum concentrations of CRP were increased in both types of infection, although when a quantitative CRP assay was used, considerably higher concentrations were detected in bacterial diseases.
Acute-Phase Reaction↗
Neuropsychological effects of antihypertensive drugs.
Antihypertensive medications are all associated with adverse reactions, and the elderly patient may be particularly sensitive. In a large longitudinal follow up study in an aged population, beta-blockers were shown to have caused no greater impairment of cognitive function or mood when compared to a control population. alpha-Methyldopa did interfere with some measures of neuropsychological functioning.
Affect↗
The phenomenon of leukergy: induction and detection of leukocyte aggregation in whole human blood.
Leukocyte aggregation is involved in the generation of vascular damage during various inflammatory conditions. So far, in vitro leukocyte aggregation has been studied by mixing patients' plasma or serum with leukocytes of a normal donor in a platelet aggregometer. We evaluated the leukergy phenomenon, that is, the occurrence of aggregated leukocytes in peripheral blood of patients with inflammatory disorders, as an alternative tool to the former method. Leukocyte aggregation could be induced by zymosan-activated plasma, phorbol myristate acetate, and formyl-methionyl-leucyl-phenylalanine, as well as by the calcium ionophore A23187 in vitro in whole human blood. This aggregation was blocked by various lipoxygenase and cyclooxygenase pathway inhibitors. Leukergy was diagnosed in peripheral blood of patients with inflammatory disorders and was generally not associated with elevated concentrations of immune complexes, lactoferrin, C3a des Arg, or C5a des Arg. To the best of our knowledge, this is the first report on leukocyte aggregation studies performed in whole blood. Such study permits evaluation of the aggregation phenomena of leukocytes in their natural milieu. Furthermore, it is possible with this method to obtain direct visualization of leukocytic aggregates in the peripheral blood of patients. The significance of our results and their possible implications are discussed in light of the pertinent literature.
Adult↗
Children of alcoholic mothers.
The effects of maternal alcohol abuse during pregnancy on the offspring were investigated in three different studies. The aim of the studies was to examine the dynamics of infant physical growth and psychological development and to analyze the outcome in relation to the environment during upbringing. Size at birth was related to later mental retardation and neuropsychological symptoms. Psychosocial problems were significantly more frequent in children brought up in their biological homes. Alcohol abuse during the second and third trimester was found to have greater consequences for growth and mental development than during the first trimester.
Adolescent↗
The leukergy test in patients with ischemic heart disease.
In search of a simple method for potential evaluation of leukocyte aggregation in states of infarction, we compared the leukergy test, which consists of leukocyte aggregation visualized in a peripheral blood test, to the neutrophil aggregation activity (NAA) test, which consists of in vitro aggregation of neutrophils from normal donors by a patient's plasma. Seventy-five patients participated in the study; 20 with ischemic heart disease and no infarction, 41 with relatively small myocardial infarctions, and 14 with large myocardial infarctions, the respective values of leukergy being 6.9 +/- 3.2, 10.8 +/- 4.6, and 20.5 +/- 14%. On the other hand, neutrophil aggregation activity was the same in a group of 10 patients without myocardial infarction and 10 with myocardial infarction. In these two groups, which showed no difference in the NAA test, the respective leukergy values were 4 +/- 1.5 and 21.7 +/- 10.6%. Thus leukergy correlates better with the clinical picture than does the NAA test.
Aged↗
Alcohol abuse in women seeking gynecologic care.
In several retrospective studies, alcoholic women have reported menstrual problems significantly more often than nonalcoholic women. There is no information, however, comparing the prevalence of alcohol abuse in women who receive periodic gynecologic care and those who seek care for menstrual disorders such as the premenstrual syndromes. This question was studied in two private practice settings. Women seeking periodic care were obtained from a suburban, general gynecology practice. Women seeking treatment for premenstrual syndrome (PMS) were obtained from a practice that specialized in the care of PMS. Ninety-five patients with PMS and 147 patients seeking periodic care were screened with the CAGE questions--a mnemonic for attempts to Cut back on drinking, being Annoyed at criticism about drinking, feeling Guilty about drinking, and using alcohol as an Eye-opener. Women who gave affirmative responses to one or more of the CAGE questions were evaluated for the presence of alcohol abuse. In the women seeking periodic care, 33% were CAGE positive and 12% were alcohol abusers. In the PMS practice, 51% were CAGE positive and 21% were alcohol abusers. Alcohol abuse is a common problem in gynecologic practice. Women who seek medical care for PMS are at much greater risk to be alcohol abusers.
Adolescent↗
The leukergy test in rheumatic diseases. New implications for an old test.
In order to assess the value of the leukergy test in which leukocytes aggregate in citrated whole blood, we examined 65 patients with various rheumatic conditions. In addition, plasma samples from 40 patients were examined for neutrophil aggregation activity in vitro. Results of the leukergy test were found to be in very good correlation with disease activity (P = 0.0001), whereas no increased neutrophil aggregation activity was found in the 40 plasma samples examined. The value of the leukergy test in assessing patients with rheumatic disease and its theoretical etiopathogenic role in these diseases are discussed.
Adult↗