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M Aronson

Publications and source records attributed to M Aronson.

At least 55 records · Page 3Linked to original sources

The state of leucocyte adhesiveness/aggregation (LAA) in the peripheral blood of burned mice: an early and sensitive inflammatory indicator and a marker of pulmonary leukostasis.

The inflammatory response during thermal injury increases the adhesiveness of white blood cells. A direct slide test was used to compare the state of leucocyte adhesiveness/aggregation (LAA) in the peripheral blood of mice subjected to a thermal injury with the findings in control animals. The state of LAA in the peripheral blood increased from baseline values of 1.1 +/- 1.1 per cent to 6.5 +/- 1.3 per cent within 1 h and to 11.0 +/- 1.2 per cent and 14.8 +/- 4 per cent after 3 and 6 h respectively following thermal injury. The respective leucocyte counts were 3075 +/- 277/mm3 (baseline), 3871 +/- 359, 3840 +/- 687 and 6395 +/- 1152 cells/mm3. The LAA values had subsided by 5 days following burning and correlated with the degree of pulmonary leukostasis. Our study suggests that the LAA is an early and sensitive marker of inflammation and that it can be used as a marker for the presence of pulmonary leukostasis during thermal injury.

Animals↗

Hypothesis: the morphology of the endothelial cell facilitates the disintegration of blood cell aggregates.

This is an attempt to find a rationale for the shape of the endothelial cell. While this type of cell is characterized by flatness, its nucleus protrudes prominently into the lumen. Functionally, flatness of the cell is conductive to smooth flowing of the blood; the position of the nucleus therefore seems problematic, as it can only disturb the blood flow. My hypothesis centers on the fact that white cells appear in the blood as aggregates, which obviously implies the need of their disaggregation, to avoid plugging of the small blood vessels.

Animals↗

Leukocyte adhesiveness/aggregation and neuroleptic drug treatment.

Leukocyte adhesiveness/aggregation as measured by the leukergy test was studied in peripheral citrated blood of two groups of schizophrenic patients treated with neuroleptic drugs. In the first group (N = 25) leukergy test was performed before and after commencement of neuroleptic treatment to acutely psychotic hospitalized patients. The second group studied (N = 25) were stabilized outpatients receiving long term neuroleptic medications for at least 3 months. There was a significant rise in leukergy rates between the drug free period and the subsequent measurements performed after 1 and 7 days of neuroleptic treatment in the first group (p less than 0.001). Similar high leukergy rates were noted in the second group of remitted patients. High leukergy rates were related to neuroleptic therapy and not to the psychotic state of the patients.

Adult↗

Detection of aggregated leukocytes in the circulating pool during stress-demargination is not necessarily a result of decreased leukocyte adhesiveness.

Leukocyte endothelial interactions are essential for a normal immune response. It is known that this response is influenced by stress and that the latter induces demargination. We examined the question of whether stress demargination results from a decreased state of leukocyte adhesiveness. Included were various volunteers and patients under different degrees of stress. 66 young athletes before beginning their daily exercises, 67 middle-aged healthy volunteers, 25 patients before ergometry for evaluation of chest pain, 75 patients who were referred to the emergency room with chest pain without ischemia/infarction, 78 patients with ischemia/infarction, 65 patients with minor trauma, 25 with a fracture and 12 with polytrauma. The leukocyte adhesiveness/aggregation (LAA) values were measured with a direct slide test. The respective LAA values were 7.4 +/- 4.7, 6.3 +/- 4.4, 5.8 +/- 3.6, 5.2 +/- 3.5, 10.8 +/- 8.5, 9.1 +/- 5.8, 12.2 +/- 6.6 and 19 +/- 12.6% of aggregated leukocytes. We conclude that an increase in aggregated white blood cells can be detected in the circulating pool during major stress. It is therefore suggested that stress demargination is not necessarily a result of diminished leukocyte adhesiveness.

Adolescent↗

Possible role for a plasma factor in the induction and/or maintenance of the state of leukocyte adhesiveness/aggregation in the peripheral blood. A study of mothers and their newborns.

The adhesive property of white blood cells is essential for a normal immune response. We examined the state of leukocyte adhesiveness/aggregation (LAA) in the peripheral blood of 31 mothers and their newborns by means of a direct slide test and found it to differ significantly, the respective per cents of aggregated leukocytes found in the peripheral blood being 15 +/- 6.4 and 5 +/- 3.3 (mean +/- SD). However, the particle concentration of white blood cells in the peripheral blood did not differ significantly (14.2 +/- 4.4 and 13.6 +/- x 10(9) l-1). By incubating a mother's plasma with her newborn's whole blood we could induce a significant (p less than 0.0001) increment in the state of LAA. We conclude that deficiency of a plasma factor that does not cross the placenta is responsible for the low LAA in the newborn's peripheral blood.

Cell Adhesion↗

Alternate splicing of mRNAs encoding human mast cell growth factor and localization of the gene to chromosome 12q22-q24.

Human mast cell growth factor (MGF) complementary DNAs (cDNAs) were cloned from HeLa cells using the polymerase chain reaction with oligonucleotides corresponding to murine and human MGF sequences. Sequencing of the cloned human MGF polymerase chain reaction products revealed two types of cDNA: a full length form corresponding in size to the murine cDNA, and an alternately spliced clone with a deletion of the sixth exon of the gene. Since membrane-bound MGF is predicted to be proteolytically cleaved within the sequences encoded by exon 6 to generate a soluble protein, this alternately spliced cDNA would likely encode a noncleavable, membrane-bound form of MGF. No difference in biological activity on human bone marrow cells was observed with recombinant, soluble forms of both types of human MGF protein. Our previous localization of the murine MGF gene to the Sl locus on chromosome 10 suggested (via conserved linkage groups) that the human MGF gene would be located on human chromosome 12. Therefore, rodent-human somatic cell hybrids with or without an entire human chromosome 12 and hybrids retaining partial 12 were tested by Southern blot analysis and used to show the presence of the human Mgf locus at chromosome region 12q. Chromosomal in situ hybridization localized the gene to 12q22-q24 in the region predicted by the comparative mapping of the murine Mgf/Sl locus.

Amino Acid Sequence↗

Hypothesis: involution of the thymus with aging--programmed and beneficial.

This is an attempt to find a teleological rationale for the involution of the thymus with aging. The thymus is the first organ in the body to age, which seems incongruent considering its cardinal role in the immune system. An analogical incongruency can be seen in the fact that acute stress is generally accompanied by a reversible involution of the thymus. We hypothesized earlier, that this reversible involution might protect the organism from the danger of autoimmune diseases. It stands to reason that, in nature, conditions leading to stress frequently entail massive tissue destruction. This may cause the appearance of "altered self" components, leading to the formation of autoantibodies. Hence, the temporary shut-off of thymic activity would be beneficial. A similar argument holds in the case of aging and will be elaborated as follows: 1) Formation of antibodies per se entails the danger of autoimmune mechanisms, hence the process is controlled at various levels; 2) The aging process is characterized by the increasing appearance of non-self components as a result of DNA errors and post-translational changes due to free radicals and other high energy oxygen derivatives; 3) Early involution serves, in our opinion, to reduce the risk of autoimmune diseases which increases with aging, and should therefore be regarded as an adaptation of the organism to aging; 4) If this notion proves to be correct the desirability of restoring full thymic activity in old people becomes questionable.

Aging↗

Heterotypic leukocyte aggregation in the peripheral blood of patients with leukemia, inflammation and stress.

This study deals with the question of whether the aggregates of leukocytes in the peripheral blood are homo- or heterotypic. One hundred-fifty individuals with leukemia, inflammation, and physical and mental stress, were examined. It was found that the various cell populations of the peripheral blood are represented in the aggregates and that aggregates are generally heterotypic. Normal and malignant leukocytes were noted in aggregates of patients with leukemia, suggesting that adhesive mechanisms are similar for both normal and malignant leukocytes. This was also supported in two animal models, one with leukocytosis of normal cells and the other with leukocytosis of leukemic cells, in which the state of leukocyte adhesiveness/aggregation in the peripheral blood correlated with tissue leukostasis. The possibility exists that "non specific stickers", present in the peripheral blood, promote interactions between the white blood cells, normal and malignant, and between these cells and the endothelium.

Adolescent↗

Lipids, vascular disease, and dementia with advancing age. Epidemiologic considerations.

Elevated plasma lipid and lipoprotein levels are associated with an increased risk of cardiovascular disease in middle-aged men and women. It is still not clear, however, whether lipid and lipoprotein abnormalities continue to be risk factors for cardiovascular disease in the elderly population. It is not even clear what normal lipid values are in the elderly, and whether diet or drug therapy should be advised on the basis of lipid values established in middle-aged populations. Ischemic heart disease does remain the leading cause of death in the elderly, and there is now preliminary evidence from epidemiologic studies that relative elevations of levels of lipid and lipoprotein fractions in an elderly population might be associated with an independent and increased risk of coronary heart disease, stroke, and possibly dementia. Intervention studies are about to begin that will assess various lipid-and lipoprotein-modifying therapies and their ability to reduce vascular disease risk in the elderly.

Aged↗

Prevalence, incidence and prognosis of recognized and unrecognized myocardial infarction in persons aged 75 years or older: The Bronx Aging Study.

The prevalence, incidence and prognosis of recognized and unrecognized Q-wave myocardial infarction (MI) was assessed in an 8-year prospective study of 390 community-based subjects (age 75 to 85 years at entry, mean 79 years). Subjects were studied at baseline and with annual follow-up electrocardiographic (ECG) exams. At baseline, 7.9% had a history of MI without ECG evidence, 6.4% had ECG evidence of Q-wave MI without clinical history, 4.1% had both clinical history and ECG evidence and 81.5% had neither history nor ECG evidence (control subjects). After an average follow-up period of 76.2 months, the total mortality rate was 5.9/100 person-years for subjects with some evidence of MI at baseline versus 3.9 in the control group (p = 0.059). The incidence of cardiovascular disease in subjects with evidence of MI was 8.8/100 person-years versus 4.7 among control subjects (p = 0.002). During the follow-up period, 115 new Q-wave MIs occurred (50 unrecognized, rate 2.4/100; 65 recognized, rate 3.2/100). There was no difference in mortality and morbidity outcome between subjects with recognized and unrecognized MIs. Those with only a history of MI at baseline had a threefold greater risk of a new MI (recognized and unrecognized) than the control group (p = 0.003). Unrecognized Q-wave MI is a common occurrence in the "old old" with subsequent morbidity and mortality prognosis comparable to that of recognized MI. History of MI alone in this age group is also associated with an increased risk of MI, suggesting the need for better diagnostic markers of myocardial ischemia in the old.

Aged↗

State of leukocyte adhesiveness/aggregation in the peripheral blood of pemphigus and psoriatic patients.

The purpose of this study was to assess the role of leukocyte adherence in the pathogenesis of the psoriatic lesion. Use was made of the fact that psoriasis and pemphigus differ considerably as to the presence of leukocytes in the respective lesions: abundance in psoriasis, and absence in pemphigus. The state of leukocyte adhesiveness/aggregation (LAA) was determined in the peripheral blood of 56 patients with psoriasis and 31 patients with pemphigus. Both classes of patients were subdivided into two categories according to the severity of the disease. It was found that in both diseases elevated values of LAA were obtained in the severe cases, whereas the mild cases did not differ significantly from normal controls. Thus, in psoriasis mean LAA values of 9.5% +/- 8% were recorded in the severe patients and 5.5% +/- 4.2% in the mild cases (p = 0.01), while in pemphigus the values were 15% +/- 9.6% and 6.6% +/- 3.7% respectively (p = 0.03). It is concluded that LAA per se does not play a primary role in causing the psoriatic lesion.

Cell Adhesion↗

The state of leukocyte adhesiveness/aggregation in the peripheral blood of patients with respiratory tract infections.

The state of leukocyte adhesiveness/aggregation (LAA) in the peripheral blood has been employed as a marker of inflammation. In the present study we examined patients with varying intensities of inflammation caused by respiratory tract infections to further investigate the reliability of the state of LAA for the detection and assessment of the severity of disease activity. The study includes 140 controls, 46 patients with upper respiratory tract infection, 30 with bronchitis, 27 with suspicion of pulmonary infiltrate, and 39 with small and 18 with large pulmonary infiltrate. Assessment was based on assuming an increasing severity of inflammation from the 1st to the 6th diagnostic category and by making use of discriminant analysis. It was found that the state of LAA proved to be the best variable to classify the patients into their diagnostic category (F to enter 27), followed by erythrocyte sedimentation rate at the 1st h (F to enter 20.8) and total white blood cell count (F to enter 8.3). These studies were followed by animal experimentation. A highly significant correlation (p = 0.005) was found between the state of LAA in the peripheral blood and the degree of pulmonary leukostasis in a model of endotoxemia in rabbits. These results suggest that the state of LAA is not an epiphenomenon and represents the tendency of the white blood cells to stick to the endothelium which facilitates their migration into the tissues.

Adolescent↗

Development of dementing illnesses in an 80-year-old volunteer cohort.

We have prospectively followed over a 5-year period 434 volunteers who were at intake ambulatory, functional, presumably nondemented, and between 75 and 85 years of age. Fifty-six (an incidence of 3.53 per 100 person-years at risk) developed a progressive dementia: 32 met diagnostic criteria for Alzheimer's disease (AD) (an incidence of 2.0 per 100 person-years at risk), 15 had vascular or mixed dementia, and 9 had other disorders or remain undiagnosed. New cases of dementia were as common as myocardial infarction and twice as common as stroke. Risk factors for both dementia and AD were age (over 80) and gender (female); other reported risk factors such as family history, prior head injury, thyroid disease, maternal age, and smoking were not risk factors for AD in this elderly cohort. Prior stroke was the major risk factor for vascular or mixed dementia; diabetes and left ventricular hypertrophy but not a history of hypertension per se were also risk factors for vascular dementia. The major predictor of the development of AD was the mental status score on entry. The 58.5% of the cohort who made zero to two errors on a 33-item mental status test had a less than 0.6% per year chance of developing AD, whereas the 16% of the cohort with five to eight errors on this test developed AD at a rate of over 12% per year. Thus, it is possible to identify a large cohort of 80-year-olds who are at low risk for AD and a smaller cohort at very high risk.

Aged↗

Influence of a thymic hormone on cultured epithelial cells of the thymus.

Addition of cortisone to primary cultures of mouse thymic stromal cells resulted in increased growth of medullary epithelial cells while cortical epithelial subpopulations were inhibited or destroyed. These adverse effects on cortical cells were ameliorated by the thymic hormone THF. Because thymocytes are also sensitive to both cortisone and THF we sought to eliminate them from the cultures by deoxyguanosine treatment. This treatment differentiated even more strongly between growth of cortical epithelial cells which were inhibited and medullary epithelium that was very strongly stimulated. These effects are discussed in relation to involution of the thymus with aging.

Animals↗

Age-related changes in excision repair of cultured epithelial cells from mouse thymus.

These experiments were performed to test the possibility of a link between involution of the thymus and decreased ability to repair damaged DNA. In a previous investigation this was not found to be the case with thymic lymphocytes, and in the present work the question was addressed to epithelial cells of the thymic stroma isolated by growth in tissue culture. DNA repair in the epithelial cells was measured as unscheduled DNA synthesis (UDS) and detected autoradiographically after UV irradiation of the cultures. In cultures derived from older mice, DNA repair was evident in the majority of the cells and continued after extended culture. When cultures were derived from preinvolution mice DNA repair activity, which was detected after short periods of culture, was lost from most of the cells after several days of growth. These unexpected findings raise the possibility that the ability of the stromal cells to repair DNA damage has enabled them to survive a selective pressure that is involved in thymic involution.

Aging↗

Comparison of rate of annual change of mental status score in four independent studies of patients with Alzheimer's disease.

Longitudinal studies of subjects with autopsy-proven Alzheimer's disease in one skilled nursing home and of clinically diagnosed cases (NINCDS/ADRDA criteria) in three community cohorts are compared with regard to the annual rate of change in the error score of the Blessed information-memory-concentration test (IMC) in which the maximum number of errors possible is 33. The four cohorts differed significantly from each other in regard to age, education, sex, and the degree of dementia as measured by the initial IMC score. Subjects spanned the age range of 52 to 96 years and had 2 to 20 years of education. The rate of change in error score per year was similar whether the initial error score was 0 to 7, 8 to 15, or 16 to 23; however, the rate was reduced when the initial error score was 24 or above, due to a ceiling effect of the test. Among subjects with initial IMC scores less than 24, the annual rate of change varied considerably. However, the mean annual rate of change, 4.4 errors (SD +/- 3.6, SEM +/- 0.3) per year, was independent of residence in a nursing home, location of the study site, and of the patient's sex or education. Of particular importance was the finding that the rate of change in mental test score was independent of age. It can be concluded that the rate of cognitive deterioration in patients with Alzheimer's disease is quite variable among individuals and is independent of the patient's age and whether the patient resides in the community or in a nursing home.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗