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M Schlesinger

Publications and source records attributed to M Schlesinger.

At least 37 records · Page 2Linked to original sources
PubMed1999

Time domain dielectric spectroscopy study of human cells. II. Normal and malignant white blood cells.

The dielectric properties of human lymphocyte suspensions were studied by time domain dielectric spectroscopy (TDDS). Nine populations of malignant and normal lymphocytes were investigated. Analysis of the dielectric parameters of cell structural parts were performed in the framework of Maxwell-Wagner mixture formula and the double-shell model of cell. The specific capacitance of the cell membranes was estimated by the Hanai-Asami-Koisumi formula. It was shown that the dielectric permittivity, capacitance and conductivity values of cell membranes are higher for normal lymphocytes than for the malignant ones. The difference of the same parameters for normal B- and T-cells is also discussed.

B-Lymphocytes↗
PubMed1999

Detection of minimal residual disease (MRD) after bone marrow transplantation (BMT) by multi-parameter flow cytometry (MPFC).

Multi-parameter flow cytometry (MPFC) was used to detect minimal residual disease (MRD) following bone marrow transplantation (BMT) in 21 patients. Bone marrow (BM)was analyzed pre-transplant and 3-4 months post-BMT while the patients were in clinical and morphological remission. MRD was detected by identifying cells with aberrant antigen expression and/or leukemia-associated phenotype (LAP) using MPFC. Prior to BMT, 8 out of 21 patients exhibited normal antigen expression based on normal BM samples while 13 BM aspirates had abnormal MPFC. Pre-BMT MPFC was abnormal in all 10 patients who were not in complete remission (CR) (>5% blasts in BM) as well as 3 patients acute lymphoblastic leukemia (ALL) who were in CR. In BM from ALL patients, an abnormal uniform B cell population was observed however antigen expression patterns varied greatly between patients. BM from acute myeloblastic leukemia (AML) patients showed an abnormal distribution of CD34+ cells. In addition, a correlation was observed between pre-BMT cytogenetics and MPFC. Only 2 out of 8 (25%) patients with normal MPFC pre-autologous bone marrow transplantation (ABMT) relapsed (AML), while 6 out of 13 (46%) patients with abnormal pre-BMT MPFC relapsed including 2 out of 3 patients who were transplanted in clinical CR. Pre-BMT MPFC may thus be an effective tool for detection of MRD by detection of a pre-transplant MPFC abnormality.

Adolescent↗
PubMed1999

Monocytes confer CD14 antigenicity on activated lymphocytes.

In the present study, exposure of human peripheral blood mononuclear cells (PBMC) to phorbol 12-myristate 13-acetate (PMA) was found to elicit the expression of CD14 on lymphocytes. Less than 3% of the lymphocytes present among freshly isolated PBMC were stained with 63D3 anti-CD14 monoclonal antibody (mAb). Within two days of exposure of PBMC to PMA, up to 30% of the lymphocytes reacted with the 63D3 anti-CD14 mAb, though not with the LeuM3 and My4 anti-CD14 mAbs. The appearance of CD14 on lymphocytes was also elicited by exposure of PBMC to phytohemagglutinin (PHA), concanavalin A (Con A), or agarose-bound phytohemagglutinin but not by exposure to lipopolysaccharide, interferon-alpha, or interleukin-2. Purified lymphocyte preparations did not acquire CD14 following stimulation with PMA. Monocytes lost their reactivity with CD14 mAbs (63D3, LeuM3, and My4) within a few hours after exposure to PMA. The level of soluble CD14 was higher in supernatant fluids of cultures of untreated PBMC than of PMA-stimulated PBMC. The addition of PMA to cultures of T cells and monocytes separated by Millipore filters lead to the expression of CD14 on the lymphocytes. The present study indicates that activation of lymphocytes in the presence of monocytes leads to the appearance of CD14 on lymphocytes, and raises the possibility that the expression of CD14 on lymphocytes may result from the transfer of CD14 molecules from monocytes to lymphocytes.

Cell Communication↗
PubMed1999

Complement factor H gene mutation associated with autosomal recessive atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (HUS) presents with the clinical features of hypertension, microangiopathic hemolytic anemia, and acute renal failure. Both dominant and recessive modes of inheritance have been reported. This study describes the genetic and functional analysis of a large Bedouin kindred with autosomal recessive HUS. The kindred consists of several related nuclear families in which all parent unions of affected children are consanguineous. A previous report demonstrated that a dominant form of HUS maps to chromosome 1q and that complement factor H (CFH), a regulatory component of the complement system, lies within the region and is involved in the dominant disorder. Early-onset and persistent hypocomplementemia in this Bedouin kindred prompted us to evaluate the CFH gene. Linkage analysis was performed, demonstrating linkage between the disorder and the markers near the CFH gene. Mutation analysis of the CFH coding region revealed a single missense mutation. Functional analyses demonstrate that the mutant CFH is properly expressed and synthesized but that it is not transported normally from the cell. This is the first study reporting that a recessive, atypical, early-onset, and relapsing HUS is associated with the CFH protein and that a CFH mutation affects intracellular trafficking and secretion.

Age of Onset↗
PubMed1999

Lymphocyte subset profile of young healthy children residing in a rural area: possible role of recurrent gastrointestinal infections.

BACKGROUND: Lymphocyte subsets in healthy children are currently characterized by age-related standards. Because antigenic stimuli play a role in maturation of the immune system after birth, there is a question of whether cellular immune development differs in infants whose living conditions entail extensive antigenic exposure and infants growing up in a more protected environment. METHODS: Peripheral blood lymphocyte subsets were studied in two populations of children of similar age and nutritional status; children belonging to a rural population residing in proximity with farm animals and children from an economically privileged urban population. In each population, children studied included a group with an acute diarrheal episode and a healthy control group. RESULTS: Among rural population children, 65% had experienced at least one episode of gastroenteritis within the previous 3-month-period, compared with less than 10% of urban population children. In the rural population group 15% had experienced two or more episodes of gastroenteritis. The proportion of helper T cells was similar in rural population and urban population children. Among helper T cells, the proportion of CD29+ "memory" cells of the total CD4+ helper T cells was more than two times higher than those in rural population children. The proportion of CD8 cells was higher in rural population children than in urban population children, and the proportion of natural killer cells, CD56+ and CD57+, was two to three times higher in rural population children. Within each population, peripheral blood lymphocyte subsets did not differ between the healthy control group and those with acute diarrhea. CONCLUSIONS: In young children exposure to environmental pathogens and specifically to gastrointestinal antigenic stimuli is a major factor affecting development of the cellular immune response. Young children who have experienced enhanced infectious exposure have a peripheral blood lymphocyte profile similar to that of adults.

Acute Disease↗
PubMed1999

Somatic mutations and intraclonal variations in the rearranged Vkappa genes of B-non-Hodgkin's lymphoma cell lines.

Three established Burkitt's lymphoma (BL) cell lines (Daudi, Raji and DG-75) and three B-non-Hodgkin's lymphoma (B-NHL) of other types (Pfeiffer, Farage and Toledo) were analyzed with respect to the presence of somatic point mutations in their rearranged immunoglobulin Vkappa genes. Two of the Vkappa sequences of BL and two of those of the B-NHL were heavily mutated (up to 11%), when compared with their closest germline variable region counterparts ("clonal mutations"). Only one of the six cell lines contained an unmutated germline Vkappa sequence. The clonal mutations have features characteristic of the mutation machinery operating in the course of the T-dependent immune response, such as a preference of mutations in purine bases, more transitions than transversions and targeting to CDR and to known "hotspot" motifs. Sequence variations among different Vkappa PCR clones isolated from each of the cell lines ("intraclonal mutations") showed that the Vkappa of Toledo exhibited about 5-fold higher mutation frequency (MF) than the background level of Taq polymerase error (approximately 0.12% mut/bp). Similarly, the MF of Vkappa of two of the BL cell lines was 3-4-fold higher than the Taq polymerase misincorporation rate. In contrast, the mutation frequencies of the Vkappa of DG-75, Farage and Pfeiffer did not significantly exceed the level of Taq polymerase error. Our combined results show that 5 out of the 6 B-cell lines studied originated from B-cells that have already somatically mutated in vivo their rearranged Vkappa genes. Moreover, two of the Burkitt's and one of the B-NHL cell lines exhibit intraclonal variation indicating that the process of somatic hypermutation continued following the neoplastic event, either in vivo or in culture. These results are in accord with the presumed origin of the majority of the BL and some types of the B-NHL, from centrocytes or centroblasts of the germinal centers in which the process of somatic hypermutation is taking place.

Base Sequence↗
PubMed1999

Depressive symptoms and plan switching under managed care.

OBJECTIVE: A central assumption underlying managed care is that plan switching is a viable option for enrollees when they are dissatisfied. The authors used a national employee survey to test the hypothesis that this mechanism is less effective for enrollees with high levels of depressive symptoms than for the remainder of the population. METHOD: The study used data from the Employee Health Care Value Survey, a 1993 survey of 20,283 employees of three major corporations. The authors used the Medical Outcomes Study 36-Item Short-Form Health Survey to identify individuals with the highest decile of depressive and physical symptoms. They examined the relationship between symptoms and dissatisfaction and, for dissatisfied individuals, how symptoms predicted plan switching. Multivariate models were used to control for potential demographic, health, and health coverage confounders. RESULTS: Depressive and physical symptoms were both associated with dissatisfaction with care. Unlike physical symptoms, depressive symptoms were associated with a significantly lower likelihood of actually disenrolling among people who were dissatisfied or who intended to disenroll. This effect was most pronounced for satisfaction with administrative aspects of care (e.g., gatekeeping, utilization review). CONCLUSIONS: People with high levels of depressive symptoms appeared to be less willing or able to act on their dissatisfaction by switching plans. In particular, they were willing to tolerate higher rates of dissatisfaction with the administrative aspects of their health coverage without disenrolling. Plan switching is an essential mechanism underpinning a health care system predicated on competition; it may be less effective for people with depressive disorders.

Attitude to Health↗
PubMed1999

Hypocomplementemia in multiple myeloma.

We report the results of a prospective study of the complement system in a cohort of 22 multiple myeloma patients: 11 women and 11 men, median age 66 years. There were 10 IgG, 8 IgA, 2 IgM and 2 light chain myeloma patients. Seven were in stage 1, 3 in stage 2 and 12 in stage 3. The serum complement component levels of the three pathways were measured in all patients and compared to normal values of 29 healthy controls. We found a depleted common pathway in 21 patients, and deficient alternative and terminal pathways in 6 patients. There was no difference in the complement profile of myeloma patients in the advanced or early stages of the disease. IgG and IgA myeloma patients had a similar complement profile. Nine patients, 7 with advanced disease, developed 17 infectious episodes. Most of these patients had a deficient classical pathway, but normal alternative and terminal pathways. This profile was not different from the complement system observed in patients without infectious complications. Activation of the three pathways of the complement system was evaluated in all 22 patients. The classical and alternative pathways were activated in most patients in early and late stages, but the terminal pathway (C5-C9) was more frequently activated in the later stages (7 of 12 patients) that in the earlier stages (1 of 10). We conclude that the complement system is deficient in multiple myeloma, most probably because of activation of the system, although no correlation could be demonstrated between the complement system and the clinical manifestations of the disease.

Adult↗
PubMed1999

No exit? The effect of health status on dissatisfaction and disenrollment from health plans.

OBJECTIVE: To examine the implications of serious and chronic health problems on the willingness of enrollees to switch health plans if they are dissatisfied with their current arrangements. DATA SOURCE: A large (20,283 respondents) survey of employees of three national corporations committed to the model of managed competition, with substantial enrollment in four types of health plans: fee-for-service, prepaid group practice, independent practice associations, and point-of-service plans. STUDY DESIGN: A set of logistic regression models are estimated to determine the probability of disenrollment, if dissatisfied, controlling for the influence on satisfaction and disenrollment of age, race, education, family income and size, gender, marital status, mental health status, pregnancy, duration of employment and enrollment in the plan, number of alternative plans, and HMO penetration in the local market. Separate coefficients are estimated for enrollees with and without significant physical health problems. Additional models are estimated to test for the influence of selection effects as well as alternative measures of dissatisfaction and health problems. DATA COLLECTION: Data were collected through a mailed survey with a response rate of 63.5 percent; comparisons to a subsample administered by telephone showed few differences. PRINCIPAL FINDINGS: In group/staff model HMOs and point-of-service plans, only 12-17 percent of the chronically ill enrollees who were so dissatisfied when surveyed that they intended to disenroll actually left their plan in the next open enrollment period. This compared to 25-29 percent of the healthy enrollees in these same plans, who reported this level of dissatisfaction and 58-63 percent of the enrollees under fee-for-service insurance. CONCLUSIONS: Switching plans appears to be significantly limited for enrollees with serious health problems, the very enrollees who will be best informed about the ability of their health plan to provide adequate medical care. These effects are most pronounced in plans that have exclusive contracts with providers. We conclude that disenrollment provides only weak safeguards on quality for the sickest enrollees and that reported levels of dissatisfaction and disenrollment represent inaccurate signals of plan performance.

Adult↗
PubMed1998

The down-modulation of CD4 induced by the GM1 ganglioside is regulated by phosphatases and kinases: evidence from enzyme inhibitors and anti-CD45 antibodies.

The involvement of protein kinases and phosphatases in the down-modulation of expression of CD4 molecules on peripheral blood lymphocytes (PBL) by gangliosides was studied. Exposure of PBL either to genistein or to H7 practically abolished the down-modulation of CD4 induced by GM1 and diminished their susceptibility to CD4+ down-modulation by exposure to GD1a. Staurosporine had no effect on the down-modulation of CD4 by either GM1 or GD1a. Orthovanadate treatment drastically inhibited the down-regulation of CD4 induced by GM1 but had no effect on down-modulation of CD4 induced by GD1a. Exposure to monoclonal antibodies (mAbs) against CD45 and CD45RA but not against CD45RO abrogated the down-modulation of CD4 by GM1. The down-modulation of CD4 elicited by GD1a, GD1b, or GT1b was not inhibited by anti-CD45RA and anti-CD45RO mAbs. MAbs against CD3, CD2, or HLA-DR had no effect on the GM1-induced down-modulation of CD4. In view of the differences obtained between GM1 and GD1a it was of interest to check whether these gangliosides competed for cellular binding sites. When PBL were first treated with anti-CD45RA and GM1 or with orthovanadate and GM1, which had a negligible effect on CD4 expression, and subsequently treated with GD1a the expression of CD4 was down-modulated. This demonstrated that GD1a binds to sites on the cell membrane to which GM1 does not bind. The present study indicates that the capacity of GM1 to down-modulate CD4 depended on the CD45 and particularly CD45RA molecules, while other gangliosides may utilize different cell surface structures to down-modulate the expression of CD4.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

[Sudden death from asthma in childhood, is it preventable?].

Sudden death from asthma is rare but occurs in the young age group. We recently faced this rare situation when 3 asthmatic children were dead on arrival at the local emergency room. All 3 had been treated with beta-2 agonist inhalation on a regular basis, without anti-inflammatory treatment, 2 of the children died while inhaling the beta-2 agonist. It is important that there be clear guidelines and full education about the management of asthma, during and between exacerbations, to prevent such deaths.

Administration, Inhalation↗
PubMed1998

Hypocomplementemic autosomal recessive hemolytic uremic syndrome with decreased factor H.

We describe the clinical course, complement components, and pathological findings of 10 infants with autosomal recessive hemolytic uremic syndrome (HUS). All patients were members of one extended highly inbred Bedouin kindred. The median age of presentation was 2 weeks (range 1-20 weeks). Eight patients died, 2 patients are alive, on dialysis. Renal biopsies revealed thrombotic microangiopathy with a predominant early arteriolar involvement and subsequent development of ischemic glomerular changes. Immunofluorescence was positive for C3 in glomeruli. All patients had low complement components levels during and between relapses, and in some this was evident soon after birth and prior to the onset of symptoms. This deficiency could not be normalized by repeated plasma transfusions. Biosynthetic labelling of patients' fibroblasts demonstrated normal rates of C3 protein synthesis. Serum factor H levels were greatly decreased or absent in 4 patients tested and moderately decreased in 15 of 23 healthy unaffected siblings and patients. This defect may cause complement activation and consumption, possibly at the endothelial cell level.

Arabs↗
PubMed1998

Tumorigenicity and immunogenicity in a murine model of B-cell leukemia/lymphoma (BCL1).

Multiple injections of intact irradiated BCL1 cells, a murine B-cell leukemia/lymphoma can trigger a dose-dependent anti-tumor immune response in naive syngeneic mice. The ability to induce anti-BCL1 immunity and the effect of various cell-modifications on BCL1 tumorigenicity and immunogenicity was evaluated. Newcastle disease virus (NDV) infection or transfer of cytokine genes by both retroviral and Adeno 5 vectors affect neither tumorigenicity nor immunogenicity of BCL1 cells given as a non-immunogenic cell-dose. New ways will have to be developed to elicit a reliable and reproducible anti-tumor effect in spontaneously arising and non-immunogenic hematological malignancies.

Adenoviridae↗
PubMed1998

Activated human T-cells bestow T-cell antigens to non-T-cells by intercellular antigen transfer.

The mechanism of the appearance of T-cell antigens on B-cells, following in vitro activation of peripheral blood lymphocytes, was analyzed using the following model: Purified T-cell suspensions were activated by exposure to phytohemagglutinin (PHA) for 3 days, and then incubated for one hour in the presence of cells of either Raji or K562 cells. The expression of T-cell antigens on the cell lines was determined using immunofluorescent F(ab)2 fragments of monoclonal antibodies (mAbs). Following exposure of the CD19+ Raji cells to activated T lymphocytes, 87.6% of the CD19+ cells coexpressed CD2. A large proportion of the CD19+ cells also expressed CD4, CD5, and CD8 antigens. Similar results were obtained with Raji cells that were prelabeled with calcein AM. In Raji cells, which were rendered CD5+ following incubation with activated T cells, only a negligible level of CD5 mRNA was detected with a sensitive RT-PCR technique, probably attributable to contamination with T cells. K562 cells incubated with activated T cells acquired CD2 but not the CD4 and CD8 antigens. Exposure of either Raji or K562 cells to mAb against CD58 inhibited the transfer of CD2. The present study indicates that following their activation, T-cells gain the capacity to transfer T-cell antigens to non-T cells and that CD2 and CD58 molecules are involved in this process.

Antibodies, Monoclonal↗
PubMed1998

Risk, motives, and styles of utilization review: a cross-condition comparison.

In the United States various forms of managed care have been introduced to control the use of expensive medical services. One of the most prominent involves utilization review of hospital admissions. While reviewing the appropriateness of inpatient treatment is appealing in principle, its application is made difficult by clinical uncertainty. Managed care plans develop and implement review criteria often without the guidance of clear clinical norms of treatment. Under these conditions, we suggest that utilization review organizations (UROs) can be expected to develop "styles" of review that respond to clinical uncertainty, influenced by their experience, professional orientation, and financial incentives. Two review styles are explored in this paper: standardization, where the URO reduces the variance in clinical practices by eliminating those practices that deviate from professional norms and stringency, whereby the URO shifts the distribution of clinical practice as it tries to change the professional norms of practice. Data from a 1992-1993 national survey of utilization review organizations are used to test whether UROs have review styles that systematically respond to organizational attributes, economic pressures, and clinical uncertainty associated with three medical conditions: cardiac catheterization, low back pain, and adolescent depression. UROs were found to adopt more stringent review strategies for conditions with weaker norms of appropriate treatment. Financial incentives and organizational experience are positively related to greater stringency. Standardization responds to professional orientation and organizational experience. Variation in the review styles of UROs has implications for the resulting distribution of clinical practices as well as the equity of access to medical care.

Adolescent↗
PubMed1998

The effect of dental alloys on mouse lymphocyte subpopulations.

The aim of the present study was to determine the effect of nickel-containing alloys on lymphocyte subsets in an experimental setting. Plates of alloys containing nickel (Ceramalloy, Talladium, Cerillium, Rexillium) or gold (Orion) were implanted subcutaneously into mice. The levels of CD4+ and CD8+ T-lymphocyte subpopulations and of Smig+ B lymphocytes were determined at various intervals following implantation, using monoclonal antibodies and flow cytometry. No changes were detected in the proportion of the lymphocyte subsets tested. One month after implantation, the mean fluorescence intensity of CD4, CD8 or Smig, in the peripheral blood lymphocytes (PBL) of the nickel alloy-implanted animals, was significantly higher than that prior to this procedure. Only a mild increase in CD4 and CD8 was noted after implantation of the gold alloy. The observed effects are most likely attributable to the surgical trauma, and do not indicate that nickel-containing dental alloys influence T cell subsets in this murine model.

Animals↗
PubMed1998

Complement activation in patients with acute myocardial infarction treated with streptokinase.

Twenty patients with acute myocardial infarction (AMI) treated with streptokinase (SK) and 11 patients with AMI not treated with SK were clinically and echocardiographically evaluated in the intensive coronary care unit (ICCU). Blood samples, in which complement components C4d, C5b-9, and Bb were measured, were taken immediately after arrival of the patient at the ICCU, 1 hour after SK infusion, and 24 hours later from the SK group, and similar time-matched samples were taken from the control group. The classic, alternative, and common complement pathways were found to be activated in AMI, but this activation was statistically significant only in the SK-treated group. Activation was not related to the site of the AMI nor to the extent of its damage, as assessed by Killip class and ejection fraction. However, in the SK-treated group and even more so in non-SK group, the C5b-9 increment was significantly higher in patients diagnosed with reperfusion, based on ST-segment recovery of > or =50% reduction from the peak ST-segment level. There was little change in complement levels when reperfusion did not occur. Detection of reperfusion without coronary angiography would have important practical clinical implications, and complement activation may predict its occurrence. However, more studies of this phenomenon are needed.

Aged↗