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Biomedical subjects

M Schlesinger

Publications and source records attributed to M Schlesinger.

At least 19 recordsLinked to original sources
PubMed2002

Hyposialated 185 kDa CD45RA+ molecules attain a high concentration in B lymphoma cells and in activated human B cells.

Alternate splicing of exons of the CD45 molecule generates multiple isoforms differing in their molecular weights (MWs). In B-lymphocytes the CD45RA isoform was previously shown to be expressed on glycoproteins with MWs of 220 and 205 kDa, while the CD45RO isoform was expressed on glycoproteins with MW of 180 kDa. The present study demonstrated that B cell lymphomas and activated B-cells contain CD45 molecules with a MW of 185 kDa that express the CD45RA and CD45RC specificities but neither the CD45RB nor the CD45RO specificities. 185 kDa CD45RA+ molecules were detected in B cell lymphoma B lines, in Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines, and in tonsillar B cells, but not in normal, unstimulated peripheral blood B cells. These molecules were not detected in neoplastic and normal T cells. CD45RA+ 185 kDa molecules were present in B cells from three non-Hodgkin's patients in leukemic phase were not detected in B lymphocytes of seven of nine CLL patients tested. Trypsin treatment eliminated only 220 kDa CD45RA+ molecules but not 185 kDa CD45RA+ molecules, indicating that the 185 kDa CD45RA+ molecules are not expressed on the cell surface. Pulse-chase experiments, and studies on the effects of tunicamycin, neuraminidase and O-glycosidase, indicated that the 185 kDa molecules are partially glycosylated CD45RABC molecules that constitute precursors of the 220 kDa molecules. The high concentration of 185 kDa CD45RA+ molecules in B lymphoma cells and in activated B cells seems to reflect a high turnover of CD45RA+ molecules characteristic for these cells.

Antigens, Neoplasm↗
PubMed2001

High prevalence of complement C7 deficiency among healthy blood donors of Moroccan Jewish ancestry.

The incidence of the specific component deficiencies in various ethnic groups is not known, although there appears to be an ethnic predilection for C6 and C8alpha-gamma deficiencies in blacks, whereas C7 and C8beta deficiencies are predominantly noted in Caucasians. Infectious diseases, particularly recurrent meningococcal infections, are observed more commonly with late component deficiencies. In the current study, we have simplified the PCR technique by using site-directed mutagenesis and designer primers in a cohort of Israeli Moroccan Jewish blood donors to ascertain allele frequency in this ethnic group, which, based on earlier studies, was considered to be at risk for C7 deficiency. The total mutant allele frequency in this ethnic cohort was 1.1% of a total of 365 healthy Israeli Moroccan Jews, including one homozygote. The identification of mutant alleles was efficient and inexpensive, and hence a large cohort was studied. The finding of complement deficiency identifies individuals at risk for Neisserial infections, which are known to be potentially life-threatening. Conversely, when a patient of Moroccan ancestry is diagnosed with a Neisserial infection, it is important to determine the complement status.

Blood Coagulation Disorders↗
PubMed2001

Suppressors of cancer cell proliferation from fig (Ficus carica) resin: isolation and structure elucidation.

A mixture of 6-O-acyl-beta-D-glucosyl-beta-sitosterols, the acyl moeity being primarily palmitoyl and linoleyl with minor amounts of stearyl and oleyl, has been isolated as a potent cytotoxic agent from fig (Ficuscarica) latex and soybeans. Identity was established by spectroscopic methods (NMR, MS) and confirmed by chemical synthesis. Both the natural and the synthetic compounds showed in vitro inhibitory effects on proliferation of various cancer cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Depressive symptoms, satisfaction with health care, and 2-year work outcomes in an employed population.

OBJECTIVE: The relationship of depressive symptoms, satisfaction with health care, and 2-year work outcomes was examined in a national cohort of employees. METHOD: A total of 6,239 employees of three corporations completed surveys on health and satisfaction with health care in 1993 and 1995. This study used bivariate and multivariate analyses to examine the relationships of depressive symptoms (a score below 43 on the Medical Outcomes Study Short-Form Health Survey mental component summary), satisfaction with a variety of dimensions of health care in 1993, and work outcomes (sick days and decreased effectiveness in the workplace) in 1995. RESULTS: The odds of missed work due to health problems in 1995 were twice as high for employees with depressive symptoms in both 1993 and 1995 as for those without depressive symptoms in either year. The odds of decreased effectiveness at work in 1995 was seven times as high. Among individuals with depressive symptoms in 1993, a report of one or more problems with clinical care in 1993 predicted a 34% increase in the odds of persistent depressive symptoms and a 66% increased odds of decreased effectiveness at work in 1995. There was a weaker association between problems with plan administration and outcomes. CONCLUSIONS: Depressive disorders in the workplace persist over time and have a major effect on work performance, most notably on "presenteeism," or reduced effectiveness in the workplace. The study's findings suggest a potentially important link between consumers' perceptions of clinical care and work outcomes in this population.

Adult↗
PubMed2001

The social roles of Medicare: assessing Medicare's collateral benefits.

The Medicare program incorporates a number of functions that go beyond providing health insurance to its beneficiaries. These activities, which we refer to as "collateral" functions, may have important health consequences but are also an increasing source of controversy. In this essay we develop a conceptual framework for categorizing these involvements, introduce some additional options that might complement Medicare's current collateral functions, assess the reaction of policy elites and Medicare's current beneficiaries to these alternatives, and evaluate the role that collateral activities play for Medicare's core mission. A case can be made for expanding some collateral involvements, but only if the Health Care Financing Administration has the strategic direction and administrative capacity to effectively implement these activities.

Aged↗
PubMed2001

Regulation of the expression of CD45 isoforms in the Farage human B cell lymphoma line and its 10.6.1 subline.

Different B-cell neoplasias vary in the expression of CD45 isoforms. In the present study two sublines of a human B cell lymphoma- the original Farage line (Farage OL) and the Farage 10.6.1 subline were used to analyze the regulation of the expression of CD45 cell surface determinants. Cells of the Farage OL line constitutively expressed both CD45RO and CD45RA determinants on their cell surface. In contrast, the majority of the cells of the Farage 10.6.1 subline expressed CD45RA, and only few cells were CD45RO+. The low molecular spliced CD45 mRNA, characteristic for CD45RO was found in Farage OL cells, but was almost undetectable in Farage 10.6.1 cells. Following exposure to interleukin-4 (IL-4) a large proportion of the Farage 10.6.1 cells expressed CD45RO while in Farage OL cells the proportion of CD45RO+ was slightly reduced. The low molecular, spliced mRNA characteristic for CD45RO, was increased in Farage 10.6.1 cells following IL4 stimulation, but was slightly reduced in Farage OL cells. The molecular weight of CD45RA molecules produced by Farage cells varied from 185 kDa to 220 kDa while that of CD45RO molecules was 175 kDa. Preliminary attempts were made to determine a possible correlation between the expression of CD45RO and apoptosis in Farage cells. In both the Farage OL and Farage 10.6.1 cells the proportion of Bcl-2+ cells was lower among CD45RO+ cells than among CD45RO- cells. The present study indicates that IL4 has different effects on the alternative splicing of CD45 mRNA in two closely related B cell lymphoma lines. Thus, factors produced by the B lymphoma cells themselves may endow the cells with different patterns of responsiveness to a single stimulatory agent.

Blotting, Western↗
PubMed2001

Early immunological defects in comatose patients after acute brain injury.

OBJECT: The aim of this prospective study was to evaluate the phagocytic, humoral, and cellular arms of the immune system in comatose patients shortly after severe brain injury and to compare the findings with those reported earlier in patients in a persistent vegetative state. The study was conducted in intensive care units and immunology laboratories of university-affiliated hospitals in central Israel. METHODS: The study group consisted of 14 men aged 16 to 65 years who were comatose as a result of acute brain injury due to mechanical trauma. All were studied within 72 hours of injury. Brain damage was severe in all cases (Glasgow Coma Scale score < 8). Healthy age- and sex-matched volunteers served as simultaneous controls. Infections arose in nine (75%) of the 12 patients in whom data were available; the cumulative mortality rate was 38% (five of 13 patients in whom outcome data were available). Every patient exhibited one or more defects in at least one arm of the immune system. Significant deficiencies were noted in neutrophil superoxide release, immunoglobulin (Ig)G, IgG1, IgM, C1q, C2, properdin, alternate C pathway, T cells, T helper cells, T suppressor cells, and natural killer cells. In an earlier series of patients examined by the authors months after the primary insult, these impairments were absent in most of the patients in the vegetative state. CONCLUSIONS: Significant deficiencies of the immune system, particularly the cellular arm, are precipitated by severe brain injury within 72 hours of the event. These impairments probably play a role in the high rate of complicating infections and multiple organ failure. Together with earlier findings, the results of this study indicate that if brain-injured patients survive these hazards, their immune system will eventually recover.

Adolescent↗
PubMed2001

Serum and mucosal immunologic responses in children following the administration of a new inactivated intranasal anti-influenza vaccine.

Children are at considerable risk for influenza infection and may constitute the main vector for transmitting the virus to adults in the community. At present, the use of available vaccines in children is limited mainly because of a fear of side effects from the injection. Intranasal immunization was assessed as a painless, side effect-free method of facilitating the enrollment of children in vaccination programs. One intranasal dose of a trivalent inactive whole virus vaccine containing 20 microg of the three recommended seasonal viral strains was administered to 28 children recruited over two separate winter periods (1997/1998 and 1998/1999). No adverse effects were recorded. Serum IgG responses were determined by the hemagglutination inhibition (HI) method and nasal IgA responses by enzyme-linked immunosorbent assay (ELISA). In both study period seasons, 77.7%-94.4% of children were found to be immune. There was a 3.7 x and 4.7 x increase in geometric mean titer (GMT) for A/H3N2 strains, 1.9 x and 3.9 x for A/H1N1 strains, and a 3.2 x and 1.7 x for B strains in 1997/1998 and 1998/1999, respectively. The increase in GMT, as well as fourfold increases in titer level, was higher when calculated among the nonimmune children prior to vaccination. Of these, 50%-87.5% became immune following immunization. Local antibody response to the three viral strains was detected in 50%-55% of the immunized children. Also, 83.3%, 73.3%, and 61.1% of the vaccinees exhibited a mucosal and/or serum antibody response to the A/Beijing, A/Sydney, and B/Harbin strains, respectively. This mucosal response may forestall influenza development in its early stages, thereby contributing significantly to the reduction of influenza spread in the community.

Administration, Intranasal↗
PubMed2000

3-m-bromoacetylamino benzoic acid ethyl ester: a new cancericidal agent that activates the apoptotic pathway through caspase-9.

The mechanism underlying the cancericidal activity of 3-m-bromoacetylamino benzoic acid ethyl ester (3-BAABE) was investigated. 3-BAABE exerted a strong cancericidal effect on human leukemia and lymphoma cells (IC(50) < 0.2 microgram/mL) and on cell lines of prostate, colon, ductal, and kidney cancer (IC(50) 0.8 to 0.88 microgram/mL). Multiple drug resistance (MDR) had no effect on the susceptibility of human lymphoma cells to 3-BAABE, since Daudi/MDR(20) and wild-type Daudi cells had a similar susceptibility to the cytotoxic effect of 3-BAABE. The cancericidal effect of 3-BAABE, which was not associated with changes in the cell cycle, was mediated by apoptosis. Thus, cells exposed to 3-BAABE displayed the DNA fragmentation ladder characteristic for apoptosis, associated with a marked increase of the activity of apoptosis effector caspases-3 and -6, which was followed by proteolytic cleavage of DNA fragmentation factor (DFF) and poly(ADP-ribose) polymerase (PARP). Exposure of tumor cells to 3-BAABE increased the activity of apical caspase-9, but had no effect on caspase-8. Complete inhibition of 3-BAABE-induced apoptosis was exerted by LEHD-FMK, a caspase-9 inhibitor. DEVD-FMK, a caspase-3 inhibitor, and VEID-FMK, a caspase-6 inhibitor, partially inhibited 3-BAABE-induced apoptosis, whereas exposure to IETD-FMK, a caspase-8 inhibitor, had no effect. The fragmentation and elevated activity of caspase-9 in 3-BAABE-treated cells and the fact that only an inhibitor of caspase-9 abrogated 3-BAABE-induced apoptosis indicate that 3-BAABE is a distinctive compound that elicits apoptosis through a pathway that is limited specifically to activation of apical caspase-9.

Animals↗
PubMed2000

Local SIgA response following administration of a novel intranasal inactivated influenza virus vaccine in community residing elderly.

Community-residing elderly were immunized twice intranasally three weeks apart with a new inactivated whole influenza vaccine. A control group was immunized intramuscularly with conventional influenza vaccine. Local antibody response was detected in about 50% of intranasally immunized subjects compared to about 20% of intramuscularly immunized subjects, to the three viral strains. Increasing the incidence of elevated IgA response may prevent influenza at its early stages thus reducing complications in the elderly.

Administration, Intranasal↗
PubMed2000

Rare Jatropha multifida intoxication in two children.

Two children were admitted to the Emergency Department (ED) after ingesting a large amount of fruit of a plant identified as Jatropha multifida. They were mildly obtunded, had intractable vomiting, and seemed dehydrated. Intravenous fluid replacement and urine alkalinization were initiated. After stabilization, their 5-day hospital stays were uneventful except for a subclinical rise of liver enzymes. Jatropha species contain the toxalbumin ricin, which causes severe vomiting and diarrhea, dehydration, shock, and renal and hepatic impairment. Ricin also has cardiotoxic and hemolytic effects and several deaths have been documented. Children are attracted by the shape and the color of the Jatropha fruits. Mortality can be prevented by immediate fluid and electrolyte replacement.

Child↗
PubMed2000

Phagocytic killing and antibody response during the first year after tetravalent meningococcal vaccine in complement-deficient and in normal individuals.

Seven individuals with late complement component (LCC) deficiency and seven control subjects were vaccinated with tetravalent meningococcal vaccine. The response to vaccination was evaluated by measuring the antibody titer and the phagocyte killing of the bacteria, before, 5-7 weeks, and 12-14 months after vaccination. Prior to vaccination, no phagocytic killing and a low titer of antibody was found in the LCC-deficient group and a low killing (mean of 40-58%, according to the serogroup) in normal controls. The phagocytic killing increased significantly 5-7 weeks after vaccination. However, while in normal controls the phagocytic killing was close to 100% after 5-7 weeks and decreased only slightly during the first year, the mean killing of the various meningococcal subgroups in LCC-deficient individuals was 70-89% and dropped to only 53-71% one year after vaccination. Six weeks after vaccination the mean antimeningococcal antibody titer increased similarly in the sera of LCC-deficient patients and controls. One year after vaccination the controls maintained the high concentration, while the LCC-deficient patients had tendency toward a decrease. In addition, the interpersonal variability of the antibody concentration, both in LCC-deficient individuals and in normal controls, was much higher than the phagocytic killing, with only a very mild increase in some individuals. Thus, it is possible that in spite of adequate increase of antimeningococcal antibody titer after vaccination of LCC-deficient individuals their immunity against the bacteria may not be optimal. Our data show also that phagocytic killing of meningococci is probably a more consistent assay than antibody titer levels for antimeningococcal immunity, especially in LCC-deficient patients.

Antibodies, Bacterial↗
PubMed2000

B-lymphocytes in CLL and NHL differ in the mRNA splicing pattern of the CD45 molecule.

In the present study the cell surface expression of CD45 isoforms on normal and neoplastic human B cells was correlated with splice products of the CD45 mRNA, using RT-PCR technology. In non-Hodgkin's lymphoma cells in the leukemic phase (NHL) the majority of the cells expressed a high level of CD45RA, while in CLL most of the cells expressed a low level. In the Raji and Daudi Burkitt B-cell lymphoma lines the main CD45 mRNA product was the largest, unspliced, full-length isoform (456) and the 56 splice product. Similar results were obtained with B-cell lymphoma cells isolated from the peripheral blood of patients with NHL in the leukemic phase. In EBV-transformed B-cell lines, the 456 and the 56 isoform of CD45 mRNA were predominant, but in addition a low level of the 5- and 0-exon splice products was detected. A strikingly different pattern was obtained with B-CLL cells. In CLL the level of the 456 and the 56 isoforms was low, while that of the 5- and 0-exon splice products was increased. Thus, in contrast to the heterogeneity in the expression of CD45RO in B-CLL, the majority of the cells contained the CD45 mRNA splice product coding for CD45RO. Analysis of splice products of the CD45 mRNA may serve as an additional tool to differentiate CLL from the leukemic phase of NHL.

B-Lymphocytes↗
PubMed2000

Natural killer (NK) and T cell-associated surface marker expression following allogeneic and autologous bone marrow transplantation (BMT).

Natural killer (NK) and T cell development was studied after allogeneic and autologous BMT. We determined the phenotypic expression and lytic ability of these subpopulations after BMT. Following T cell-depleted (TCD) BMT, the number of CD16+ and CD56+ cells peaked at 39 and 46 days, respectively, and constituted the majority of peripheral blood lymphocytes (PBL). Coexpression of CD3 and CD16 was <10% up to 14.5 weeks after transplant. Following allogeneic non-T cell-depleted (NTCD) BMT, the number of CD16+ and CD56+ cells peaked at 6 weeks. CD3 expression was normal (70%-80%), % CD8+ cells was high (40%), and % CD4+ cells was low (20%). Following autologous BMT (ABMT), % CD3+ T cells was 80%, of which 70% expressed the CD8 marker. In contrast, CD4 expression was low (20%). CD16+ cells appeared 2.5-3 weeks after ABMT but with low frequency (20%), at which point 20%-30% of the CD3+ cells coexpressed CD16. A positive correlation was found between CD16 expression and cytotoxic capability. In conclusion, a marked difference was observed in NK and T cell-associated markers following TCD BMT, NTCD BMT, and ABMT. Following NTCD or ABMT, but not TCD BMT, a high percentage of cells co-express CD16 and CD3, which may indicate the possibility of a common NK and T cell progenitor.

Adolescent↗
PubMed2000

Local and systemic immune response in community-dwelling elderly after intranasal or intramuscular immunization with inactivated influenza vaccine.

Intramuscular (IM) influenza vaccines are about 50% effective in preventing clinical illness among the elderly and their effectiveness in eliciting mucosal response may be even lower. The aim of the present study was to evaluate the immunological effect of a novel inactivated intranasal (IN) trivalent whole influenza virus vaccine among community-dwelling elderly. Sixty-one subjects were vaccinated with two doses of an IN vaccine and a control group of 31 subjects was vaccinated with a commercial IM vaccine. Viral strains in the 1997/8 vaccine used were A/Nanchang/933/95(H3N2), A/Johannesburg/82/96(H1N1) and B/Harbin/7/94. Serum IgG and nasal IgA were determined by HI and ELISA, respectively. Only a few minor local adverse events were reported after vaccination. Seroconversion for the three antigens tested was higher after IM vaccination, although not statistically significant. Local antibody response to the three antigens tested was detected in 50-53% and 19-26% of IN and IM immunized subjects, respectively. The IN vaccine tested was significantly more effective than the IM vaccine in inducing mucosal IgA response. This may prevent influenza at its early stages and thus contribute to the reduction of complications in the elderly.

Administration, Intranasal↗
PubMed2000

Some distinctive features of the impact of managed care on psychiatry.

Past research suggests that the spread of managed care is affecting the treatment of mental and physical illnesses differently. This article develops six hypotheses that could explain the differential effects of managed behavioral health care, based on characteristics of mental disorders, professional norms of treatment, and the broader societal consequences of untreated mental illness. Using data from the 1998 Socioeconomic Monitoring System fielded by the American Medical Association, we tested these hypotheses by comparing the experiences of psychiatrists under managed care with those of primary care providers and medical specialists. We found the following: (1) psychiatrists face substantially more aggressive external review than do primary care providers and are less successful in overturning denials; (2) psychiatrists feel significantly more at risk for disaffiliation from health plans; (3) psychiatrists report facing review protocols that are more confusing than those for primary care physicians, but psychiatrists' staff spend less time on external review; (4) psychiatrists are more likely than other physicians to report that their patients have difficulty making informed choices about managed care; and (5) psychiatrists evidence greater time commitment to advocacy on behalf of their patients with respect to managed care.

Cost Allocation↗