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Biomedical subjects

S M Friedman

Publications and source records attributed to S M Friedman.

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

[Assessment of normal growth patterns in rats by Z score].

Malnutrition is one of the most important causes of normal growth disruption. Anthropometric methods are highly valuable in clinic pediatric diagnosis to determine the nutritional status of children and as recovery monitoring. In previous studies, we have demonstrated that the standards weight-age, height-age and weight-height of growing rats had similar distribution to those in normal children. However, to improve the diagnostic effectiveness of anthropometric information, statistical analysis to normally and non-normally distributed variables should be applied. One hundred Wistar rats (50 male and 50 female rats) from weaning (day = 25, weight = 35-40 g) to 70 days of age were fed with a commercial diet. Water and diet were offered "ad libitum". Body weight and height were recorded every two or four days, respectively. Percentiles of weight vs age, height vs age and weight vs height were plotted for male and female rats. The statistical criterion for classifying the anthropometric measurements into nutritional categories was based on percentiles cutoff and Z-score. The Z-score was calculated according to: Z = (standard mean value-subject value/standard deviation of standard). The statistical anthropometric categories of growing rats were similar to those obtained in children. This evidence suggest that the rat can be used as an experimental model to infer and predict the nutritional response in children.

Animals↗
PubMed1998

Chronic lymphocytic leukemia B cells can express CD40 ligand and demonstrate T-cell type costimulatory capacity.

Chronic lymphocytic leukemia (CLL) is characterized by a clonal expansion of CD5(+) B cells in the peripheral blood. Associated immune aberrations include abnormal Th-cell function and pathogenic autoantibodies. Under most circumstances, CLL B cells do not proliferate in culture and express a limited repertoire of surface antigens, including CD19, CD20, CD23, CD27, CD40, and CD70. In this report, we demonstrate that freshly isolated B cells from a subset of CLL cases constitutively express CD40 ligand (CD40L, CD154), a member of the tumor necrosis factor family which is normally expressed by activated CD4(+) T cells and mediates T-cell-dependent B-cell proliferation and antibody production. The degree of CD40L expression varied considerably among the CLL cases examined. CD40L was detected in purified CLL B cells by immunofluorescence flow cytometry, by RT-PCR, and by immunoprecipitation. To demonstrate that CD40L in the CLL B cells is functional, we used irradiated CLL cells to stimulate IgG production by target, nonmalignant B cells in coculture. The CLL B cells induced IgG production by normal B cells to a similar degree as did purified T cells in a process which was partially inhibited by monoclonal antibody to CD40L. This is one of the first reports of CD40L expression in a B-cell tumor. The data suggest that CD40L in the tumor cells may be a factor in the generation of pathologic antibodies by normal B cells in some patients with CLL.

B-Lymphocytes↗
PubMed1998

CD40 ligation impedes lymphoblastoid B cell proliferation and S-phase entry.

The CD40 cell surface antigen and member of the tumor necrosis factor (TNF) receptor superfamily is expressed in many cell types, including normal and neoplastic B cells. Signaling through CD40 induces B cell proliferation, differentiation and, in some circumstances, protects the B cell from apoptosis. Lymphoblastoid cells (LCLs) resemble the malignant B cells that comprise the Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disorders, in that the cells bear a highly activated phenotype and, unlike most other EBV positive tumor cells, express the majority of latent EBV genes. In this study, we use assays of cell viability, proliferation, cell cycle and apoptosis to demonstrate that ligation of the CD40 receptor in EBV-transformed LCLs inhibits their growth. The process does not involve apoptosis, but is characterized by reduced S-phase entry from G0/G1. A better understanding of the negative effects of CD40 ligation in these cells may offer clues for the development of novel therapies in EBV-related B cell disorders.

Antibodies, Monoclonal↗
PubMed1998

Influence of dietary calcium concentration on body size and bone composition in rats during recovery from malnutrition.

OBJECTIVE: The purpose of our study was to assess the influence of different levels of calcium (Ca) in a diet containing 30% protein on the rehabilitated of the body size from protein-energy malnutrition (PEM) and to establish the optimal Ca/protein ratio for attaining a normal body composition. METHODS: Weanling female Wistar rats were fed with protein-free diet up to a weight deficit of 20 +/- 1%. Then they were arranged in groups (TO) and fed diets with 30% protein and 0.0, 0.2, 0.4, 0.6, 0.9 or 1.2% Ca for 28 days (T28). Food and deionized water were given ad libitum. Body weight and length were recorded every 3 days. At T28, the animals were sacrificed to determine femur composition. RESULTS: At T13, weight-for-age (W/A) was within the normal range for rats consuming > or = 0.6% Ca. At T28 all groups showed adequate W/A. Although length-for-age was adequate during rehabilitated period, rate of weight gain improved when Ca was > or = 0.6%. Femur length did not show significant difference between groups. Total femur Ca content and mg Ca/g of dry-weight tissue increased with increments in dietary Ca concentration and tended to plateau with 0.4% Ca. Ca/P ratio reached the highest value with 0.9% Ca. CONCLUSIONS: Our findings indicate that at a dietary protein level of 30% the Ca/protein ratio is a limiting factor in attaining of normal body size; this is achievable when Ca concentration is 1.2% and the Ca/protein ratio is 0.04.

Aging↗
PubMed1998

Rapidly progressive herpetic retinal necrosis: a blinding disease characteristic of advanced AIDS.

Eleven patients with rapidly progressive herpetic retinal necrosis (RPHRN) complicating AIDS were investigated retrospectively to study the disease spectrum, systemic involvement, and therapy. The mean CD4 cell count was 24/microL. There was a characteristic disease pattern with rapid progression, 82% bilaterality, relative resistance to intravenous antiviral therapy, and 70% retinal detachment. Varicella-zoster virus was the probable cause in 10 patients (detected by polymerase chain reaction in two eyes investigated), and herpes simplex virus was the probable cause in one. Cutaneous zoster occurred previously in 73% but was not concurrent. Seventy-three percent had central nervous system disease, possibly virus-related. RPHRN may be a local herpetic recrudescence in an immune-privileged site with transneural spread. Only four of 20 affected eyes retained useful vision. Poor ocular bioavailability, retinal ischemia, acquired drug resistance, and strain pathogenicity may underlie treatment failure. Acyclovir therapy appears relatively ineffective. Combined intravenous and intravitreal therapy with foscarnet and ganciclovir may be the best current management. Research advances are needed urgently.

AIDS-Related Opportunistic Infections↗
PubMed1998

Structural motifs in rheumatoid T-cell receptors.

The linkage of rheumatoid arthritis (RA) to HLA-DR haplotypes, high levels of HLA-DR expression, and T-cell infiltration in the joints, indicate a central role for the interaction of T-cell receptors (TCR) with antigen (Ag) + major histocompatibility complex (MHC) complexes in pathogenesis. Receptor analysis in RA has uncovered a restricted heterogeneity of TCR transcripts, suggesting an antigen-driven response. We analyzed the sequence and structural features of RA-associated TCRs in light of the recently published TCR crystal structures. The surface-exposed residues of the third complementarity-determining region (CDR3s) showed preferential use of certain amino acid residues when sequences derived from synovial fluid or tissue were compared with those derived from peripheral blood, particularly for alpha chains. Sequence alignment of oligoclonal synovial TCR CDR3s revealed groupings with similar CDR3 lengths and amino acid compositions, which suggests shared antigen recognition. Given the limitations of analyzing TCR sequences without knowing their structures, we developed several in vivo-activated synovial-tissue Vbeta17 + RA T-cell clones. Two Vbeta17/V alpha7 clones with different CDR3 sequences were analyzed by molecular modeling. Although distinct topologic features were seen, a central patch of residues with similar chemical and geometric characteristics was present in both. Electrostatic maps revealed similar binding surfaces of both alpha domains and central patches, with differences in the beta domains. This suggests that an alpha-domain-focused binding trajectory would allow shared antigen recognition by these TCRs. These studies support recognition of a limited diversity of Ag + MHC complexes by synovial RA TCRs.

Amino Acid Sequence↗
PubMed1998

[Nutrition dwarfism: longitudinal analysis of anthropometric and metabolic parameters in rats].

UNLABELLED: Nutritional dwarfing (ND) is the result of nonorganic causes reflective of a voluntary or unintentional reduction in food intake, inappropriate eating behavior, dissatisfaction with body weight or unhealthy approaches toward weight control. Patients with ND have reached an equilibrium between their genetic growth potential and their nutritional intake. This study was undertaken to compare on a growing rat model the metabolic alterations in terms of substrate utilization (SU), oxygen consumption (VO2) and growth rate velocity. Twenty male weanling Wistar rats were randomized to 3 groups: control (C), experimental 4 (E4) and 8 (E8). C was fed "ad libitum" with a stock diet, E4 and E8 were underfed by 80% of the requirements during four or eight weeks, respectively. During the depletion phase the following measurements were performed: 1a) body weight (Wt), 1b) length, 1c) Weight for Length ratio z-score, 2) Body composition (BC) by EM-SCAN Tobec Model 3 000, Springfield. USA, 3) VO2 by indirect calorimetry, ECO-OXYMAX. RESULTS: 1) wt for length was -0.70 +/- 0.43 for E4 (t = 4 weeks) and 1.44 +/- 0.32 for E8 (t = 8 weeks), 2% of fat mass was within the normal range, 3) VO2 was not significantly different between groups. Chronic suboptimal nutrition (80%) decreased growth velocity which was the sole manifestation of nutritional inadequacy.

Animals↗
PubMed1997

Fas ligand expression and function in systemic lupus erythematosus.

Mutations in the Fas receptor or its ligand (FasL) lead to lupus-like systemic autoimmune diseases in mice and in some humans. To determine whether a significant number of patients with systemic lupus erythematosus (SLE) have impaired FasL function, we compared T cell effector function by superantigen-activated CD4+ T cell lines or by anti-CD3- and IL-2-generated cytotoxic T cells. No differences were observed between SLE and normal control superantigen-derived CD4+ T cells in either the ability of these cells to up-regulate Fas expression or to induce apoptosis of the Fas-sensitive target B cells. When anti-CD3/IL-2-activated T cells were examined, SLE T cells had a modest reduction (-8%) in T cell cytotoxicity compared with normal controls, but the reduction was similar to the rheumatoid arthritis disease controls. A modest reduction in cytotoxicity was evident in both the Fas and perforin/granzyme pathways as determined by testing Fas-positive and -negative targets as well as by selective blockade of the perforin/granzyme pathway with concanamycin. These results indicate that no specific defects in FasL function are evident in the majority of SLE patients under the in vitro conditions tested. The proportional reduction in FasL and perforin/granzyme function in SLE and rheumatoid arthritis patients following anti-CD3/IL-2 stimulation most likely reflects subtle differences in activation in patient-derived vs normal control T cells.

Animals↗
PubMed1997

Bilateral subinternal limiting membrane hemorrhage with Terson syndrome.

PURPOSE: To report the anatomic location of bilateral dome-shaped posterior pole hemorrhages in a patient with Terson syndrome. METHODS: Case report. We performed bilateral vitrectomy for vitreous hemorrhage in a patient with Terson syndrome. After removal of vitreous hemorrhage, the tissue overlying a large discrete hemorrhage in the posterior pole was removed, and the tissue from one eye was examined histologically. RESULT: The discrete dome-shaped hemorrhage in the posterior pole was confined to the retina anteriorly by the internal limiting membrane. CONCLUSION: Large dome-shaped retinal hemorrhages with Terson syndrome can be located beneath the internal limiting membrane of the retina.

Basement Membrane↗
PubMed1997

Characterization of cartilage metabolic response to static and dynamic stress using a mechanical explant test system.

A new mechanical explant test system was used to study the metabolic response (via proteoglycan biosynthesis) of mature, weight-bearing canine articular cartilage subjected to static and dynamic compressive stresses. Stresses ranging from 0.5 to 24 MPa were applied sinusoidally at 1 Hz for intervals of 2-24 h. The explants were loaded in unconfined compression and compared to age-matched unloaded explants. Both static and dynamic compressive stress significantly decreased proteoglycan biosynthesis (range 25-85%) for all loading time intervals. The inhibition was proportional to the applied stress but was independent of loading time. After rehydration upon load removal, the measured water content of the loaded explants was not different from the unloaded explants for all test variables. Autoradiographic and electron microscopic analysis of loaded explants showed viable chondrocytes throughout the matrix. Our results suggest that the decreased metabolic response of cyclically loaded explants may be dominated by the static component (RMS) of the dynamic load. Furthermore, the observed decreased metabolism may be more representative of the in situ tissue response than that of unloaded explants, in which we found an increasing rate of metabolism for up to 6 days after explant removal.

Animals↗
PubMed1997

Positive vitreous cultures from eyes without signs of infectious endophthalmitis.

BACKGROUND AND OBJECTIVE: There is little information on the rate of false-positive vitreous cultures, because cultures from presumably sterile vitreous are not routinely taken in clinical practice. The objective of this study was to determine the rate of positive vitreous cultures from patients who have no signs of endophthalmitis. PATIENTS AND METHODS: Aerobic cultures from vitreous biopsies were taken from 36 consecutive eyes in which there was no clinical evidence of endophthalmitis. Effluent collected in cassettes during pars plana vitrectomies was processed and cultured in a standard manner. Balanced salt solution was processed intraoperatively through the vitrector and cultured as a negative control. RESULTS: Positive cultures were obtained in 8 of 36 eyes (22.2%). Coagulase-negative Staphylococcus and Corynebacteria accounted for 7 of the 9 identified organisms. No organism was grown in more than one medium. None of the patients were treated for endophthalmitis after surgery, and none had signs of intraocular infection. CONCLUSIONS: A substantial number of vitrectomy cultures from effluent specimens grow low-virulence organisms in the absence of clinical signs of endophthalmitis. The absence of inflammation at the time of surgery suggests that these positive cultures are contaminants.

Aspergillus niger↗
PubMed1996

Allelic variants of human TCR BV17S1 defined by restriction fragment length polymorphism, single strand conformation polymorphism, and amplification refractory mutation system analyses.

Several human TCR BV gene subfamilies, including BV3, BV14, and BV17S1, are single member genes but are overutilized among activated CD4+ synovial T cells in the rheumatoid arthritis (RA). To define the role of these TCR BV genes in the pathogenesis of disease, it is critical to characterize the genomic organization and the allelic variations of these genes. In this study we describe allelic variations of BV17S1 defined by restriction fragment length polymorphism (RFLP), single strand conformation polymorphism (SSCP), and amplification refractory mutation system (ARMS) analyses. A single nucleotide replacement (C/T) results in an amino acid substitution (F/L) in the leader and distinguishes BV17S1*1 from BV17S1*2. This nucleotide substitution was found to create a BsmAI restriction enzyme recognition site in BV17S1*2. Therefore genotypic analyses can be performed either by the SSCP or RFLP method. The analyses of 75 unrelated individuals show that the frequency for allele BV17S1*1 is 52.7% and for allele BV17S1*2 is 47.3%. Both alleles are functionally expressed and are distributed within CD4+/CD8+ T cell subsets. Another point mutation in the CDR2 region of BV17S1, which results in the amino acid replacement of Gln by His, originally identified form a cDNA clone, has now been confirmed as an allele by ARMS analysis using genomic DNA preparations and designated to as BV17S1*3. Screening of this CDR2 related variant among normal populations indicates that this is a rare allele (1 of 75). Although this variant may be of functional significance, the genotypic analysis and functional studies are difficult due to the low frequency of BV17S1*3. In an attempt to define a correlation between BV17S1 allelic usage and susceptibility to RA, the germline distribution of BV17S1 alleles *1 and *2 has been examined in a small number of RA patients and no skewed usage has been identified.

Alleles↗
PubMed1996

CD4+ T-cell induction of Fas-mediated apoptosis in Burkitt's lymphoma B cells.

Cytotoxic function of CD4+ Th1 cells is mediated by Fas (CD95, APO-1) and its ligand (Fas ligand). Recent studies using nontransformed B cells and the Ramos Burkitt's lymphoma (BL) B-cell line cells show that CD40 ligation at the B-cell surface by activated, CD40 ligand (CD40L)-bearing, CD4+ T cells upregulates Fas expression on B cells and primes B cells for Fas-mediated death signals. In this work, we examine whether this CD4+ T-cell-dependent molecular pathway for Fas upregulation and B-cell apoptosis reflects a peculiarity of the Ramos B-cell line or is applicable to other Burkitt's tumors as well. In 5 of the 6 Epstein-Barr virus-negative BL cell lines examined, the cells constitutively express undetectable or low levels of Fas and are resistant to Fas-mediated signals induced by monoclonal anti-Fas antibody. All 6 of the BL cell line B cells upregulate Fas in response to CD40 ligation, and in 4 of the cases they become sensitive to Fas-mediated death signals. In one BL cell line, the cells are constitutively sensitive to Fas-mediated cytolysis and are unaffected by CD40 signals. Next, we applied these immunologic manipulations to cells from a refractory clinical sample and observed that the tumor cells could be induced to express Fas and undergo apoptosis in our system. These results establish CD4+ T cells and the Fas-Fas ligand system as important immune regulators of Burkitt's lymphoma B cells and indicate that the susceptibility of tumor cells to Fas-mediated death signals can be modulated by specific activation events at the cell surface.

Apoptosis↗
PubMed1996

Fas expression and apoptosis in human B cells.

Mechanisms of B cell apoptosis are critical in reducing aberrant B cell proliferations such as those that arise in autoimmune disease and in B cell malignancies. The physiologic interaction of CD4+ helper T cells and B lymphocytes has been extensively studied over the past two decades. Although CD4+ T cells are considered primarily to offer positive costimulatory signals for B cell differentiation into active immunoglobulin-secreting cells, recent studies have shown that CD4+ T cells are crucial in downregulating the humoral immune response. In the course of cognate interaction between CD40 ligand (CD40L)-bearing CD4+ T cells and CD40-expressing germinal center B cells, CD40 ligation results in augmented Fas expression at the B cell surface. Like CD40L, Fas ligand is expressed on activated CD4+ Th1 cells and when bound to Fas receptor on the B cell surface, initiates an apoptotic signal in that cell. Thus, CD4+ T cells limit the growth of autologous germinal center B cells by first inducing Fas expression and then instigating a death signal via Fas ligand. In this work, we will consider these observations about CD4+ T-cell-induced, Fas-mediated B cell death in the context of other factors that affect apoptosis in B cells, normal and malignant.

Apoptosis↗
PubMed1996

Alar and apples: newspapers, risk and media responsibility.

During 1989, a major environmental and health risk issue, the spraying of Alar on apples, created a furor among the American people. After hearing charges from the Natural Resources Defense Council (NRDC) that eating Alar-laden apples significantly increased a child's risk of developing cancer, numbers of school districts dropped apples from their menus and parents poured apple juice down the drains. Apple sales plummeted. The NRDC's charges, which were disseminated by a well-planned and effective public relations campaign, brought counter-charges from the US environmental Protection Agency, which accused the NRDC of basing its study on poor data, among other things. The core of the dispute was in the risk figures and risk interpretations being used by each organization.

Fruit↗
PubMed1996

T helper cell-dependent, microbial superantigen-mediated B cell activation in vivo.

We have utilized a severe combined immune-deficient (SCID) mouse adoptive transfer model to explore the in vivo immunostimulatory effects of bacterial superantigens (SAg). B cell reconstituted SCID recipients were treated with the Staphylococcus aureus-derived toxic shock syndrome toxin (TSST-1) alone or in conjunction with syngeneic L3T4+ TSST-1-reactive Th cells. Over several months of study, the repetitive administration of TSST-1 resulted in a prompt, transient increase in serum IgG levels. This response required both biologically active TSST-1 and Th cells. These findings demonstrate that certain bacterial SAgs can promote Th cell-dependent B cell activation and differentiation in vivo. These studies strengthen the analogy between SAg-mediated and allospecific Th-B cell interactions responsible for the autoimmune sequelae of graft-versus-host disease.

Animals↗