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N Cohen

Publications and source records attributed to N Cohen.

At least 199 records · Page 11Linked to original sources
PubMed1990

Non-inherited maternal HLA antigens and protection against sensitisation.

To test the hypothesis that non-inherited maternal antigens (NIMAs), which reportedly afford protection against sensitisation by random transfusions, can provide protection against repetitive antigenic exposure of donor-specific transfusion (DST), 140 DST patients whose donors were mismatched for NIMAs and 71 whose donors were mismatched for non-inherited paternal antigens (NIPAs) were studied. The rate of sensitisation in the two groups of patients was similar (22.1% vs 15.5%). There was no difference in sensitisation to NIMAs and NIPAs between patients who received azathioprine and those who did not. The formation of donor specific HLA antibody was comparable in the two groups. After kidney transplantation there were no differences in 1-year graft survival or the incidence of rejection episodes. These findings suggest that NIMAs do not provide lifelong protection against subsequent repetitive antigen challenge and sensitisation.

Adult↗
PubMed1990

Novel 6-hydroxychroman-2-carbonitrile inhibitors of membrane peroxidative injury.

Novel 6-hydroxychroman-2-carbonitrile compounds have been synthesized, and their antiperoxidant activity against superoxide-dependent, iron-promoted mycocardial phospholipid peroxidation has been evaluated quantitatively. With few exceptions, these compounds afforded significant, concentration-dependent antiperoxidant protection to myocardial-membrane phospholipid at sub- to low-micromolar concentrations. Structure-activity correlation demonstrated that R1-, R2-, and R3-methyl groups in the aromatic ring enhanced antiperoxidant activity, whereas hydrophobic groups at either R4 or R5 of the pyran ring compromised antiperoxidant efficacy. The most efficacious antiperoxidant synthesized contained a catechol moiety at R4 and was some 10-fold more potent than alpha-tocopherol. None of the 6-hydroxychroman-2-carbonitrile antiperoxidants scavenged superoxide or inhibited the enzymatic superoxide generator, xanthine oxidase, at effective antiperoxidant concentrations. The ability of these compounds to interrupt the propagatory phase of an on-going peroxidation reaction indicated that they acted as antiperoxidants by trapping chain-carrying lipid peroxyl radicals. Since a number of the 6-hydroxychroman-2-carbonitriles were most potent antiperoxidants than a variety of known chain-breaking compounds, this new class of phenolic antioxidants may represent a novel approach to the design of therapeutics against diseases in which lipid peroxidation is a causative factor or in which lipid peroxidases serve as mediators.

Animals↗
PubMed1990

Immunoglobulin heavy chain gene organization and complexity in the skate, Raja erinacea.

Immunoglobulin heavy chain genes from Raja erinacea have been isolated by cross hybridization with probes derived from the immunoglobulin genes of Heterodontus francisci (horned shark), a representative of a different elasmobranch order. Heavy chain variable (VH), diversity (DH) and joining (JH) segments are linked closely to constant region (CH) exons, as has been described in another elasmobranch. The nucleotide sequence homology of VH gene segments within Raja and between different elasmobranch species is high, suggesting that members of this phylogenetic subclass may share one VH family. The organization of immunoglobulin genes segments is diverse; both VD-J and VD-DJ joined genes have been detected in the genome of non-lymphoid cells. JH segment sequence diversity is high, in contrast to that seen in a related elasmobranch. These data suggest that the clustered V-D-J-C form of immunoglobulin heavy chain organization, including germline joined components, may occur in all subclasses of elasmobranchs. While variation in VH gene structure is limited, gene organization appears to be diverse.

Amino Acid Sequence↗
PubMed1990

Fixation-associated quantitative variations of DNA fluorescence observed in flow cytometric analysis of hemopoietic cells from adult diploid frogs.

We have examined, by flow cytometry, the apparent DNA content of frog blood cells that had been fixed with either 50% ethanol, 70% ethanol, or 66% methanol, before being stained with either mithramycin, propidium iodide, or Hoechst 33258. After 50% ethanol fixation, regardless of the dye used, the DNA content of the hemopoietic cells appeared unimodal, but after either 70% ethanol or 66% methanol fixation, it appeared bimodal. Cell sorting revealed that the lower and upper modes are represented by erythrocytes (RBCs) and leukocytes (WBCs), respectively. In amphibians, the chromatin of metabolically inactive RBCs is highly condensed relative to the chromatin of metabolically active WBCs. The bimodal distribution of DNA contents seen with 66% methanol and 70% ethanol, but not 50% ethanol, seems to reflect this disparity in the degree of chromatin condensation existing between the RBCs and WBCs. This, in turn, implies that the accessibility of fluorescent DNA dyes to the chromatin of fixed frog hemopoietic cells, especially of RBCs, can be affected by the concentration of alcohol used for their fixation.

Animals↗
PubMed1990

Increased pulmonary metastases and natural killer cell activity in mice following handling.

We have demonstrated that holding BALB/c female mice for two minutes per day for two weeks prior to injection of line 1, a BALB/c derived alveolar carcinoma, results in a significant increase in pulmonary metastases compared to unhandled controls. Handling did not affect splenic in vitro or in vivo natural killer (NK) cell activity but, surprisingly, was associated with increased NK cell activity in the lungs of these handled mice. These results demonstrate that a simple psychosocial manipulation may effect the metastatic process. The implications of these findings and potential mechanisms are discussed.

Animals↗
PubMed1990

Zinc metabolism in patients treated with captopril versus enalapril.

Several zinc parameters were assessed in 13 patients with essential hypertension who were chronically taking only captopril (six subjects) or enalapril (seven subjects), as well as in six untreated hypertensives, and nine healthy controls. Serum zinc levels were comparable in all groups. Twenty-four-hour urinary zinc excretion was significantly increased in the captopril-treated patients compared with the other three groups. The zinc:creatinine ratio in 24-hour urine was significantly increased in both captopril and enalapril groups, but was significantly greater in the former. Although plasma zinc concentrations were comparable in all groups, red blood cell (RBC) zinc values were significantly decreased in the captopril group compared with the other three groups. We conclude that (1) although both captopril and enalapril produce renal zinc loss, this loss is far greater in patients receiving captopril; and (2) captopril administration over 3 months or more generates RBC zinc depletion.

Captopril↗
PubMed1990

Voluntary consumption of cyclophosphamide by nondeprived Mrl-lpr/lpr and Mrl +/+ mice.

Cyclophosphamide dissolved in several dilutions of chocolate milk was presented for 20 hr daily to nondeprived, symptomatic, autoimmune Mrl-lpr/lpr and asymptomatic Mrl +/+ mice. In the absence of cyclophosphamide, daily consumption was inversely related to the concentration of the chocolate milk solutions and increased from the first to the fourth day of exposure. There were no effects of strain or sex on the consumption of plain chocolate milk. Consumption of 0.1 or 0.2 mg cyclophosphamide per ml of different dilutions of chocolate milk increased over days 1-4 and decreased on day 8. Consumption of 0.4 mg/ml cyclophosphamide did not change over days. Generally, consumption was inversely related to the cyclophosphamide concentration. Females consumed more cyclophosphamide than males. Autoimmune lpr/lpr mice consumed more cyclophosphamide than +/+ mice. Dilution of chocolate milk had no effect on consumption of cyclophosphamide. Lymphoproliferation and anti-ssDNA antibody titer were reduced by the consumption of cyclophosphamide-chocolate milk solutions. It is hypothesized that autoimmune lpr/lpr mice voluntarily consume more cyclophosphamide than asymptomatic +/+ mice in an effort to "correct" their immune system dysregulation.

Animals↗
PubMed1990

Evolution of the MHC: antigenicity and unusual tissue distribution of Xenopus (frog) class II molecules.

Antibodies that recognize Xenopus class II molecules have been developed. Mouse monoclonal antibodies were prepared by immunizing BALB/c mice with frog MHC antigens that had been partially purified with alloantisera, and by immunizing mouse spleen cells in vitro with activated Xenopus T lymphocytes. In addition, five mouse monoclonal antibodies specific for human class II antigens were found to cross-react with Xenopus class II antigens. A.TH mice, which do not express E class II molecules, always produce immunoprecipitating antibodies reactive with frog class II molecules after immunization with frog lymphocytes; other mouse strains rarely produce such antibodies. Two of the monoclonal antibodies raised against frog class II molecules recognize the denatured class II beta chain on Western blots, and the other three appear to recognize only the class II heterodimeric complex. The antibodies display differential reactivity with the allelic class II products of Xenopus. The monoclonal antibodies react with all adult lymphocytes in the spleen and peripheral blood, T cells and B cells having equivalent levels of class II antigens per cell. Class II molecules are "differentiation antigens" on adult thymocytes as the expression is greatest on the mature medullary population. The number of class II molecules/lymphocyte increases after culturing in medium containing fetal bovine serum. Sequential immunoprecipitation and isoelectric focusing experiments have shown that cell surface class II molecules immunoprecipitated with the monoclonal antibodies are the same as those immunoprecipitated with the cross-reactive antiserum specific for DR antigens which was previously used to identify frog class II molecules.

Animals↗
PubMed1990

A monoclonal antibody against the human IL-2 receptor binds to paraformaldehyde-fixed but not viable frog (Xenopus) splenocytes.

Others have reported that a monoclonal anti-human IL-2 receptor antibody (anti-CD25) specifically binds a membrane receptor on Xenopus laevis PHA-induced and paraformaldehyde-fixed splenic blasts. In this paper, we present evidence suggesting that this binding is an artifact of membrane damage. Specifically, significant binding of anti-CD25 could only be achieved if the lymphoblasts were acid-washed and/or paraformaldehyde-fixed prior to being incubated with the fluoresceinated antibody. For example, in a representative experiment 95% of paraformaldehyde-fixed blasts, about 19% of acid-washed but not fixed blasts, but fewer than 2% of viable (untreated) blasts were positive for the CD25 epitope. Paraformaldehyde is known to alter membrane permeability. The DNA dye propidium iodide (PI) was used to demonstrate that the acid washing procedure also causes membranes to become permeable. Flow cytometric analyses of acid-washed PHA-induced splenic blasts doubly stained with the anti-CD25 antibody and PI showed that only 1.5% of the cells that were positive for CD25 did not stain with PI. Additionally, the anti-CD25 antibody, which immunoprecipitated a molecule from human lymphoblasts of between 50 and 60 kDa, did not immunoprecipitate any surface molecules from 125I-labeled Xenopus splenic blasts. Since binding of anti-CD25 to Xenopus splenic blasts appears to occur only after membrane damage, the antibody may be recognizing a cross-reactive internal epitope that is not involved in ligand binding on the cell surface.

Animals↗
PubMed1990

Use of principal components analysis to develop a composite score as a primary outcome variable in a clinical trial. The VA Cooperative Study Group on Cochlear Implantation.

This article describes the use of principal components analysis to derive a composite score from a battery of 24 audiologic tests. The composite score is being used as the primary outcome variable in a clinical trial comparing the efficacy of three cochlear implant devices for people with bilateral, profound hearing loss. The first principal component from the within-class pooled variance-covariance matrix over four time periods was chosen to establish the coefficients for the composite score. This component accounted for 61% of the total variance of the 24 audiologic tests. The first principal component had its largest coefficients associated with the most difficult audiologic tests. The mean composite score of all patients improved over time; some patients showed dramatic improvement. The changes in the composite score over time were also closely related to subjective impressions of implant performance by the patient, audiologist, and otolaryngologist.

Analysis of Variance↗
PubMed1990

The effects of stress on the development of immunological memory following low-dose antigen priming in mice.

Observable stress effects on immune responses may be a function of the quantitative and qualitative characteristics of the stressor, and the outcome measurement of immunity. Further, the effects of stress on humoral immunity, in particular, may be sensitive to the concentrations of antigen used to elicit a response. We have studied the effects of footshock stress during the time of priming with low concentrations of antigen on the secondary response to another low dose of antigen. The secondary humoral immune response of C3H/HeJ mice to the protein antigen keyhole limpet hemocyanin was examined following footshock, exposure to the apparatus without shock, or exposure to the home cage. Footshock reproducibly depressed the IgG anti-KLH response, and the effect on the IgM response was sporadic. Initially, footshock was administered for 7 days before and 7 days after priming with low amounts of antigen. Subsequent studies demonstrated that a single footshock session delivered 24 h after priming could suppress the IgG anti-KLH response.

Animals↗
PubMed1990

Aeromonas in adult diarrhea: an enteropathogen or an innocent bystander?

This is a study from a district hospital in Israel serving a population of 250,000. During 1986-1987, 1,005 stool specimens were cultured from 932 adult inpatients with acute diarrhea. Seventeen yielded Aeromonas species. Of the 12 strains phenotyped, 10 qualified as enteropathogenic. Five hundred stool specimens from asymptomatic control subjects, inhabitants of the same region, were negative for Aeromonas. The finding of Aeromonas as the apparently sole pathogen in acute adult diarrhea in a geographical area with a negligible asymptomatic carriage rate lends support to the possibility that Aeromonas is an enteropathogen in adults.

Adolescent↗
PubMed1990

Interactions between the brain and the immune system.

The observations and research described in this communication derive from a nontraditional view of the immune system. It has become abundantly clear that there are probably no organ systems or homeostatic defense mechanisms that are not, in vivo, subject to the influence of interactions between behavioral and physiological events. The complex mechanisms underlying these interactions and their relationship to health and illness, however, are imperfectly understood. The most imperfectly understood, perhaps, are the interrelationships among brain, behavior, and immune processes. Without attempting to cover all the literature, we have used stress effects and conditioning phenomena as illustrations to point out that behavior can influence immune function. We have also described data indicating that the immune system can receive and respond to neural and endocrine signals. Conversely, behavioral, neural, and endocrine responses seem to be influenced by an activated immune system. Thus, a traditional view of immune function that is confined to cellular interactions occurring within lymphoid tissues is insufficient to account for changes in immunity observed in subhuman animals and man under real world conditions. These data question seriously the notion of an autonomous immune system. Most of the research on the regulation of immune responses has been predicated on the assumption that such regulation is accomplished by the interacting components of the immune system itself, e.g. interactions among helper and suppressor T-lymphocytes, B-cells, and accessory cells that can result in the production of antibody and effector T cells. The immune system is, indeed, capable of considerable self-regulation, and immune responses can be made to take place in vitro. The functions of that component of adaptive processes known as the immune system that are of ultimate concern, however, are those that take place in vivo. There are now compelling reasons to believe that in vivo immunoregularity processes influence and are influenced by the neuroendocrine environment in which such processes actually take place--an environment that, on the one hand, can generate signals that resting and/or activated leukocytes can receive, and, on the other hand, is exquisitely sensitive to the individual's perception of and capacity to adapt to the demands of the environment. The immune system appears to be modulated, not only by feedback mechanisms mediated through neural and endocrine processes, but by feedforward mechanisms as well. The immunologic effects of learning, an essential feedforward mechanism, suggest that, like direct neural and endocrine processes, behavior can, under appropriate circumstances, serve an immunoregulatory function in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

The kinetics of recovery of leukocyte number and lymphocyte function following an injection of a single high dose of cyclophosphamide in C3H/HeJ mice.

The short-term effects of the immunosuppressive drug cyclophosphamide (Cy) are well-documented, but the long-term consequences are not as well studied. Here we report on the kinetics of leukocyte number and immune function recovery following a single intraperitoneal injection of 100 mg/kg or 300 mg/kg Cy. The leukocyte number in spleen, lymph node, bone marrow and thymus was unchanged in C3H/HeJ mice injected with the lower dose of Cy, and was severely but transiently depressed in mice injected with 300 mg/kg Cy. Recovery was complete by day 21. Humoral immunity was unchanged with the lower dose of Cy; mice injected with 300 mg/kg recovered normal antibody production after 3-5 weeks. Natural killer cell function was also transiently depressed in animals receiving the higher but not the lower concentration of Cy. Surprisingly, splenic mitogen responses were markedly inhibited in mice injected with either concentration of Cy. The T-cell proliferative response remained depressed even after 5 weeks in mice injected with 300 mg/kg Cy. Lymphocyte subpopulations in spleen were examined by flow cytometry, and, although some deviations were observed, it is unlikely that these changes are responsible for the highly depressed mitogen response. Thus, there is a loss of the proliferative response to mitogens in Cy-treated mice long after recovery of other lymphocyte functions.

Animals↗
PubMed1989

Secretion of genetically engineered human/mouse class I antigens.

Two soluble, secreted forms of HLA-B7 were engineered by the creation of hybrid human/mouse molecules containing the polymorphic 5' region of the HLA-B7 gene and the secretory 3' region of the mouse Q10d gene. The hybrid, designated F1, is the first construct with only human extracytoplasmic domains, consisting of exons for the leader peptide and the three extracellular domains (alpha 1, alpha 2, alpha 3) of B7 spliced to the exons for the Q10d truncated transmembrane and 3' untranslated (3'UT) sequences. The second construct, designated C2, is similar but has the human alpha 3 replaced by the Q10 alpha 3 domain. Protein product from each construct was best demonstrated after gene transfection into the J27.2 cell line. In particular, secretion of the F1 product proves that the Q10 alpha 3 domain is not necessary for secretion of class I/Q10 hybrids. Moreover, the two soluble B7 forms, which differ only in their alpha 3 domain, are similarly recognized by monoclonal antibodies W6/32 (anti-HLA-ABC), BBM.1 (anti-human beta 2 microglobulin), and allo-B7-antibody, but differentially recognized by monoclonal antibody Q1/28 (anti-HLA class I heavy chain). Production of such soluble hybrid class I molecules in large amounts should allow critical structural and functional studies of these proteins.

Animals↗
PubMed1989

Repeated intraperitoneal injections of saline attenuate the antibody response to a subsequent intraperitoneal injection of antigen.

The results of two experiments with male C3H/HeJ mice indicated that repeated intraperitoneal (ip) injections of sterile saline over a 2-week period resulted in an attenuated antibody response to the subsequent ip injection of a soluble protein antigen, keyhole limpet hemocyanin. There were no differences among experimental groups that received a different number of preimmunization injections of saline, and comparable effects were obtained simply by the daily handling of mice. Neither repeated ip injections nor handling altered preimmunization (baseline) corticosterone levels, and only previously unmanipulated mice showed an elevation in corticosterone levels 30 min after ip immunization. These latter results suggest that the depressed IgM and IgG responses were not due to the immunosuppressive effects of endogenously elevated adrenocortical steroids.

Animals↗
PubMed1989

Voluntary consumption of cyclophosphamide by Mrl mice.

Fluid-deprived, lupus-prone Mrl-lpr/lpr and congenic Mrl +/+ mice were provided with a single drinking bottle containing varying concentrations of cyclophosphamide (CY) dissolved in chocolate milk. Eighteen- and 20-week-old Mrl-lpr/lpr males with manifest symptoms of autoimmune disease voluntarily consumed more of the CY solution than Mrl +/+ mice of the same age after 1 week of 1 hr/day exposures. The volume of CY-laced chocolate milk consumed was sufficient to attenuate lymphadenopathy and the elevated anti-DNA antibody titers in these animals. When testing began before the development of manifest symptoms of autoimmune disease, there were no differences between the two substrains. These results are consistent with the hypothesis that behavioral processes can act to correct homeostatic imbalances within the immune system.

Animals↗