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Biomedical subjects

C Cunningham

Publications and source records attributed to C Cunningham.

At least 55 records · Page 3Linked to original sources
PubMed1988

The alloantibody response to semiallogeneic pregnancy in the rat. I. Alloantibodies in sera and placental eluates directed to RT1A antigens.

Maternal alloantibodies to paternal cells were monitored by cellular ELISA, the indirect hemagglutination and erythrocyte antibody rosette inhibition assays in sera and placental eluates from primigravid and multigravid inbred rats. In primigravid animals, antibodies in sera were routinely detected only by the indirect hemagglutination assay and were of low titer; weak antibody activity was detectable only by indirect hemagglutination in 1 of the 8 placental eluates assayed from these animals. Alloantibodies in high titer were present in sera and placental eluates from multigravid rats and were found to be directed predominantly to the RT1A (class I MHC) antigens of the paternal strain. These data provide no support for the hypothesis that the difficulty in detecting maternal antibodies during a 1st pregnancy is due to their preferential binding to antigenic determinants expressed on the placenta.

Animals↗
PubMed1988

The alloantibody response to semiallogeneic pregnancy in the rat. II. Antibodies in serum directed to multiple epitopes on conventional RT1A antigens.

Evidence for a unique class I MHC antigen (termed Pa), which is believed to be expressed on rat trophoblast during pregnancy and which stimulates alloantibody formation with unusual interstrain cross-reactivity, has been examined in inbred rats. The previously reported pattern of crossreactivity was confirmed but was not unique to antisera produced by pregnancy. Antibody blocking studies using biotinylated rat monoclonal antibodies to distinct epitopes on RT1Aa antigens suggested that antibodies present in pregnancy sera, especially from multiparous rats, reacted with several epitopes on these molecules. Moreover, a rat monoclonal antibody, 381- 1E10, directed against the putative Pa epitope was shown by synergistic lysis and cold antibody competition to be directed to the immunodominant S epitope on RT1Aa. These data argue against the existence of a distinct Pa antigen or epitope detected by pregnancy sera.

Animals↗
PubMed1988

Alloantibody and transferable suppressor activity induced by cyclosporine and blood transfusions in the rat.

The effect of cyclosporine on the alloantibody response to blood transfusion was investigated in inbred strains of rats by IHA and CELISA; recipient animals differed from the donors at the class I (RT1A) or both class I and class II (RT1B) antigens of the major histocompatibility complex. Alloantibody titers stimulated in high responder PVGu/c animals by blood transfusions were attenuated by cyclosporine; this effect was not demonstrated in low responder PVGc rats, as alloantibody titers decreased after further blood transfusions whether or not cyclosporine was given. Cyclosporine not only reduced the initial IgM response but suppressed the subsequent production of IgG. Splenocytes from rats receiving cyclosporine and blood transfusions from donors that differed from the recipients at the class I antigen were effective in suppressing the subsequent antibody response to blood transfusion. When blood transfusions from donors which differed from the recipients at both class I and class II antigenic loci were given after splenocyte transfer, a greater degree of immunosuppression was detected than if the transfusion donor differed only at the class I locus. These data suggest that the sensitization produced by blood transfusions and the persistence or decline of the alloantibody response depend upon the responder status of the recipient. Blood transfusions given with cyclosporine are capable of inducing suppressor activity that is transferable in spleen homogenates. Subsequent alloantibody responses are influenced by the class I and class II disparities of the donor and recipient animals. If these results can be extrapolated to clinical practice, cyclosporine should be given with pretransplant blood transfusions to prevent sensitization, and the transfusion donor should differ from the recipient at both class I and class II antigenic loci.

Animals↗
PubMed1988

Human placenta--an antibody sponge?

Maternal IgG antibodies in sera and placenta eluates were studied by a cellular enzyme-linked immunosorbent assay (CELISA) method. Antibodies were not detectable in any of the serum samples obtained before or after delivery from nine normal primigravid women. Antibody activity was, however, present in five of nine placental eluates and two of nine neonatal sera tested in CELISA. Lymphocytotoxic antibodies were not detected in any of the samples tested. These results support the concept that the absence of antibody activity in maternal sera may be caused by the immunosorbent effect of the placenta.

Birth Weight↗
PubMed1988

Unexplained hypotension in Hodgkin's disease.

A 51-year-old black male with progressive polymyositis presented to our hospital with respiratory failure. Hemodynamic monitoring revealed tachycardia, arterial hypotension, a high cardiac index, and low systemic vascular resistance. Evaluation for common etiologies of this hemodynamic pattern was unrewarding. He was found to have Hodgkin's disease of the bone marrow. Aggressive combination chemotherapy led to normalization of heart rate and arterial pressure. It is postulated that Hodgkin's disease through some undetermined mechanism can cause a hyperdynamic circulatory pattern. This hemodynamic state reversed with suppression of the tumor.

Blood Circulation↗
PubMed1988

Antiidiotypic activity in sera from sensitised potential transplant recipients.

Antiidiotypic activity was determined in non-cytotoxic sera from highly sensitised dialysis patients who previously possessed broad-spectrum lymphocytotoxic antibodies. At least four non-cytotoxic sera from six transfused patients were tested in the short antiidiotypic antibody assay against lymphocytes known to be lysed by cytotoxic sera from the same patient. Of 87 sera/cell combinations studied, antiidiotypic activity was detected in 42 (48%). Antiidiotypic activity was present in IgG fractions and F(ab')2 fragments of two active sera. These results indicate that non-cytotoxic sera from patients who were once highly sensitised possess antiidiotypic activity. Fluctuating levels of lymphocytotoxic antibodies frequently encountered in sera from dialysis patients may be explained at least in part by the development of antiidiotypic antibodies.

Adolescent↗
PubMed1988

The influence of cyclosporin A on alloantibody responses in inbred rats: provisional evidence for a serum factor with antiidiotypic activity.

The effect of cyclosporin A (CsA) on alloantibody synthesis has been investigated in inbred F344 (RTl1v1) rats receiving weekly transfusions of DA (RT1a) rat whole blood. Whereas repeated transfusion resulted in a persistent alloantibody response (Group I) administration of CsA (15 mg/kg/day) from either days 0-7 (Group II), days 8-49 (Group III) or days 15-49 (Group IV) resulted in the eventual suppression of alloantibody responses before the end of the experiment on day 49. Antiidiotypic activity was detected in sera obtained on day 49 from animals in Groups II, III and IV, shown to reside in the serum fraction of apparent molecular mass of between 150 and 170 kD and to be specific for alloantisera raised in F344 and the closely related LEW (RTl1) rats but not the unrelated AO (RTlu) strain. These experiments suggest that the immunosuppressive action of CsA may, in part, be due to the development of anti-idiotypic activity whose nature remains to be more fully characterized.

Animals↗
PubMed1987

Viral RNAs synthesized in cells infected with Germiston Bunyavirus.

A rapidly growing strain of Germiston virus was used to study intracellular viral RNA synthesis in BHK cells. The RNAs were separated by electrophoresis into seven bands which fell into three size classes: large (bands L1 and L2), medium (bands M1 and M2), and small (bands S1, S2, and S3). Blot hybridisation established that bands L1, M1, and S1 contained the negative-sense genomic RNAs, while bands L2, M2, S2, and S3 contained positive-sense RNAs complementary to the genomic RNAs within the same size class. After glyoxal treatment the RNAs separated into a large, a medium, and two small bands, indicating that the positive-sense RNAs originally present in bands L2, M2, and S2 are similar in size to their genomic RNAs, while the RNA in S3 is shorter than the small genomic segment. These results suggest that band S2 contains the replicative intermediate RNA and band S3 the messenger RNA of the small genomic segment and also that bands L2 and M2 contain both replicative intermediate and messenger RNAs. Long after virus development had ceased in the infected cells the amounts of RNAs in bands L1, M1, S1, and S2 remained the same, those in bands L2 and M2 were reduced, while only trace amounts of RNAs were observed in band S3, suggesting that the genomic RNAs and the replicative intermediate RNAs form ribonuclease-resistant ribonucleoprotein complexes while the messenger RNAs do not form such complexes. Synthesis of RNA in the infected cells was first evident in bands S3 and M2, after which synthesis was soon observed in all seven bands reaching a maximum rate at the logarithmic phase of growth, suggesting that the pattern of Germiston virus development resembles that of other negative-strand RNA viruses. The presence of defective-interfering particles was indicated by the observation that purified virus preparations contained a minor RNA component originating from the large RNA segment.

Animals↗
PubMed1987

Maternal alloantibody responses during early pregnancy detected by a cellular enzyme-linked immunospecific assay.

Using a cellular enzyme-linked immunospecific assay (CELISA), we have examined sera from nulliparous women and women in the first trimester of a first or subsequent pregnancy for the presence of antibodies directed to surface determinants on peripheral blood lymphocytes from unrelated donors. Maternal antibody activity was found in sera from 1/13 nulliparae, 19/37 primigravidae, and 8/12 multigravidae. Cytotoxic antibody activity was present in 3/12 multigravidae but in no other group. Absorption with packed, pooled platelets did not remove the antibody activity from three of the primigravid sera; unabsorbed sera, however, bound equally well to T and B lymphocytes. These data suggest that the antibody detected by CELISA is not directed to any of the classical HLA antigen series (-A, -B, -C, or -DR) but may be directed to the HLA linked non-class I HT antigen system.

Antigens, Surface↗
PubMed1987

The role of RT1 antigen differences in semi-allogeneic rat pregnancy.

The immunological mechanisms involved in sustaining normal semi-allogeneic pregnancies and in the enhancement of organ allografts were investigated in inbred rats. The antigenic targets for alloantibodies formed after leucocyte transfusions and multiple allogeneic pregnancies were defined by the EA rosette inhibition (EAI) assay in several congenic and recombinant inbred rat strains. Alloantibodies produced by leucocyte immunization (conventionally induced antisera) were directed only to RT1-encoded (major histocompatibility complex, MHC) antigens. Both RT1A (class I MHC) and either RT1B, D (class II MHC) or RT1C (Qa-like) antigens were targets for these alloantibodies; responses to the latter three antigens could not be separated with available congenic recombinant inbred rat strains. Alloantibodies produced as a consequence of multiple semi-allogeneic pregnancies (pregnancy-induced antisera) were directed only to RT1A antigens. Allogeneic pregnancies in which the paternal strain differed from the maternal strain only at the RT1A gene locus produced suppression of a subsequent maternal immune response.

Animals↗
PubMed1986

The effect of cyclosporine on humoral and cellular alloreactivity to allogeneic pregnancy in rats.

We have evaluated the effect of a therapeutic dose (10 mg/kg/day) of the immunosuppressant cyclosporine (CsA) on humoral and cell-mediated immunity in rats during an allogeneic first pregnancy. Virgin female Lewis rats mated with DA males and treated with CsA vehicle produced a humoral response, as measured by both the erythrocyte rosette inhibition (EAI) and indirect hemagglutination assays. The capacity of Lewis splenocytes to mediate a graft-versus-host (GVH) reaction in six-week old F1 (Lewis X DA) hybrid rats was unaffected by either pregnancy or CsA. In mothers treated with CsA, however, no antibody production was detected, and a significant reduction in GVH reactivity was observed using their cells. This reduction was specific for the paternal strain. When compared with vehicle-treated primiparas, suppression of the immune response by CsA had no effect on either the number or viability of fetuses present in utero at day 20. These data suggest that antipaternal antibodies may not be essential to protect the fetus when there is concomitant suppression of the capacity of the mother's T cells to express a cell-mediated antipaternal response.

Animals↗
PubMed1986

Micro-scale ultracentrifugation as an alternative to ultrafiltration for the determination of the unbound fraction of phenytoin in human serum.

Free phenytoin has been determined using micro-scale ultracentrifugation followed by analysis by EMIT. The effect of temperature on the determined free fraction was investigated and the ultracentrifugation procedure validated against ultrafiltration. Ultracentrifugation gave free fractions which were on average 16% lower than those obtained using ultrafiltration, but correlation was good, as was the correlation with measurements of total phenytoin (r = 0.90). Micro-scale ultracentrifugation is a simple procedure which can be of great utility in the measurement and investigation of free drug levels.

Blood Proteins↗
PubMed1985

Amelioration of cyclosporin-induced nephrotoxicity in rats by induction of hepatic drug metabolism.

The aim of this study was to determine the effect of altered hepatic drug metabolism on the nephrotoxic and immunosuppressive properties of cyclosporin A (CsA) in the rat. From a consideration of the structures of those CsA metabolites identified so far, it seemed probable that the metabolism of CsA would occur at the hepatic cytochrome P-450 (cyt P-450) enzyme system. CsA (50 mg/kg/24 hr) administered orally for 14 days resulted in significant increases in both serum urea concentration and urinary N-acetyl-beta-D-glucosaminidase activity, accompanied by renal proximal tubular vacuolation. The concomitant administration of either Aroclor 1254 (25 mg/kg/24 hr, i.p.) or phenobarbitone (PB) (40 mg/kg/24 hr, i.p.) but not 3-methylcholanthrene (3-MC) (15 mg/kg/72 hr, i.p.) resulted in abolition of the nephrotoxicity, assessed both biochemically and histologically, whilst the suppressive effect on the humoral response to SRBC was unaltered. Phenobarbitone also significantly decreased serum CsA concentrations. These results suggest that the PB-inducible set of cyt P-450 isoenzymes may be responsible or partly responsible for hepatic CsA metabolism.

Animals↗
PubMed1985

Isolation and point of action of a factor from Escherichia coli required to reconstruct translation.

To study the mechanism of translation we have attempted to reconstruct the process from purified components. Protein synthesis was programmed by the RNAs of wild-type or amber mutants of bacteriophages f2 or MS2. Translation programmed by MS2 or f2am3 RNA does not occur using ribosomes, precharged aminoacyl-tRNAs, and the sum of the purified proteins involved in initiation (initiation factors; IF-1, IF-2, and IF-3), propagation (elongation factors; EF-Tu, EF-Ts, and EF-G) and termination (release factors; RF-1 or RF-2) of protein synthesis. The requirement for a protein called W was demonstrated. Protein W was purified free of all translation factors, activating enzymes, and other proteins such as the RR, "rescue," and EF-P implicated in translation. The stimulation of propagation by W depended on the position of the amino acid residue to be added in the synthesis of the NH2-terminal hexapeptide of the coat protein. In the reconstructed system, with the sum of all translation factors but in the absence of W, only dipeptides and smaller quantities of tripeptides were synthesized under the direction of f2am3 RNA. W stimulated the synthesis of the hexapeptide, fMet-Ala-Ser-AspNH2-Phe-Thr directed by this RNA. In addition, W stimulated ejection of non-cognate tRNAs that bind to ribosomal particles.

Bacterial Proteins↗