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Biomedical subjects

C C Anderson

Publications and source records attributed to C C Anderson.

At least 37 records · Page 2Linked to original sources
PubMed1994

Polycythaemia associated with homozygosity for the abnormal haemoglobin Sherwood Forest (beta 104 (G6)Arg-->Thr).

We describe a 22-year-old Pakistani male with polycythaemia associated with homozygosity for a high-affinity haemoglobin mutant, Hb Sherwood Forest. This haemoglobin variant has an amino acid substitution in the beta globin chain at position 104, Arg-->Thr. In the two previously reported instances of this haemoglobin mutant the individuals were heterozygotes and were haematologically normal. We show here that the homozygous state for the mutation is associated with a compensatory erythrocytosis resulting from decreased delivery of oxygen to the tissues. A family study showed that both parents and two siblings are heterozygotes for the haemoglobin mutant and are haematologically normal. To our knowledge, this represents the first example of a beta-globin mutation producing polycythaemia in homozygotes but not in heterozygotes.

Adult↗
PubMed1993

Immunoregulatory characteristics of the in vitro anti-ssDNA response.

Continuous blockade of B-cell antigen receptors (BCRs) with Fab alpha sIg prevents the anti-ssDNA response of high, but not low, density B cells. Signaling via the BCRs, by prior exposure to crosslinking F(ab')2 alpha sIg, had no effect on the spontaneous anti-DNA response, but prevented a lipopolysaccharide-induced anti-DNA response. Pretreatment with intact alpha sIg, which provides exogenously derived Fc signals, reduced the response. An Fc-signal-blocking agent, F(ab')2 anti-IgG-Fc antibody, increased the number of anti-DNA antibody-forming cells produced in the absence of exogenous IgG anti-ssDNA antibody. Thus, activation is dependent on the availability of the BCRs, prior BCR crosslinking does not interfere with activation, and endogenous IgG anti-ssDNA antibody limits the activation of anti-ssDNA-specific B cells most of which are T-cell independent. These results indicate that the anti-ssDNA response is driven through the BCR.

Animals↗
PubMed1993

A protein with anion exchange properties found in the kidney proximal tubule.

One important mechanism for reabsorption of chloride in the kidney proximal tubule involves anion exchange of chloride for a base. Anion exchange transport systems in general demonstrate sensitivity to inhibition by disulfonic stilbenes, probenecid, furosemide, and the arginyl amino group modifier phenylglyoxal. Using disulfonic stilbene affinity chromatography, we have identified and partially purified a protein with anion exchanger properties in luminal membrane vesicles isolated from rabbit kidney cortex. This protein has a molecular weight of 162 kD. The binding of the 162 kD protein to the stilbene affinity matrix is inhibited by disulfonic stilbenes, probenecid, furosemide, and phenylglyoxal. Reconstitution of the proteins eluted from the affinity matrix into liposomes demonstrates anion exchange activity as assayed by radiolabeled chloride influx. Deletion of the 162 kD protein from the eluted mixture by probenecid diminishes the anion exchanger activity in the reconstituted liposomes. Further purification of the disulfonic stilbene column eluant by Econo-Pac Q ion exchange chromatography resulted in significant enrichment in 162 kD protein abundance and also anion exchange activity in reconstituted liposomes. The results of the above experiments strongly suggest that the 162 kD protein is an anion exchanger. Insight into the functional and molecular characteristics of this protein should provide important information about the mechanism(s) of chloride reabsorption in the kidney proximal tubule.

Animals↗
PubMed1993

Blockade of immunoregulatory Fc-signalling by HIV peptides: oligopeptides from HIV gp120 and gp41 bind the Fc portion of IgG and increase the in vitro anti-ssDNA response.

Concomitant ligation of antigen receptors with Fc-receptors negatively signals B cells. Antibodies to the Fc portion of IgG prevent this negative Fc-signalling, provided that these antibodies do not emit Fc signals. Prevention of Fc signals leads to augmented antibody responses to self and foreign antigens, and reduces the requirement for T cells by 10- to 100-fold in T cell-dependent antibody responses. In ELISA assays, peptides from conserved portions of the glycoproteins, HIV-1 gp120 or gp41 from HIV-1 and HIV-2 bind to the Fc portion of IgG, but do not bind the F(ab')2 portion of IgG. HIV-derived peptides, which bind to the Fc portion of IgG, augment the antibody-forming cell response to single-stranded (ss)DNA. The spontaneous response to ssDNA using spleen cells from young mice, and the response in the presence of exogenous DNA using spleen cells from old mice, are augmented to the greatest extent. These results demonstrate that HIV peptides bind to the Fc portion of IgG and augment immune responses to DNA; they suggest the possibility that blockade of the Fc portion of IgG antibodies is associated with a reduction in Fc-mediated regulation of anti-self responses. Blockade of regulatory Fc-signalling may account for increased circulating immunoglobulins and autoantibodies in clinical AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Mutual antagonism between antigen- and lipopolysaccharide-induced antibody production.

B cells are induced to antibody production by antigens or by mitogens, such as lipopolysaccharide (LPS). We observed a mutually antagonistic relationship between activation through the antigen-receptor (AgR) and LPS-receptor (LPSR) in vitro. Prior exposure of B cells to AgR-ligating antibody prevented antibody forming cell (AFC) production induced by LPS, but not that induced by specific antigen (SRBC, TNP-Ficoll, or TNP-LPS). AFC production induced by antigen could be abrogated by concomitant exposure to LPS; the shutdown of the antigen-driven response was apparent when LPS-induced AFC were prevented by pre-exposure to antibody against the AgR. The ability of signaling through the AgR to inhibit antibody production stimulated by LPS was seen in DBA/2 and BALB/c mouse strains, and not in the New Zealand Black (NZB) strain. The results suggest that mutual antagonism is distinct from other forms of immune hyporesponsiveness, and that defects in antagonism may be a factor in the development of autoimmune disease.

Animals↗
PubMed1992

Regulation of an anti-self response: lack of influence of exogenous DNA on the in vitro anti-DNA response.

Anti-DNA antibodies occur in outwardly normal individuals as well as in various forms of autoimmune disease. A number of publications have reported on the ability of added DNA to either induce or inhibit the in vitro production of anti-DNA antibody. In this study, the in vitro production of IgM anti-single stranded DNA (alpha ssDNA) antibody by spleen cells from normal or autoimmune mice neither depends upon, nor is inhibited by, the addition of high molecular weight DNA to the culture. The decrease in antibody forming cell plaques, reported previously, is due solely to the artifactual carryover of inhibitory material into the assay system, where it interferes with the expression of plaques by preventing anti-DNA antibody from reaching the DNA-coated erythrocytes. Similarly, plaque forming cell (PFC) methods have not detected alpha ssDNA antibody producing cells in murine spleen cells without culturing, but various other systems for measuring antibody normally detect anti-DNA antibodies in vivo. This discrepancy is also due to inadequate washing of freshly harvested cells to rid them of inhibitory substances which prevent them from registering as PFC. While S1 nuclease was able to prevent PFC interference by purified DNA, it did not remove the inhibitory substances from the culture supernatants; therefore substances other than ssDNA are able to interfere with alpha ssDNA PFC, suggesting that the alpha ssDNA PFC detected are polyspecific. Levels of alpha ssDNA PFC in spleen cells from non-autoimmune mice begin at one-quarter of the peak in vitro response, decrease to one-tenth in the first day and then reach peak values after 3 to 5 days of culture, suggesting that spleen cells are actively producing alpha ssDNA antibodies an in vivo and that then in vitro response is observed. Despite this evidence for an in vitro alpha ssDNA response, this response was not inhibited markedly by 1000 rad gamma-irradiation, while the response to sheep erythrocytes (SRBC) was profoundly suppressed. These findings suggest that anti-self B lymphocytes are resistant to interphase, possibly apoptotic, lymphocyte death due to gamma-irradiation, while anti-nonself B lymphocytes remain sensitive.

Animals↗
PubMed1991

Low incidence of non-A, non-B post-transfusion hepatitis in London confirmed by hepatitis C virus serology.

To see whether the introduction of screening tests for post-transfusion non-A, non-B hepatitis (NANBH) in the UK would be worth while, the incidence of such hepatitis was assessed among patients receiving blood during operations at five hospitals served by the North London Blood Transfusion Centre. 387 patients, who each received blood or blood components from an average of 3 donors were followed up prospectively and blood samples were taken every 2 weeks for 3 months and then each month for a further 3 months. 229 patients also provided a sample at 12 months. All available patient and donor samples were tested for alanine aminotransferase concentrations and for antibody to hepatitis C virus (anti-HCV) by ELISA. Repeatedly anti-HCV positive samples were submitted to supplementary HCV assays. 1 of the 387 patients showed biochemical evidence of acute post-transfusion NANBH after exclusion of non-viral causes. Anti-HCV developed in this patient and the seroconversion was confirmed by recombinant immunoblot assay and polymerase chain reaction. Serum from 1 of the 8 donors whose blood he received was positive for anti-HCV by all three methods. In another patient HCV seroconversion was shown by ELISA but alanine aminotransferase concentrations remained normal throughout follow-up. His samples and those of his 2 donors were negative for HCV by the polymerase chain reaction. A third patient showed rises in alanine aminotransferase compatible with post-transfusion NANBH, but serology and polymerase chain reaction assays for HCV were negative for her samples and those of her donors. Anti-HCV reactivity likely to be false positive (negative by both confirmatory tests and no adverse effects in recipients) was seen in 6 of 1283 donors. This study, despite its being carried out in the part of the UK with the highest frequency of infectious markers in blood donations, has shown a very low incidence of post-transfusion NANBH.

Acute Disease↗
PubMed1991

Primary thrombocythaemia in pregnancy.

Nine pregnancies in six patients with primary thrombocythaemia are reported. Eight pregnancies resulted in the delivery of normal infants. One pregnancy ended in spontaneous abortion at 7 weeks gestation. One pregnancy was complicated by superficial thrombophlebitis and a postpartum haemorrhage. We suggest that pregnancy in patients with primary thrombocythaemia can have a favourable outcome, but requires close monitoring. Administration of aspirin during pregnancy may be of benefit.

Abortion, Incomplete↗
PubMed1991

[3H]SCH 39166, a new D1-selective radioligand: in vitro and in vivo binding analyses.

SCH 39166 [(-)-trans-6,7,7a,8,9, 13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo-[d]naphtho[2, 1b]azepine] has recently been described as a selective D1 antagonist and has entered clinical trials for the treatment of schizophrenia. The tritiated analogue of this compound, [3H]SCH 39166, has now been synthesized and characterized for its in vitro and in vivo binding profiles. [3H]SCH 39166 binds to D1 receptors in a saturable, high-affinity fashion, with a KD of 0.79 nM. In competition studies, D1-selective antagonists like SCH 23390 displaced the binding of [3H]SCH 39166 with nanomolar affinities, whereas antagonists of other receptors exhibited poor affinity. In vivo, [3H]SCH 39166 bound to receptors in rat striatum in a fashion suggestive of D1 selectivity. Further, when the time course for the binding of [3H]SCH 39166 was compared with the behavioral time course of the unlabeled compound, the two durations of action were virtually indistinguishable. Similar studies were performed for SCH 23390 and its tritiated analogue, but the in vivo binding of this radioligand exhibited a duration of action far greater than the behavioral activity of the unlabeled drug. In concert, these data demonstrate that [3H]SCH 39166 selectively labels D1 receptors in vitro and in vivo, and that this drug is superior for in vivo imaging of the D1 receptor.

Animals↗
PubMed1988

A sampling and analytical method for airborne m-phenylenediamine (MPDA) and 4,4'-methylenedianiline (MDA).

A method has been developed and validated for monitoring worker exposure to airborne m-phenylenediamine (MPDA) and 4,4'-methylenedianiline (MDA) in an epoxy resin manufacturing operation. Aerosol and vapor MPDA and MDA are collected on an acid-coated, glass-fiber filter to stabilize them as their amine salts. The amines are extracted from the filter with a mixture of acetonitrile in aqueous base and then treated with acetic anhydride to form the diacetamide derivatives. Studies were performed on the acetylation reaction to establish sample work-up conditions. The derivatives are analyzed by high performance liquid chromatography with UV detection. The method was tested for precision and accuracy using the National Institute for Occupational Safety and Health (NIOSH) criteria for a valid industrial hygiene method. The method may be used with confidence to measure from 0.90 to 755 micrograms of MPDA and/or 0.36 to 55 micrograms of MDA in a total air volume of 200 to 630 L, sampling at a rate of 1.5 to 2.0 L/min. Collected samples remain stable on filters for at least 1 week before analysis. The method will not suffer from interference from high relative humidity or other process volatiles, including diglycidyl ether of bisphenyl A and bis(2,3-epoxycyclopentyl) ether. Test atmospheres of the process materials were prepared in the laboratory for validation of the overall sampling and analytical method. This method can be applied to most aromatic amines and is recommended for monitoring both ambient and workplace air.

Acetylation↗
PubMed1987

Autologous bone marrow transplantation for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia--a comparison.

Forty-two patients with acute leukaemia were treated with autologous bone marrow transplantation (ABMT) using a combination chemotherapy protocol for bone marrow ablation. The response to high-dose chemotherapy and ABMT and its associated morbidity and mortality have been compared in 24 patients with acute myeloid leukaemia (AML) and 18 patients with acute lymphoblastic leukaemia (ALL). In 16 patients with AML treated with ABMT during first complete remission (CR), ten patients (62.5%) remain in unmaintained remission; median follow up is 32 months. In eight patients with ALL treated in first CR, only one remains in remission 32 months post-ABMT, with three patients dying non-leukaemic deaths. Fourteen of 18 patients (AML and ALL) treated after first remission have died of recurrent leukaemia, two died non-leukaemic deaths and two remain well 31 and 55 months post-ABMT; both have ALL. The length of hospital stay and the amount of blood product support were similar in both groups. Haematological recovery post-ABMT was delayed in patients with AML compared to patients with ALL but this difference was not significant. Rapidly progressive lung infection was thought to be the cause of four early deaths (4/18) in patients with ALL but none in patients with AML. Severe gram-negative infections were significantly more common in patients with AML.

Adolescent↗
PubMed1986

Very high dose chemotherapy with autologous bone marrow rescue in adult patients with resistant relapsed lymphoma.

Seventeen patients with advanced lymphoma were treated with high-dose chemotherapy with autologous bone marrow rescue. In 11 patients with non-Hodgkin's lymphoma (NHL) there were 2 complete remissions (CRs) and 2 partial remissions (PRs), and in 6 patients with Hodgkin's disease there were 5 CRs. Three patients remain well in unmaintained remission (days 874, 446 and 351), and a further 2 are alive and still receiving treatment (days 650 and 558). This type of therapy appears useful and should now be considered earlier in the course of the disease.

Adult↗
PubMed1986

Autologous bone marrow transplantation following high dose chemotherapy for the treatment of adult patients with acute myeloid leukaemia.

24 adult patients with acute myeloid leukaemia (AML) were treated with intensive chemotherapy followed by autologous marrow rescue. The procedure was repeated twice in eight patients. 11 of 16 patients treated in first remission continue in first unmaintained remission (9-54 months, median 17 months). Eight patients treated at relapse or second remission have relapsed again and died within 14 months of their first autologous bone marrow transplant (ABMT). This form of intensification therapy would appear valuable for adult AML patients in first remission.

Adult↗
PubMed1986

A rise in the percentage of large unstained cells in the peripheral blood determined by the Hemalog D90 automated differential counter is a feature of impending myeloid engraftment following bone marrow transplantation.

The early phase of bone marrow regeneration has been monitored by automated differential counts on the peripheral blood using a Hemalog D90, following 107 transplant procedures. An elevated percentage of large unstained cells (LUCs) was detected in over 98% of cases and in 72% of cases the rise in percentage LUCs preceded the rise of the total leucocyte count into the detectable range on a Coulter counter (greater than 0.3 X 10(9)/1) by an average of 4 days. These LUCs are shown to be CD8 + T lymphocytes. The ability to detect the earliest signs of regeneration is particularly useful when regeneration is delayed and repeat marrow infusion is considered.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1979

The treatment of pulmonary edema in the absence of renal function. A role for sorbitol and furosemide.

In doses sufficient to induce a rapid osmotic loss of fluid from the bowel, sorbitol can provide an alternate method of removing fluid in patients who lack renal function. Two patients with acute pulmonary edema and oliguric renal failure were treated with a combined therapy of sorbitol and furosemide. Their clinical, hemodynamic, and metabolic responses were strikingly similar to those achieved with furosemide therapy alone in patients with normal renal function.

Acute Kidney Injury↗
PubMed1978

Cardiovascular effects of Azadirachta indica extract.

A crude extract of the leaves of Azadirachta indica was studied for its effects on the cardiovascular system of anesthetized guinea pigs and rabbits. These effects include profound hypotension and a minimal negative chronotropic effect, which increased at higher doses. In one rabbit, 200 mg of extract/kg decreased the heart rate from 280 to 150 beats/min. The extract also exhibited a weak antiarrhythmic activity in rabbits against ouabain-induced dysrhythmia.

Animals↗