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Biomedical subjects

R Carter

Publications and source records attributed to R Carter.

At least 253 records · Page 14Linked to original sources
PubMed1989

Longitudinal course of extrinsic allergic alveolitis in pigeon breeders.

The purpose of this study was to assess the longitudinal course of pigeon breeders' disease by evaluating 24 patients with the acute form of the disease 10 years after their original diagnosis. Twenty one patients attended for clinical assessment, pulmonary function studies, chest radiography, and antibody measurement. Eighteen had continued to keep pigeons, emphasising their commitment to the hobby. Despite continued antigen exposure pigeon related symptoms had improved in most patients and only five still had troublesome symptoms. Four patients had residual abnormalities of pulmonary function or chest radiographs and three had chronic bronchitis. Fanciers had attempted to regulate their exposure to the birds by use of masks and by spending less time in their lofts but this is an unlikely explanation for the benign course of their disease, as levels of antibody to pigeon gammaglobulin remained high, suggesting that appreciable antigen exposure was still occurring. In most cases a state of equilibrium between host and antigen appeared to have developed. This observation has implications for the clinical management and understanding of the nature of the disease.

Adult↗
PubMed1989

Demand oxygen delivery for patients with restrictive lung disease.

The demand oxygen delivery system has been reported to improve oxygen delivery 7:1 vs steady flow during rest and exercise in COPD patients. The present study evaluates the DODS during rest and exercise in eight patients with restrictive lung disease. It was concluded that the DODS provides substantial oxygen savings in RLD patients, particularly during exercise.

Exercise↗
PubMed1989

Quantitative study of radioiodinated metaiodobenzylguanidine uptake in children with neuroblastoma: correlation with tumor histopathology.

Six children with neuroblastoma and one with ganglioneuroma received [125I] metaiodobenzylguanidine (MIBG) before major surgery. Uptake of [125I]MIBG in the excised tissues was measured by scintillation counting, and the material was submitted for histopathology. The ranges of uptake of [125I]MIBG, expressed as percent of the injected dose per gram of tissue, were as follows: for neuroblastoma 0.0013-0.071, for ganglioneuroma 0.0017-0.0028, and for non-neoplastic control tissues 0.0002-0.011. The quantitative uptake of [125I]MIBG by neuroblastoma varied between different patients and between different parts of individual tumors. The more undifferentiated tumors took up more [125I]MIBG and may be more likely to respond to targeted radiotherapy with MIBG.

3-Iodobenzylguanidine↗
PubMed1988

Limited immunological recognition of critical malaria vaccine candidate antigens.

Current vaccine development strategies for malaria depend on widespread immunological responsiveness to candidate antigens such as the zygote surface antigens and the sporozoite coat protein, the circumsporozoite (CS) protein. Since immunological responsiveness is controlled mainly by genes mapping within the major histocompatibility complex (MHC), the humoral immune response to the zygote surface antigens and the cytotoxic T lymphocyte (CTL) response to the CS protein were examined in MHC-disparate congenic mouse strains. Only two of six strains responded to the 230-kilodalton zygote surface antigen and another two strains responded to the 48/45-kilodalton surface antigen. From two mouse strains, expressing between them five different class I MHC molecules, there was recognition of only a single CTL epitope from the CS protein, which was from a polymorphic segment of the molecule. The restricted CTL response to this protein parallels the restricted antibody response to this protein observed in humans and mice. These findings suggest that subunit malaria vaccines now being developed may be ineffective.

Animals↗
PubMed1988

Function of neutral endopeptidase on the cell membrane of human neutrophils.

Intact human neutrophils hydrolyzed N-formyl-Met-Leu-[3H]Phe (fMLP) and released Leu-[3H]Phe, cleaving 45-50% of the peptide within 20 min at 37 degrees C. The dipeptide after its release was then hydrolyzed to free amino acids by a dipeptidase (EC 3.4.13.11). This activity, present in plasma membrane-enriched fractions of neutrophil lysates, was also inhibited over 90% by phosphoramidon, an inhibitor of neutral endopeptidase (NEP, EC 3.4.24.11). Dithiothreitol and EDTA inhibited the activity to a comparable degree, suggesting the requirement for a heavy metal cofactor. Bestatin and amastatin, inhibitors of aminopeptidases (but not human kidney NEP), did not inhibit the rate of fMLP degradation but prevented the production of free phenylalanine and enhanced the accumulation of Leu-Phe. Of other inhibitors, alpha 1-antitrypsin and alpha 2-macroglobulin slightly enhanced the rate of fMLP hydrolysis by neutrophils, and others tested were ineffective. Rabbit antiserum to homogeneous human kidney NEP reacted specifically with a 100-kDa protein present in sodium dodecyl sulfate-solubilized neutrophils. The Mr of this protein was slightly larger than that of the kidney enzyme in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The antiserum incubated with intact cells specifically inhibited the degradation of fMLP over 70%. First, we confirm that NEP present on the plasma membrane cleaves fMLP at the Met-Leu bond; then the dipeptide Leu-Phe is cleaved by a dipeptidase. Finally, inhibition of NEP completely blocks fMLP-mediated chemotaxis. Thus, the enzyme may play an important role in modulating chemotactic responses.

Anti-Bacterial Agents↗
PubMed1988

Bronchial hyperreactivity in patients who cough after receiving angiotensin converting enzyme inhibitors.

Angiotensin converting enzyme inhibitors cause cough in some patients, but the mechanism of this effect is not known. Six patients in whom these inhibitors had caused cough and a further two patients in whom they were suspected to have caused worsening of bronchial asthma were studied. Nine patients in whom angiotensin converting enzyme inhibitors had not been associated with cough served as controls. In the controls lung function and bronchial reactivity were measured once; for the study patients these and the cough index were measured twice before rechallenge for two weeks with an angiotensin enzyme inhibitor and once afterwards. Rechallenge with drug for two weeks caused a significant decrease in the mean concentration of histamine causing a 35% fall in airways conductance and a significant increase in the cough index. Patients with cough showed bronchial hyperactivity compared with the controls, which increased after rechallenge with the inhibitors. Cough associated with converting enzyme inhibitors may be a variant of the cough in asthma.

Adult↗
PubMed1988

Allelic forms of gp195, a major blood-stage antigen of Plasmodium falciparum, are expressed in liver stages.

Mature exoerythrocytic (EE) forms of two cloned lines (3D7 and HB3) of Plasmodium falciparum were obtained in the livers of splenectomized chimpanzees. Sectioned preparations were examined by immunofluorescence (IFA) using mAbs that distinguished allelic variants of the blood-form antigen gp195 and mAbs that recognized multiple conserved epitopes of gp195. EE forms and blood schizonts exhibited identical IFA reactions for each respective clone, showing that the antigen was expressed identically in liver and blood-stage parasites. A third chimpanzee was infected with sporozoites derived from a mixture of 3D7 and HB3 gametocytes that had undergone cross-fertilization in the mosquitoes. IFAs on the EE forms in this animal showed that segregation of each gp195 allele had occurred earlier in the life cycle, providing evidence that the parasite is haploid for the whole of its mammalian development.

Alleles↗
PubMed1988

Treatment of infantile phytanic acid storage disease: clinical, biochemical and ultrastructural findings in two children treated for 2 years.

Two patients with infantile phytanic acid storage disease (infantile Refsum disease), one of whom showed the presence of morphologically normal peroxisomes in a liver biopsy, were treated with a low phytanic acid diet for more than 2 years and the effects of treatment on certain clinical, biochemical and ultrastructural parameters were examined. Both patients showed evidence of either an improvement or stabilisation in their clinical condition. Plasma phytanic acid levels decreased to near normal values in approximately 6 weeks after the introduction of the diet; plasma pipecolic acid also declined markedly but the decrease was not so rapid and its level remained abnormal. C26:C22 fatty acid ratios decreased very slowly and even after 2 years the values remained grossly abnormal. Despite the marked reduction of phytanic acid in the liver, there was an increase in the C26:C22 fatty acid ratios and this appeared to be paralleled by an increase in inclusion bodies. Our data suggest that some patients with the infantile form of Refsum disease may show some clinical benefit from dietary management and this is reflected biochemically by decreases in the plasma levels of phytanic acid and pipecolic acid.

Eicosanoic Acids↗
PubMed1988

Meta-analysis of the effects of educational and psychosocial interventions on management of diabetes mellitus.

A meta-analysis of the literature of controlled studies of educational and psychosocial interventions in the treatment of diabetes mellitus yielded 93 studies of 7451 patients testing the effects of eight intervention types: (1) didactic education, (2) enhanced education, (3) diet instruction, (4) exercise instruction, (5) self-monitoring instruction, (6) social learning/behavior modification, (7) counseling, and (8) relaxation training. An overall mean effect size (ES) of +0.51 +/- 0.11 was found moderate but significant (P less than 0.05) improvements for all intervention subjects. Physical outcome and knowledge gain were most affected, followed by psychological status and compliance. Diet instruction and social learning interventions showed the strongest (ES = +0.68 +/- 0.58 and ES = +0.57 +/- 0.42, respectively) and relaxation training the weakest (ES = +0.30 +/- 0.74) effects. Associations between study and sample characteristics and mean ES values were explored with type of setting and methodological weaknesses such as single group design and non-random assignment achieving statistical significance. Neither intervention type, number of visits, sex, age, nor type of diabetes were significantly correlated with mean ES values. Implications of these findings for clinical treatment and future research are discussed.

Diabetes Mellitus↗
PubMed1988

Measurement of malarial infectivity of human populations to mosquitoes in the Madang area, Papua, New Guinea.

The proportion of blood meals taken on humans which are infectious to mosquitoes in the Madang area, Papua New Guinea was estimated by two methods. In the first, laboratory reared Anopheles farauti were fed on individuals of all ages at village surveys. The results showed that 3.8% of people were infectious and that the mean percentage of mosquitoes which became infected by feeding on these people was 37.9%. From the average proportion of mosquitoes infected, the probability that a mosquito feeding on a human would pick up infection was 0.013 +/- 0.005. In the second approach mosquitoes were fed on identified Plasmodium falciparum, P. vivax and P. malariae gametocyte carriers. The results indicated that 46% of gametocyte carriers were infectious and that the mean probability of a mosquito becoming infected after feeding on a gametocyte carrier was 0.151 +/- 0.029. Gametocyte prevalence rates in all ages measured over 18 months in three villages averaged 3.3% P. falciparum, 4.0% P. vivax and 0.7% P. malariae, totalling 8.0 +/- 0.7%. Combining gametocyte prevalence rates with the probability of a mosquito becoming infected from a gametocyte carrier, the probability of a mosquito becoming infected following a blood meal on a member of the human population was estimated to be 0.012 +/- 0.003.

Age Factors↗
PubMed1988

Plasmodium falciparum gene encoding a protein similar to the 78-kDa rat glucose-regulated stress protein.

Genes homologous to heat shock protein 70 have been described in parasitic protozoa. It has been proposed that they may be important to the parasite as it moves from the vertebrate host at 37 degrees C to the insect. We now describe a genomic DNA clone isolated from Plasmodium falciparum that encodes a protein similar in sequence to a mammalian heat shock-related protein, the 78-kDa glucose-regulated protein of rat and hamster. The gene is expressed during the erythrocytic stage in both asexual and sexual parasites (RNA blot analysis) and a 72-kDa protein is immunoprecipitated from erythrocytic stage parasites. Importantly, the sequence of the clone is similar to the canonical sequence at the carboxyl termini of glucose-regulated proteins of mammals that determines their localization within endoplasmic reticulum. Since the parasite sequence has only three (Asp-Glu-Leu) of the four carboxyl-terminal amino acids, its location and its function within the parasite remain to be determined.

Amino Acid Sequence↗
PubMed1988

Adverse effect of cyclosporin on plasma cholesterol in renal transplant recipients.

A prospective study of changes in plasma lipids after renal transplantation was performed in order to compare the effects of cyclosporin and conventional immunosuppression. Twenty-eight patients were studied, 18 of whom were allocated randomly to immunosuppression with either cyclosporin alone (nine subjects) or azathioprine and prednisolone (nine subjects). A further ten patients received cyclosporin and prednisolone. Total cholesterol, triglycerides and HDL, LDL and VLDL cholesterol subfractions were measured before transplantation, 21 and 90 days after transplantation, and also, in 12 patients (six on cyclosporin and prednisolone, and six on azathioprine and prednisolone), 2 years after transplantation. Triglycerides were initially elevated, and decreased after transplantation in all three groups. Total cholesterol was unchanged in the azathioprine and prednisolone group, whereas it increased significantly by 90 days in both the cyclosporin group and the cyclosporin and prednisolone group. This was due primarily to LDL cholesterol, which increased by 45% in the cyclosporin group and 28% in the cyclosporin and prednisolone group. Both total and LDL cholesterol remained elevated 2 years after transplantation in patients receiving cyclosporin and prednisolone, but were unchanged in the azathioprine and prednisolone group. There was no relationship between renal function and plasma lipid changes.

Adult↗
PubMed1988

Antibodies to Plasmodium falciparum gamete surface antigens in Papua New Guinea sera.

Sera from individuals living in malaria endemic areas of Papua New Guinea were tested for their effect on infectivity of Plasmodium falciparum gametocytes grown in culture to Anopheles freeborni mosquitoes. Consistent reduction of infectivity to less than 5% of control was observed with nine out of the 41 sera from the endemic area tested and also with three out of seven sera tested from individuals rarely exposed to malaria infection. Gamete surface antigens recognized by the sera were investigated by immunoprecipitation from 125I surface-labelled gametes extracted in SDS and Triton X-100. The main antigens recognized were of the same mol. wt (230, 48 and 45 kD) as those known to be targets of transmission-blocking monoclonal antibodies. A significant negative correlation was observed between the total ct/min immunoprecipitated from surface-labelled gametes by the sera and the average number of oocysts per gut observed in membrane feeding experiments with these sera. Spearmann's rank correlation coefficient indicated that suppression of infectivity correlated strongly with the presence of antibodies against the 230 kD protein; there was no significant correlation between suppression and antibodies to the 48/45 kD proteins. The antibody response to the different gamete surface antigens varied greatly in sera from the endemic areas suggesting that individuals respond differently to each gamete antigen.

Animals↗
PubMed1988

Naturally occurring antibodies to an epitope on Plasmodium falciparum gametes detected by monoclonal antibody-based competitive enzyme-linked immunosorbent assay.

The antibody response to an epitope on gamete antigens of Plasmodium falciparum in persons naturally exposed to malaria has been investigated by competitive enzyme-linked immunosorbent assay. The assay detects antibodies to an epitope on the 48/45-kilodalton (kDa) gamete surface antigen by competition with horseradish peroxidase-labeled monoclonal antibody IIC5-B10. Five sera previously shown to immunoprecipitate the 230- and 48/45-kDa antigens significantly inhibited IIC5-B10 binding to an average of 24.2% of control. The one serum which precipitated only the 48/45-kDa antigen did not inhibit IIC5-B10 binding. For 26 sera which were negative by immunoprecipitation, mean binding in the assay was 112.7% of control (pooled London nonimmune sera). Recognition of both 230-kDa and 48/45-kDa antigens was associated with a titer of 1:9 or greater (reciprocal geometric mean titer, 27.6) for inhibition to more than 2 standard deviations from the mean of the negative sera. The results show that the IIC5-B10 binding site is a naturally immunogenic epitope recognized by the majority of persons who had antibodies to the 48/45-kDa protein. An additional finding was enhancement of binding of IIC5-B10 to an average of 154.4% of control by five sera which recognized only the 230-kDa antigen, presumably due to conformational alteration of the gamete antigen complex.

Animals↗
PubMed1988

Boosting of transmission-blocking immunity during natural Plasmodium vivax infections in humans depends upon frequent reinfection.

The infectivity to mosquitoes of 31 acute Plasmodium vivax patients was measured by permitting mosquitoes to feed directly on the patients. The infectivity of these patients correlated closely with titers of antibodies in their serum as measured by indirect immunofluorescence against air-dried female gametes of P. vivax. Infectivity by direct feeding was also closely parallel to the transmission-blocking activity of the sera of patients as measured by the suppression of infectivity of parasitized blood by autologous serum relative to normal (nonmalarial) human serum when fed to mosquitoes through a membrane. These results are consistent with serum antibodies in human P. vivax infections as major factors determining the infectivity of an infected individual to mosquitoes. It was further noted that individuals having a second attack of P. vivax within less than 4 months were considerably less infectious to mosquitoes than first-attack patients were. This "boosting" of transmission-blocking immunity was much less if longer intervals intervened between attacks. We discuss the immunological implications and possible epidemiological significance of this short-term boosting of transmission-blocking immunity by successive P. vivax infections.

Acute Disease↗
PubMed1988

Abnormal haemostasis in small cell lung cancer.

Disorders of haemostasis and altered platelet activity have been documented in patients with malignant disease but their relation to response to treatment and prognosis are not known. Thrombin activity (fibrinopeptide A (FpA), plasmin mediated fibrinolysis (B beta 15-42) antigen), and platelet alpha granule release (beta thromboglobulin) were studied in 37 patients with small cell lung cancer to find out whether these indices show a relationship to chemoresponse. There was evidence of considerably increased thrombin activity, with a median fibrinopeptide A concentration of 13.2 (normal less than 4) pmol/ml, but only modestly increased fibrinolysis, with a median B beta 14-42 antigen concentration of 5.6 (normal less than 3) pmol/ml. Thus the ratio of fibrinopeptide A to B beta 15-42 concentration (FpA:B beta) was raised, with a median value of 2.2 (normal less than 1.33). In addition, 57% of patients had increased platelet alpha granule release, the median beta thromboglobulin concentration being 50 (normal less than 50) ng/ml. There was a significant association between increased thrombin generation and lack of response to chemotherapy. Furthermore, non-responders had higher FpA:B beta ratios. The same haemostatic markers were studied in nine patients who have been in complete remission for at least two years after chemotherapy for small cell lung cancer. There was a significant difference in thrombin activity and also in the ratio of thrombin activity to lysis between the pretreatment group and the group of two year survivors. Lack of response to chemotherapy appears to be related to increased thrombin activity. Such an association has not previously been reported in patients with malignant disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Monoclonal and polyclonal antibodies both block and enhance transmission of human Plasmodium vivax malaria.

Antibodies against gametes of the malarial parasite inhibit the development of the parasite in the mosquito and curtail the transmission of malaria. We now report that a monoclonal antibody against gametes of the human malaria pathogen Plasmodium vivax and antibodies induced during natural infections of P. vivax in humans which suppress infectivity of the parasites to the vector at high concentrations can, at lower concentrations, have the opposite effect and enhance the level of malaria infection in the mosquitoes. Infectivity enhancing effects of up to 12-fold were demonstrated when a transmission blocking monoclonal antibody and immune human sera were diluted, in some undiluted immune human sera, and in the sera of vivax malaria patients during convalescence after drug cure.

Animals↗