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Biomedical subjects

D Parker

Publications and source records attributed to D Parker.

At least 271 records · Page 15Linked to original sources
PubMed1982

Effect of cyclophosphamide on immunological control mechanisms.

Cyclophosphamide (CY) given before immunization causes greatly increased delayed hypersensitivity skin reactions. Increased cell-mediated immunity is associated with depletion of B-lymphocytes from lymphoid tissue and a depression of those lymphocytes whose precursors turn over more rapidly. In the guinea pig, replacement studies showed that the depleted cells were not T-lymphocytes and had immunoglobulin adherent to their surface, a characteristic of B-lymphocytes. Delayed hypersensitivity reactions increased by CY include chemical contact sensitivity, the tuberculin reaction, delayed hypersensitivity to tularemia vaccine and the Jones-Mote reaction to soluble protein antigens. Pretreatment with CY can also increase the antibody response to some antigens, but depress the response to others. In addition, CY has been found to reverse immunological tolerance where this form of unresponsiveness is due to suppressor cells. CY can also enhance the immune response following depression by antigenic competition or desensitization. Other drugs with a similar, but lesser, effect include melphalan, azathioprine and methotrexate.

Animals↗
PubMed1982

Kinetics of the relation between suppressor and effector mechanisms in contact sensitivity in the guinea-pig.

Cyclophosphamide (300 mg/kg) given before or up to 2 days after sensitization, induces increased contact skin reactions at 8 days. Reactions were suppressed with cyclophosphamide (CY) given between 3 and 5 days after sensitization; reactivity returned on day 10. CY, given on days 6 to 8, only suppressed reactions when skin tests were made 4 days later. This temporary depression of contact sensitivity corresponds with the maximal reduction of peripheral blood lymphocytes. CY given 1-2 days after DNFB produced decreased T-cell proliferation in local lymph nodes 4 days after sensitization. CY given 3 days after DNFB produced maximal T-cell suppression on 5 day nodes. Massive increase in T-cell proliferation in 5 day nodes occurred when CY was given on the day of sensitization or the day before. Thus CY given around sensitization acts mainly on suppressor cells whereas given later, the action is principally on the effector functions.

Animals↗
PubMed1982

In vivo macrophage suppression of delayed hypersensitivity in the guinea-pig.

The nature of the suppressive activity in the peritoneal exudate cells (PEC) of guinea-pigs immunized with dinitrophenyl bovine gamma globulin (DNP50-BGG) was investigated. A method was developed to isolate from the peritoneal exudate large numbers of macrophages. Using density gradient centrifugation on Percoll it was possible to obtain a population of cells which contained over 90% macrophages. This macrophage preparation was found to respond to lymphokine but to be incapable of passively transferring delayed hypersensitivity reactions. When these immune macrophages were transferred into antigen immunized animals, which had been pretreated with cyclophosphamide (CY), the skin reactions were suppressed to the same extent as when the total PEC was transferred. PEC from guinea-pigs immunized with ovalbumin in Freund's incomplete adjuvant did not suppress the skin reactions in CY-pretreated DNP50BGG immunized animals. However, in contrast, macrophages from these animals did suppress the skin reactions in the recipient guinea-pigs indicating that the macrophage suppression was not antigen specific.

Animals↗
PubMed1981

Heterogeneity of guinea-pig caseins synthesized and sequestered by cell-free protein-synthesizing systems.

1. Individual mRNA species encoding guinea-pigs caseins A, B and C, and alpha-lactalbumin, were purified by hydridization to recombinant milk-protein plasmid DNA immobilized on diazobenzyloxymethyl-paper or diazobenzyloxymethyl-cellulose. Addition of the purified mRNA species to a reticulocyte-lysate cell-free system, in the presence or absence of a dog pancreas microsomal membrane fraction, established a precursor-product relationship between the primary translation products and those sequestered within microsomal vesicles, as determined by polyacrylamide-gel analysis in one and two dimensions. 2. Three sequestered variants of sequestered casein A were identified, but only single forms of sequestered casein B and alpha-lactalbumin. Sequestered variants of casein C proved to be unexpectedly basic, and did not focus on the pH gradient utilized. 3. Comparative analysis of milk proteins synthesized in the reticulocyte-lysate and wheat-germ cell-free systems by two-dimensional gel electrophoresis demonstrated both quantitative and qualitative differences. In particular, marked but variable heterogeneity was apparent within the primary translation products of casein A and casein B. Pre-casein C did not focus. Limited N-terminal processing of the primary translation products was also evident. These observations are discussed in relation to (i) unscheduled post-translational modifications by cell-free protein-synthesizing systems and (ii) multiplicity of signal sequences. 4. Overall we demonstrate that complex precursor-product relationships between primary translation products and their sequestered variants, programmed in vitro by a mixed mRNA population, may be readily analysed by using individual mRNA sequences purified by hybridization to immobilized cloned complementary-DNA sequences.

Animals↗
PubMed1981

The construction, identification and partial characterization of plasmids containing guinea-pig milk protein complementary DNA sequences.

A complementary DNA (cDNA) plasmid library has been constructed in the plasmid pAT153, using poly(A)-containing RNA isolated from the lactating guinea-pig mammary gland as the starting material. Double stranded cDNA was inserted into the EcoRI site of the plasmid using poly(dA . dT) tails, then transformed into Escherichia coli HB101. From the resulting colonies we have selected and partially characterized plasmids containing cDNA copies of the mRNAs for casein A, casein B, casein C and alpha-lactalbumin. However, the proportion containing casein C cDNA was exceptionally low, and these contained at best 60% of the mRNA sequence.

Animals↗
PubMed1981

Differential expression of alpha-lactalbumin and casein genes during the onset of lactation in the guinea-pig mammary gland.

1. The expression of alpha-lactalbumin and casein genes was examined in guinea-pig mammary tissue taken from animals both pre- and post-partum. 2. Analysis of total RNA by RNA excess hybridization with sequence-specific complementary DNA probes demonstrated that alpha-lactalbumin mRNA was present late in pregnancy, and that maximum concentrations were present at parturition. Casein gene transcripts were absent late in pregnancy (62 days), but by parturition were present at concentrations identical to those found at all time points examined throughout lactation. 3. Studies using mammary explants in organ culture showed that tissue from pregnant animals, or animals at parturition, synthesized and secreted only alpha-lactalbumin. After parturition, at the onset of casein synthesis, differential rates of secretion of alpha-lactalbumin and the caseins were observed. 4. The results are discussed in terms of the multiple intracellular mechanisms involved in the regulation of milk protein gene expression in the guinea-pig mammary gland.

Animals↗
PubMed1981

Effects of lithium carbonate on methylphenidate-induced mood, behavior, and cognitive processes.

Evidence is presented which suggests that lithium modifies the mood and behavioral alterations resulting from IV methylphenidate. Specifically, lithium significantly reduces the level of arousal-activation, euphoria-grandiosity, and the total score of manic-state ratings following a methylphenidate challenge. In addition, lithium appears to be capable of modifying the growth hormone response to methylphenidate.

Adult↗
PubMed1981

The effect of photochemotherapy (PUVA) on cell mediated immunity in the guinea pig.

Guinea pigs were injected intraperitoneally with 8-methoxypsoralen (8-MOP) and afterwards the shaved right flank was irradiated with UV-A. This treatment was performed daily for 14 days. Seven days after treatment started they were immunized with ovalbumin in Freund's complete adjuvant and 7 days later skin tested with ovalbumin on the unirradiated left flank. Photochemotherapy (8-MOP plus UV-A) did not alter the total white blood cells or the proportion of lymphocytes or granulocytes. However, this treatment significantly depressed the delayed hypersensitivity reaction to ovalbumin; nonspecific inflammation, induced by intradermal turpentine, was not altered. In addition, treatment with 8-MOP alone suppressed the skin reaction to ovalbumin, but not to the same extent as treatment with 8-MOP and UV-A. 8-MOP plus UV-A had no effect on macrophage migration inhibition factor but it did significantly depress mitogen and antigen specific lymphocyte transformation.

Animals↗
PubMed1981

The effect of cyclophosphamide and role suppressor cells in the desensitization of delayed hypersensitivity.

Desensitization of guinea-pigs with ovalbumin (OA) or bovine gamma globulin (BGG) induces strong specific desensitization and is associated with a non-specific energy to tuberculin--PPD. Similarly, it was found that animals receiving desensitizing injections of PPD have suppressed delayed hypersensitivity reactions to OA or BGG. PPD also induced strong specific desensitization. Cyclophosphamide (CY) given in one large dose (300 mg/kg) 3 days before immunization failed to affect the specific desensitization induced by all three antigens. However, if CY was given 1 day after immunization, it was not possible to induce specific desensitization. The induction of non-specific desensitization was prevented in all three antigen systems if CY was given either 3 days before or 1 day after immunization. Desensitization with either OA or BGG markedly suppressed the specific 4 hr Arthus reactions.

Animals↗
PubMed1981

Suppression of delayed hypersensitivity to tuberculin by antigenic competition. A positive immunoregulatory mechanism sensitive to cyclophosphamide.

Effector mechanisms that produce delayed hypersensitivity reactions to tuberculin are subject to positive immunoregulation. Two different immunoregulatory mechanisms can be demonstrated. One is specific and the other, antigenic competition, is non-specific; both are sensitive to cyclophosphamide (CY). Delayed hypersensitivity to purified protein derivative PPD in guinea-pigs can be enhanced by the administration of cyclophosphamide 3 days before but not after immunization. The enhanced response seems to result from the reduced influence on effector cells of CY-sensitive suppressor cells. Passive transfer of delayed hypersensitivity to PPD is facilitated by the use of cells from CY treated animals. The response to both immunization and skin testing with ovalbumin in animals immunized with this antigen in Freud's complete adjuvant (FCA) produces a marked, non-specific reduction in the delayed hypersensitivity response to PPD. CY given 3 days before or 1 day after immunization prevents this suppression of the PPD response by antigenic competition. The data suggests that in the generation of both the specific suppressor cells for tuberculin and the non-specific suppressor cells of antigenic competition, that can influence effector cells for tuberculin, a period of rapid cell proliferation occurs that renders both mechanisms sensitive to cyclophosphamide.

Animals↗
PubMed1980

Transcutaneous estimation of arterial PO2 and PCO2 in newborn infants with a single electrochemical sensor.

A transcutaneous electrochemical sensor designed to estimate arterial oxygen (PaO2) and carbon dioxide (PaCO2) tensions simultaneously and continuously was evaluated in newborn infants with respiratory illnesses. After calibration of the sensor against a sample of arterial blood from the infant, the accuracy of estimation of PaO2 and PaCO2 seemed sufficient for clinical purposes.

Arteries↗
PubMed1980

Liver damage in children with acute leukaemia and non-Hodgkin's lymphoma on oral maintenance chemotherapy.

Eight of 36 children receiving maintenance chemotherapy for acute lymphoblastic leukaemia or non-Hodgkin's lymphoma had liver biopsies on the basis of clinical abnormalities and/or elevated serum enzyme levels. Six biopsies were abnormal, including one in a boy with spider naevi who showed micronudular cirrhosis; he appeared to retain methotrexate in the blood for a prolonged period and his SGOT level did not return to normal for 19 months after maintenance chemotherapy was discontinued. The five other abnormal biopsies showed minor changes in the portal tracts. The six children with abnormal liver histology showed a wide variation in their early handling of an oral methotrexate dose. There was a statistically significant rise in mean SGOT and alkaline phosphatase during treatment, but the wide scatter in values precluded their use as accurate indicators of liver damage in these children.

Adolescent↗