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Biomedical subjects

J A Powell

Publications and source records attributed to J A Powell.

At least 73 records · Page 4Linked to original sources
PubMed1976

Specific blastogenesis and lymphokine production in DNCB-sensitive human leucocyte cultures stimulated with soluble and particulate DNP-containing antigens.

A soluble hapten (dinitrobenzene sulphonic acid (DNBSO3)) and particulate antigens consisting of DNCB, DNFB or DNBSO3 complexed with erythrocytes, all induce a specific blastogenic response and lymphokine production in leucocyte cultures from human subjects topically sensitized to dinitrochlorobenzene (DNCB). While low concentrations (50-100 mug/ml) of DNBSO3 could be left in human leucocyte cultures the entire 4 or 5 days of culture and result in reasonable levels of blastogenesis, it was found that consistently higher degrees of blast transformation resulted when DNCB-sensitive leucocytes were exposed to high concentrations of DNBSO3 (500 mug/ml) for a short period (2 hr). Cell-free supernatants from DNCB-sensitive leucocyte cultures harvested after 48 hr induced blastogenesis and DNA synthesis in secondary target leucocyte cultures from subjects not sensitized to DNCB. Such a blastogenic factor or lymphokine appeared to stimulate even in the absence of any residual antigen, since DNCB complexed to erythrocytes was removed by simple filtration through a 0-45 mum Millipore filter. In contrast to DNCB complexes, the antigenic activity of DNBSO3 complexed with erythrocytes was not removed by such filtration. Thus, several DNP-containing haptens (DNCB, DNFB, DNBSO3) induce specific lymphocyte transformation and lymphokine production when exposed in several different manners to leucocytes from humans sensitized to DNCB. The ability to use either a particulate or soluble stimulant in vitro offers a versatile system for studying cell-mediated immunity in humans with a broad range of potential applicability in both investigate and clinical medicine.

Antigens↗
PubMed1975

Studies on the contact sensitization of man with simple chemicals. III. Quantitative relationships between specific lymphocyte transformation, skin sensitivity, and lymphokine activity in response to dinitrochlorobenzene.

Dinitrochlorobenzene (DNCB) coupled to peripheral blood erythrocytes or leukocytes forms a particulate complex, DNCB-antigen. The addition of DNCB-antigen induced blastogenesis and DNA synthesis in leukocyte cultures from DNCB-sensitized human subjects and not in leukocyte cultures from nonsensitized controls. In general, sensitized subjects who displayed a higher degree of cutaneous reactivity to DNCB, as manifested by duration and intensity of dermatitis, also showed a greater blastogenic response to DNCB-antigen in vitro. This quantitative correlation, however, was not invariant. Certain soluble factor(s), or lymphokines are released following the addition of DNCB-antigen to leukocyte cultures prepared from some sensitive subjects who were rechallenged one or more times with DNCB. These lymphokines induce blastogenesis in secondary target leukocyte populations from nonsensitized subjects. Extended studies are presented which slow little or no lymphokine activity in peripheral blood leukocyte cultures during a primary immune response, despite high degrees of blastogenic activity in response to DNCB-antigen. Significant lymphokine activity was observed only following additional rechallenge with DNCB. Blastogenesis and skin reactivity specific for DNCB have been shown to develop at about the same time during a primary immune response. This, along with the quantitative correlation shown in this communication, suggests that both processes probably reflect thymic-dependent cellular immunity. The appearance of lymphokine activity following rechallenge with DNCB suggests that DNCB-induced lymphokines may represent an amplifying mechanism of the cellular immune response that involves recruitment of previously uncommitted lymphocytes.

Antigens↗
PubMed1975

Papaverine: its effects on cyclic AMP in vitro and psoriasis in vivo.

Psoriatic epidermis shows excessive cell proliferation, incomplete morphogenesis, and glycogen accumulation. These three features may result from coordinate misregulation by the previously reported abnormal lesional ratio of cyclic AMP/cyclic GMP. If so, it is possible that psoriasis might improve by topical application of an agent known to alter cellular levels of cyclic nucleotides. In the present study papaverine (3.0 x 10-4 m) produced a 210percent increase (.02 smaller than p smaller than .05) in epidermal cyclic AMP levels in vitro. Therefore, 1 percent papaverine cream (approximately 2.7 x 10-2m papaverine) was chosen to establish whether a cyclic AMP elevating agent could improve a soriatic lesion. A double-blind comparison of 1 percent papaverine cream versus cream alone was conducted on matched lesions in 45 patients. Of those patients showing differential improvement (i.e., only one lesion of the pair improved), 81 percent (p=0.011) of those showing a response in the center of the lesion and 77 percent (p=0.046) of those improving at the edge had applied papaverine. Although no attempts were made to develop a papaverine formulation with immediate therapeutic utility, the numerically significant papaverine results suggest future therapeutic developments.

Animals↗
PubMed1975

Studies on the contact sensitization of man with simple chemicals. IV. Timing of skin reactivity, lymphokine production, and blastogenesis following rechallenge with dinitrochlorobenzene using an automated microassay.

An automated microassay was adapted to the sutdy of specific in vitro lymphocyte transformation to dinitrochlorobenzene (DNCB) erythrocyte complexes (DNCB-antigen). Studies of culture conditions indicated that in flat-bottomed microtiter culture plates, 0.2ml culturese containing 4x105 leukocytes and a total culture time of 4 or 5 days yeild satisfactory results for the relatively low responses seen with specific antigens such as DNCB-antigen. Culture were incubated for 3 hr with tritiated thymidine and harvested with the Multipe Automated Sample Harvester(MASH II). The effect of DNCB rechallenge on in vitro lymphocte transformation was stuided using this automated microassay. DNCB rechallenge boosted the in vitro response to DNON 25 TO 31 MM Hg; four patients (hypercapnic, group II) at a co2 from 54 to57 mm Hg. AH 8165 0.25 mg/kg (one quarter of the dose required for intubation) was given by rapid central venous injection. Haemodynamic responses were similar in the two groups; these were increase in heart rate ranging from 45 to 60 percent, increases in mean arterial pressure of 17-20 pre cent, and increases in cardiac output of 22-32 per cent. The intensity of neuromusclar blockade of the forearm muscles after AH 8165 was similar in the two groups, and there was no significant difference in recovery rates; roup I patients were 80 per cent recovered in 36.6 min, group II patinets in 47.3 min. It was concluded that the activity of AH 8165 was not influenced by moderate changes in respiratory acid-base status.

Antigens↗
PubMedDate not supplied

Neurons induce contractions in myotubes containing only muscular dysgenic nuclei.

Muscular dysgenic (mdg/mdg) myotubes cultured alone do not contract. Glucosephosphate isomerase (GPI-1) isozymes were analyzed to determine the final genotype of cultured dysgenic (mdg/mdg, gpi-1a/a) myotubes to which normal embryonic spinal cord and limb cells (CBA/J +/+, gpi-1b/b) had been added. Although both myoblast and spinal cord cell additions caused induction of spontaneous contractions, only myoblasts fused with the myotubes to create functional heterokaryons. Spinal cord cells did not fuse with dysgenic myotubes, but formed functional synapses.

Animals↗
PubMedDate not supplied

Molecular characterisation of a Rhodococcus ohp operon.

The ohp operon of Rhodococcus strain V49 consists of five genes, ohpR, ohpA, ohpB, ohpC and ohpD which encode putative regulator and transport proteins and confirmed monooxygenase, hydroxymuconic semialdehyde hydrolase and catechol 2,3-dioxygenase enzymes, respectively. These enzymes catalyse the conversion of 3-(2-hydroxyphenyl)propionic acid to the corresponding linear product via a meta-cleavage pathway. Confirmation that the ohp gene cluster formed an operon was provided by gene disruption during which expression of Bacillus levansucrase was confirmed in Rhodococcus. Following biochemical assays of cell-free extracts from recombinant Escherichia coli expressing ohpB (monooxygenase), ohpC (hydroxymuconic-semialdehyde hydrolase) and ohpD (catechol 2,3-dioxygenase), the ortho-hydroxyphenylpropionic acid catabolic pathway in Rhodococcus strain V49 (ATCC 19070) has been predicted.

Catechol 2,3-Dioxygenase↗