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Biomedical subjects

D Parker

Publications and source records attributed to D Parker.

At least 253 records · Page 14Linked to original sources
PubMed1984

Kinetics of the effect of a single dose of cyclosporin-A on antibody and cell mediated immune responses in the guinea pig.

The effect of 100 mg/kg cyclosporin-A (CS-A), given as a single dose either before or after immunization, on antibody levels and skin test reactivity was investigated. CS-A was found to suppress both primary and secondary anti-hapten and anti-carrier IgG1 and IgG2 antibodies. However, CS-A was also capable of inducing enhanced anti-hapten antibodies. CS-A showed a similar effect on contact sensitivity reactions to 2,4-dinitrofluorobenzene (DNFB) as has been shown for cyclophosphamide (CY) in that, given before sensitization, skin reactions were enhanced, whereas given after sensitization they were suppressed. However, the effect of CS-A on the T-cell proliferation in the lymph node, draining the site of sensitization to DNFB, differed from that of CY. Although CS-A induced a depression of T-cell proliferation, this suppression was more prolonged than that found in CY treated animals. Also, these draining lymph nodes never showed increased T-cell proliferation as did those in animals treated with CY before sensitization. This work demonstrates that a single dose of CS-A can both suppress or enhance antibody production and delayed hypersensitivity. The timing of the dose of CS-A in relation to the time of primary immunization is important. However, both IgG1 and IgG2 primary and secondary antibody responses can be altered. Comparison with the effect of CY on antibody levels and contact sensitivity would indicate that in some ways CS-A reacts similarly to antimitotic agents and in other ways is different.

Animals↗
PubMed1984

Comparison of DNFB and K2Cr2O7 'flare-up' reactions in the guinea pig.

A comparison has been made of the 'flare-up' of 2,4-dinitrofluorobenzene (DNFB) contact reactions with that of 'flare-up' of potassium dichromate (K2Cr2O7) contact sensitivity reactions following the intravenous injection of dinitrobenzenesulphonic acid (DNBSO3) or K2Cr2O7. Differences in time course were noted and these were confirmed by increase in vascular permeability and histological appearance. Failure to influence the reactions with indomethacin would appear to exclude the participation of an Arthus-type phenomenon, despite evidence of a drop in the circulating antibody levels. Increased numbers of basophils were found particularly in the DNFB/DNBSO3 reaction during its resolution. These reactions could therefore be broadly included among the cutaneous basophil hypersensitivities.

Animals↗
PubMed1984

The effect of cyclophosphamide on immunological control mechanisms.

Cyclophosphamide (CY) given three days before immunization with a range of antigens increases the intensity of cell-mediated immune responses. CY given around the time of immunization also reverses immunological tolerance, blocks antigenic competition and modifies desensitization. The effect on antibody production is not so predictable. However, it may increase the IgE response without affecting IgG1 or IgG2 response to the same antigen and may abolish immunological memory. The action of CY is on rapidly-turning-over cell populations. Lymphocytes are maximally at risk 48 hours before they transform into large pyroninophilic cells, that is just before the S phase of cell division. CY has a preferential effect on both T- and B- suppressor cells. The application of these findings to experimental cancer models is discussed. These findings are not restricted to CY, as a wide range of cytotoxic drugs with different actions at the cellular level may have similar profound effects on the regulation of the immune response.

Animals↗
PubMed1983

Central nervous system metastases of choriocarcinoma. 23 years' experience at Charing Cross Hospital.

Between 1957 and February 1981, 782 patients received cytotoxic chemotherapy for gestational trophoblastic tumors (GTT) in the Department of Medical Oncology, Charing Cross Hospital (London, England). Sixty-nine (8.8%) patients had central nervous system (CNS) metastases. Thirty-three of them (48%) presented with CNS disease prior to treatment (CNS presentation group), and 36 (52%) developed CNS disease while on treatment, or relapsed in the CNS after an initial complete or partial remission (late CNS group). Treatment included systemic and intrathecal chemotherapy, and, in several cases neurosurgery, whole brain irradiation, and immunotherapy. Life-table analysis projects an overall survival of 49% for the CNS presentation group and 6% for the late CNS group. Prognosis has improved with time; prior to 1974, 38% of the CNS presentation group and none of the late CNS group survived. After 1974 overall survival has been 80% in the CNS presentation group and 25% in the late CNS group. The principal elements in the successful management of such cases are: (1) CNS prophylaxis with intrathecal methotrexate for patients at risk of developing brain metastases; (2) early detection of CNS lesions by prompt recognition of their clinical features, measurement of the ratio of CSF to serum human chorionic gonadotropin concentration, and appropriate use of computerized tomography of the brain; and (3) a combination of systemic and intrathecal therapy for patients developing brain secondaries.

Adult↗
PubMed1983

Further advances in the management of malignant teratomas of the testis and other sites.

Between 1979 and 1982, 69 men with metastatic malignant teratoma completed sequential combination chemotherapy (POMB/ACE). Although two-thirds of these patients initially had advanced and bulky disease, life-table analysis projects a survival of 83%. Multivariate analysis indicates that the strongest predictor of survivals is not the clinical and radiological extent of disease but the initial serum concentration of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP). In patients presenting with HCG levels below 50 000 IU/l and AFP levels below 500 kU/l the survival in 47 patients was 96%. This contrasts with the survival projected at 56% in 22 patients presenting with tumour markers at higher concentrations.

Antineoplastic Agents↗
PubMed1983

Distribution of disulfiram in brain after carotid ligation in gerbils.

Aiming whether intraperitoneal administration of disulfiram (tetraethyl thiuram disulfide, DS) achieves potentially therapeutic drug concentrations in brain tissue, the behaviour of blood-brain barrier (BBB) to 14C-labelled DS in cerebral ischemia with and without simultaneous administration of dimethylsulfoxide (DMSO) was studied in Mongolian gerbils subjected to left common carotid artery (CCA) occlusion. The results indicated that: (a) the permeability of DS through the BBB was significantly enhanced in the ischemic brain during the initial 30 min duration after DS administration; (b) administration of DMSO increased the entry of DS into the ischemic brain five-fold during the first 30 min and it was significantly higher even at the 60 min sampling period; (3) in general, the content of DS in the brain was quickly reduced with time.

Animals↗
PubMed1983

The effect of cyclophosphamide on immunological memory.

The intradermal injection of bovine gammaglobulin (BGG) anti-BGG immune complexes, in antibody excess, in Freund's complete adjuvant, induced strong delayed hypersensitivity and a state of priming which was recognized by an antihapten and anticarrier humoral immune response following injection of DNP9-BGG nine days later. Cyclophosphamide (CY), given either as small multiple doses over the first seven days after sensitization, or as a single dose on various days, had a strongly selective effect on the antihapten and anticarrier response. The drug treatment, using multiple doses, suppressed the development of a priming for the antihapten IgG2, but not for IgG1 production. Pretreatment with a large dose of CY (250 mg/kg) led only to an enhanced production of anti-DNP IgG2 and not of IgG1 antibodies. This suggests that CY inhibits the suppressor cells regulating the IgG2, but not the IgG1, antibody response. CY, given on day +3 but not on days 0 and +7 impaired both the IgG1 and the IgG2 response. Anticarrier-specific IgG1 could not be detected and the IgG2 was completely suppressed by the drug, given either as multiple doses or as a single large dose administered on days 0, +3 or +7. The selective influence of CY given about the time of the initial immunization suggests that the IgG1 and IgG2 responses involve memory cells with different susceptibilities to CY. Moreover, these memory cells appear to have a different susceptibility to CY as compared with that of the effector cells involved in delayed hypersensitivity.

Animals↗
PubMed1983

The effect of a single dose of cyclophosphamide on the kinetics of antibody production in the guinea pig.

Cyclophosphamide (CY) 250 mg/kg was given before, at the same time or after immunization with dinitrophenylated bovine gammaglobulin (DNP47-BGG) in Freund's incomplete adjuvant (FIA). CY, given on day +3 or +7 strongly suppressed both IgG subclasses. CY, on the day of immunization, reduced the IgG2 but not IgG1 anti-DNP antibody synthesis. Carrier BGG, injected 42 days after initial immunization, caused a secondary anti-hapten IgG1 response. This was not altered by CY treatment. The secondary anti-BGG response in animals pretreated with CY was also not affected. However, IgG1 anti-BGG in the other groups given CY on day 0, +3 or +7 was delayed and reduced. IgG2 anti-BGG was suppressed in guinea-pigs treated with CY, 3 or 7 days after primary immunization. DNP-BGG-specific IgE serum antibodies, not detectable in CY untreated animals, were found in guinea pigs given CY on days 0, +3 or +7. It is suggested that the kinetics of the IgG1 and IgG2 primary immune response differ, as does the development of IgG1 and IgG2 specific immunological memory.

Animals↗
PubMed1983

A comparison of the conjugation of DNTB and other dinitrobenzenes with free protein radicals and their ability to sensitize or tolerize.

Of several dinitrobenzenes tested, 2,4-dinitrothiocyanatebenzene (DNTB) was found to be the only one that did not induce contact sensitivity when applied to the guinea pig ear epicutaneously, but when applied epicutaneously it induced tolerance to 2,4-dinitrofluorobenzene (DNFB). The manner in which DNFB, DNTB, and other dinitrobenzene compounds conjugated in vitro to soluble proteins, at physiologic pH, was examined. By measuring the free amino and sulfydryl radicals in the protein before and after conjugation, it was possible to determine to which groups the hapten was bound. It was found that although all the haptens bound to the free sulfydryl groups, DNTB was the only one that did not bind to amino groups. It is suggested that to be an epicutaenous tolerizer, as opposed to sensitizer, a hapten should bind to sulfydryl groups exclusively. It is hoped that a search for agents binding in a similar manner will reveal epicutaneous tolerizers for important industrial sensitizers.

Animals↗
PubMed1983

Contact sensitivity to acrylate compounds in guinea pigs.

As reports of contact dermatitis in humans due to acrylate compounds have increased considerably in recent years, it was decided to investigate the ability of these chemicals to evoke contact sensitivity skin reactions in guinea pigs. 21 different acrylate and methacrylate compounds were scanned for their ability to induce contact sensitivity, using 5 different sensitization protocols. Contact reactions of varying intensities were produced to all the mono-, di- and triacrylates tested. However, it was not possible to sensitize guinea pigs to any methacrylates. It would appear that guinea pigs cannot be contact sensitized to acrylate chemicals that are substituted on carbon 2.

Acrylates↗
PubMed1983

Experimental model for dermal granulomatous hypersensitivity in Q fever.

Q fever has been associated with granulomatous changes in clinical biopsy material obtained from liver and bone marrow. Local reactions to skin testing have been described in previously sensitized humans, but histological studies of such reactions have not been reported. We note that delayed hypersensitivity reactions to whole-cell phase I Q fever vaccine in immunized guinea pigs have a time course of development of induration characteristic of granulomatous hypersensitivity. Histological examination of such skin reactions on day 9 after testing revealed epithelioid cell infiltration and the presence of large numbers of multinucleated giant cells. Prominent in the sections were fragments of disintegrating polymorphonuclear leukocytes having the appearance of leukocytoclasis. Electron microscopic studies confirmed the presence of epithelioid changes in cells of the mononuclear phagocyte series, as well as extensive collagen deposition. This animal system affords a readily reproducible model of dermal granulomatous hypersensitivity and an opportunity to analyze the immunological basis of this reaction.

Animals↗
PubMed1983

Effective treatment for malignant mediastinal teratoma.

Primary malignant mediastinal teratoma is a rare tumour previously regarded as inevitably fatal. In a series of eight male patients with a mean age of 24 years five remain alive and well. All patients showed raised serum concentrations of human chorionic gonadotrophin or alpha fetoprotein. The patients were treated with intermittent combination chemotherapy that included cisplatin. Six patients responded to chemotherapy with a fall in human chorionic gonadotrophin or alpha fetoprotein to near normal levels and they then had radical excision of the remaining tumour. Living malignant tumour was found in four of the specimens and these patients received postoperative chemotherapy. One patient died after eight months and the remaining five patients are alive and well 13-136 months after the start of treatment. The two patients who did not undergo surgery died at one month and 15 months. Intermittent combination chemotherapy and carefully timed radical excision of these tumours would appear to have produced better results than have been reported in other series.

Adolescent↗
PubMed1983

Chronic cell-mediated immune reactions to metals.

Cell mediated immune reactions may underly toxic reactions to certain metals, particularly Cr, Ni, Zr, Be, and Hg. Metal conjugated to a carrier protein forms the immunogen, but how the metal acts as a hapten is poorly understood. The possibility that the metal changes the antigenicity of the protein by changing its configuration is discussed and could explain cross reactions between Zr and Cr. Most reactions are contact sensitivity reaction, but granulomas may also develop to Be and Zr. These are epithelioid cell lesions associated with fibroblast proliferation and increased collagen synthesis. Sensitization of guinea pigs to Be and Hg is possible by epicutaneous contact. Cr, Ni, and Zr sensitivity need Freund's adjuvant and frequent intradermal injections. Three initial protocols have been compared and their efficacy for each metal assessed. Specific unresponsiveness for Cr and Ni can be induced by intratracheal installation prior to attempted sensitization. After sensitivity has developed, unresponsiveness to Cr can be induced by intravenous injection of the metal together with an epicutaneous application given within 24 hours. Flare up of old Cr reaction sites can also be induced by intravenous injection of the metal. The reaction lasts for 48 hours, is associated with increased vascular permeability and subepidermal infiltration with basophil leucocytes.

Animals↗
PubMed1982

Encephalopathy and fatal myopathy in two siblings. Their association with partial deficiency of muscle carnitine.

Two brothers had intermittent episodes of muscle weakness, lethargy, hyperammonemia, rhabdomyolysis, and elevated activities of creatine phosphokinase (CPK), lactic dehydrogenase, and SGOT in serum associated with low muscle carnitine but normal serum carnitine concentrations. These siblings represent a "mixed" form of carnitine deficiency with the elements of both systemic and myopathic carnitine deficiency. The older sibling died suddenly after a 24-hour fast. The younger boy has received carnitine for three years. During this period, serum CPK activity has remained elevated and increased further during illnesses, but no clinical symptoms of encephalopathy or myopathy have appeared.

Carnitine↗