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Biomedical subjects

D C Henderson

Publications and source records attributed to D C Henderson.

At least 55 records · Page 3Linked to original sources

Immunological parameters in peripheral blood of patients with renal cell carcinoma before and after nephrectomy.

OBJECTIVE: To determine the effects of nephrectomy on the immune response of patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Five patients with RCC were monitored before and over a period of up to 3 months after nephrectomy. The aspects measured were the phenotypic expression of markers on circulating lymphocytes, circulating concentrations of cytokines, markers of inflammatory and immune responses, and natural killer (NK) cell and lymphokine-activated killer (LAK) cell activity in peripheral blood mononuclear cells (PBMC). The suppressive activity of patients' plasma on NK activity and ability to generate interleukin-2 (IL-2) induced LAK cells in PBMC of normal volunteers was also investigated. RESULTS: The results indicated that high CD4/8 ratios were present pre-nephrectomy with evidence of inflammatory responses and immune activation in some patients, particularly those with metastatic disease. CONCLUSION: The effect of nephrectomy was to decrease the inflammatory response and increase immune activation. Various defects in NK cell activity and LAK cell generation were demonstrated pre-surgery which slowly improved once the primary tumour had been removed and it is suggested that such defects could have contributed to tumour growth and development due to an ineffective immune response.

Adult↗

Inter-relationships between pterins and cytokines produced during allogeneic immune reactions and possible use as early markers of immune activation.

The pterins neopterin and xanthopterin have been measured together with the cytokines IFN-gamma, TNF-alpha and TNF-beta in the supernatants of 20 allogeneic mixed lymphocyte reactions. We have calculated rank correlation coefficients between these analytes and the immune response. Our findings confirm that neopterin is a sensitive early marker of immune activation and show that another pterin, xanthopterin could be used likewise. Cytokine production was also proportional to immune activation but none could be used consistently as early markers of immune activation.

Biomarkers↗

Immune changes in peripheral blood resulting from locally directed interleukin-2 therapy in squamous cell carcinoma of the head and neck.

Interleukin-2 (IL-2) was administered locally by constant intra-arterial infusion in four escalating doses from 3 x 10(4)-3 x 10(7) IU/day to 12 patients with squamous cell carcinoma of the head and neck (SCCHN) in a phase I trial. Lymphocyte phenotypic markers and serum cytokine concentrations were measured over the course of treatment. Serum IL-1-alpha, -beta and IL-6 were not induced at any dose level. Tumour necrosis factor (TNF)-alpha was induced in the 2 patients who showed a clinical response (at the lowest dose) as well as in 4/10 of the non-responders. In addition TNF-beta was induced in 3/10 and IFN-gamma in 5/10 non-responders. Soluble IL-2 receptor concentrations were increased at the two higher doses. The highest dose of IL-2 produced a lymphocytosis after day 5 until the end of administration reflected by a general rise in lymphocyte phenotypic markers. CD25, CD3/HLA-DR and CD56 showed an additional upregulation not accounted for by the lymphocytosis with a suggestion of a bell-shaped dose-response curve for CD25 and CD3/HLA-DR. Administration of IL-2 in this manner has been shown to be well tolerated and has some anti-tumour activity at low doses, with little toxicity.

Adult↗

Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects.

OBJECTIVE: The authors' goal was to study the relationship between smoking status and clinical characteristics in schizophrenic patients. METHOD: Seventy-eight schizophrenic outpatients were assessed by a single rater using the Brief Psychiatric Rating Scale (BPRS), the Abnormal Involuntary Movement Scale, and the Simpson-Angus Scale for extrapyramidal symptoms. Current smokers (N = 58) were compared with nonsmokers (N = 20) on clinical variables by independent t tests and chi-square tests. Differences in outcome variables were tested by multiple analysis of covariance (ANCOVA) with smoking status and gender as factors and age, neuroleptic dose, and caffeine consumption as covariates. RESULTS: Seventy-four percent of patients were current smokers and reported a mean of 19 cigarettes smoked per day. Compared to nonsmokers, current smokers were significantly more likely to be men, to be younger, and to have had an earlier age at onset and a greater number of previous hospitalizations. Current smokers and nonsmokers received mean neuroleptic doses of 1160 and 542 mg/day (chlorpromazine equivalents); the difference was significant. Current smokers also displayed significantly less parkinsonism and more akathisia and had higher total scores on the BPRS. Overall multiple ANCOVA demonstrated a significant main effect for smoking status but not gender or the interaction between gender and smoking status. Univariate ANCOVAs demonstrated a significant main effect of smoking status only for the Simpson-Angus Scale score. CONCLUSIONS: Cigarette smokers receive significantly higher neuroleptic doses, in part because of a smoking-induced increase in neuroleptic metabolism. Smoking is also associated with significant reduction in levels of parkinsonism. Smoking status is a significant factor that should be considered in assessment of neuroleptic dose requirements and neuroleptic side effects.

Adult↗

Stimulatory effects of FK156 in a panel of tests designed to detect changes in immune function.

There is a need to evaluate the utility of experimental models in immune function assessment if these are to be accepted in preclinical safety studies. We have evaluated a panel of tests measuring cellularity and functions of the lymphoid system in the Fischer rat in order to determine whether they would detect immunostimulation, rather than suppression. Injection of the peptide immunostimulant FK156 (D-lactyl-L-alanyl-y-D-glutamyl-(L)-meso-diaminopimelyl- (L)-glycine) increased the numbers of macrophages recovered from the peritoneal cavity, and stimulated their activity, as measured by chemiluminescence, adherence, and secretion of interleukin 1. In vitro, T lymphocytes had an increased background incorporation of tritiated thymidine, increased response to sub-optimal concentrations of concanavalin A, and an increase in secretion of interleukin 2 at optimal concentrations of concanavalin A. There was no change in the proliferative responses of B lymphocytes in vitro. Antibody responses to tetanus toxoid in vivo were increased. These changes were not reflected in consistent, statistically significant alterations in the numbers of lymphocytes bearing either lineage markers or the interleukin 2 receptor as a marker of activation.

Adjuvants, Immunologic↗

Case report: splenic-gonadal fusion--the ultrasound appearances.

We report the ultrasound appearances, with pathological correlation, of splenic-gonadal fusion in a patient who presented with an asymptomatic scrotal swelling. Ultrasound examination showed an echo-poor 2 cm diameter lesion in the upper pole of the left testicle. Histologically the lesion was normal spleen. Splenic-gonadal fusion should be considered in the differential diagnosis of scrotal swellings.

Female↗

Cytokine induction of neopterin production.

The pteridine neopterin is a marker of immunological activation and has been shown to be a useful marker of graft-versus-host disease (GVHD) in bone marrow transplant patients. High levels of both neopterin and interferon-gamma (IFN-gamma) were produced in vitro during mixed lymphocyte responses, which may be considered to be a model of the primary events leading to GVHD. Neopterin was shown to be produced by monocytes in response to stimulation with IFN-gamma, but not other cytokines. However, the interleukins IL-1 alpha, IL-1 beta, IL-2, and tumour necrosis factor (TNF) alpha and beta, but not IL-6, stimulated neopterin production by unfractionated peripheral blood mononuclear cells (PBMC), and culture supernatants from PBMC stimulated with IL-1 alpha, IL-1 beta, IL-2 and IL-6, but not TNF-alpha or TNF-beta induced neopterin production following transfer to fresh monocyte cultures. It therefore appears that cytokines may generate neopterin by induction of IFN-gamma, by synergy with low levels of induced IFN-gamma, or by non-IFN-gamma-dependent mechanisms.

Biopterins↗

Adolescents and chemical dependency.

Practitioners seeking to develop effective treatment strategies for chemically dependent adolescents confront a literature which is overwhelming in volume and confusing and contradictory in content. The intent of this article is to critically review the literature relevant to this population. Incidence, prevalence, patterns, correlates, and consequences of use are discussed, along with their implications for social work treatment, research, and policy.

Adolescent↗

Immunological studies on paroxetine, a novel anti-depressant drug.

Paroxetine is a novel and selective neuronal 5-hydroxy-tryptamine uptake inhibitor with anti-depressant activity. Paroxetine was examined for its ability to induce adverse immunological reactions, either as a consequence of a specific immune response or by a direct or indirect effect on the immune system. Paroxetine did not react in vitro with protein amino or thiol groups, suggesting that it lacks the capacity to form potentially immunogenic hapten protein conjugates. No anti-paroxetine antibody was detected in plasma or serum samples from patients and rats following oral administration over prolonged periods, or from epicutaneously exposed guinea pigs, or from rabbits given paroxetine in Freund's adjuvant, suggesting that paroxetine does not have the capacity to elicit humoral immune responses. Guinea pigs epicutaneously exposed to paroxetine did not develop contact sensitivity, suggesting that it does not have the capacity to elicit cell-mediated immune responses. These results suggest that paroxetine lacks intrinsic immunogenicity. Anti-SRBC antibody plaque-forming cell responses in mice were unaffected by oral administration of paroxetine, and paroxetine had no significant effect on ex vivo and in vitro murine macrophage phagocytosis of opsonized SRBC or on ex vivo murine splenocyte mitogen responses, suggesting that paroxetine does not exert modulatory effects on the immune system or on macrophage function. These findings, together with the results of pre-clinical safety evaluation studies, suggest that paroxetine is unlikely to have immunotoxic effects.

Adult↗

Sudden death in incomplete Kawasaki's disease.

A boy of 12 years died suddenly of myocardial infarction, which was due to coronary artery aneurysm typical of Kawasaki's arteritis. Two years earlier he had an obscure illness, recognised retrospectively as incomplete Kawasaki's disease. We recommend routine echocardiography even if only one or two features of the syndrome are present.

Child↗

Group B streptococcal infection presenting as sudden death in infancy.

Two infants aged 3 and 8 months were found dead in their cots. Postmortem cultures yielded group B streptococci from multiple internal sites, and cytomegalovirus was also isolated from the lungs of one. These cases show the value of microbiological culture in the investigation of sudden infant death.

Cytomegalovirus Infections↗

Suppression of murine IgE responses with amino acid polymer/allergen conjugates. V. By intranasal administration.

Serum IgE antibody responses were generated in mice by intranasal exposure to grass pollen extract. Primary IgE responses were suppressed by the concomitant intranasal administration of a conjugate of polysarcosine and pollen extract which has been shown to be a potent tolerogen when given parenterally. Partial suppression of boosted IgE responses was observed when the conjugate was applied intranasally with a secondary challenge of unmodified extract. The data suggest that clinical schedules of intranasal application of tolerogenic conjugates can be devised to bring about specific IgE suppression.

Administration, Intranasal↗

Immunogenicity of acrylate chemicals as assessed by antibody induction.

The immunogenicities of two acrylate chemicals, trimethylolpropane triacrylate (TMPTA) and methyl acrylate (MeAc), and one related vinyl compound, 4-vinyl pyridine (4VP), were investigated by determining the in vivo induction of IgG antibodies in guinea pigs. The injection of the chemicals emulsified in Freund's complete adjuvant resulted in the induction of serum antibody responses against MeAc and 4VP but not TMPTA. However, antibody with anti-TMPTA activity was produced following immunization of guinea pigs with TMPTA conjugated to protein, which allowed comparisons to be made of the immunogenic structural features of the compounds.

Acrylates↗

Immunogenicity in guinea pigs and tolerance in grass pollen-sensitive volunteers of enteric-coated grass pollen allergens.

An acid-insoluble, methacrylic acid, methyl methacrylate copolymer (Eudragit L-100) was used to give an enteric coating to a grass pollen extract in order to protect it against gastric degradation. Substantial protection against the degradative effects of simulated gastric secretion was demonstrated using this preparation which was well tolerated by grass pollen-allergic volunteers. The enteric-coated allergen induced a greater secondary antibody response than did an aqueous presentation when administered orally to guinea pigs which had been primed previously by subcutaneous injection. This result indicates that an effective hyposensitisation regimen could consist of a short series of initial parenteral injections, followed by an oral course of the protected allergen.

Acrylic Resins↗

Antibody responses of mice to intragastric and parenterally administered aeroallergens.

Intragastric administration of aeroallergens (pollen extract)-primed mice to produce transient serum IgE antibody responses following subsequent parenteral stimulation while the same initial dose of extract, given parenterally, did not have this effect. In previously immunized animals, intragastric administration of pollen extract was found to enhance systemic antibody production. These observations indicate that exposure of gut-associated lymphoid tissue to aeroallergens can have a profound effect on subsequent reaginic antibody production. This procedure provides a useful model for studying IgE responses to allergens without the complication of an initial injection with adjuvant. A combination of parenteral immunization with oral administration may therefore offer a convenient immunotherapeutic manoeuvre for patients with seasonal rhinitis/asthma.

Administration, Oral↗