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Biomedical subjects

P Mann

Publications and source records attributed to P Mann.

At least 55 records · Page 3Linked to original sources
PubMed1980

Immunological properties of the cell envelope components of Vibrio cholerae.

Several immunobiological properties of cell envelope components of Vibrio cholerae such as mitogenicity, antigenicity, adjuvanticity and toxicity were tested in mice. Killed whole bacteria, spheroplasts, lipopolysaccharide and outer membrane proteins possessed mitogenic activity as determined by [3H]thymidine uptake in spleen cell cultures. All these components predominantly stimulated murine bone-marrow derived (B) lymphocytes. The mitogenicity induced by V. cholerae lipopolysaccharide was similar in magnitude to that observed with Salmonella typhimurium lipopolysaccharide. Vibrio cholerae lipopolysaccharide was mitogenic for gut-associated lymphocytes such as those obtained from Peyer's patches and small intestine. Antibody formation at the cellular level was detected by the haemolytic plaque assay. Plaque-forming cells to V. cholerae lipopolysaccharide were only detected when mice were immunized intraperitoneally with intact cells or with spheroplasts. Among the various cell envelope components, lipopolysaccharide alone possessed adjuvant properties as it increased the number of plaque-forming cells to sheep erythrocytes fourfold in mouse spleens. Also, lipopolysaccharide was the only component found to be toxic for the mouse (LD50 0 . 5 mg). Neither spheroplasts nor outer membrane of V. cholerae showed adjuvanticity or toxicity in mice.

Adjuvants, Immunologic↗
PubMed1979

Effect of dicarboxylic acids on normal human melanocytes in dispersed tissue culture.

Since dicarboxylic acids are competitive inhibitors of tyrosinase, and effective in treatment of hyperpigmentary disorders, such as chloasma and lentigo maligna, probably due to a cytotoxic effect on abnormal melanocytes, it is of interest to examine their effect on normal melanocytes in tissue culture. Azelaic or dodecandioic acids were added (150-200 micrograms/ml) to dispersed cultures of epidermal cells, and melanocytes were examined by electron microscopy after 7, 10, 15, 20 and 30 days. Apart from a stimulation of melanogenesis, the presence of dicarboxylic acids in the culture medium caused no detectable damage to melanocytes, nor did they prevent growth of a second generation of cells.

Culture Techniques↗
PubMed1977

Immediate hypersensitivity to tuberculin. In vivo and in vitro studies.

Immediate responses of hypersensitivity to skin testing with purified derivative of tuberculin (PPD) were observed in 2.3 percent of 3,248 patients seen in an allergy clinic, and the relationship to delayed responses was questioned. Immediate cutaneous reactions to testing with PPD appeared in all age groups and occurred in nonatopic patients but were more common in atopic patients (p less than 0.005). Delayed cutaneous reactions to testing with PPD occurred in only three out of 76 patients with immediate reactivity. Antihistaminic suppression of immediate reactivity was not followed by evidence of delayed cutaneous reactivity. In vitro tests of lymphocytic stimulation revealed indices of stimulation with PPD to be similar both in patients with immediate and delayed cutaneous reactivity. Failure to manifest delayed cutaneous reactivity following immediate cutaneous reactions alone may be explained by antigen-antibody binding and phagocytosis, by suppressor T-lymphocytes, or by impaired release or lack of response to T-lymphocytic mediators. Adverse reactions to administration of BCG vaccine in patients with immediate cutaneous reactivity might be anticipated.

Adolescent↗
PubMedDate not supplied

Partial arytenoidectomy in the horse with and without mucosal closure.

Left-sided partial arytenoidectomy was performed in eight horses to evaluate healing. Four horses underwent conventional partial arytenoidectomy with suture apposition of the mucosa. In four horses, most of the arytenoid cartilage, including overlying mucosa, vocal fold, and laryngeal saccule, were excised en bloc without mucosal closure. The horses were monitored clinically by endoscopic examination. One horse from each group was euthanatized at weeks 2, 4, 8, and 16. Complete necropsies with gross and histologic examination of the arytenoidectomy sites were performed. Postoperative complications such as coughing, dysphagia, and aspiration pneumonia were not encountered and problems with wound healing were minimal in both groups. The defect created by partial arytenoidectomy without mucosal closure initially filled to the level of the luminal surface with granulation tissue, with a gradual transition to mature fibrous connective tissue. Grossly, the defect appeared to be healed and was completely epithelialized by week 16 without apparent narrowing of the laryngeal lumen. Partial arytenoidectomy sites with mucosal closure healed in a similar pattern by week 8. Partial dehiscence of the dorsal portion of the sutured mucosa occurred in three horses.

Animals↗
PubMedDate not supplied

Epiglottic augmentation in the horse.

Epiglottic augmentation with injectable bovine collagen or an autogenous or allogenous auricular cartilage graft was performed in 12 horses with endoscopically and radiographically normal epiglottises. The grafting procedures were easy to perform and did not cause apparent discomfort. Cartilage graft extrusion or resorption may have occurred, but was not seen by endoscopy and lateral laryngeal radiography. Only collagen implants remained evident endoscopically, as smooth round submucosal bulges ventral to the epiglottic cartilage. Two horses with collagen implants, and all horses with cartilage autografts and allografts, were euthanatized at week 16. One horse with a collagen implant was euthanatized at week 4 and one at week 6. The epiglottis appeared thickened in three horses with collagen implants, two horses with autogenous grafts, and three horses with allogenous grafts. Pharyngeal lymphoid tissue was hyperplastic in two horses with autografts and three horses with allografts, but not in horses with collagen implants. Collagen grafts persisted as one or two smooth bulges 8 mm in diameter. Collagen incited a brisk foreign body reaction that was surrounded by a fibrous connective tissue capsule. Epiglottises of the horses with collagen implants were significantly thicker 20 mm from the tip than those of normal horses and horses with allografts. Cartilage graft incorporation was not evident grossly and was seen on microscopic examination in only one autograft. Thickening was caused by submucosal fibrosis.

Animals↗
PubMedDate not supplied

The fungicide procymidone alters sexual differentiation in the male rat by acting as an androgen-receptor antagonist in vivo and in vitro.

Procymidone is a dicarboximide fungicide structurally related to the well-characterized fungicide vinclozolin. Vinclozolin metabolites bind to mammalian androgen receptors (AR) and act as AR antagonists, inhibiting androgen-dependent gene expression in vivo and in vitro by inhibiting AR-binding to DNA. The current study was designed to determine if procymidone acted as an AR antagonist in vitro and to describe the dosage levels of procymidone that alter sexual differentiation in vivo. In vitro, procymidone inhibited androgen from binding the human AR (hAR) in COS (monkey kidney) cells transfected with hAR at 3.16 microM. In vitro, procymidone acted as an androgen antagonist, inhibiting dihydrotestosterone (DHT)-induced transcriptional activation at 0.2 microM in CV-1 cells (cotransfected with the hAR and a MMTV-luciferase reporter gene). In vivo, maternal procymidone exposure at 0, 25, 50, 100, or 200 mg kg-1 day-1 during gestation and early lactation (gestational day 14 to postnatal day 3) altered reproductive development of male offspring at all dosage levels tested. Male offspring exhibited shortened anogenital distance (at 25 mg kg-1 day-1 and above), permanent nipples, reduced weight of several androgen-dependent tissues (levator ani and bulbocavernosus muscles, prostate, seminal vesicles, Cowper's gland and glans penis), and malformations (hypospadias, cleft phallus, exposed os penis, vaginal pouch, hydronephrosis, occasional hydroureter, epididymal granulomas, and ectopic, undescended testes). In addition, perinatal procymidone treatment had a marked effect on the histology of the lateral and ventral prostatic and seminal vesicular tissues of the offspring (at 50 mg kg-1 day-1 and above). These effects consisted of fibrosis, cellular infiltration, and epithelial hyperplasia. This constellation of effects is similar to that produced by perinatal exposure to vinclozolin. However, procymidone appears to be slightly less potent in inducing malformations than vinclozolin by a factor of about two. In summary, the antiandrogenic activity of procymidone was demonstrated in vivo and in vitro in cell lines transfected with hAR. Since the role of androgens in mammalian sexual differentiation is highly conserved, it is likely that humans would be adversely affected by procymidone in a predictable manner if the human fetus was exposed to sufficient levels during critical stages of intrauterine and neonatal life.

Androgen Receptor Antagonists↗
PubMedDate not supplied

Administration of potentially antiandrogenic pesticides (procymidone, linuron, iprodione, chlozolinate, p,p'-DDE, and ketoconazole) and toxic substances (dibutyl- and diethylhexyl phthalate, PCB 169, and ethane dimethane sulphonate) during sexual differentiation produces diverse profiles of reproductive malformations in the male rat.

Antiandrogenic chemicals alter sexual differentiation by a variety of mechanisms, and as a consequence, they induce different profiles of effects. For example, in utero treatment with the androgen receptor (AR) antagonist, flutamide, produces ventral prostate agenesis and testicular nondescent, while in contrast, finasteride, an inhibitor of 5 alpha-dihydrotestosterone (DHT) synthesis, rarely, if ever, induces such malformations. In this regard, it was recently proposed that dibutyl phthalate (DBP) alters reproductive development by a different mechanism of action than flutamide or vinclozolin (V), which are AR antagonists, because the male offsprings display an unusually high incidence of testicular and epididymal alterations--effects rarely seen after in utero flutamide or V treatment. In this study, we present original data describing the reproductive effects of 10 known or suspected anti-androgens, including a Leydig cell toxicant ethane dimethane sulphonate (EDS, 50 mg kg-1 day-1), linuron (L, 100 mg kg-1 day-1), p,p'-DDE (100 mg kg-1 day-1), ketoconazole (12-50 mg kg-1 day-1), procymidone (P, 100 mg kg-1 day-1), chlozolinate (100 mg kg-1 day-1), iprodione (100 mg kg-1 day-1), DBP (500 mg kg-1 day-1), diethylhexyl phthalate (DEHP, 750 mg kg-1 day-1), and polychlorinated biphenyl (PCB) congener no. 169 (single dose of 1.8 mg kg-1). Our analysis indicates that the chemicals discussed here can be clustered into three or four separate groups, based on the resulting profiles of reproductive effects. Vinclozolin, P, and DDE, known AR ligands, produce similar profiles of toxicity. However, p,p'-DDE is less potent in this regard. DBP and DEHP produce a profile distinct from the above AR ligands. Male offsprings display a higher incidence of epididymal and testicular lesions than generally seen with flutamide, P, or V even at high dosage levels. Linuron treatment induced a level of external effects consistent with its low affinity for AR [reduced anogenital distance (AGD), retained nipples, and a low incidence of hypospadias]. However, L treatment also induced an unanticipated degree of malformed epididymides and testis atrophy. In fact, the profile of effects induced by L was similar to that seen with DBP. These results suggest that L may display several mechanisms of endocrine toxicity, one of which involves AR binding. Chlozolinate and iprodione did not produce any signs of maternal or fetal endocrine toxicity at 100 mg kg-1 day-1. EDS produced severe maternal toxicity and a 45% reduction in size at birth, which resulted in the death of all neonates by 5 days of age. However, EDS only reduced AGD in male pups by 15%. Ketoconazole did not demasculinize or feminize males but rather displayed anti-hormonal activities, apparently by inhibiting ovarian hormone synthesis, which resulted in delayed delivery and whole litter loss. In summary, the above in vivo data suggest that the chemicals we studied alter male sexual differentiation via different mechanisms. The anti-androgens V, P, and p,p'-DDE produce flutamide-like profiles that are distinct from those seen with DBP, DEHP, and L. The effects of PCB 169 bear little resemblance to those of any known anti-androgen. Only in depth in vitro studies will reveal the degree to which one can rely upon in vivo studies, like those presented here, to predict the cellular and molecular mechanisms of developmental toxicity.

Aminoimidazole Carboxamide↗
PubMedDate not supplied

Proliferation and substrate effects on endothelial cell thrombogenicity.

The effects of the cellular differentiation status and the adhesive-substrate on endothelial cell function in cell culture were measured with an enzyme based assay of surface thrombogenicity. A solid plastic, microporous polymeric, and fibronectin (FN) treated microporous polymeric were used as substrates for growth of endothelial cells. The microporous and FN treated synthetic substrates have been shown to aid in the induction of cellular differentiation mechanisms. Cells were studied under proliferative and nonproliferative growth conditions. The thrombogenicity of the surface created by the endothelial cell monolayers under various experimental conditions was determined using an enzyme based assay of fibrin deposition. Actively proliferating cells on the solid plastic substrate produced the most thrombogenic surface, while confluent endothelial cell monolayers grown on FN treated microporous substrate were the least thrombogenic surfaces. These data suggest that endothelial cell surface thrombogenicity is under substrate control, and also related to the cellular differentiation status. These findings are being used to design a novel approach to the small diameter synthetic vascular graft problem.

Animals↗