Cryptosporidium parvum antigens induce mouse and human dendritic cells to generate Th1-enhancing cytokines.

Cryptosporidium parvum is an opportunistic intracellular parasite that causes mild to severe diarrhoea, which can be life-threatening in an immunocompromised host. To increase our understanding of the mechanisms that play a role in host immune responses, we investigated the effects of C. parvum antigens on the phenotype of mouse and human dendritic cells (DCs). Cryptosporidium parvum antigens induced DC activation as indicated by upregulation of the maturation marker CD209, as well as by the production of the cytokines interleukin-12 p70, IL-2, IL-1beta, IL-6. In particular, significant increases in the expression of IL-12 p70 were observed from mouse DCs derived from bone marrow in response to solubilized sporozoite antigen and the recombinant cryptosporidial antigens, Cp40 and Cp23. We observed a small but significant increase in IL-18 expression following the exposure to Cp40. We found that the induction of Th1 cytokines was MyD88 dependent (MyD88 knockout mouse DCs were unresponsive). Additionally, both sporozoite preparations (solubilized and live) significantly induced IL-12 production by human monocytic dendritic cells (MoDCs). This finding indicates that solubilized as well as recombinant antigens can induce the maturation of DCs and subsequently initiate an innate immune response.

Effect of short-term treatment with a monoclonal antibody to P-selectin on balloon catheter-induced: intimal hyperplasia, re-endothelialization, and attenuation of endothelial-dependent relaxation.

The effects of an anti-P-selectin monoclonal antibody (MAb, PB1.3; Cytel Corporation) on neoendothelialization; neoendothelial function, as evidenced by acetylcholine-induced relaxation (nitric oxide formation); and intimal hyperplasia following embolectomy catheter-induced injury to the rabbit thoracic aorta were investigated. Catheter injury was induced in two groups of New Zealand White rabbits. One group received no treatment, while the second group received short-term treatment with the MAb (i.p., immediately before and 12 h after induction of catheter injury). A third group underwent a sham operation and served as uninjured controls. Following sacrifice at 2 weeks after injury, aortic rings were assessed for degree of intimal hyperplasia, neoendothelial morphology (scanning electron microscopy), and acetylcholine-induced relaxation. Aortic tissue from catheter-injured animals that received treatment exhibited improved neoendothelial morphology, as compared with tissue from untreated but catheterized animals; however, no statistically significant attenuation of the hyperplastic response or improvement in the attenuated neoendothelial-dependent acetylcholine-induced relaxant response that is characteristic of neoendothelium that forms after catheter denudation was observed. These data suggest that short-term attenuation of P-selectin-mediated polymorphonuclear leukocyte (PMN)/endothelium, PMN/platelet interactions, and/or thrombin formation beneficially affects neoendothelialization of the vascular wall following balloon catheter-induced injury.

L-arginine inhibits balloon catheter-induced intimal hyperplasia.

Intimal hyperplasia that results from therapeutic revascularization is an important etiologic factor in the failure of these procedures (i.e., restenosis). Drugs which donate nitric oxide have been shown to inhibit the proliferation of vascular smooth muscle cells in vitro. We tested the hypothesis that administration of L-arginine (0.5 g/kg/day), the precursor of nitric oxide, would inhibit development of intimal hyperplasia following balloon catheter-induced injury. L-arginine administration from 2 days prior to and 2 weeks following catheter-induced injury to the rabbit thoracic aorta attenuated the development of intimal hyperplasia by 39% as compared with untreated controls. This effect was due to decreased intimal area. The effect of L-arginine was inhibited by co-administration of an inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester (0.5 g/kg/day). These data demonstrate that L-arginine attenuates intimal hyperplasia and suggest that the mechanism for this effect is the conversion of L-arginine to nitric oxide.

Macrophage culture from untreated leprosy cases.

Macrophage cultures from the peripheral blood were performed in 25 untreated bacteraemic leprosy patients. The monocytes on conversion to macrophages in culture continued to harbour solidly stained M. Leprae till the termination of culture. It is suggested that the majority of these bacilli are viable and capable of multiplication intracellularly in macrophages if cultures could be maintained for sufficiently long periods. It was observed that bacteraemia in Leprosy can be detected by the culture technic. It has been found to be more sensitive than the leukocyte adherence method.

Behaviour of macrophages to Mycobacterium leprae. A tissue culture study.

Macrophage culture was performed on 45 healthy adults who were initially categorised on the basis of their Lepromin reactivity using Dharmendra antigen. There were 25 individuals in the Lepromin positive group and 20 in the Lepromin negative group. The cultures were challenged with M. leprae and the macrophages studied at varying time intervals of culture. No difference was evident in the behaviour of cultured macrophages to M. leprae in both the groups. The Lepra bacilli were phagocytosed by the macrophages and retained essentially intact till the termination of culture. The Lepromin reactivity of a healthy individual was not reflected on the macrophage function in vitro. The observations suggested against the possibility of an intrinsic genetically determined macrophage defect in dealing with M. leprae.

Persistence and distribution of Mycobacterium leprae in Aedes aegypti and Culex fatigans experimentally fed on leprosy patients.

Laboratory reared Aedes aegypti and Culex fatigans were experimentally fed on untreated lepromatous leprosy patients and the proboscides, guts and faeces of the mosquitoes were examiend at 12 hour intervals to determine the persistence and distribution of Mycobacterium leprae. In A. aegypti, bacilli persisted in proboscis till 156 hours, in gut 96 hours, and in faeces 72 hours after feeding. In C. fatigans--proboscides 144 hours, gut 96 hours and faeces 72 hours after feeding. In A. aegypti solid bacilli were present in proboscis upto 96 hours; in gut 48 hours and in faeces 42 hours after feeding. Corresponding figures for C. fatigans were: 144 hours for proboscis, 48 hours for gut, solid bacilli being absent in faeces. The results are discussed from the point of view of arthropod transmission.

Darier's Disease.

Fifteen cases of Darier's disease were studied. Males and females were in the ratio of 3:2. The disease appeared between the ages of 5 and 16 in majority (80%) of the patients. Family history was positive in only 60% cases. Itching was the main symptom in 2/3rd (66.6%) of cases. Seven cases experienced aggravation of the disease in summer. Recurrent skin infection and eczematisation were present in 5 cases. Majority of patients had typical lesions. Severity of the disease was directly related to its duration. Acrokeratosis verruciformis like lesions over the hands and feet were present in all the cases and 86.6% of cases had palmoplantar keratoderma. Mucosal lesions were seen in 73.3 % of cases. These unusual findings are not often stressed in clinical practice and need to be highlighted. Leucoderma guttate yet another unusual finding was seen in 20% of cases.

Malignant Melanoma of Oral Cavity.

Primary malignant melanoma of oral cavity is very rare. A case of oral melanoma who died due to metastasis a year after the excision of the primary lesion is reported along with a brief review of the literature.