Cell-mediated immunity in experimental Nocardia asteroides infection.

Experimental mycetoma-like lesions developed in guinea pigs after subcutaneous injection of Nocardia asteroides. Although delayed hypersensitivity appeared earlier, increased macrophage migration inhibition and microbicidal activity appeared after 7 weeks. When the lesions healed, high cell-mediated immunity was present. Cell-mediated immunity was transferred to normal recipient guinea pigs from healed donor guinea pigs by spleen cell transfer. Recipient guinea pigs showed marked protection against challenge with N. asteroides.     

The flickery block of ATP-dependent potassium channels of skeletal muscle by internal 4-aminopyridine

We have examined the effects of 4-aminopyridine (4-AP) on single ATP-dependent potassium channels in patches excised from frog skeletal muscle. 4-AP applied to the internal face of the membrane caused a flickery block. We could not detect any flickery block when 10 mM 4-AP was applied to the external surface of the membrane. The reduction in mean unitary current by internal 4-AP was consistent with 11 binding with a K _d of 3.3 mM at 0 mV. The block was voltage-dependent, increasing with depolarization with an effective valency of 0.57. Rate constants for blocking and unblocking by 4-AP were obtained by fitting functions to the distribution of current amplitudes. Both rate constants were voltage-dependent. At 0 mV they were 17 mM^–1 ms^–1 and 61 ms^–1. Simulation of the block using these rate constants produced a flickery block very similar to that observed experimentally.     

Shared allergenic and antigenic determinants in Alternaria and Stemphylium extracts

To develop a model for mold allergen extract standardization, we studied eight commercial Alternaria extracts from various suppliers by a variety of immunochemical and physicochemical techniques, including measurement of Alt-I, a purified allergenic fraction of Alternaria. Wide variations were noted in the allergenic and antigenic potencies of these extracts. Estimates of Alt-I content measured by Alt-I RAST inhibition and by radioimmunoassay correlated significantly (p < 0.05), but Alt-I activity by either method could not be correlated with allergenic potency as measured by RAST inhibition using solid-phase Alternaria. Each test extract produced unique and differing patterns of Coomassie blue-stained bands in isoelectrofocusing gels and in crossed immunoelectrophoresis gels using rabbit antibodies to Alternaria. The optimal method for mold allergen standardization involves a combination of RAST inhibition, isoelectrofocusing, and crossed immunoelectrophoresis techniques, and, if possible, quantitation of individual allergens.     

Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease

Two closely related genes, the presenilins ( PS ), located at chromosomes 14q24.3 and 1q42.1, have been identified for autosomal dominant Alzheimer disease (AD) with onset age below 65 years (presenile AD). We performed a systematic mutation analysis of all coding and 5'-non-coding exons of PS -1 and PS -2 in a population-based epidemiological series of 101 unrelated familial and sporadic presenile AD cases. The familial cases included 10 patients of autosomal dominant AD families sampled for linkage analysis studies. In all patients mutations in the amyloid precursor protein gene ( APP ) had previously been excluded. Four different PS -1 missense mutations were identified in six familial cases, two of which where autosomal dominant cases. Three mutations resulted in onset ages above 55 years, with one segregating in an autosomal dominant family with mean onset age 64 years (range 50-78 years). One PS -2 mutation was identified in a sporadic case with onset age 62 years. Our mutation data provided estimates for PS -1 and PS -2 mutation frequencies in presenile AD of 6 and 1% respectively. When family history was accounted for mutation frequencies for PS -1 were 9% in familial cases and 18% in autosomal dominant cases. Further, polymorphisms were detected in the promoter and the 5'-non-coding region of PS -1 and in intronic and exonic sequences of PS -2 that will be useful in genetic association studies.      

Methimazole protects from experimental autoimmune uveitis (EAU) by inhibiting antigen presenting cell function and reducing antigen priming

Methimazole (methyl-mercapto-imidazole, MMI), a compound used clinically in therapy of Graves' thyroiditis, was found to inhibit development of several autoimmune diseases in animal models. It was suggested on the basis of in vitro data that inhibition is through down-regulation of interferon-gamma (IFN-gamma)-induced expression of major histocompatibility complex class I and class II molecules. Here, we investigate the effect of MMI on experimental autoimmune uveoretinitis (EAU) and study its mechanism(s). Treatment of EAU with MMI administered in drinking water inhibited induction of the disease and associated antigen (Ag)-specific proliferation and cytokine production by draining lymph node cells (LNCs). The treatment was protective only if administered during the first but not during the second week after immunization, suggesting an effect on the induction phase of EAU. It is interesting that MMI inhibited disease in IFN-gamma knockout mice, indicating that the in vivo protective effect is IFN-gamma-independent. Flow cytometric analysis of draining LNCs extracted 5 days after immunization showed that MMI partly to completely reversed the increase in Mac-1(+)/class I(+)/class II(+) cells induced by immunization and reduced the proportion of B7-1 and CD40-positive cells, suggesting a deficit in the Ag-presenting cell (APC) population. APC from untreated mice largely restored antigen-specific proliferation of MMI-treated LNCs. We suggest that MMI inhibits EAU at least in part by preventing the recruitment and/or maturation of APC, resulting in reduced generation of Ag-specific T cells.     

Bedside hemoglobinometry in hemodialysis patients: lessons from point-of-care testing

The HemoCue B-hemoglobin test system (HemoCue, Inc., Mission Viejo, CA) is a photometric method for rapid bedside determination of hemoglobin (Hb). We compared the performance of HemoCue measured Hb against Coulter STK-S (CSTK) measured Hb in chronic hemodialysis (HD) patients in two different settings. In the first setting, Hemocue analysis was performed by multiple HD technicians (n = 132). In the second setting, a nurse trained in proper specimen handling performed the HemoCue analysis (n = 74). Simultaneous measurement of Hb by the CSTK method was performed. First setting: Hb was 11.1+/-1.66 (SD) g/dl by CSTK and 11.7+/-2.29 g/dl by HemoCue. The HemoCue method consistently overestimated Hb by an average (SD) of 0.63 (1.267) g/dl (95% CI = 0.42 to 0.85). Hb was overestimated in 25.7% and underestimated in 2.3% of the patients by 1 g/dl or more. Thus, the HemoCue system was accurate within 1 g/dl only 72% of the time. Second setting: HemoCue overestimated Hb by an average (SD) of 0.29 (0.52) g/dl (95% CI, 0.17 to 0.41). Only 4% of all patients had errors in estimation of 1 g/dl or more. Thus, HemoCue was accurate in 96% of the patients within 1 g/dl. After reviewing the two protocols, the primary difference in the two studies was the technique used to obtain the specimens. When performed properly, Hb testing using the HemoCue testing system had a high level of agreement with CSTK. Appropriate training in specimen handling, as well as test performance, will increase accuracy and reliability of bedside hemoglobinometry.     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Malignant paraganglioma of the larynx

Paraganglioma of the larynx are rare tumours and only 25 cases have been reported in the world literature. Paraganglioma of larynx are paired superior and inferior laryngeal glomus bodies in association with superior and recurrent laryngeal nerves respectively. The tumours arising from laryngeal glomus bodies appear in subglottic space, in trachea, as a supraglottic mass and as a neck swelling. A case of malignant paraganglioma of the larynx with metastasis to the cervical lymphnodes and lungs have been presented with brief review of literature.     

Neural hamartoma of nose

Hamartoma is characterized by an excessive amount of cell proliferation which reaches maturity and then cease to reproduce, hence hamartoma are self limiting. Therefore the hamartoma is a tumour like but are not tumours. A case of neural hamatoma of nose is reported here.