Does hyperimmunoglobulinemia-E protect tropical populations from allergic disease?

The Waorani Indians of eastern Ecuador have the highest blood concentration of IgE reported in a human population. Evidence obtained by medical history, physical examination, and immediate hypersensitivity skin tests suggests that pollen allergy and other atopic diseases are rare among the Waorani. A similar association between parasite-induced hyperimmunoglobulinemia-E and a low prevalence of conventional atopic disease has been reported in numerous other tropical populations. Saturation of mast cell IgE receptors with antibodies directed to the parasite and/or other antigens and competitive inhibition of passive binding of pollen allergen-specific IgE is one hypothetical cause of this association. We have tested this interesting conjecture by passively sensitizing the skin of Waorani Indians with serum containing pollen allergen-specific IgE antibodies. Waorani Indians with hyperimmunoglobulinemia-E can be adoptively sensitized with human ragweed or rye grass hyperimmune IgE antisera. This suggests that the cutaneous mast cells of healthy Waorani have active IgE receptors. The high circulating plasma concentrations of IgE in the Waorani do not prevent adoptive cutaneous sensitization with pollen-specific IgE antibodies.     

Sequence variation and size ranges of CAG repeats in the Machado-Joseph disease, spinocerebellar ataxia type 1 and androgen receptor genes

A subgroup of trinucleotide repeat diseases result from abnormalexpansions of CAG repeats which are translated into polyglutaminestretches. As yet there is little understanding of how the polyglutaminesfunction either normally, or when expanded. We have investigatedthese sequences in the Machado-Joseph disease, androgen receptorand spinocerebellar ataxia type 1 genes in humans and otherprimates. None of the 748 normal chromosomes that were examinedhad more than 34 uninterrupted gluta-mine codons in the Machado-Josephdisease gene. Similarly, no normal alleles with more than 39uninterrupted glutamine codons have been reported for the otherdisease genes associated with polyglutamine expansions. Sequenceanalyses of the repeats in primates revealed shorter polyglutaminestretches in some of the non-human primates at all three lociand marked diversions from the expected polyglutamines in theorang-utan Machado-Joseph gene and in the marmoset spinocerebellarataxia type 1 gene. These data suggest that conservation ofthese polyglutamine stretches may not always be necessary fornormal gene function.     

Comparison of the expression of p53, p21, Bax and the induction of apoptosis between patients with basal cell carcinoma and normal controls in response to ultraviolet irradiation

AIM: Ultraviolet light (UV) is known to cause DNA damage in the epidermis. The damaged DNA is repaired or deleted by apoptosis to prevent the generation of cancer. It has been suggested that a deficient apoptotic mechanism may predispose individuals to skin cancer. Therefore, the response of normal controls and patients with basal cell carcinoma (BCC) to UV irradiation was investigated. METHODS: The buttock skin from normal volunteers and patients with BCC was irradiated using solar simulated radiation (SSR). SSR mimics the effect of natural sunlight. Skin biopsies were excised and examined for p53, p21, and Bax protein expression and for the induction of apoptosis. RESULTS: At 33 hours after UV irradiation, the induction of apoptosis was significantly higher (p = 0.04) in patients with BCC than in normal volunteers (Mann Whitney test). A trend towards higher p21 expression was found at 33 hours in patients with BCC (mean, 18.69 positive cells/field) than in normal volunteers (mean, 9.89), although this difference was not significant (p = 0.05 positive cells/field). CONCLUSION: These results may imply that patients with BCC have enhanced sensitivity to UV irradiation or that there is some defect in the cell arrest or repair pathways, which results in damaged cells been pushed into apoptosis rather than repair.     

Specific immune response in the respiratory tract after administration of an oral polyvalent bacterial vaccine.

An oral killed polyvalent bacterial vaccine was assessed in a double-blind trial involving healthy volunteers. Three courses of oral vaccine were given over a 2-month period; each course contained 10(10) Haemophilus influenzae and 7 X 10(9) Staphylococcus aureus organisms. Immunity was assessed by monitoring antibody in saliva and serum over a 3-month period. No evidence of a nonspecific effect on immune parameters (immunoglobulin levels and Escherichia coli antibody) was detected in saliva or serum. An increase in H. influenzae antibody in saliva was detected in 55% of subjects receiving the vaccine compared with 6.7% of the placebo group. Antibody was associated with immunoglobulin A (IgA), IgG, and IgM, but the greatest increases over preimmunization levels were detected in the IgA class. No increase in serum antibody levels was detected. Subjects with higher preimmunization levels of salivary antibody to H. influenzae were less likely to respond to the oral bacterial vaccine. No increase in S. aureus antibody was detected in saliva or serum.     

Purification of actin from Candida albicans and comparison with the Candida 48,000-Mr protein.

Actin was purified from Candida albicans cells by affinity chromatography by DNase-Sepharose and was recognized by immunoblotting with monoclonal antibody directed against chick muscle actin. The C. albicans 48-kilodalton protein recognized by sera from patients with invasive candidiasis was shown by DEAE chromatography and immunoblotting not to be identical with the purified C. albicans actin.     

Serum IgD concentrations in sarcoidosis and tuberculosis

Studies of the serum level of IgD in patients with tuberculosis and sarcoidosis reveal evidence of a difference in humoral immunity. Radial diffusion measurements were done of IgD in serums from fifty patients with active tuberculosis, fifty-three patients with sarcoidosis and 103 age, race and sex matched healthy controls. IgD was detected in serums from 20% more tuberculosis patients (P<0·0250) and 20·7% fewer sarcoidosis patients than respective controls (P<0·0005). Multivariate statistical analysis of log_e transformed IgD serum levels revealed significantly lower geometric mean IgD levels in sarcoidosis patients (P=0·0018). The age dependence of serum IgD was highly significant (P<0·0001). Age dependent disease effects were detected. High levels of IgD occurred predominantly in older tuberculosis patients while depression of IgD occurred in middle-aged sarcoidosis patients. It is suggested that the elevated levels of serum IgM in patients with sarcoidosis may represent a compensatory change associated with low levels of serum IgD.     

Identification of an IGF-1R kinase regulatory phosphatase using the fission yeast Schizosaccharomyces pombe and a GFP tagged IGF-1R in mammalian cells.

AIMS: To study the regulation of type 1 insulin like growth factor receptor (IGF-1R) tyrosine kinase activity using the fission yeast Schizosaccharomyces pombe and a green fluorescent protein (GFP) tagged, full length IGF-1R. METHODS: The beta chain of the IGF-1R (betawt) was expressed under inducible conditions in the fission yeast S. pombe. Western blot analysis with antiphosphotyrosine antibodies was used to assess the kinase activity of betawt. A GFP tagged IGF-1R (GFP-IGF-1R) was constructed to study the tyrosine kinase activity of the full length IGF-1R. The signalling capabilities of GFP-IGF-1R in response to IGF-1 stimulation were investigated in transiently transfected fibroblasts. Immunofluorescent staining for cellular phosphotyrosine content was used to assess the localisation and tyrosine kinase activity of GFP-IGF-1R. RESULTS: The betawt protein displayed functional tyrosine kinase activity in S pombe and phosphorylated endogenous yeast proteins. In response to IGF-1 stimulation, the GFP-IGF-1R became autophosphorylated and also activated the phosphatidylinositol 3-kinase and mitogen activated protein kinase pathways. Tyrosine phosphorylation and kinase activity of the GFP-IGF-1R could be visualised by immunofluorescence with antiphosphotyrosine antibodies. Coexpression of a mammalian tyrosine phosphatase PTP1B with betawt completely inhibited this tyrosine kinase activity in yeast and also reduced the tyrosine phosphorylation in COS cells transfected with the GFP-IGF-1R. CONCLUSIONS: Schizosaccharomyces pombe can be used to analyse the tyrosine kinase activity of the IGF-1R beta chain and its regulation by tyrosine phosphatases. In addition, the regulation of IGF-1R tyrosine kinase activity can be studied using a GFP tagged IGF-1R. Using both of these methods, IGF-1R kinase activity was shown to be inhibited by the protein tyrosine phosphatase, PTP1B.     

Diagnostic impact of core-needle biopsy on fine-needle aspiration of non-Hodgkin lymphoma

We retrospectively reviewed 74 fine-needle aspiration (FNA) cases of presumptive non-Hodgkin lymphoma (NHL). All the cases had cytology and core-needle biopsy and 53 cases had concurrent flow cytometric analysis. FNA (cytology and flow cytometry) and core-needle biopsy were evaluated independently. FNA was diagnostic of diffuse large B-cell lymphoma (DLBL) in 25% (13/53) of cases and small B-cell NHL in 15% (8/53) of cases, whereas core-needle biopsy was diagnostic of DLBL in 37% (27/74) of cases and small B-cell NHL in 8% (6/74) of cases. Subclassification of small B-cell NHL was reached in 3/6 cases by core-needle biopsy. Insufficient cases were observed in both FNA (47%; 25/53) and core-needle biopsy (28%; 21/74) groups. With the combination of FNA and core-needle biopsy, diagnostic cases of DLBL increased to 43% (32/74) and insufficient samples were reduced to 16% (12/74). There was no clear advantage in the diagnosis and classification of small B-cell NHL by adding core-needle biopsy to FNA (14%; 10/74). We conclude that core-needle biopsy is a useful adjunct to FNA in the diagnosis of DLBL and shall be encouraged. In small B-cell NHL, core-needle biopsy does not add to the diagnostic ability of FNA. Cases insufficient for diagnosis may be seen in both core-needle biopsy and FNA. A combined approach reduces the number of insufficient cases and is recommended in routine FNA practice.