bluuebunny/crossref_metadata_2025 huggingface dataset:
Taxonomy of Meloidogyne (Nematodea: Heteroderidae) with descriptions of four new species*
Authors: Whitehead A. G.
Published: August 2010

A review of the literature on Meloidogyne Goeldi, 1887 (endoparasitic gall‐forming nematodes in roots of higher plants) emphasised the need for a detailed morphological study of the genus to provide an adequate basis for the identification of its species. The taxonomic study reported here confirmed the morphological distinctness of 23 species, including four new ones–M. decalineata sp. n., M. ethiopica sp. n. and M. megadora sp. n. from Africa and M. indica sp. n. from India. M. inornata Lordello, 1956a and M. tadshikistanica Kiryanova & Ivanova, 1965 may also be distinct species but M. poghossianae Kiryanova, 1963 is regarded as a species inquirenda. Meloidogyne spp. can be identified by the posterior cuticular pattern of the females and the morphology of the water‐hatched, fixed larvae and of the males. Measurements, especially of water‐hatched, fixed larvae are also useful in the differentiation of species. An improved technique for identification of Meloidogyne spp. is proposed and keys based on adults and on larvae are presented. Types are designated for M. exigua Goeldi, 1887, M. arenaria (Neal, 1889) Chitwood, 1949, M. hapla Chitwood, 1949, M. incognita (Kofoid & White, 1919) Chitwood, 1949, M. javanica (Treub, 1885) Chitwood, 1949 and M. thamesi Chitwood in Chitwood, Specht & Havis, 1952 (Goodey, T., 1963). The genus Hypsoperine Sledge & Golden, 1964 is rejected and two of its species renamed M. graminis (Sledge & Golden, 1964) comb. n. and M. spartinae (Rau & Fassuliotis, 1965) comb, n., while H. acronea (Coetzee, 1956) Sledge & Golden, 1964 is returned to M. acronea Coetzee, 1956.
The characteristics and affinities of the Amphisbaenia
Authors: Gans Carl
Published: August 2010

The amphisbaenians, to judge from the many changes of opinion regarding their appropriate position among the vertebrates, appear to have puzzled most students of herpetology. Re‐evaluation suggests that a case may now be made for classifying the amphisbaenians as an order, separate from the lizards and snakes, but included with them in a superorder Squamata. Evidence for such a position may be derived from several dozen systems in which amphisbaenians differ from lizards, from snakes, or from both. Although individual character states are occasionally equivalent to those shown by one or another family of lizards, there is no “closest” family. This suggests that the Amphisbaenia probably diverged from the remainder of the Squamata before the diversification of all present families of lizards. Unfortunately many of the character states are still known from only a limited number of amphisbaenians and information for other groupings of squamates is similarly inadequate.
The breeding biology and early development of Clarias gariepinus (Pisces: Clariidae) in Lake Sibaya, South Africa, with a review of breeding in species of the subgenus Clarias (Clarias)
Authors: Bruton M. N.
Published: August 2010

The breeding biology and early development of the common southern African clariid catfish, Clarias gariepinus (Burchell), are described. C. gariepinus reaches maturity towards the end of the second year (350 mm TL, rarely towards the end of the first year, 240 mm TL). The modal size of breeding fishes is 540 mm in females and 580 mm in males. A modal size female produces about 50,000 eggs, but large females may produce over 150,000 eggs. Gonadal maturation stages are described. Gonadal maturation is associated with increasing water temperatures and photoperiod from July to September, and the spawning season extends from September to March (Summer). Spawning takes place at night, usually after heavy rain in recently inundated marginal areas. There is a massive aggregation of catfish before spawning, and courtship is preceded by aggressive encounters between males. Mating takes place between isolated pairs in shallow water among inundated terrestrial or semi‐aquatic grasses and sedges.

There is no parental protection of the young (as found in many other catfish families) except by the careful choice of a suitable spawning site. Egg and larval development is rapid and the larvae are capable of swimming strongly within 48 hours of fertilization. The larvae are secretive and feed on small invertebrates which are abundant in the shallow inshore areas which they inhabit.

As C. gariepinus awaits suitable environmental conditions for spawning, this species is far more dependent on external factors, especially rainfall and water level, than two cichlids, a guarder and a mouth‐brooder, which also occur in Lake Sibaya.

The breeding biology of other species of Clarias (mainly in the subgenus Clarias (Clarias)) is reviewed and compared with that of C. gariepinus. The marked dichotomy between nest‐guarding in two Asian species, and non‐guarding, open‐substrate spawning in all other Asian and African species, is noted. Finally, further interesting lines of research on the breeding biology of Clarias species are outlined.
A transmission and scanning electron microscopy study of the cuticle and epidermis of Pomatoceros lamarckii (Polychaeta: Serpulidae)
Authors: Bubel Andreas
Published: August 2010

The structure of the cuticle and epidermis in different regions of the body of the serpulid, Pomatoceros lamarckii Quatrefages, is described by means of transmission and scanning electron microscopy. The thickness and ultrastructure of both the cuticle and epidermis is seen to vary in different regions of the body. The cuticle of the opercular filament, thorax and main parts of the branchial filaments, pinnules and collar is composed of layers of orthogonally arranged fibres embedded in an amorphous matrix and capped by a thin superficial filamentous layer. The cuticular fibres are unstriated and are formed of bundles of thin fibrils. In contrast, the cuticle covering the abdomen and parts of the collar and pinnules is composed of a filamentous matrix. However, over all the body the cuticle is traversed by microvilli from underlying epidermal cells. Evidence is presented that the epidermal cells are the source of the cuticle material.

A single gland cell type is found within the epidermis of the pinnules, whereas two gland cell types are found within the epidermis of the thorax. The gland cells possess secretory granules with distinctive contents that arise from polarized Golgi complexes. The thorax gland cells are found to secrete their contents to the exterior of the animal through channels in the cuticle. Scattered throughout the epidermis of the opercular filament, branchial filaments and collar are small groups of sensory cilia which pass vertically through the cuticle. Discussion centres around the nature of the cuticle, the mode of cuticle secretion, the nature and function of the gland cells and the distribution of epidermal sensory cells. The significance of these findings is compared with those in other annelids.
The effects of CP 17193, an immunosuppressive pyrazaloquinoline, on the development of spontaneous lupus disease in NZBW F1 hybrid mice
Authors: BUNDICK R V , EADY R P
Published: August 2010

The effects of the immunosuppressive agent CP 17193 on the development of spontaneous lupus disease in female NZBW F1 hybrid mice were investigated. Long term dosing with CP 17193 markedly delayed the onset of mortality but did not extend the long term survival of the mice. CP 17193 significantly inhibited immune complex deposition in the glomeruli of 30- and 35-week-old mice and also reduced the levels of proteinuria in the 35-week-old mice. There was a slight reduction in the levels of circulating antinuclear antibody to ds DNA in CP 17193-treated mice but this was not statistically significant. Studies on immune cell function of 35-week-old mice dosed with CP 17193 showed significant reduction in the total numbers of spontaneous polyclonal antibody producing cells. Analysis of the results revealed these effects to result from a marked reduction in total spleen cell numbers in CP 17193-treated mice. When results were expressed as activity per cell unit the differences between drug-treated and control mice were small. Spleen cells from mice given a shorter dosing schedule of 7 weeks with CP 17193 showed an augmentation of IL-2 production and responsiveness. These results show CP 17193 having interesting selective immunomodulating activity on the immunopathogenesis of spontaneous murine lupus disease. Furthermore, compounds with this profile of activity may have a potential role in the treatment of some autoimmune diseases.
Cyclophosphamide treatment antagonizes thein vitrodevelopment ofMycobacterium lepraemurium-induced suppressor cell precursors
Authors: GOSSELIN D , TURCOTTE R , LEMIEUX S
Published: August 2010

The in vitro-inducible maturation of splenic suppressor cell precursors detected during the early phase of Mycobacterium lepraemurium infection can be abrogated when a high dose of cyclophosphamide (Cy) is inoculated to infected mice 2 days before assay. The drug does not act directly on adherent suppressor cell precursors, but rather inhibits their activation by a non-adherent cell subset whose phenotype has not yet been elucidated. It was established by flow cytometry analyses, that despite a marked increase in the total number of splenic non-adherent cells following M. lepraemurium infection, the effect of Cy on Ia+, Thy-1+, CD4+ and CD8+ cells in infected mice was comparable to that observed in normal controls. It was not possible to determine the duration of the inhibiting effect of Cy on non-adherent regulatory cells, because the drug was itself inducing suppressor cells from 7 days after inoculation. By the time spleen cell suspensions were totally free of Cy-induced suppressor cells, infection-dependent suppressor cell precursors were once again detected, indicating that Cy treatment did not prevent their in vivo accumulation. Therefore, even though M, lepraemurium induced adherent suppressor cell precursors are themselves fully resistant to Cy, their development is transiently abrogated by the drug, most probably through the impairment of a non-adherent cell subset regulating their maturation.
T cell heterogeneity in patients with common variable immunodeficiency as assessed by abnormalities of T cell subpopulations and T cell receptor gene analysis
Authors: PANDOLFI F , TRENTIN L , MARTIN J E SAN , WONG J T , KURNICK J T , MOSCICKI R A
Published: August 2010

T lymphocyte regulation of immunoglobulin production may be abnormal in some patients with common variable immunodeficiency (CVI). Phenotypic analysis of peripheral blood T lymphocytes from nine patients with CVI was conducted to examine whether an abnormal distribution could be detected in a functionally distinct T lymphocyte subpopulation. The percentage of CD8+ lymphocytes proved to be increased in some patients and decreased in others. In comparison with normal controls, many patients with CVI had reduced percentages of lymphocytes expressing both CD4 and CD45RA, a phenotype associate with naive CD4+ cells. There was no significant difference in CD4+ populations bearing CD29 or leucocyte adhesion molecule-1 (LAM-1) antigens. The pattern of gene rearrangement of the T cell antigen receptor (TCR) was studied using peripheral blood lymphocytes from these patients with CVI. Genomic DNA from freshly isolated lymphocytes as well as from selectively propagated CD4+ or CD8+ populations were examined using Southern blot analysis and a probe for the β chain of the TCR. A polyclonal pattern of TCR gene rearrangement, without the appearance of dominant non-germline bands, was demonstrated in all patient samples. These data suggest that the T lymphocytes in patients with CVI have a polyclonal pattern of TCR rearrangement despite an abnormal distribution of T cell subpopulations in some patients.
Raised serum neopterin levels in patients with primary hypogammaglobulinaemia; correlation to other immunological parameters and to clinical and histological features
Authors: AUKRUST P , FRØLAND S S , MÜLLER F
Published: August 2010

Serum neopterin levels were analysed in 43 patients with primary hypogammaglobulinaemia (25 common variable immunodeficiency (CVI), 12 congenital hypogammaglobulinaemia (CH), six X-linked hypogammaglobulinaemia (XLH)), and in 33 healthy controls. The neopterin values were correlated to lymphocyte subset counts in peripheral blood, lymphocyte mitogen responses and clinical and histological manifestations in the study group. Serum neopterin levels were significantly elevated in all subgroups of patients and particularly in the CVI groups where the highest concentrations were found (P < 0.001, CVI versus controls). Furthermore, in CVI and CH patients elevated neopterin levels were strongly correlated to decreased number of CD4+ lymphocytes (rs=– 0.61, P < 0.005 and rs=– 0.83, P < 0.001, respectively). In the CVI group high neopterin levels were also significantly correlated to low number of circulatory B (CD19+) lymphocytes (rs=– 0.58, P < 0.05). Both patients with moderately and those with severely depressed lymphocyte mitogen responses had significantly higher neopterin levels than those with normal responses. In addition, high neopterin levels were significantly associated with the occurrence of splenomegaly and nodular intestinal lymphoid hyperplasia. The immunological findings were consistently observed in longitudinal testing, and appeared to be characteristic for the individual patient. High serum neopterin levels are thought to be a marker for hyperactivity in monocytes/macrophages, and dysfunction of these cells may therefore be associated with fundamental immune pathology in some subgroups of primary hypogammaglobulinaemia.
Analysis of T cell receptors in rheumatoid arthritis: the increased expression of HLA-DR antigen on circulating γδ+ T cells is correlated with disease activity
Authors: LAMOUR A , JOUEN-BEADES F , LEES O , GILBERT D , LE LOET X , TRON F
Published: August 2010

The phenotypic characteristics of peripheral blood T cells, isolated from 37 rheumatoid arthritis (RA) patients and 17 healthy controls were determined with special emphasis on γδ+ T cells and CD4−CD8−αβ+ T cells. Two- and three-colour automated flow cytometry analyses were performed using a panel of MoAbs directed against differentiation antigens and T cell receptor molecules. The results demonstrated: (i) no significant difference between the percentages or CD4−CD8−αβ+ T cells in patients and controls; (ii) a significant decrease of the γδ+ T cell level in the peripheral blood of RA patients relative to controls; (iii) phenotypic abnormalities of circulating γδ+ T cells in RA patients suggestive of an activation status in vivo. These abnormalities included a significant reduction in the density of the T cell differentiation antigen CD3 and an increase in the expression of HLA-DR antigen. The level of circulating HLA-DR+/γδ+ T cells was significantly higher in patients with active disease. HLA-DR+/γδ+ T cells were also present in the synovial fluid obtained from three patients with an active disease. In addition, preliminary experiments showed that the activated γδ+ T cells were predominantly Vδ1. Taken together, these data support the involvement of γδ+ T cells in the pathogenesis of RA.
Acceleration of onset of collagen-induced arthritis by intra-articular injection of tumour necrosis factor or transforming growth factor-beta
Authors: COOPER W O , FAVA R A , GATES C A , CREMER M A , TOWNES A S
Published: August 2010

We examined whether tumour necrosis factor (TNF) or transforming growth factor-beta 1 (TGF-β1) could alter the course of collagen-induced arthritis (CIA). Injection of 100 ng TNF or 500 ng TGF-β1 into ankle joints of normal rats induced a very limited inflammatory response, observable only upon histological analysis. However, when injected into ankle joints of rats 9 days after immunization with bovine type II collagen (CII), identical doses of TNF or TGF-β1 induced a sustained, clinically obvious inflammation and oedema that began within 8 h on average, as compared to 90 h in CII-inimunized control rats given no injections or intra-arlicular injections of buffer. The incidence of arthritis at 2 weeks post-immunization was 100% for TNF-injected hindpaws, compared with 55% for the control groups, a statistically significant difference. In rats passively immunized with a subarthritic dose of affinity purified antibody to rat-CII, intra-articular injection of 100 ng TNF or 500ng of TGF-β1 also induced intense, though transient arthritis. The rapid proinflammatory effects in CIA described in this study and the synergy demonstrated between anti-CII IgG and either cytokine, suggest that these cytokines can participate locally in the pathogenesis of arthritis.
Interferon-gamma (IFN-γ) and macrophage inflammatory proteins (MIP)-1 and -2 are involved in the regulation of the T cell-dependent chronic peritoneal neutrophilia of mice infected with mycobacteria
Authors: APPELBERG R
Published: August 2010

In mycobacterial infections of mice there is a chronic, immune-mediated mobilization of neutrophils to the infectious site. In this study we evaluated the role played by cytokines in the chronic peritoneal neutrophilia which occurs in mice intraperitoneally infected with Mycobacterium bovis BCG or M. avium. Antibodies to IFN-γ and to MIP-1 and -2 were effective in reducing peritoneal neutrophilia when given during the infection. Whereas the former antibody was only effective when given early, the latter two were effective when administered late in infection, suggesting the MIPs were direct mediators of neutrophil recruitment. Recombinant IFN-γ given intraperitoneally induced the accumulation of neutrophils and primed the peritoneal cells for an enhanced recruitment of neutrophils. Our data show that chronic neutrophilia during mycobacterial infection is regulated by different cytokines acting at different stages and levels of neutrophil recruitment.
Anti-myeloperoxidase autoantibodies react with native but not denatured myeloperoxidase
Authors: FALK R J , BECKER M , TERRELL R , JENNETTE J C
Published: August 2010

We wondered whether anti-myeloperoxidase (MPO) autoantibodies (MPO-ANCA) found in patients with systemic vasculitis react with a conformational epitope or epitopes on the MPO molecule. Sera from 15 human MPO-ANCA, and a polyclonal and a monoclonal anti-MPO antibodies were reacted with MPO in native and denatured states. Human MPO-ANCA and mouse monoclonal anti-MPO reacted with native MPO, and a 120-kD band representing the MPO hologenzyme, but not with denatured MPO fragments; however, MPO-ANCA and mouse anti-MPO did not demonstrate competitive inhibition of binding to MPO. Polyclonal rabbit anti-MPO reacted with both native and denatured MPO. All MPO-ANCA tested showed the same patterns of reactivity with native and denatured MPO in dot blot and Western blot analyses. Both polyclonal and monoclonal anti-MPO antibodies inhibited MPO's protein iodination by over 90%, whereas MPO-ANCA IgGs, normal IgGs and disease control IgGs did not. These data suggest that (i) MPO-ANCA interact with a conformational epitope on the MPO molecule; and (ii) MPO-ANCA from different patients have similar reactivity with native versus denatured MPO.
Severe malaria in Gambian children is not due to lack of previous exposure to malaria
Authors: ERUNKULU O A , HILL A V S , KWIATKOWSKI D P , TODD J E , IQBAL J , BERZINS K , RILEY E M , GREENWOOD B M
Published: August 2010

The reasons why only a small proportion of African children infected with Plasmodium falciparum develop severe or fatal malaria are not known. One possible reason is that children who develop severe disease have had less previous exposure to malaria infection, and hence have less acquired immunity, than children who develop a mild clinical attack. To investigate this possibility we have measured titres of a wide range of anti-P. falciparum antibodies in plasma samples obtained from children with severe malaria, children with mild malaria and from children with other illnesses. Mean antibody levels in patients with malaria were higher than those in patients with other conditions but. with only one exception, there were no significant differences in antibody litres between cases of severe or mild malaria. A parasitized-erythrocyte agglutination assay was used to estimate the diversity of parasite isolates to which children had been exposed; plasma samples obtained from children with cerebral malaria recognized as many isolates as did samples obtained from children with mild disease. Our findings do not provide any support for the view that the development of severe malaria in a small proportion of African children infected with P. falciparum is due to lack of previous exposure lo the infection.
Potentiation of a weakly active ricin A chain immunotoxin recognizing the neural cell adhesion molecule
Authors: DERBYSHIRE E J , STAHEL R A , WAWRZYNCZAK E J
Published: August 2010

A ricin A chain immunotoxin, SEN36-ricin A chain, directed against the neural cell adhesion molecule (N-CAM) had no selective cytotoxic activity against three different small cell lung cancer (SCLC) cell lines in tissue culture despite expression of the target antigen on more than 98% of cells in each line detected by indirect immunofluorescence. Treatment of the SW2 SCLC cell line with suramin and interferons alpha and gamma increased the level of N-CAM expression only slightly and had no significant effect on the cytotoxic activity of the SEN36 immunotoxin. In the presence of the carboxylic ionophore monensin at a concentration of 0·1 μM, the toxicity of SEN36-ricin A chain to the SW2 cell line was enhanced by 12 000-fold. In contrast, lysosomotropic amines showed little or no potentiation of activity, suggesting that lysosomal degradation was not the major factor limiting the action of the anti-N-CAM immunotoxin. The findings of this study indicate that ricin A chain immunotoxins directed against N-CAM on SCLC are unlikely to have sufficient activity to be useful therapeutic agents in the absence of potentiating agents such as monensin, which can interfere with the normal intracellular pathways of antigen routing.
Mononuclear cells from HIV-infected patients produce factors which enhance functional activity of polymorphonuclear neutrophils from healthy subjects
Authors: GABRILOVICH D I , SHEPELEVA G K , SEREBROVSKAYA L V , AVDEEVA L A , SUVOROVA Z K , ROSLY I M , OGANEZOV V K , SAIDOV M Z , PANYUTICH A V , POKROVSKY V V
Published: August 2010

The influence of mononuclear cell supernatants (MNCS) from nine healthy donors and 35 HIV-infected patients (17 with lymphoadenopathy syndrome (LAS), 15 with ARC and three with AIDS) on functional activity of polymorphonuclear neutrophils (PMN) from healthy donors was investigated. MNC after short-term cultivation (24 h) produced factors which enhanced chemiluminescence (CL) and chemotaxis of PMN. This augmentation did not depend on stimulation of MNC by mitogens (lipopolysaccharide Escherichia coli (LPS) and concanavalin A (Con A)) or on activation of PMN by FMLP. After 48 h of cultivation only MNC stimulated by LPS produced these factors. MNCS from HIV-infected patients provoked a more pronounced augmentation of PMN CL compared with MNCS from healthy subjects. This enhancement was observed in patients at all stages of infection, but was more pronounced in patients with LAS, MNCS impact on PMN CL was not connected with proliferative activity of MNC but was correlated with the level of CD4 cells. It was shown that removal of adherent cells from MNC fraction resulted in decreased MNCS impact. Treatment of MNCS by antibody to IL-1β, IL-8, interferon-alpha (IFN-α) and tumour necrosis factor-alpha (TNF-ş) did not decrease MNCS impact on PMN CL.
Predictors of infection in chronic lymphocytic leukaemia (CLL)
Authors: GRIFFITHS H , LEA J , BUNCH C , LEE M , CHAPEL H
Published: August 2010

A group of patients with chronic lymphocytic leukaemia (CLL) were studied to determine whether particular clinical and laboratory parameters might help to identify those patients at risk of recurrent infection who would benefit from immunoglobulin replacement therapy. The case notes of 59 patients were reviewed with regard to stage and duration of disease, chemotherapy and frequency of infection over the preceding 2 years. Serum IgG levels and specific antibodies to tetanus, diphtheria and pneumococcal capsular polysaccharide were measured at the end of the 2-year period. A group of 56 healthy age-matched volunteers were used as controls. Eighteen patients had severe or multiple infections during the study period, 11 patients had recurrent infections and the remaining 30 patients had only minimal infections. Overall, serum IgG levels were low in 32 patients but in none of the control group (P=8·8 × 10−11). However, less than half of those patients with hypogammaglobulinaemia suffered from severe or multiple infections. Specific antibodies to pneumococcal capsular polysaccharide were low in 23 patients compared with six of the control group (P=4·9 × 10−4). The majority of patients with severe or multiple infections (13/18) had low levels of both total IgG and specific antibodies to pneumococcal capsular polysaccharide. However, in the groups of patients with less frequent infections, a higher proportion had low serum IgG than low pneumococcal antibody levels. Low levels of pneumococcal antibodies were particularly associated with severe or multiple infections (P= <0·00001).
The macrophage response to bacteria. Modulation of macrophage functional activity by peptidoglycan fromMoraxella (Branhamella) catarrhalis
Authors: KELLER R , GUSTAFSON J E , KEIST R
Published: August 2010

Moraxella (Branhamella) catarrhalis organisms have been shown to be particularly efficient in inducing in a pure population of bone marrow-derived mononuclear phagocytes secretory and cellular activities. In the present study, the ability of peptidoglycan from this Gram-negative organism to trigger a macrophage response was compared with that elicited by peptidoglycan from Staphylococcus aureus and Bacillus subtilis. The results show that the three peptidoglycans were similarly active in triggering the secretion of tumour necrosis factor and tumouricidal activity but differed considerably in their ability to induce the generation of nitrite in macrophages; in this respect, peptidoglycan from M. catarrhalis was particularly potent. The impressive capacity of M. catarrhalis peptidoglycan to induce in low concentration the secretion of tumour necrosis factor and nitrite and tumouricidal activity may, in addition to its lipopolysaccharide, contribute to the extraordinary potential of this organism to trigger the functional activities of macrophages.
Characterization of B cell epitopes on the 16K antigen ofMycobacterium tuberculosis
Authors: VERBON A , HARTSKEERL R A , MORENO C , KOLK A H J
Published: August 2010

To characterize the antigenic parts of the 16K protein of Mycobacterium tuberculosis, overlapping peptides according to the amino acid sequence of the 16K protein were synthesized. In total, 14 peptides of 20 amino acids in length with an overlap of 10 amino acids and two additional decapeptides (amino acids 31–40 and 61–70) were tested with eight anti-16K MoAbs and human sera. The common recognition site of MoAbs F67-8and F67-16 was LRPTFDTRLM (amino acids 31–40) and of MoAbs F159-1 and F159-11 DPDKDVDIM V (amino acids 61-70). However, for binding of the MoAbs to these peptides additional amino acids were required at either the N- or C-terminus, suggesting that some kind of conformation is required. The recognition sites of the MoAbs F23-41, F23-49, F24-2 and TB68 could not be identified using the peptides, indicating that the MoAbs only bound to conformational epitopes and not to peptides which may contain parts of these epitopes. The MoAbs bound to β-galactosidase fusion proteins comprising parts of the 16K protein, indicating that some kind of native conformation is present on the recombinant proteins. Sera from 14 of 19 patients with tuberculosis and none from 19 controls reacted with the purified 16K protein. Sera from four of these 14 patients reacted with two overlapping peptides (amino acids 71–100). Apparently, antibodies in patients' sera against the 16K protein are predominantly directed against conformational epitopes.
Hepatitis C: a possible etiology for cryoglobulinaemia type II
Authors: PECHÈRE-BERTSCHI A , PERRIN L , de SAUSSURE P , WIDMANN J J , GIOSTRA E , SCHIFFERLI J A
Published: August 2010

Out of 15 successive patients with mixed essential cryoglobulinaemia type II (monoclonal IgM kappa /IgG), 13 had serological evidence for hepatitis C infection as shown by specific enzyme immunoassays and immunoblot. RNA was purified from the serum of seven patients and hepatitis C sequences were identified in five following reverse transcription and DNA amplification. The liver histology showed chronic active hepatitis with or without cirrhosis in the 12 patients with hepatitis C who had a liver biopsy. The two patients without serological evidence of hepatitis C suffered from haematological malignancies. Hepatitis C may be a major etiological agent of cryoglobulinaemia type II.
Soluble CD23 levels are elevated in the serum of patients with primary Sjögren's syndrome and systemic lupus erythematosus
Authors: BANSAL A , ROBERTS T , HAY E M , KAY R , PUMPHREY R S H , WILSON P B
Published: August 2010

The low affinity IgE receptor FcɛRII (CD23) is important in several aspects of T and B cell function. In this study serum levels of soluble CD23 (sCD23) were measured in three groups: 26 female patients with systemic lupus erythematosus (SLE), 21 females with primary Sjögren's syndrome (pSS) and 25 normal healthy females. The concentration of sCD23 was determined using an enhanced chemiluminescent sandwich ELISA developed in this laboratory. Increased levels of sCD23 were observed in pSS and in SLE patients compared with controls (median 23·0 versus 8·6, P <0·0002 and 18·1 versus 8·6, P <0·002 respectively). While the median level of sCD23 was found to be higher in pSS than in SLE the difference was not statistically significant. Patients with SLE and pSS on glucocorticoid treatment had significantly lower levels of sCD23 than patients not on this treatment (median 28·9 versus 14·4, P <0·05). Amongst the control patients sCD23 was inexplicably lower in the female members relative to the males (median 8·5 versus 12·3, P <0·05). Although serum IgG and IgA levels were significantly elevated in pSS and SLE patients relative to controls there was no direct correlation between sCD23 and the serum levels of these immunoglobulins. We conclude that B cell hyperactivity which occurs in both pSS and SLE is associated with raised levels of sCD23.
T cell responses to synthetic TSH receptor peptides in Graves' disease
Authors: TANDON N , FREEMAN M A , WEETMAN A P
Published: August 2010

Twenty-eight peptides, representing the entire extracellular domain of the TSH receptor, were synthesised to investigate which parts of this autoantigen may be targets for the T cell response in Graves' disease (GD). T cells from 11 of 21 controls and 26 of 36 newly diagnosed GD patients proliferated in response to one or more peptides with a stimulation index (SI) of > 2·0 (χ2 = 2·31, P > 0·1). The response of patients and controls to any of the individual peptides was also not statistically different. However, individual patients gave high SIs with certain peptides to which controls either gave an absent or very weak response. HLA-DR3 was not associated with any particular response to TSHR peptides. Three out of seven GD patients whose T cells were evaluated before and after treatment showed a response of this kind only early in the course of their disease. Intrathyroidal T cells from four GD patients did not give a consistent proliferative response to pools of five peptides, and depleting peripheral blood T cells of their CD8+ population did not affect the proliferative response. These results indicate that the T cell response to the TSH receptor in GD does not seem to be directed against any one particular epitope on the peptides we have tested which cover the extracellular domain.
Increased expression of IgG Fc receptor type I on neutrophils and monocytes from HIV-infected subjects
Authors: CAPSONI F , MINONZIO F , ONGARI A M , COLOMBO G , RIZZARDI G P , BONARA P , D'ARMINIO-MONFORTE A , ZANUSSI C
Published: August 2010

Interferon-gamma (IFN-γ) induces de novo expression of IgG Fc receptor type I (FcRI) on neutrophils and significantly raises the level of these receptors on monocytes. Since increased concentrations of IFN-γ have been observed in sera from patients with HIV infection, FcRI expression might also be increased on these subjects' phagocytes. FcRI expression was assessed by indirect immunofluorescence staining of phagocytes in whole blood from 40 healthy controls and 55 HIV+ subjects, 24 belonging to CDC class III and 31 to CDC class IV; 42 were intravenous drug abusers (IVDA) and 13 were homosexual men. Plasma levels of IFN-γ were measured using a modified immunoradiometric assay. The mean linear fluorescence intensity, used as a relative measure of receptor expression, was significantly higher on unseparated neutrophils from HIV+ subjects in CDC classes III (P<0·001) and IV (P < 0·0001) than from controls. Similar changes in FcRI expression were observed on monocytes from HIV+ subjects. While no differences were observed between IVDA and homosexual HIV+ patients, there was a significant association between FcRI expression and the patients' CDC stage, those in class IV having the highest FcRI levels. Plasma IFN-γ concentrations were significantly higher in HIV + patients than in controls and a positive correlation with the stages of HIV infection was again observed. FcRI expression was also increased on freshly purified neutrophils from five HIV+ patients in CDC class IV but did not increase further after 18 h incubation with IFN-γ, a treatment that up-regulated FcRI expression on control neutrophils. These data suggest that: (i) FcRI evaluation may be a sensitive marker for the biological activity of IFN-γin vivo; (ii) phagocytes from HIV+ subjects are activated in vivo by IFN-γ, expressing increased levels of FcRI; (iii) these IFN-γ-activated cells may play a role in the pathogenesis of AIDS.
Natural killer (NK) cell activity during HIV infection: a decrease in NK activity is observed at the clonal level and is not restored afterin vitrolong-term culture of NK cells
Authors: SCOTT-ALGARA D , VUILLIER F , CAYOTA A , DIGHIERO G
Published: August 2010

NK cell activity is impaired in HIV-infected patients. The mechanisms behind the altered NK functions are not clear, and conflicting data concerning NK and antibody-dependent cellular cytotoxicity (ADCC) activity have been reported. In order to investigate whether this impairment is also observed at the clonal level and whether it is related to a defect at the target cell binding and/or the post-binding level, we evaluated highly purified NK cell lines and cloned NK cells obtained from 22 HIV-infected patients at different stages of disease and compared them with normal controls for their ability to: (i) kill K-562 and U-937 cell lines using a 51Cr release assay; (ii) bind and kill K-562 and U-937 cells at the single cell binding level; (iii) release NK cytotoxic factor (NKCF), tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ); (iv) kill anti-IgM preincubated Daudi cell line (ADCC activity). This study with cloned NK cells or NK cell lines from HIV-infected individuals showed: (i) a decrease in their lytic capability against target cell lines; (ii) a low ability to form conjugates with K-562 and U-937 cell lines with respect to controls; (iii) a decreased ability to kill bound target cells; (iv) low levels of released NKCF, TNF-α and IFN-γ after incubation with U-937 cells. Taken together, these findings suggest that the impaired NK cell function during HIV infection is also observed at the clonal level and is related to defects both at the target and post-binding levels. However, the precise mechanisms remain to be determined. The inability to restore normal NK activity after long-term culture in the presence of high levels of recombinant IL-2 is in agreement with the hypothesis of a ‘general anergic process’ during HIV infection.
Cellular immunity in tuberculous pleural effusions: evidence of spontaneous lymphocyte proliferation and antigen-specific accelerated responses to purified protein derivative (PPD)
Authors: LORGAT F , KERAAN M M , RESS S R
Published: August 2010

The kinetics of in vitro cellular proliferation against a PPD of Mycobacterium tuberculosis or streptococcal antigen (streptokinase-streptodornase) was evaluated in pleural fluid and peripheral blood mononuclear cells (PBMC) from patients with tuberculous and non-tuberculous pleuritis. The peak proliferative response to PPD by mononuclear cells from pleural fluid occurred earlier (day 3) in 65% of patients with tuberculosis, a finding not seen in non-tuberculous effusions. Spontaneous lymphocyte proliferation of both peripheral blood lymphocytes and pleural effusion lymphocytes was frequently observed, irrespective of etiology. However, 20 of 21 tuberculous patients manifesting spontaneous lymphocyte proliferation had accelerated kinetics of proliferation to PPD, which was antigen-specific. These results suggest that spontaneous lymphocyte proliferation occurs as a response to antigen stimulation at the site of disease, and is not a non-specific response to inflammation. Furthermore, enhanced reactivity against mycobacterial antigen, manifested by accelerated kinetics of proliferation, has diagnostic potential in patients with pleural effusions.
Detection and characterization of immunoconglutinins in patients with systemic lupus erythematosus (SLE): serial analysis in relation to disease course
Authors: NILSSON B , NILSSON EKDAHL K , SJÖHOLM A , NILSSON U R , STURFELT G
Published: August 2010

The levels of IgA, IgG and IgM immunoconglutinins (IK) were assessed in sera from 20 patients with SLE which were followed for 8-month periods. At the time of the exacerbation, IgG IKs were significantly increased to 226 ± 90 arbitrary units (mean ± s.e.m.) compared with both the minimum value of 75 ± 28 in the SLE patients and with 31 ± 2 in healthy controls (P <0·05). There was no difference between SLE patients and controls in the levels of IgM and IgA IKs. Most of the SLE patients in this material showed maximal IgG IK levels before exacerbation, but there was no correlation between the clinical disease index and the levels of IgG IK. The specificity of IgG IKs showed a broad diversity for microtitre-fixed C3b, iC3b, C3c and C3dg. The antibodies were of IgG1, IgG3 and in two patients, IgG4 subclass. IgG IKs were correlated to the C3d/C3 ratio which suggested that the IK responses were secondary to C3 activation. In summary, unlike other conditions associated with complement activation where elevated IgM IKs are common, an increase in IgG IK levels was observed. It is possible that this diverging IK response contributes to the pathophysiology of the disease.
The putative role of cytokines in the induction of primary anti-phospholipid syndrome in mice
Authors: FISHMAN P , BAKIMER R , BLANK M , SREDNI D , DJALDETTI M , SHOENFELD Y
Published: August 2010

Antiphospholipid syndrome (APLS) is characterized by thrombocytopenia, thromboembolic phenomena and recurrent fetal loss, associated with anti-cardiolipin antibodies (ACA) and/or lupus anticoagulant. The syndrome may be primary or may be associated with other conditions such as systemic lupus erythematosus (SLE). In this study we induced primary APLS following immunization of BALB/c mice with a human monoclonal ACA (H-3). Analysis of the cytokine profile of the mice with experimental APLS indicated low production of IL-2, IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) by concanavalin A (Con A)-slimulated splenocytes of H-3 immunized mice. It seems that the low levels of IL-3 and GM-CSF have a potential role in the fetal loss of the APLS. Whatever the mechanism of IL-3 and GM-CSF in preventing fetal loss, these results may have therapeutic bearing on the reproductive outcome in women and other species with APLS.
Expression of T cell receptors αβ and γδ in the ileal mucosa of patients with Crohn's disease and with spondylarthropathy
Authors: CUVELIER C A , DE WEVER N , MIELANTS H , DE VOS M , VEYS E M , ROELS H
Published: August 2010

The expression of the αβ and γδ heterodimer of the T cell receptor (TCR) was studied in normal human ileal mucosa or in ileal biopsies featuring Crohn's disease or acute and chronic spondylarthopathy-related gut inflammation. With an immunohistochemical technique we demonstrated that the increase of mucosal lymphocytes per mm mucosa in Crohn's disease and spondylarthropathy-related ileitis is exclusively due to expansion of the αβ+ T cell compartment. In Crohn's disease and chronic ileitis observed in some spondylarthropathy patients the αβ+ T cells were increased amongst intraepithelial lymphocytes (IEL). The lamina propria lymphocytes (LPL) were augmented in all studied inflammatory conditions. The γδ+ T cells showed no changes in IEL or LPL and their proportions were not altered. They were evenly dispersed throughout the ileal mucosa and did not seem to participate in the inflammatory process. This study confirms that γδ T cells are a distinct subset in the intestinal mucosa. The increase in αβ+ T cells suggests augmented mucosal antigen handling and involvement of the major histocompatibility complex in the pathogenesis of spondylarthropathy-related gut inflammation and Crohn's disease.
The role of T cells and the effect of hydrocortisone on interleukin-4-induced IgE synthesis by non-T cells
Authors: NÜSSLEIN H G , TRÄG T , WINTER M , DIETZ A , KALDEN J R
Published: August 2010

The role of T cells for IL-4-induced IgE synthesis by peripheral blood mononuclear cells (PBMC) was investigated. The removal of monocytes from PBMC abolished IL-4-induced IgE synthesis. When PBMC were separated into T and non-T cells, non-T cells alone were not able to secrete significant amounts of IgE in the presence of IL-4. Depending on the separation procedure, the reconstitution of non-T cells with T cells prepared by rosetting did not restore IgE secretion, whereas T cells obtained by the use of anti-CD3 antibodies could co-induce IgE formation. However, when the T cells were first irradiated, large amounts of IgE were produced, which strongly exceeded those found in unscparated PBMC cultures. IL-4-induced IgE synthesis was also obtained in co-cultures of formaldehyde-fixed T cells with non-T cells. Furthermore, not only autologous but also allogeneic T cells, which have been irradiated or fixed, could provide the costimulatory effect on IgE formation by non-T cells in the presence of IL-4. Mitogenically pre-activated T cells, however, were not able to support IgE synthesis. Hydrocortisone (HC) potentiated the IL-4-induced IgE synthesis by PBMC and enabled non-T cells to secrete IgE in the presence of IL-4. Adding both HC and T cells led to a marked synergistic effect on IL-4-induced IgE production. We conclude that monocytes are required for the induction of IgE synthesis in PBMC in addition to T cells and IL-4. Our results support the view that the T cell signal is delivered via cognate and non-cognate T/B cell membrane interaction. Furthermore, active and proliferating T cells rather suppress IgE synthesis. Finally, HC appears to be a potent alternative stimulus, which bypasses the necessity for T cells in IL-4-induced IgE formation.
Production of serum amyloid A and C-reactive protein by HepG2 cells stimulated with combinations of cytokines or monocyte conditioned media: the effects of prednisolone
Authors: SMITH J W , McDONALD T L
Published: August 2010

The hepatic production of the acute phase proteins in response to inflammatory cytokines, and the interaction of corticosteroids within this response, has been the subject of considerable recent research. In this study we have examined the effects of the corticosteroid prednisolone on the production of IL-1α and IL-I/β by lipopolysaccharide(LPS)-stimulaied monocytes, and the ability of the monocyte conditioned media (MOCM) obtained under these conditions to induce human hepatoma HepG2 cells to produce serum amyloid A (SAA) and C-reactive protein (CRP). We also examined the production of SAA and CRP by HepG2 cells exposed to different combinations and concentrations of recombinant human (rh) IL-lα, rhIL-1/β rhIL-6, recombinant human tumour necrosis factor-alpha (rhTNF-α) and prednisolone. The findings indicate: (i) prednisolone substantially inhibits the production of both IL-lα and IL-lβ by LPS-stimulated monocyles. The MOCM from prednisolone-treated monocyles induced less SAA and CRP production by HepG2 cells; (ii) IL-1α and IL-1β both induced CRP and SAA synthesis by HepG2 cells, but only in the presence of IL-6. IL-lβ was the more potent inducer for SAA production, but for CRP production IL-1α and IL-lβ were equivalent; (iii) prednisolone enhances the production of SAA by HepG2 cells, but docs not enhance the production of CRP; (iv) TNF-a in the presence or absence of IL-6 and/or prednisolone did not induce the production of SAA or CRP by HepG2 cells. These findings offer a tenable solution to a disparate production of SAA compared with CRP in corticosteroid-treated cystic fibrosis (CF) patients.
The acquisition of anti-pneumococcal capsular polysaccharideHaemophilus influenzaetype b and tetanus toxoid antibodies, with age, in the UK
Authors: HAZLEWOOD M , NUSRAT R , KUMARARATNE D S , GOODALL M , RAYKUNDALIA C , Da WANG GONG , JOYCE H J , MILFORD-WARD A , FORTE M , PAHOR A
Published: August 2010

Antibody levels specific for capsular polysaccharides of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) and to tetanus toxoid (TT). were measured in serum samples of 750 age-stratified subjects from the UK. The study subjects comprised healthy adult volunteers and hospitalized children undergoing elective surgery, excluding those with a history of infection or under investigation for immunological or haematological disorders. These antibody levels were calibrated by comparison with serum pool obtained from healthy adult volunteers, who were immunized with Hib polyribose-phosphate vaccine (Merieux). The data are intended to provide reference ranges to assist in the interpretation of specific antibody measurements in the clinical setting. Maternal IgG pneumococcal capsular polysaccharide (PCP) specific antibody levels, geometric-mean titre (GMT) 1/22, were lost by 6 months of age (GMT of 1/9). They remained low until 3–5 years (GMT of 1/20), and consisted principally of IgGl. Thereafter, IgG anti-PCP antibody titres increased steadily to adult levels (GMT of 1/275), of which 80% was IgG2. Anti-PCP antibody titres of the IgM isotype rose steadily from a GMT 1/21 (0–6 months) to 1/420(3–5 years), a level which was maintained until adulthood. Anti-Hib antibody concentrations, determined by RABA, again demonstrated the decline in maternal antibody, from 0.18 μg/ml in the 0.6 month age cohort, to 0.09 μg/ml between 6 and 12 months. Geomctric-mcan antibody concentrations remained below 0.2 μg/ml until 3–5 years, then increased with age, attaining the mean adult level of 1.02 μg/ml. Anti-TT antibody concentrations were measured in the same sera, by ELISA. Two peaks in anti-TT antibody levels were seen in children of 0.059 IU/ml and 0.166 IU/ml corresponding to the schedule of routine childhood immunization in the first year and at 5 years of age.