bluuebunny/crossref_metadata_2025 huggingface dataset:
FS01.4 Hailey Hailey disease – a significant hazard to consider when patch testing
Authors: Walker S , Williams Jason , O’Driscoll J , Beck M
Published: August 2010

A 42 year old man was referred to the Contact Dermatitis Investigation Unit because of a 12 month history of an inflammatory eruption affecting his neck. He was patch tested to our standard series, textile series and his own medicaments. At the 48 hour reading the patches were removed and there were large areas of unusual painful superficial erosions where the patch test tape – Scanporä had been in contact with the skin. This appearance was difficult to explain. He denied interfering with the patches. The erosions were dressed with non‐adherent dressings held in place by a different tape‐ Microporeä. At the 96 hour reading these dressings were removed and in the areas under the Microporeä tape there were further erosions around the edge and also some thin walled vesicles and small bullae. There were ++ allergic reactions to sodium metabisulphite, disperse blue 35, 124 and 106 all of which were felt to be relevant as he had used Trimovateâ cream and regularly wore dark nylon clothing when refereeing lacrosse matches. A biopsy was taken for histology and immunofluorescence from an area of blistering. This demonstrated suprabasal acantholysis with vesicle formation. There were occasional corps ronds. The immunofluorescence was negative. Anti‐epidermal (skin) antibodieswere also negative. This striking and alarming clinical presentation after removal of patch tests had been encountered once previously in our Contact Dermatitis Investigation Unit. The possibility that the disorder was artefactual either due to an irritant introduced under the tapes or perhaps due to a contaminant within the tape adhesive was considered but no conclusion was reached In this case the clue to diagnosis became apparent at the second patch test reading when small vesicles and bullae could be seen at the edge of where the Microporeâ had been. A diagnosis of Hailey Hailey disease (HHD) trigered by the trauma caused by the adhesive tapes and their removal was made. The relatively persistent nature of his presenting problem makes Grover’s disease less likely. The affected sites healed after two weeks. Allergic contact dermatitis particularly to medicaments is reported to be a frequent complication and routine patch testing has been advocated1. There has been a previous report of blistering at the site of patch testing however he was an individual already known to have HHD2. Despite having patch tested around 30 000 people in the last 22 years this complication had not been encountered until this year. We present this case whose clinical features are distinctive as we feel similar instances may have been or will be seen by colleagues. Diagnosis may be difficult if there are no blisters in association with the painful erosions.
FS02.1 The role of metallurgy in allergic contact dermatitis to metals
Authors: Hooper Roger , Newson T
Published: August 2010

The critical factor in determining if an alloy may induce metal sensitisation or elicit allergic contact dermatitis is the release rate of soluble metal ions of allergenic metals at the skin surface. Metals or alloys in direct and prolonged contact with body fluids may result in electrochemical reactions (commonly called corrosion) that release metal ions. Induction or elicitation of metal allergy results if a sufficient amount of metal ions are released and absorbed through the skin where they react with the human immune system. The virtual insolubility of most metals and alloys in aqueous media (including body fluids) limits the bioavailability of metal ions. Several factors influence the rate of corrosion: metal or alloy metallurgical structure, surface films, surface finish, geometry, process history, and composition; body fluid composition, amount, pH, electrolytic properties, dissolved oxygen and other gas content; and the service environment (e.g. temperature, flow rate, etc). A review of recently published studies on metal allergy from a metallurgical perspective provides information that helps explain why certain metals and alloys cause allergic reactions and others (e.g. most stainless steels) do not. This information is useful in predicting what alloys will cause allergic reactions under varying conditions. In order to predict allergic reactions and responses to metals and alloys, metallurgical aspects of ion release should be taken into account. This presentation will increase understanding and interpretation of results of clinical or other scientific studies (e.g. studies in vitro) of reactions and responses to metals and alloys by providing a metallurgical perspective.
FS02.6 Patch test reactivity to nickel sulphate and fragrance mix in unselected children
Authors: Jøhnke Hanne , Norberg LA , Vach W , Bindslev‐Jensen C , Høst A , Andersen KE
Published: August 2010

Objectives:  Study patch test reactivity to nickel sulphate and fragrance mix in a population of unselected infants with focus on reproducibility, clinical relevance, and nickel patch test concentration.

Method:  The data presented is part of a clinical epidemiological study of allergic diseases in newborns followed prospectively with questionnaire, clinical examination and testing at 0, 3, 6, 12 and 18 months of age. TRUE Test patches were used with nickel sulphate in 3 concentrations: 200, 66, 22 ìg/cm2 and fragrance mix 430 ìg/cm2. A positive reaction suggesting sensitisation was defined as at least palpable erythema present at both the 12 and 18 months follow‐up visits.

Results:  A total of 543 children (268 girls, 275 boys) were patch tested at least once, 304 children were tested at both 12 and 18 months. The prevalence of a reproducible positive reaction to nickel sulphate 200 ìg/cm2 was 8.6%(20 girls, 6 boys). A transient reactivity was observed in 111 children (53 girls, 58 boys). A clinical relevance to nickel was found in only one child. There was no association between number of patch test procedures performed and reactions to nickel sulphate. Reproducible reactivity to fragrance mix was not found.

Conclusion:  A high proportion of transient patch test reactivity to nickel sulphate 200 ìg/cm2 was found. Patch testing with nickel in concentrations used for adults cannot be recommended in infants. The interpretation of a singular positive nickel patch test in small children must be assessed with caution. Allergic reactions to fragrance mix were not found in this age group.
FS02.8 Patch testing with gold trichloride can give false test results
Authors: Gruvberger Birgitta , Ahnlide I , Möller H , Bruze M
Published: August 2010

Background:  Hydrochloric acid is formed in water solutions of gold trichloride. Hydrochloric acid in contact with aluminium generates hydrogen gas which can reduce and transform trivalent gold to elemental gold.

Objective:  To investigate whether patch testing with aqueous gold trichloride can cause false positive (irritant) reactions in patients without contact allergy to gold and false negative reactions in patients with gold allergy.

Methods:  13 patients with and 13 patients without positive patch test reactions to gold sodium thiosulfate were tested with gold trichloride in 2 different vehicles, water and alkaline buffer, using 2 different test techniques, the Finn Chamber technique with aluminium chambers and van der Bend technique with polypropene chambers.

Results:  Irritant patch test reactions were obtained with aqueous gold trichloride tested in van der Bend chambers in 10 patients without gold allergy. In gold‐allergic patients no positive test reactions were obtained from aqueous gold trichloride in Finn chambers while 2 positive test reactions were obtained from gold trichloride in alkaline buffer tested in van der Bend chambers.

Conclusion:  If gold trichloride is patch tested in wrong vehicle and with wrong test technique irritant test reactions may occur which can be misinterpreted as positive allergic reactions in patients without gold allergy as well as negative reactions in patients with gold allergy.
The caecum of monotremes and marsupials
Authors: Hill W. C. Osman , Rewell R. E.
Published: August 2010

A description is given of the caecal region of the gut in a number of monotremes and marsupials, covering most genera, some of which are now very rare and possibly even extinct. As in a previous memoir, particular attention is given to the peritoneal folds attached to the viscus and to its blood supply.

Monotremes exhibit a simple caecum tethered by a single median fold, or none (e.g. Zaglossus).

Marsupials as a group show a more complex arrangement, although, as in Primates, the caecum is typically anchored by a median anangious fold with flanking vascular folds on the morphologically sinistral and dextral sides. However, many complex specializations exist to modify this arrangement. One artery is typically the larger, and this is more often the sinistral than the dextral.

The size of the caecum may possibly depend on some factor in the diet of the animal, but this cannot be simply the proportion of vegetable material it contains, nor is it the only factor concerned.

Specialization within the viscus occurs in many marsupials, but never proceeds so far as to form an appendix caecalis.
Shell attachment and associated musculature in the Notaspidea and Anaspidea (Gastropoda: Opisthobranchia)
Authors: Brace R. C.
Published: August 2010

An account is given of the muscles of the head‐foot of the notaspidean (Pleurobran‐chomorpha) Berthella plumula (Montagu) and of the anaspidean (Aplysiomorpha) Aplysia punctata Cuvier, with special reference to those concerned in anchoring the shell. This is an internal dorsal plate in both animals.

It is shown that parallel evolution has occurred so that in both orders the reduced shell is anchored by a ring of dorsoventral muscles, broken on the right where the mantle complex lies. In addition, some intrinsic longitudinal muscles of the dorsal body wall of Aplysia fasten to the shell margin. In both Aplysia and Berthella the columellar muscle takes the form of a pair of lateral tracts, and in the latter, forms the buccal mass retractor. This retractor muscle, together with some fibres of the left tract, is the only part of the columellar muscle of Berthella to originate on the shell. No such attachment occurs in Aplysia.

By reference to this musculature and the gross anatomy, the changes in bodily organization necessary to derive the Notaspidea and Anaspidea from primitive stocks of infaunal cephalaspideans (Bullomorpha), are deduced. The primitive anaspid, Akera, in which the head‐foot has narrowed and partially assumed slug‐like form, provides an annectant example. Upon (1) further reduction in the shell, (2) loss of the posterior mantle lobe and proximal columellar muscle simultaneous with further posterior elongation of the mesopodium and (3) dorsoventral growth of the head‐foot posteriorly, the bodily form typical of the aplysiids was produced. This last change in proportion raised the shell well above the horizontally‐aligned columellar tracts. Slug‐like proportions have also been attained in the Notaspidea by posterior elongation of the mesopodium, but unlike anaspids, there was a simultaneous reduction of the dorsal body wall, so that the anterior mantle border came partially to overlie the rhinophores.

It is concluded that the changes in gross bodily form which converted a cephalaspid stock into anaspids facilitate a herbivorous existence, crawling on weed. The adaptations necessary to derive the Notaspidea were involved in the change from an infaunal mode of life to an epifaunal one on either mixed bottoms or hard substrata.
Functional anatomy of the buccal apparatus of Onchidoris bilamellata (Mollusca: Opisthobranchia)
Authors: Crampton Denise M.
Published: August 2010

The ingestive cycle of Onchidoris is described based upon an anatomical investigation of the buccal apparatus together with observations of feeding activity and spontaneous and induced movements of the buccal apparatus. Feeding is accomplished by a complex series of movements of 25 buccal muscles operating the odontophore and the buccal pump. Protraction of the buccal apparatus is largely passive and is dependent upon increased blood pressure within the head whereby blood is isolated in a number of distinct haemocoels surrounding the buccal apparatus. The odontophore is everted through the mouth by the contraction of ventral and lateral odontophoral protractor muscles and the radular teeth are erected by a deformation of the odontophoral cartilage. The effective stroke of the radula results in the piercing of the barnacle mantle and the opercular plates are discarded by ciliary currents around the mouth of the dorid. Retraction of the buccal apparatus follows due to the contraction of buccal retractor and retractor of the buccal lip muscles and this is accompanied by the inhalant phase of the buccal pump. As a result of these last activities, all the soft parts of the barnacle, including the cirri, are taken into the buccal cavity. It is suggested that Onchidoris represents a high degree of specialization in its feeding behaviour because, although many of the buccal muscles are homologous with those described in other opisthobranchs, their methods of operation, particularly in conjunction with a piercing, grasping radula and a buccal pump that can operate during both ingestion and swallowing, are unique. The buccal apparatus of Onchidoris is compared with that of a number of other opisthobranchs including Philine, Cylichna and Archidoris.
Aplysiid species from Eastern Australia with notes on the Pacific Ocean Aplysiomorpha (Gastropoda, Opisthobranchia)
Authors: Bebbington Alan
Published: August 2010

Nineteen species of the opisthobranch order Aplysiomorpha collected from eastern Australia and adjoining parts of the Pacific Ocean are described. Notes on 18 other Pacific species of this order are given. The 44 species of Aplysiomorpha which are reliably reported from the Indo‐Pacific are listed with their distribution, together with a key for the identification of the Australian species.
The food and feeding behaviour of Clarias gariepinus (Pisces: Clariidae) in Lake Sibaya, South Africa, with emphasis on its role as a predator of cichlids
Authors: Bruton M. N.
Published: August 2010

The morphological and behavioural adaptations for feeding, and the food of C. gariepinus in Lake Sibaya are described. C. gariepinus is equipped to feed on a wide variety of food items, from minute crustaceans to fish. Predation is more efficient on invertebrate prey. Most feeding takes place at night on active benthic organisms, but they may also feed during the day and at the water surface. Individual bottom foraging is the normal mode of feeding although catfish may also feed in groups at the water surface. The advantages of social hunting are discussed.

Food preferences are scored by three different methods and presented for the total catfish population and for different length groups, seasons, habitats and lake levels. Increasing lake levels during the study period resulted in a change in the relative density of three cichlid prey in the shallow water feeding area of C. gariepinus. The effect of changing cichlid densities on catfish predation was studied using field collections and experimental observations. C. guriepinus was found to feed on whichever cichlid prey was in greatest abundance, with some deviations which can be explained in terms of prey accessibility and other factors. An important aspect of their success as predators is their ability to switch from one prey to another as prey availability (= density + accessibility) changes.

Predation by Clarias species on cichlids in Africa is reviewed, and the movements and interaction of C. gariepinus and three cichlid species in Lake Sibaya are described in detail. Catfish predation is discussed in terms of recent predation theory, and their role as predators of cichlids is tentatively postulated as three‐fold:

to enhance species fitness by removing enfeebled individuals, i.e. to act as a “cleanser”

to restrict the distribution of prey under certain conditions, i.e. to act as a “restrictor”

to dampen fluctuations in prey abundance, i.e. to act as a “regulator”.

The relative importance of these roles is unknown at this stage, and may change at different lake levels and in different ecosystems.
The role of diel inshore movements by Clarias gariepinus (Pisces: Clariidae) for the capture of fish prey
Authors: Bruton M. N.
Published: August 2010

The diel movements of predator and prey populations of freshwater fish in a natural lake in south‐east Africa are described. The predator, Clarias gariepinus (Burchell) feeds in inshore areas at night although its main fish prey Sarotherodon mossambicus (Peters) mainly inhabits these areas during the day. Field and laboratory observations revealed that C. gariepinus has difficulty catching S. mossambicus during the day whereas this prey is more readily caught during the nocturnal inshore movement. Three factors were identified and shown to increase the predation efficiency of C. gariepinus on S. mossambicus (i) decreased water depth, (ii) decreased light intensity, (iii) increased predator numbers. By feeding in shallow areas as a group at night, C. gariepinus is able to catch fish prey which is normally too elusive. As fish prey contribute more energy than do invertebrate prey, C. gariepinus can afford to expend a considerable amount of energy on their capture, including that used during the diel inshore movements.
Crab zoeal morphology and its bearing on the classification of the Brachyura
Authors: Rice A. L.
Published: August 2010

The current knowledge of brachyuran crab morphology is reviewed and its bearing on the classification of the group is examined. Brachyuran classification in the past has been based entirely on adult characters, but since adult crabs exhibit adaptations for a wide range of life styles some of the proposed groupings have resulted from a failure to recognize convergence. Since the zoeal stages of all crabs are adapted to the same mid‐water habitat, a classification based on larval characters should be largely free from such problems.

Attempts to categorize crab zoeae in the past have generally failed to produce groupings which correspond closely to those based on the adults. In this paper, by using more characters than has usually been the case, and particularly the detailed setation of the mouthparts, a close correspondence with the adult groupings is demonstrated, at least at the family and sub‐family level. At a higher taxonomic level the zoeal groups are often at variance with the widely accepted adult ones and strongly suggest the need for a fairly radical rearrangement. The major groups indicated by the zoeal features correspond most closely with those suggested by Guinot (1978) in her proposed extensive revision of brachyuran systematics. However, in both cases the major groups are not natural ones since they tend to identify grades of evolution rather than phylogenetic lines.

A key for the identification of zoeae to family or sub‐family is provided, together with an extensive bibliography.
Poly (γ, L‐glutamic acid)‐cisplatin bioconjugate exhibits potent antitumor activity with low toxicity: A comparative study with clinically used platinum derivatives
Authors: Feng Zhen , Lai Yuping , Ye Haifeng , Huang Jing , Xi Xu Guang , Wu Zirong
Published: August 2010

We have recently synthesized a new platinum derivative, poly (γ, L‐glutamic acid)‐cisplatin conjugate (γ‐PGA‐CDDP), and shown that it displayed remarkable antitumor activity against breast tumor in a mouse model. The purpose of this study is to systematically compare this new drug with three platinum derivatives currently used in the clinic: cisplatin, carboplatin and oxaliplatin. Here, we show that γ‐PGA‐CDDP displays impressive antitumor activity over the current clinically used platinum drugs. More interestingly and more importantly, γ‐PGA‐CDDP conjugate significantly reduces cytotoxicity, mitigates oxidative stress and improves antioxidative capability in vivo. Animals treated with γ‐PGA‐CDDP display the same profile of body weight as the control animals, while the tumors in γ‐PGA‐CDDP‐treated animals are significantly suppressed compared with those treated with carboplatin and oxaliplatin. Our data suggest that γ‐PGA could be used as an effective carrier for drug delivery and that γ‐PGA‐CDDP conjugate may have potential therapeutic applications in human cancers that are sensitive to treatment with CDDP‐based chemotherapy such as ovarian cancer. (Cancer Sci 2010; 101: 2476–2482)
4β‐hydroxycholesterol, an endogenous marker of CYP3A4/5 activity in humans
Authors: Diczfalusy Ulf , Nylén Hanna , Elander Pontus , Bertilsson Leif
Published: August 2010

We have proposed that 4β‐hydroxycholesterol (4β‐OHC) may be used as an endogenous marker of CYP3A activity. The cholesterol metabolite 4β‐OHC is formed by CYP3A4. Treatment of patients with strong inducers of CYP3A enzymes, e.g. anti‐epileptic drugs, resulted in 10‐fold increased concentrations of plasma 4β‐OHC, while treatment with CYP3A inhibitors such as ritonavir or itraconazole resulted in decreased plasma concentrations. There was a relationship between the 4β‐OHC concentration and the number of active CYP3A5*1 alleles showing that 4β‐OHC was not only formed by CYP3A4, but also by CYP3A5. The concentration of 4β‐OHC was higher in women than in men, confirming previous studies indicating a gender difference in CYP3A4/5‐activity. The rate of elimination of 4β‐OHC is slow (half‐life 17 days) which results in stable plasma concentrations within individuals, but limits its use to study rapid changes in CYP3A activity. In short‐term studies exogenous markers such as midazolam or quinine may be superior, but in long‐term studies 4β‐OHC is a sensitive marker of CYP3A activity, especially to assess induction but also inhibition. Under conditions where the cholesterol concentration is changing, the ratio of 4β‐OHC : cholesterol may be used as an alternative to 4β‐OHC itself. The use of an endogenous CYP3A marker has obvious advantages and may be of value both during drug development and for monitoring CYP3A activity in patients.
Rapamycin prevents the onset of insulin-dependent diabetes mellitus (IDDM) in NOD mice
Authors: BAEDER W L , SREDY J , SEHGAL S N , CHANG J Y , ADAMS L M
Published: August 2010

The effect of the immunosuppressive agent rapamycin (RAPA) was assessed in the non-obese diabetic (NOD) mouse which is an autoimmune model of IDDM. RAPA was prepared in a vehicle of 8% cremophor EL/2% ethanol and investigated in two studies. NOD/MrK female mice (six per group, study no. 1; 10 per group, study no. 2) were dosed three times per week p.o. by gavage from 56 to 170 days of age (study no. 1) or from 64 to 176 days or age (study no. 2). Mice treated with RAPA at 06 mg/kg, 6 mg/kg, or 12 mg/kg maintained normal plasma glucose through 170 or 176 days of age with 10%, 0%, and 0% incidence of diabetes respectively. In contrast, naive, vehicle-treated, or RAPA 0.06 mg/kg-treated mice exhibited elevated plasma glucose and disease incidence typical for female NOD mice. Mice which became diabetic had elevated levels of β-hydroxybutyrate, triglycerides and cholesterol. These plasma lipid concentrations were positively correlated with the duration of hyperglycaemia (r= 0.85, 0.87 and 0.84 respectively). Outside of its ability to prevent diabetes, RAPA itself did not affect the lipid profile of the mice. Intervention therapy with RAFA was ineffective at reversing the course of disease after IDDM onset under these experimental conditions. Finally, we report here that prophylactic treatment with RAPA was able to protect against IDDM development in some RAPA-treated mice 41 weeks after cessation of treatment. These data show that orally administered RAPA is effective in preventing onset of disease in the NOD mouse, a relevant model of autoimmune type I diabetes in man.
Possible role of IL-2 deficiency for hypogammaglobulinaemia in patients with common variable immunodeficiency
Authors: RUMP J A , JAHREIS A , SCHLESIER M , DRÄGER R , MELCHERS I , PETER H H
Published: August 2010

Common variable immunodeficiency (CVID) patients are unable to produce specific immunoglobulins after antigen contact in vivo. The aim of this study was to investigate whether in some cases of CVID a decreased de novo synthesis of IL-2 might be the cause of immunodeficiency and whether this deficiency can be corrected by IL-2 supplementation in vitro. Mononuclear cells from 17 CVID patients and from 10 healthy controls were cultured with monoclonal anti-CD3 antibody OKT3, pokeweed mitogen (PWM) or tetanus toxoid (TT) to stimulate IL-2 synthesis. In parallel, in vitro IgG and IgM synthesis was stimulated with Staphylococcus aureus Cowan I (SAC), PWM or TT in the presence or absence of IL-2. While lymphocytes of 11 out of 17 patients produced low to normal amounts of IL-2 upon stimulation with anti-CD3, only three patients showed low IL-2 production in response to PWM and five in response to TT. Regarding immunoglobulin synthesis in vitro, five patients completely failed to produce IgM or IgG upon stimulation with PWM, SAC or TT irrespective of the addition of IL-2. By contrast, four patients did not show any defect in vitro and synthesized normal amounts of IgM and IgG with any of the three stimuli. Finally, eight patients could be reconstituted for PWM-, SAC- and TT-induced IgM and/or IgG synthesis in vitro, by adding IL-2 to the culture system. This enhancing effect of IL-2 could be blocked by adding anti-IL-2 receptor antibodies to the cultures. Our findings indicate that a defective IL-2 synthesis after antigen stimulation may be one reason for the impaired immunoglobulin production in some cases of CVID.
IL-4 down-regulates the surface expression of CD5 on B cells and inhibits spontaneous immunoglobulin and IgM-rheumatoid factor production in patients with rheumatoid arthritis
Authors: HIDAKA T , KITANI A , HARA M , HARIGAI M , SUZUKI K , KAWAGUCHI Y , ISHIZUKA T , KAWAGOE M , NAKAMURA H
Published: August 2010

There is evidence to suggest that CD5+ B cells may be associated with autoimmunity, e.g. they are increased in patients with rheumatoid arthritis (RA). In this study, we found that the expression of CD5 on RA B cells increased spontaneously, following culture for up to 4 days in vitro in the absence of T cells, supporting the idea that the CD5+ B cell possesses distinctive features. The spontaneous increase of CD5 expression was down-regulated by recombinant IL-4 (rIL-4). Other cytokines studied (rIL-1α, rIL-2, rIL-5, rIL-6) did not alter CD5 expression. Studies of antibody production showed that rIL-4 could reduce spontaneous production of total IgG and IgM in non-stimulated RA T plus B cell cultures. Spontaneous production of IgM rheumatoid factor (IgM-RF), measured by a newly developed avidin-biotin complex ELISA, was also reduced by rIL-4. Furthermore, rIL-4 reduced the increase in IgM-RF production observed on stimulation with Staphylococcus aureus Cowan I (SAC) or pokeweed mitogen (PWM). Thus, IL-4 might act as a regulator of the development of abnormal B cell differentiation in patients with RA.
Induction of experimental systemic lupus erythematosus (SLE) in mice with severe combined immunodeficiency (SCID)
Authors: SEGAL R , GLOBERSON A , ZINGER H , MOZES E
Published: August 2010

A model in which experimental SLE is induced in normal mice by the injection of a human anti-DNA MoAb expressing a common idiotype 16/6 Id has been established in our laboratory. In the present study we have attempted the induction of experimental SLE in mice with SCID by the transfer of lymphocytes obtained from mice with experimental SLE. Disease could not be induced by direct immunization of SCID mice with the 16/6 Id nor by transfusion of normal splenocytes and immunization with the 16/6 Id thereafter. In contrast, disease was induced in SCID mice which were transplanted with splenic lymphocytes obtained from SLE afflicted BALB/c mice. The disease was expressed by the presence of high titres of antibodies and glomerular immune complex deposits were present in the kidney sections of these mice. Mice that received spleen cells from donors with experimental SLE together with the 16 /6 Id developed higher titres of autoantihodies anti had, in addition to the immune complex deposits, glomerular histological pathology. The model of experimental SLE induction in SCID mice should help in the elucidation of the role of different cell types in the pathogenesis of SLE.
Disease association of antibodies to human and mycobacterial hsp70 and hsp60 stress proteins
Authors: ELSAGHIER A , PRANTERA C , BOTHAMLEY G , WILKINS E , JINDAL S , IVANYI J
Published: August 2010

Structural homology between microbial and human stress proteins has been postulated to be a basis for autoimmunization in chronic inflammatory diseases. Therefore, we estimated by ELISA titration the antibody levels to mycobacterial (M) and human (H) recombinant hsp70 and M-hsp65 heat-shock proteins in sera of patients with Crohn's disease (n= 29), ulcerative colitis (n= 20) and non-tuberculous mycobacterial disease of the lungs (n= 20). Antibodies to H-hsp60, separated by two-dimensional gel electrophoresis, were tested in six sera of each group of patients. In Crohn's disease, antibody titres to the M-hsp65 antigen without detectable H-hsp60 binding were significantly elevated in 52% of the patients. In contrast titres to both M-hsp70 and H-hsp70 were demonstrable and correlated, but increased over control values only in lour (14%) patients. The antibody pattern in ulcerative colitis was found to be quite different: anti-H-hsp60 binding was demonstrable in most patients, although anti-M-hsp65 titres were not elevated. Furthermore. 25% of patients had significantly elevated titres to M-hsp70, but not to H-hsp70. In non-tuberculous mycobacterial pulmonary disease, about 50% of patients had elevated titres to both hsp65and hsp71 mycobacterial antigens but not to the corresponding human proteins; patients with Mycobacterium xenopi infection had the highest titres in this group. These results demonstrate the existence of distinct disease-associated patterns in the human antibody response to stress protein antigens. However, these data are not sufficient to imply sensitization with mycobacteria in patients with inflammatory bowel diseases, since certain epitopes of heat-shock proteins are shared by several bacterial genera.
IgA-containing immune complexes after challenge with food antigens in patients with IgA nephropathy
Authors: JACKSON S , MOLDOVEANU Z , KIRK K A , JULIAN B A , PATTERSON T F , MULLINS A L , JILLING T , MESTECKY J , GALLA J H
Published: August 2010

The possibility that patients with IgA nephropathy (IgAN) might have abnormal IgA immune responses to immunogens commonly encountered at mucosal surfaces, resulting in the formation of circulating immune complexes (CIC), was examined. Since it is generally held that such increased IgA responses are characterized by detectable aberrancies in handling of IgA-containing CIC, IgAN patients and controls were given a large volume of bovine milk (after dietary deprivation of bovine antigens) and immune complex levels were measured over a period of 12 h. An assay based on binding of CIC containing C3 to solid-phase anti-C3 and subsequent development with isotype-specific antibody revealed no differences in responses of patients and controls with respect to IgG- and IgM-containing CIC. Although IgAN patients tended to have higher levels of IgA-containing CIC, there were no differences in response patterns when IgA CIC levels after ingestion of the milk stimulus were related to baseline levels. Polymorphonuclear leucocytes (PMNC), which bear surface receptors for IgA, were isolated from some subjects at the same times as the samples for CIC levels and examined by two-colour immunfluorescence for the coincident presence of IgA and milk antigens. In contrast to the data obtained in the CIC assays, these experiments revealed the simultaneous presence of IgA and two of three milk proteins in PMNC of IgAN patients but not controls. Follow-up experiments designed to assess more quantitatively the coincidental presence of IgA and milk antigens indicated no significant differences between patients and controls. However, milk proteins seemed to be more commonly associated with IgA in PMNC of IgAN patients, suggesting the presence of non-complement-fixing IgA/antigen CIC after mucosal challenge of some IgAN patients.
Elevated serum levels of soluble tumour necrosis factor receptors (sTNF-R) in patients with HIV infection
Authors: KALINKOVICH A , ENGELMANN H , HARPAZ N , BURSTEIN R , BARAK V , KALICKMAN I , WALLACH D , BENTWICH Z
Published: August 2010

Serum levels of the soluble form of tumour necrosis factor receptor type II (p75) (sTNF-R) were determined in HIV-infected individuals and risk groups and were then correlated with the course of infection and prognosis. sTNF-R levels were determined by an ELISA with MoAbs and polyclonal antibodies to urine-derived sTNF-R proteins. The mean ±s.e. levels of sTNF-R in the sera of 49 HIV+ male homosexuals, 34 HIV− male homosexuals and 44 matched controls were 6·1 ± 0·3 ng/ml, 4·4 ± 0·3 ng/ml and 3·4 ± 0·2 ng/ml, respectively. All these values were significantly different between each of the groups (P < 0·001–0·05). Sequential studies of sTNF-R revealed higher levels following seroconversion in 5/8 individuals, remained persistently high during the asymptomatic phase of the infection and became even more elevated in some ARC and AIDS patients. At the same time TNF-α was undetectable in sera obtained from HIV+ male homosexuals and from healthy controls. This was independent of stage of HIV infection, serum sTNF-R level and type of ELISA kit used. These findings suggest that TNF-α/TNF-R system is turned on before and during HIV infection and raise the possibility that sTNF-R, the natural inhibitor of TNF, may be of importance in determining the course and probably prognosis of the disease.
Impaired proliferative responses of peripheral blood B cells from splenectomized subjects to phorbol ester and ionophore
Authors: FOSTER P N , TREJDOSIEWICZ L K
Published: August 2010

The responses of peripheral blood B cells to mitogenic stimulation were examined in 12 splenectomized subjects without residual splenic function, as determined by pitted erythrocyte counts. These were compared to a group of healthy controls matched for age and sex. Polyclonal antiimmunoglobulin evoked a normal transient elevation in intracellular free Ca2+ in splenectomized subjects, thereby suggesting that the early events of the signal transduction pathway are not impaired. However, mitogenic stimulation by pre-treatment with phorbol ester and culture in presence of a calcium ionophore (Ionomycin) resulted in reduced uptake of 3H-thymidine and subsequent proliferation. Nevertheless, entry into the mitotic cycle, as assessed by expression of Ki67, was slightly, but not significantly impaired. Unlike in normal controls, where up to 7% of freshly-isolated B cells were Ki67+, almost no ki67+ peripheral B cells were observed in splenectomized subjects. The data are consistent with the hypothesis that peripheral B cells in splenectomized subjects are in a reduced state of activation compared with normal controls and require additional growth factor stimulation before they can undergo mitosis.
Cells with natural killer activity in human rabies
Authors: PANPANICH T , HEMACHUDHA T , PIYASIRISILP S , MANATSATHIT S , WILDE H , PHANUPHAK P
Published: August 2010

Cytotoxic lymphocyte function in 13 patients with rabies was studied by counting the number of CD56 cells and assessing natural killer (NK) cell activity. There was no significant difference in the number of killer cells between rabies patients and 31 normal controls (P > 0·05). Two of six non-fatal encephalitic patients due to causes other than rabies had reduced CD56 numbers. Base-line NK cell responses versus K562 Cell targets did not differ among the normal control and rabies groups (P > 0·05). Study of the non-rabies encephalitis group showed heterogeneous results with wide variation. Significant enhancement of NK activity was seen in four rabies patients and in 10 normal control subjects tested after interferon-alpha (IFN-α) and IL-2. None of the four patients with encephalitis due to causes other than rabies showed such enhancement. Our results suggest that NK cells of rabies patients are not fully stimulated and that this might contribute to the virulence of rabies. The cause of this phenomenon remains unknown.
Stimulation of synovial fluid mononuclear cells with the human 65-kD heat shock protein or with live enterobacteria leads to preferential expansion of TCR-γδ+ lymphocytes
Authors: HERMANN E , LOHSE A W , MAYET W J , VAN DER ZEE R , VAN EDEN W , PROBST P , PORALLA T , MEYER zum BÜSCHENFELDE K-H , FLEISCHER B
Published: August 2010

T lymphocyte responses to heterologous or self 65-kD heat shock protein (hsp) have been implicated in the pathogenesis of various forms of arthritis. To delineate the relationship of 65-kD hsp to different synovial fluid (SF) T cell subsets, we stimulated synovial fluid (SFMC) and peripheral blood mononuclear cells (PBMC) from patients with different inflammatory rheumatic diseases and from healthy controls with human or mycobacterial 65-kD hsp, tetanus toxoid (TT), heat-killed or live Yersinia enterocotitica. Phenotyping of the resulting T cell lines revealed an increase of up to 97% TCR-γδ+ lymphocytes in the 65-kD hsp-stimulatcd SF-derived lines. This expansion of TCR-γδ+ cells was less pronounced with cultures of PBMC. A preferential expansion of TCR-γδ+ cells was also shown after SFMC stimulation with live, but not with heat-killed Yersinia or with TT. We conclude that a common mechanism is involved in the selective expansion of TCR-γδ+ lymphocytes upon SFMC infection with live Yersinia or upon contact with 65-kD hsp. Out of a panel of TCR-γδ+ T lymphocyte clones (TLC) derived from a human 65-kD hsp-stimulated line, only a minority of TLC proliferated weakly upon restimulation with this antigen in the presence of autologous monocytes, whereas TCR-αβ+ TLC responded vigorously to the human 65-kD hsp and in some cases also cross-recognized the mycobacterial hsp homologue and/or heat-killed Yersinia. This implies that additional factors or cells may be present in the milieu of SFMC cultures that propagate the expansion of TCR-γδ+ cells in response to 65-kD hsp or live bacteria.
Agalactosyl IgG in pristane-induced arthritis. Pregnancy affects the incidence and severity of arthritis and the glycosylation status of IgG
Authors: THOMPSON S J , HITSUMOTO Y , ZHANG Y W , ROOK G A W , ELSON C J
Published: August 2010

The effect of pregnancy on the incidence and severity of pristane-induced arthritis was examined along with the glycosylation status of IgG during the ante-natal and post-partum periods. Il was found that pristane-induced arthritis is prevented by pregnancy. In addition, the levels of agalactosyl IgG fall during pregnancy but rise lo greater than normal within a few days of parturition, before resetting towards the norm shortly afterwards. Interestingly, the level of agalactosyl IgG correlates with the severity of arthritis. As previously reported IL-6may bean important factor, not necessarily the only one, in the production of agalactosyl IgG. Here it is clearly demonstrated that the kinetics of IL-6 activity post-pristane injection parallels the kinetics of agalactosyl IgG production. In addition, the overshoot in agalactosyl IgG levels immediately post-partum coincides with a burst in IL-6 activity. It is considered that these changes in IgG glycoform levels, or the factors which control them, may be related to the mechanisms underlying prevention/remission of arthritis during pregnancy.
Oestrogen-induced suppression of collagen arthritis; 17β-oestradiol is therapeutically active in normal and castrated F1 hybrid mice of both sexes
Authors: JANSSON L , HOLMDAHL R
Published: August 2010

The F1 hybrid mouse strain, from B10Q and DBA/1 parentals (the QD strain), is highly susceptible to induction of type II collagen-induced arthritis, an experimental model for rheumatoid arthritis. Males are more susceptible than females. Oophorectomy enhances susceptibility to arthritis and treatment with physiological doses of 17β-oestradiol (E2) suppresses disease. E2 treatment lowers the incidence of arthritis also in non-castrated and castrated males, showing that the anti-arthritic effect by oestrogen is not dependent on either sex hormone imprinting effects or interference with male sex hormones. Testosterone treatment of normal females, but not of castrated females, exaggerated development of the disease. In the testosterone-treated normal females, the oestrogen effect on vaginal smear was abolished and ovarian weight decreased, suggesting that the testosterone-mediated enhancing effect is caused by inhibition of ovarian oestrogen production. The crucial importance of oestrogens for the development of arthritis is focused on the effectiveness of treatment with gestation-related doses of E2 of normal, non-castrated females.
Induction of a pharmacologically active clonotypic B cell response directed to an immunogenic region of the human β2-adrenergic receptor
Authors: GUILLET J-G , LENGAGNE R , MAGNUSSON Y , TATE K , STROSBERG A D , HOEBEKE J
Published: August 2010

It has been reported that autoantibodies against the β2-adrenergic receptors are involved in the pathology of allergic disorders and of Chagas' disease. Therefore, the immune response against a peptide (H26Q) corresponding to the putative second extracellular loop of the human β2-adrenergic receptor, which could be a target for autoantibody attack, was analysed in view of its possible immunogenicity. The free peptide induced a T cell-mediated humoral response in the context of three different murine MHC haplotypes. The T cell epitope was found to be localized in the N-terminal region of the peptide. Highly specific T helper cells were capable of stimulating B cells with the potential to generate a large antibody repertoire reactive with the loop peptide. MoAbs were screened to analyse this B cell response for antibodies potentially interfering with receptor function and a MoAb was found that impaired ligand binding to the receptor.
Signal transduction pathways leading to the production of IL-8 by human monocytes are differentially regulated by dexamethasone
Authors: ANTTILA H S I , REITAMO S , CESKA M , HURME M
Published: August 2010

Previous studies have shown that IL-8 gene expression is enhanced by various stimuli, which induce different signal transduction pathways. A lipopolysaccharide (LPS)-induced pathway has been reported to be inhibited by glucocorticoids in monocytes. We have now examined the effect of dexamethasone on the LPS-induced and other signal transduction pathways leading to the production of IL-8 by human monocytes. Dexamethasone Inhibited the production of IL-8 stimulated with a cyclic adenosine monophosphate analog or LPS. In contrast, dexamethasone had no significant effect on a phorbol ester (PMA)-stimulated IL-8 production. These results suggest that the signal transduction pathways leading to the production of IL-8 by human monocytes are differentially regulated by dexamethasone.
Selection of a muramyl peptide based on its lack of activation of nuclear factor-κB as a potential adjuvant for AIDS vaccines
Authors: SCHRECK R , BEVEC D , DUKOR P , BAEUERLE P A , CHEDID L , BAHR G M
Published: August 2010

Activation of the cellular transcription factor nuclear factor-κB (NF-κB) by cytokines and other immunostimulants has been tightly linked with enhanced replication of human immunodeficiency virus-type 1 (HIV-1) in infected cells. Various immunomodulators are currently being examined in animal and human trials for their suitability as adjuvants in potential vaccines against acquired immunodeficiency syndrome (AIDS). It may prove to be beneficial to select adjuvants that do not induce NF-κB activation and particularly if the vaccines are to be aimed at seropositive individuals. We have examined a battery of synthetic immunostimulants of the muramyl peptide family for their ability to activate NF-κB in human and mouse cell lines. In this report, we demonstrate selective activation of NF-κB in different cell lines and by different muramyl peptides possessing immunostimulatory activities. The mechanism of such activation is apparently via production of reactive oxygen intermediates (RO1) since pretreatment of cells with antioxidants blocked subsequent activation of NF-κB. However, among all the molecules tested only one lipophilic, non-pyrogenic adjuvant active muramyl peptide showed a complete lack of NF-κB activation in all cell lines tested. This molecule could well become the adjuvant of choice in future AIDS vaccines.
Herpesvirus serology, aberrant specific immunoglobulin G2 and G3 subclass patterns and Gm allotypes in individuals with low levels of IgG3
Authors: LINDE A , SÖDERSTRÖM R , EDVARD SMITH C I , SÄLLBERG M , DAHL H , GRUBB R , BJÖRKANDER J , HAMMARSTRÖM L
Published: August 2010

One objective of this study was to determine whether IgG3-deficient individuals have an increased frequency of reactivated herpesvirus infections. Serum titres to Epstein-Barr virus (EBV) and human herpesvirus-6 were examined in 10 healthy and in 10 symptomatic persons with serum IgG3 < 0·1 g/l. Atypical titres were found in 16% of the IgG3-deficient individuals. Reactivations of these viruses thus do not seem common in IgG3 deficiency. Antigen-specific IgG responses were also determined. A lowered frequency of IgG3 to an EBV-derived peptide was found only in symptomatic, IgG3-deficient individuals. Levels of IgG2 to a bacterial polysaccharide were lowered in the same group, despite normal serum levels of total IgG2. A functional IgG2 deficiency may contribute to symptoms in IgG3 deficiency. The G3(g) allotype, known to be associated with low total IgG3, dominated in IgG3-deficient persons (13/17) independently of presence or absence of symptoms. A linkage of G3(g) to the G2(n) negative allotype, associated with low IgG2, was equally common irrespective of symptoms. G3(g) and absence of G2(n) seem to be one prerequisite for most of IgG3 deficiency combined with low specific IgG2.
Immunoglobulin allotypes and IgG subclass antibody response to Pseudomonas aeruginosa antigens in chronically infected cystic fibrosis patients
Authors: PRESSLER T , PANDEY J P , ESPERSEN F , PEDERSEN S S , FOMSGAARD A , KOCH C , HØIBY N
Published: August 2010

Chronic Pseudomonas aeruginosa lung infection is the leading cause of death in patients with cystic fibrosis (CF). Poor prognosis correlates with a high number of anti-pseudomonas precipitins and with high levels of IgG2 and IgG3 anti-pseudomonas antibodies. Reports of several highly significant associations between certain Gm (genetic markers of IgG on human chromosome 14) and Km (k-type light chain determinants on chromosome 2) phenotypes and immune responsiveness to various antigens suggest that allotype-linked immune response genes do exist in man. Furthermore correlation between Gm types and IgG subclass levels has been reported. A group of 143 CF patients were investigated (31 non-infected and 112 chronic infected). The IgG subclass antibodies to three different P. aeruginosa antigens (P. aeruginosa standard antigen (St-Ag), alginate and LPS) were determinated. Immunoglobulin allotypes were determined by haemagglutination inhibition. Samples were typed for G1m(1,2,3, and 17), G2m(23), G3m(5,21), and Km(1,3). Statistical analysis of our data demonstrate that IgG3 anti-pseudomonas antibody levels and Gm markers are related. IgG3 antibody levels to all investigated P. aeruginosa antigens are significantly higher in sera homozygous for Gm(3;5), somewhat lower in heterozygous sera, and significantly lower in sera homozygous for Gm(1,2,17;21). We suggest that genetic differences between the patients may explain the present differences in subclass patterns.