Prolactin suppresses malonyl-CoA concentration in human adipose tissue.

Prolactin is best known for its involvement in lactation, where it regulates mechanisms that supply nutrients for milk production. In individuals with pathological hyperprolactinemia, glucose and fat homeostasis have been reported to be negatively influenced. It is not previously known, however, whether prolactin regulates lipogenesis in human adipose tissue. The aim of this study was to investigate the effect of prolactin on lipogenesis in human adipose tissue in vitro. Prolactin decreased the concentration of malonyl-CoA, the product of the first committed step in lipogenesis, to 77+/-6% compared to control 100+/-5% (p=0.022) in cultured human adipose tissue. In addition, prolactin was found to decrease glucose transporter 4 ( GLUT4) mRNA expression, which may cause decreased glucose uptake. In conclusion, we propose that prolactin decreases lipogenesis in human adipose tissue as a consequence of suppressed malonyl-CoA concentration in parallel with decreased GLUT-4 expression. In the lactating woman, this regulation in adipose tissue may enhance the provision of nutrients for the infant instead of nutrients being stored in adipose tissue. In hyperprolactinemic individuals, a suppressed lipogenesis could contribute to an insulin resistant state with consequences for the health.

Prevalence and incidence of HIV-1 and HIV-2 before, during and after a civil war in an occupational cohort in Guinea-Bissau, West Africa.

OBJECTIVES: To study prevalence and incidence of HIV-1 and HIV-2 between 1990 and 2007 and to examine impact of the civil war in 1998-1999. We also wanted to investigate possible interaction between HIV-1 and HIV-2. DESIGN: Open prospective cohort study of 4592 police officers in Guinea-Bissau, West Africa. METHODS: Analysis of HIV-1 and HIV-2 prevalence and incidence divided in 2-3 years time strata. RESULTS: HIV-1 prevalence (including HIV-1/HIV-2 dual reactivity) increased gradually from 0.6 to 3.6% before the war and was 9.5% in the first serosurvey after the war. HIV-1 incidence more than doubled during and shortly after the war, from 0.50 to 1.22 per 100 person-years. Both prevalence and incidence of HIV-1 decreased in the following periods after the war. HIV-2 prevalence decreased from 13.4 to 6.2% during the entire study period and HIV-2 incidence decreased from 1.38 to 0.18 per 100 person-years. Adjusted incidence rate ratios of HIV-1 incidence in HIV-2-positive participants compared with HIV-negative participants ranged from 1.02 to 1.18 (not significant) depending on the confounding variables included. CONCLUSION: HIV-1 has increased, whereas HIV-2 has decreased and the risk of acquiring HIV-1 is now more than four times higher as compared with HIV-2. The civil war in 1998-1999 appears to have induced a temporary increase in HIV-1 transmission, but now a stabilization of HIV-1 incidence and prevalence seems to have taken place. There was no evidence of a protective effect of HIV-2 against HIV-1 infection.

Does gold concentration in the blood influence the result of patch testing to gold?

BACKGROUND: We have recently found a correlation between contact allergy to gold sodium thiosulphate (GSTS) and gold concentration in the blood (B-Au) in a stented population: the higher the B-Au, the stronger the patch-test reaction. OBJECTIVES: To further investigate the correlation between B-Au and patch-test reactivity to gold. METHODS: In this provocation control cross-over trial of 24 patients with dermatitis with a known contact allergy to gold, the patients were randomized into two groups where one was topically provoked to gold (15 mg GSTS) and one to the control. All patients were simultaneously patch tested with GSTS in 10 aqueous dilutions (1.1 mg GSTS). Patch-test readings were performed and blood was drawn. After 6 weeks, the experiment was repeated and the group that had previously been provoked with gold was now provoked with the control and vice versa. RESULTS: B-Au was higher after gold provocation whereas no treatment effect was discerned for minimal eliciting concentration (MEC) or summarized test score (STS). Instead, significant differences in period effect were observed implying higher B-Au and STS and lower MEC on test occasion II. The most likely explanation is the increased B-Au and /or booster effect from test occasion I. There was a correlation between B-Au and MEC: the higher the B-Au, the lower the MEC. CONCLUSIONS: The correlation between B-Au and MEC indicates that the B-Au is of importance for the skin reactivity to gold.

Interaction of cholera toxin with three life-cycle stages of Schistosoma mansoni: adult worm, egg and cercaria.

We have previously reported that there is an immunological cross-reactivity between Schistosoma mansoni and cholera toxin (CT). In this study, using an immunofluorescence technique with anti-CT antibody, we provide further evidence for this cross-reactivity by demonstrating an antigen, localized in the tegument of S. mansoni adult worms which is cross-reactive with a CT antigen. Anti-CT antibodies also reacted with structures in S. mansoni cercariae and eggs. Additionally, CT itself was found to bind strongly to the gut of the adult worm, gut cells of cercaria and the egg shell. The binding of CT to the parasite was blocked when parasite sections were incubated with CT which had been incubated with the ganglioside GM1. Lipid extraction and isolation of gangliosides demonstrated the presence of GM1 in adult worms. For further analysis of CT-binding structures, the possible interaction of CT with two major schistosome gut antigens, circulating cathodic antigen (CCA) and circulating anodic antigen (CAA), was studied. We found that CT blocked the binding of anti-CCA antibody to the gut of adult worms and that anti-CCA blocked the binding of CT to the worm gut. These findings indicate that CT binds to CCA present in the gut of the parasite and thus has, in addition to GM1, a second binding specificity.

Association of -1087 IL10 and -308 TNFA gene polymorphisms with serological markers of coeliac disease.

Coeliac disease (CD) is known to have a strong genetic background. We analyzed the association between serological markers of CD and the -1087 IL10 and -308 TNFA gene polymorphisms in Swedish patients. A higher frequency of the TNF2 allele was present in the patients compared with the controls (p < 0.0001). The frequency of the AA genotype of the IL10 gene in the patients was unexpectedly higher in comparison with the controls (p < 0.05). The levels of IgA anti-endomysium and antitissue transglutaminase antibodies were associated with IL10 but not with TNFA genotype. The patients with the AA or GG -1087 IL10 genotypes had significantly lower levels of antibodies in comparison with those with the AG genotype (p < 0.05 to p < 0.0005). However, when divided according to potential level of IL-10 production, the group of potentially high IL-10 producers among the CD patients demonstrated significantly lower levels of antitissue transglutaminase antibodies compared to potentially low IL-10 producers (p = 0.01). Our results show a relationship between the levels of IgA antibodies involved in CD with the IL10 genotypes. This suggests a possible involvement of IL-10 in the development of the disease.

Adult coeliac patients do tolerate large amounts of oats.

OBJECTIVE: The aim of the present study was to investigate whether adult patients with coeliac disease in remission could include large amounts of oats in their daily gluten-free diet for an extended period of time without adverse effects. DESIGN, SUBJECTS AND METHODS: Twenty adult coeliac patients in remission included large amounts of uncontaminated rolled oats in their daily diet for a prolonged period. The examinations, performed four times during the study period, included small bowel endoscopy with biopsies, blood samples (nutritional status, serological analysis), height and body weight, gastrointestinal symptoms and dietary records. Gastrointestinal symptoms and diet were also investigated through unannounced telephone interviews once a month during the study period. RESULTS: No adverse effects of a large intake of oats were seen in small bowel histology, serology nor in nutritional status in the 15 subjects who completed the whole study period. Two of the subjects dropped out because of gastrointestinal symptoms and three for non-medical reasons. The median intake of oats was 93 g/day and the compliance to the oat diet was found to be good. Examinations of the patients after drop-out did not show any deterioration in small bowel histology or nutritional status nor raised levels of antibodies. CONCLUSION: Results from this study indicate that adult patients with coeliac disease in remission can include large amounts of controlled wheat-free rolled oats for an extended period of time without adverse effects.

The fibre-web blood sampling technique applied to serological diagnosis of schistosomiasis mansoni.

The fibre-web technique for sampling, storing and transport of venous or capillary blood has been evaluated, in 84 schoolchildren from the Mwanza region of Tanzania, with regard to diagnostic efficacy for determination of the schistosome circulating anodic antigen (CAA) under conditions similar to those prevailing in the field. Although the average concentrations determined in fibre-web eluates were only about half of those determined in serum, the prevalences of CAA-positive individuals for the 2 sample materials were approximately the same. The average coefficient of variation calculated on determination of CAA in venous-blood fibre-web eluates amounted to 7%. The study shows that the fibre-web technique is well suited for use under field conditions.

Role of immunosuppressive therapy in refractory sprue-like disease.

Patients with malabsorption and histological findings consistent with celiac disease, who are unresponsive to gluten free diet, and in whom other causes of flat mucosa have been excluded, are considered to suffer from so called unclassified or refractory sprue. Although the true nature of this condition needs to be further elucidated, it is known to represent a difficult therapeutical problem with potentially fatal course. Herein, we report a patient with refractory sprue-like disease who after failing to respond to corticosteroids and TPN was in a critical condition. He responded promptly to cyclosporine and made a remarkable recovery. In contrast to previous reports, the cyclosporine treatment in this patient was pursued only for 1 month, whereupon the patient turned responsive to steroids. Subsequent treatment with azathioprine allowed corticosteroids to be reduced to a low maintenance dose and eventually all drugs could be discontinued without reappearance of symptoms. Cyclosporine therapy might be lifesaving in occasional patients with refractory sprue-like disease and it may result in reversal of steroid resistance. Moreover, azathioprine seems to have a steroid sparing effect in this setting. Short term immunosuppressive treatment may have an advantage of lower risk for drug related side effects.

Immunological cross reactivity between Schistosoma mansoni and cholera toxin.

Intranasal administration of schistosome antigens in combination with appropriate adjuvant may be an effective route for immunization against schistosomes, since the lungs represent an important site of elimination of schistosomulae. Our previous studies have shown that in mice intranasal administration of cholera toxin (CT) before infection with Schistosoma mansoni results in an enhancement of the worm burden in comparison to nontreated infected animals. In the present study, it was shown that mice treated intranasally with CT displayed high numbers of schistosome-reactive IgM-secreting cells in the spleen as well as high levels of schistosome-reactive serum IgM antibodies, whereas no significant immunological response against two other antigens, ovalbumin (OVA) or keyhole limpet haemocyanin (KLH) was noted. Sera from mice treated intranasally with CT recognized a 22 kDA antigen on SWAP blots. This band was not demonstrable after absorption of the sera with SWAP. These findings indicate a possible cross reactivity between cholera toxin and schistosome antigens. Further analysis by Western blot revealed that a 22 kDa antigen was detected on CT blots by sera from mice and humans infected with S. mansoni. This band was not demonstrable after absorption of the mouse or the human sera with CT. The 22 kDa cross reactive antigen was heat-stable. The antibodies against the 22 kDa antigen were only found within the IgM class but not within other Ig isotypes. Our findings also indicate that the 22 kDa antigen detected by anti-S. mansoni antibodies represents the A1 fragment of the cholera toxin.

Polypropylene fibre web, a new matrix for sampling blood for immunodiagnosis of schistosomiasis.

Blood sampling on filter paper is widely used for immunodiagnostic and epidemiological purposes. However, elution of conventional filter papers impregnated with sera containing Schistosoma mansoni circulating anodic antigen (CAA) recovered only a small fraction of the antigen, thereby reducing the sensitivity of the assay. Polypropylene-based non-woven fibre web is a new sampling material with a low density of fibres and with a small surface area of contact. When it was impregnated with serum containing CAA, approximately 90% of the antigen could be extracted. The yield of antibodies against S. mansoni from the new sampling material did not differ from that from conventional filter papers.

Intranasal administration of Schistosoma mansoni adult worm antigen in combination with cholera toxin induces a Th2 cell response.

Mice immunized with soluble adult worm antigen (SWAP) in combination with cholera toxin (CT) displayed significantly larger numbers of IgG1, IgM and IgA secreting cells in the spleen and in the lungs as compared to mice which had received SWAP only. The ratio of SWAP-specific IgG1 to IgG2a antibody-secreting spleen cells was also significantly higher in the SWAP-CT group. Analysis of cytokine responses revealed that SWAP-stimulated spleen and lung cells from the SWAP-CT group produced lower levels of IFN-gamma but higher levels of IL-4 and IL-5 as compared to cells from the SWAP group. These findings indicate that intranasal administration of SWAP-CT induces a Th2 cell response in the spleen and in the lungs. Our findings also suggest that CT was responsible for induction of this Th2 cell response, since intranasal administration of SWAP alone induced a Th1 type response in the spleen and in the lungs.

Diagnosis of female genital schistosomiasis by indirect disease markers: determination of eosinophil cationic protein, neopterin and IgA in vaginal fluid and swab eluates.

Based on assumptions about the pathophysiology of egg-related lesions in the lower reproductive tract, putative indirect disease markers were investigated in vaginal fluids from 54 Malawi adolescent girls and women infected with S. haematobium. These women received a careful gynecological examination during which biopsies were taken from the cervix, and, if present, also from suspicious lesions in the vagina and the vulva. If the biopsies, either in wet crushed preparations or in histological sections, contained eggs the patients were considered to have female genital schistosomiasis (FGS; n = 33). The remainder (n = 21) were classified as having urinary schistosomiasis only. Eosinophil cationic protein (ECP), a cytotoxic granule protein of eosinophils, neopterin, a second messenger molecule generated during the activation of macrophages, and IgA as an indicator of local B-cell activation were quantitatively determined in vaginal fluid. To clarify the origin of ECP, this protein was also looked for in histological sections by an immunohistochemical method. In order to explore whether such disease markers can be detected after absorption to a tampon-like material, ECP and IgA were also assessed after elution from a non-porous, polypropylene fibre web impregnated with vaginal fluid. The concentration of ECP in vaginal fluid and the degree of immunohistochemical staining in histological sections were significantly higher in patients with FGS than in women with urinary schistosomiasis only. The amount of ECP detected in histological sections correlated to the number of eggs/mm2 of compressed genital tissue (rho = 0.36, P = 0.02), and the concentration of ECP in vaginal fluid correlated to the concentration of neopterin as well as to that of IgA (rho = 0.52, P = 0.004 and rho = 0.37, P = 0.02, respectively). Median neopterin concentration in vaginal fluid was also higher in the FGS group, but the difference was not statistically significant. ECP could also be detected in eluates from impregnated fibre webs, but the concentration was approximately one power of 10 less than in the original vaginal fluid. These results demonstrate that indicators of immunological mechanisms related to the egg-granuloma might be useful as indirect disease markers for women with FGS if assessed in vaginal washings or swab eluates.

A comparative study on specific antibodies and circulating antigen (CAA) in serum and parasitological findings for diagnosis of schistosomiasis mansoni in an endemic area in Tanzania.

A baseline study to evaluate the prevalence of Schistosoma mansoni infection as well as the diagnostic efficacy of serodiagnostic tests was performed in Kabaganga village, Kome island, Lake Victoria, Tanzania. A total of 1108 individuals were examined parasitologically and clinically. Egg excretion was demonstrated by one-sample Kato-Katz test. Specific IgG1 and IgG4 antibodies against S. mansoni adult worm (SAWA) and egg (SEA) antigens as well as circulating anodic antigen (CAA) were determined in serum samples from 250 of these subjects. As a control population 41 individuals from a non-endemic area were examined parasitologically, clinically and serologically. In the parasitologically examined Kabaganga population 45% were excreting eggs. The pattern of egg excretion was typical for an endemic area with a peak in the age group 10-14 years. Sixty-five percent of the serologically tested villagers were positive in the CAA test. A total of 80% were positive in either of the two tests, indicating an active infection. In 67-95% of these individuals the levels of isotype specific antibodies were increased. The prevalence of CAA positivity corresponded fairly well with that of Kato-Katz results in the age groups 10-29 years, but in the younger age groups a considerably greater number of individuals were positive in the CAA test than in the Kato-Katz test. The results obtained indicate that virtually all of the Kabaganga villagers, regardless of age, had an ongoing, active infection or had previously been infected with S. mansoni. This population, therefore, may be useful for evaluation of the diagnostic efficacy of various antibody tests. The highest degree of discrimination between the endemic and the non-endemic village populations was noted for anti-egg IgG4 antibodies. It is concluded that the combined determination of parasite eggs in faeces and CAA in serum provides high sensitivity as regards active infection. Increased levels of isotype-specific antibodies, particularly of the IgG4 subclass, is a sensitive indicator of past or present infection, and the prevalence of individuals with such increased levels may be a simple and reliable indicator of the frequency of schistosomiasis in a community.

Visceral leishmaniasis in Somalia. Significance of IgG subclasses and of IgE response.

We have determined the levels of IgG subclasses and IgE as well as specific antibodies of these isotypes in sera from 22 patients with clinical visceral leishmaniasis (VL) from Somalia. The results are compared with those obtained from 30 Somali and 23 Swedish controls. We found markedly increased concentrations of IgG1 in the VL sera, indicating that the pronounced increase in IgG in VL which is generally considered to be due to polyclonal B-cell activation is mainly restricted to this subclass. The IgG2 concentrations were significantly decreased. The IgG3 and IgG4 concentrations, on the other hand, did not differ between the two groups of Somali sera. The Somali control sera contained higher concentrations of IgG1 and IgG3, but significantly lower concentrations of IgG2 as compared to Swedish controls. The IgG4 values, on the other hand, were not different between the two groups of control sera. Anti-leishmania antibodies belonging to all IgG subclasses, were found in the patients' sera. There was no significant difference in total IgE between sera from VL patients and controls and specific IgE antibodies were only detected in a few patients. The Western blot assay (WB), revealed the presence of two bands corresponding to 74 kDa and 88 kDa in all patients' sera, indicating a possible diagnostic role for WB in this particular population.

Lack of interferon-gamma receptor does not influence the outcome of infection in murine schistosomiasis mansoni.

Studies of vaccine-induced immunity in experimental schistosomiasis in mice have suggested that interferon-gamma (IFN-gamma) is an important factor for the induction of protective immunity against schistosomiasis. The present study compares some parameters during primary schistosome infection in IFN-gamma receptor deficient mice and wild type mice. No significant difference in worm burden between the two groups was found. Almost the same number of eggs in the liver as well as typical granulomas with numerous macrophages and eosinophils were observed in both groups of mice. Furthermore, IFN-gamma receptor deficient mice infected with S. mansoni displayed a significant reduction in the number of IgG2a secreting cells in the spleen and a significant enhancement of IgA secreting cells in the spleen and in the lungs. These findings suggest that the lack of IFN-gamma activity may result in an enhanced dominance of Th2 cells which, however, does not influence the development of a primary schistosome infection.

Value of serologic markers for clinical diagnosis and population studies of coeliac disease.

BACKGROUND: There is a need for serologic markers in selecting patients with symptoms compatible with coeliac disease for intestinal biopsy and for population screening. Few comparative studies have been done. METHODS: Sera from 55 patients with coeliac disease and 65 referents, aged between 8 months and 79 years, were investigated. Anti-gliadin, anti-reticulin, anti-endomysium, and anti-jejunal antibodies were measured. The sensitivities, specificities, and positive predictive values for different disease prevalence levels were calculated. Confidence intervals, rarely used in this type of study, were calculated. RESULTS AND CONCLUSIONS: In most tests the antibody levels were age-correlated. The highest sensitivities in combination with high specificities were found for IgA anti-gliadin antibodies in children less than 5 years of age and IgA anti-endomysium antibodies in older children and adults. These tests were most useful for testing a population with a high disease prevalence, such as patients with gastrointestinal symptoms, although the results for many tests had overlapping confidence intervals. For screening unselected populations with a low disease prevalence, in which a test with maximum specificity is desired, only anti-endomysium antibodies had sufficiently high predictive value to be of practical use.