Ingestion of Escherichia coli O83 bacteria by adults resulted in a transient irregular colonization leading to a serum antibody response in only four out of 14 cases examined. In all of three pregnant women, however, IgA antibodies against E. coli O83 antigen were released from colostral cells after similar bacterial ingestion although no serum antibody response was noted. The findings indicate a link between the antigenic exposure to the gut and secretory antibodies of the IgA class, presumably locally formed in the mammary gland. Antibodies of the secretory IgA class registered in colostrum may, at least partly, reflect the antigenic exposure of the gut. These antibodies are probably important in protecting against E. coli infections in the neonate, as suggested by the findings of antibodies in human milk against O and K antigens of non-enteropathogenic as well as enteropathogenic serotypes of E. coli. Furthermore, in milk of women from low socio-economic groups in Pakistan, neutralizing antibodies were present against enterotoxins of E. coli bacteria and occasionally against Vibrio cholerae enterotoxins. In addition, secretory IgA antibodies against food proteins were detected in human milk. This suggests that intestinal exposure to such antigens could stimulate a local immune response in the gut resulting in triggered lymphoid cells homing to the mammary gland. These human milk secretory IgA antibodies against bovine milk proteins may help to prevent cow's milk allergy in infants on mixed feeding, since these infants tend to have a lower serum antibody response to cow's milk proteins than infants fed mostly artificially. Furthermore, children suffering from cow's milk protein intolerance and gluten enteropathy may have higher serum levels of antibody to cow's milk protein antigens than normal children, possibly reflecting increased permeability of the intestinal mucosa for various antigens.

Adult↗

PubMedDate not supplied

Defence of mucous membranes by antibodies, receptor analogues and non-specific host factors.

Most infections reach man via the mucosal membranes, and more than half of the lymphoid system is found in connection with mucosae. The major antibodies found on mucous membranes are secretory IgA, which function primarily by binding microorganisms and thereby preventing their contact with the host tissues. The optimal mode of immunization to obtain a secretory IgA response is not well defined. Repeated mucosal exposure with antigen may result in oral tolerance, with decreasing circulating antibodies but a remaining secretory IgA response. The secretory IgA response is usually short-lived and can be difficult to boost. IgM as well as IgG antibodies may add to host defence at the mucosal level, but when engaged, they usually induce inflammation in host tissues. Analogues to bacterial receptors on mucosal epithelium may be present in exocrine secretions such as human milk. During an attack on the host, it is possible that such receptor analogues may aid in the prevention of attachment of bacteria to mucous membranes used as an initial site. A number of non-specific host factors support mucosal defence. One of them is lactoferrin. Lactoferrin deficiency seems to result in recurrent bacterial infections, suggesting its importance in normal host defence.

Administration, Oral↗

PubMedDate not supplied

Immunogenicity and reactogenicity of rhesus rotavirus vaccine given in combination with oral or inactivated poliovirus vaccines and diphtheria-tetanus-pertussis vaccine.

Immunogenicity and reactogenicity of the oral rhesus rotavirus vaccine (RRV) were assessed among 72 infants (6 weeks old) in Lahore, Pakistan, from August to December 1985. Special emphasis was placed on the possible interaction or interference caused by giving RRV at the time infants received their first polio immunization. RRV was given to the infants at the same time as diphtheria-tetanus-pertussis (DTP), oral poliovirus vaccine (OPV), or inactivated poliovirus vaccine (IPV). The immune response to RRV was assessed by plaque-reduction neutralization 3 weeks after immunization and serum immunoglobulin (Ig) G and IgA antibody levels to poliovirus type 1 were tested by enzyme-linked immunosorbent assay (ELISA) after polio immunizations. Of the infants in the group given RRV with OPV, 50% had a two- to four-fold rise in neutralization titre against rotavirus, compared with 22% in the group given RRV with DTP and 20% in the group given RRV and IPV (P less than 0.05). Interference by live oral polio vaccination in the response to RRV seems unlikely. We observed no significant difference in rates of seroconversion of IgG antibodies to poliovirus type 1 among infants aged 18 and 21 weeks who received RRV and OPV (81%), RRV with delayed OPV (67%), or RRV and IPV (59%). Administration of RRV was safe and was not associated with adverse reactions in the 6 weeks old infants. The low rate of seroconversion to rotavirus suggests that a more antigen-rich vaccine or multiple doses of the same vaccine might produce a better immune response.

Antibodies, Viral↗

PubMedDate not supplied

False-positive treponemal serology in patients with diabetes mellitus.

In sera from 476 diabetic outpatients, positive reaction in the Fluorescent Treponemal Antibody-Absorption (FTA-Abs) test, a commonly used serological test for syphilis, was found in 36 of the patients. None of 100 healthy control subjects were positive in the FTA-Abs test. Additional treponemal and nontreponemal tests confirmed the diagnosis of syphilis in only three of the diabetic patients. In 10 of the 36 patients, the positive FTA-Abs reactivity appeared to be due to cross-reactivity between the treponemal antigen and Borrelia burgdorferi, which causes Lyme borreliosis. In the remaining 23 patients (5%), no other explanation for a false-positive FTA-Abs reactivity was found besides diabetes. Diabetic patients with false-positive FTA-Abs reactivity had similar degree of long-term metabolic control and prevalence of islet cell antibodies (ICA) as well as late diabetic complications as FTA-Abs negative diabetic patients, matched regarding to sex, age, type, and duration of diabetes. In conclusion, false-positive FTA-Abs reactivity is not rare in diabetic patients. The reason for this phenomenon is unknown, but could be a sign of autoimmunity of its own. Hence, in diabetic patients with FTA-Abs test indicating syphilis, the diagnosis must be verified with a combination of other tests.

Adolescent↗

PubMedDate not supplied

Characterization of bacterially expressed rat estrogen receptor beta ligand binding domain by mass spectrometry: structural comparison with estrogen receptor alpha.

Functional rat estrogen receptor beta ligand binding domain (rER beta LBD, aa 210-485) and human estrogen receptor alpha ligand binding domain (hER alpha LBD, aa 301-553) were expressed in Escherichia coli. Hormone binding assays revealed that both ER beta and ER alpha LBDs bound the natural ligand estradiol (E2) with similar affinity (Kd approximately 100 pM). Competitive binding experiments were carried out with ICI 164384, 4-hydroxytamoxifen, 16 alpha-bromo-estradiol, and genistein employing [3H]E2 as a tracer. No significant differences in responses of ER alpha and ER beta LBDs to ICI 164384 and 4-hydroxytamoxifen were observed, 16 alpha-Bromo-estradiol and genistein discriminated between the ER subtypes and acted as ER alpha and ER beta selective ligands, respectively. Final purification of recombinant proteins was achieved on an E2 affinity column, where they were subjected to in situ carboxymethylation. The partially carboxymethylated proteins actively bound E2. The carboxymethylated rER beta LBD had a molecular mass of 32251.6 Da, equivalent to the calculated mass with the addition of three carboxymethyl groups. No other proteins (of lower or higher molecular mass) were detected, so the LBD was considered structurally authentic and pure. By using a combination of intact protein mass spectrometric fragmentation and trypsin proteolysis (98% sequence coverage), it was established that rER beta cysteine-289 and -354 were not carboxymethylated on the affinity column, suggesting that they were shielded from alkylation in the E2-bound conformational state. Concurrent analysis of hER alpha LBD showed that under the same experimental conditions, the two equivalent ER alpha cysteines were not alkylated (alpha C381 and alpha C447). These data support close structural relationship between the E2-bound ER alpha LBD and ER beta LBD proteins.

Alkylation↗

PubMedDate not supplied

The secretory IgA system.

The secretory IgA system is common to all mucosal membranes and is presumably of great importance for their defense. In addition to the secretory IgA antibodies produced in a mucosa in response to a local antigenic stimulus there is a spread of this type of IgA response via committed lymphocytes. They originate from central lymphoid organs in the intestinal (Peyer's patches) and bronchial mucosa (bronchus-associated lymphoid tissue, BALT) which they leave after antigenic exposure. They migrate, or "home", to exocrine glands such as the lacrimal, salivary, mammary and prostatic glands and mucosal membranes of the respiratory, gastrointestinal and genito-urinary tract. Almost half of all lymphocytes may be involved in the production of IgA antibodies. The secretory IgA antibodies are the dominating immunoglobulins in exocrine secretions on mucous membranes. They function primarily by preventing contact between the microbe and the host tissue most commonly attacked in infections, the mucous membrane. The fact that breast-feeding protects the infant against intestinal infections is one good example of the clinical significance of secretory IgA antibodies. This mode of protection can be enhanced by vaccination.

Breast Feeding↗

PubMedDate not supplied

Different secretory IgA antibody responses after immunization with inactivated and live poliovirus vaccines.

The influence on secretory IgA antibody levels in milk and saliva of vaccination with oral, live poliovirus vaccine ( OPV ) and inactivated poliovirus vaccine (IPV) was studied. IPV, especially the antigen-rich Dutch vaccine, more often induced increases in antibody titers in milk (50%) than did OPV (26%) (P less than .01). OPV more often decreased the antibody levels in milk (40%) than did IPV (10%) (P less than .01). It was striking that mainly high prevaccination titers were decreased. The increases of IgA antibody in saliva were less striking. IPV caused increases as often in milk as in saliva, whereas OPV more often induced increases in IgA antibody in saliva, but there was a poor correlation between the changes in antibody titers in milk and those in saliva.

Antibodies, Viral↗

PubMedDate not supplied

Dynamic and kinetic effects of chronic citalopram treatment in experimental hepatic encephalopathy.

Chronic hepatic encephalopathy (HE) is a neuropsychiatric syndrome that arises in liver-impaired subjects. Patients with HE display various neuropsychiatric symptoms including affective disturbances and may therefore likely receive treatment with novel thymoleptics like citalopram (CIT). The simultaneous pharmacokinetic and pharmacodynamic outcome of the commonly used serotonin-selective thymoleptic drugs in liver-impaired subjects with pending chronic HE is far from understood today. We therefore investigated the effects of chronic, body-weight-adjusted (10 mg x kg(-1) x day(-1)), treatment with CIT in rats with and without portacaval shunts (PCS). Open-field activity was monitored. The 5-HT, 5-HIAA, noradrenaline (NA), and dopamine (DA) output were assessed in the frontal neocortex. The racemic levels of CIT and its metabolites DCIT and DDCIT, including the S- and R-enantiomers, were determined in serum, brain parenchyma, and extracellular fluid. The rats with PCS showed higher (2-3-fold) levels of CIT than rats undergoing a sham treatment with CIT in all compartments investigated. The PCS rats also showed elevated levels of DCIT and DDCIT. No major differences in the S/R ratios between PCS rats and control rats could be detected. The CIT treatment resulted in neocortical output differences between PCS rats and control rats mainly within the 5-HT and DA systems but not within the NA system. For the 5-HT system, this change was further evidenced by outspoken elevation in 5-HT output after KCI-depolarizing challenges. Moreover, the CIT treatment to PCS rats was shown to "normalize" the metabolic turnover of 5-HT, measured as a profound lowering of a basal elevation in the 5-HIAA levels. The CIT treatment resulted in an increased or "normalized" behavioral activity in the PCS group. Therefore, a dose-equal chronic treatment with CIT in PCS rats produced pharmacokinetic and pharmacodynamic changes not observed in control rats. The results further support the contention of an altered 5-HT neurotransmission prevailing in the chronic HE condition. However, the tentatively beneficial behavioral response also seen following chronic CIT treatment to PCS rats in this study has to be viewed in relation to both the pharmacokinetic and pharmacodynamic changes observed.

Animals↗