Interleukin 2 and gamma interferon production, interleukin 2 receptor expression, and DNA synthesis induced by tularemia antigen in vitro after natural infection or vaccination.

The T-cell response induced by Francisella tularensis antigen in sensitized subjects was characterized in vitro by measuring DNA synthesis in whole-blood and mononuclear cell cultures, interleukin 2 (IL-2) and gamma interferon (IFN-gamma) production, and IL-2 receptor expression. Correlations between these variables were estimated. The strengths of the responses were compared in 21 subjects naturally infected 2 years ago, 6 subjects vaccinated 5 to 6 years ago, and 13 control subjects with no history of infection or vaccination. Subjects with a history of natural infection synthesized more DNA in both whole-blood and mononuclear cell cultures, secreted more IL-2 and IFN-gamma, and expressed more IL-2 receptors than control subjects did. All these responses differed highly significantly (P less than 0.001) from those of the control subjects. The vaccinees exhibited somewhat lower responses than the naturally immunized subjects did, but the vaccinees could be distinguished from the control subjects by their DNA synthesis, receptor expression, and IFN-gamma production (P less than 0.01 to 0.001). The vaccinees showed a lower response, in terms of DNA synthesis and IL-2 secretion (P less than 0.05), than the infected group did but responded in a manner similar to that of this group, with respect to receptor positivity and IFN-gamma secretion (P greater than 0.10). The correlations between all the T-cell functions were good, with highly significant correlations (P less than 0.001) between whole-blood DNA synthesis and IL-2 and IFN-gamma secretion and between the two lymphokines (P less than 0.001). The results not only increase our knowledge of the T-cell response to tularemia antigen but also give an alternative approach to DNA synthesis measurement for the quantitation of T-cell responses. The results for the low-responding sensitized subjects seem to indicate that the parameters were comparable in sensitivity.     

Distribution and mRNA expression of tenascin-C in developing human lung

Tenascin-C is an extracellular matrix glycoprotein that is spatially expressed during organogenesis, in inflammatory and fibrotic disorders, and in neoplasms. The aim of this study was to analyze its expression in developing human lung tissues during pseudoglandular, canalicular, saccular, and alveolar periods corresponding to Weeks 12 to 40. Lung tissues were obtained at autopsy from 34 nonmalformed cases. An immunohistochemical analysis and a messenger RNA (mRNA) in situ hybridization method combined with light microscopy were used. The extent of tenascin-C immunoreactivity was scored as absent, low, moderate, or strong in and around different types of pulmonary cells. The immunohistochemical expression for tenascin-C was strong beneath the airway epithelium, especially at the sites of airway subdivision during Weeks 12 to 23, whereas its expression was moderate or weak underneath alveolar and bronchiolar epithelia between Weeks 24 and 40. The expression for tenascin-C was strong in the intima of veins, especially in the canalicular period, i.e., Weeks 17 to 28. A moderate or strong immunoreactivity for tenascin-C was also observed around chondrocytes in every case studied during all periods. The increased expression of tenascin-C mRNA was most often seen in the cells below the airway epithelium. Taken together, tenascin-C is expressed in human lung during all developmental periods, and its expression is especially strong below the airway epithelium at the sites of airway subdivision.     

The hydrolethalus syndrome: delineation of a "new", lethal malformation syndrome based on 28 patients

We describe a lethal malformation syndrome in 28 newborn infants from 18 families. The main manifestations were hydrocephalus (often with an unusual structure of the brain and the occipital bone), very small mandible, Polydactyly, congenital heart defect, abnormalities of the respiratory organs, and (different from the Meckel syndrome) normal kidneys. Polyhydramnios and stillbirth or neonatal death were the rule. Autosomal recessive inheritance is evident. This syndrome is another in the group of rare recessive disorders which are found in Finland. Because of the 25 % recurrence risk and possibilities for prenatal diagnosis, this syndrome should be recognized by paediatricians and, because of the frequent stillbirths, also by obstetricians and pathologists. The name hydrolethalus syndrome (hydramnios, hydrocephalus, lethality) may be of help in this.     

Antibodies against Streptococcus pneumoniae, Haemophilus influenzae and Branhamella catarrhalis in middle ear effusion during early phase of acute otitis media

Serum type (IgG, IgM and IgA-class) and secretory type antibodies specific to Streptococcus pneumoniae (Pn), Haemophilus influenzae (Hi) and Branhamella catarrhalis (Br) were measured by enzyme-linked immunosorbent assay (ELISA) in 46 serum and 114 middle ear effusion (MEE) samples from 85 children with acute otitis media (AOM). The samples were obtained within 12 h from the onset of the ear symptoms. Serum (but not secretory) type antibodies to the infecting Pn serotype were found in 24% of the MEE samples of the patients with Pn AOM and, correspondingly, serum and/or secretory type antibodies to Hi and Br were seen in 54% and 63% of the MEE samples of the patients with Hi or Br AOM, respectively. Moreover, antibodies against bacteria other than the causative one could also be found in the MEE. The occurrence of the serum type antibodies against these bacteria in the MEE was closely correlated with their serum levels. The findings of this study indicate that during the very early phase of AOM, the MEE contains both serum type antibodies originating from the serum, and secretory antibodies of middle ear origin. Among them there are antibodies specific to the three most common bacteria causing AOM (Pn, Hi, and Br) regardless of the bacterial etiology of the AOM attack in question.     

Roentgenologic findings of the hydrolethalus syndrome

The hydrolethalus syndrome is an autosomal recessive malformation syndrome which has been recently described in Finland. The name hydrolethalus refers to the main findings, namely polyhydramnios, hydrocephalus and lethality. The patients are either stillborn or die soon after birth. The typical roentgenologic findings are hypoplasia of the tibia associated with the anomalies of the respective bone ray, e.g. metatarsus primus varus atavisticus, hallux varus or hallux duplex varus and hydrocephalus with extreme micrognathia and a specific midline defect of the occipital bone.     

Inherited interstitial del(Xp) with minimal clinical consequences: with a note on the location of genes controlling phenotypic features.

In a routine cytogenetic investigation of the outpatients of a hospital for the mentally retarded, a 26-year-old women with a presumptive interstitial deletion of the short arm of one of the X chromosomes was found. The same aberration was found in her phenotypically normal mother and in one of her four sisters, all phenotypically normal. By GTG- and QFQ-banding methods, the deletion was interpreted to involve the entire band Xp21 and adjacent parts of p11 and p22. The karyotype is written 46,X,del(X)(pter leads to p22::p11 leads to qter). By autoradiography and Bud R acridine orange technique, the deleted X was the late replicating one in all three affected persons. The deletion apparently causes shortness of stature but no other phenotypic symptoms or signs. Hence a gene or genes controlling stature is located in band Xp21 or regions immediately adjacent to this band. Since the absence of this region does not cause streak gonads, it does not contain genes controlling the formation of the ovaries. This appears to be the first example of a heritable chromosome deletion compatible with a normal phenotype and reproduction.     

Atopy and depression: results from the Northern Finland 1966 Birth Cohort Study

Several studies have suggested an association between IgE-mediated atopic allergies and depression. The present study extends our understanding about putative gender differences of this association and provides further epidemiological evidence for our previous finding that the association between atopy and depression may be characteristic for females only. In order to clearly determine the presence of atopic disorders and depression, we used more valid tools than had been employed earlier and we had access to a database (the Northern Finland 1966 Birth Cohort), in which individuals were followed up prospectively until the age of 31 years. The information on allergic symptoms, verified by skin-prick tests and comprising data of 5518 individuals, was used to ascertain the presence of atopy. Depression was assessed with the help of Hopkins' Symptom Checklist-25 and self-reported doctor-diagnosed depression. After adjusting for a father's social class, mother's parity, and place of residence, logistic regression analyses showed that the risk of developing depression increased in parallel with the increasing severity of depression and, when compared with nonatopic subjects, was 3.0 to 4.7-fold up in atopic females and statistically significant. In atopic males, the association between atopy and depression was statistically significant only in the highest depression scores, the odds ratio being 6.3-fold. The results indicate that females suffering from atopic diseases might possess an elevated risk of developing depression already during early adulthood. In males, the association between these two disorders is evident only among the most severe manifestations of depression. Possible background theories, that is, genetic abnormalities in serotonin metabolism, HPA-axis dysfunction, and histamine theory are discussed.     

Gastrointestinal findings in atopic children

36 children aged 0.13 to 13.05 years with severe manifestations of atopy were studied for circulating parietal cell antibodies (PCA), fasting serum gastrin and ferritin. Gastric acid secretion was measured using a pentagastrin test. In addition, 21 gastric and 28 jejunal biopsies were taken for evaluation of the mucosal morphology. In infants the gastric secretion studies were repeated after a three month hypoallergic diet.Maximal acid output (MAO) was significantly (P<0.01) diminished in atopic infants under one year of age. In this group one girl with transient PCA was achlorhydric and seven others were hypochlorhydric, as compared with controls of the same age. Acid secretion returned to normal in most children while on the elimination diet, and only two remained hypochlorhydric thereafter. The picture was more complex in the older children as some continued to exhibit hyposecretion in their second year of life, while others were even hyperchlorhydric. Epithelial degeneration, found in 13 out of the 21 samples, was the most striking feature in the gastric biopsies. Jejunal biopsies revealed increased eosinophilic infiltration of the lamina propria in 10 out of 28 diagnostic samples; two had slight and another two partial villous atrophy.It is concluded that in atopic children gastric hyposecretion and epithelial degeneration may promote the passage of unhandled food allergens through the jejunal mucosa, predisposing to more severe changes, as seen in cow's milk intolerance. Slight villous atrophy with eosinophilic infiltration and oedema of the lamina propria may cause mild absorption defects, growth and nutritional deficiencies in these children. Atopy should be considered as a possible aetiological factor in prolonged gastrointestinal disorders in infants.