Accumulation of atopic disorders within families: a sibling effect only in the offspring of atopic fathers

BACKGROUND: Several studies have reported an association between a child's risk of atopic disorders and family size. However, the inverse association might not be the same in populations with a different genetic disposition for atopic disorders. OBJECTIVE: This longitudinal study was designed to assess risk factors of atopy. METHODS: Lifetime prevalence of asthma, hay fever and eczema of 1440 families including 3165 offspring was ascertained by means of standardized questionnaires. RESULTS: After possible confounders had been controlled for, an inverse association between atopic disorders and the number of older siblings was found only in the offspring of atopic fathers (trend for older siblings: chi2 = 13.38, degrees of freedom [d.f.] = 1, P= 0.0002; odds ratio 'no older sibling'= 2.87 (95% confidence interval 2.18-3.78); '1 older sibling' = 2.11 [1.52-2.92], '2 older siblings' = 1.29 [0.74-2.23]; '3 or more older siblings' = 0. 15 [0.02-0.981). No such relationship was found for children without a history of paternal atopy (trend for older siblings: chi2 = 1.5 1, d.f. = 1, P = 0.22; odds ratio 'no older sibling' = 1 [reference]; '1 older sibling' =0.82 [0.63-1.06]; '2 older siblings' = 0.97 [0.67-1.40]; '3 or more older siblings' = 0.64 [0.31-1.33]). The trend for older siblings in the case of paternal atopy was significantly different from the trend for older siblings without a history of paternal atopy (chi2 = 8.68, d.f. = 1, P = 0.003). The number of younger siblings was not related to child's risk of atopy (trend for younger siblings: chi2 = 0.001, d.f. = 1, P = 0.97). CONCLUSIONS: Data from this study suggest a protective effect of sibship size only in children with a history of paternal atopy and if older siblings are present. The reason for this combined effect remains unclear. Thus, further investigations are needed to interpret the biological cause of the so called 'sibling effect'.     

Increased phagocytic capacity of the blood,but decreased phagocytic activity per individual circulating neutrophil after an ultradistance run

The effect of a long strenuous endurance exercise on the phagocytic function of neutrophils was examined. 9 athletes [7 males, 2 females, age: 36–68 years, body mass: 64 (SD 10) kg, height: 175 (SD 10) cm] completed a competetive 100 km run in 8:07 (median value; range: 7:29–9:50 hours). In a whole blood assay the phagocytosis of opsonized E. coli, the receptor density of the Fc receptor 3 (CD16) and the complement receptor 3 (CD11b, direct immunofluorescence) of neutrophils were measured on a per cell basis by flow cytometry before and up to 3 hours after the race. The phagocytic rate (percentage of neutrophils incorporating bacteria) was unchanged after exercise, whereas the phagocytic activity (number of incorporated bacteria per cell) was significantly reduced by –34 (SD 8) % (Wilcoxon test, P<0.001). The total phagocytic capacity of the blood increased 2-3fold post exercise. The surface antigen expressions of CD11b and CD16 were unaffected by the ultradistance run. The results indicate either a reduced phagocytic function of neutrophils on a single cell basis or the mobilization of neutrophils of the marginal pool with a lower phagocytic activity. However, after a long endurance exercise the phagocytotic capacity of the blood was enhanced due to increased cell concentrations.     

Comparative Analysis of Apoptosis and Inflammation Genes of Mice and Humans

Apoptosis (programmed cell death) plays important roles in many facets of normal mammalian physiology. Host-pathogen interactions have provided evolutionary pressure for apoptosis as a defense mechanism against viruses and microbes, sometimes linking apoptosis mechanisms with inflammatory responses through NFκB induction. Proteins involved in apoptosis and NFκB induction commonly contain evolutionarily conserved domains that can serve as signatures for identification by bioinformatics methods. Using a combination of public (NCBI) and private (RIKEN) databases, we compared the repertoire of apoptosis and NFκB-inducing genes in humans and mice from cDNA/EST/genomic data, focusing on the following domain families: (1) Caspase proteases; (2) Caspase recruitment domains (CARD); (3) Death Domains (DD); (4) Death Effector Domains (DED); (5) BIR domains of Inhibitor of Apoptosis Proteins (IAPs); (6) Bcl-2 homology (BH) domains of Bcl-2 family proteins; (7) Tumor Necrosis Factor (TNF)-family ligands; (8) TNF receptors (TNFR); (9) TIR domains; (10) PAAD (PYRIN; PYD, DAPIN); (11) nucleotide-binding NACHT domains; (12) TRAFs; (13) Hsp70-binding BAG domains; (14) endonuclease-associated CIDE domains; and (15) miscellaneous additional proteins. After excluding redundancy due to alternative splice forms, sequencing errors, and other considerations, we identified cDNAs derived from a total of 227 human genes among these domain families. Orthologous murine genes were found for 219 (96%); in addition, several unique murine genes were found, which appear not to have human orthologs. This mismatch may be due to the still fragmentary information about the mouse genome or genuine differences between mouse and human repertoires of apoptotic genes. With this caveat, we discuss similarities and differences in human and murine genes from these domain families.     

Increased plasma levels of LDL cholesterol in rabbits after adenoviral overexpression of human scavenger receptor class B type I

Scavenger receptor class B type I (SR-BI), a CD36 family member, plays a key role in high-density lipoprotein (HDL) metabolism, reverse cholesterol transport, and whole body cholesterol homeostasis, and is shown to be involved in the development of atherosclerosis in mice. In this report, we describe the effects of the adenoviral overexpression of human SR-BI (hSR-BI) in New Zealand White (NZW) rabbits, a wild-type animal model that expresses cholesteryl ester transfer protein (CETP) in plasma, displays a manlike lipoprotein profile, and is susceptible to atherosclerosis. A total of 1×10¹² adenoviral particles containing either hSR-BI or lacZ complementary deoxyribonucleic acid (control) were infused into the ear vein of NZW rabbits. Transgene expression was ascertained by TaqMan Real Time polymerase chain reaction measurements. Rabbits infected with Ad/hSR-BI (adenoviral plasmids containing hSR-BI) showed a faster clearance of administered [³H]HDL cholesterol and significantly decreased apolipoprotein (apo) A-I levels when compared to control rabbits, respectively. Interestingly, we found markedly increased levels of low-density lipoprotein (LDL) cholesterol exclusively in SR-BI-overexpressing rabbits. These changes were not accompanied by alterations in LDL receptor expression but by increased levels of CE transfer in these animals. By lowering HDL cholesterol and increasing plasma apoB-containing lipoprotein levels, the overexpression of SR-BI leads to a lipoprotein pattern, which is believed to enhance the development of atherosclerosis. The role of SR-BI in lipoprotein metabolism and atherogenesis in rabbits—a CETP-expressing animal model displaying a manlike lipoprotein profile—may therefore be different from the one found in rodents.     

Fibroblast Growth Factor Enhances Long-term Potentiation in the Hippocampal Slice

Recently we reported that perfusion of hippocampal slices with epidermal growth factor (EGF) lead to enhancement of potentiated responses after tetanic stimulation. In the present study we report that basic fibroblast growth factor (FGF) can also lead to an enhancement of potentiated responses. FGF is a mitogen for several cell types and exhibits neurotrophic effects on neurons of the central nervous system (CNS). Rat hippocampal slices were perfused with FGF at a concentration of 10-9 M. During extra- and intracellular recordings in the CA1-region, the addition of FGF to the perfusing medium produced no change in evoked responses if single pulse or paired pulse stimulation was used. Furthermore FGF had no influence on the resting membrane potential and input resistance. However, after tetanic stimulation, FGF-treated slices showed an increase in the magnitude of potentiation compared to control slices. Taken together with the EGF data these results support the hypothesis that growth factors like FGF with neurotrophic potential on CNS-neurons can influence synaptic efficacy. Furthermore these results show that factors which are able to modulate developmental plasticity and regenerative plasticity can also modulate synaptic plasticity.     

Asthma und asthmatypische Beschwerden bei Schulkindern: Vergleich von Gebieten in Deutschland und Osterreich

Conclusion

Geographical differences in morbidity of asthma and asthmalike complaints were ascertained and remained stable after adjustment for potential confounders. However, the choice of the way of presentation (relative risk versus deviation from the weighted mean of the prevalences) can provoke different suggestive effects.     

Fertilization and pregnancies following intracytoplasmic injection of testicular spermatozoa

Purpose Intracytoplasmic injection (ICSI) with testicular sperm was performed in 16 couples. All men had ductal obstruction and failed previous attempts of epididymal sperm microaspiration.Methods Testis tissue was obtained by excisional biopsies and incubated in HEPES buffered EBSS medium over 24 h at 37C. Motile sperm (Grade 1 to 2) were recovered in 13 patients and fertilized a total of 62 oozytes. Four pregnancies were achieved.Results One healthy boy and two girls (twin pregnancy) were born.Conclusions The ongoing pregnancies revealed no fetal abnormalities on ultrasound scanning.Presented at the IXth World Congress on In Vitro Fertilization and Alternate Assisted Reproduction, April 3–7, 1995, Vienna, Austria.     

Exposure to polychlorinated biphenyls and levels of thyroid hormones in children.

As part of an epidemiologic study on exposure to a toxic waste incineration plant we investigated whether blood concentrations of polychlorinated biphenyls (PCBs), lead, and cadmium, as well as concentration of mercury in 24-hr urine samples were associated with thyroid hormone status. As an indication of status, we determined levels of thyroid-stimulating hormone (TSH), free thyroxine (FT(4)), and free triiodothyronine (FT(3)) in children living in households where [less than/equal to] 10 cigarettes were smoked per day. Eight PCB congeners (PCBs 101, 118, 138, 153, 170, 180, 183, and 187) were measured in whole blood samples. Of these, seven congeners (PCB 101 was not detected in any sample) and the sum of all PCB congeners were analyzed as predictors for thyroid hormone status in separate linear regression models adjusted for potential confounders. In addition, the possible effects of cadmium, lead, and mercury on levels of thyroid hormones were examined. Blood concentrations and information on questionnaire data were available for 320 children 7-10 years of age. We found a statistically significant positive association between the mono-ortho congener PCB 118 and TSH as well as statistically significant negative relationships of PCBs 138, 153, 180, 183, and 187 to FT(3). There was no association for the PCB congeners and FT(4). Blood cadmium concentration was associated with increasing TSH and diminishing FT(4). Blood lead and urine concentration of mercury were of no importance to thyroid hormone levels. The results stress the need for future studies on the possible influences of PCB and cadmium exposure on thyroid hormones, particularly in children. These studies should also take neurologic development into account.