Biomedical subjects

J Floros

Publications and source records attributed to J Floros.

94 records · Page 6Linked to original sources

PubMedDate not supplied

Human surfactant protein-C: genetic homogeneity and expression in RDS; comparison with other species.

Human surfactant protein C (SP-C) mRNA is detected early during fetal lung development before the differentiation of the type II cell and the need for surfactant. Later in life SP-C contributes to the surface-lowering properties of surfactant, as shown by several investigators. In this study we sequenced both coding and noncoding regions of 12 genomic SP-C clones from several human groups including RDS, whites, and black Nigerians, and examined the expression of SP-C in tissues from RDS and from non-RDS. The data showed that all clones had identical DNA sequences, not only within coding regions, consistent with previous observations, but also within intervening, 5' flanking, and 3' untranslated regions. Some differences from the previously published sequence were noted. The expression of SP-C in tissues from RDS and non-RDS as determined by tissue in situ hybridization was comparable between the two groups, suggesting that altered SP-C expression, the result of pretranslational regulatory abnormalities, is an unlikely contributor to the pathogenesis of RDS. In addition the results show, using genomic blot analysis, that a remarkable conservation within coding and 5' flanking but not within 3' untranslated sequences exists in all mammalian species examined. These data taken together suggest that strong evolutionary pressures have been exerted on SP-C to maintain conservation, not only among humans but also among species, which may underscore important roles of SP-C in as yet unknown developmental/functional lung processes.

Animals↗

PubMedDate not supplied

Racial differences in allelic distribution at the human pulmonary surfactant protein B gene locus (SP-B).

Variable numbers of composite repetitive motifs are found in different individuals within intron 4 of the surfactant protein B (SP-B) gene (Biochem J. 1995;305:583). This study tests the hypothesis that the distribution of SP-B alleles differs among racial/ethnic groups. A total of 412 SP-B alleles were analyzed: 206 from Caucasian, 68 from African-American, and 138 from Nigerian individuals. Twelve groups of alleles (A-L) carrying 3 to 18 motifs were found. The distribution of the 12 alleles in the Caucasian group differs from that found in the Nigerian (p < .001) and African-American (p < .001) populations. The overall distribution of alleles between the African-American and the Nigerian populations were not statistically different. Specific alleles were also present in different proportions among the groups studied. For example, the most common allele (allele E) in all three populations is present at a significantly higher frequency in Caucasians than in the other two populations, but its frequency does not differ from the Nigerian and African-American groups. A less frequent allele, H, also differs significantly when Caucasians are compared with each of the other two populations, but the frequency of this allele is comparable between the African-American and Nigerian populations. To assess the importance of having comparable racial composition between the control and the case groups, a group of African-Americans with respiratory distress syndrome (RDS) (n = 40) was compared with the African American and the Caucasian groups studied above. No significant difference was observed between the racially matched groups but a significant difference (p = .006) was observed between the racially mixed groups. The results indicate that the distribution of SP-B alleles differs between the racial groups but not between the ethnic groups studied. Thus, racial composition of the groups under study is important when considering whether particular alleles at this locus predispose to inherited disorders.

Alleles↗

PubMedDate not supplied

Expression and cDNA sequence of helix destabilizing protein (HDP) in rat lung.

The current study was undertaken to investigate genes that show alteration in expression during late fetal rat lung development. Using the differential display (DD) method, an initially unknown transcript was found to be abundant on day 18 compared to day 22 of gestation. This finding was confirmed by RNA blot analysis. Subsequent screening of a rat lung cDNA library with the unknown DD cDNA as a probe revealed a clone that encodes helix destabilizing protein (HDP), similar to that reported in rat brain (J Biol Chem. 1986, 261:3536-3543). Although there were several differences between lung and brain cDNAs at the 3' untranslated region (UTR), the 5' end was well conserved. There was a gradual decrease in HDP mRNA content beyond day 18 of gestation, as lung maturation increased. Similarly, a lower content of HDP mRNA was observed in maternal heart and brain tissues than in fetal heart and brain tissues from day 18 of gestation. Maternal dexamethasone treatment that promotes lung maturation did not have an impact on HDP expression. Because of the much higher abundance of HDP mRNA during fetal organ development compared to adult tissues, we speculate that HDP plays an important role during lung development. A portion of this work was previously presented (FASEB J. 1996;10:A26).

Animals↗

PubMedDate not supplied

Both human SP-A1 and Sp-A2 genes are expressed in small and large intestine.

The human SP-A locus consists of two functional genes and one pseudogene, and SP-A is shown to play a role in local host defense and the regulation of inflammation in lung. Because the intestine, like the lung, is constantly exposed to foreign and potentially harmful substances, we investigated the hypothesis that both human SP-A genes are expressed in intestine. We demonstrate that both SP-A genes are expressed in human small and large intestine. The presence of SP-A mRNA in human intestine was detected by reverse transcription polymerase chain reaction (RT-PCR), Northern blot analysis, and immunohistochemistry. The size of intestinal SP-A mRNA is the same as that in human lung, but the level of expression, compared with that in the lung, is very low in both the small and large intestine. Immunohistochemical analysis revealed positive reactivity for SP-A in a subgroup of epithelial cells in the intestine. Expression of both SP-A1 and SP-A2 genes was established by gene-specific PCR amplification, PCR-based converted RFLP discrimination, and direct sequencing of RT-PCR products. We speculate that SP-A in the intestine plays a role in local host defense and inflammation.

Blotting, Northern↗