Biomedical subjects
Publications and source records attributed to J T Thomas.
The authors describe their use of outcomes research in improving the care of infants in a ten-hospital network of neonatal intensive care units. Improvements in the processes of care for infants born with very low birth weights, and those suffering from chronic lung disease and nosocomial infections, are among the issues discussed.
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Failure of nurses and other health care providers to recognize the influence of culture on child development may lead to inappropriate expectations and mislabeling of children as developmentally slow. The effect of cultural influences on parental expectations of children was evident in a study of child-rearing beliefs of 30 Cuban and 30 Haitian immigrant mothers in South Florida. Both Cuban and Haitian children would be considered lagging developmentally when compared with measurements on the personal-social dimension of the Denver II and expectations of American society. Culture-specific implications for transcultural nursing care based on the concept of culture brokerage are discussed.
Type X collagen is a homotrimeric, short-chain, nonfibrillar extracellular-matrix component that is specifically and transiently synthesized by hypertrophic chondrocytes at the sites of endochondral ossification. The precise function of type X collagen is not known, but its specific pattern of expression suggests that mutations within the encoding gene (COL10A1) that alter the structure or synthesis of the protein may cause heritable forms of chondrodysplasia. We used the PCR and the SSCP techniques to analyze the coding and upstream promoter regions of the COL10A1 gene in a number of individuals with forms of chondrodysplasia. Using this approach, we identified two individuals with metaphyseal chondrodysplasia type Schmid (MCDS) with SSCP changes in the region of the gene encoding the carboxyl-terminal domain. Sequence analysis demonstrated that the individuals were heterozygous for two unique single-base-pair transitions that led to the substitution of the highly conserved amino acid residue tyrosine at position 598 by aspartic acid in one person and of leucine at position 614 by proline in the other. The substitution at residue 598 segregated with the phenotype in a family of eight (five affected and three unaffected) related persons. The substitution at residue 614 occurred in a sporadically affected individual but not in her unaffected mother and brother. Additional members of this family were not available for further study. These results suggest that certain amino acid substitutions within the carboxyl-terminal domain of the chains of the type X collagen molecule cause MCDS. These amino acid substitutions are likely to alter either chain recognition or assembly of the type X collagen molecule, thereby depleting the amount of normal type X collagen deposited in the extracellular matrix, with consequent aberrations in bone growth and development.
The entire mouse collagen X gene (Col10a-1) has been isolated. The gene is composed of three exons and two introns spanning 7.0 kb of the DNA sequence. Exons 2 and 3 together encode 15-bp of 5' untranslated sequence, a 2040-bp open reading frame and an 895-nucleotide 3' non-coding region. In the 5' flanking region of the gene, two consensus TATA-box sequences were found. Identification of the first exon by ribonuclease-protection assays and the determination of the 5' end of Col10a-1 mRNA transcripts by primer-extension analyses show that the more 3' TATA box is probably predominantly used and that there are at least three transcription start sites in the exon 1 sequence 3' to this, resulting in 5' untranslated regions of 78, 77 and 55 nucleotides. By means of rapid amplification of cDNA ends by polymerase chain reaction, an additional mRNA species was detected which overlapped the other Col10a-1 transcripts, including the 3' TATA box sequence, giving a 5' untranslated sequence of approximately 235 bases. This latter transcript starts approximately 20 bp 3' to the more 5' TATA box. The data suggest alternative use of promoters and transcription starts for the Col10a-1 gene. Comparison of the combined nucleotide and deduced amino acid sequences of exons 2 and 3 with chicken, bovine and human collagen X genes, showed a high degree of similarity indicating conservation of this gene throughout evolution. Mouse Col10a-1 mRNA was shown to be approximately 3.0 kb and the pepsinized protein, as detected by SDS/PAGE, was approximately 45 kDa. The mRNA and protein sizes correlate with that predicted by the open reading frame. Reverse-transcription polymerase chain reaction assays indicate that the mouse collagen X gene is first expressed at 13.5 days post coitum, temporally preceding the onset of endochondral ossification. In agreement with the generally accepted association of type-X collagen with endochondral ossification, in situ hybridization analyses indicate that Col10a-1 mRNA are restricted to the hypertrophic regions of growth cartilage.
A sequence comparison of the C-termini of collagens X, VIII, the collagen-like complement factor C1q, and the fibrillar collagens showed a conserved cluster of aromatic residues. This conserved cluster was in a domain of approximately 130 amino acids that exhibited marked similarities in hydrophilicity profiles between the different collagens, despite a low level of sequence similarity. These data suggest that the 'collagen X-like family' and the fibrillar collagens contain a domain within their C-termini that adopts a common tertiary structure, and that a conserved cluster of aromatic residues in this domain may be involved in C-terminal trimerization.
Lack of information about health education from the perspective of immigrants was the basis of a descriptive survey of 30 Haitian mothers in southeast Florida. Subjects were interviewed regarding the value of health education received while seeking preventive health care for infants and preschool children in community health settings, their access to other sources of health education, and their perceptions of what community health care providers could do to assist them in improving child health. Ninety-seven percent took children for well-child care to medical facilities, and 66% received health education during the visits. Seventy percent had access to health-education programs through clinics or the media. Impediments to effective health education were lack of providers who speak Haitian Creole, need for more nurses, and long clinic waiting periods. Nurses were considered the best persons to do health teaching; radio and clinic lectures were the preferred media. Teaching was valuable if it was understandable and practical, reinforced parenting abilities, and allowed time for questions. Results are related to socioeconomic and political factors, traditional Haitian health culture, and cultural views of the cognitive development in children. Culture-specific strategies related to the modes and foci of health education are discussed.
Type X collagen is a homotrimeric, short chain, nonfibrillar collagen that is expressed exclusively by hypertrophic chondrocytes at the sites of endochondral ossification. The distribution and pattern of expression of the type X collagen gene (COL10A1) suggests that mutations altering the structure and synthesis of the protein may be responsible for causing heritable forms of chondrodysplasia. We investigated whether mutations within the human COL10A1 gene were responsible for causing the disorders achondroplasia, hypochondroplasia, pseudoachondroplasia, and thanatophoric dysplasia, by analyzing the coding regions of the gene by using PCR and the single-stranded conformational polymorphism technique. By this approach, seven sequence changes were identified within and flanking the coding regions of the gene of the affected persons. We demonstrated that six of these sequence changes were not responsible for causing these forms of chondrodysplasia but were polymorphic in nature. The sequence changes were used to demonstrate discordant segregation between the COL10A1 locus and achondroplasia and pseudoachondroplasia, in nuclear families. This lack of segregation suggests that mutations within or near the COL10A1 locus are not responsible for these disorders. The seventh sequence change resulted in a valine-to-methionine substitution in the carboxyl-terminal domain of the molecule and was identified in only two hypochondroplasic individuals from a single family. Segregation analysis in this family was inconclusive, and the significance of this substitution remains uncertain.
We report on the complete primary translated sequence of human alpha 1(X) collagen, deduced from a genomic clone, and the chromosomal localization of the human collagen X gene. The primary translated product of human collagen X is encoded by two exons of 169 bp and approx. 2940 bp. The 169 bp exon encodes 15 bp of 5'-end untranslated sequence, 18 amino acid residues (54 bp) of signal peptide and 33 1/3 amino acid residues (100 bp) of the N-terminal non-collagenous domain. The 2940 bp exon encodes 4 2/3 amino acid residues (14 bp) of the N-terminal non-collagenous domain, the complete triple-helical domain of 463 amino acid residues (1389 bp), the complete C-terminal non-collagenous domain of 161 amino acid residues (483 bp) and 1054 bp of 3'-end untranslated sequence up to and including a potential cleavage/polyadenylation signal. The size of the intron separating the two exons, as estimated by partial sequencing and Southern-blot analyses, is approx. 3200 bp. By a combination of somatic cell hybrid screening and hybridization in situ the human collagen X gene (COL10A1) has been assigned to the distal end of the long arm of chromosome 6 at the locus 6q21-6q22.3.
The complete primary structure of the bovine alpha 1(X) collagen chain was determined by nucleotide sequencing of cDNA clones. The overlapping cDNA clones encode 3144 bp with a 5'-terminal untranslated region of 148 bp, a 2025 bp reading frame and a 3'-terminal untranslated region of 971 bp. This represents the first complete sequence of a mammalian type X collagen cDNA and has allowed a number of informative comparisons to be made with the previously published chick alpha 1(X) sequence. The primary translation products of both bovine and chick type X collagen are 674 amino acid residues in length and there is a 73.3% identity at the amino acid level (67.8% at the base level). Sequence analyses reveal that the greatest degree of identity between the two species occurs within the triple-helical domain and the C-terminal non-collagenous domain, whereas the identity within the N-terminal non-collagenous domain is markedly lower. The interchain disulphide-bonding observed previously within the triple helix of bovine type X collagen is explained by the presence of two cysteine residues within an imperfection of the triple-helical domain encoded by -Gly-Xaa-Cys-Xaa-Yaa-Cys-Xaa-Yaa-Gly-. Southern blot analyses of bovine genomic DNA demonstrate that the bovine type X collagen gene is likely to have a condensed structure, similar to that of the chick, with at least 1.3 kb of the coding sequence being contained within one exon.
The function of collagen X, a unique homotrimer synthesised by hypertrophic chondrocytes, is not known but its localisation and transient expression at sites of calcification suggest that it is likely to be associated with events in the early stages of endochondral bone formation. Osteoarthritis (OA) is a disorder characterised by new bone formation but the role of type X collagen in its pathogenesis is unclear. A 700-bp restriction fragment encoding most of the C-terminal non-collagenous domain and part of the 3'-untranslated region of the human collagen X gene has been used for in situ hybridisation studies on human OA joints removed from hip and knee replacement operations and the results compared with immunohistochemical localisation of type X collagen gene product. Collagen X gene expression was detected in chrondrocytes present in OA tissue in areas where there appeared to be a re-initiation of the endochondral bone formation process including osteophytes and areas of subchondral bone sclerosis.
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Thirty immigrant Haitian mothers in Southeast Florida were interviewed regarding their beliefs and practices about preventive health care (illness prevention and health maintenance measures) for infants and preschool children (up to age 5). All mothers used preventive health care measures from both the Western biomedical and traditional Haitian ethnomedical (folk) systems. Ninety-seven percent used magico-religious measures; 47% administered home remedies; 47% gave children over-the-counter drugs; and 35% utilized a variety of measures to ensure cold air did not enter neonates and cause illness or pain. The Haitian mothers considered the preventive health care measures effective because the children remained healthy and will likely use them again. They sought consultation from a variety of individuals who formed their health management groups and child caretaker networks. Infants and toddlers were considered at higher risk than newborns for illness due to "evil harm" inflicted by other people and/or voodoo spirits. Implications for transcultural nursing practice include developing community outreach programs, implementing nursing interventions that combine biomedical and ethnomedical preventive health care measures, and functioning as part of the health management group. The authors wish to thank Maude Vincent, R.N., for her assistance in data gathering and analysis.
Chondrocytes from the cephalic region of 18-day chick embryo sterna were cultured within type I collagen gels in the presence of increasing concentrations of calcium beta-glycerophosphate (Ca beta GP) (2.5 mM, 5 mM and 10 mM) or 2 mM levamisole. Addition of Ca beta GP produced an increase in type X collagen synthesis and when 10 mM Ca beta GP was used, mineral deposits were observed in the matrix elaborated by the chondrocytes. Measurement of mRNA levels of type II and type X collagen microgram-1 total RNA revealed that the level of alpha 1(II) mRNA decreased whereas the level of alpha 1(X) mRNA remained relatively constant in the presence of Ca beta GP. Thus, Ca beta GP appears to increase type X collagen synthesis by enhancing the rate of collagen type X mRNA translation. In levamisole-treated cultures the synthesis of type X collagen and its deposition within the matrix were inhibited. Measurement of mRNA levels micrograms-1 total RNA revealed that the level of alpha 1(II) mRNA increased whereas the level of alpha 1(X) mRNA was markedly decreased in the presence of levamisole. Consequently, it must be concluded that levamisole inhibits type X collagen synthesis by inhibiting type X collagen gene transcription. These results add support for type X collagen having an important role in the mineralization process and have demonstrated that type X collagen synthesis is probably regulated at the mRNA translational stage during chondrocyte hypertrophy.
Chick embryo sternal chondrocytes from the caudal and cephalic regions were cultured within type I collagen gels and type I collagen/proteoglycan aggregate composite gels in normal serum. Caudal region chondrocytes were also cultured within type I collagen gels in the presence of fibronectin-depleted serum. There was a marked stimulation of type X collagen synthesis by the caudal region chondrocytes after 9 days in the presence of fibronectin-depleted serum and after 14 days in the presence of proteoglycan aggregate. These results provide evidence for the ability of chondrocytes from a zone of permanent cartilage to synthesise type X collagen and for the involvement of extracellular matrix components in the control of type X collagen gene expression.
The problem of teenage pregnancy continues to impact private and public resources, affecting all socioeconomic and cultural groups. A key factor for nurse practitioners to consider when planning sex education programs is the differing parental attitudes toward teenage sexuality. These attitudes are especially important to keep in mind when dealing with parents from minority cultural groups, as these groups are often highly influential in determining the nature of adolescent sexual behavior and attitudes toward reproduction. A study of Cuban and Haitian child-rearing practices clearly demonstrates two divergent parental views of adolescent sexuality. Nurse practitioners must recognize these differing views, and individualize their approach, in order to develop culturally sensitive sex education programs for adolescents and their parents. Suggestions are provided for development of such programs for Cuban and Haitian parents and children.
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