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S R Woodward

Publications and source records attributed to S R Woodward.

16 recordsLinked to original sources

Haplogroup-associated differences in neonatal death and incidence of low birth weight at elevation: a preliminary assessment.

OBJECTIVE: We sought to assess reproductive fitness differences between mitochondrial deoxyribonucleic acid haplogroups at high altitude. STUDY DESIGN: This study considers differences in outcomes of conception, birth weight, and neonatal mortality rates for 62 women classified according to haplogroups (B or non-B). RESULTS: The number of low-weight births (<2500 g) for the non-B group was significant (P =.019). Mothers in the non-B group reported more spontaneous abortions (P =.171) and stillbirths (P =.301). The difference in conceptions per woman between groups was significant (P =.036). However, no difference in infants alive at 1 month of age was evident. Neonatal death was significant (P =.017). The odds of an unsuccessful outcome among mothers in the B group was compared with mothers in the non-B group and was significant (P =.029). The chance of an adverse outcome, that is, fetal or infant death before 1 month, for mothers in the B group was between 11.1% and 88.7% lower than for mothers in the non-B group. CONCLUSIONS: The neonatal mortality rate for the non-B group was significantly elevated relative to the B group. The molecular basis for these observations is not clear.

Abortion, Habitual↗

DNA sequence polymorphisms in two strains of Fasciola hepatica from Egypt and Europe.

A new PCR based system was used that had broad detection capability among parasites based on a conserved region of the 18 S ribosomal DNA gene. Five samples each of European and Egyptian Fasciola hepatica of bovine origin were obtained and DNA was isolated. The target of the PCR primers was a fragment of approximately 600 nucleotides in length corresponding to a region of the 18 S rRNA gene. Sequences were compared over a 107 base pair region that identified polymorphism between the strains. All five Egyptian isolates were identical. Likewise all of the European isolates had identical sequence. There were polymorphisms between the two strains and also with F. hepatica isolates from North America. Both the European and Egyptian isolates have a single base addition in the polymorphic region. In addition there is a single base substitution in the Egyptian isolates when compared to the others. This region is a small target that can be used to identify the origins of different F. hepatica isolates.

Animals↗

Complete sequence of the gene encoding a chorionic gonadotropin-like protein from Xanthomonas maltophilia.

Our laboratory has previously reported that: (i) Xanthomonas maltophilia (Xm) produces a protein which has immunological resemblance to the beta-subunit of human chorionic gonadotropin (hCG) and (ii) possesses a high-affinity receptor which binds holo hCG, and the endogenous ligand, Xm chorionic gonadotropin (xCG), but does not bind human luteinizing hormone (hLH). We have also previously published a 492-bp partial nucleotide sequence of the gene (xcg) coding for xCG. We report herein the entire xcg sequence of 1362 bp, which codes for a 48-kDa protein. This sequence confirmed the 492-bp sequence, as well as two partial amino acid (aa) sequences which we have previously reported. The sequence has a region which is homologous to aa 56-139 of the beta-subunit of hCG, and a second region homologous to the C-terminal tail of hCG. This is the first report of a prokaryotic gene homologous to the hCG beta-subunit-encoding gene.

Amino Acid Sequence↗

DNA sequence from Cretaceous period bone fragments.

DNA was extracted from 80-million-year-old bone fragments found in strata of the Upper Cretaceous Blackhawk Formation in the roof of an underground coal mine in eastern Utah. This DNA was used as the template in a polymerase chain reaction that amplified and sequenced a portion of the gene encoding mitochondrial cytochrome b. These sequences differ from all other cytochrome b sequences investigated, including those in the GenBank and European Molecular Biology Laboratory databases. DNA isolated from these bone fragments and the resulting gene sequences demonstrate that small fragments of DNA may survive in bone for millions of years.

Animals↗

A bacterial protein has homology with human chorionic gonadotropin (hCG).

Studies from our laboratory have demonstrated the presence of a 48.5 kD cell wall protein in the bacterium, Xanthomonas maltophilia, which immunologically resembles the beta subunit of human chorionic gonadotropin. Primers were designed from the amino acid sequences of enzymatically cleaved peptide fragments of this protein. These primers were used to obtain PCR amplified products, which were subsequently cloned in a PCR11TA cloning vector, and a 492 base pair nucleotide sequence was obtained with a 164 amino acid open reading frame. When this nucleotide sequence was aligned with exon 2 of genes 5 and 6 of the beta hCG gene, a 53% homology was observed. The translated protein sequence had a 35% homology with hCG and a 25% homology with human luteinizing hormone.

Amino Acid Sequence↗

Locus controlling Bordetella pertussis-induced histamine sensitization (Bphs), an autoimmune disease-susceptibility gene, maps distal to T-cell receptor beta-chain gene on mouse chromosome 6.

Pertussis toxin (PTX) is the primary component responsible for eliciting the majority of biological activities associated with Bordetella pertussis, including the induction of several tissue-adjuvant models of organ-specific autoimmune disease. PTX, when administered in vivo, enhances vascular permeability, which is made manifest by a concomitant increase in sensitivity to a variety of agents and treatments affecting the vascular bed. One such agent is histamine, and the response to PTX, as measured by hypersensitivity following vasoactive amine challenge, is genetically controlled by the Bphs locus. Susceptibility to the induction of both experimental allergic encephalomyelitis (EAE) and experimental allergic orchitis (EAO) in mice is associated with, and in the latter case linked to, a susceptible allele at this locus. We report here the mapping of the Bphs locus to mouse chromosome 6, telomeric of Tcrb and centromeric of Prp (D6Nds8). This region also contains a number of loci of immunologic relevance including Igk, Ly-2, Ly-3, Il-5r, Ly-35, Ly-4, and Tnfr-2.

Animals↗

Partial nucleotide sequence of the Xanthomonas maltophilia chorionic gonadotropin-like receptor.

Xanthomonas maltophilia possesses a unique high-affinity binding site which binds human chorionic gonadotropin (hCG), but not human luteinizing hormone (hLH) or other glycoprotein hormones. We designed primers from the known nucleotide sequence of the human LH/CG receptor, spanning an area extending from transmembrane region 2 to transmembrane region 6. Genomic DNA extracted from Xanthomonas maltophilia was used to obtain a PCR amplified product using the above primers. The primary amplification product was cloned in a pCR11 TA cloning vector, and the partial nucleotide sequence of the gene determined. This determined sequence showed 73% identity with the human, as well as the rat LH/CG receptor. Comparison of the translated protein sequence with the human, rat and porcine receptor protein sequences showed a 52% similarity.

Amino Acid Sequence↗

The identification of Y chromosome-linked markers with random sequence oligonucleotide primers.

The polymerase chain reaction (PCR)-based technique of random amplification of polymorphic DNA (RAPD) is extremely useful for developing DNA-based markers. We previously identified a linkage group of eight unmapped RAPD markers that distinguish C57BL/6J and DBA/2J mice (Mammalian Genome 3: Woodward et al., 73-78, 1992). In this study, we report that all eight markers are Y Chromosome (Chr)-linked. One additional Y-linked RAPD was discovered serendipitously during the screening of a C3H/HeJ x (C3H/HeJ x SJL/J)F1 BC1 population. The segregation of all nine markers was analyzed with a panel of 14 independent inbred strains of male mice. The nine markers could be divided into three distinct groups: (1) DYByu2, DYByu5, DYByu6, and DYByu8 identify both the M.m. musculus and M.m. domesticus type Y Chr; (2) DYByu1, DYByu3, DYByu4, and DYByu7 are specific for the M.m. musculus type; and (3) DYByu9 is specific for the M.m. domesticus type. The results clearly indicate that the RAPD technique can be used to identify Y Chr-linked, DNA-based markers in mammalian species.

Animals↗

Random sequence oligonucleotide primers detect polymorphic DNA products which segregate in inbred strains of mice.

The random amplification of polymorphic DNA (RAPD) using primers of arbitrary nucleotide sequence has been extremely valuable in identifying heritable markers in a variety of systems. The present studies examined whether the RAPD technique can identify large numbers of polymorphisms that can be used to construct genetic maps in inbred strains of mice. By screening the inbred mouse strains C57BL/6J and DBA/2J with 481 random 10-mer oligonucleotide primers, we identified 95 polymorphisms and mapped 76 of these by use of the BXD series of recombinant inbred (RI) strains. The results clearly demonstrate that the RAPD technique allows for the identification of large numbers of DNA-based polymorphisms that distinguish these two inbred strains of mice, and that such markers can readily be used to construct molecular genetic linkage maps.

Animals↗

Diversity of Conus neuropeptides.

Conus venoms contain a remarkable diversity of pharmacologically active small peptides. Their targets are ion channels and receptors in the neuromuscular system. The venom of Conus geographus contains high-affinity peptides that act on voltage-sensitive calcium channels, sodium channels, N-methyl-D-aspartate (NMDA) receptors, acetylcholine receptors, and vasopressin receptors; many more peptides with still uncharacterized receptor targets are present in this venom. It now seems that the Conus species (approximately 500 in number) will each use a distinctive assortment of peptides and that the pharmacological diversity in Conus venoms may be ultimately comparable to that of plant alkaloids or secondary metabolites of microorganisms. The cone snails may generate this diverse spectrum of venom peptides by a "fold-lock-cut" synthetic pathway. These peptides are specific enough to discriminate effectively between closely related receptor subtypes and can be used for structure-function correlations.

Amino Acid Sequence↗

Constant and hypervariable regions in conotoxin propeptides.

Conotoxins are small cysteine rich peptides found in the venom of the predatory cone snails (Conus) which have prove to be useful high affinity ligands for various receptors and ion channels. The first cloning data for conotoxins, reported here, were obtained for the King-Kong peptide, a 27 amino acid conotoxin found in the venom of the cloth-of-gold cone, Conus textile. Analysis of cDNA clones of the King-Kong peptide revealed a family of related toxin transcripts. Three different propeptide cDNA sequences were obtained; only one of these encoded sequence for the King-Kong peptide. The other cDNA sequences encoded two different peptides (KK-1 and KK-2). When the predicted propeptide sequences are compared, well defined conserved and hypervariable regions can be identified. The hypervariable regions comprise four regions between Cys residues in the final peptide toxins; the remainder of the propeptide sequences, i.e. the excised N-terminal regions and the disulfide bonded Cys residues, are highly conserved. We suggest that the conserved regions may direct the formation of a specific disulfide configuration in the King-Kong family of conotoxins.

Amino Acid Sequence↗

Experimental allergic orchitis in mice. VI. Recombinations within the H-2S/H-2D interval define the map position of the H-2-associated locus controlling disease susceptibility.

Susceptibility to autoimmune orchitis is associated with an immune response (Ir) gene (now designated Orch-1) which was preliminarily shown to reside at or near the H-2D subregion of the major histocompatibility complex in the mouse (H-2). In this study, the role of H-2 in controlling both disease susceptibility and the phenotypic expression of infertility associated with autoimmune orchitis has been significantly extended. Of nine C57BL/10SnJ and three BALB/cAnN H-2 congenic strains, only those mice possessing the H-2d, H-2p haplotypes exhibited autoimmune orchitis accompanied by infertility. All other congenic strains, including those expressing the H-2 haplotypes v, q, b, s, r, f, and k were of the low responder phenotype. In addition, disease susceptibility was found to be inherited as a dominant trait in H-2 congenic F1 hybrid mice. In order to map the precise location of the Orch-1 locus within H-2, 32 intra-H-2 recombinant congenic strains possessing defined crossovers in various locations throughout the H-2 region were studied. The results of the analysis indicate that Orch-1 maps within the interval between the H-2S and H-2D regions. Our results also indicate that class II genes, i.e., A and E region-encoded genes, have little discernable effect in controlling disease susceptibility and resistance despite the fact that testicular lesions can be adoptively transferred with Ia-restricted CD4+ effector T cells. A comparison of the Orch-1 alleles with the genotypes of two additional markers which map within the H-2S/H-2D interval suggests the following gene order: H-2S--TNP-Ficoll--Orch-1--Tnfa--H-2D.

Alleles↗

Evaluation of chromosomal diagnosis for hereditary adenomatosis of the colorectum.

Hereditary adenomatosis, particularly familial polyposis coli (FPC) and Gardner's syndrome (GS), has been investigated from family pedigrees and chromosomal markers for precancer and cancer. FPC and GS are much alike in phenotypes. Studies are in progress to determine if the two adenomatous diseases are controlled by the same DNA sequence. Chromosome numerical and structural instability is a good diagnostic criterion for hereditary adenomatous diseases where risk factors are already determined to the level of 0.5 probability from pedigree analysis. This has been applied successfully at the pediatric age level to identify family members who carry the gene but have no adenomas in the colorectum. Sister chromatid exchange (SCE) did not distinguish plasma samples from FPC, GS, or solitary adenoma patients form each other or from controls with no adenomas. SCE did distinguish invasive from recurrent and noninvasive cancer. The chromosome #2 polymorphism observed at 2q-21.3 has not been confirmed as a deletion, but is under investigation with more refined methods.

Adenoma↗

The immunogenetics of susceptibility and resistance to murine experimental allergic orchitis.

The results of both clinical and experimental studies suggest that immunologic mechanisms may be significant in the pathogenesis of idiopathic infertility. We have defined and preliminarily characterized a number of immunoregulatory genes which control the phenotypic expression of infertility associated with autoimmune disease of the testis. Our studies utilizing the murine model of experimental allergic orchitis have clearly demonstrated that both classical (class II antigens) and nonclassical major histocompatibility complex-linked immune response genes play a central role in controlling disease susceptibility. We have mapped one nonclassical immune response gene, orchitis susceptibility gene-1 (Orch-1), to an interval of ca. 100 kilobases within the H-2S-H-2D region. In addition, immunogenetic analyses have identified two immune suppression genes, Orch-2 and Orch-3, which control active immunoregulatory mechanisms governing the phenotypic expression of disease resistance. The genetic control of autoimmune infertility in this model therefore appears to be polygenic.

Animals↗