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Biomedical subjects

S Best

Publications and source records attributed to S Best.

At least 19 recordsLinked to original sources
PubMed2000

An integrated map of human 6q22.3-q24 including a 3-Mb high-resolution BAC/PAC contig encompassing a QTL for fetal hemoglobin.

Genetic studies have previously assigned a quantitative trait locus (QTL) for hemoglobin F and F cells to a region of approximately 4 Mb between the markers D6S408 and D6S292 on chromosome 6q23. An initial yeast artificial chromosome contig of 13 clones spanning this region was generated. Further linkage analysis of an extended kindred refined the candidate interval to 1-2 cM, and key recombination events now place the QTL within a region of <800 kb. We describe a high-resolution bacterial clone contig spanning 3 Mb covering this critical region. The map consists of 223 bacterial artificial chromosome (BAC) and 100 P1 artificial chromosome (PAC) clones ordered by sequence-tagged site (STS) content and restriction fragment fingerprinting with a minimum tiling path of 22 BACs and 1 PAC. A total of 194 STSs map to this interval of 3 Mb, giving an average marker resolution of approximately one per 15 kb. About half of the markers were novel and were isolated in the present study, including three CA repeats and 13 single nucleotide polymorphisms. Altogether 24 expressed sequence tags, 6 of which are unique genes, have been mapped to the contig.

Base Sequence↗
PubMed1999

Contrasting effects of ENU induced embryonic lethal mutations of the quaking gene.

Multiple alleles of the quaking (qk) gene have a variety of phenotypes ranging in severity from early embryonic death to viable dysmyelination. A previous study identified a candidate gene, QKI, that contains an RNA-binding domain and encodes at least three protein isoforms (QKI-5, -6 and -7). We have determined the genomic structure of QKI, identifying an additional alternative end in cDNAs. Further we have examined the exons and splice sites for mutations in the lethal alleles qkl-1, qkkt1, qkk2, and qkkt3. The mutation in qkl-1 creates a splice site in the terminal exon of the QKI-6 isoform. Missense mutations in the KH domain and the QUA1 domains in qkk2 and qkkt3, respectively, indicate that these domains are of critical functional importance. Although homozygotes for each ENU induced allele die as embryos, their phenotypes as viable compound heterozygotes with qkv differ. Compound heterozygous qkv animals carrying qkkt1, qkk2, and qkkt3 all exhibit a permanent quaking phenotype similar to that of qkv/qkv animals, whereas qkv/qkl-1 animals exhibit only a transient quaking phenotype. The qkl-1 mutation eliminates the QKI-5 isoform, showing that this isoform plays a crucial role in embryonic survival. The transient quaking phenotype observed in qkv/qkl-1 mice indicates that the QKI-6 and QKI-7 isoforms function primarily during myelination, but that QKI-5 may have a concentration-dependent role in early myelination. This mutational analysis demonstrates the power of series of alleles to examine the function of complex loci and suggests that additional mutant alleles of quaking could reveal additional functions of this complex gene.

Animals↗
PubMed1999

Finasteride in the treatment of men with frontal male pattern hair loss.

BACKGROUND: Finasteride, a specific inhibitor of type II 5alpha-reductase, decreases serum and scalp dihydrotestosterone and has been shown to be effective in men with vertex male pattern hair loss. OBJECTIVE: This study evaluated the efficacy of finasteride 1 mg/day in men with frontal (anterior/mid) scalp hair thinning. METHODS: This was a 1-year, double-blind, placebo-controlled study followed by a 1-year open extension. Efficacy was assessed by hair counts (1 cm2 circular area), patient and investigator assessments, and global photographic review. RESULTS: There was a significant increase in hair count in the frontal scalp of finasteride-treated patients (P < .001), as well as significant improvements in patient, investigator, and global photographic assessments. Efficacy was maintained or improved throughout the second year of the study. Finasteride was generally well tolerated. CONCLUSION: In men with hair loss in the anterior/mid area of the scalp, finasteride 1 mg/day slowed hair loss and increased hair growth.

5-alpha Reductase Inhibitors↗
PubMed1998

The cement setting reaction in the CaHPO4-alpha-Ca3(PO4)2 system: an X-ray diffraction study.

The setting reactions of calcium phosphate cements in the CaHPO4-alpha-Ca3(PO4)2 (DCP-alpha-TCP) system have been investigated. X-ray diffraction (XRD) analyses were performed on DCP-alpha-TCP cement samples of varying calcium to phosphorus (Ca/P) ratios after setting for 24 h in Ringer's solution at 37 degrees C. XRD measurements showed that the intensity of the DCP peaks decreased linearly as the Ca/P ratio of the mixture increased. However, the intensity of the peaks of a new calcium-deficient hydroxyapatite [CDHA; Ca9(HPO4)(PO4)5OH] precipitating phase increased linearly as the Ca/P ratio increased. Alpha-TCP was not detected after 24 h of setting in any sample. A two-phase mixture XRD model was applied to explain the results, and suitable fits were obtained between observed and expected values of the relevant peak heights. The method used for this study also can be applied to studies of the kinetic behavior of other cement systems.

Bone Cements↗
PubMed1998

Carbonate substitution in precipitated hydroxyapatite: an investigation into the effects of reaction temperature and bicarbonate ion concentration.

Carbonate substitution in the apatite crystal lattice can occur in either the hydroxyl or the phosphate sites, designated as A or B type, respectively, and previous investigations generally have described precipitated carbonate hydroxyapatite as being B type on the basis of infra red and X-ray data. This paper documents the effects of two precipitation variables, namely temperature and bicarbonate ion concentration, on the morphology, phase composition, and calcium, phosphorus, and carbon contents of precipitated carbonate hydroxyapatite. Variations in both temperature and bicarbonate concentration could yield either acicular or spheroidal crystals. X-ray diffraction and infra red spectroscopy indicated the presence of carbonate in the A site for low carbonate contents (< 4 wt%), and at higher carbonate contents (> 4 wt%), the carbonate was located predominantly in the B site. On the basis of these observations and chemical analyses, a new AB carbonate substitution mechanism is proposed that better describes the experimental data than the B-type models used previously.

Bicarbonates↗
PubMed1998

Effect of heat treatment on pulsed laser deposited amorphous calcium phosphate coatings.

Amorphous calcium phosphate coatings were produced by pulsed laser deposition from targets of nonstoichiometric hydroxyapatite (Ca/P = 1.70) at a low substrate temperature of 300 degrees C. They were heated in air at different temperatures: 300, 450, 525 and 650 degrees C. Chemical and structural analyses of these coatings were performed using X-ray diffraction (XRD), FTIR, and SEM, XRD analysis of the as-deposited and heated coatings revealed that their crystallinity improved as heat treatment temperature increased. The main phase was apatitic, with some beta-tricalcium phosphate in the coatings heated at 525 and 600 degrees C. In the apatitic phase there was some carbonate substitution for phosphate and hydroxyl ions at 450 degrees C and almost solely for phosphate at 525 and 600 degrees C as identified by FTIR. This was accompanied by a higher hydroxyl content at 525 and 600 degrees C. At 450 degrees C a texture on the coating surface was observable by SEM that was attributable to a calcium hydroxide and calcite formation by XRD. These phases almost disappeared at 600 degrees C, probably due to a transformation into calcium oxide.

Calcium Phosphates↗
PubMed1997

Endogenous retroviruses and the evolution of resistance to retroviral infection.

The current AIDS epidemic has rekindled interest in the evolution of retroviruses and the development of resistance to infection. Retroviruses and their vertebrate hosts have coexisted for millions of years, during which time a variety of host defence mechanisms has evolved. One repeated strategy is to use endogenous retroviruses to combat infection by their exogenous relatives.

Animals↗
PubMed1996

Positional cloning of the mouse retrovirus restriction gene Fv1.

Vertebrate evolution has taken place against a background of constant retrovirus infection, and much of the mammalian genome consists of endogenous retrovirus-like elements. Several host genes have evolved to control retrovirus replication, including Friend-virus-susceptibility-1, Fv1, on mouse chromosome 4 (refs 3, 4). The Fv1 gene acts on murine leukaemia virus at a stage after entry into the target cell but before integration and formation of the provirus. Although restriction is not absolute, Fv1 prevents or delays spontaneous or experimentally induced viral tumours. In vitro, Fv1 restriction leads to an apparent 50-1,000 fold reduction in viral titre. Genetic evidence implicates a direct interaction between the Fv1 gene product and a component of the viral preintegration complex, the capsid protein CA (refs 7-9). We have now cloned Fv1: the gene appears to be derived from the gag region of an endogenous retrovirus unrelated to murine leukaemia virus, implying that the Fv1 protein and its target may share functional similarities despite the absence of nucleotide-sequence homology.

Amino Acid Sequence↗
PubMed1996

Mullerian inhibiting substance in humans: normal levels from infancy to adulthood.

Mullerian-inhibiting substance (MIS) is a gonadal hormone synthesized by Sertoli cells of the testis and granulosa cells of the ovary. To facilitate the use of MIS for the evaluation of intersex disorders and as a tumor marker in women with MIS-expressing ovarian tumors, we measured MIS in 600 serum samples from males and females. These data show that mean MIS values for males rise rapidly during the first year of life and are highest during late infancy, then gradually decline until puberty. In contrast, MIS values in females are lowest at birth and exhibit a minimal increase throughout the prepubertal years. Whereas MIS is uniformly measurable in all prepubertal boys studied, it is undetectable in most prepubertal female subjects. These data reveal an easily discernible sexually dimorphic pattern of expression and confirm that MIS can be used as a testis-specific marker during infancy and early childhood. MIS values that are above the upper limits for females are discriminatory for the presence of testicular tissue or ovarian tumor, and those below the lower limits for males are consistent with dysgenetic or absent testes or the presence of ovarian tissue. These data will enable normal and abnormal levels of MIS to be differentiated with higher precision and will facilitate the use of MIS in the management of gonadal disorders.

Adolescent↗
PubMed1995

Genetic map of the region surrounding the retrovirus restriction locus, Fv1, on mouse chromosome 4.

The Friend virus susceptibility-1 (Fv1) gene maps to mouse Chromosome (Chr) 4 close to a cluster of four endogenous murine leukemia viruses (MLVs). To investigate the feasibility of cloning Fv1 by a positional approach, we have performed an extensive genetic analysis of this region of Chr 4. We have typed 368 backcross mice for the four proviruses, Nppa, Lck, and D4Smh6b. Recombinant animals were screened in a hierarchical fashion with a variety of other markers, including Fv1 and the isozyme marker Gpd1. A detailed genetic map of the region surrounding Fv1 was derived. Three markers, Xmv9, Nppa, and Iap3rc11, were identified that showed no recombination with Fv1. By combining backcross and recombinant inbred strain data, we estimated that Xmv9 and Nppa must lie within 0.6 cM of one another and Fv1.

Animals↗
PubMed1994

Structure and expression of the hairless gene of mice.

The hairless mutation of mice was caused by insertion of a murine leukemia virus. Starting with sequences flanking the provirus, a series of overlapping clones surrounding the viral integration site were obtained. By using a combination of sequencing, PCR, and exon-trapping techniques, the hairless gene was identified. It encodes a predicted protein of 1182 amino acids, including a potential zinc-finger domain. The expression patterns of the gene closely reflect the phenotype of animals carrying the hairless mutation.

Amino Acid Sequence↗
PubMed1992

Mothers' and fathers' perceptions of stress and coping with children who have severe disabilities.

Stress in families with children who have special needs, which has been the focus of much research interest, is usually assessed solely from a maternal perspective. In this study, the short form of the Questionnaire on Resources and Stress (QRS-F, Friedrich, Greenberg, & Crnic, 1983) was completed separately by mothers and fathers of children with severe developmental disabilities. To compare responses of mothers and fathers, we employed factor analysis of parcels using the parallel analysis criterion rather than the more traditional item level analysis with minimum eigenvalue criterion. Results indicated that the QRS-F differed only slightly in both factor structure and correlates as a function of parental gender. Overall, validity of the QRS-F for use with both mothers and fathers of children with severe disabilities was supported.

Activities of Daily Living↗
PubMed1991

Characterization of the breakpoint of a 3.5-kb deletion of the beta-globin gene.

The precise extent and breakpoints of a deletion of the beta-globin gene in a Thai patient have been determined using direct sequencing of a PCR product. This lesion is not detectable by current screening methods using PCR to analyze the beta-globin genes and is, therefore, a potential source of error in the diagnosis and prenatal detection of beta-thalassemia.

Base Sequence↗
PubMed1991

Planning for community care. Long-stay populations of hospitals scheduled for rundown or closure.

Using the Community Placement Questionnaire, the long-stay populations of five hospitals were surveyed. The results suggest that there is little need for large hospitals if adequate community provision is made. However, a small number of patients continue to accumulate for whom community placement is hard to envisage. Investigating the characteristics of the 'new long-stay' patients suggests that the usual definition should be extended to include those over 65 years old with no diagnosis of dementia and those in hospital for 1-10 years. About 20% of 'new long-stay' patients have organic diagnoses and the needs of this group require assessment.

Adult↗