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Biomedical subjects

F Wright

Publications and source records attributed to F Wright.

At least 19 recordsLinked to original sources
PubMed2000

Genomic structure of the gene for the human P1 protein (MCM3) and its exclusion as a candidate for autosomal recessive polycystic kidney disease.

The locus PKHD1 (polycystic kidney and hepatic disease 1) has been linked to all typical forms of the autosomal recessive polycystic kidney disease (ARPKD) and maps to chromosome 6p21.1-p12. We previously defined its genetic interval by the flanking markers D6S1714 and D6S1024. In our current work, we have fine-mapped the gene for the human P1 protein (MCM3), thought to be involved in the DNA replication process, to this critical region. We have also established its genomic structure. Mutation analyses using SSCP were performed in ARPKD patients' cDNA samples, leading to the exclusion of this gene as a candidate for this disorder. We also identified two intragenic polymorphisms that allowed families with critical recombination events to be evaluated. Although neither marker was informative in these individuals, they are the closest yet described for PKHD1 and may help to refine the candidate region.

Cell Cycle Proteins↗
PubMed2000

The use of the self in group leadership: a relational perspective.

This article, written from a relational perspective, describes a shift that is taking place in the thinking of many psychodynamically oriented psychotherapists regarding the practice of therapy and the implications it has for group therapists. The shift, from one-person to two-person and multi-person theory, has particular importance for group leaders since it recommends making the subjective involvement of the therapist in the interactional field of the group much more a part of the treatment process. Theory and research on the use of countertransference, non-interpretive interventions, humor, and spontaneity by the leader are reviewed and vignettes are presented to illustrate the application of these ideas. Guidelines regarding the application of such ideas in group therapy are also discussed.

Countertransference↗
PubMed2000

Laparoscopic colon resections: a five-year retrospective review.

In recent years, laparoscopic surgery has become a matter of growing interest. It has been shown that laparoscopic colectomy is well tolerated and safe for benign disease. However, there is some uncertainty about using this method for malignant disease when curative resection is the aim. These uncertainties mainly consist of spread of cancer to port site, long-term survival, and adequacy of resection. The majority of laparoscopic colectomies are technically assisted procedures in which anastomosis is performed outside the abdomen. However, some surgeons are now performing this surgery totally laparoscopically with the anastomosis performed inside the abdomen. Laparoscopic colectomy is currently practiced with great frequency by general surgeons. Its performance requires a steep learning curve and a large number of cases to obtain proficiency. The indications for laparoscopic colectomy are different from one institution to another. In some institutions all patients with colorectal disease are candidates for laparoscopic colectomy and in others it may be limited to benign disease only. The purpose of this review is to analyze all laparoscopic colectomies performed at our medical center since 1992. We conducted a retrospective chart review of both hospital and clinic charts of patients who underwent colectomies at our hospital. A total of 338 patient charts were reviewed. In a comparison of both laparoscopic (n = 285) and converted (n = 53) methods, the age and operative time were about the same. Age average and operating room time average were similar for both groups. With laparoscopy, there was a 3-day drop in length of hospital stay as well as a 1-day-earlier regaining of bowel function. Hospital cost dropped 5000 dollars average for the laparoscopic colectomy. The conversion rate at our center was 15 per cent. Complication rates were lower in the laparoscopic group. Recurrence of cancer at the port site (0.7%) was no higher than in the converted group (incisional recurrence, 1.8%). We conclude that laparoscopic colectomy does show an improvement in return of bowel function, hospital cost, and shorter hospital stay. Long-term follow-up will be necessary to determine the effectiveness of laparoscopic colon resection for colorectal cancer.

Age Factors↗
PubMed1999

Effect of Medrogestone on 17beta-hydroxysteroid dehydrogenase activity in the hormone-dependent MCF-7 and T-47D human breast cancer cell lines.

Estradiol (E2) is one of the most important hormones supporting the growth and evolution of breast cancer. Consequently, to block this hormone before it enters the cancer cell, or in the cell itself, has been one of the main targets in recent years. In the present study we explored the effect of Medrogestone (Prothil) on 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activities of the hormone-dependent MCF-7 and T-47D human breast cancer cell lines. Using physiological doses of estrone ([3H]-E1: 5 x 10(-9) mol/l) this estrogen is converted in a great proportion to E2 in both cell lines. After 24 h of the cell culture, Medrogestone significantly inhibits this transformation in a dose-dependent manner by 39% and 80% at 5 x 10(-8) M and 5 x 10(-5) M, respectively in T-47D cells; the effect is less intense in MCF-7 cells: 25% and 55% respectively. The IC50 values are 0.45 micromol/l in T-47D and 17.36 micromol/l in MCF-7 cells. It is concluded that the inhibition provoked by Medrogestone on the reductive 17beta-HSD activity involved in the local biosynthesis of the biologically active estrogen estradiol, may constitute a new therapeutic approach for the treatment of breast cancer.

17-Hydroxysteroid Dehydrogenases↗
PubMed1999

Genes influencing resistance to Coccidioides immitis and the interleukin-10 response map to chromosomes 4 and 6 in mice.

Coccidioidomycosis is a fungal infection that is endemic in the southwestern United States. Infection is more severe in blacks and Filipinos, which suggests that there is a genetic basis for susceptibility to this infection in humans. We found that there is also a difference in resistance to Coccidioides immitis infection among inbred mouse strains: B6 mice are susceptible, while DBA/2 mice are resistant (T. N. Kirkland and J. Fierer, Infect. Immun. 40:912-916, 1983). In this paper we report the results of our efforts to map the genes responsible for resistance to this infection in mice. Mice were infected by intraperitoneal inoculation, and 15 days later the numbers of viable fungi in their lungs and spleens were enumerated. We also determined the amounts of interleukin-10 mRNA made in the infected lungs. These three phenotypes were mapped as quantitative traits by using the 26 available lines of recombinant inbred mice derived from a cross between B6 and DBA/2 mice. The best associations were those between the regions near the Lv locus on chromosome 4 and the Tnfr1 locus on chromosome 6. We then infected backcross mice [(B6 x DBA/2) x B6] and confirmed these associations; 14 of 16 (87%) mice that were heterozygous at both Lv and Tnfr1 were resistant to infection, whereas only 4 of 16 (25%) mice that were homozygous B6 at both loci were resistant. These are the first genetic loci to be associated with susceptibility to C. immitis, but there may be additional genes involved in murine resistance to this infection.

Animals↗
PubMed1998

A cysteine desulphurase gene from the cellulolytic rumen anaerobe Ruminococcus flavefaciens.

A gene whose predicted product shows 40-50% sequence identity with the products of nifS genes from nitrogen-fixing bacteria was found downstream from a cellulase gene in a DNA fragment from the cellulolytic rumen anaerobe, Ruminococcus flavefaciens 17. The R. flavefaciens gene product released sulphur from l-cysteine when expressed in Escherichia coli, indicating that the R. flavefaciens NifS enzyme may play a role in sulphuration, perhaps, as in nitrogen-fixing bacteria, supplying sulphur to FeS proteins. Sequences hybridising with the R. flavefaciens 17 nifS-like gene were also detected in R. flavefaciens 007 and in R. albus SY3.

Amino Acid Sequence↗
PubMed1998

Isolation of the 3-phosphoglycerate kinase gene of the arbuscular mycorrhizal fungus Glomus mosseae (Nicol. & Gerd.) Gerdemann & Trappe.

The 3-phosphoglycerate kinase (PGK) gene of the arbuscular mycorrhizal fungus Glomus mosseae has been isolated by differential RNA display (DD). Experimentally, the technique of DD was utilized to simultaneously compare the mRNA transcript populations from Lycopersicon esculentum root systems colonized by the arbuscular mycorrhizal fungus G. mosseae and non-mycorrhizal plants. A differentially expressed band was isolated and cloned from mycorrhizal tissue. The isolated DD fragment was screened and sequenced. A reverse transcription-PCR (RT-PCR) technique detected transcripts in germinated spores and G. mosseae-colonized root systems but not in uncolonised root systems. The full-length cDNA was isolated by RACE and corresponded to the 3-phosphoglycerate kinase gene of G. mosseae. The cDNA encodes a polypeptide of 416 amino acids, with a predicted molecular weight of 44 764 Da. The PGK proteins shows high homology to those PGKs of other fungi and the phylogenetic relationship among 14 isolated fungal PGK sequences is illustrated.

Amino Acid Sequence↗
PubMed1998

TOPAL: recombination detection in DNA and protein sequences.

UNLABELLED: TOPAL scans a multiple sequence alignment for evidence of recombinant sequences, prior to phylogenetic analysis. AVAILABILITY: The TOPAL package may be accessed at http://www.bioss.sari.ac.uk/grainne, and by anonymous ftp at ftp.bioss. sari.ac.uk in the directory pub/phylogeny/topal. CONTACT: grainne@bioss.sari.ac.uk

Computational Biology↗
PubMed1997

A graphical method for detecting recombination in phylogenetic data sets.

Current phylogenetic tree reconstruction methods assume that there is a single underlying tree topology for all sites along the sequence. The presence of mosaic sequences due to recombination violates this assumption and will cause phylogenetic methods to give misleading results due to the imposition of a single tree topology on all sites. The detection of mosaic sequences caused by recombination is therefore an important first step in phylogenetic analysis. A graphical method for the detection of recombination, based on the least squares method of phylogenetic estimation, is presented here. This method locates putative recombination breakpoints by moving a window along the sequence. The performance of the method is assessed by simulation and by its application to a real data set.

Computer Simulation↗
PubMed1997

Diverse decisions. How culture affects ethical decision making.

Even under optimal conditions, assisting patients and families in making ethical decisions is difficult at best. Often these decisions revolve around the end-of-life issues that require acknowledgement that the patient is unlikely to survive, which may be perceived as a failure to both the family and the staff. At the very least, it can be a sad time, fraught with uncertainty and indecision. When these difficulties are coupled with ineffective communication related to cultural insensitivity or unawareness, the effects can be devastating to the decision-making process. All CCNs are expected to master the skills necessary for assisting patients and families through the harrowing experience of life-threatening illness. Whereas much of critical care focuses on managing pathophysiologic disturbances, emotional needs are equally important. It follows then that the CCN must assume responsibility for assisting patients and families in coping with the crisis of critical illness and working through ethical issues, which often include end-of-life decisions and organ donation. Culturally competent care is required when addressing patient needs holistically, but it is so much more. It is an opportunity to enrich and deepen the CCN/patient/family relationship, advocate for the patient, and broaden the opportunities for communication among staff. This article has provided some beginning steps for increasing nursing cultural awareness and has offered some initial strategies to consider when designing a plan of care. Through continuing efforts, CCNs and organizations can do much to decrease the alienation that many patients and families have traditionally encountered in the CCU, an estrangement that is exacerbated when their culture is different from the predominant culture of the unit. The effort to become more culturally aware may appear to require extraordinary effort; however, the rewards of optimizing patient care are unsurpassed.

Attitude to Health↗
PubMed1996

Informed choice in fragile X syndrome and its effects on prevalence.

We present the effect of case finding, cascade testing, and counselling for fragile X syndrome in a population of 6.5 million over a decade. Carrier females made informed choices that resulted in a 10-fold decrease in the prevalence of affected males in their offspring.

Choice Behavior↗
PubMed1996

Predominant expression of 5 alpha-reductase type 1 in pubic skin from normal subjects and hirsute patients.

Dihydrotestosterone (DHT), the 5 alpha-reduced metabolite of testosterone, is the active molecule triggering androgen action, and 5 alpha-reductase (5 alpha-R), the enzyme converting testosterone to DHT, is a key step in this mechanism. Skin, like prostate, is a DHT- dependent tissue. Our laboratory demonstrated, many years ago, that 5 alpha-R in external genitalia was not regulated by androgens, whereas it was androgen dependent in public skin. As two genes, 5 alpha-R types 1 and 2, encoding for 5 alpha-R enzymes have been recently cloned, we undertook the present study to determine whether the two enzymes we had postulated on the basis of regulation studies were coincident with the cloned isoforms. The expression of the two isoforms was studied in genital and pubic skin fibroblasts from normal men, normal women, and hirsute patients. Messenger ribonucleic acid analysis, using Northern blot and RT-PCR techniques, indicated that both 5 alpha-R1 and -2 messenger ribonucleic acids are expressed in genital skin as well as in public skin fibroblasts. In contrast, studies using specific inhibitors of 5 alpha-R1 (LY306089) and 5 alpha-R2 (finasteride) showed that 5 alpha-R2 is predominant in pubic skin of normal men, normal women, and hirsute patients. These data raise the question of the possible use of specific 5 alpha-R1 inhibitors in the treatment of idiopathic hirsutism.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1995

A native plasmid of Pasteurella haemolytica serotype A1: DNA sequence analysis and investigation of its potential as a vector.

The complete nucleotide sequence of a 4.3 kilobase pair plasmid, pAB2, isolated from a bovine strain of Pasteurella haemolytica serotype A1, was determined. It encodes a Rob-1 type beta-lactamase and a region with homology to the mobilisation (mob) region of the Escherichia coli plasmid, ColE1. An insertion mutant of pAB2 (pTC2/81) carrying a copy of Tn5 was transferred to E coli K12 by conjugation. Subsequently pTC2/81 could be transferred by transformation to E coli HB101, but not to P haemolytica serotypes A1 or A2. However, a derivative of this construct containing only a fragment of the Tn5 insertion sequence was able to transform P haemolytica. A further construct containing a fragment of the P haemolytica A1 leucotoxin A gene, was similarly restricted to transforming E coli. These results demonstrate that the pAB2 plasmid is capable of acting as an E coli/P haemolytica shuttle vector. However, the nature of the cloned DNA sequences are important to transformation.

Base Sequence↗
PubMed1995

[5-alpha-reductases: physiology and pathology].

In most androgen target tissues, the first step of androgen action is the 5 alpha-reduction of testosterone to DHT which binds to the androgen receptor with an affinity 3 to 4 fold higher than testosterone. Two genes, encoding two isozymes of 5 alpha-reductase (5 alpha-R) have been cloned. The two isoforms, 5 alpha-R1 and 5 alpha-R 2 are located on chromosomes 5 and 2 respectively and differ in optimal pH, substrate and inhibitor affinities and tissue expression. 5 alpha-R 2 is responsible for sexual differentiation. It is the major form expressed in the prostate where it seems necessary for embryonic growth and development. 5 alpha-reductase deficiency results in androgen insensitivity due to abnormal 5 alpha-R 2. Affected patients are XY individuals with a very peculiar form of male pseudohermaphroditism: they have feminine genitalia at birth and masculinize at puberty. 29 mutations, spanning the whole coding portion of the gene, have been described; correlation between mutations and enzyme activity have led to the suggestion that both the N- and the C-terminal end of the gene are involved in substrate binding, whereas the cofactor binding-site is located in the C-terminus. In contrast to androgen insensitivity due to 5 alpha-reductase deficiency, increased 5 alpha-reductase activity can result in androgen hypersensitivity as described in idiopathic hirsutism or benign prostatic hyperplasia. In these case 5 alpha-R 1 could possibly be involved.

Cholestenone 5 alpha-Reductase↗
PubMed1994

Asymptotic theory for gene mapping.

In genetic linkage mapping, the precision of the location estimate depends on both the number of individuals and the number of markers. Convergence rates and limit laws are established for several situations in which the number of markers depends on the sample size. Practical implications of the results are discussed.

Chromosome Mapping↗
PubMed1994

Cloning of a cDNA encoding ovine interleukin-3.

A cDNA encoding the ovine hematopoietic growth factor interleukin-3 (IL-3), has been cloned. A 560-bp cDNA, containing the entire protein coding region, was amplified from activated mesenteric lymph node cells. The cDNA was found to share 58% nucleotide identity with hIL-3 and 48% identity with mIL-3. The predicted ovine amino-acid sequence shares 36 and 30% identity, respectively, with the corresponding human and murine proteins.

Amino Acid Sequence↗