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Biomedical subjects

M Scott

Publications and source records attributed to M Scott.

At least 91 records · Page 5Linked to original sources

Prion protein of 106 residues creates an artifical transmission barrier for prion replication in transgenic mice.

A redacted prion protein (PrP) of 106 amino acids with two large deletions was expressed in transgenic (Tg) mice deficient for wild-type (wt) PrP (Prnp0/0) and supported prion propagation. RML prions containing full-length PrP(Sc)produced disease in Tg(PrP106)Prnp0/0 mice after approximately 300 days, while transmission of RML106 prions containing PrP(Sc)106 created disease in Tg(PrP106) Prnp0/0 mice after only approximately 66 days on repeated passage. This artificial transmission barrier for the passage of RML prions was diminished by the coexpression of wt MoPrPc in Tg(PrP106)Prnp+/0 mice that developed scrapie in approximately 165 days, suggesting that wt MoPrP acts in trans to accelerate replication of RML106 prions. Purified PrP(Sc)106 was protease resistant, formed filaments, and was insoluble in nondenaturing detergents. The unique features of RML106 prions offer insights into the mechanism of prion replication, and the small size of PrP(Sc)106 should facilitate structural analysis.

Amino Acid Sequence↗

Arthrospira ('Spirulina') strains from four continents are resolved into only two clusters, based on amplified ribosomal DNA restriction analysis of the internally transcribed spacer.

We present the results of a phylogenetic study, based on amplified ribosomal DNA restriction analysis of the rDNA operon, of 37 Arthrospira ('Spirulina') cultivated clonal strains from four continents. In addition, duplicates from different culture collections or markedly different morphotypes of particular strains established as clonal cultures were treated as separate entries, resulting in a total of 51 tested cultures. The strain Spirulina laxissima SAG 256.80 was included as outgroup. The 16S rRNA genes appeared too conserved for discrimination of the strains by amplified ribosomal DNA restriction analysis, and thus the internally transcribed spacer was selected as molecular taxonomic marker. The internally transcribed spacer sequences situated between the 16S and the 23S rRNA were amplified by polymerase chain reaction and yielded amplicons of about 540 bp. Direct use of cells for polymerase chain reaction seemed to inhibit the amplification reaction. This was overcome by the design of a crude lysis protocol and addition of bovine serum albumin in the polymerase chain reaction mix. The amplicons were digested with four restriction enzymes (EcoRV, Hhal, Hinfl, Msel) and the banding patterns obtained were analyzed. Cluster analysis showed the separation of all the strains into two main clusters. No clear relationships could be observed between this division into two clusters and the geographic origin of the strains, or their designation in the culture collections, or their morphology.

Cyanobacteria↗

Gastroesophageal reflux disease: diagnosis and management.

Gastroesophageal reflux disease (GERD) is a chronic, relapsing condition with associated morbidity and an adverse impact on quality of life. The disease is common, with an estimated lifetime prevalence of 25 to 35 percent in the U.S. population. GERD can usually be diagnosed based on the clinical presentation alone. In some patients, however, the diagnosis may require endoscopy and, rarely, ambulatory pH monitoring. Management includes lifestyle modifications and pharmacologic therapy; refractory disease requires surgery. The therapeutic goals are to control symptoms, heal esophagitis and maintain remission so that morbidity is decreased and quality of life is improved.

Chronic Disease↗

Symptomatic gastro-oesophageal reflux disease: double blind controlled study of intermittent treatment with omeprazole or ranitidine. The European Study Group.

OBJECTIVE: To assess intermittent treatment over 12 months in patients with symptomatic gastro-oesophageal reflux disease. DESIGN: Randomised, multicentre, double blind, controlled study. Patients with heartburn and normal endoscopy results or mild erosive changes received omeprazole 10 mg or 20 mg daily or ranitidine 150 mg twice daily for 2 weeks. Patients remaining symptomatic had omeprazole 10 mg or ranitidine dose doubled for another 2 weeks while omeprazole 20 mg was continued for 2 weeks. Patients who were symptomatic or mildly symptomatic were followed up for 12 months. Recurrences of moderate or severe heartburn during follow up were treated with the dose which was successful for initial symptom control. SETTING: Hospitals and primary care practices between 1994 and 1996. SUBJECTS: 677 patients with gastro-oesophageal reflux disease. MAIN OUTCOME MEASURES: Total time off active treatment, time to failure of intermittent treatment, and outcomes ranked from best to worst. RESULTS: 704 patients were randomised, 677 were eligible for analyses; 318 reached the end of the study with intermittent treatment without recourse to maintenance antisecretory drugs. The median number of days off active treatment during follow up was 142 for the entire study (281 for the 526 patients who reached a treatment related end point). Thus, about half the patients did not require treatment for at least 6 months, and this was similar in all three treatment groups. According to outcome, 378 (72%) patients were in the best outcome ranks (no relapse or one (or more) relapse but in remission until 12 months); 630 (93%) had three or fewer relapses in the intermittent treatment phase. Omeprazole 20 mg provided faster relief of heartburn. The results were similar in patients with erosive and non-erosive disease. CONCLUSIONS: Intermittent treatment is effective in managing symptoms of heartburn in half of patients with uncomplicated gastro-oesophageal reflux disease. It is simple and applicable in general practice, where most patients are seen.

Adult↗

Crystallization and preliminary crystallographic analysis of the endo-polygalacturonase from Erwinia carotovora ssp. carotovora.

Crystals of endo-polygalacturonase from Erwinia carotovora ssp. carotovora have been grown from polyethylene glycol 6000 by the hanging-drop method. Polygalacturonase is important in the virulence of this plant pathogen. The protein crystallizes in space group C2 with unit-cell parameters a = 81.3, b = 53.0, c = 103.1 A, beta = 112.6 degrees and with a single molecule in the asymmetric unit. The crystals diffract to 1.9 A.

Bacillus subtilis↗

A comparison of CD34+ cell selected and unselected autologous peripheral blood stem cell transplantation for multiple myeloma: a case controlled analysis.

Following ASCT for multiple myeloma, it is unclear whether relapse is due solely to the presence of residual myeloma cells after myeloablation, or whether it is in part attributable to contamination of the stem cell harvest with viable malignant cells. Positive selection of CD34+ cells markedly reduces plasma cell contamination. We performed a case controlled analysis in which 15 patients with myeloma who underwent autologous PBSCT with CD34+cell selection using the Ceprate System (index group), were compared with 15 matched controls. All subjects received an identical preparative regimen. The median times to neutrophils >/=0.5 x 10(9)/l and unsupported platelets >/=50 x 10(9)/l were 14 and 23 days for the CD34+cell selected group and 11 (P = 0.03) and 14 (P = 0.029) for the case controls. Median follow-up of purged patients from autologous PBSCT was 32 months (range 18-43). At 36 months, the probability of PFS was 47 +/- 14% and 46 +/- 14% in the index and control groups (P = 0.44). The 3 year probability of OS was 69 +/- 13% for the CD34+ cell selected arm and 66 +/- 12.4% in unpurged patients (P = 0.91). Median PFS for the cell selected group is 24 months (CI 19.1-36.0), and 29 months for controls (CI 7.1-50.9). Eleven patients undergoing cell selection remain alive, seven of whom are progression free. At the same time-point after unpurged autologous PBSCT, the corresponding figures are 12 patients alive, with seven remaining progression free. Autologous PBSCT with CD34+ cell selection is both feasible and safe, but results in delayed engraftment as compared to case controls. The 3 year probability of PFS and OS in the cell selected arm was similar to that of the unpurged controls. Our findings indicate that autologous PBSCT with CD34+ cell selection appears not to have any favourable effect on disease progression. However, the results of this case controlled analysis should be cautiously interpreted, and the role of CD34+ selection in autologous PBSCT should be further investigated by large randomised trials.

Adult↗

Outcome of colectomy for slow transit constipation.

OBJECTIVE: To review the outcome data for colectomy performed for patients with slow transit constipation (STC). BACKGROUND: The outcome of surgical intervention in patients with STC is unpredictable. This may be a consequence of the lack of effectiveness of such interventions or may reflect heterogeneity within this group of patients. METHODS: The authors reviewed the data of all series in the English language that document the outcome of colectomy in > or = 10 patients in the treatment of STC. RESULTS: Thirty-two series fulfilled the entry criteria. There was widespread variability in patient satisfaction rates after colectomy (39% to 100%), reflecting large differences in the incidence of postoperative complications and in long-term functional results. Outcome was dependent on several clinical and pathophysiologic findings and on the type of study, the population studied, and the surgical procedure used. CONCLUSIONS: It may be possible to predict outcome on the basis of preoperative clinical and pathophysiologic findings. This review suggests a rationale for the selection of patients for colectomy.

Colectomy↗

Crystallization and preliminary X-ray analysis of arabinanase A from Pseudomonas fluorescens subspecies cellulosa.

Crystals of 1,5-alpha-arabinanase A from Pseudomonas fluorescens subspecies cellulosa have been obtained by vapour diffusion. The crystals belong to the space group P6122 with unit-cell parameters a = b = 91.6, c = 179.4 A with one molecule in the asymmetric unit. The native crystals and, to a much greater extent, heavy-atom soaked crystals are sensitive to radiation which necessitates cryocooling. Suitable cryocooling conditions have been established, though a shrinkage of the unit cell is observed, with a = b = 88.8 and c = 176.9 A.

Cold Temperature↗

Th1 cytokine patterns in cervical human papillomavirus infection.

The host's immune response to cervical human papillomavirus (HPV) infection is poorly understood. In a longitudinal cohort of women with cervical HPV infections, defined by PCR-based HPV DNA testing, we used exfoliated cervical cells and reverse transcription-PCR to examine the cervical mucosal mRNA expression of cytokines involved in regulating cell-mediated immunity. We identified seven HPV-positive subjects who were found to have cleared their HPV infections 4 months later. In all seven, a T-helper type 1 (Th1) cytokine pattern (expression of gamma interferon and absence of interleukin-4) preceded clearance. The more variable cytokine patterns seen in HPV-negative subjects suggest that the Th1 pattern in the women with subsequent clearance was a response to the HPV infection. This contention is supported by additional cross-sectional data showing a Th1 pattern in a majority of HPV-positive women. This study establishes a feasible means for assessing local cytokine expression in the cervical milieu and demonstrates that a Th1 cytokine response is associated with subsequent clearance of cervical HPV infection.

Cervix Uteri↗

International reference reagents: antihuman globulin. An ISBT/ICSH joint working party report. International Society of Blood Transfusion. International Committee for Standardization in Haematology.

An international working party has conducted a study designed to select a suitable reference reagent for antihuman globulin, to replace those first made available in 1987. The chosen preparation contains levels of anti-IgG and anti-C3 (anti-C3c and anti-C3d) potency that are considered suitable to serve for reference when evaluating either polyspecific antihuman globulin reagents or those containing their separate monospecific components. The reference material is available in 2-ml freeze-dried aliquots from seven assigned distribution centres.

Coombs Test↗

Involving men in reproductive health: the Young Men's Clinic.

OBJECTIVES: This report describes the population of young men who use the Young Men's Clinic in New York City, presents a profile of their reproductive behaviors, and describes the clinic's model of service delivery. METHODS: Data were gathered through a routine clinic visit form administered by clinic staff. RESULTS: The clinic sees approximately 1200 predominately Dominican young men each year for a wide range of clinical and mental health services. Two thirds of clients had ever been sexually active, three quarters had ever used birth control, and 69% had used birth control at their last sexual encounter. CONCLUSIONS: The Young Men's Clinic may serve as a model for health care delivery to adolescent and young adult males.

Adolescent↗

Cost effectiveness of omeprazole and ranitidine in intermittent treatment of symptomatic gastro-oesophageal reflux disease.

OBJECTIVE: This 1-year study compared the cost effectiveness of omeprazole and ranitidine when used as initial therapy in an intermittent treatment strategy for the management of patients with symptomatic gastro-oesophageal reflux disease with or without erosive oesophagitis. DESIGN AND SETTING: A prospective health economic analysis was conducted alongside an international multicentre randomised, double-blind clinical study. The economic analysis was performed from a societal perspective. PATIENTS: A total of 704 patients in the UK, the Republic of Ireland, Germany, France, Italy and Spain were randomised to 1 of the 3 treatment groups. INTERVENTIONS: Patients were randomised to receive either omeprazole 20 mg once daily, omeprazole 10 mg once daily or ranitidine 150 mg twice daily. Initial treatment failure resulted in dose titration and drug switching from ranitidine to omeprazole, and subsequently open maintenance treatment. MAIN OUTCOME MEASURES AND RESULTS: The estimated mean direct medical costs (medication and number of visits and endoscopies) were found to be lower for both dosages of omeprazole than for ranitidine in all countries except Germany. However, none of the differences were statistically significant. The differences between omeprazole 10 mg and omeprazole 20 mg were small and nonsignificant. With regard to numbers of symptom-free days, both omeprazole 20 mg and omeprazole 10 mg were found to be more effective than ranitidine. However, none of the differences were statistically significant. CONCLUSIONS: Following a pragmatic interpretation, incorporating intermediate short term results, the results in this study give no support to the notion that a step-up approach, either as dose titration from omeprazole 10 mg to omeprazole 20 mg or as drug switching from ranitidine to omeprazole, will result in cost savings and thereby be cost effective.

Algorithms↗

Growth inhibition of Candida albicans by vaginal cells from naïve mice.

Recurrent vulvovaginal candidiasis (RVVC) is a common idiopathic mucosal infection caused by Candida albicans. Current data suggests that local immunity is more important than that in the peripheral circulation for protection against infection. In the present study, anti-Candida innate resistance at the vaginal mucosa was investigated using a murine model. For this, splenic and vaginal cells were assessed for in vitro growth inhibition (GI) of C. albicans and cytotoxicity of natural killer (NK) cell-sensitive tumour targets (YAC-1). As expected, significant GI of C. albicans by splenic cells was mediated predominantly by polymorphonuclear leucocytes (PMNL) at effector to target (E:T) ratios of 100 and 50:1. From the vaginal mucosa, naïve unfractionated, but not nylon wool non-adherent (NWN), cells extracted from whole vaginal tissue showed significant GI of C. albicans at E:T ratios as low as 1:1, but only modest killing of YAC-1 targets at all E:T ratios. Subsequent experiments showed significant GI of C. albicans by vaginal epithelioid-enriched cells and with several epithelial cell lines, but not in supernatants collected from the co-cultures. In contrast, lymphoid cell lines had no anti-Candida activity. These results suggest that anti-Candida activity is present at the vaginal mucosa, but unlike that from the spleen, the vaginal activity appears to be predominantly mediated by epithelial cells.

Animals↗