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Biomedical subjects

A Murray

Publications and source records attributed to A Murray.

At least 163 records · Page 9Linked to original sources

Superstimulation of ovarian follicular growth with FSH oocyte recovery, and embryo production from Zebu (Bos indicus) calves: effects of treatment with a GnRH agonist or antagonist.

The capacity of heifer calves of a late sexually maturing Zebu (Bos indicus) genotype to respond to superstimulation with FSH at a young age and in vitro oocyte development were examined. Some calves were treated with a GnRH agonist (deslorelin) or antagonist (cetrorelix) to determine whether altering plasma concentrations of LH would influence follicular responses to FSH and oocyte developmental competency. Brahman calves (3-mo-old; 140 +/- 3 kg) were randomly assigned to 3 groups: control (n = 10); deslorelin treatment from Day -8 to 3 (n = 10); and cetrorelix treatment from Day -3 to 2 (n = 10). All calves were stimulated with FSH from Day 0 to 2, and were ovariectomized on Day 3 to determine follicular responses to FSH and to recover oocytes for in vitro procedures. Before treatment with FSH, heifers receiving deslorelin had greater (P < 0.001) plasma LH (0.30 +/- 0.01 ng/ml) than control heifers (0.17 +/- 0.02 ng/ml), while plasma LH was reduced (P < 0.05) in heifers treated with cetrorelix (0.13 +/- 0.01 ng/ml). Control heifers had a surge release of LH during treatment with FSH, but this did not occur in heifers treated with deslorelin or cetrorelix. All heifers had large numbers of follicles > or = 2 mm (approximately 60 follicles) after superstimulation with FSH, and there were no differences (P > 0.10) between groups. Total numbers of oocytes recovered and cultured also did not differ (P > 0.05) for control heifers and heifers treated with deslorelin or cetrorelix. Fertilization and cleavage rates were similar for the 3 groups, and developmental rates to blastocysts were also similar. Zebu heifers respond well to superstimulation with FSH at a young age, and their oocytes are developmentally competent.

Animals↗

Primary mycobacterial infection of the uvula.

Tuberculosis, and non-tuberculous mycobacterial infections are becoming more common thus it is more likely that otolaryngologists will encounter these conditions. We describe an otherwise well patient, with symptoms and signs from chronic uvular inflammation, who proved to have a primary mycobacterial infection. This is an unique presentation in the literature and reminds clinicians of the need, where uncertainty exists in diagnosis, to consider mycobacterial infections.

Adult↗

Reproducibility of three different methods of measuring baroreflex sensitivity in normal subjects.

1. Baroreflex sensitivity is a useful tool for investigating cardiovascular reflexes in a number of clinical settings. Several different methods of measuring baroreflex sensitivity are available. In order to determine a clinically useful non-invasive method of measuring baroreflex sensitivity we compared two methods (spectral analysis and the Valsalva manoeuvre) with regard to reproducibility, agreement with a standard invasive method (phenylephrine infusion) and failure rate.2.Twenty-six healthy subjects aged 22 to 63 years attended on three separate occasions for measurement of baroreflex sensitivity using the different methods. The effect of a recent head-up tilt on baroreflex sensitivity was measured.3. Reproducibility was best for the low-frequency component of the spectral method [coefficient of variation 25.0% (range 3.5-42.4%)] and worst for the Valsalva method [coefficient of variation 29.3% (range 13.8-93.1%)]. Both non-invasive methods overestimated values compared with the phenylephrine method [bias of low-frequency component of the spectral method, 1.17 (0.38-3.6); bias of the Valsalva method, 1.13 (0.19-6.7)]. The high-frequency component of the spectral method did not agree with the phenylephrine method.4. The spectral analysis method had the fewest failures (seven subjects with a failure on at least one occasion), and the phenylephrine method the most (16 subjects with a failure on at least one occasion). A short head-up tilt did not affect the subsequent non-invasive measurement of baroreflex sensitivity.5. It was concluded that the low-frequency component of the spectral method was the most clinically useful non-invasive measurement of baroreflex sensitivity.

Adult↗

Postural stability of normal subjects measured by sway magnetometry: pathlength and area for the age range 15 to 64 years.

Fifty-eight subjects with no known vestibular pathology, postural problems or cerebrovascular disease were studied to determine the range of sway values in a normal working-age population. Sway was measured with a magnetometry system, previously shown to be highly successful in distinguishing sway with and without the eyes open in individual subjects. 30 subjects were aged 15-29 years and 28 aged 30-64 years. With the subject standing on a firm base the pathlength and area enclosed by movement of the hips in the horizontal plane were measured over 30 second periods with eyes open and eyes closed. There were no significant differences between the two age ranges. We obtained the following upper limits of normal values for the age range 15 to 64 years: pathlength with eyes open 140 mm, pathlength with eyes closed 200 mm, area with eyes open 150 mm2, and area with eyes closed 300 mm2. The mean and standard deviation of the Romberg coefficient (sway with eyes open/sway with eyes closed) was 0.73 +/- 0.09 for pathlength measurement and 0.70 +/- 0.26 for area measurement.

Adolescent↗

Repeatability of body sway measurements; day-to-day variation measured by sway magnetometry.

The postural stability of 30 normal subjects in the age range 15 to 64 years was measured on five separate occasions, using the sway magnetometry technique, to determine the day-to-day repeatability of this measurement technique. On each occasion the pathlength and area enclosed by movement of the hips in a horizontal plane were measured over two 30 s periods with eyes open and eyes closed, with subjects standing on a firm base. Day-to-day repeatability had a standard deviation of 14% for pathlength and 42% for area. Neither the age nor the sex of the subject had any demonstrable effect on the results.

Adolescent↗

Dynamics of centromeres during metaphase-anaphase transition in fission yeast: Dis1 is implicated in force balance in metaphase bipolar spindle.

In higher eukaryotic cells, the spindle forms along with chromosome condensation in mitotic prophase. In metaphase, chromosomes are aligned on the spindle with sister kinetochores facing toward the opposite poles. In anaphase A, sister chromatids separate from each other without spindle extension, whereas spindle elongation takes place during anaphase B. We have critically examined whether such mitotic stages also occur in a lower eukaryote, Schizosaccharomyces pombe. Using the green fluorescent protein tagging technique, early mitotic to late anaphase events were observed in living fission yeast cells. S. pombe has three phases in spindle dynamics, spindle formation (phase 1), constant spindle length (phase 2), and spindle extension (phase 3). Sister centromere separation (anaphase A) rapidly occurred at the end of phase 2. The centromere showed dynamic movements throughout phase 2 as it moved back and forth and was transiently split in two before its separation, suggesting that the centromere was positioned in a bioriented manner toward the poles at metaphase. Microtubule-associating Dis1 was required for the occurrence of constant spindle length and centromere movement in phase 2. Normal transition from phase 2 to 3 needed DNA topoisomerase II and Cut1 but not Cut14. The duration of each phase was highly dependent on temperature.

Anaphase↗

Re-examination of factors associated with expansion of CGG repeats using a single nucleotide polymorphism in FMR1.

In at least 98% of fragile X syndrome cases, the disease results from expansion of the CGG repeat in the 5' end of FMR1. The use of microsatellite markers in the FMR1 region has revealed a disparity of risk between haplotypes for CGG repeat expansion. Although instability appears to depend on both the haplotype and the AGG interspersion pattern of the repeat, these factors alone do not completely describe the molecular basis for the linkage disequilibrium between normal and fragile X chromosomes, in part due to instability of the marker loci themselves. In an effort to better understand the mechanism of dynamic mutagenesis, we have searched for and discovered a single nucleotide polymorphism in intron 1 of FMR1 and characterized this marker, called ATL1, in 564 normal and 152 fragile X chromosomes. The G allele of this marker is found in 40% of normal chromosomes, in contrast to 83% of fragile X chromosomes. Not only is the G allele exclusively linked to haplotypes over-represented in fragile X syndrome, but G allele chromosomes also appear to transition to instability at a higher rate on haplotypes negatively associated with risk of expansion. The two alleles of ATL1 also reveal a highly significant linkage disequilibrium between unstable chromosomes and the 5' end of the CGG repeat itself, specifically the position of the first AGG interruption. The data expand the number of haplotypes associated with FMR1 and specifically allow discrimination, by ATL1 alleles, of single haplotypes with differing predispositions to expansion. Such haplotypes should prove useful in further defining the mechanism of dynamic mutagenesis.

Adenine Nucleotides↗

A familial case of X chromosome deletion ascertained by cytogenetic screening of women with premature ovarian failure.

The association between X chromosome deletions and premature ovarian failure is well established. Previous anecdotal reports however, have not documented the prevalence of X deletions in women with premature ovarian failure. We therefore performed cytogenetic analyses on 79 women with primary or secondary amenorrhoea to assess the utility of screening for a genetic marker for familial premature ovarian failure. A normal karyotype was found in 77 women. One woman with primary amenorrhoea had an XY karyotype and a woman with secondary amenorrhoea had a deletion at Xq 26.1. This second case had a family history of premature ovarian failure, and her mother who underwent premature ovarian failure at 28 years shared this deletion. The early diagnosis of familial X deletions causing premature ovarian failure allowed for the prediction of impending menopause and the implementation of manoeuvres to advance conception. Although cytogenetic aberrations are rare in secondary amenorrhoea, the ability to predict premature ovarian failure can be vital.

Adult↗

Fragile X premutation screening in women with premature ovarian failure.

We have screened 132 women with premature ovarian failure for fragile X (FRAXA) premutations. Three out of 23 (13%) pedigrees with the familial premature ovarian failure and 3/106 (3%) of women with the sporadic form of premature ovarian failure have FRAXA premutations compared with an expected prevalence of 1:590 (P=0.02). The mechanism of the association between FRAXA premutations and premature ovarian failure is unknown but as a genetic marker, FRAXA screening will be particularly valuable in predicting premature ovarian failure in some pedigrees and in the identification of families at risk of transmitting fragile X syndrome.

Adult↗

Meiosis-activating sterol promotes resumption of meiosis in mouse oocytes cultured in vitro in contrast to related oxysterols.

The sterol 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol (FF-MAS [follicular-fluid meiosis-activating sterol]) from human follicular fluid has recently been identified as a compound that induces the resumption of meiosis. FF-MAS and various oxysterols have been reported to transactivate the orphan receptor LXRalpha. The objective was to determine the biological activity of synthetic FF-MAS on the resumption of meiosis and final maturation of mouse oocytes in vitro. In order to evaluate whether LXRalpha might mediate FF-MAS action on the oocyte, we compared the capability of various compounds to activate LXRalpha-dependent transcription and to induce resumption of meiosis in the oocyte assay. Ovaries were isolated from immature mice primed with FSH 48 h before collection. Naked oocytes (NkO) and cumulus enclosed oocytes (CEO) were isolated from follicles. The oocytes were cultured in two groups, NkO and CEO, respectively, in media containing either 3 mM hypoxanthine, 5 microM IBMX, or 0.100 mM dbcAMP to maintain the oocytes in the germinal vesicle stage. The resumption of meiosis was assessed by the frequency of germinal vesicle breakdown (GVBD) after 24 h of in vitro culture. FF-MAS overcame the meiotic inhibition by hypoxanthine in both the NkO group and CEO group in a dose-dependent manner within the concentration range 0.07-7 microM. FF-MAS displayed similar potency in all inhibitory agents used. Also, FF-MAS significantly increased the formation of polar bodies in both the CEO and NkO group. The oxysterols 22(R)-hydroxycholesterol (a potent ligand for the LXRalpha receptor), 16-hydroxycholesterol, 25-hydroxycholesterol, and 27-hydroxycholesterol, as well as cholesterol, were tested without any significant effect on maturation compared to that of controls. Oxysterols and FF-MAS were observed to activate LXRalpha. In conclusion, the results reported here clearly demonstrate that synthetic FF-MAS exclusively is capable of mediating resumption of meiosis in vitro in both NkO and CEO irrespective of the inhibitory substance used. In contrast, the oxysterols and cholesterol had no significant biological activity on this oocyte function, and consequently we found no correlation between LXRalpha activation and meiosis stimulation.

1-Methyl-3-isobutylxanthine↗

Microscopic image analysis for quantitative measurement and feature identification of normal and cancerous colonic mucosa.

The development of an automated algorithm for the categorization of normal and cancerous colon mucosa is reported. Six features based on texture analysis were studied. They were derived using the co-occurrence matrix and were angular second moment, entropy, contrast, inverse difference moment, dissimilarity, and correlation. Optical density was also studied. Forty-four normal images and 58 cancerous images from sections of the colon were analyzed. These two groups were split equally into two subgroups: one set was used for supervised training and the other to test the classification algorithm. A stepwise selection procedure showed that correlation and entropy were the features that discriminated most strongly between normal and cancerous tissue (P < 0.0001). A parametric linear-discriminate function was used to determine the classification rule. For the training set, a sensitivity and specificity of 93.1% and 81.8%, respectively, were achieved, with an overall accuracy of 88.2%. These results were confirmed with the test set, with a sensitivity and specificity of 93.1% and 86.4%, respectively, and an overall accuracy of 90.2%.

Colon↗

Design of ligands for the purification of anti-MUC1 antibodies by peptide epitope affinity chromatography.

The fine specificity of epitope recognition of the anti-MUC1 mucin monoclonal antibody, C595 has been studied using solid-phase replacement net (RNET) analysis. Two peptides (RAAP and RPPP) showed increased reactivity with C595 antibody compared with the native epitope (RPAP). These were synthesized as integral motifs within MUC1 immunodominant peptides and analyzed by fluorescence quenching (FQ) and circular dichroism (CD). They were also tested as ligands for the purification of C595 antibody using epitope affinity chromatography. Affinity matrices were compared with respect to capacity, affinity, and quality of the purified product. In FQ tests the native epitope peptide (APDTRPAPG) and the alanine substituted peptide had similar association constants when reacting with C595 antibody, whereas the proline substituted peptide (APDTRPPPG) had a higher association constant. This order of affinity for C595 was confirmed in chromatography experiments in which antibody was eluted from the former two peptide matrices at approximately the same point on the NaSCN elution gradient, whereas antibody was desorbed from APDTRPPPG at a higher NaSCN concentration. Circular dichroism analysis showed that the thermodynamically preferred conformation of these peptides in aqueous solution is the P-II extended helix, the conformation preferred for an extended bound form of the peptide held by interactions with the peptide amides. The stronger binding peptide (APDTRPPPG) has the higher population of the P-II helix in solution. In conclusion, RNET analysis is useful in the rational design of peptide ligands so that the performance of affinity matrices may be regulated.

Animals↗

Dibiphytanyl ether lipids in nonthermophilic crenarchaeotes.

The kingdom Crenarchaeota is now known to include archaea which inhabit a wide variety of low-temperature environments. We report here lipid analyses of nonthermophilic crenarchaeotes, which revealed the presence of cyclic and acyclic dibiphytanylglycerol tetraether lipids. Nonthermophilic crenarchaeotes appear to be a major biological source of tetraether lipids in marine planktonic environments.

Animals↗

Validation of an automated technique for determining the mechanical characteristics of coronary arteries during balloon angioplasty: laboratory assessment with necropsy segments.

OBJECTIVES: To develop a technique for automatic inflation of a percutaneous transluminal coronary angioplasty (PTCA) balloon, with continuous measurement of the balloon pressure and volume; to validate the technique for determining the mechanical characteristics of coronary arteries. METHODS: During necropsy examination of the hearts of nine patients, 17 coronary artery samples were obtained for histological examination. A PTCA balloon was inserted into each artery, and the balloon pressure and volume were measured continuously during four repeat automatic inflations of the balloon. RESULTS: Of the 17 arteries, eight showed elastic, six plastic, and three fracture pressure-volume deformation characteristics. For the plastic deformations, the first inflation required a higher pressure than subsequent repeat inflations of 82 (61) kPa (mean (SD), range 25 to 175 kPa). For the three in the fracture group, the pressure drop because of the fracture occurred between 210 and 540 kPa. Two of these three showed a tear on visual inspection, and the other showed disruption of the intimal plaque on blinded histological examination. Of the six with plastic deformation characteristics alone, one showed a tear, and on histological examination two others showed splitting of the internal and external elastic lamina and one showed separation of intima and media. None in the elastic group showed any of these characteristics. CONCLUSIONS: Plastic and fracture deformation characteristics could be differentiated from elastic characteristics. Visual or histological evidence of fracturing was present in all three arteries identified during angioplasty as having pressure-volume fracture characteristics.

Angioplasty, Balloon, Coronary↗

Studies of FRAXA and FRAXE in women with premature ovarian failure.

Recent reports suggest that women with FRAXA premutations have an increased likelihood of having premature ovarian failure (POF). We screened 147 women with idiopathic POF for the number of trinucleotide repeats at the FRAXA and FRAXE loci. We found six women with FRAXA premutations, including four familial and two sporadic cases, but no women with FRAXA full mutations. At the FRAXE locus there were no pre- or full mutations but there was an excess of small alleles with fewer than 11 repeats, including at least one small deletion at or near the triplet. The association of FRAXA premutations with POF confirms that premutation alleles can affect ovarian development or function or both.

Alleles↗