Signal sources in bold contrast fMRI.
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Animals↗
Biomedical subjects
R Turner
Publications and source records attributed to R Turner.
Deletion analysis of a translational enhancer upstream from the coat protein open reading frame of potato virus S.
We have previously demonstrated that the 101 nucleotides upstream from the ATG of the potato virus S (PVS) coat protein gene has the ability to act as a translational enhancer in vitro and in vivo when fused to a range of marker genes. These 101 nucleotides, which have been designated VTE (viral translational enhancer), contain a block of nucleotide homology that is conserved between members of the carlavirus group, centered around a core sequence of CCTTTAGGTT. When deletions were generated that lacked 47 of the 5' nucleotides, but still retained the conserved block, and analysed in vitro and in vivo, it was observed that these leaders had lost their ability to act as translational enhancers. These results suggest that the sequences 5' to the conserved block may be acting as a translational enhancer or may be important in placing the conserved block in optimal context. This is confirmed to some extent by hybrid arrest translation results in which the effects on translation of oligonucleotides, complementary to regions within the VTE leader, were investigated. It was observed that oligonucleotides complementary to the nucleotides 5' to the conserved block had a dramatic effect on the translational competence of transcripts derived from VTE-luciferase constructs, decreasing levels by 53%, whereas oligonucleotides complementary to sequences 3' to the conserved block reduced levels of translation by only 15.6%.
Base Sequence↗
A 30-year progress report on a VA satellite psychiatric clinic program.
This paper describes a program of rural satellite psychiatric clinics that has evolved within a Veterans Affairs medical center over the past three decades. The eight clinics are staffed by a single team that includes a psychiatrist, a psychiatric nurse, and two mental health technicians. The team travels to the eight sites at least once each month. The program has achieved its goal of providing outpatient screening, diagnosis, and treatment services to veterans who would otherwise have no access to specialty psychiatric care due to distance and transportation problems.
Adult↗
UKPDS 20: plasma leptin, obesity, and plasma insulin in type 2 diabetic subjects.
We measured plasma leptin and insulin concentrations across a spectrum of obesity in 829 white Caucasian, 154 Afro-Caribbean, and 204 Asian type 2 diabetic subjects. Although the leptin concentrations covered a large range, there were no subgroups of diabetic subjects with very high or low leptin levels that would suggest mutations in the leptin gene or leptin receptor gene comparable to the obese diabetic ob/ob and db/db mice models respectively. In all three ethnic groups, leptin concentrations correlated with body mass index (BMI) in a similar manner to nondiabetic patients and were higher in females than males after adjustment for BMI, with no difference between ethnic groups. In a multivariate regression analysis, plasma leptin was associated with gender and BMI, (both P < 1 x 10(-17)) and with fasting plasma insulin concentrations (P = 5 x 10(-9)). Subjects treated with insulin had both raised insulin and leptin concentrations. When matched for different therapies, gender, and BMI, diabetic subjects with high leptin levels also had high insulin levels (P < 0.0009). High leptin concentrations may in part be influenced by hyperinsulinemia or impaired insulin sensitivity.
Aged↗
A pragmatic approach to educating rural health services on quality management.
Despite the popularity of Total Quality Management (TQM) with its use of multidisciplinary process improvement teams, little appears to have been achieved in rural health services using this approach. Reviewing the literature suggests few publications. Even traditional Quality Assurance (QA) activities in many of the smaller rural health services are reasonably undeveloped. Against this backdrop, the Rural Health Education and Research Centre successfully marketed and ran several experiential TQM workshops for rural health workers across NSW, resulting in 60 TQM projects being successfully completed. The purpose of this paper is to present the model we use to enable more rural health workers to participate in and benefit from quality management.
Humans↗
Who's doing what with quality?
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Australia↗
Molecular detection of tumor-associated antigens shared by human cutaneous melanomas and gliomas.
Both melanocytes and glial cells are derived embryologically from the neural ectoderm. Their malignant transformed counterparts, melanoma and glioma cells, respectively, may share common antigens. Numerous tumor-associated antigens have been identified in melanomas but only a few a gliomas. Using an established reverse transcriptase polymerase chain reaction plus Southern blot assay, we compared the mRNA expression of melanoma-associated antigens (MAAs) of melanomas to brain tumors primarily derived from glial cells. The MAAs studied included tyrosinase (Tyr), tyrosinase-related protein-1 and -2 (TRP-1 and TRP-2), gp100, human melanoma antigen-encoding genes 1 and 3 (MAGE-1 and MAGE-3), and melanotransferrin (p97). Glioblastoma multiforme (n = 21), anaplastic astrocytoma (n = 3), ependymoma (n = 2), meningioma (n = 3), oligodendroglioma (n = 1), and melanoma (n = 12) tumor specimens were assayed for MAA mRNA expression. Glioblastoma multiforme, astrocytoma, and melanoma cell lines were also assayed. We observed that individual MAA mRNAs were expressed in these brain tumors and cell lines at varying frequencies. The melanogenesis-pathway-related MAAs Tyr, TRP-1, TRP-2, and gp100 mRNAs were also expressed at different levels in normal brain tissues but at a much lower frequency than in glioblastoma multiforme and melanoma. MAGE-1 and MAGE-3 mRNA were expressed in different types of tumor specimens and cell lines but never in normal brain tissue. Tumor antigen p97 was expressed in all types of tumors and also in normal brain tissues. These studies demonstrate that melanomas and primary brain tumors express common MAAs and could be exploited in patients with malignant glioma by active specific immunotherapy against these common MAAs.
Antigens, Neoplasm↗
Proliferative myositis: an unusual cause of multiple subcutaneous nodules.
Proliferative myositis is a rare inflammatory condition which clinically has an apparently aggressive growth pattern reminiscent of a sarcoma. Histopathological features are characteristic but not widely recognized, so misdiagnosis may occur. We describe a patient presenting to the Dermatology Department and review the literature and current diagnostic techniques.
Adult↗
Mapping of monilethrix to the type II keratin gene cluster at chromosome 12q13 in three new families, including one with variable expressivity.
Monilethrix is an autosomal dominant disorder chiefly affecting hair. The degree of hair dystrophy is highly variable, as is the presence of additional features, such as follicular keratoses. In three British families of monilethrix, linkage has recently been reported to the type II keratin gene cluster at chromosome 12q13, and it has been suggested that the disease is due to a defect in the hard keratins of hair and nail. If monilethrix is a keratin disorder, we would predict that some pedigrees might map to the type I keratin gene cluster on 17q where hard keratin genes are also found. We have now studied clinically and by linkage analysis three new and unrelated pedigrees from England, Scotland and Spain, the first of which showed a variant phenotype. In this family the disease was expressed in four of 12 cases only as a follicular-keratosis of the neck, elbows and knees, and without clinical or historical evidence of hair anomalies; non-penetrance in an obligate carrier was also observed. In all three families, we have established linkage to a series of microsatellite markers at the type II locus at 12q13 (Zmax = 6.34 at theta = 0.00 for D12S368) and have excluded linkage from the type I keratin gene cluster on 17q. It remains probable that monilethrix is a disorder of hard keratins, but at present there is no evidence that it is due to defects in type I keratins.
Alopecia↗
[Treatment of rectal stenosis by linear stapler following laparoscopic correction of rectal prolapse].
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Aged↗
Inguinal hernia repair: totally preperitoneal laparoscopic approach versus Stoppa operation: randomized trial of 100 cases.
In a prospective randomized trial comparing the totally preperitoneal (TPP) laparoscopic approach and the Stoppa procedure (open), 100 patients with inguinal hernias (Nyhus IIIA, IIIB, IV) were followed over a 3-year period. Both groups were epidemiologically comparable. In the laparoscopic group, operating time was significantly longer (p = 0.01), but hospital stay (3.2 vs. 7.3 days) and delay in return to work (17 vs. 35 days) were significantly reduced (p = 0.01). Postoperative comfort (less pain) was better (p = 0.001) after laparoscopy. In this group, morbidity was also reduced (4 vs. 20%; p = 0.02). The mean follow-up was 605 days, and 93% of the patients were reviewed at 3 years. There were three (6%) recurrences after TPP, especially at the beginning of the surgeon's learning curve, versus one for the Stoppa procedure (NS). For bilateral hernias, the authors suggest the use of a large prosthesis rather than two small ones to minimize the likelihood of recurrence. In the conditions described, the laparoscopic (TPP) approach to inguinal hernia treatment appears to have the same long-term recurrence rate as the open (Stoppa) procedure but a real advantage in the early postoperative period.
Adult↗
[Laparoscopic resection of gastric conjunctive tumor. Apropos of 2 cases].
We report two cases of benign gastric tumours which were resected laparoscopically. The lesions were diagnosed pre-operatively by upper endoscopy and endoscopic ultrasound. Excisions were complete with satisfactory resection margins. The post-operative courses were uncomplicated: the length of hospital stay for both patients was 6 days. This technique would appear to be a promising alternative to laparotomy for selected cases.
Endosonography↗
The c-Mos proto-oncogene product stimulates c-Jun transcriptional activity by a MAP kinase-dependent mechanism.
The AP-1 transcription factor family is subject to sophisticated regulation in response to cell growth and stress stimuli. We show here that the transcriptional activity of c-Jun, a key AP-1 component, is stimulated by overexpression of the c-Mos proto-oncogene product in mammalian cells. This stimulation requires serines 63 and 73 of c-Jun, indicating that it is likely to be mediated by proline-directed kinase(s). Co-transfection of MKP-1, a specific MAP kinase antagonist, blocks the stimulation of c-Jun by c-Mos, while co-transfection of a dominant negative form of c-Raf-1 does not. Conditioned medium from c-Mos transfected cells fails to activate c-Jun in recipient cells, arguing against the involvement of a diffusible mitogen. These data suggest that c-Mos exerts its effect on c-Jun directly through a MAP kinase, acting downstream of c-Raf-1.
3T3 Cells↗
Detection of metastatic breast cancer by beta-hCG polymerase chain reaction.
Reverse transcriptase-polymerase chain reaction (RT-PCR) for detection of occult malignancies in breast cancer patients is evolving as a useful diagnostic tool. However, no reliable molecular mRNA markers are available. We developed an RT-PCR plus Southern blot assay using beta-hCG (beta-subunit of human chorionic gonadotropin) gene expression as a tumor marker for detection of breast malignancies metastatic to tumor-draining lymph nodes and blood. Breast carcinoma cell lines, primary breast malignancies and human placenta were used as positive controls for establishing the beta-hCG RT-PCR assay. Peripheral blood leukocytes (PBL) from normal volunteer donors, normal breast tissue and lymph nodes from cancer-free patients were used as negative controls. beta-hCG RT-PCR was used to assess tumor cell presence in PBL and tumor-draining axillary nodes from patients with AJCC stage I-IV breast cancer. The assay sensitivity and specificity were enhanced by restriction endonuclease digestion of an Sty I site of the RT-PCR cDNA product followed by Southern blot analysis. beta-hCG mRNA was expressed in all breast cancer cell lines and 80% of primary breast cancers; it was not expressed in negative controls. The assay reliably detected one cancer cell in > 10(7) PBL, with a sensitivity of 10(-5) microgram RNA. Eighty percent of PBL and 61% of tumor-draining axillary nodes from breast cancer patients expressed beta-hCG mRNA. The assay is a sensitive and specific method of identifying breast cancer cells in breast tissues, lymph nodes and blood.
Biomarkers, Tumor↗
United Kingdom Prospective Diabetes Study 17: a 9-year update of a randomized, controlled trial on the effect of improved metabolic control on complications in non-insulin-dependent diabetes mellitus.
PURPOSE: To report the progress (after 9-year follow-up) of a study designed to determine whether improved glucose control in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) is effective in reducing the incidence of clinical complications. DATA SOURCE: A multicenter, randomized, controlled trial of different therapies for NIDDM. After initial diet therapy, 4209 asymptomatic patients who remained hyperglycemic (fasting plasma glucose levels, 6.0 to 15.0 mmol/L) were assigned to either a conventional therapy policy, primarily with diet alone, or to an intensive therapy policy, aiming for fasting plasma glucose levels of less than 6.0 mmol/L, with assignment to primary therapy with sulfonylurea or insulin (which increased insulin supply) or metformin (which enhanced insulin sensitivity). RESULTS: All three modes of pharmacologic therapy in the intensively treated group-sulfonylurea, insulin, and metformin-had similar efficacy in reducing the fasting plasma glucose and glycated hemoglobin levels. Over 9 years, patients assigned to intensive therapy with sulfonylurea or insulin had lower fasting plasma glucose levels (median, 7.3 and 9.0 mmol/L, respectively) than patients assigned to conventional therapy. Regardless of the assigned therapy, however, the fasting plasma glucose and hemoglobin A1c levels increased, and maintaining near-normal glycemia was, in general, not feasible. Even insulin therapy did not achieve the therapeutic goal of near-normal glycemia because of the difficulty in treating marked hyperglycemia and the risk for hypoglycemic episodes. Nine years after the diagnosis of diabetes, 29% of the patients had had a diabetes-related clinical end point, 20% had had a macrovascular complication, and 9% had had a microvascular complication. CONCLUSIONS: A report will be published in 1998 after a median duration from randomization of 11 years (range, 6 to 20 years) with an 81% power at a 1% level of significance of detecting whether the obtained improvement in glucose control causes a 15% decrease or increase in the incidence of major complications and whether any specific therapy is advantageous or disadvantageous.
Adult↗
A model for quantification of perfusion in pulsed labelling techniques.
A model for quantification of perfusion in pulsed labelling techniques is described, based on solving the modified Bloch equation including the effects of flow. The model is designed to fit experimental data acquired in two separate measurements (inversion and control, or selective and non-selective inversions) for different inversion times using a biexponential. Although the signal contrast is 50% less than the continuous labelling technique, it seems more appropriate for human studies because of its lower power deposition, shorter transit time and the use of an interleaved acquisition. The importance is shown of including in the model the difference in relaxation time between blood and tissue. Neglecting this difference can lead to an overestimation of flow, which can be as big as 100% in white matter and 20% in grey matter.
Cerebrovascular Circulation↗
Movement-related effects in fMRI time-series.
This paper concerns the spatial and intensity transformations that are required to adjust for the confounding effects of subject movement during functional MRI (fMRI) activation studies. An approach is presented that models, and removes, movement-related artifacts from fMRI time-series. This approach is predicated on the observation that movement-related effects are extant even after perfect realignment. Movement-related effects can be divided into those that are a function of position of the object in the frame of reference of the scanner and those that are due to movement in previous scans. This second component depends on the history of excitation experienced by spins in a small volume and consequent differences in local saturation. The spin excitation history thus will itself be a function of previous positions, suggesting an autoregression-moving average model for the effects of previous displacements on the current signal. A model is described as well as the adjustments for movement-related components that ensue. The empirical analyses suggest that (in extreme situations) over 90% of fMRI signal can be attributed to movement, and that this artifactual component can be successfully removed.
Artifacts↗
Apparent diffusion coefficients in benign and secondary progressive multiple sclerosis by nuclear magnetic resonance.
The diffusion characteristics of water in brain white matter were studied in patients with benign and secondary progressive multiple sclerosis (MS), and also in normal controls. In the MS patients, both lesions and normal-appearing white matter (NAWM) were examined to assess whether pathological differences might be evident from the diffusion behavior. A volume-selective technique was used to reduce data acquisition time and improve the reliability and precision of the measurements. This also allowed the time-dependence of apparent diffusion coefficients to be assessed. While lesions from both patient groups showed an elevated diffusion coefficient, no differences between the two groups were found. In addition, NAWM was elevated for both patient groups compared with the control group, although this was only statistically significant for patients with a benign disease course. The degree of elevation of the diffusion coefficient within the individual lesions measured was not related to the disability of the patient. Pathological differences between lesions in patients with different disease courses, if they exist, have not been detected in this study of brain water diffusion.
Brain↗