Biomedical subjects

R Turner

Publications and source records attributed to R Turner.

At least 91 records · Page 5Linked to original sources

PubMed1999

Discrimination, adjusted correlation, and equivalence of imprecise tests: application to glucose tolerance.

Comparison studies between physiological tests are often unsatisfactory for assessing their ability to distinguish between subjects. We recommend a simple but comprehensive protocol, using duplicate testing, that compares tests using 1) the discriminant ratio (DR) between the underlying between- and within-subject SDs, 2) correlation coefficients adjusted for attenuation due to test imprecision, and 3) unbiased estimation of the underlying linear relationship between test results. The following five alternative methods for assessing glucose tolerance were compared: fasting plasma glucose (FPG) as a single sample or as the mean of three 5-min samples (FPG3); the 1- and 2-h glucose during a low-dose intravenous glucose infusion (CIG); and the 2-h plasma glucose from a 75-g oral glucose tolerance test (OGTT). All tests had similar DRs ranging from 2.6 to 4.2. The adjusted correlation between FPG and CIG tests approached unity, and those between OGTT and other tests were approximately 0.9, showing that FPG3 provides similar information to the OGTT. FPG concentrations of 6.0 and 7.1 were found equivalent to the 1985 World Health Organization OGTT thresholds for impaired glucose tolerance and diabetes (7.8 and 11.1 mmol/l).

Administration, Oral↗

PubMed1999

Cyclooxygenase inhibitors increase Na-K-2Cl cotransporter abundance in thick ascending limb of Henle's loop.

Cyclooxygenase inhibitors, such as indomethacin and diclofenac, have well-described effects to enhance renal water reabsorption and urinary concentrating ability. Concentrating ability is regulated in part at the level of the thick ascending limb of Henle's loop, where active NaCl absorption drives the countercurrent multiplication mechanism. We used semiquantitative immunoblotting to test the effects of indomethacin and diclofenac, given over a 48-h period, on the expression levels of the ion transporters responsible for active NaCl transport in the thick ascending limb. Both agents strongly increased the expression level of the apical Na-K-2Cl cotransporter in both outer medulla and cortex. Neither agent significantly altered outer medullary expression levels of other thick ascending limb proteins, namely, the type 3 Na/H exchanger (NHE-3), Tamm-Horsfall protein, or alpha1- or beta1-subunits of the Na-K-ATPase. Administration of the EP3-selective PGE(2) analog, misoprostol, to indomethacin-treated rats reversed the stimulatory effect of indomethacin on Na-K-2Cl cotransporter expression. We conclude that cyclooxygenase inhibitors enhance urinary concentrating ability in part through effects to increase Na-K-2Cl cotransporter expression in the thick ascending limb of Henle's loop. This action is most likely due to elimination of an EP3-receptor-mediated tonic inhibitory effect of PGE(2) on cAMP production.

Animals↗

PubMed1999

Cortical and subcortical control of tongue movement in humans: a functional neuroimaging study using fMRI.

We have used voluntary tongue contraction to test whether we can image activation of the hypoglossal nuclei within the human brain stem by using functional magnetic resonance imaging (fMRI). Functional images of the whole brain were acquired in eight subjects by using T2-weighted echo planar imaging (blood oxygen level development) every 6.2 s. Sequences of images were acquired during 12 periods of 31-s "isometric" rhythmic tongue contraction alternated with 12 periods of 31-s tongue relaxation. Noise arising from cardiac- and respiratory-related movement was removed either by filtration (high pass; cutoff 120 s) or by inclusion in the statistical analysis as confounding effects of no interest. For the group, tongue contraction was associated with significant signal increases (P < 0.05 corrected for multiple comparisons) in the sensorimotor cortex, supplementary motor area, operculum, insula, thalamus, and cerebellum. For the group and for six of eight individuals, significant signal increases were also seen within the medulla (P < 0.001, predefined region of interest with no correction for multiple comparisons); this signal is most likely to reflect neuronal activation associated with the hypoglossal motor nuclei. The data demonstrate that fMRI can be used to detect, simultaneously, the cerebral and brain stem control of tongue movement.

Adult↗

PubMed1999

Decreased abundance of collecting duct aquaporins in post-ischemic renal failure in rats.

Increased urine flow is often a feature of mild to moderate acute renal failure. This study examines the possible role of dysregulation of collecting duct aquaporins as a factor in this increase. In rats, the left renal pedicle was clamped for 45 min followed by contralateral nephrectomy. Control rats were identical except that the renal pedicle was not clamped. Rats were sacrificed and the kidneys were homogenized at various time points after release of the clamp for semiquantitative immunoblotting of collecting duct aquaporins, as well as the thick ascending limb Na-K-2Cl cotransporter and the proximal tubule water channel, aquaporin-1. Urinary flow rate was significantly increased 18 h after the ischemic insult and remained increased through 72 h. Whole kidney aquaporin-2 protein abundance was 45% of controls at 18 h, 55% of controls at 36 h, and returned to normal 72 h after ischemia. Whole kidney aquaporin-3 protein abundance was 37% of controls at 18 h, 13% of controls at 36 h, and 45% of controls at 72 h. The decline in aquaporin-2 and -3 was confirmed by immunocytochemistry. Abundance of the thick ascending limb Na-K-2Cl cotransporter protein was not significantly decreased. Aquaporin-1 protein abundance was not significantly decreased at 18 h after the ischemic insult, but was significantly reduced after 36 h. Thus, the post-ischemic state is associated with decreased levels of the collecting duct aquaporins, coinciding with an increase in water excretion. It is concluded that decreased aquaporin protein abundance in collecting duct cells is a contributing factor in the increased urine flow seen in moderate post-ischernic acute renal failure.

Acute Kidney Injury↗

PubMed1999

Renal expression of aquaporins in liver cirrhosis induced by chronic common bile duct ligation in rats.

Semiquantitative immunoblotting was used to investigate the expression levels of the four major renal aquaporins, the Na-K-2Cl cotransporter of the thick ascending limb, the type 3 Na-H exchanger, and the Na-K-ATPase in kidneys from rats with cirrhosis secondary to common bile duct ligation (CBDL). These rats had significant water retention and hyponatremia. In contrast to models of cirrhosis induced by carbon tetrachloride, aquaporin-2 expression in CBDL-induced cirrhosis was decreased. Thus, these results show that in the setting of extracellular fluid volume expansion, excessive water retention with hyponatremia can occur in the absence of increases in aquaporin-2 abundance. In addition, the expression levels of the two basolateral collecting duct aquaporins (aquaporin-3 and -4) were decreased in CBDL rats relative to sham-operated control rats. Similarly, the Na-K-2Cl cotransporter of the thick ascending limb and the type 3 Na-H exchanger showed decreases in expression. In contrast, the expression levels of aquaporin-1 and the all subunit of the Na-K-ATPase were not decreased. Thus, dysregulation of multiple water channels and ion transporters may play a role in water balance abnormalities associated with CBDL-induced cirrhosis in rats.

Animals↗

PubMed1999

Crucial points at diagnosis. Type 2 diabetes or slow type 1 diabetes.

Two major types of diabetes have been recognized since the late 1930s. However, in recent times there have been major changes in classification and understanding of these types, including improved knowledge of maturity-onset diabetes in the young, with the identification of mutations relating to impaired insulin secretion and the recognition of slow-onset type 1 diabetes in adults now designated as latent autoimmune diabetes in adults (LADA). A major problem area in diabetes classification concerns cases of slowly progressive forms of type 1 and type 2 diabetes, particularly in adults aged 25-50 years. This is a more contemporary problem because cases of type 2 diabetes are presenting at an increasingly younger age. In the landmark U.K. Prospective Diabetes Study of type 2 diabetes, islet cell antibodies (ICAs) and antibodies to glutamic acid decarboxylase (anti-GAD) were measured at diagnosis in 3,672 patients. The overall proportion with ICAs was 6%, and anti-GADs was 10%. These subjects clearly had type 1 diabetes or LADA by both phenotypic and genotypic features. The presence of auto antibodies correlated particularly with a younger age and phenotypic features consistent with type 1 diabetes (e.g., early age at diagnosis, lower BMI, and reduced beta-cell function). Overall, of patients requiring insulin by 6 years, 38% were anti-GAD+ at baseline compared with 5.3% of those not on insulin at 6 years. Antibodies to GAD indicate an underlying autoimmune process and have a high positive predictive value for type 1 diabetes and future insulin dependency in adults.

Adult↗

PubMed1999

Thromboembolism in laparoscopic surgery: risk factors and preventive measures.

The aim of this study was to assess the risk of clinical thromboembolism in laparoscopic digestive surgery. From June 1992 to June 1997, 2,384 consecutive patients were studied. All received perioperative prophylaxis with low-molecular-weight heparin (LMWH), which was continued until full mobility was regained. Eight cases (0.33%) of deep venous thrombosis were noted, but there were no cases of pulmonary embolus. In six cases (five cholecystectomies with reverse Trendelenburg position and one inguinal hernia repair), release of the pneumoperitoneum took longer than 2 hours, and in two cases (one rectopexy and one sigmoid colectomy for diverticulitis), longer than 3 hours. In six of the eight cases, the diagnosis of DVT was made after LMWH had been ceased and the patient had been discharged. All cases were diagnosed before the 10th postoperative day. Pneumoperitoneum is felt to predispose to deep venous thrombosis. Long operations and reverse Trendelenburg position are further potentiating factors. Thromboprophylaxis for laparoscopy should be the same as for conventional surgery, i.e., tailored to individual risk and continued for a minimum of 7 to 10 days. We also recommend using graduated compression stockings, maintaining a relatively low insufflation pressure, keeping use of the reverse Trendelenberg position to a minimum, and intermittently releasing the pneumoperitoneum in longer procedures.

Adolescent↗

PubMed1999

Religious and spiritual case reports on MEDLINE: a systematic analysis of records from 1980 to 1996.

OBJECTIVE: To undertake a systematic analysis of case reports involving religious or spiritual issues published between 1980 and 1996. DATA SOURCES: MEDLINE, the National Library of Medicine's bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, and the preclinical sciences. STUDY SELECTION: A search of 4,306,906 records indexed on MEDLINE from 1980 to 1996. DATA EXTRACTION: A total of 364 abstracts were found, then subjected to coding analysis. DATA SYNTHESIS: Categories were developed for (1) types of healthcare situations involving religious/spiritual issues, (2) religious and spiritual interventions, (3) collaboration between healthcare and religious professionals, (4) psychopathology and sensitivity themes, and (5) religious faith/spiritual path. Although all of these case reports involved religious and spiritual issues, only 45 (12%) explicitly mentioned a religious professional. Of these, only 8 (2%) indicated any collaboration between healthcare and religious professionals. CONCLUSIONS: A paucity of published case report literature exists on religious and spiritual issues (.008% of the MEDLINE records), indicating that the increasing acceptance of these factors by patients and healthcare professionals is not yet reflected in scientific and clinical journals. A need exists for more documented examples of collaboration between healthcare and religious professionals.

Humans↗

PubMed1998

The thiazide-sensitive Na-Cl cotransporter is an aldosterone-induced protein.

Although the collecting duct is regarded as the primary site at which mineralocorticoids regulate renal sodium transport in the kidney, recent evidence points to the distal convoluted tubule as a possible site of mineralocorticoid action. To investigate whether mineralocorticoids regulate the expression of the thiazide-sensitive Na-Cl cotransporter (TSC), the chief apical sodium entry pathway of distal convoluted tubule cells, we prepared an affinity-purified, peptide-directed antibody to TSC. On immunoblots, the antibody recognized a prominent 165-kDa band in membrane fractions from the renal cortex but not from the renal medulla. Immunofluorescence immunocytochemistry showed TSC labeling only in distal convoluted tubule cells. Semiquantitative immunoblotting studies demonstrated a large increase in TSC expression in the renal cortex of rats on a low-NaCl diet (207 +/- 21% of control diet). Immunofluorescence localization in tissue sections confirmed the strong increase in TSC expression. Treatment of rats for 10 days with a continuous subcutaneous infusion of aldosterone also increased TSC expression (380 +/- 58% of controls). Furthermore, 7-day treatment of rats with an orally administered mineralocorticoid, fludrocortisone, increased TSC expression (656 +/- 114% of controls). We conclude that the distal convoluted tubule is an important site of action of the mineralocorticoid aldosterone, which strongly up-regulates the expression of TSC.

Aldosterone↗

PubMed1998

A specific role for the thalamus in mediating the interaction of attention and arousal in humans.

The physiological basis for the interaction of selective attention and arousal is not clearly understood. Here we present evidence in humans that specifically implicates the thalamus in this interaction. We used functional magnetic resonance imaging to measure brain activity during the performance of an attentional task under different levels of arousal. Activity evoked in the ventrolateral thalamus by the attentional task changed as a function of arousal. The highest level of attention-related thalamic activity is seen under conditions of low arousal (secondary to sleep deprivation) compared with high arousal (secondary to caffeine administration). Other brain regions were also active during the attentional task, but these areas did not change their activity as a function of arousal. Control experiments establish that this pattern of changes in thalamic activity cannot be accounted for by nonspecific effects of arousal on cerebral hemodynamics. We conclude that the thalamus is involved in mediating the interaction of attention and arousal in humans.

Adult↗

PubMed1998

Transmembrane protein insertion orientation in yeast depends on the charge difference across transmembrane segments, their total hydrophobicity, and its distribution.

The determinants of transmembrane protein insertion orientation at the endoplasmic reticulum have been investigated in Saccharomyces cerevisiae using variants of a Type III (naturally exofacial N terminus (Nexo)) transmembrane fusion protein derived from the N terminus of Ste2p, the alpha-factor receptor. Small positive and negative charges adjacent to the transmembrane segment had equal and opposite effects on orientation, and this effect was independent of N- or C-terminal location, consistent with a purely electrostatic interaction with response mechanisms. A 3:1 bias toward Nexo insertion, observed in the absence of a charge difference, was shown to reflect the Nexo bias conferred by longer transmembrane segments. Orientation correlated best with total hydrophobicity rather than length, but it was also strongly affected by the distribution of hydrophobicity within the transmembrane segment. The most hydrophobic terminus was preferentially translocated. Insertion orientation thus depends on integration of responses to at least three parameters: charge difference across a transmembrane segment, its total hydrophobicity, and its hydrophobicity gradient. Relative signal strengths were estimated, and consequences for topology prediction are discussed. Responses to transmembrane sequence may depend on protein-translocon interactions, but responses to charge difference may be mediated by the electrostatic field provided by anionic phospholipids.

Amino Acid Sequence↗

PubMed1998

Hemispheric specialization for English and ASL: left invariance-right variability.

Functional magnetic resonance imaging (fMRI) was used to compare the cerebral organization during sentence processing in English and in American sign language (ASL). Classical language areas within the left hemisphere were recruited by both English in native speakers and ASL in native signers. This suggests a bias of the left hemisphere to process natural languages independently of the modality through which language is perceived. Furthermore, in contrast to English, ASL strongly recruited right hemisphere structures. This was true irrespective of whether the native signers were deaf or hearing. Thus, the specific processing requirements of the language also in part determine the organization of the language systems of the brain.

Adult↗

PubMed1998

The acquisition of skilled motor performance: fast and slow experience-driven changes in primary motor cortex.

Behavioral and neurophysiological studies suggest that skill learning can be mediated by discrete, experience-driven changes within specific neural representations subserving the performance of the trained task. We have shown that a few minutes of daily practice on a sequential finger opposition task induced large, incremental performance gains over a few weeks of training. These gains did not generalize to the contralateral hand nor to a matched sequence of identical component movements, suggesting that a lateralized representation of the learned sequence of movements evolved through practice. This interpretation was supported by functional MRI data showing that a more extensive representation of the trained sequence emerged in primary motor cortex after 3 weeks of training. The imaging data, however, also indicated important changes occurring in primary motor cortex during the initial scanning sessions, which we proposed may reflect the setting up of a task-specific motor processing routine. Here we provide behavioral and functional MRI data on experience-dependent changes induced by a limited amount of repetitions within the first imaging session. We show that this limited training experience can be sufficient to trigger performance gains that require time to become evident. We propose that skilled motor performance is acquired in several stages: "fast" learning, an initial, within-session improvement phase, followed by a period of consolidation of several hours duration, and then "slow" learning, consisting of delayed, incremental gains in performance emerging after continued practice. This time course may reflect basic mechanisms of neuronal plasticity in the adult brain that subserve the acquisition and retention of many different skills.

Adult↗

PubMed1998

Cerebral organization for language in deaf and hearing subjects: biological constraints and effects of experience.

Cerebral organization during sentence processing in English and in American Sign Language (ASL) was characterized by employing functional magnetic resonance imaging (fMRI) at 4 T. Effects of deafness, age of language acquisition, and bilingualism were assessed by comparing results from (i) normally hearing, monolingual, native speakers of English, (ii) congenitally, genetically deaf, native signers of ASL who learned English late and through the visual modality, and (iii) normally hearing bilinguals who were native signers of ASL and speakers of English. All groups, hearing and deaf, processing their native language, English or ASL, displayed strong and repeated activation within classical language areas of the left hemisphere. Deaf subjects reading English did not display activation in these regions. These results suggest that the early acquisition of a natural language is important in the expression of the strong bias for these areas to mediate language, independently of the form of the language. In addition, native signers, hearing and deaf, displayed extensive activation of homologous areas within the right hemisphere, indicating that the specific processing requirements of the language also in part determine the organization of the language systems of the brain.

Adult↗

PubMed1998

Nonlinear event-related responses in fMRI.

This paper presents an approach to characterizing evoked hemodynamic responses in fMRI based on nonlinear system identification, in particular the use of Volterra series. The approach employed enables one to estimate Volterra kernels that describe the relationship between stimulus presentation and the hemodynamic responses that ensue. Volterra series are essentially high-order extensions of linear convolution or "smoothing." These kernels, therefore, represent a nonlinear characterization of the hemodynamic response function that can model the responses to stimuli in different contexts (in this work, different rates of word presentation) and interactions among stimuli. The nonlinear components of the responses were shown to be statistically significant, and the kernel estimates were validated using an independent event-related fMRI experiment. One important manifestation of these nonlinear effects is a modulation of stimulus-specific responses by preceding stimuli that are proximate in time. This means that responses at high-stimulus presentation rates saturate and, in some instances, show an inverted U behavior. This behavior appears to be specific to BOLD effects (as distinct from evoked changes in cerebral blood flow) and may represent a hemodynamic "refractoriness." The aim of this paper is to describe the theory and techniques upon which these conclusions were based and to discuss the implications for experimental design and analysis.

Brain↗

PubMed1998

Event-related fMRI: characterizing differential responses.

We present an approach to characterizing the differences among event-related hemodynamic responses in functional magnetic resonance imaging that are evoked by different sorts of stimuli. This approach is predicated on a linear convolution model and standard inferential statistics as employed by statistical parametric mapping. In particular we model evoked responses, and their differences, in terms of basis functions of the peri-stimulus time. This facilitates a characterization of the temporal response profiles that has a high effective temporal resolution relative to the repetition time. To demonstrate the technique we examined differential responses to visually presented words that had been seen prior to scanning or that were novel. The form of these differences involved both the magnitude and the latency of the response components. In this paper we focus on bilateral ventrolateral prefrontal responses that show deactivations for previously seen words and activations for novel words.

Evoked Potentials↗

PubMed1998

The time course of changes during motor sequence learning: a whole-brain fMRI study.

There is a discrepancy between the results of imaging studies in which subjects learn motor sequences. Some experiments have shown decreases in the activation of some areas as learning increased, whereas others have reported learning-related increases as learning progressed. We have exploited fMRI to measure changes in blood oxygen leve-dependent (BOLD) signal throughout the course of learning. T2*-weighted echo-planar images were acquired over the whole brain for 40 min while the subjects learned a sequence eight moves long by trial and error. The movements were visually paced every 3.2 s and visual feedback was provided to the subjects. A baseline period followed each activation period. The effect due to the experimental conditions was modeled using a square-wave function, time locked to their occurrence. Changes over time in the difference between activation and baseline signal were modeled using a set of polynomial basis functions. This allowed us to take into account linear as well as nonlinear changes over time. Low-frequency changes over time common to both activation and baseline conditions (and thus not learning related) were modeled and removed. Linear and nonlinear changes of BOLD signal over time were found in prefrontal, premotor, and parietal cortex and in neostriatal and cerebellar areas. Single-unit recordings in nonhuman primates during the learning of motor tasks have clearly shown increased activity early in learning, followed by a decrease as learning progressed. Both phenomena can be observed at the population level in the present study.

Adult↗

PubMed1998

Functional magnetic resonance imaging of the human brain: data acquisition and analysis.

It is now feasible to create spatial maps of activity in the human brain completely non-invasively using magnetic resonance imaging. Magnetic resonance imaging (MRI) images in which the spin magnetization is refocussed by gradient switching are sensitive to local changes in magnetic susceptibility, which can occur when the oxygenation state of blood changes. Cortical neural activity causes increases in blood flow, which usually result in changes in blood oxygenation. Hence changes of image intensity can be observed, given rise to the so-called Blood Oxygenation Level Dependent (BOLD) contrast technique. Use of echo-planar imaging methods (EPI) allows the monitoring over the entire brain of such changes in real time. A temporal resolution of 1-3 s, and a spatial resolution of 2 mm in-plane, can thus be obtained. Generally in a brain mapping experiment hundred of brain image volumes are acquired at repeat times of 1-6 s, while brain tasks are performed. The data are transformed into statistical maps of image difference, using the technique known as statistical parametric mapping (SPM). This method, based on robust multilinear regression techniques, has become the method of reference for analysis of positron emission tomography (PET) image data. The special characteristics of functional MRI data require some modification of SPM algorithms and strategies, and the MRI data must be gaussianized in time and space to conform to the assumptions of the statistics of Gaussian random fields. The steps of analysis comprise: removal of head movement effects, spatial smoothing, and statistical interference, which includes temporal smoothing and removal by fitting of temporal variations slower than the experimental paradigm. By these means, activation maps can be generated with great flexibility and statistical power, giving probability estimates for activated brain regions based on intensity or spatial extent, or both combined. Recent studies have shown that patterns of activation obtained in human brain for a given stimulus are independent of the order and spatial orientation with which MRI images are acquired, and hence that inflow effects are not important for EPI data with a TR much longer than T1.

Artifacts↗