Search PubMed⌕ Search

Biomedical subjects

A Rankin

Publications and source records attributed to A Rankin.

At least 19 recordsLinked to original sources
PubMed2006

Definition of novel GP6 polymorphisms and major difference in haplotype frequencies between populations by a combination of in-depth exon resequencing and genotyping with tag single nucleotide polymorphisms.

BACKGROUND: Common genetic variants of cell surface receptors contribute to differences in functional responses and disease susceptibility. We have previously shown that single nucleotide polymorphisms (SNPs) in platelet glycoprotein VI (GP6) determine the extent of response to agonist. In addition, SNPs in the GP6 gene have been proposed as risk factors for coronary artery disease. METHODS: To completely characterize genetic variation in the GP6 gene we generated a high-resolution SNP map by sequencing the promoter, exons and consensus splice sequences in 94 non-related Caucasoids. In addition, we sequenced DNA encoding the ligand-binding domains of GP6 from non-human primates to determine the level of evolutionary conservation. RESULTS: Eighteen SNPs were identified, six of which encoded amino acid substitutions in the mature form of the protein. The single non-synonymous SNP identified in the exons encoding the ligand-binding domains, encoding for a 103Leu > Val substitution, resulted in reduced ligand binding. Two common protein isoforms were confirmed in Caucasoid with frequencies of 0.82 and 0.15. Variation at the GP6 locus was characterized further by determining SNP frequency in over 2000 individuals from different ethnic backgrounds. CONCLUSIONS: The SNPs were polymorphic in all populations studied although significant differences in allele frequencies were observed. Twelve additional GP6 protein isoforms were identified from the genotyping results and, despite extensive variation in GP6, the sequence of the ligand-binding domains is conserved. Sequences from non-human primates confirmed this observation. These data provide valuable information for the optimal selection of genetic variants for use in future association studies.

Amino Acid Sequence↗
PubMed2004

Case report: sarcomatoid carcinoma arising from the ureter: a rare case and a treatment dilemma.

We report an interesting case of a patient with sarcomatoid carcinoma arising from the left ureter who presented with left iliac fossa pain. The diagnosis was based on CT and histological findings. To our knowledge, this is the first case of sarcomatoid carcinoma arising from the ureter reported. The literature review also highlights the rarity and the poor prognosis of the disease despite aggressive interventions.

Aged↗
PubMed2003

Dorsal spinocerebellar tract neurons respond to contralateral limb stepping.

Proprioceptive sensory information carried by spinocerebellar tracts provides a major input to the spinocerebellum, which has an important role in coordinating motor output for posture and locomotion. Until recently it was assumed that the information transmitted by the dorsal spinocerebellar tract (DSCT) was organized to represent single muscles or single joints in the ipsilateral hindlimb. Recent studies have shown, however, that DSCT activity represents global kinematic parameters of the hindlimb. We now present evidence that the DSCT neurons are also modulated by passive step-like movements of either hindlimb, implying they receive a bilateral sensory input. About two-thirds of 78 cells studied had significant responses to movements of the contralateral limb alone and about 70% responded differently to bipedal movements than to ipsilateral movement alone. The same basic behavior was observed in anesthetized, paralyzed cats and in unanesthetized, decerebrate cats, although decerebrate cats may have had larger responses on average. The results suggest that many DSCT cells may encode information about interlimb coordination.

Action Potentials↗
PubMed2003

Modulation of dorsal spinocerebellar responses to limb movement. I. Effect of serotonin.

Spinocerebellar neurons (DSCT) receive converging sensory information from various sensory receptors in the hindlimbs and lower trunk. Previous studies have shown that sensory processing by DSCT neurons results in a representation of global hindlimb kinematic parameters such as the length and the orientation of the limb axis. In addition to the sensory input, the DSCT circuitry also receives a descending input from the raphe nuclei in the brain stem. Recent studies have demonstrated that the raphe serotonergic terminals synapse directly on DSCT neurons and exert a differential modulatory influence on their sensory inputs. We examined the role of serotonergic modulation on the DSCT representation of hindlimb kinematic parameters by recording DSCT activity during passive hindlimb movements before and after perturbing serotonergic transmission. We used two types of perturbation: electrical stimulation of the raphe areas in the brain stem to release serotonin in the spinal cord (42 neurons) and intravenous administration of serotonergic agonists or antagonists, mostly the 5HTP2 antagonist ketanserin (30 neurons). We found that movement responses were altered in approximately 70% of the DSCT units studied with each protocol. Changes could include shifts in mean firing rate, increases or decreases in response amplitude, and changes in response waveform. We used a principal component analysis (PCA) to examine waveform components and to determine how they contributed to the response waveform changes caused by serotonin perturbation. Such changes could be explained by new or different response components that might indicate a modification in the data processing or by a different weighting of existing components that might indicate a modification of synaptic weighting. The results were consistent with the second alternative. We found that the same underlying response components could account for both control responses and those altered by serotonin perturbations. The observed changes in waveform could be entirely accounted for by a re-weighting of response components. In particular, the changes observed after raphe stimulation could be accounted for by selective changes in the weighting of the first principal component (PC) with only minor changes of the weighting of the second PC. Because these response components were shown previously to correlate with the limb axis orientation and length trajectories respectively, the finding is consistent with the idea that limb axis length and orientation information are processed separately within the spinal circuitry.

Animals↗
PubMed2001

The efficacy of 0.5% proparacaine stored at room temperature.

OBJECTIVE: To evaluate the efficacy of 0.5% proparacaine stored at room temperature for 6 weeks. ANIMALS STUDIED: Six normal dogs, evaluated on a weekly basis for 6 weeks. PROCEDURE: Proparacaine stored at 4 degrees C or at room temperature, was evaluated in the right and left eye of each dog, respectively. Corneal sensitivity was assessed with a Cochet-Bonnet aesthesiometer before and after instillation of proparacaine at each time point. RESULTS: A statistically significant difference was seen in corneal sensitivity beginning at week 3 for the eyes receiving room-temperature proparacaine compared to refrigerated proparacaine. Differences were not seen between right and left eyes before instillation of proparacaine for any time point, nor for eyes receiving refrigerated proparacaine over the 6 week study period. CONCLUSION: Short-term storage of proparacaine at room temperature did not affect efficacy, but storage at room temperature for more than 2 weeks resulted in a decrease in drug effect.

Anesthetics, Local↗
PubMed2001

Mitochondrial function and oxygen supply in normal and in chronically ischemic muscle: a combined 31P magnetic resonance spectroscopy and near infrared spectroscopy study in vivo.

PURPOSE: We used (31)P magnetic resonance spectroscopy (MRS) and near-infrared spectroscopy (NIRS) as a means of quantifying abnormalities in calf muscle oxygenation and adenosine triphosphate (ATP) turnover in peripheral vascular disease (PVD). METHODS: Eleven male patients with PVD (mean age, 65 years; range, 55-76 years) and nine male control subjects of similar age were observed in a case-control study in vascular outpatients. Inclusion criteria were more than 6 months' calf claudication (median, 1.5 years; range, 0.6-18 years); proven femoropopliteal or iliofemoral occlusive or stenotic disease; maximum treadmill walking distance (2 km/h, 10 degrees gradient) of 50 to 230 m (mean, 112 m); ankle-brachial pressure index of 0.8 or less during exercise (mean, 0.47; range, 0.29-0.60). Exclusion criteria included diabetes mellitus, anemia, and magnet contraindications. Simultaneous (31)P MRS and NIRS of lateral gastrocnemius was conducted during 2 to 4 minutes of voluntary 0.5 Hz isometric plantarflexion at 50% and 75% maximum voluntary contraction force (MVC), followed by 5 minutes recovery. Each subject was studied three times, and the results were combined. RESULTS: Compared with control subjects, patients with PVD showed (1) normal muscle cross-sectional area, MVC, ATP turnover, and contractile efficiency (ATP turnover per force/area); (2) larger phosphocreatine (PCr) changes during exercise (ie, increased shortfall of oxidative ATP synthesis) and slower PCr recovery (47% +/- 7% [mean +/- SEM] decrease in functional capacity for oxidative ATP synthesis, P = .001); (3) faster deoxygenation during exercise and slower postexercise reoxygenation (59% +/- 7% decrease in rate constant, P = .0009), despite reduced oxidative ATP synthesis; (4) correlation between PCr and NIRS recovery rate constants (P < .02); and (5) correlations between smaller walking distance, slower PCr recovery, and reduced MVC (P < .001). The precision of the key measurements (rate constants and contractile efficiency) was 12% to 18% interstudy and 30% to 40% intersubject. CONCLUSION: The primary lesion in oxygen supply dominates muscle metabolism. Reduced force-generation in patients who are affected more may protect muscle from metabolic stress.

Adenosine Triphosphate↗
PubMed1997

The herpesvirus protease: mechanistic studies and discovery of inhibitors of the human cytomegalovirus protease.

The herpesvirus protease is a recently identified enzyme which is essential for viral replication. It is found in all herpesviruses and offers a new molecular target for therapeutic intervention. Its genomic structure has recently been described and consists of a large open reading frame which encodes a fusion protein containing an amino-terminal protease domain in-frame with a carboxyl-terminal "assembly protein-like" domain. Auto-processing releases the amino-terminal protease as a maturational enzyme. The herpesvirus protease has been characterized as a novel serine protease. Four surface accessible sulfhydryl groups have been identified in the human cytomegalovirus (HCMV) protease. Utilizing a fluorogenic DABCYL-EDANS substrate assay, directed screening has identified a class of sulfhydryl-modifying benzimidazolylmethyl sulfoxides which inhibits recombinant HCMV protease. Site-directed mutagenesis studies suggest oxidative modification of surface-accessible HCMV protease Cys138 (and possibly Cys161) by this class of inhibitors. The benzimidazolylmethyl sulfoxide 1 inhibits HCMV protease (IC50 = 1.9 microM), exhibits selectivity vs. mammalian serine proteases, and exhibits antiviral activity in an HCMV infected cell culture assay.

Antiviral Agents↗
PubMed1996

Representation of passive hindlimb postures in cat spinocerebellar activity.

1. We report here about the modulation of dorsal spinocerebellar tract (DSCT) activity by limb posture. In principle, DSCT activity could represent limb position in one of several ways. According to a classical notion of DSCT function, DSCT activity might be expected to correlate with changes in individual joint angles. However, given the evidence for extensive polysynaptic convergence onto DSCT units, it is reasonable to propose that DSCT activity represents more global variables such as the orientation of limb segments or the length and orientation of the whole limb. 2. In six anesthetized cats we recorded the activity of 96 antidromically identified DSCT neurons while a robot arm passively positioned the left hindfoot in 20 positions distributed in the sagittal plane, holding each position for 8 s. For each position we measured the joint angles, limb segment angles, and the length and orientation of the limb axis (defined as the line connecting the hip joint to the hindpaw). We used regression statistics to quantify 1) possible relationships among geometric variables of the hindlimb and 2) relationships between DSCT firing rate and limb variables. 3. First, we found a statistically significant relationship among the joint angles that could be described by a covariance plane accounting for approximately 70 percent of the total variance. Thus the 3 degrees of freedom represented by the joint angles in the sagittal plane are effectively reduced to only 2 by the coupling between joints. This finding resembles that described for the behaving cat during stance. However, the correlation between the hip and ankle angles in the passively displaced hindlimb was just the opposite of that observed during active stance. Moreover, we observed that the length and the orientation of the limb axis is determined simply by a linear combination of the three joint angles. 4. Most of the DSCT neurons (82 of 96) were significantly modulated by changes in foot position (1-way analysis of variance, P < 0.001). For those cells, we explored systematically how their activity was related to limb geometric variables. We found mostly linear relationships between individual joint or limb segments angles and DSCT firing rates. However, although these relationships were statistically significant, the random variance was often quite high. Moreover, approximately 70% of the cells were modulated by more than one joint or limb segment angle, suggesting that a model incorporating global geometric variables might explain a larger fraction of the variance in the neural data. 5. Consequently we tested how well DSCT activity was modulated by the length and the orientation of the limb axis with the use of a linear regression model with length and orientation (or the equivalent linear combination of joint angles) as predictors. We found that this model explained a larger fraction of the variability in the firing pattern of nearly every modulated cell than did any of the single joint models tested. 6. We also attempted to account for the effect of the mechanical joint covariance on this result by accounting for correlated independent variables in the analysis. We used a regression model incorporating all three joint or limb segment angles and performed a backward elimination of insignificant or redundant variables. The result was that 67% of the neurons were independently modulated by at least two joint angles, indicating that the modulation did not necessarily reflect the biomechanical constraint of joint angle covariation, but rather a central convergence of sensory information from more than a single joint. 7. From these results we conclude that the firing rates of a majority of DSCT neurons encode the position of the hindfoot relative to the hip joint.(ABSTRACT TRUNCATED)

Animals↗
PubMed1993

A case of transfusion-acquired hepatitis C.

The Blood Transfusion Service introduced screening for Hepatitis C antibody (HCV) in September 1991. This is done by second generation enzyme linked immunosorbent assay (ELISA) tests. We present a case of post-transfusion hepatitis C hepatitis in a patient with myeloma. Infection was acquired before screening was introduced. Both the patient and the infected blood donor were diagnosed using ELISA assays and the polymerase chain reaction (PCR). In this way we prevented the blood donor from spreading the virus via subsequent blood donations. There were some interesting discrepancies in the HCV assays. Blood samples, when tested by different methods, gave both positive and negative results. The results also varied according to when the blood samples to be tested were taken. The case illustrates the importance of confirming positive results and that no single laboratory test is entirely satisfactory in diagnosing HCV infection.

Aged↗
PubMed1993

The effects of multiple gestation and selective reduction on fetal outcome.

A group of 32 women with at least 3 or more viable fetuses by sonography at approximately 8 weeks gestation were given the option of selective reduction. They were advised that this was a relatively new procedure but heretofore in a small series was not associated with a significant increase in fetal demise. Only 7 of 32 women chose this option. six of these 7 had triplets reduced to twins, 1 woman had quadruplets reduced to twins. Thirteen of 14 viable babies were successfully delivered at a mean of 36.8 weeks gestation; 2 of 7 (28.6%) delivered before 37 weeks. In contrast, 7 of 25 (24%) not having reduction lost all babies (6 triplets, 1 quadruplet). Four other women lost at least 1 of their gestations (total of 5 babies). Pre-term deliveries (< 37 weeks) occurred in 16 of 18 (88.8%) patients delivering at least 1 live baby, with a mean of 33.7 weeks gestation. Thus the high rate of total fetal loss and prematurity for multiple gestation and the low pregnancy wastage and pre-term delivery rate following selective reduction might make the latter a reasonable therapeutic option to patients interested in having the best chance of delivering healthy viable babies.

Abortion, Therapeutic↗
PubMed1989

Post abortion syndrome.

While many would debate the very reality of Post Abortion Syndrome, the author of this article has experienced Post Abortion Syndrome first hand. Excerpted from a speech she gave before a Florida meeting of the National Organization of Episcopalians for Life (NOEL), the article outlines the various stages and symptoms of Post Abortion Syndrome: denial, repression, guilt, anxiety, depression. She then describes the process for healing and recovery, and presents a model for a Post Abortion support group which is patterned after Alcoholics Anonymous.

Abortion, Induced↗
PubMed1986

The risk of fetal anomalies as a result of progesterone therapy during pregnancy.

The incidence of congenital anomalies in infants born to 382 women treated with P was noted. Only five anomalies occurred in the infants born to women who had taken P. This study supports the data of Rock et al. by demonstrating a similar low incidence of birth defects in a much larger series of patients who also took a much higher dosage of P. Similarly, because only 1 of 189 patients treated with both P and 17-OHP developed anomalies, the data supports the study by Katz et al., suggesting no increase in anomalies related to 17-OHP therapy.

17-alpha-Hydroxyprogesterone↗