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Biomedical subjects

L Taylor

Publications and source records attributed to L Taylor.

At least 127 records · Page 7Linked to original sources

Dated co-occurrence of Homo erectus and Gigantopithecus from Tham Khuyen Cave, Vietnam.

Tham Khuyen Cave (Lang Son Province, northern Vietnam) is one of the more significant sites to yield fossil vertebrates in east Asia. During the mid-1960s, excavation in a suite of deposits produced important hominoid dental remains of middle Pleistocene age. We undertake more rigorous analyses of these sediments to understand the fluvial dynamics of Pleistocene cave infilling as they determine how skeletal elements accumulate within Tham Khuyen and other east Asian sites. Uranium/thorium series analysis of speleothems brackets the Pleistocene chronology for breaching, infilling, and exhuming the regional paleokarst. Clast analysis indicates sedimentary constituents, including hominoid teeth and cranial fragments accumulated from very short distances and under low fluvial energy. Electron spin resonance analysis of vertebrate tooth enamel and sediments shows that the main fossil-bearing suite (S1-S3) was deposited about 475 thousand years ago. Among the hominoid teeth excavated from S1-S3, some represent Homo erectus and Gigantopithecus blacki. Criteria are defined to differentiate these teeth from more numerous Pongo pygmaeus elements. The dated co-occurrence of Homo erectus and Gigantopithecus blacki at Tham Khuyen helps to establish the long co-existence of these two species throughout east Asia during the Early and Middle Pleistocene.

Animals↗

Evaluation of a pooling method for routine anti-HCV screening of blood donors to lower the cost burden on blood banks in countries under development.

A pooling system was developed for use in anti-HCV screening of voluntary blood donors at the local Central American Red Cross blood banks, in Nicaragua, El Salvador and Honduras. The commercially available second generation anti-HCV screening kit from Abbott Laboratories (North Chicago, IL) was used with a modification in the initial serum dilution procedure. Pools of five sera were selected for routine screening, based on comparative studies of individual samples and of pools with different sample sizes. During the years 1993 and 1994 a total of 89, 148 voluntary blood donors were screened and a positive prevalence rate of 0.35% was established. Of the initially positive samples, 54% confirmed positive, 30% were indeterminate and 16% were negative using the Abbott Matrix test. Significant differences of positive screening prevalence rates were found in the three countries, with average values of 0.50%, 0.23% and 0.08%, respectively, in Nicaragua, El Salvador and Honduras. These initially positive samples also showed a different confirmatory pattern with a positive rate of 64% in Nicaragua, in contrast to 20% in El Salvador. Only a few samples were available for RT-PCR amplification of HCV-RNA; however, this highly sensitive method did not appear to be more helpful than serology in confirming the HCV donor status. Overall, the data obtained indicate a fluctuation of HCV prevalence in voluntary blood donors among the three Central American countries. Further, differences were found in the percentages of initially screened positives and confirmation patterns. This information appears useful for establishing criteria in future screening policies. Thus, we suggest that the use of pooling for anti-HCV screening is beneficial in countries under development, since there are potential cost savings, as well as benefits in establishment of initial prevalence rates.

Blood Banks↗

Deficiency of complex II of the mitochondrial respiratory chain in late-onset optic atrophy and ataxia.

Defects of the mitochondrial respiratory chain are increasingly being recognized as an important cause of neurological disease in humans. In many of these patients, the biochemical defect results from an abnormality of the mitochondrial genome. Respiratory chain defects involving complex II, which is entirely encoded by the nuclear genome, are comparatively rare. We report the clinical and biochemical findings in 2 elderly sisters who presented with late-onset neurodegenerative disease. In both patients, a partial deficiency of complex II (approximately 50% of control values) was shown to be present in mitochondria from muscle and platelets. The enzyme defect was not expressed in cultured skin fibroblasts or immortalized lymphocytes. There was an overexpression of the 70-kd flavoprotein subunit in muscle mitochondria from both patients, although we showed that this subunit is present in normal amounts in mitochondrial membranes. Our studies highlight the diversity of the clinical presentation of respiratory chain disease and that complex II deficiency should enter the differential diagnosis of certain patients with late-onset neurodegenerative disease.

Ataxia↗

Acute Myocardial Infarction in Canada: New Epidemiologic Insights on Incidence, Therapy, and Risk.

Objective: To define the changing incidence, risk, and therapy of acute myocardial infarction (A311). Data sources: Review of contemporary AMI data from the University of Alberta Hospitals, six other sites of the Clinical Quality Improvement Network (CQIN), and other Canadian and international centers. Data synthesis: Ischemic heart disease is age-related and the Canadian population is rapidly aging. At the University of Alberta Hospitals, the incidence of Q wave AMI (per 100,000 population) in 1985 was 113 and has remained unchanged (NS) since that time (129 in 1994). In contrast, the combined incidence of non.Q-wave AMI and unstable angina has increased markedly, from 74 in 1985 to 226 in 1994 (p < 0.05). The use of proven efficacious therapies for AMI has greatly increased in recent years, with thrombolytic drugs being given to approximately 35;percnt; of all patients by 1993; and beta-blockers and aspirin to 75;percnt; and 98;percnt; of patients, respectively. However, females and patients older than 70 years' despite their greater risk, received significantly less efficacious medication than males and younger AMI patients. The use of calcium antagonists decreased from a peak utilization rate of 60;percnt; for all AMI patients in 1989 to less than 10;percnt; by 1993. In-hospital AMI mortality risk has also decreased in the last several years, particularly among higher risk older patients (35;percnt;, 1987 vs. 19;percnt;,1993). In a population of 3896 consecutive AMI patients, recruited largely in 1992 and 1993 from seven CQIN sites, logistic regression analyses revealed aspirin was associated with the greatest relative risk reduction (61%); beta-blocker and thrombolytic therapy were related to risk reductions of 55;percnt; and 16;percnt;, respectively. Incremental age was the most important factor associated with increased relative risk in AMI, overall and in both sexes; sex was not an independent risk predictor. Qualitatively very similar AMI incidence, risk, and treatment data have also been recently observed in other centers in Canada, the United States, and elsewhere. Conclusions: Although widespread primary or secondary prevention is possibly contributory, the recent static incidence of Q-wave AMI and the marked increase in unstable angina and non-Q-wave AMI are more likely due to enhanced health awareness and diagnosis-seeking behavior in the population at risk. The decline in AMI mortality, at least for high-risk acute care patients, is compatible with a clinically relevant secondary prevention effect. There are still, however, windows of opportunity to further improve AMI outcomes by increasing the utilization of proven efficacious therapy, especially among women and older patients. Another particularly attractive epidemiologic benefit in the immediate future would accrue from the further development and effective use of efficacious therapies directed against unstable angina and n-Q-wave AMI.

Journal Article↗

Rats rapidly develop tolerance to the locomotor-inhibiting effects of the novel neuropeptide orphanin FQ.

We examined the effects of intracerebroventricular (i.c.v.) administration of orphanin FQ (OFQ) on locomotor activity in rats. The rats were habituated to locomotor-testing boxes and then injected i.c.v. with OFQ (0 - 10 nmoles). Acute injections of OFQ produced dose-orderly reductions in horizontal locomotion and rearing activity. This suppression of motor activity was characterized by a disruption of balance and muscle control. Within minutes of i.c.v. injection of the higher doses of OFQ, the rats exhibited flaccid muscle tone. They each lay in an atypical posture, pressing the abdomen against the floor, and splaying the hindlimbs. When these rats locomoted, their gate was unsteady. They wobbled from side to side, and frequently fell over. Repeated daily injections of OFQ resulted in a rapid development of tolerance to the OFQ-induced suppression of locomotion and rearing activity. Tolerance to the observed impairments of motor control were also apparent. In the rats that were repeatedly treated with the highest dose (10 nmol) of OFQ, tolerance to the motoric effects was still apparent after 7 days without OFQ treatment.

Analysis of Variance↗

Multiparameter fluorescence imaging microscopy: reagents and instruments.

Fluorescence imaging microscopes and fluorescent reagents have both evolved greatly in the past 10 years. Sensitive imaging cameras developed over the last decade allow detection of fluorescence signals from even a single fluorescent tag on a protein. At the same time, numerous antibody markers for growth control proteins and DNA probes for chromosomal alterations have been discovered and these can be labeled with the new multicolor fluorescent dyes for detection by microscopy. Image analysis software automatically localizes and quantifies of as many as 5-6 of these different color fluorescent markers in the individual cells of a preparation. The results is that powerful methods for multiparameter analysis of molecular structures and dynamic processes are now accessible to the pathologist.

DNA Probes↗

Narrative development in late talkers: early school age.

Children with slow expressive language development (SELD) as toddlers and a control group of children with normal language development (NL) were followed to early school age. Children with SELD were, at that point, subdivided into two groups: those who had moved within the normal range of expressive language (the History of Expressive Language Delay [HELD] subgroup); and those who continued to score below the normal range in expressive language at school age (the Expressive Language Delay [ELD] subgroup). During their kindergarten, first, and second grade years, they were administered a narrative generation task. Narratives were analyzed for MLU, lexical diversity, amount of information included, proportion of complete cohesive ties, and overall stage of narrative maturity. In kindergarten, children with normal language history scored significantly higher than those with HELD and ELD on lexical diversity and narrative stage; and higher than those with ELD in proportion of complete cohesive ties. In first grade, children with normal language history again scored significantly higher than those with HELD and ELD on narrative maturity, with no other significant differences. In second grade, there were no significant differences among the groups.

Age Factors↗

The species-specific RNA polymerase I transcription factor SL-1 binds to upstream binding factor.

Transcription of the 45S rRNA genes is carried out by RNA polymerase I and at least two trans-acting factors, upstream binding factor (UBF) and SL-1. We have examined the hypothesis that SL-1 and UBF interact. Coimmunoprecipitation studies using an antibody to UBF demonstrated that TATA-binding protein, a subunit of SL-1, associates with UBF in the absence of DNA. Inclusion of the detergents sodium dodecyl sulfate and deoxycholate disrupted this interaction. In addition, partially purified UBF from rat cell nuclear extracts and partially purified SL-1 from human cells coimmunoprecipitated with the anti-UBF antibody after mixing, indicating that the UBF-SL-1 complex can re-form. Treatment of UBF-depleted extracts with the anti-UBF antibody depleted the extracts of SL-1 activity only if UBF was added to the extract prior to the immunodepletion reaction. Furthermore, SL-1 activity could be recovered in the immunoprecipitate. Interestingly, these immunoprecipitates did not contain RNA polymerase I, as a monospecific antibody to the 194-kDa subunit of RNA polymerase I failed to detect that subunit in the immunoprecipitates. Treatment of N1S1 cell extracts with the anti-UBF antibody depleted the extracts of SL-1 activity but not TFIIIB activity, suggesting that the binding of UBF to SL-1 is specific and not solely mediated by an interaction between UBF and TATA-binding protein, which is also a component of TFIIIB. These data provide evidence that UBF and SL-1 interact.

Animals↗

Detection of integrated high risk human papillomavirus in adenoid cystic carcinoma of the uterine cervix.

AIM: To investigate the role of human papillomavirus (HPV) in adenoid cystic carcinoma of the uterine cervix. METHODS: Eleven archival, paraffin wax embedded specimens were analysed by non-isotopic in situ hybridisation (NISH) for HPV types 6, 11, 16, 18, 31, and 33 using digoxigenin labelled probes. The polymerase chain reaction (PCR) was carried out on each of the cases using consensus primers to HPV. RESULTS: A total of eight adenoid cystic carcinomas harboured the HPV genome by NISH, of which five were PCR positive. Integrated HPV 16 DNA was demonstrated in seven of the eight NISH positive cases. One adenoid cystic carcinoma showed integrated HPV 31. HPV DNA was not detected in the three remaining cases. CONCLUSIONS: Integrated high risk HPV genome, in particular type 16, is associated with this uncommon type of primary cervical cancer.

Aged↗

The 3'-nontranslated region of rat renal glutaminase mRNA contains a pH-responsive stability element.

Rat kidney expresses two forms of glutaminase (GA) mRNA which probably result from the use of alternative polyadenylation signals. The two mRNAs are increased coordinately in response to metabolic acidosis via a mechanism that apparently does not involve transcriptional or translational regulation. A 956-bp fragment that contains the 3'-nontranslated sequence of the smaller GA cDNA was cloned into an expression vector (p beta G) that encodes a chimeric beta-globin growth hormone mRNA. Both the parent and the derived construct (p beta G-GA) were transfected into LLC-PK1-F+ cells. Stable transfectants express sixfold lower levels of beta G-GA mRNA than that of the parent beta G mRNA. However, only the beta G-GA mRNA is increased 2.5-fold by growth in acidic medium (pH 6.9, 10 mM HCO3-). The apparent half-life of the beta G mRNA (> 24 h) is unaffected by the pH of the growth media. In contrast, the apparent half-life of the beta G-GA mRNA is increased from 4.5 h to approximately 24 h when cells are transferred to acidic medium for 8 h. The observed pH response is not reproduced when the beta G-GA construct is stably transfected into COS-7 cells or when a beta-globin-phosphoenolpyruvate carboxykinase chimeric gene is expressed in LLC-PK1-F+ cells. Thus the 3'-nontranslated region of the GA mRNA contains a pH-responsive stability element.

Animals↗

Informal care for illness in rural southwest Uganda: the central role that women play.

In rural Uganda care for those who are ill tends to be home based because of inadequate and expensive health care facilities, lack of medication and poor staffing levels in health units. Research findings suggest that women are responsible for the bulk of caring activities. This paper questions the assumption that female informal carers are in a position to cope with illness episodes in the home. Data were collected from 54 female informants in a rural population in southwest Uganda. Supplementary data from in-depth interviews with survey participants and counsellors were also collected. Findings suggest that women are the main providers of informal care within the home. Many women, particularly in female-headed households, did not own or have direct access to the necessary finances to meet the family's health care needs as expected of them. Although relatives and friends were seen as a valuable resource, because of poor household proximity and financial constraints they were not always in a position to offer or provide assistance. The women also identified themselves as responsible for a variety of home and agricultural tasks; such activities were frequently disrupted by illness episodes. As women take on the additional burden of care for those with HIV/AIDS an inevitable conclusion is that their resources, both social and economic, will not be adequate. These data indicate the need for additional research and stress the importance of appropriate support and relief programs for those responsible for informal care.

Adolescent↗

Mental Health in the Schools: Promising Directions for Practice.

Discontent with the state-of-the-art of mental health services being provided in schools has led to fundamental shifts in thinking about these services. This article reviews existing programs and highlights emerging trends in school mental health services. The authors demonstrate how mental health programs are changing from narrowly focused to comprehensive, from fragmented to coordinated, from problem-specific to cross-disciplinary, and from being supplementary services in the school to essential components that enable learning.

Journal Article↗

Assessing appropriateness of treatment: a case study of transplantation in older patients with congestive heart failure.

OBJECTIVE: To evaluate the appropriateness of transplantation therapy for older patients with congestive heart failure (CHF). DATA SOURCES: Comparative review of contemporary survival and quality of life data of CHF patients treated medically versus by transplantation. DATA SYNTHESIS: Approximately 300,000 Canadians have CHF and the incidence is increasing as the population ages; suitable donor allografts are found for about 300 CHF patients each year. Overall survival among cardiac allograft recipients, with a mean age of 48 years, is approximately 80% at two years. However, risk from all causes appears higher, and survival lower (range 40 to 78%), for transplant patients 55 years of age and older. Among medically treated patients, with mean age over 60 years, survival is inversely related to level of functional disability, averaging more than 90% at two years for patients with mild limitation and decreasing to 75% and 40% for patients with moderate and severe symptoms, respectively. Perceived quality of life is low in all CHF patients, but is significantly improved by intense out-patient care and education, irrespective of medical or transplant allocation. CONCLUSIONS: Among adults with CHF, the greatest benefit of transplantation is enhanced survival in younger severely disabled patients. However, noncardiac risks are substantial, particularly for older recipients. The great discrepancy between donor and candidate availability prohibits transplantation from being a life expanding therapy for the whole CHF population. When physicians are, simultaneously, patients' and society's advocates a utilitarian decision model using the totality of efficacy data, including degree of efficacy and population effectiveness, may assist determination of the most appropriate therapy.

Activities of Daily Living↗

Geriatric hemodialysis patients: a comparative study of vascular access.

OBJECTIVES: To compare vascular access in hemodialysis patients > or = 65 years of age with those < 65 years on the following: 1) comorbid disease status, 2) types of vascular access used, and 3) outcome. SAMPLE/SETTING: Hemodialysis patients in a four-state region (Iowa, Kansas, Nebraska, and Missouri) from both free-standing and hospital-affiliated providers were sampled (n = 267). A stratified sampling strategy was used in order to obtain approximately equal-sized age groups (< 65 years and > or = 65 years). DESIGN: A descriptive, longitudinal study with a 1-year follow-up period. METHODS: Following the placement of a permanent vascular access, information was collected by the dialysis nursing staff about the configuration of the access, needle gauge used for cannulation, dialysis prescriptions, diabetic status, and other comorbid disease conditions. Odds ratios (OR) for vascular access thrombosis (VAT) risk were calculated between the two age groups. RESULTS: Comparisons between the two age groups suggest a higher frequency of polytetrafluorethylene (PTFE) grafts in the > or = 65-year-old age group. Peripheral vascular disease (PVD) prevalence was also higher in elders. Oral anticoagulants reduced the risk of VAT in those < 65-year-old group. Patients age > or = 65 years with a PTFE graft experienced a higher risk of VAT (OR 3.38, 95% confidence interval 1.43, 8.11) than those in the same age group with an arteriovenous fistula (AVF). CONCLUSIONS: PTFE grafts are used more frequently among geriatric hemodialysis patients, possibly due to the increased prevalence of peripheral vascular disease (PVD). While use of oral anticoagulants is effective in reducing the risk of VAT among those < 65 years, it did not significantly reduce VAT risk in geriatric hemodialysis patients. This observation may be due to the higher frequencies of PTFE grafts in elderly patients.

Aged↗

A chimeric study of the molecular basis of affinity and selectivity of the kappa and the delta opioid receptors. Potential role of extracellular domains.

Within the large family of G-protein-coupled receptors, a picture is emerging which contrasts the binding of small ligands and the binding of peptides to the seven-helix configuration of the proteins. Because of its unique richness in both peptide and non-peptide ligands, the opioid receptor family offers several advantages for achieving a better understanding of similarities and differences in ligand/receptor interactions across different classes of agonists and antagonists. Since multiple, naturally occurring, ligands interact with the multiple receptors with varying degrees of selectivity, this family is also an excellent model for examining the structural basis of selectivity. Thus, the molecular basis of binding affinity and selectivity of the kappa and the delta opioid receptors was investigated by the construction of four kappa/delta chimeric receptors. The pharmacological profiles of these chimeras as well as those of the wild type kappa and delta receptors were determined by their binding with several different categories of opioid ligands. A linear model was used to deduce the relative contribution of each corresponding pairs of kappa-delta receptor segments to the binding of a given ligand. The results show that the kappa and delta receptors bind the same opioid core differently and achieve their selectivity through different mechanisms. In addition, the interaction of a peptide ligand with a receptor appears to be different from that of a small ligand. Furthermore, these results point to a particularly important role of the second extracellular loop and the top half of transmembrane domain 4 in the binding of prodynorphin products. Together, the results suggest that these peptide receptors can be bound and activated via multiple binding pockets as a function of their own topography and the nature of the interacting ligand.

Amino Acid Sequence↗

Acidic FGF and FGF receptors are specifically expressed in neurons of developing and adult rat dorsal root ganglia.

Employing complementary technical approaches, we have studied the expression of acidic fibroblast growth factor (aFGF) and FGF receptors in rat dorsal root ganglia. The results clearly showed that within spinal nerves aFGF and two high-affinity FGF receptors, FGFR-1 and FGFR-2, were prominently expressed in neurons, while expression in Schwann cells was undetectable. FGFR-3 and FGFR-4 were not expressed in dorsal root ganglia. Acidic FGF mRNA was detected in the majority of dorsal root ganglion neurons, including all size classes: FGFR-1 and FGFR-2 transcripts were only detected in subpopulations of mainly large and medium size neurons. In subcellular fractionation studies on dorsal root ganglion and spinal root tissue, aFGF was recovered in the soluble fraction and was thus not tightly associated with neuronal membranes. During development FGFR-1 and FGFR-2 mRNAs were found to be present at all stages examined (embryonic days 15-21 and postnatal days 1-120). Acidic FGF mRNA and protein were first detected at embryonic day 18, and their expression then increased progressively up to postnatal levels. In cultures of dorsal root ganglion neurons derived from day 15 embryos, aFGF expression was first detected 3 days after plating. The resulting neuron cultures continued to express aFGF in a Schwann cell-independent manner. In combination, these results indicate that aFGF expression in dorsal root ganglia is initiated and maintained in postmitotic neurons. Furthermore, the data suggest that the physiological function of aFGF in the peripheral nervous system is connected to processes specific to the mature sensory (and motor) system, such as the maintenance and survival of peripheral nerve neurons.

Animals↗

The RNA polymerase I transcription factor UBF is the product of a primary response gene.

Transcription of the ribosomal RNA genes by RNA polymerase I is tightly coordinated with the rate of cell growth. The RNA polymerase I transcription factor, UBF, activates transcription by binding to elements within the promoter and enhancer elements within the intergenic spacer but is not required for basal transcription. To assess the role of UBF in modulating ribosomal DNA transcription, we studied its expression in NIH3T6 fibroblasts when transcription was repressed in response to serum starvation and stimulated following refeeding. Our results demonstrate a correlation between the amounts of UBF protein and the rates of ribosomal DNA transcription in quiescent and serum-stimulated cells. Nuclear run-on assays and Northern blot analyses demonstrated that the UBF gene was a primary response gene, exhibiting characteristics similar to those of c-myc and SRF. These results suggest that the regulation of transcription of the UBF gene by polymerase II represents a pathway by which cells modulate transcription by RNA polymerase I.

3T3 Cells↗