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Biomedical subjects

J Anderson

Publications and source records attributed to J Anderson.

At least 181 records · Page 10Linked to original sources
PubMed1999

Dundee step test: a simple method of measuring the blood pressure response to exercise.

The exercise systolic blood pressure (BP) response provides prognostic information over and above that of resting clinic BP in both normotensive and hypertensive individuals. We have developed a 3-min step test as a method of measuring the exercise systolic BP. Healthy volunteers and patients referred for assessment of hypertension took part in validating this exercise test. We assessed the reproducibility of the exercise systolic BP response, and this was compared with that obtained using the cycle ergometry at an equivalent workload. We also compared the baseline characteristics, BP profiles and exercise systolic BP responses in different subject groups. The intra-observer coefficient of variation assessed in 25 subjects was 5.9% with a mean difference of 1.8 mm Hg. The values for between observer were 8.3% and 2.5 mm Hg respectively. Exercise systolic BP measured with the step test correlated with that of cycle ergometer (n = 37, r = 0.93, P < 0.01). Exercise systolic BP data from healthy volunteers (n = 107) showed a normal distribution. An exercise systolic BP of >/=180 mm Hg was greater than 2 standard deviations from the mean and was taken as an abnormally high BP during exercise. There was a positive correlation between exercise BP and increasing age in healthy volunteers (r = 0.57, P < 0.01). This was also present in hypertensive subjects (n = 46, r = 0.48, P = 0.001), however the slope of this relationship was twice as steep as in the normal subjects. Hypertensive subjects with high exercise systolic BP had significantly higher clinic BP, ABPM and a greater BP rise during exercise. The Dundee step test is quick, reproducible and may be prognostically useful.

Adult↗
PubMed1999

Disruption of imprinted genes at chromosome region 11p15.5 in paediatric rhabdomyosarcoma.

Rhabdomyosarcomas are characterized by loss of heterozygosity (LOH) at chromosome region 11p15.5, a region known to contain several imprinted genes including insulin-like growth factor 2 (IGF2), H19, and p57(KIP2). We analyzed 48 primary tumour samples and found distinct genetic changes at 11p15.5 in alveolar and embryonal histological subtypes. LOH was a feature of embryonal tumours, but at a lower frequency than previous studies. Loss of imprinting (LOI) of the IGF2 gene was detected in 6 of 13 informative cases, all harbouring PAX3-FKHR or PAX7-FKHR fusion genes characteristic of alveolar histology. In contrast, H19 imprinting was maintained in 14 of 15 informative cases and the case with H19 LOI had maintenance of the IGF2 imprint indicating separate mechanisms controlling imprinting of IGF2 and H19. The adult promoter of IGF2, P1, was used in 5 of 14 tumours and its expression was unrelated to IGF2 imprinting status implying a further mechanism of altered IGF2 regulation. The putative tumour suppressor gene p57(KIP2) was expressed in 15 of 29 tumours and expression was unrelated to allele status. Moreover, in tumours with p57(KIP2) expression, there was no evidence for inactivating mutations, suggesting that p57(KIP2) is not a tumour suppressor in rhabdomyosarcoma.

Adult↗
PubMed1999

Increased cytotoxicity and decreased in vivo toxicity of FdUMP[10] relative to 5-FU.

The efficacy of treatment with 5-Fluorouracil (5-FU) is limited, in part, by its inefficient conversion to 5-Fluoro-2'-deoxyuridine-5'-O-monophosphate (FdUMP). We present data indicating that FdUMP[10], designed as a pro-drug for intracellular release of FdUMP, is cytotoxic as a consequence of uptake of the multimeric form. FdUMP[10] is stable in cell culture medium, with more than one-half of the material persisting as multimers of at least six nucleotides after a 48 h incubation at 37 degrees C. FdUMP[10] is more than 400 times more cytotoxic than 5-FU towards human colorectal tumor cells (H630). FdUMP[10] also has decreased toxicity in vivo, with doses as high as 200 mg/kg/day (qdx3) administered to Balb/c mice without morbidity, compared to a maximum tolerated dose of 45 mg/kg/day for 5-FU using the same protocol. FdUMP[10] shows reduced sensitivity to OPRTase- and TK-mediated drug resistance, relative to 5-FU and FdU, respectively, and is much more cytotoxic than 5-FU towards cells that overexpress thymidylate synthase. Thus, FdUMP[10] is less susceptible to resistance mechanisms that limit the clinical utility of 5-FU. The increased cytotoxicity, decreased toxicity in vivo, and reduced sensitivity to drug resistance of FdUMP[10], relative to 5-FU, indicates multimeric FdUMP is potentially valuable as an anti-neoplastic agent, either as a single agent, or in combination with 5-FU.

Adenocarcinoma↗
PubMed1999

Prevalence of lower genital tract infections among human immunodeficiency virus (HIV)-seropositive and high-risk HIV-seronegative women. HIV Epidemiology Research Study Group.

This study was undertaken to assess whether the prevalence of lower genital tract infections among human immunodeficiency virus (HIV)-seropositive women was higher than among high-risk HIV-seronegative women at their baseline visit for the HIV Epidemiology Research Study. Results were available for 851 HIV-seropositive and 434 HIV-seronegative women. Human papilloma virus (HPV) infection was more prevalent among HIV-seropositive women (64% vs. 28%). Bacterial vaginosis was common (35% vs. 33%), followed by trichomoniasis (12% vs. 10%), syphilis (8% vs. 6%), Chlamydia trachomatis infection (4% vs. 5%), candidal vaginitis (3% vs. 2%), and Neisseria gonorrhoeae infection (0.8% vs. 0.3%). Alcohol use (odds ratio [OR], 1.8; 95% confidence interval [CI], 1. 3-2.4) and smoking (OR, 1.8; 95% CI, 1.3-2.5) were associated with bacterial vaginosis. Bacterial vaginosis (OR, 2.3; 95% CI, 1.5-3.4), trichomoniasis (OR, 2.3; 95% CI, 1.1-4.7), and syphilis (OR, 3.1; 95% CI, 1.3-7.4) were found to be more prevalent among black women. Our study showed no statistically significant difference in the prevalence of lower genital tract infections except for HPV between HIV-infected and demographically and behaviorally similar HIV-uninfected high-risk women.

Adult↗
PubMed1999

Successful PBSC mobilization with high-dose G-CSF for patients failing a first round of mobilization.

PBSC are the preferred source of stem cells for autologous transplantation. However, regardless of the mobilization procedure used, 10%-20% of patients fail to collect an adequate number to ensure prompt engraftment. There is as yet no standard mobilization procedure for patients who fail a first mobilization attempt. Here, we describe a highly efficient strategy to obtain an adequate number of stem cells for patients who failed a first mobilization attempt. Seventy-four patients with various hematologic malignancies underwent initial mobilization with various regimens including hematopoietic growth factors with or without chemotherapy. In 72% of patients, > or =2 x 10(6) CD34+ stem cells/kg were collected in the initial mobilization attempt, and patients engrafted in a median of 10 days for neutrophils and 12 days for platelets. Eighteen patients failed to mobilize adequate numbers of stem cells, defined as the inability to collect 0.2 x 10(6) CD34+ stem cells/kg/day in the first 2-3 days. These patients had their apheresis halted. Patients were immediately given G-CSF (32 microg/kg/day) for 4 days as a second attempt at mobilization. Eighty-eight percent of these patients achieved the target of > or =2 x 10(6) CD34+ cells/kg, with a median duration of apheresis of 5 days (including the first and second mobilizations). The mean CD34+ cells/kg/day increased after administration of high-dose G-CSF from 0.16 after the first mobilization attempt to 0.61 (p = 0.0002) after the second mobilization. All patients engrafted in a median of 11 and 13 days for neutrophils and platelets, respectively. We conclude that patients whose apheresis yield is <0.4 x 10(6) CD34+ cells/kg after the first two apheresis collections can be successfully mobilized if high-dose G-CSF is administered immediately and continued until achieving > or =2 x 10(6) CD34+ stem cells/kg.

Adult↗
PubMed1999

Positive interaction between 5-FU and FdUMP[10] in the inhibition of human colorectal tumor cell proliferation.

Interaction between 5-fluorouracil (5-FU) and FdUMP[10], a novel pro-drug formulation of the thymidylate synthase (TS) inhibitory nucleotide 5-fluoro-2'-deoxyuridine-5'-O-monophosphate (FdUMP), was investigated to evaluate the feasibility of using these two forms of fluorinated pyrimidine in combination chemotherapy regimens. 5-FU and FdUMP[10] are expected to differ in their relative intracellular distribution of active metabolites, and their combined administration may result in either a positive or a negative interactive effect. The dose-response behaviors of 5-FU and FdUMP[10] toward H630 and H630-10 (human colorectal tumor) cells were first investigated separately. Effects on cell viability were measured using an assay for 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), while cytotoxicity and apoptosis were investigated using clonogenic and TUNEL assays, respectively. Exposure of H630 cells to concentrations of FdUMP[10] insufficient to inhibit cell proliferation as a single agent markedly increased the cytotoxicity of 5-FU. The results indicate that 5-FU and FdUMP[10] interact in a positive manner, and that combining these two forms of fluorinated pyrimidine may be clinically beneficial.

Antimetabolites, Antineoplastic↗
PubMed1999

Solubility of various forms of strontium titanate in lungs: in vitro and in vivo studies.

At the In-Tank Precipitation Facility of the Savannah River Site, strontium and other radionuclides are removed from high-level radioactive waste and sent to the Defense Waste Processing Facility. Strontium removal is accomplished by adsorption using a slurry that includes monosodium titanate, which forms strontium titanate with unknown lung solubility characteristics. The purpose of this study was to determine the solubility of strontium titanate in the form created at the In-Tank Precipitation facility. An in vitro dissolution study was done with a slurry simulant and with several types of strontium titanate, and the results were compared. An in vivo study was also performed with high-fired SrTiO3 in rats. Strontium and titanium were measured by inductively-coupled plasma/atomic emission spectrometry. The data from both studies were used independently to assign the compounds to an absorption type based on criteria specified in ICRP 71. Results of the in vitro studies showed that the Defense Waste Processing Facility simulant should be assigned to Type M and the strontium titanate should be assigned to Type S. Results of the in vivo study verified that SrTiO3 should be assigned to Type S. Lung clearance data of SrTiO3 from rats showed that 85% cleared within the first 24 h and the remaining 15% cleared with a half-time of 130 d. The initial rapid clearance is attributed to deposition in airways as compared to the alveolar region.

Animals↗
PubMed1999

Enhancing the multivariate signal of [15O] water PET studies with a new nonlinear neuroanatomical registration algorithm.

This paper addresses the problem of neuro-anatomical registration across individuals for functional [15O] water PET activation studies. A new algorithm for three-dimensional (3-D) nonlinear structural registration (warping) of MR scans is presented. The method performs a hierarchically scaled search for a displacement field, maximizing one of several voxel similarity measures derived from the two-dimensional (2-D) histogram of matched image intensities, subject to a regularizer that ensures smoothness of the displacement field. The effect of the nonlinear structural registration is studied when it is computed on anatomical MR scans and applied to coregistered [15O] water PET scans from the same subjects: in this experiment, a study of visually guided saccadic eye movements. The performance of the nonlinear warp is evaluated using multivariate functional signal and noise measures. These measures prove to be useful for comparing different intersubject registration approaches, e.g., affine versus nonlinear. A comparison of 12-parameter affine registration versus non-linear registration demonstrates that the proposed nonlinear method increases the number of voxels retained in the cross-subject mask. We demonstrate that improved structural registration may result in an improved multivariate functional signal-to-noise ratio (SNR). Furthermore, registration of PET scans using the 12-parameter affine transformations that align the coregistered MR images does not improve registration, compared to 12-parameter affine alignment of the PET images directly.

Algorithms↗
PubMed1999

Autoimmune cholangitis and primary biliary cirrhosis--an autoimmune enigma.

AIMS/BACKGROUND: Autoimmune cholangitis/cholangiopathy (AIC) is an enigmatic disease marked by chronic cholangitis, antinuclear antibodies (ANA) and sero-negativity for conventionally detected antimitochondrial antibodies (AMA). We examined whether AIC is a distinct entity, an AMA-negative variant of primary biliary cirrhosis (PBC), or a cholangiopathic variant of autoimmune hepatitis (AIH) by comparing the clinical, laboratory and autoantibody profiles of 21 cases of AIC, 37 cases PBC and 16 cases of AIH from selected Japanese patients. METHODS: The specificities of AMA and ANA were determined by immunofluorescence, immunoblotting and enzyme inhibition assays using various mitochondrial and nuclear autoantigens, and the frequencies for these groups were compared. RESULTS: By clinical, biochemical and histological data, AIC and PBC were similar and both were clearly distinct from AIH. Serologically, by immunofluorescence of AMA and ANA, there was polarisation. By immunoblotting, and notwithstanding the negative test for AMA, a proportion of the AIC sera reacted with the E2 subunits of the 2-oxo-acid dehydrogenase enzyme complexes, but more particularly with the lower molecular weight E2 subunits. The antinuclear reactivity in AIC was with centromere, Sp100 and nuclear pore complex proteins as in PBC, but preferentially with the nuclear pore complex. CONCLUSION: Our results demonstrate that AIC and PBC are similar diseases. However this duo is of interest because, usually, among sets of autoimmune syndromes, differences in serological targetting are matched by differences in clinical presentation: AIC and PBC are an exception to this.

Adult↗
PubMed1999

Correlation of cytokine elaboration with mononuclear cell adhesion to platelet storage bag plastic polymers: a pilot study.

The basis for many febrile nonhemolytic transfusion reactions associated with platelet transfusion therapy is cytokine elaboration and accumulation in the storage bag, which correlate with the leukocyte content and the length of platelet storage. We propose that a possible additional variable in the elaboration and accumulation of cytokines is the differential adhesion of mononuclear cells to the plastic substrate of the platelet storage bag. We hypothesize that mononuclear cell adhesion-induced cytokine release is greater in random-donor platelet bags composed of the polyolefin polymer compared to the single-donor apheresis platelet bags composed of the polyvinyl chloride polymer with the tri-(2-ethylhexyl) trimellitate (TEHTM) plasticizer. For four blood donors, we demonstrate preferential mononuclear cell adhesion, in vitro, to discs of polyolefin polymer versus discs of polyvinyl chloride polymer with the TEHTM plasticizer. Scanning electron microscopy corroborates this. In addition, proinflammatory cytokine (interleukin 1beta [IL-1beta] and tumor necrosis factor alpha [TNF-alpha]) levels are greater in culture wells containing discs of polyolefin polymer than in those containing discs of polyvinyl chloride polymer with the TEHTM plasticizer, and even more so in storage bags containing polyolefin polymer versus polyvinyl chloride polymer with the TEHTM plasticizer (IL-1beta, TNF-alpha, IL-6, and IL-8). This study suggests, for the first time, that differential plastic substrate mononuclear cell adhesion may contribute to cytokine release during platelet storage. This may represent an additional variable in the pathophysiology of febrile nonhemolytic transfusion reactions in patients receiving stored platelet units.

Blood Platelets↗
PubMed1999

GCD14p, a repressor of GCN4 translation, cooperates with Gcd10p and Lhp1p in the maturation of initiator methionyl-tRNA in Saccharomyces cerevisiae.

Gcd10p and Gcd14p were first identified genetically as repressors of GCN4 mRNA translation in Saccharomyces cerevisiae. Recent findings indicate that Gcd10p and Gcd14p reside in a nuclear complex required for the presence of 1-methyladenosine in tRNAs. Here we show that Gcd14p is an essential protein with predicted binding motifs for S-adenosylmethionine, consistent with a direct function in tRNA methylation. Two different gcd14 mutants exhibit defects in cell growth and accumulate high levels of initiator methionyl-tRNA (tRNAiMet) precursors containing 5' and 3' extensions, suggesting a defect in processing of the primary transcript. Dosage suppressors of gcd10 mutations, encoding tRNAiMet (hcIMT1 to hcIMT4; hc indicates that the gene is carried on a high-copy-number plasmid) or a homologue of human La protein implicated in tRNA 3'-end formation (hcLHP1), also suppressed gcd14 mutations. In fact, the lethality of a GCD14 deletion was suppressed by hcIMT4, indicating that the essential function of Gcd14p is required for biogenesis of tRNAiMet. A mutation in GCD10 or deletion of LHP1 exacerbated the defects in cell growth and expression of mature tRNAiMet in gcd14 mutants, consistent with functional interactions between Gcd14p, Gcd10p, and Lhp1p in vivo. Surprisingly, the amounts of NME1 and RPR1, the RNA components of RNases P and MRP, were substantially lower in gcd14 lhp1::LEU2 double mutants than in the corresponding single mutants, whereas 5S rRNA was present at wild-type levels. Our findings suggest that Gcd14p and Lhp1p cooperate in the maturation of a subset of RNA polymerase III transcripts.

Alleles↗
PubMed1999

Gender-related differences in vascular smooth muscle cell proliferation: implications for prevention of atherosclerosis.

Premenopausal women have a significant reduction in coronary artery disease compared to age-matched males. Little is known about the mechanism underlying this cardioprotective effect of estrogen. Contradictory evidence has been published and our lack of basic understanding of hormone interactions and bioavailability of different estrogens prevents definitive interpretation of these data. We demonstrate gender-specific effects in the proliferation of coronary artery vascular smooth muscle cells obtained from a sexually mature animal model. Vascular smooth muscle cells are an integral component of the atherosclerotic plaque, and inhibition of cell proliferation by estrogen may be one mechanism by which estrogen exerts its cardioprotective effect. Various types of estrogen may also have different mechanistic actions on the vascular system. No differences are demonstrated in overall estradiol binding in vascular smooth muscle cells obtained from male or female animals: however, differences in c-jun, c-fos and TIEG gene expression were gender related. Inhibition of vascular smooth muscle cell proliferation may have important implications in the prevention of atherosclerotic disease and these studies may provide evidence for the cardioprotective effect of estrogen.

Animals↗
PubMed1999

Reflex and muscular adaptations in rat soleus muscle after hindlimb suspension.

Reflex, mechanical and histochemical adaptations of the soleus muscle following 3 weeks of hindlimb suspension (HS) were measured in the rat. HS transformed the soleus muscle fibre type composition from predominantly slow, type I, to approximately equal proportions of fast, type II and slow fibres. Consistent with this transformation was an increase in the maximum shortening velocity, V(max), and a decrease in the stiffness of the series elastic component. Disuse also produced muscle atrophy and a resultant decrease in twitch and tetanic force. Reflex responses of the ankle extensors were also obtained at 5 and 9 weeks of age for six control rats (C group) and six rats subjected to HS for 3 weeks (HS group). The soleus reflexes to a mechanical tap applied to the Achilles tendon (T reflex) and to an electrical stimulation of the sciatic nerve (H reflex) were measured. The maximal amplitude of these reflexes (T(max) and H(max)) were normalised to the maximal direct motor response (M(max)) and the T(max)/H(max) ratio was also calculated to give an index of the relative adaptations of the peripheral and central components of the reflex pathway. The HS group showed significantly higher H reflex gains than the C group, possibly due to changes in synaptic efficiency after HS. Conversely, the HS group presented strongly inhibited T reflexes and negative gains for the T(max)/H(max) ratios. This result indicated a reduced spindle solicitation after HS, which may reflect changes in the spindle sensitivity itself, but it could also be due to the decrease in stiffness of the musculo-tendinous elements in series with the muscle spindles. Such mechanical changes may play an important part in the decreased T reflex responses.

Adaptation, Physiological↗
PubMed1999

Worksite cholesterol and nutrition: an intervention project in Colorado.

The study purpose was to determine whether group intervention or an individual self help program proved to be more effective at lowering heart disease risk factors among employees in different worksites. Eight worksites and 502 employees in the Denver metropolitan area were selected for the project, with four randomized to Usual Care and four to the Special Intervention. Most worksites had < 200 employees. Employees were randomly assigned to either a control group receiving usual nutrition education or one of two special intervention groups in which employees selected to attend group nutrition education classes or complete an individual self paced nutrition education program. Results indicated that offering a choice of methods for the special nutrition education intervention was valuable, and both approaches modified behavior and certain physiological outcomes. Results suggested that enhanced nutrition education efforts in worksites may be effective and will realize greater benefits than a pamphlet or brief discussion following a worksite screening.

Adolescent↗
PubMed1999

Surveillance of construction worker injuries: the utility of trade-specific analysis.

Construction is a dangerous industry, with high rates of both fatal and nonfatal injuries. To learn more about the causes of nonfatal construction worker injuries, and to identify injury cases for further work site-based investigations or prevention programs, we established an emergency department-based surveillance program in November 1990. This article describes circumstances of injury, diagnoses, and demographic characteristics of injured construction workers for 2,791 cases identified through mid-August, 1997. Lacerations and strains and sprains were the most frequent diagnoses; cutting and piercing objects were the leading causes of injury among all construction workers, followed by falls and overexertion. Because of the variety of work performed in this industry, more detailed injury descriptions, by trade, are most useful for thinking about injury prevention. To illustrate this, we profile injury patterns among workers from four specific trades: carpenters, electricians, plumbers, and ironworkers. Areas of concern highlighted by the trade-specific analyses include eye injuries among plumbers; falls from ladders among electricians and plumbers; slips, trips, and falls on the same level among ironworkers; electrical exposure among electricians; and, amputations among carpenters.

Adult↗