A simple and inexpensive medium for culture of splenic aspirates in visceral leishmaniasis.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
K Martin
Publications and source records attributed to K Martin.
Stranger in a strange land: the use of overbreadth in abortion jurisprudence.
Plaintiffs seeking to avoid prosecution under an allegedly unconstitutional statute can ask a court to do one of two things: award facial relief, in which case any enforcement of the offending statutory provision is enjoined, or award as-applied relief, in which case enforcement of the provision against the plaintiff is enjoined, but officials may attempt to apply the statute to others. As-applied relief might also take the form of partial facial invalidation: The provision may not be applied to others similarly situated to the plaintiff. In United States v. Salerno, the Court ruled that judges should only provide total facial invalidation if there is "no set of circumstances" under which the statute could be applied consistent with the Constitution. This general rule, however, has had a historical exception for First Amendment jurisprudence, known as the overbreadth doctrine, and more recently Planned Parenthood v. Casey extended a similar exception to abortion jurisprudence. Most literature has been supportive of this extension, and some have suggested replacing the Salerno rule with the Casey rule as a general matter. This Note argues that the reasons given for the Casey exception are unpersuasive, that Salerno as a matter of history and doctrine is the correct rule to apply to facial challenges, and for that reason that Salerno should remain the general rule and Casey's "large fraction" test should be eliminated.
Abortion, Legal↗
Age changes in stem cells of murine small intestinal crypts.
Cell senescence is seen in many types of differentiated cells but age changes in stem cells have not previously been clearly demonstrated. Changes in stem cells may be of great importance for the ageing process, because any decline with age in the numbers and functional integrity of stem cells can lead to progressive deterioration of function and of proliferative homeostasis in tissues. Stem cells of the murine small intestine provide an excellent model system because these cells occupy a well-defined position near the base of the crypts of Lieberkühn. We examined mice aged between 5 and 32 months and found age-related alterations in the histology of the small intestine and in the apoptotic response of stem cells to low-dose irradiation. Apoptosis in the crypts is concentrated around the stem cell position and can be markedly elevated by exposure to radiation or cytotoxic agents, suggesting that "suicide" of damaged stem cells may be an important system for long-term tissue maintenance. Animals aged 5, 15, 18, and 29 months were exposed to either 1 or 8 Gy gamma irradiation. A twofold increase in the level of apoptosis was seen following 1 Gy gamma irradiation in the 29-month-old animals, compared to the young and middle-age groups. After 8 Gy irradiation the level of apoptosis in all age groups was high and the age effect less pronounced. The data suggest that stem cells do undergo some functional alteration with age.
Aging↗
The acetyltransferase activity of CBP stimulates transcription.
The CBP co-activator protein possesses an intrinsic acetyltransferase (AT) activity capable of acetylating nucleosomal histones, as well as other proteins such as the transcription factors TFIIE and TFIIF. In addition, CBP associates with two other TSs, P/CAF and SRC1. We set out to establish whether the intrinsic AT activity of CBP contributes to transcriptional activation. We show that a region of CBP, encompassing the previously defined histone AT (HAT) domain, can stimulate transcription when tethered to a promoter. The stimulatory effect of this activation domain shows some promoter preference and is dependent on AT activity. Analysis of 14 point mutations reveals a direct correlation between CBP's ability to acetylate histones in vitro and to activate transcription in vivo. We also find that the HAT domains of CBP and P/CAF share sequence similarity. Four conserved motifs are identified, three of which are analogous to motifs A, B and D, found in other N-acetyltransferases. The fourth motif, termed E, is unique to CBP and P/CAF. Mutagenesis shows that all four motifs in CBP contribute to its HAT activity in vitro and its ability to activate transcription in vivo. These results demonstrate that the AT activity of CBP is directly involved in stimulating gene transcription. The identification of specific HAT domain motifs, conserved between CBP and P/CAF, should facilitate the identification of other members of this AT family.
Acetyltransferases↗
An automatic device for the assessment of cardiovascular autonomic function.
Autonomic neuropathy is a common complication of diabetes mellitus and is associated with significant morbidity and possibly an increase in mortality. Despite this, however, autonomic dysfunction is not usually sought in the routine assessment of diabetic patients. We report the development and testing of a small, portable and reliable device that allows the routine testing of cardiac autonomic function in the outpatient setting with minimal inconvenience to the patient. This should facilitate the accurate assessment both of patients with symptoms suggestive of autonomic dysfunction and of autonomic function in research.
Arrhythmias, Cardiac↗
Treating disability in knee osteoarthritis with exercise therapy: a central role for self-efficacy and pain.
OBJECTIVE: To examine the effects of aerobic and resistance exercise on self-efficacy beliefs in older adults with knee osteoarthritis (OA) and to determine whether self-efficacy and knee pain mediated the effects of the treatments on stair time performance and health perceptions. METHODS: Measures of self-efficacy, knee pain, stair climbing performance, and health perceptions were collected prior to randomization and again at an 18-month followup in older adults with knee OA who were assigned to 1 of 3 treatment conditions: aerobic exercise, resistance training, or health education control. All analyses were conducted on the intention-to-treat principle. RESULTS: Both exercise treatments increased self-efficacy for stair climbing in comparison to the health education control group. Both knee pain and self-efficacy mediated the effect of the treatments on stair climb time, whereas only knee pain mediated health perceptions. CONCLUSIONS: The findings suggest that control beliefs and changes in physical symptoms such as knee pain are important outcomes in physical activity programs with patients who have OA of the knee. Moreover, these variables mediate the effects that such programs have on disability and health perceptions.
Adult↗
Costs and benefits of nest cover for ptarmigan: changes within and between years.
Selecting an 'optimal' nest site is believed to be an important component of fitness for birds, but paradoxically there is often considerable intraspecific variation in nest sites. Few studies have tested whether nest-site selection by birds changes after experience with nest predators. Using data collected over 9 years, we examined within- and between-year variation in 331 nests of white-tailed ptarmigan, Lagopus leucurus. We found the first direct evidence for a fitness trade-off with amount of cover at the nest; concealed sites were less often detected by predators but were more risky for incubating hens. Small ptarmigan and those in good body condition used sites with less cover, while large ptarmigan nested at higher elevations. Nesting success was not related to age or spring body condition. Responses to experience with predators were less clear. Successful females tended to use less cover the following year, whereas unsuccessful females tended to change cover types, but not the amount of cover, in subsequent years. Overall, characteristics of nest sites showed strong seasonal patterns, suggesting that microclimate may be a more important selective pressure than predation. Copyright 1998 The Association for the Study of Animal Behaviour.
Journal Article↗
Induction of anesthesia by titration of eltanolone compared with thiopental and etomidate for coronary artery bypass grafting.
STUDY OBJECTIVE: To evaluate whether induction of anesthesia with eltanolone in coronary artery bypass graft (CABG) patients is associated with greater hemodynamic stability than either thiopental sodium or etomidate. DESIGN: Randomized, controlled study. SETTING: University hospital. PATIENTS: 75 ASA physical status III and IV patients scheduled for elective CABG over 18 years of age, with left ventricular ejection fraction over 30%. INTERVENTIONS: The participants were prospectively randomized into three groups, each group consisting of 25 patients. Anesthesia was induced by titration of either eltanolone, thiopental sodium, or etomidate. The end point was "loss of verbal contact." MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables were recorded in the awake state, 2 minutes after induction, after administration of fentanyl 0.01 mg/kg, and 2 and 5 minutes after intubation. After induction of anesthesia, cardiac index (CI) decreased from 2.6 +/- 0.5 to 2.2 +/- 0.5 Lxmin-1xm-2 in the eltanolone group and remained at this value throughout the study period in contrast to the control groups. After fentanyl was given, mean arterial pressure was significantly lower in the case of eltanolone (69 +/- 15 mmHg) compared with thiopental (81 +/- 19 mmHg) and etomidate (84 +/- 18 mmHg). Mean arterial pressure remained significantly lower at the points of measurement after intubation. Two minutes after intubation, CI was likewise significantly lower in the eltanolone group (2.2 +/- 0.4 Lxmin-1xm-2) compared with the thiopental group (2.7 +/- 0.7 Lxmin-1xm-2). CONCLUSIONS: Eltanolone produces more hemodynamic depression compared with etomidate and thiopental when administered in combination with fentanyl 10 micrograms/kg.
Aged↗
General practitioners' attitudes to psychiatric and medical illness.
BACKGROUND: General practitioners are increasingly involved in the care of patients with long-term psychiatric disorders. We have previously reported that general practitioners are less willing to treat patients with schizophrenia than those without such a diagnosis, but this may have been attributable to a reluctance to treat patients with any psychiatric or chronic illness. We, therefore, examined general practitioners' attitudes to patients with chronic psychiatric or medical illnesses. METHODS: A random sample of 260 local general practitioners were each sent one of our case vignettes which were identical apart from mention of a previous diagnosis of schizophrenia, depression, diabetes or no illness. The general practitioners were asked to indicate their level of agreement with 13 attitudinal statements based on the vignette. RESULTS: One hundred and sixty-six (66%) of the general practitioners responded to the case vignettes. Those responding to the vignette about the patient with schizophrenia were less happy to have that patient on their practice list and were more concerned about the risk of violence and the child's welfare. Those responding to the depression vignette were more likely to offer the patient antidepressants or counselling; and those who replied to the diabetes case were most likely to refer the patient to a hospital specialist. These differences were not attributable to the personal or practice characteristics of the general practitioners. CONCLUSIONS: Patients with schizophrenia arouse concerns in general practitioners that are not simply due to those patients suffering from a psychiatric or chronic illness. Our results suggest that some patients with schizophrenia may find it difficult to register with a general practitioner and receive the integrated community-based health care service they require. Psychiatrists should provide education and support to general practitioners who look after patients with schizophrenia.
Adult↗
Reversal of P-glycoprotein-mediated multidrug resistance by XR9051, a novel diketopiperazine derivative.
XR9051 (N-(4-(2-(6,7-Dimethoxy-1,2,3,4-tetrahydro-2-isoquinolyl)ethyl)phe nyl)-3-((3Z,6Z)-6-benzylidene-1-methyl-2,5-dioxo-3-pipera zinylidene) methylbenzamide) was identified as a potent modulator of P-glycoprotein-mediated multidrug resistance (MDR) following a synthetic chemistry programme based on a natural product lead compound. The activity of XR9051 was determined using a panel of human and murine drug-resistant cell lines (H69/LX4, 2780AD, EMT6/AR 1.0, MC26 and P388/DX Johnson). XR9051 was able to reverse resistance to a variety of cytotoxic drugs, including doxorubicin, etoposide and vincristine, which are associated with classical MDR. At a concentration of 0.3-0.5 microM, XR9051 was able to fully sensitize resistant cells to cytotoxics, whereas little or no effect was observed on the corresponding parental cell lines. No effect of XR9051 was observed on the response of cells to non-MDR cytotoxics such as methotrexate and 5-fluorouracil. XR9051 was consistently more potent than cyclosporin A (CsA) and verapamil (Vpm) in all assays used. XR9051 inhibited the efflux of [3H]daunorubicin from preloaded cells and, unlike CsA and Vpm, remained active for several hours after removal of resistance-modifying agent. In photoaffinity labelling experiments employing [3H]azidopine, XR9051 was able to displace binding to P-glycoprotein. In binding studies using [3H]vinblastine, XR9051 was shown to be a potent inhibitor of the binding of the cytotoxic to P-glycoprotein (EC50 = 1.4 +/- 0.5 nM). Taken together, the results indicate that XR9051 reverses the MDR phenotype through direct interaction with P-glycoprotein.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Skin2--an in vitro human skin model: the correlation between in vivo and in vitro testing of surfactants.
The availability of an in vitro test system to replace animal testing of potential irritants is becoming more and more urgent especially in Europe as a consequence of the European Community Cosmetics Directive. To evaluate the ability of Advanced Tissue Sciences' (ATS) ZK1301 skin model to predict the skin irritation potential of surfactants, we performed a pilot validation study utilizing four different laboratories. The in vitro protocol was designed as a quantitative pre-screen for the clinical patch studies. Sixteen substances, representing various surfactant categories and ranges of irritation potential, were tested. The 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was used to quantitate viability in vitro. We documented the viability of tissues exposed to unknown substances for specific periods. The in vitro results were calculated as percent distilled water controls (DWC). The time required to reduce the viability of each tissue to 50% of the distilled water controls (T50) was compared to mean erythema and edema scores from the clinical studies by Pearson's correlation. The individual laboratories demonstrated coefficients of 0.72. The results indicated that the 30 min percent untreated control values best predicted the 24 h clinical patch scores. No statistically significant interlab variability was found. Only one false negative was seen when non/mild and moderate/severe irritant categories were assigned according to the in vitro scores. These results demonstrate that the skin2 in vitro test system may serve as a good screening method prior to clinical patch studies.
Adolescent↗
The tryptophanase gene cluster of Haemophilus influenzae type b: evidence for horizontal gene transfer.
Among strains of Haemophilus influenzae, the ability to catabolize tryptophan (as detected by indole production) varies and is correlated with pathogenicity. Tryptophan catabolism is widespread (70 to 75%) among harmless respiratory isolates but is nearly universal (94 to 100%) among strains causing serious disease, including meningitis. As a first step in investigating the relationship between tryptophan catabolism and virulence, we have identified genes in pathogenic H. influenzae which are homologous to the tryptophanase (tna) operon of Escherichia coli. The tna genes are located on a 3.1-kb fragment between nlpD and mutS in the H. influenzae type b (Eagan) genome, are flanked by 43-bp direct repeats of an uptake signal sequence downstream from nlpD, and appear to have been inserted as a mobile unit within this sequence. The organization of this insertion is reminiscent of pathogenicity islands. The tna cluster is found at the same map location in all indole-positive strains of H. influenzae surveyed and is absent from reference type d and e genomes. In contrast to H. influenzae, most other Haemophilus species lack tna genes. Phylogenetic comparisons suggest that the tna cluster was acquired by intergeneric lateral transfer, either by H. influenzae or a recent ancestor, and that E. coli may have acquired its tnaA gene from a related source. Genomes of virulent H. influenzae resemble those of pathogenic enterics in having an island of laterally transferred DNA next to mutS.
Amino Acid Sequence↗
A tyrosine-rich region in the N terminus of CCR5 is important for human immunodeficiency virus type 1 entry and mediates an association between gp120 and CCR5.
Human immunodeficiency virus type 1 (HIV-1) requires the presence of specific chemokine receptors in addition to CD4 to enter target cells. The chemokine receptor CCR5 is used by the macrophage-tropic strains of HIV-1 that predominate during the asymptomatic stages of infection. Here we identify a small tyrosine-rich region of CCR5 proximal to the N-terminal cysteine that is critical for entry of macrophage-tropic and dual-tropic variants of HIV-1. HIV-1 infection of cells expressing CCR5 mutants with changes in this region was substantially reduced compared with the infection of cells bearing wild-type CCR5. Simian immunodeficiency virus (SIVmac239) entry was also ablated on a subset of these mutants but enhanced on others. These differences in virus entry were correlated with the relative ability of soluble, monomeric HIV-1 and SIVmac239 gp120 glycoproteins to bind the CCR5 mutants. These results identify a region of CCR5 that is necessary for the physical association of the gp120 envelope glycoprotein with CCR5 and for HIV-1 infection.
Animals↗
The orphan seven-transmembrane receptor apj supports the entry of primary T-cell-line-tropic and dualtropic human immunodeficiency virus type 1.
Human immunodeficiency virus type 1 (HIV-1) enters target cells by sequential binding to CD4 and specific seven-transmembrane-segment (7TMS) coreceptors. Viruses use the chemokine receptor CCR5 as a coreceptor in the early, asymptomatic stages of HIV-1 infection but can adapt to the use of other receptors such as CXCR4 and CCR3 as the infection proceeds. Here we identify one such coreceptor, Apj, which supported the efficient entry of several primary T-cell-line tropic (T-tropic) and dualtropic HIV-1 isolates and the simian immunodeficiency virus SIVmac316. Another 7TMS protein, CCR9, supported the less efficient entry of one primary T-tropic isolate. mRNAs for both receptors were present in phytohemagglutinin- and interleukin-2-activated peripheral blood mononuclear cells. Apj and CCR9 share with other coreceptors for HIV-1 and SIV an N-terminal region rich in aromatic and acidic residues. These results highlight properties common to 7TMS proteins that can function as HIV-1 coreceptors, and they may contribute to an understanding of viral evolution in infected individuals.
Amino Acid Sequence↗
Altered stem cell regeneration in irradiated intestinal crypts of senescent mice.
Ageing is associated with a progressive deterioration in the functions of many organs within the body. In tissue with high cell turnover, the maintenance of the stem cells is of particular importance. Any accumulation of damage in stem cells may affect their function and hence threaten the homeostasis and regenerative capacity of the tissue. The small intestine represents a good model for the study of stem cells because of its spatial and hierarchical organisation. We have examined the effect of age on stem cell regenerative capacity after irradiation, using the microcolony assay. Crypt survival levels, the growth rate of surviving crypts, and the number of cells able to repopulate a crypt have been investigated by irradiating groups of 6-7 month old and 28-30 month old ICRFa male mice. After high doses of irradiation, the surviving crypts in old mice were both smaller and fewer in number than in young mice. The growth rate of surviving crypts was determined by measuring the crypt area and the number of cells/crypt at various times after 14 Gy irradiation. There was a growth delay of between about one half and one day in the older mice. Surprisingly, the number of clonogenic cells per crypt was estimated to be greater in the older mice. These studies indicate important age-related alterations in the capacity to regenerate the crypts after radiation damage.
Aging↗
A comparative analysis of integrating visual representations with haptic displays.
As further advances in visual display technologies and force feedback devices are integrated in virtual systems, questions remain: What level of reality does the system provide to the user? Is the environment convincing enough to engage the user and to maximize transfer? Are the visual and haptic displays fully integrated to provide seamless operation in the simulated environment? Does the system provide not only the ability to navigate through a simulated environment, but also realistic interaction with instrumentation and structures? We report on our advances in developing a virtual simulation system for training in functional endoscopic sinus surgery (FESS). Specifically, we will present work on subject trials exploring the realism provided by integrated visual and haptic displays, and compare and contrast surface vs. volume representation for presenting realistic models of the anatomy for surgical interaction.
Computer Simulation↗
A comparison of the efficacies and duration of action of the angiotensin II receptor blockers telmisartan and amlodipine.
OBJECTIVES: To compare the antihypertensive effects and duration of action of the angiotensin II receptor antagonist, telmisartan, amlodipine, and placebo in patients with mild-to-moderate hypertension using both conventional clinic blood pressures and ambulatory blood pressure monitoring (ABPM). METHODS: After a 4-week single-blind, placebo run-in period, qualifying patients were randomly allocated in double-blind manner to be administered 40 mg telmisartan (n = 73; increased to 80 and 120 mg as necessary for patients whose diastolic blood pressure (DBP) remained > 90 mmHg); 5 mg amlodipine (n = 78; titrated to 5 mg and titrated to 10 mg for patients whose DBP remained > 90 mmHg); or placebo (n = 81). ABPM was performed at the end of the baseline period and again at the end of 12 weeks of double-blind treatment. RESULTS: Telmisartan and amlodipine treatments significantly decreased trough supine systolic blood pressure and DBP (P < 0.001, measured conventionally) to a similar extent (by 13.1/7.1 and 14.0/7.1 mmHg, respectively, at the end of 12 weeks' treatment) compared with placebo. Both drugs also significantly reduced 24 h mean systolic blood pressures and DBP compared with placebo (P < 0.0001), measured using ABPM, maintaining control of blood pressure throughout the dosing period. Reductions in DBP with telmisartan were greater (P < 0.05) than those with amlodipine during the night-time interval and the last 4 h of the dosing period. Twenty-four-hour mean ABPM DBP < 85 mmHg were observed in 71% of telmisartan patients and in 55% of patients administered amlodipine. In addition, heart rates in patients treated with telmisartan were lower than heart rates in those treated with amlodipine during the final 4 h of the dosing period (P = 0.0003) and during the morning interval (P = 0.005). Generally, both telmisartan and amlodipine were well tolerated, however, drug-related edema occurred significantly more commonly (P < 0.05) among the patients administered amlodipine than it did among patients administered either telmisartan or placebo. CONCLUSIONS: Clinic blood pressure measurements detected no difference between the antihypertensive effects and durations of action of telmisartan and amlodipine, both agents producing statistically significant reductions compared with placebo. ABPM measurements, however, revealed differences between the efficacies at specific time points within the dosing periods. These findings highlight the potential importance of the use of ABPM for evaluating and comparing efficacies of antihypertensive agents.
Journal Article↗
Isolation of circovirus from lesions of pigs with postweaning multisystemic wasting syndrome.
Postweaning multisystemic wasting syndrome (PMWS), an apparently new disease, has been recognized in swine herds in western Canada. Young pigs with this disease have progressive weight loss, tachypnea, dyspnea, and jaundice, accompanied by interstitial pneumonia, lymphadenopathy, hepatitis, and nephritis. We examined more than 400 pigs from more than 70 herds in Alberta, Saskatchewan, and Manitoba with cases of PMWS. A small virus was isolated from a range of tissues from 8 of 8 affected pigs examined. The agent was identified as a circovirus-like virus using electron microscopy, immunohistochemical staining with porcine and rabbit immune serum, and in situ hybridization. Immunohistochemical examination of tissues from more than 100 affected pigs has revealed widespread viral antigen, often contained in circovirus-like inclusion bodies, in lesions from numerous organs. Although Koch's postulates remain to be fulfilled, these results demonstrate a high degree of association between the presence of the circovirus-like virus and PMWS in affected swine.
Alberta↗