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Biomedical subjects

P Mason

Publications and source records attributed to P Mason.

At least 37 records · Page 2Linked to original sources

Constraints faced by sex workers in use of female and male condoms for safer sex in urban zimbabwe.

We investigated whether female condoms are acceptable to sex workers in Harare and whether improved access to male and female condoms increases the proportion of protected sex episodes with clients and boyfriends. Sex workers were randomly placed in groups to receive either male and female condoms (group A, n = 99) or male condoms only (group B, n = 50) and were followed prospectively for about 3 months each. We found a considerable burden of human immunodeficiency virus (HIV) and sexually transmitted infections (STIs) in our cohort at enrollment (86% tested HIV positive and 34% had at least one STI). Consistent male condom use with clients increased from 0% to 52% in group A and from 0% to 82% in group B between enrollment and first follow-up 2 weeks later and remained high throughout the study. Few women in group A reported using female condoms with clients consistently (3%-9%), and use of either condom was less common with boyfriends than with clients throughout the study (8%-39% for different study groups, visits, and types of condom). Unprotected sex still took place, as evidenced by an STI incidence of 16 episodes per 100 woman-months of follow-up. Our questionnaire data indicated high self-reported acceptability of female condoms, but focus group discussions revealed that a main obstacle to female condom use was client distrust of unfamiliar methods. This study shows that a simple intervention of improving access to condoms can lead to more protected sex episodes between sex workers and clients. However, more work is needed to help sex workers achieve safer sex in noncommercial relationships.

Adult↗

Contributions of the medullary raphe and ventromedial reticular region to pain modulation and other homeostatic functions.

The raphe magnus is part of an interrelated region of medullary raphe and ventromedial reticular nuclei that project to all areas of the spinal gray. Activation of raphe and reticular neurons evokes modulatory effects in sensory, autonomic, and motor spinal processes. Two physiological types of nonserotonergic cells are observed in the medullary raphe and are thought to modulate spinal pain processing in opposing directions. Recent evidence suggests that these cells may modulate stimulus-evoked arousal or alerting rather than pain-evoked withdrawals. Nonserotonergic cells are also likely to modulate spinal autonomic and motor circuits involved in thermoregulation and sexual function. Medullary serotonergic cells have state-dependent discharge and are likely to contribute to the modulation of pain processing, thermoregulation, and sexual function in the spinal cord. The medullary raphe and ventromedial reticular region may set sensory, autonomic, and motor spinal circuits into configurations that are appropriate to the current behavioral state.

Animals↗

Classification and identification of Pfiesteria and Pfiesteria-like species.

Dinoflagellates can be classified both botanically and zoologically; however, they are typically put in the botanical division Pyrrhophyta. As a group they appear most related to the protistan ciliates and apicomplexans at the ultrastructure level. Within the Pyrrhophyta are both unarmored and armored forms of the dominant, motile flagellated stage. Unarmored dinoflagellates do not have thecal or wall plates arranged in specific series, whereas armored species have plates that vary in thickness but are specific in number and arrangement. In armored dinoflagellates, the plate pattern and tabulation is a diagnostic character at the family, subfamily, and even genus levels. In most cases, the molecular characterization of dinoflagellates confirms the taxonomy on the basis of external morphology; this has been demonstrated for several groups. Together, both genetic and morphological criteria are becoming increasingly important for the characterization, separation, and identification of dinoflagellates species. Pfiesteria and Pfiesteria-like species are thinly armored forms with motile dinospore stages characterized by their distinct plate formulae. Pfiesteria piscicida is the best-known member of the genus; however, there is at least one other species. Other genetically and morphologically related genera, now grouped under the common names of "Lucy," "Shepherd's crook," and cryptoperidiniopsoid, are being studied and described in separate works. All these other heterotrophic dinoflagellate groups, many of which are thought to be benign, co-occur in estuarine waters where Pfiesteria has been found.

Animals↗

Prenatal transmission of subtype C HIV-1 in Zimbabwe: HIV-1 RNA and DNA in maternal and cord blood.

Maternal and cord samples from HIV-seropositive women and their infants in Zimbabwe, where subtype C is the predominant strain of HIV, were analyzed to determine the frequency of detection of HIV RNA and DNA. HIV RNA was detected in 90% of maternal and in 38% of cord plasma at levels at least 25% of maternal plasma. Heteroduplex mobility assays and sequencing of virus envelope (C2-V5) demonstrated closely related, but unique, subtype C viruses in maternal and cord RNA, and a significantly greater frequency of cord viremia among women with homogenous, compared with heterogeneous viral envelope RNA. Quantification of RNA, measures of envelope viral diversity, and phylogenetic analysis of maternal and cord plasma RNA provide evidence for the frequent exposure and potential transmission of HIV from mother to infant before birth.

Adult↗

The slow-binding inhibition of cathepsin K by its propeptide.

A peptide corresponding to the full-length proregion (amino acids 16-114) of human cathepsin K was expressed and purified from Escherichia coli. This recombinant propeptide was investigated for its ability to inhibit the activity of three cysteine proteinases: cathepsins K, L, and B. Kinetic studies showed the propeptide to be a potent slow-binding inhibitor of its parent enzyme with a K(i) = 2. 61 nM at pH 6. This inhibition was pH-dependent, with a decrease in pH from 6 to 4 leading to a concomitant increase in K(i) to 147 nM. The propeptide also inhibited cathepsin L with a K(i) = 26.1 nM at pH 6, but showed little inhibition of cathepsin B at concentrations up to 400 nM.

Antibodies, Monoclonal↗

P-TEFb kinase recruitment and function at heat shock loci.

P-TEFb, a heterodimer of the kinase Cdk9 and cyclin T, was isolated as a factor that stimulates formation of productive transcription elongation complexes in vitro. Here, we show that P-TEFb is located at >200 distinct sites on Drosophila polytene chromosomes. Upon heat shock, P-TEFb, like the regulatory factor HSF, is rapidly recruited to heat shock loci, and this recruitment is blocked in an HSF mutant. Yet, HSF binding to DNA is not sufficient to recruit P-TEFb in vivo, and HSF and P-TEFb immunostainings within a heat shock locus are not coincident. Insight to the function of P-TEFb is offered by experiments showing that the direct recruitment of a Gal4-binding domain P-TEFb hybrid to an hsp70 promoter in Drosophila cells is sufficient to activate transcription in the absence of heat shock. Analyses of point mutants show this P-TEFb stimulation is dependent on Cdk9 kinase activity and on Cdk9's interaction with cyclin T. These results, coupled with the frequent colocalization of P-TEFb and the hypophosphorylated form of RNA polymerase II (Pol II) found at promoter-pause sites, support a model in which P-TEFb acts to stimulate promoter-paused Pol II to enter into productive elongation.

Animals↗

The LIM-domain protein FHL1 (SLIM 1) exhibits functional regulation in skeletal muscle.

The LIM domain protein FHL1 (SLIM 1) transcript is preferentially expressed in postnatal skeletal muscle but almost nothing is known about its function in this tissue. In this study we have examined the expression of the FHL1 transcript at the cellular level by in situ hybridisation. Muscle fibers exist as a number of discrete subpopulations or "types" which are differentiated by their contractile and metabolic properties. It was observed that the FHL1 transcript was not fiber-type specific but was however more abundant in oxidative fibers. Muscle atrophy induced by disuse caused a significant decline in the expression of the transcript but atrophy induced by short-term denervation did not. Hypertrophy of skeletal muscle induced by passive stretch was associated with an up-regulation of the FHL1 transcript. These data are consistent that FHL1 is involved in synthetic processes within the muscle fibre.

Animals↗

High prevalence of diarrhea but infrequency of documented Clostridium difficile in autologous peripheral blood progenitor cell transplant recipients.

Autologous peripheral blood progenitor cell (PBPC) transplant recipients frequently receive multiple antibiotics for neutropenic fever in addition to high-dose chemotherapy. Although there are many possible causes for diarrhea in this population, empiric therapy for possible C. difficile colitis is common in some centers. This study sought to define the frequency of diarrhea and of a positive C. difficile toxin assay in PBPC transplant recipients. Data were collected on 80 patients enrolled in a randomized trial of two different antibiotic regimens during PBPC transplant. Data included the presence or absence of diarrhea, all microbiologic studies performed during the transplant admission, and all antimicrobials administered during the transplant admission. Of 80 patients enrolled, 61 (76.3%) developed diarrhea. Only 3/61 (4.9%) had a positive C. difficile toxin assay. A total of 122 C. difficile toxin assays were performed; for each positive C. difficile assay, 41 stool samples were analyzed. Twenty courses of oral metronidazole (18/20 empiric) and 10 courses of oral vancomycin (8/10 empiric) were given. A total of 25 of 61 patients with diarrhea (41%) received therapy for possible C. difficile. Diarrhea is common during autologous PBPC transplant but a positive C. difficile assay is uncommon. The practice of empiric therapy for C. difficile in this population in a non-outbreak setting should be re-evaluated. Bone Marrow Transplantation (2000) 25, 67-69.

Administration, Oral↗

Impact of quality improvement activities on care for acute myocardial infarction.

OBJECTIVE: To examine the relationship between quality improvement activities reported to a peer review organization (PRO) and improvements in quality of care for patients with acute myocardial infarction (AMI). DESIGN: Time-series, comparative study of changes in care for AMI patients from 1992 to 1995 in hospitals reporting self-measurement or system changes compared to all other hospitals in the state. SETTING: One-hundred and seventeen acute care hospitals in Iowa. STUDY PARTICIPANTS: Patients hospitalized with a principal diagnosis of AMI. INTERVENTIONS: Each hospital was given hospital-specific performance data, statewide aggregate data, and peer comparisons and was asked to provide the PRO with a plan to improve care for AMI patients. MEASUREMENTS: Chart audits were performed before and after the intervention. Quality of care was based on eight explicit process measures of the quality of AMI care (quality indicators). RESULTS: Statewide, quality of care improved on five out of eight quality indicators. Of the 117 hospitals, 44 (38%) reported that they had implemented their own measurement activities or systematic improvements. These 44 hospitals showed significantly greater improvements than the other hospitals in use of aspirin during the hospitalization, recommendations for aspirin at discharge, and prescriptions for beta blockers at discharge. CONCLUSIONS: While quality of care for AMI patients throughout Iowa is improving, the pace of improvement is greatest in hospitals reporting that they are measuring their own performance or implementing systematic changes in care processes. Continued efforts to encourage hospitals to implement these types of improvement activities are warranted.

Cardiology Service, Hospital↗

Serotonergic Raphe magnus cells that respond to noxious tail heat are not ON or OFF cells.

Pharmacological studies have suggested that serotonergic cells in RM contribute to both the inhibition and facilitation of spinal nociceptive transmission. Physiological studies in the medullary nucleus raphe magnus (RM) and adjacent nucleus reticularis magnocellularis have identified putative nociceptive-inhibitory OFF cells and nociceptive-facilitatory neurons ON cells by their responses to noxious thermal stimulation. The present study was designed to determine 1) whether any serotonergic RM cells respond to noxious thermal stimulation and 2) whether noxious heat-responsive serotonergic cells should be classified as ON or OFF cells. Serotonergic cells (n = 150) were identified by physiological criteria in anesthetized rats; 30 of 32 cells tested contained serotonin immunoreactivity. Noxious tail heat elicited a neuronal response in less than a quarter of the serotonergic cells. Most serotonergic cells that responded to tail heat were excited (n = 25), while a small minority of the cells tested were inhibited (n = 8). The tail heat-evoked responses of serotonergic cells were small in magnitude, averaging five to eight spikes in 10 s. Excitatory responses rarely persisted for more than 10 s, while inhibitory responses rarely persisted for more than 20 s. The tail heat-evoked responses of serotonergic cells were compared to those of non-serotonergic cells (n = 186). Non-serotonergic cells that responded to noxious tail heat had significantly greater response magnitudes, averaging 75-95 spikes in 10 s, than heat-responsive serotonergic cells. In addition, most heat-responsive non-serotonergic cells responded for at least 30 s after stimulus onset. These results demonstrate that the tail heat-evoked responses of serotonergic RM cells are qualitatively and quantitatively distinct from those of non-serotonergic ON and OFF cells. It is therefore unlikely that serotonergic RM cells, even the subpopulation that responds to noxious tail heat, share a physiological function with ON and OFF cells.

Animals↗

[Alloreactive helper T cell responses in kidney transplant patients].

OBJECTIVE: To study allo-specific immune responses of CD4+ helper T lymphocytes (Th) in patients with long-term and well-functioning renal grafts. METHODS: Peripheral blood mononuclear cells (PBMC) were collected from 16 patients with long-term (3-15 years) and well-functioning live-related renal grafts. Donor-specific Th precursor (Th-p) frequencies in the PBMC were determined by limiting dilution analysis(LDA). RESULTS: Eight out of the 16 patients showed donor-specific hyporesponsiveness. Donor-specific Th-p from the other 8 patients was susceptible to anti-CD4 inhibition. CONCLUSION: Some of the patients carrying long-term and well-functioning renal grafts had become immunologic tolerant to donor cells. Donor-specific Th-p from patients who did not show donor-specific hyporesponsiveness were of low avidity type.

Adult↗

The novel sarcomeric protein telethonin exhibits developmental and functional regulation.

We have isolated a cDNA clone from a mouse skeletal muscle library which is preferentially expressed in striated muscle and exhibits a high homology to human telethonin, a sarcomeric protein. The mouse telethonin transcript is developmentally regulated in both cardiac and skeletal muscle in vivo and is down-regulated in response to denervation. In the C2C12 muscle cell-line the mouse telethonin transcript exhibited a pattern of accumulation similar to that observed for a contractile protein and suggests a role in myofibrillar assembly.

Amino Acid Sequence↗

Low temperature and pressure stability of picornaviruses: implications for virus uncoating.

The family Picornaviridae includes several viruses of great economic and medical importance. Poliovirus replicates in the human digestive tract, causing disease that may range in severity from a mild infection to a fatal paralysis. The human rhinovirus is the most important etiologic agent of the common cold in adults and children. Foot-and-mouth disease virus (FMDV) causes one of the most economically important diseases in cattle. These viruses have in common a capsid structure composed of 60 copies of four different proteins, VP1 to VP4, and their 3D structures show similar general features. In this study we describe the differences in stability against high pressure and cold denaturation of these viruses. Both poliovirus and rhinovirus are stable to high pressure at room temperature, because pressures up to 2.4 kbar are not enough to promote viral disassembly and inactivation. Within the same pressure range, FMDV particles are dramatically affected by pressure, with a loss of infectivity of more than 4 log units observed. The dissociation of polio and rhino viruses can be observed only under pressure (2.4 kbar) at low temperatures in the presence of subdenaturing concentrations of urea (1-2 M). The pressure and low temperature data reveal clear differences in stability among the three picornaviruses, FMDV being the most sensitive, polio being the most resistant, and rhino having intermediate stability. Whereas rhino and poliovirus differ little in stability (less than 10 kcal/mol at 0 degrees C), the difference in free energy between these two viruses and FMDV was remarkable (more than 200 kcal/mol of particle). These differences are crucial to understanding the different factors that control the assembly and disassembly of the virus particles during their life cycle. The inactivation of these viruses by pressure (combined or not with low temperature) has potential as a method for producing vaccines.

Adult↗

Central mechanisms of pain modulation.

Bulbospinal serotonergic neurons and two physiological classes of bulbospinal nonserotonergic cells interact to modulate pain transmission. Recent studies have begun to elaborate targets of descending pain modulation other than the well-studied flexion withdrawal pathways. Site-specific, naloxone-sensitive placebo analgesia, which is hard to reconcile with current models of descending pain modulation, presents an exciting challenge to the field.

Analgesics↗

Physiological properties of raphe magnus neurons during sleep and waking.

Neurons in the medullary raphe magnus (RM) that are important in the descending modulation of nociceptive transmission are classified by their response to noxious tail heat as ON, OFF, or NEUTRAL cells. Experiments in anesthetized animals demonstrate that RM ON cells facilitate and OFF cells inhibit nociceptive transmission. Yet little is known of the physiology of these cells in the unanesthetized animal. The first aim of the present experiments was to determine whether cells with ON- and OFF-like responses to noxious heat exist in the unanesthetized rat. Second, to determine if RM cells have state-dependent discharge, the activity of RM neurons was recorded during waking and sleeping states. Noxious heat applied during waking and slow wave sleep excited one group of cells (ON-U) in unanesthetized rats. Other cells were inhibited by noxious heat (OFF-U) applied during waking and slow wave sleep states in unanesthetized rats. NEUTRAL-U cells did not respond to noxious thermal stimulation applied during either slow wave sleep or waking. ON-U and OFF-U cells were more likely to respond to noxious heat during slow wave sleep than during waking and were least likely to respond when the animal was eating or drinking. Although RM cells rarely respond to innocuous stimulation applied during anesthesia, ON-U and OFF-U cells were excited and inhibited, respectively, by innocuous somatosensory stimulation in the unanesthetized rat. The spontaneous activity of >90% of the RM neurons recorded in the unanesthetized rat was influenced by behavioral state. OFF-U cells discharged sporadically during waking but were continuously active during slow wave sleep. By contrast, ON-U and NEUTRAL-U cells discharged in bursts during waking and either ceased to discharge entirely or discharged at a low rate during slow wave sleep. We suggest that OFF cell discharge functions to suppress pain-evoked reactions during sleep, whereas ON cell discharge facilitates pain-evoked responses during waking.

Action Potentials↗

Dedicated education units: 1. A new concept for clinical teaching and learning.

The Dedicated Education Unit (DEU) is a new concept in clinical nurse education. The DEU plays a major role in enhancing links between health care providers and The Flinders University of South Australia (FUSA) School of Nursing. This collaborative venture has created a more positive clinical learning environment, maximized the achievement of student learning outcomes, and nurtured closer partnership between clinicians and academics. Recognition of mutuality, respect and trust among all stakeholders is central to its success. This paper (part one) explains the rationale for the DEU and describes its inherent values. Part two reports on an evaluation of the DEU.

Academic Medical Centers↗