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Biomedical subjects

L Meadows

Publications and source records attributed to L Meadows.

At least 19 recordsLinked to original sources
PubMed2001

The intracellular segment of the sodium channel beta 1 subunit is required for its efficient association with the channel alpha subunit.

Sodium channels consist of a pore-forming alpha subunit and auxiliary beta 1 and beta 2 subunits. The subunit beta 1 alters the kinetics and voltage-dependence of sodium channels expressed in Xenopus oocytes or mammalian cells. Functional modulation in oocytes depends on specific regions in the N-terminal extracellular domain of beta 1, but does not require the intracellular C-terminal domain. Functional modulation is qualitatively different in mammalian cells, and thus could involve different molecular mechanisms. As a first step toward testing this hypothesis, we examined modulation of brain Na(V)1.2a sodium channel alpha subunits expressed in Chinese hamster lung cells by a mutant beta1 construct with 34 amino acids deleted from the C-terminus. This deletion mutation did not modulate sodium channel function in this cell system. Co-immunoprecipitation data suggest that this loss of functional modulation was caused by inefficient association of the mutant beta 1 with alpha, despite high levels of expression of the mutant protein. In Xenopus oocytes, injection of approximately 10,000 times more mutant beta 1 RNA was required to achieve the level of functional modulation observed with injection of full-length beta 1. Together, these findings suggest that the C-terminal cytoplasmic domain of beta 1 is an important determinant of beta1 binding to the sodium channel alpha subunit in both mammalian cells and Xenopus oocytes.

Animals↗
PubMed2000

Risk factors for suicide attempts among African American women.

The aim of this study was to examine psychological and interpersonal risk factors for suicidal behavior in low income, African American women; 285 African American women who reported being in a relationship with a partner in the past year were studied, 148 presented to the hospital following a suicide attempt, and 137 presented for general medical care. Cases were compared to controls with respect to psychological symptoms, alcohol and drug abuse, family violence (intimate partner abuse, childhood trauma), relationship discord, and social support. Psychological risk factors for suicide attempts at the univariate level included psychological distress [Crude Odds Ratio (COR) = 6.5], post traumatic stress disorder (PTSD) symptoms (COR = 3.8), hopelessness (COR = 7.7), and drug abuse (COR = 4.2). Interpersonal risk factors at the univariate level included relationship discord (COR = 4.0), physical partner abuse (COR = 2.5), nonphysical partner abuse (COR = 2.8), childhood maltreatment (COR = 3.2), and low levels of social support (COR = 2.6). A multivariate logistic regression model identified four variables that were strongly and independently associated with an increased risk for suicide attempts: psychological distress, hopelessness, drug abuse, and relationship discord. The model predicted suicide attempt status correctly 77% of the time. The results reveal that African American women who report high levels of psychological distress, hopelessness, drug use, and relationship discord should be assessed carefully for suicidal ideation and referred for appropriate mental health care.

Adaptation, Psychological↗
PubMed2000

Analysis of Drosophila salivary gland, epidermis and CNS development suggests an additional function of brinker in anterior-posterior cell fate specification.

Salivary glands are simple structured organs which can serve as a model system in the study of organogenesis. Following a large EMS mutagenesis we have identified a number of genes required for normal salivary gland development. Mutations in the locus small salivary glands-1 (ssg-1) lead to a drastic reduction in the size of the salivary glands. The gene ssg-1 was cloned and subsequent sequence and genetic analysis showed identity to the recently published gene brinker. The salivary gland placode in brinker mutants appears reduced along both the anterior-posterior and dorso-ventral axis. Analysis of the brinker cuticle phenotype revealed a similar loss of anterior-posterior as well as lateral cell fates. The abdominal ventral denticle belts show a reduced number of setae in the first denticle row. Furthermore, we observed a preferential loss of lateral neuroblasts in the anterior parasegment. Together, these phenotypes suggest that brinker not only plays a role in dorso-ventral but also in anterior-posterior axis patterning.

Adhesins, Bacterial↗
PubMed1999

Experience with procedural sedation in a pediatric burn center.

BACKGROUND: Burn care requires daily debridement, dressing changes, and assessment regarding the need for skin grafting. These procedures are painful and may require an operating room environment. METHODS: The authors reviewed their experience with 912 consecutive procedural sedations (PS) in 220 pediatric burn patients over a 2-year period to identify what influence PS had on patient care. Median patient age was 32 months, and body surface area burn was 7.2%+/-6%. Pharmacological techniques included oral and intravenous medications and N2O. The authors included all sedations given in the burn treatment area and excluded all treatments given in the intensive care unit or emergency unit. RESULTS: PS allowed for early aggressive wound debridement, virtually eliminated the need for operating room debridement (used in only 22 patients), and eliminated patient discomfort and fear often associated with subsequent debridements. Burn wound-related complications occurred in 54 patients and included wound infection (n = 18), graft loss (n = 9), and pneumonia (n = 4). The incidence of PS complications was 7% with the most common problems including decreased arterial saturation (n = 41), emesis (n = 11), and agitation (n = 8). No patient required intubation or transfer to an intensive care unit bed. The average length of stay (LOS) for all patients was 8.7+/-6.2 days, and 6.2+/-3.8 days in the 200 patients not admitted to the intensive care unit. This compares favorably with the 9.5-day LOS of patients treated in 1990. CONCLUSIONS: PS in burn patients allows for early aggressive debridement, decreases the use of the operating room for debridement, and a decrease in length of stay when compared with our previous burn patients. PS has a modest risk of complications, enhances the family's cooperation and satisfaction with health care provided, and should be an integral part of burn care in children.

Adolescent↗
PubMed1999

Partner abuse and posttraumatic stress disorder as risk factors for suicide attempts in a sample of low-income, inner-city women.

This study examined partner abuse and posttraumatic stress disorder (PTSD) as risk factors for suicidal behavior among women, and whether or not PTSD mediated the partner abuse-suicidal behavior association. Attempters (n = 119) were approximately three times more likely to be above clinical cut-points for physical partner abuse, nonphysical abuse, and PTSD than nonattempters (n = 85). Physical partner abuse, but not nonphysical partner abuse, was associated with an increased risk for PTSD. Further, PTSD mediated the link between physical partner abuse and suicidality, such that when PTSD was statistically controlled, the association between physical partner abuse and suicide attempt status was reduced to nonsignificance. Implications of findings for interventions for female victims of partner abuse, and women who make nonfatal suicide attempts are discussed.

Adult↗
PubMed1999

Effect of gel re-organization and tensional forces on alpha2beta1 integrin levels in dermal fibroblasts.

Mechanical forces are known to play an important role in regulating cell function in a wide range of biological systems. This is of particular relevance to dermal fibroblast function, given that the skin is known to be held under an intrinsic natural tension. To understand more about the generation of force by dermal fibroblasts and their ability to respond to changes in it, we have studied the role of the beta1 integrin receptors expressed by dermal fibroblasts in their ability to generate tensional forces within a collagen type I matrix and the effect of altered tensional force on integrin expression by dermal fibroblasts. Using a purpose-built culture force monitor, function-blocking antibodies directed towards the beta1 receptors dramatically reduced the tensional forces generated by dermal fibroblasts in a 3D collagen I matrix. However, the specific involvement of alpha1 or alpha2 subunits could not be demonstrated. Analysis of cellular response demonstrated that cells isolated from contracting collagen gels expressed fourfold higher levels of alpha2 mRNA than cells isolated from fully restrained gels. The levels of beta1 messenger RNA were relatively unaffected by reductions in force. Cells exposed to single reductions in force, however, did not exhibit alterations in either alpha1 or beta1 mRNA levels. We propose, therefore that alpha2beta1 integrin receptor levels in dermal fibroblasts are not altered in response to single reductions of gel tension, but do change following a continual change in force and associated matrix re-organization

Antigens, CD↗
PubMed1999

A molecular basis for the different local anesthetic affinities of resting versus open and inactivated states of the sodium channel.

Voltage-gated sodium channels are inhibited by local anesthetic drugs. This inhibition has complex voltage- and frequency-dependent properties, consistent with a model in which the sodium channel has low affinity for local anesthetics when it is in resting states and higher affinity when it is in open or inactivated states. Two residues, a phenylalanine (F1710) and a tyrosine (Y1717), in transmembrane segment IVS6 of the channel alpha subunit are critical for state-dependent block. We examined how these residues determine channel sensitivity to local anesthetics by introducing mutations that varied their size, hydrophobicity, and aromaticity. Block of resting channels by tetracaine was correlated with hydrophobicity at position 1710, as if hydrophobic drug-receptor interactions stabilize binding to resting states. In contrast, drug action on open or inactivated channels required an aromatic residue at this position. We propose that the native phenylalanine at position 1710 stabilizes drug binding to open or inactivated states by either cation-pi or aromatic-aromatic interactions between the aromatic side chain of the amino acid and charged or aromatic moieties on the drug molecule. We also consider the alternative possibility that mutations at this position affect drug action by either altering access to the receptor or by allosteric changes in receptor conformation. Mutations at position 1717 also altered drug action; however, these effects were not well-correlated with the size, hydrophobicity, or aromaticity of the substituted amino acid. These results suggest that the residue at this position does not contribute directly to the drug receptor.

Anesthetics, Local↗
PubMed1998

The class I antigen-processing pathway for the membrane protein tyrosinase involves translation in the endoplasmic reticulum and processing in the cytosol.

Formation of major histocompatibility complex class I-associated peptides from membrane proteins has not been thoroughly investigated. We examined the processing of an HLA-A*0201-associated epitope, YMDGTMSQV, that is derived from the membrane protein tyrosinase by posttranslational conversion of the sequence YMNGTMSQV. Only YMDGTMSQV and not YMNGTMSQV was presented by HLA-A*0201 on cells expressing full-length tyrosinase, although both peptides have similar affinities for HLA-A*0201 and are transported by TAP. In contrast, translation of YMNGTMSQV in the cytosol, as a minigene or a larger fragment of tyrosinase, led to the presentation of the unconverted YMNGTMSQV. This was not due to overexpression leading to saturation of the processing/conversion machinery, since presentation of the converted peptide, YMDGTMSQV, was low or undetectable. Thus, presentation of unconverted peptide was associated with translation in the cytosol, suggesting that processing of the full-length tyrosinase occurs after translation in the endoplasmic reticulum. Nevertheless, presentation of YMDGTMSQV in cells expressing full-length tyrosinase was TAP (transporter associated with antigen processing) and proteasome dependent. After inhibition of proteasome activity, tyrosinase species could be detected in the cytosol. We propose that processing of tyrosinase involves translation in the endoplasmic reticulum, export of full-length tyrosinase to the cytosol, and retransport of converted peptides by TAP for association with HLA-A*0201.

Amino Acid Sequence↗
PubMed1997

Susceptibility to ankylosing spondylitis correlates with the C-terminal residue of peptides presented by various HLA-B27 subtypes.

Susceptibility to spondyloarthropaties is strongly associated with some HLA-B27 alleles. Evidence suggests a direct pathogenic role for the B27 molecules which possibly present an arthritogenic peptide to the T cells. If this hypothesis is true, B27 subtypes that differ structurally but are disease-associated ought to be capable of presenting such peptide(s), while non-disease-associated ones would not. We have recently described a B27 subtype, B*2709, and shown its absence in ankylosing spondylitis (AS) patients. Here, we show the elution and sequence of peptides from HLA-B*2709 molecules. Similar to other B27 subtypes, these peptides are mainly nonamers with an Arg at position P2. Comparison of the C-terminal anchors of peptides eluted from B*2702 and B*2705 with those eluted from B*2709 reveals that, while B*2702 and B*2705 have a broader specificity, B*2709 molecules appear to only accept C-terminal hydrophobic residues. A common feature shared by the two caucasoid AS-associated subtypes (B*2702 and B*2705) but different from B*2709, is the presence of a Tyr as peptide C-terminal anchor. The substitution of Val for Tyr at the C terminus in one of the eluted peptides greatly reduces the binding to B*2709 molecules. This finding suggests Tyr as a discriminative amino acid allowed at the C terminus of peptides bound to the AS-associated B27 subtypes, but not to those which are not associated with AS.

Amino Acid Sequence↗
PubMed1997

The HLA-A*0201-restricted H-Y antigen contains a posttranslationally modified cysteine that significantly affects T cell recognition.

A peptide recognized by two cytotoxic T cell clones specific for the human minor histocompatibility antigen H-Y and restricted by HLA-A*0201 was identified. This peptide originates from SMCY, as do two other H-Y epitopes, supporting the importance of this protein as a major source of H-Y determinants in mice and humans. In naturally processed peptides, T cells only recognize posttranslationally altered forms of this peptide that have undergone modification of a cysteine residue in the seventh position. One of these modifications involves attachment of a second cysteine residue via a disulfide bond. This modification has profound effects on T cell recognition and also occurs in other class I MHC-associated peptides, supporting its general importance as an immunological determinant.

Animals↗
PubMed1997

Diagnosis of perinatal human immunodeficiency virus infection by polymerase chain reaction and p24 antigen detection after immune complex dissociation in an urban community hospital.

Results of polymerase chain reaction (PCR) and p24 antigen detection after immune complex dissociation (p24-ICD) were compared with antibody results after 18 months of age for human immunodeficiency virus (HIV) diagnosis in 345 prospectively followed, perinatally exposed infants. Of 59 infected and 286 uninfected infants tested at 1-6 months of age, sensitivity and specificity were, respectively, 100% and > 97% for PCR and 90% and > 97% for p24-ICD. Testing was done on > or = 2 occasions in the first 6 months of life in 43 infected infants; 77% had > or = 2 positive results with the same test. Of these infants, 68% had 2 positive p24-ICD tests. In uninfected infants, 96% had only negative tests; none had > 1 positive. By 6 months, all uninfected infants with > or = 2 PCR results could have been diagnosed. HIV status can be determined by PCR by age 6 months in most HIV-exposed infants. p24-ICD should not be used alone, because of its lower sensitivity, but may be useful in areas without advanced laboratory support.

Antigen-Antibody Complex↗
PubMed1995

The measure and mismeasure of the tibia: implications for stature estimation.

Trotter and Gleser's stature estimation formulae, based on skeletons of the Terry collection and on WWII casualties, have been widely used in forensic work. Our work with the Terry and WWII data yielded tibia lengths too short compared to other data sets. Using Trotter's original measurements, we discovered that she consistently mismeasured the tibia. Contrary to standard practice and her own definitions, she omitted the malleolus from the measurement. Trotter's measurements of the tibia are 10 to 12 mm shorter than they should have been, resulting in stature estimations averaging 2.5 to 3.0 cm too great when the formulae are used with properly measured tibia. We also examined tibia lengths of Korean War casualties, which were measured by technicians rather than by Trotter. Korean tibia measurements are also too short, but by a smaller amount than Terry and WWII. Since the Korean tibia are unavailable for restudy, it is unclear how they were measured. Estimation of stature from Trotter and Gleser's tibia formulae is to be avoided if possible. If necessary, the 1952 formulae could be used with tibia measured in the same manner that Trotter measured, excluding the malleolus.

Asian People↗
PubMed1995

Allometric secular change in the long bones from the 1800s to the present.

Allometric secular changes in the six long limb bones for White and Black males from the mid 1800s to the present are examined. Long bone lengths are available from the Terry collection and WWII casualties. We conducted two types of analysis to reveal secular changes. First, allometry scaling coefficients were derived by regressing log bone length onto log stature. These showed that the femur, tibia and fibula were positively allometric with stature, while the humerus, radius and ulna were isometric. The lower limb bones were more positively allometric in the WWII sample than in the Terry sample. Second, secular changes in length of femur and tibia and in the tibia/femur ratio were evaluated, using modern forensic cases in addition to the Terry and WWII samples. This analysis shows that secular increase in lower limb bone length is accompanied by relatively longer tibiae. Secular changes in proportion may render stature formulae based on nineteenth century samples, such as the Terry collection, inappropriate for modern forensic cases. The positive allometry of the lower limb bones argues against using simple femur/stature ratio, which assumes constant proportionality, as an alternative to regression equations.

Black People↗
PubMed1995

Population structure of Algonquian speakers.

Speakers of Algonquian languages are widely dispersed geographically but are homogeneous linguistically. We examine anthropometric differentiation among Algonquian-speaking populations distributed from New Brunswick to Montana. Head and face measurements and body measurements were analyzed separately in an attempt to address the effect of phenotypic plasticity on relationships. The head and face and body dimensions yield somewhat different pictures of relationships. From the head and face data an east to west geographic pattern can be discerned. The principal feature of the body measurements is the distinctiveness of the Ojibwa located northwest of Lake Superior. The formal correlation between the two sets of measurements is low and not significant. Only the head and face dimensions correlate significantly with geographic distances. Language distances do not correlate with anthropometric distances. The set of populations is also more strongly differentiated with respect to body measurements than to head and face measurements. We interpret this as reflecting phenotypic plasticity and possibly greater interobserver variation.

Anthropometry↗
PubMed1994

Putting prevention into practice.

In primary medical care settings, disease prevention services are delivered at lower rates than recommended. Furthermore, practitioners tend to overestimate the rate at which they perform them. There are essentially two steps in delivering evidence-based preventive services: (1) knowing what the evidence is for performing various detection and intervention manoeuvres, and (2) integrating the preventive services into daily practice. The first is a scientific process and is carried out in Canada by the Canadian Task Force on the Periodic Health Examination. However, after a decade of experience with evidence-based guidelines, we now know that guidelines are not enough. Integrating clinical prevention into busy practices is a political and logistical process. This truth is best captured by the quip, "An ounce of prevention requires a pound of office system change". A number of studies have demonstrated that continuing medical education (CME) courses and workshops for physicians are not enough to ensure that clinical preventive services are incorporated into practice. According to Lomas, the traditional CME educational approaches need to be complemented by strategies from such paradigms as the social influence model, the diffusion of innovation model and the adult learning model. Battista, in "From Science to Practice," points out the complexity of the communication process required for the diffusion of innovation into practice. Walsh's Systems Model of Clinical Preventive care best captures the interacting factors that mediate between practitioners' intentions and their actions when it comes to delivering clinical prevention services. This paper reports on a practical example of helping family practitioners develop a "sustaining office system in prevention" that minimizes barriers, focuses energy and integrates clinical prevention into office routines. The key components are (i) a practice coordinator for prevention, (ii) clear clinical prevention-related job descriptions for all persons who deal with patients, (iii) an information management system that reinforces prevention, and (iv) a practice feedback and problem solving strategy.

Aged↗
PubMed1993

Characterization of Centers for Disease Control group NO-1, a fastidious, nonoxidative, gram-negative organism associated with dog and cat bites.

Seventeen strains of fastidious, nonoxidative, gram-negative rods, isolated from human wounds resulting primarily from dog or cat bites, formed a distinct group, which was designated Centers for Disease Control (CDC) group nonoxidizer 1 (NO-1). The phenotypic characteristics of CDC group NO-1 were most similar to non-acid-producing Acinetobacter species, with the major difference being a negative reaction in the transformation assay test for Acinetobacter spp. The cellular fatty acid composition of CDC group NO-1 was different from those of Acinetobacter species and all other bacteria tested to date. The isolates were susceptible to a variety of antimicrobial agents including the aminoglycosides, beta-lactam antibiotics, tetracyclines, quinolones, and sulfonamides. Fifty percent of the isolates were resistant to trimethoprim. Ubiquinone-8 was present as the major isoprenoid quinone in CDC group NO-1.

Acinetobacter↗
PubMed1992

Estimation of stature from metacarpal lengths.

Formulae for the estimation of stature from metacarpal lengths are presented. Two samples of metacarpal specimens were employed in the analysis: one of 212 individuals from the Terry Collection, and one of 55 modern males, all of whom had measured statures. One measurement, the midline length, was taken on each metacarpal. Stature was regressed on the basis of the metacarpal length to derive equations for the Terry Collection individuals. Comparisons between the Terry Collection males and the modern sample showed the latter to have longer metacarpals and greater statures. The Terry equations were tested using the modern male sample. In spite of the differences noted, the Terry equations perform acceptably on modern individuals. The performance was slightly better for whites than for blacks. Since the female equations were not tested, they should be employed with greater caution.

Black People↗