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Biomedical subjects

L Meadows

Publications and source records attributed to L Meadows.

At least 19 recordsLinked to original sources
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

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↗
PubMed1990

Time since death and decomposition of the human body: variables and observations in case and experimental field studies.

Much of the difficulty in determining the time since death stems from the lack of systematic observation and research on the decomposition rate of the human body. Continuing studies conducted at the University of Tennessee, Knoxville, provide useful information on the impact of carrion insect activity, ambient temperature, rainfall, clothing, burial and depth, carnivores, bodily trauma, body weight, and the surface with which the body is in contact. This paper reports findings and observations accumulated during eight years of research and case studies that may clarify some of the questions concerning bodily decay.

Animals↗
PubMed1979

Deficiency of the fifth component of complement in human subjects. Clinical, genetic and immunologic studies in a large kindred.

The discovery of a large kindred with a heritable deficiency of the fifth component of complement (C5) has permitted the accumulation of new clinical, genetic and immunologic data concerning the role of C5 in human subjects. The proband, who has had nine episodes of disseminated gonococcal infection, has a hemolytic C5 level of approximately 0.5 per cent of normal. No C5 protein was detectable, but low levels of functional C5 activity could be found using a sensitive bactericidal assay. The proband's twin as well as another sister also had extremely low levels of hemolytic C5(approximately 0.5 per cent normal), but both these subjects have been healthy. Hemolytic complement and bacteriolytic activity could be restored by the addition of purified C5. No chemotactic activity for polymorphonuclear leukocytes could be generated in the C5-deficient serums upon activation of either the classic or alternative pathways, again demonstrating the importance of C5 in human subjects for the production of chemotactic factors. The chemotactic responsiveness of the patients' polymorphonuclear leukocytes and monocytes to preformed chemotactic factors was not depressed. Twenty-two of 32 other family members from three generations had depressed whole hemolytic complement levels. In 19 of 30 family members, levels of hemolytic C5 ranged from 13 to 64 per cent of normal. No linkage for C5 deficiency and the A or B loci of the major histocompatibility complex could be found. These data suggest an autosomal codominant mode of inheritance of C5 deficiency. Deficiency of C5 is compatible with good health, but it can be associated with repeated disseminated gonococcal infection.

Adult↗
PubMed1979

Hereditary C2 deficiency associated with cutaneous lupus erythematosus: clinical, laboratory, and genetic studies.

Selective congenital deficiency in the second component of complement has been described in association with lupus erythematosus (LE) and other connective tissue disorders. We identified a 59-year-old woman with a 13-year history of cutaneous LE and no detectable serum C2. The patient's photosensitivity, large polycyclic erosive cutaneous lesions, lack of renal disease, paucity of serological findings, and high incidence of bacterial infection is consistent with previously described patients with this association. Uniquely, the patient demonstrated secondary infection with Staphylococcus aureus and Trichophyton rubrum in the skin lesions themselves. Immunologic studies disclosed depression in both humoral and cellular immunity. Moderation in her clinical disease and immunologic measurements has been observed after treatment with levamisole hydrochloride. Immunogenetic studies of the patient's four-generation kindred was consistent with an autosomal recessive inheritance of C2 deficiency genetically linked to HLA, segregating with the B18 allele. Mixed lymphocyte culture determinations reinforce evidence for linkage between the HLA-D locus and the trait for C2 deficiency.

Complement C2↗
PubMed1978

Abnormal monocyte chemotaxis in patients with breast cancer: evidence for a tumor-mediated effect.

The chemotactic responsiveness of peripheral blood monocytes was measured in 194 individuals: 37 patients with breast cancer, 17 patients with a history of breast cancer but clinically free of disease after surgery, 42 patients with benign breast masses, and 98 normal controls. Monocyte chemotactic responsiveness (MCR) in vitro was not significantly different from normal [mean = 72.8 migrating monocytes/oil immersion field, +/- 9.3 (1 SD)] in 2 groups of patients: a) those with benign breast masses (mean = 72.6 +/- 15.1; P greater than 0.3) and b) those previously having breast cancer resected and remaining clinically free of disease (mean = 69.0 +/- 12.5; P greater than 0.4). However, MCR was significantly depressed in the group of patients with active breast cancer (mean = 57.2 +/- 20.7; P less than 0.0025). Resection of malignant breast masses resulted in a significant change in MCR (P less than 0.0025), whereas resection of benign lesions did not (P greater than 0.4). MCR was abnormal in all clinical stages of breast cancer, including breast cancer without evidence of metastasis to regional lymph nodes. These data supported the hypothesis that neoplasms adversely affect monocyte function and may thereby hinder immunologically mediated destruction of malignant cells.

Adenocarcinoma↗
PubMed1978

Epiphysiolysis as a method of limb lengthening.

Epiphysiolysis followed by distraction was performed at the proximal tibial growth plates in 18 young rabbits. Union across the distracted plate occurred in all animals. In 12 rabbits skeletally immature at operation, premature fusion of the separated plate resulted in growth arrest of the operated limb. The contralateral control limb was longer at maturity by an average 1.10 cm. In 6 rabbits near skeletal maturity at epiphysiolysis, the operated limb was the longer at maturity by the amount distracted, an average of 0.62 cm. In all animals a permanent loss of joint motion resulted. Epiphyseal distraction in the very young rabbit does not appear to be practical due to consistent premature fusion of the distracted growth plate. It is possible to lengthen the limbs of rabbits near skeletal maturity with this procedure. An added advantage is that union between the epiphysis and the metaphysis always occurred, eliminated the problem of delayed ana non union found in diaphyseal lengthening. However, at this time, until the effects of distraction and compression on the adjacent joint can be minimized, epiphysiolysis as a method of limb lengthening is not recommended in children.

Age Factors↗