Search PubMed⌕ Search

Biomedical subjects

K Williams

Publications and source records attributed to K Williams.

At least 361 records · Page 20Linked to original sources

Developmental sequences for catching a small ball: a prelongitudinal screening.

Developmental sequences are identified for many skills (e.g., hopping and throwing). Sequences are hypothesized but not validated for catching. Two purposes of this investigation were to validate hypothesized catching sequences and examine the importance of task constraints on catching performance. Seventy-two subjects (5-12 years of age) were videotaped as they attempted to catch a small (10-cm) ball, tossed to three locations: (a) directly to the body, (b) at the forehead, and (c) to various other locations. Trials were categorized using developmental sequences including four components: arm preparation, arm reception, hands, and body. The data were analyzed by catching condition using the prelongitudinal screening procedure described by Roberton, Williams, and Langendorfer (1980). Preliminary screening resulted in clarification of descriptions for several developmental levels. Movement sequences for hand and body components were comprehensive and age-related for the groups studied. Task conditions differently constrained children of different ages. Arm components did not meet the Roberton et al. criteria. Combining them may be warranted. Varying ball size or type is needed to test the comprehensiveness of the proposed sequences for other catching skills.

Aging↗

Levels of exposure to wood dust.

Surveys of exposure to inhalable dust have been carried out in two woodworking machine shops and five other woodworking shops where both manual and machine tool work is carried out. The Occupational Exposure Limits for wood dust were found to be frequently exceeded in some workshops. It is possible that the fraction of dust projected from woodworking machines towards the operator may have contributed both to measured dust concentrations and to exposure. Dust exposure may be reduced by careful attention to enclosure and ventilation, possibly using total enclosure at some machines. Emission of dust from portable orbital type sanding machines was considerably reduced by the use of low-volume high-velocity type extraction. It is suggested that suppliers of woodworking machines should provide data on dust emission to assist the user to manage better the introduction of new machines.

Air Pollutants, Occupational↗

The determination of nitroaromatics and nitramines in ground and drinking water by wide-bore capillary gas chromatography.

A method has been developed to determine the concentration of nitroaromatics and nitramines in drinking water at levels below those previously achieved by gas chromatography. The nitroaromatics and nitramines are extracted from water using toluene and isoamyl acetate, respectively. The extracts are analyzed via a gas chromatograph equipped with a DB-1301 widebore fused-silica capillary column and an electron capture detector. Method detection limits of 0.003 micrograms/L for 2,6-dinitrotoluene (2,6-DNT), 0.04 micrograms/L for 2,4-dinitrotoluene (2,4-DNT), 0.06 micrograms/L for 2,4,6-trinitrotoluene (TNT), 0.3 micrograms/L for cyclotrimethylenetrinitramine (RDX), and 6.0 micrograms/L for cyclotetramethylenetetranitramine (HMX) have been obtained using this method.

Azocines↗

Activation of in vitro proliferation of human T cells by a synthetic peptide of toxic shock syndrome toxin 1.

A 21-mer synthetic peptide (KGEKVDLNTKRTKKSQHTSEG), designated TSST-1(58-78), was constructed from the primary structure of the toxic shock syndrome toxin 1 (TSST-1). The peptide reacted with a panel of neutralizing monoclonal antibodies (MAbs) to whole TSST-1 in solid-phase immunoassays. TSST-1(58-78) promoted the in vitro proliferation of human peripheral blood mononuclear cells (PBMC) in a dose-dependent manner. Minimum dose required for stimulation (P less than or equal to .05 microM) was 0.75 microM peptide. This mitogenic effect was abrogated by incubation of the peptide with MAbs to whole TSST-1 before addition to PBMC. The ability of TSST-1(58-78) to stimulate the proliferation of highly purified resting human T cells was analyzed. Significant proliferation (P less than or equal to .01) was observed only in the presence of increasing populations of monocytes added to the cultures. Adherent human monocytes exposed to TSST-1(58-78) released tumor necrosis factor. Thus, some of the immunoregulatory properties attributed to TSST-1 are demonstrated by the region of the toxin represented by the peptide TSST-1(58-78).

Amino Acid Sequence↗

Polyamines modulate the binding of [3H]MK-801 to the solubilized N-methyl-D-aspartate receptor.

Spermine and spermidine enhance the binding of [3H](+)-5- methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]MK-801) to N-methyl-D-aspartate (NMDA) receptors in membranes prepared from rat brain. These polyamines also enhance binding of [3H]MK-801 to NMDA receptors that have been solubilized with deoxycholate. Other polyamines selectively antagonize this effect, a finding indicating that the polyamine recognition site retains pharmacological and structural specificity after solubilization. In the presence of spermidine, an increase in the affinity of the solubilized NMDA receptor for [3H]MK-801 is observed. However, the rates of both association and dissociation of [3H]MK-801 binding to solubilized NMDA receptors are accelerated when assays are carried out in the presence of spermidine. When kinetic data are transformed, pseudo-first-order association and first-order dissociation plots are nonlinear in the presence of spermidine, an observation indicating a complex binding mechanism. Effects of spermidine on solubilized NMDA receptors are similar to effects previously described in studies of membrane-bound receptors. The data indicate that polyamines interact with a specific recognition site that remains associated with other components of the NMDA receptor complex after detergent solubilization.

Animals↗

Throwing patterns of older adults: a follow-up investigation.

Previous investigations of the movement patterns of older adults have focused on functional movements. Performance declines have been reported with increasing age. Many investigations, however, do not require older adults to perform maximal, force producing actions. Smaller declines might be observed if older adults made a maximal effort. This investigation examined changes in a maximal skill--the overarm throw for force. Active, older adults were videotaped as they threw tennis balls. Thirteen people were filmed for two consecutive years. Gender and age differences were examined for movement patterns, ball velocity, and selected kinematic measures. Participants threw using patterns and velocities generally observed in children in middle elementary-school years. This result suggested there was a decline in this force production skill. Some older adults regressed in the movement patterns they used over the two years of testing. Older males threw faster, using more advanced movement patterns than older females.

Aged↗

Activation of MAP-2 kinase activity by the CD2 receptor in Jurkat T cells can be reversed by CD45 phosphatase.

We have recently characterized a serine kinase in T lymphocytes which phosphorylates microtubule-associated protein-2 (MAP-2) in vitro. This kinase is activated in a rapidly reversible fashion during ligation of CD3/Ti by a process which involves tyrosine phosphorylation of the enzyme itself. We show that the stimulatory anti-CD2 mAb combination, anti-(T11(2) + T11(3), stimulates MAP-2K activity in Jurkat cells with kinetics that are more prolonged than during anti-CD3 treatment. The principal difference is not in the rate of response induction, but in the decline of the response beyond the peak, to which end anti-CD2 stimulation resembles the sustained phytohaemagglutin (PHA) response. Parallel immunoblotting, utilizing anti-phosphotyrosine antibodies, also revealed differences in the rate at which tyrosine phosphorylation of pp43 (MAP-2K) disappears after induction. In spite of these differences, CD2 was absolutely dependent on the presence of CD3 for inducing a MAP-2K response in Jurkat cells. These results indicate that, even though CD2 and CD3 are using a common signalling pathway in Jurkat cells, additional differences such as the involvement of a tyrosine phosphatase may have to be considered in response generation. We also demonstrate that the common CD45 isoform, when cross-linked to CD2 by mAb, could inhibit the MAP-2K response during both induction as well as the disappearing phase of the response.

Antibodies, Monoclonal↗

Developmental changes in the sensitivity of the N-methyl-D-aspartate receptor to polyamines.

The binding of [125I]I-MK-801 to N-methyl-D-aspartate (NMDA) receptors on membranes prepared from cultured cerebral cortical neurons and from forebrain of rats of different ages was investigated. Specific binding of [125I]I-MK-801 was enhanced by glutamate, glycine, and polyamines and was inhibited by divalent cations and open-channel blockers of the NMDA receptor, indicating that [125I]I-MK-801 selectively labels a component of the NMDA receptor/ion channel complex. The ability of spermine to enhance the binding of [125I]I-MK-801 was lower in membranes prepared from cultured cerebral cortical neurons or from neonatal rat brain than in membranes prepared from adult rat brain. There was a progressive increase in the potency of spermine and in the magnitude of the stimulatory effect of spermine in rat forebrain between days 3 and 10 of postnatal life. In contrast, the apparent affinity of the NMDA receptor for spermine remained unchanged in cerebral cortical neurons maintained in culture for up to 5 weeks. Mg2+ also enhanced the binding of [125I]I-MK-801 and was more potent in membranes prepared from adult than from 3-day-old rat forebrain. The potency of glutamate for enhancing the binding of [125I]I-MK-801 was not altered in 3-day-old, compared with adult, brain tissue. The increase in the affinity of the polyamine recognition site on the NMDA receptor complex in rat forebrain during the first 2 weeks of postnatal life suggests that the macromolecular properties of the NMDA receptor are altered during development. This may suggest that the subunit composition of the NMDA receptor is under developmental control. Cultured cortical neurons may represent a useful system for investigating factors that regulate developmental changes in the properties of the NMDA receptor.

Age Factors↗

Effects of severe reduction in maternal placental blood flow on blood flow distribution in the sheep fetus.

To test the hypothesis that fetal lambs are able to maintain oxygen delivery to myocardial, brain and adrenal tissues during reduction in uterine blood flow to 25% of control, we performed experiments on five ewes and their fetuses. A snare occluder was placed around the maternal common hypogastric artery and catheters were placed for measurement of blood pressures, flows, blood gas tensions, pH and oxygen content. After a five day recovery period, control measurements were made. The snare occluder was then closed until the artery was fully occluded. The arterial occlusion caused uteroplacental blood flow to fall to 32 +/- 4% and maternal placental blood flow to fall to 25 +/- 3% of control values. This level of asphyxia was maintained for 19 +/- 3 minutes, when maternal and fetal blood flows were measured again. In response to occlusion, fetal ascending aortic PO2 fell from 21 +/- 2 (SEM) to 13 +/- 2 mmHg (P less than or equal to 0.01), oxygen content from 4.3 +/- 0.3 to 1.4 +/- 0.2 mM (P less than or equal to 0.01) and pH from 7.37 +/- 0.01 to 7.21 +/- 0.05 (P less than or equal to 0.01). PCO2 rose from 48 +/- 1 to 62 +/- 3 mmHg (P less than or equal to 0.01). Fetal arterial blood pressure increased from 51 +/- 3 to 61 +/- 3 mmHg (P less than or equal to 0.001) and heart rate decreased from 172 +/- 10 to 104 +/- 4 beats.min-1 (P less than or equal to 0.01). The heart, brain and adrenals showed vasodilation in response to the asphyxic stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Nonarticular complication of heterotopic ossification: a clinical review.

Heterotopic ossification (HO) is a complication in neurologic lesions such as head injury and spinal cord injury. Limitation of range of motion and ankylosis as results of HO are well documented. In this report, ten instances of nonarticular complications after development of HO are described. There were three instances of vascular compression, five instances of ulnar nerve compression at the elbow, and two instances of suspected lymphedema. Clinical findings and radiographic evidence of these complications are described. Clinicians should be aware of these complications when HO is diagnosed. In addition, HO should be considered in the differential diagnosis of deep venous thrombosis in spinal cord injured and head injured patients.

Adolescent↗

CD-3-mediated activation of MAP-2 kinase can be modified by ligation of the CD4 receptor. Evidence for tyrosine phosphorylation during activation of this kinase.

The CD4R has been shown to exert variable effects on T cell activation responses. Depending on the manner of ligation, the CD4R has been demonstrated to have positive as well as negative effects on the generation of [Ca2+]i flux by the CD3R. Coaggregation of CD3 with CD4 enhanced Ca2+ flux while their independent ligation and aggregation diminished this response. To further elucidate these paradoxical CD4 effects, we studied induction of a microtubule-associated protein 2 kinase (MAP-2K) activity during ligation of the CD3R. Lymphoid MAP-2K activation by CD3 is an evanescent event that is dependent on phosphorylation of 43-kDa MAP-2K via a pathway that involves protein kinase C. Coaggregation of CD4 and CD3 with cross-linking antibodies and avidin enhanced the CD3-mediated MAP-2K response almost twofold. In contrast, independent ligation and cross-linking of CD4 reduced the CD3-induced MAP-2K response by approximately 50%. An important requirement for this inhibitory effect was that CD4 be ligated before stimulation with anti-CD3. The negative effect of anti-CD4 mAb was specific as other mAb failed to simulate this event. The PMA-induced MAP-2K response was not inhibited by anti-CD4. Intact 32P-labeled Jurkat and normal human T cells demonstrated the appearance of a single 43-kDa tyrosine phosphoprotein during stimulation with PMA and anti-CD3. When these crude cellular extracts were extensively fractionated across DEAE- and hydrophobic columns, MAP-2K was resolved into two peaks of activity, each containing a single tyrosine phosphoprotein around 43 kDa. In addition to tyrosine-specific labeling, mitogenic stimulation of normal human T cells also induced threonine-specific labeling of MAP-2K. These results imply that activation of lymphoid MAP-2K is a dual process requiring at least two independent kinases for optimal activity. Inasmuch as CD3 activates protein kinase C and CD4 is associated with a tyrosine kinase, pp56lck, we suggest that their coaggregation may create the conditions whereby MAP-2K may be activated by dual phosphorylation. Independent aggregation of these receptors may lead to physical separation and breakdown of this interactive mechanism.

Adult↗

Active nucleoprotein filaments of single-stranded binding protein and recA protein on single-stranded DNA have a regular repeating structure.

When E. coli single-stranded DNA binding protein (SSB) coats single-stranded DNA (ssDNA) in the presence of 1 mM MgCl2 it inhibits the subsequent binding of recA protein, whereas SSB binding to ssDNA in 12 mM MgCl2 promotes the binding of recA protein. These two conditions correspond respectively to those which produce 'smooth' and 'beaded' forms of ssDNA-SSB filaments. By gel filtration and immunoprecipitation we observed active nucleoprotein filaments of recA protein and SSB on ssDNA that contained on average 1 monomer of recA protein per 4 nucleotides and 1 monomer of SSB per 20-22 nucleotides. Filaments in such a mixture, when digested with micrococcal nuclease produced a regular repeating pattern, approximately every 70-80 nucleotides, that differed from the pattern observed when only recA protein was bound to the ssDNA. We conclude that the beaded ssDNA-SSB nucleoprotein filament readily binds recA protein and forms an intermediate that is active in the formation of joint molecules and can retain substantially all of the SSB that was originally bound.

Chromatography, Gel↗

Stimulation of MAP-2 kinase activity in T lymphocytes by anti-CD3 or anti-Ti monoclonal antibody is partially dependent on protein kinase C.

Signaling via the alpha-beta T cell Ag receptor (Ti)-CD3 complex is a complicated event that implicates several protein kinases, most notably protein kinase C (PKC). We have recently identified a serine kinase in T lymphocytes with the following characteristics: molecular mass 43 kDa, in vitro substrate affinity for microtubule associated protein 2 (MAP-2) with a preference for Mn2+ during the catalytic reaction, and elution from DEAE resin over a salt range 100 to 200 mM NaCl. This kinase is activated in a rapidly reversible fashion during ligation of CD3/Ti by a process which involves prior phosphorylation; in vitro exposure of activated 43-kDa MAP-2 kinase (MAP-K) to an immobilized phosphatase abrogated its kinase activity. We now show that a MAP-2K response could also be obtained during treatment with mAb to Ti and the specific PKC agonist, PMA. Although the kinetics of the former response was rapidly reversible, PMA elicited a more prolonged response. The dose responsiveness for PMA was similar to the requirements for PKC activation in intact lymphocytes. Moreover, as with PKC, we found that the CD3-induced MAP-2K response could be further enhanced by using a second layer cross-linking antibody. The specificity of CD3/Ti in the Jurkat cell response is demonstrated by the fact that OKT-11(CD2) and anti-CD4 mAb did not stimulate a MAP-2K response. It was also not possible to elicit a response in a Jurkat cell mutant that lacks surface expression of CD3 and Ti. The specificity of PKC in these events was further explored with the cell permeant diacylglycerol, 1-oleoyl-2-acetylglycerol, and the nonagonist phorbol ester, 4 alpha-phorbol 12,13-didecanoate: whereas the former was an effective inducer of the MAP-2K response, the latter failed to yield any stimulation. Prior exposure of Jurkat cells to 100 mM PMA for 24 h eliminated greater than 60% of the MAP-2K response during anti-CD3 treatment. This response could also be inhibited in dose-dependent fashion by prior treatment of Jurkat cells with the potent PKC inhibitor 1-(5-isoquinolinesulfonyl) 2-methylpiperazine dihydrochloride. Although a Ca2(+)-ionophore failed to synergize with PMA at inducing a MAP-2K response, depletion of extracellular Ca2+ by EGTA abrogated anti-CD3 responsiveness. The events culminating in MAP-2K activation were slightly inhibited in the presence of cholera toxin but not pertussis toxin.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗

Lanthanum probing of cell membrane permeability in the rat heart: pathological versus artefactual alterations.

The influence of fixation on membrane permeability has been examined in the isolated rat heart using lanthanum as a permeability probe. Normal and ischaemic hearts were probed at various stages during a conventional fixation programme with either ionic or colloidal lanthanum and compared with lanthanum saline administered prior to fixation. Fixation of the myocardium coincident with or followed by lanthanum probing resulted in an influx of the probe into most myocytes in normal tissue. Alterations in permeability after ischaemic episodes could not be distinguished from the artefact. However, lanthanum saline prior to fixation showed exclusion of the probe from normal tissue, while the increased permeability demonstrated after ischaemia was associated with declining myocardial performance during subsequent reperfusion. These results illustrate the need for caution in the application and evaluation of methods determining permeability in fixed tissue. Probes of differing size and charge permeated fixed tissue to varying degrees thereby implicating the formation of specific lesions during chemical fixation.

Animals↗

Uterine sarcoma: steroid receptors and response to hormonal therapy.

Seventy-three patients with uterine sarcomas were treated between 1976 and 1987. Steroid receptors were analyzed in 60 cases; 48% were estrogen receptor (ER) positive, and 30% progesterone receptor (PR) positive. Only 1 of 28 patients with residual or recurrent disease showed a response to hormonal therapy. Neither receptor status of the primary tumor nor use of adjuvant hormonal therapy affected survival.

Adult↗

Sensitivity and specificity of standardized screens of cognitive impairment and dementia among elderly black and white community residents.

Six standardized published measures of cognitive function were evaluated as screens of dementia in a sample of 164 (83 black, 81 white) community residents aged 65 and over selected from the Duke University EPESE (Established Populations for Epidemiologic Studies of the Elderly), a biracial cohort of 4164 residents in a five county area of piedmont North Carolina. Of these 164 persons, 26 were subsequently diagnosed as demented. The weighted data from this sample represent the estimated performance of these measures among elderly blacks and whites in a five county area. The 6 measures evaluated in this study (specificity figures for blacks precede those for whites) were (1) Orientation-Memory-Concentration Test (38%, 79%), (2) Mental Status Questionnaire (71%, 96%), (3) Mini-Mental State (58%, 94%), (4) Storandt et al. Battery (42%, 69%), (5) Iowa Battery (26%, 69%) and (6) Kendrick Cognitive Tests (92%, 97%). All but the Kendrick Cognitive Tests showed substantial sensitivity (90-100%) in detecting the presence of dementia. The specificity of the tests was particularly poor for blacks. The briefer, simpler measures tended to have greater accuracy than the longer and more complex measures. With rare exceptions, the scores obtained on these screens correlated with race and education.

Aged↗