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Biomedical subjects

K Chapman

Publications and source records attributed to K Chapman.

At least 91 records · Page 5Linked to original sources
PubMed1990

Production of tumor necrosis factor by human osteoblasts is modulated by other cytokines, but not by osteotropic hormones.

Human osteoblast cultures derived as out-growths from trabecular bone released tumor necrosis factor (TNF alpha) upon stimulation of the cells with human recombinant interleukin 1 (IL1; 10(-13)-10(-11) M), human recombinant granulocyte-macrophage colony-stimulating factor (100-1000 U/ml), and bacterial lipopolysaccharide (5-500 ng/ml). The osteotropic hormones 1,25-dihydroxyvitamin D3, PTH, and calcitonin had no effect on TNF production. The TNF released by the osteoblasts was identified as TNF alpha, using a specific anti-TNF alpha monoclonal antibody to neutralize its activity. Immunohistochemical staining of the cells using the same antibody revealed that all of the cells in the cultures were capable of producing TNF alpha, including those that also expressed alkaline phosphatase activity. Immunoreactive protein could be detected in the perinuclear region when cells were cultured in the presence of monensin, suggesting accumulation of newly synthesised protein in the Golgi apparatus. These results suggest that human osteoblasts, which have been shown previously to respond to TNF alpha, can synthesize and release TNF in response to IL1 and granulocyte-macrophage colony-stimulating factor. TNF may, therefore, not only have a pathological role in conditions of chronic inflammation, but also may act as a local paracrine or autocrine regulator of osteoblast function.

Calcitonin↗
PubMed1990

Identification of a high molecular weight steroid response element binding protein.

In this study we report the identification of a Steroid Response Element-Binding Protein (SRE-BP) present in whole cell extracts of HeLa cells and GH3 pituitary tumor cells which specifically binds to two classes of functionally distinct SREs. In gel retardation experiments SRE-BP binds preferably to oligonucleotides containing an estrogen response element (ERE) or a symmetrical glucocorticoid response element (GRE); it binds less well to a mutant GRE and poorly, if at all, to a thyroid response element (TRE). The SRE-BP does not recognize transcription factor binding sites present in the promoter of the Herpes Simplex Virus thymidine kinase gene. We have shown, using gel filtration chromatography that the SRE-BP has a relative molecular weight under nondenaturing conditions of 205 K (+/- 20 K). The SRE-BP is not a steroid receptor as evidenced by different DNA sequence specificity, cell type distribution, and molecular weight. We propose that by modulating the interaction of steroid receptors with target SREs, the SRE-BP plays a role in specificity of steroid hormone action.

Base Sequence↗
PubMed1987

Geometry of isolated sensory neurons in culture. Effects of embryonic age and culture substratum.

Sensory neurons were dissociated from lumbar dorsal root ganglia of embryonic chick and put into culture, either directly or after removing non-neuronal cells by density gradient centrifugation. The cells were grown on culture substrata of various kinds in medium containing nerve growth factor (NGF). After 24 h the cultures were fixed, mounted and analysed. Lengths of neurites were measured, and the numbers of primary processes formed at the cell body and of growth cones were counted. From these values, the rates of growth cone advance and frequency of growth cone branching were calculated. Neuronal outgrowths increased strikingly in length and complexity with embryonic age; there was a 3.5-fold increase in total neurite length and a 3-fold increase in the number of growth cones when neurons from 15-day embryos (E15) were compared with those from 8-day embryos (E8) grown on the same substratum (glass). Growth was markedly greater on surfaces prepared with laminin or conditioned medium compared with plain glass or air-dried collagen. When E15 neurons grown on glass were compared with those grown on laminin, for example, a 2.5-fold increase in total neurite length and a 3-fold increase in the number of growth cones was observed. Calculations showed that a major factor in these changes was an increase in the frequency of growth cone branching. The number of initial processes emanating from the cell body changed with age, but not with the different substrata tested. Non-neuronal cells when present in low numbers and in contact with neurons did not appear to influence neuronal geometry in a systematic way. Our results document the fact that both external factors (in this case, the nature of the culture substratum) and intrinsic factors (stage of development of the neuron) can influence the geometry of neurite outgrowth.

Animals↗
PubMed1986

cDNA sequence of human beta-preprotachykinin, the common precursor to substance P and neurokinin A.

The nucleotide sequence of cDNA encoding the human substance P precursor, beta-preprotachykinin (beta-PPT), has been determined. The source of mRNA was a human laryngeal carcinoid tumour that contained a high concentration of immunoreactive substance P. The human beta-PPT polypeptide is 129 amino acids long and contains regions encoding substance P and neurokinin A, each flanked by basic amino acid residues. Residues 72-107 of the human beta-PPT polypeptide encode the sequence of neuropeptide K, an N-terminally extended form of neurokinin A recently isolated from porcine brain.

Animals↗
PubMed1986

A novel microtubule-associated protein from mammalian nerve shows ATP-sensitive binding to microtubules.

We report the isolation of a protein from mammalian nerve which shows ATP-sensitive binding to microtubules and ATPase activity. This protein, which we have designated HMW4, was prepared from bovine spinal nerve roots by microtubule affinity and ATP-induced release, and was further purified by sucrose density gradient centrifugation. It is a high molecular weight protein with a denatured Mr of 315,000, a Stokes radius of 90 A, and a sedimentation value of approximately 19S. It can be resolved electrophoretically from the well-characterized bovine brain microtubule-associated proteins (MAPs) and also appears to be distinct from MAP 1C. HMW4 has a vanadate-sensitive and azide-insensitive ATPase activity which averages 20 nmol Pi/min per mg protein and is different from dynein and myosin ATPases. HMW4 prepared on sucrose gradients exhibits binding to MAP-free microtubules in the absence of ATP which is reduced by ATP addition. Assayed by darkfield microscopy, HMW4 causes bundling of MAP-free microtubules which is reversed by ATP addition.

Adenosine Triphosphate↗
PubMed1985

Identification and characterization of mutants affecting transcription termination at the threonine operon attenuator.

Mutations that map in or delete the attenuator of the threonine (thr) operon of Escherichia coli were isolated and characterized. These mutations disrupt or delete the transcription termination structure encoded by the attenuator leading to increased transcriptional readthrough into the thr operon structural genes. Most of the base substitutions and single base-pair insertions and deletions map in the G + C-rich region of dyad symmetry in the attenuator and decrease the calculated stabilities of the attenuator RNA secondary structures to similar extents (from -30.8 kcal/mol to approximately -21 kcal/mol). Most of the mutants showed a three- to fourfold increase in homoserine dehydrogenase (thrA gene product) synthesis relative to the wild-type parent strain. The mutation in one mutant (thrL153 + G) lowered the calculated stability of the RNA secondary structure only slightly (from -30.8 to 27.8 kcal/mol) but the mutant still exhibited high levels of homoserine dehydrogenase synthesis. In addition, three base substitution mutants (thrL135U, thrL139A and thrL156U) showed only slightly (1.5 to 2-fold) elevated levels of homoserine dehydrogenase activity, even though the calculated stabilities of the attenuator RNA secondary structures were reduced as much as most of the other mutants. Two of the mutations (thrL135U and thrL156U) mapped in the G + C-rich-A + T-rich junction of the attenuator. The third mutation (thrL139A) creates an A X C pair in the center of the G + C-rich region of the attenuator stem. The results obtained for these mutants show that the stability of the RNA secondary structure does not always correlate with the efficiency of transcription termination. Finally, analysis of the base changes in the substitution mutations showed that the mutational changes do not appear to be random.

Base Sequence↗
PubMed1985

Facilitating word combination in language-impaired children through discourse structure.

The influence of an adult-child discourse structure on the production of early word combinations was examined in language-impaired children. The subjects were 10 children (2:8-3:4) at the single-word utterance level. Eight of the children were engaged in 10 experimental sessions utilizing vertical structures (e.g., Adult: "Who's this?" Child: "Daddy." Adult: "What's Daddy throwing?" Child: "Ball." Adult: "Yeah, Daddy's throwing the ball."), while the remaining children, serving as controls, were engaged in an alternate activity. Examination of pretest and posttest data as well as session data revealed a substantial increase in the number of multiword productions for most of the children in the experimental group but not for the children serving as controls. These findings indicate that vertical structures have a facilitating effect on the multiword productions of language-impaired children comparable to that found in an identical procedure with normally developing children. The use of a naturally occurring adult-child discourse structure as an intervention procedure is discussed.

Child Language↗
PubMed1985

Homonymy and the voiced-voiceless distinction in the speech of children with specific language impairment.

Two studies are reported in which homonymy in the speech of children with specific language impairment (SLI) was examined. In the first study, the degree of homonymy reflected in the speech of 14 SLI children was found to resemble that seen in the speech of a group of language-matched children with normal language (NL). Within each group there was considerable variation in the degree of homonymy observed. An examination of the sound changes that contributed to the children's use of homonymy suggested that homonyms arising from prevocalic voicing were more frequent in the speech of the NL children. The second study represented a more systematic examination of prevocalic voicing differences between NL and SLI children. Minimal pairs differing only in the voicing feature of the initial consonant were produced by four SLI and four language-matched NL children. The SLI children showed greater ability to distinguish the minimal pairs by means of a voiced-voiceless initial consonant contrast, as measured by voice onset time as well as by phonetic transcription. The linguistic and neuromotor factors contributing to the findings are discussed.

Articulation Disorders↗
PubMed1985

Analysis of microspike movements on the neuronal growth cone.

Growth cones of chick sensory ganglion neurons in tissue culture were photographed at 60-sec intervals as they advanced over the substratum. Numbers of microspikes (or "filopodia") were recorded together with the time and position of their appearance, their rate of elongation, their lateral movements, their lifespan, and the position and manner of their disappearance. All microspikes go through cycles of extension, lateral movement, and shortening. These are irregular and unpredictable but show systematic differences depending on where on the growth cone they occur. At the leading edge of the growth cone microspike extension occurs at highest frequency and microspike shortening occurs at the lowest frequency; when the latter occurs in this region it often involves the advance of the margin of the cell in the form of a lamellipodium. Microspike loss occurs most often at the base of the growth cone, usually by the retraction of the microspike into the cell. Calculations of the gain and loss of microspikes at different regions of the growth cone show that they undergo a net retrograde flow, the rate of which is correlated with the forward advance of the growth cone. Individual microspikes can also move backward from the growth cone onto the axon (or "neurite"), an event that occurs most often on adhesive substrata. Our observations support a direct role of microspike movement in the advance of the growth cone. The primary force for axonal elongation appears to be the contraction of microspikes pulling the leading margin of the growth cone forward. At more proximal and peripheral regions of the growth cone, microspikes undergo a retrograde sweeping motion, followed by retraction into the cell, which may also contribute to the forward movement of the growth cone. We interpret these movements as arising from a flow of actin filaments and associated proteins which are incorporated into microspikes and lamellipodia at the leading edge of the growth cone, passing backward, and being deposited into the actin-rich membrane-associated cortex of the axonal cylinder.

Actins↗
PubMed1983

Inappropriate word extensions in the speech of young language-disordered children.

The purpose of this study was to determine the frequency of inappropriate word extensions in the spontaneous speech of young language-disordered children, and how these extensions should be characterized. Inappropriate word extensions were identified and tested, first in a production task and then in a comprehension task for nine language-disordered children (age 2:8 to 3:4). Results indicated that the percentage of inappropriate word extensions seen in the speech of these children was comparable to that seen in normal children at the same level of linguistic development. As with normal children, these inappropriate word extensions reflected varying levels of lexical knowledge. The findings of this study are discussed in terms of their clinical applicability for lexical training with language-disordered children.

Child, Preschool↗
PubMed1983

Linguistic and nonlinguistic features of style in normal and language-impaired children.

This study explored two questions concerning the language-learning styles described in recent investigations of early child language. The first question was whether features suggestive of language-learning style, for example, extent of pronoun use, jargon-like speech, formulaic speech, and certain play behaviors occurred in clusters consistent with the specific lexical distribution patterns of young normal children delineated by Nelson (1973). The second portion of the study addressed whether language-impaired children could be characterized as reflecting the same language-learning styles attributed to normal children. Eight children, four normally-developing and four language-impaired, were classified as "referential" or "expressive" speakers on the basis of their lexical distribution. For both the normal and language-impaired children, linguistic features suggested in the literature as correlating to one or another language-learning style were found to exist in clusters consistent with the children's pattern of lexical distribution. In addition, analyses of videotaped samples coded for the focus and context of the normal and language-impaired children's play behaviors revealed object-based and social-interaction-based activities that were generally consistent with the children's lexical distribution.

Child Language↗
PubMed1983

Performative and presuppositional skills in language-disordered and normal children.

The presuppositional and performative abilities of language-disordered and normal children were compared, controlling for the children's ability to use the lexical items required in the experimental tasks. Subjects were 36 children, 18 normal and 18 language-disordered, functioning at a single-word level of linguistic development. Results revealed that both the language-disordered and the normal children showed a tendency to encode changing rather than unchanging situational elements. The two groups of children also demonstrated similar levels of imperative and declarative performance intent. For both groups, performative and presuppositional behaviors were usually in the form of word productions. Discrepancies between the findings of this and other investigations are discussed with respect to the size of the children's lexicons, their expressive command of the lexicon, chronological age, and representational skills.

Child Language↗
PubMed1982

Early lexical acquisition in children with specific language impairment.

This study examined the characteristics of early lexical acquisition in children with specific language impairment. Sixteen unfamiliar words and referents were exposed across 10 sessions to language-impaired and normal children matched for level of linguistic development. Posttesting revealed similar comprehension-production gaps in the two groups of children. In addition, both groups showed greater comprehension and production of words referring to objects than words referring to objects than words referring to actions. However, the language-impaired children's object word bias was not as marked as that of the normal children. For both groups, words containing initial consonants within the children's production repertoires were more likely to be acquired in production than words containing consonants absent from the children's phonologies. A similar tendency was not seen for comprehension.

Child, Preschool↗
PubMed1977

Viloxazine, sleep, and subjective feelings.

The sleep of eight volunteers (mean age 55) was recorded electrophysiologically while viloxazine 200 mg was taken daily for 3 weeks, preceded and followed by a week of matching blanks. The volunteers also made ratings of their feelings on visual analogue scales. Another 15 volunteers (mean age 34) took viloxazine 300 mg daily for 3 weeks, preceded and followed by 3 weeks of matching blanks, and they also made daily ratings of feelings. The drug diminished sleep duration and caused more frequent and longer transitions into wakefulness and drowsiness. Slow-wave sleep decreased and stage 2 increased. REM sleep was markedly reduced, especially initially, and there was a withdrawal rebound. Viloxazine impaired subjective concentration mood, and quality of sleep. Three volunteers, however, had striking mood elevation. The drug caused a small loss of weight, which correlated with gastrointestinal symptoms. Three older subjects experienced withdrawal vomiting and prostration. Viloxazine shares properties with imipramine and with amphetamines.

Adult↗