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Biomedical subjects

C A Smith

Publications and source records attributed to C A Smith.

At least 307 records · Page 17Linked to original sources
PubMed1994

Ventilatory afterdischarge and central respiratory drive interactions in the awake goat.

We have previously established the existence of ventilatory afterdischarge (VAD) in the awake goat by means of an isolated perfused carotid body (CB) technique. In the present series of experiments we used this animal preparation to examine the effects of systemic (central nervous system) hypoxia, mild hypercapnia, and hypocapnia on the manifestation of VAD in ventilatory variables and respiratory muscle electromyogram activity after hypoxic stimulation of the isolated CB. With systemic isocapnic normoxia, inspired minute ventilation remains above control for 30-40 s (time constant = 16.8 s) after termination of CB hypoxia; however, with systemic hypocapnia, VAD is short (time constant = 5.5 s) and hypoventilation is common after removal of CB stimulation. During mild systemic hypercapnia, VAD is prolonged (time constant = 39.9 s). However, systemic (central nervous system) hypoxia did not decrease VAD (time constant = 17.0 s). These results indicate that the manifestation of VAD is more sensitive to the level of arterial PCO2 and central chemoreceptor activity than it is to the state of central oxygenation. Inspiratory and expiratory muscle electromyogram activities qualitatively tracked ventilation during CB stimulation and during the VAD period in all conditions.

Animals↗
PubMed1994

A volume-dependent apneic threshold during NREM sleep in the dog.

We determined the causes of central apnea that commonly follow the hyperpnea resulting from brief airway occlusion during non-rapid-eye-movement (NREM) sleep. Ventilation and end-tidal gases were measured before, during, and after 214 trials of 15-20 s of tracheal occlusion in three dogs during NREM sleep. Airway occlusion was accompanied by progressive increases in inspiratory effort and was followed by transient one- to four-breath hyperapneas, with subsequent central apnea [3-15 times eupneic control expiratory duration (TE)] in 62% of occlusion trials. Significant TE prolongation after hyperventilation did not occur until tidal volume (VT) was three times greater than control; i.e., there was a volume-dependent apneic threshold. Transient electroencephalogram arousal at the end of the occlusion often augmented VT, thereby contributing to the subsequent central apnea; however, arousal was not required for the apnea to occur. Significant transient hypocapnia (up to -12 Torr arterial PCO2) commonly occurred after release of airway occlusion but was not closely correlated with the length of central apnea. During vagal blockade, after release of airway occlusion, significant transient hyperventilation occurred but at VT < 40% greater than control, and TE prolongation was markedly reduced. In summary, after release of airway occlusion in NREM sleep, 1) VT greater than three times eupnea was necessary to cause central apnea, 2) transient arousal at the termination of airway occlusion caused longer apneas by augmenting VT, and 3) transient hypocapnia per se made a significant but minor contribution to the postocclusion central apnea.

Airway Obstruction↗
PubMed1994

Positive selection by purified MHC class II+ thymic epithelial cells in vitro: costimulatory signals mediated by B7 are not involved.

We have investigated the possibility that the costimulatory signals required for activation of mature T cells also play a role in providing differentiation signals for positive selection during T-cell development. We show that purified MHC Class II+ thymic epithelial cells are able to support positive selection in vitro but lack both the functional capacity to deliver costimulatory signals and expression of the costimulatory ligand B7. Our results suggest that the additional signals provided by costimulatory ligands are not required for TCR-mediated positive selection, although other ancillary signals provided by thymic epithelial cells may be involved.

Animals↗
PubMed1994

The lived experience of care within the context of cultural diversity.

This study explored the health promotion experiences of 10 Euro-American advanced practice nurses who provided care in rural settings to predominantly African American families. Relational themes that emerged from the discussions of the participants were authentic connecting, unconditional help giving, and openness to knowing. The constitutive pattern that emerged across all the texts was care as uncovering healing. The nurses' knowledge or lack of knowledge about differences in cultural health beliefs and practices was in the background, whereas the relationship was the contextual core of the experience that transcended the knowledge of differences.

Adolescent↗
PubMed1994

Form C of the MHLC scales: a condition-specific measure of locus of control.

Form C of the Multidimensional Health Locus of Control (MHLC) scales is an 18 item, general purpose, condition-specific locus of control scale that could easily be adapted for use with any medical or health-related condition. Data from 588 patients with one of four conditions--rheumatoid arthritis, chronic pain, diabetes, or cancer--were utilized to establish the factor structure of Form C and to establish the reliability and validity of the resultant four subscales: Internality; Chance; Doctors; and Other (powerful) People. The alpha reliabilities of the subscales are adequate for research purposes. Data from the arthritis and chronic pain subjects established that the Form C subscales were moderately stable over time and possessed considerable concurrent and construct validity. Some discriminant validity of Form C with Form B of the MHLC was also demonstrated.

Arthritis, Rheumatoid↗
PubMed1994

The warm-up procedure: to stretch or not to stretch. A brief review.

Stretching exercises are either performed alone or with other exercises as part of the athlete's warm-up. The warm-up is designed to increased muscle/tendon suppleness, stimulate blood flow to the periphery, increase body temperature, and enhance free, coordinated movement. The purpose of this paper is to review the literature regarding stretching, with the aim of defining its role during the warm-up. Implications of stretching on muscle/tendon flexibility, minimizing injury, enhancing athletic performance, and generally preparing the athlete for exercise are discussed. Physiology applied to stretching is also discussed together with different related techniques and practical aspects. A proposed model stretching regime is presented based on the literature reviewed.

Athletic Injuries↗
PubMed1994

Productive re-arrangement at both alleles of the T-cell receptor beta-chain locus in CD4 T-cell clones specific for influenza haemagglutinin.

T-cell receptor (TcR) beta-chain usage, and VDJ junctional region sequences thereof in a panel of CD4+ T-cell clones Ad-, or Ak- or Ek-restricted for major antigenic sites of influenza haemagglutinin (H3 subtype), were investigated. Direct sequencing of cDNA, obtained by polymerase chain reaction, revealed that the majority of T-cell clones contained both productive and non-productive rearranged transcripts. Moreover, T-cell clones specific for p206-227 (Ad) or p245-265 (AK) contained double-productive re-arranged transcripts (V beta 6 J beta 2.6, V beta 4, J beta 1.2) and (V beta 6 J beta 1.3, V beta 8.2, J beta 1.5) respectively. However, FACS analysis with V beta-specific monoclonal antibodies established that, for each of these T-cell clones, only a single beta-chain was expressed at the cell surface, thereby indicating post-transcriptional editing.

Alleles↗
PubMed1994

Dis-attachment.

Explore the source record for details and available documents.

Adolescent↗
PubMed1994

Human PAX gene expression and development of the vertebral column.

The human gene HuP48 is a member of the PAX family of developmental control genes. Common to all members of this family is a highly conserved DNA sequence, the paired box sequence. In several species, paired box-containing genes function in normal embryonic morphogenesis. To investigate the possible involvement of PAX genes in the development of the human skeleton, the authors analyzed the expression of the paired box-containing gene, HuP48, in the fetal human vertebral column. In addition, the authors sequenced the paired box region of HuP48 from patients with congenital vertebral anomalies associated with Klippel-Feil syndrome. Using in situ hybridization, it was observed that HuP48 is expressed in a segmented pattern in the developing spine, specifically in the cells of the intervertebral disks of seven- to eight-week-old fetuses. At this stage in development, HuP48 expression appears to be restricted to the vertebral column. The pattern of expression of HuP48 indicates that it plays a role in establishing the segmented pattern of the vertebral column, perhaps by helping to establish and/or maintain, or both, a border between two different populations of cells, those of the prevertebrae and those of the intervertebral disks. Analysis of HuP48 paired box sequences in genomic DNA obtained from patients with congenital segmentation anomalies revealed no mutations in this highly conserved sequence.

Base Sequence↗
PubMed1994

Immunodominance correlates with T-cell receptor (alpha beta) gene usage in the class II-restricted response to influenza haemagglutinin.

Class II-restricted T-cell clones elicited by natural infection with influenza A virus (H3N2 subtype) exhibit extensive diversity in their recognition specificity for the envelope glycoprotein, haemagglutinin, and focus on hypervariable regions of the HA1 subunit that feature in antigenic drift. However, T-cell clones established from the same individual focus on a single antigenic site with differing fine specificity for mutant viruses. We wished to determine whether such diversity of the haplotype and contrasting immunodominance of the individual's repertoire was mirrored in T-cell receptor (TcR) gene usage. A structural analysis was undertaken of the alpha and beta chains of TcR from a panel of CD4+ T-cell memory clones established in vitro after natural infection with X31 virus and specific for eight distinct antigenic sites of the HA1 subunit: p48-67 (Ak), p58-73 (Ad), p120-139 (Ak), p177-199 (Ad), p186-200 (Ad), p226-245 (Ek), p246-265 (Ek) and p269-288 (Ak). Direct sequencing of the alpha and beta chains, using the polymerase chain reaction, revealed that T-cell clones derived from the same donor used identical V beta D beta J beta and V alpha J alpha elements. Moreover there was extensive diversity in usage of V beta (V beta 1 or V beta 4 or V beta 8) genes between individual mice, in association with diverse J beta and V alpha J alpha elements for the recognition of a common antigenic peptide. We conclude that the CD4+ T-cell memory repertoire of the individual, following primary exposure to infectious virus, is oligoclonal and recruited from a limited number of precursor cells.

Amino Acid Sequence↗
PubMed1993

Effect of tamoxifen on serum cholesterol and lipoproteins during chemohormonal therapy.

The effect of tamoxifen on serum cholesterol, high density lipoprotein cholesterol (HDL-cholesterol), low density lipoprotein cholesterol (LDL-cholesterol) and the ratio of LDL-cholesterol to HDL-cholesterol (LDL-C/HDL-C) was investigated in breast cancer patients undergoing therapy for advanced disease. Longitudinal studies in 24 patients treated with tamoxifen (10 mg, twice daily) indicated average decreases in total serum cholesterol (17%) and LDL-cholesterol (27%), whereas the effect of tamoxifen on HDL-cholesterol varied with the individual patient. There was a significant decrease in the LDL-C/HDL-C ratio (33%) consistent with a decreased risk for coronary artery disease. This beneficial influence of tamoxifen on risk factors associated with cardiovascular disease was evident in both premenopausal and postmenopausal patients whether tamoxifen was administered alone or in combination with cytotoxic chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Immunocytochemical localization of the plasma membrane calcium pump, calbindin-D28k, and parvalbumin in Purkinje cells of avian and mammalian cerebellum.

A monoclonal antibody produced against the human erythrocyte plasma membrane calcium pump (PMCA) was shown to react immunohistochemically with an epitope of the PMCA in avian and mammalian cerebellum. Western blot analysis of purified synaptosomes and homogenates from avian cerebellum revealed major immunoreactive proteins with molecular masses (130 kDa and 138 kDa) similar to those of purified erythrocyte PMCA. Dual-imaging confocal immunofluorescence microscopy of avian cerebellum showed that the PMCA antibody stained the periphery of the soma whereas calbindin-D28k was located in the cytosol. PMCA heavily stained the more distal dendrites of the Purkinje cells and, within the resolution of the fluorescence procedure, colocalized with calbindin-D28k. By using alkaline phosphatase-conjugated second antibody, PMCA was again localized to the peripheral soma, to a segmental pattern in dendrites, and to presumed spiny elements. The soma periphery and dendrites of Purkinje cells of the rat cerebellum were also prominently stained with anti-PMCA antibody and compared to parvalbumin localization. Dendritic depolarization and dendritic spiking behavior are significant Ca(2+)-dependent events of Purkinje cells. The rapid decline of intracellular free Ca2+ after the rapid rise time of Ca2+ transients is considered to be due to sequestration by Ca2+ buffers, uptake by intracellular stores, and Ca2+ extrusion mechanisms, the latter a function of PMCA now shown immunohistochemically to be a prominent feature of Purkinje cell dendrites.

Alkaline Phosphatase↗
PubMed1993

Herpes simplex virus infected cell polypeptide 4 preferentially represses Sp1-activated over basal transcription from its own promoter.

Herpes simplex virus type 1 infected cell polypeptide 4 (HSV-1 ICP4) is a multifunctional phosphoprotein that is essential for viral infection. It is both a repressor and an activator of viral gene expression depending upon the promoter. ICP4 represses transcription from its own promoter. In the present study, we used general transcription factors from HeLa cell nuclear extracts, recombinant TATA binding protein (TBP) and TFIIB, and the transcriptional activator Sp1 to reconstitute in vitro transcription for the ICP4 promoter and to examine the effects of purified ICP4 on transcription. ICP4 was able to effectively repress Sp1-induced transcription from ICP4 promoter templates that contain one or multiple Sp1 binding sites. The observed inhibition required the ICP4 binding site that spans the transcription initiation site. ICP4 did not inhibit basal transcription as inferred by its inability to inhibit transcription when (i) Sp1 was not included in transcription reactions, (ii) the templates contained no Sp1 binding sites, and (iii) TBP was used in place of TFIID in the reactions. The in vitro observations were consistent with the behavior of the same constructs expressed in cells from the herpes simplex virus type 1 genome. DNase I footprinting experiments revealed that ICP4 could co-occupy the ICP4 promoter region with TBP-TFIIB, indicating that ICP4 does not necessarily exclude these factors from binding to the TATA region. The data suggest that the repressive effects of ICP4 observed in this study result from ICP4 interfering with the interactions contributing to Sp1-induced transcription.

Base Sequence↗
PubMed1993

Comparative analysis of binding of human damaged DNA-binding protein (XPE) and Escherichia coli damage recognition protein (UvrA) to the major ultraviolet photoproducts: T[c,s]T, T[t,s]T, T[6-4]T, and T[Dewar]T.

Human cells contain a protein that binds to UV-irradiated DNA with high affinity. This protein, the damaged DNA-binding protein (DDB), is absent from some xeroderma pigmentosum complementation group E cell strains; therefore, it has been suggested that it may be the damage recognition subunit of a human excision nuclease complex. However, the identity of the UV photoproduct bound by DDB and the role of this protein in nucleotide excision repair have been controversial. In this study, we used several synthetic DNA substrates, each of which contains one of the major UV photoproducts, and DDB purified to apparent homogeneity to quantify the specific binding of DDB to various photoproducts. For comparison, the binding of the same photoproducts by the Escherichia coli damage recognition protein UvrA, which is known to be a subunit of the E. coli excision nuclease, was also measured. UvrA and DDB each bound with high affinity to T[t,s]T, T[6-4]T, and T[Dewar]T, but only marginally discriminated between an undamaged oligomer and an oligomer with a T[c,s]T. In contrast to these similarities with regard to the binding to UV photoproducts, UvrA bound to another excision repair substrate, the psoralen-thymine monoadduct, with high specificity, whereas DDB was unable to distinguish between psoralen-adducted DNA and undamaged DNA. We conclude that DDB may play a special role in the repair of UV damage, but it cannot be the sole damage recognition subunit of human excision nuclease.

Adenosine Triphosphatases↗