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Biomedical subjects

C Smith

Publications and source records attributed to C Smith.

At least 217 records · Page 12Linked to original sources
PubMed2000

Depression among victims of south Mississippi's methyl parathion disaster.

Human-induced disasters have long been considered responsible for a wide array of physiological, psychological, and economic distress. This study examined depressive symptoms among victims of south Mississippi's methyl parathion disaster. Results indicated that irrespective of the level of methyl parathion contamination in respondents' dwellings, more than half the victims interviewed reported depressive symptoms at levels suggesting probable clinical depression. Those at greatest risk of depressive symptoms were people who had been exposed to the neurotoxin for the longest period of time, among whom there was an overrepresentation of women and African Americans. Despite high statistical levels of depression, few victims used mental health services. Implications for social work's response to human-induced disasters are provided.

Adult↗
PubMed2000

Mucosa-associated lymphoid tissue lymphomas in two patients with rheumatoid arthritis on second-line agents, and secondary Sjögren's syndrome.

We report two patients with rheumatoid arthritis and secondary Sjögren's syndrome whose disease was complicated by a mucosa-associated lymphoid tissue (MALT) lymphoma. Although this particular type of lymphoma is associated with primary Sjögren's syndrome, it has not been described, to our knowledge, in the context of rheumatoid arthritis and Sjögren's syndrome. The potential causative factors are discussed.

Adult↗
PubMed2000

Hematopoietic stem cells.

Hematopoietic stem cells are rare cells found in the bone marrow, peripheral blood, placenta, and elsewhere that sustain the hematopoietic system. The current review will focus on the evolving views of the biology of these cells. Because hematopoietic stem cells have been studied and transplanted for several decades, lessons learned from studying these cells may provide useful paradigms for the study of mesenchymal stem cells.

Animals↗
PubMed2000

Inflammatory activation of human brain endothelial cells by hypoxic astrocytes in vitro is mediated by IL-1beta.

Leukocyte infiltration into the brain contributes to the development of ischemic brain damage and is mediated by endothelial/leukocyte adhesion molecules, cytokines, and chemokines released by ischemic brain cells. In this study, we provide evidence that human astrocytes (FHAs) subjected to in vitro hypoxia produce proinflammatory mediator(s) capable of up-regulating inflammatory genes, including intercellular adhesion molecule-1, interleukin (IL)-1beta, tumor necrosis factor-alpha, IL-8, and monocyte chemotactic protein-1 (MCP-1) in human cerebromicrovascular endothelial cells (HCECs). FHAS were exposed to hypoxia in an anaerobic chamber for 4 hours, followed by reoxygenation for 24 hours. Astrocyte-conditioned media (ACM) collected from normoxic FHAS or FHAS subjected to hypoxia/reoxygenation were applied to HCEC cultures for 4 to 24 hours. Semiquantitative reverse transcription-polymerase chain reaction, immunocytochemistry, and enzyme-linked immunosorbent assay demonstrated up-regulation of intercellular adhesion molecule-1 in HCECs exposed to hypoxic ACM. A pronounced elevation in cytokine IL-1beta and tumor necrosis factor-alpha, and chemokine IL-8 and MCP-1 mRNA, accompanied by increased release of immunoreactive cytokines and chemokines into cell media was observed in HCECs exposed to hypoxic ACM. Hypoxia/reoxygenation induced a transient (4 to 18 hours of reoxygenation) up-regulation of IL-1beta mRNA in FHAS and a two- to threefold increase in IL-1beta levels secreted into ACM. Pretreatment of FHAS with 10 micromol/L dexamethasone inhibited both hypoxia-induced expression/secretion of IL-1beta and the ability of hypoxic ACM to induce inflammatory phenotype in HCECs. The ability of hypoxic ACM to up-regulate inflammatory genes in HCECs was inhibited in the presence of IL-1 receptor antagonist (IL-1Ra) and by pretreating ACM with the blocking anti-IL-1beta antibody. These findings strongly implicate IL-1beta secreted by hypoxic astrocytes in triggering inflammatory activation of HCECs and thereby influencing inflammatory responses at the site of the blood-brain barrier.

Antisense Elements (Genetics)↗
PubMed2000

Breast cancer, passive and active cigarette smoking and N-acetyltransferase 2 genotype.

The relationship of breast cancer to cigarette smoking is inconsistent in the literature, possibly due in part to heterogeneity in carcinogen metabolism. N-acetyltransferase 2 (NAT2) enzyme activity is believed to play a role in the activation of tobacco smoke carcinogens. We examined the effect of NAT2 genetic polymorphisms on risk of breast cancer from active and passive smoking. Women were recruited from those who had suspicious breast masses detected clinically and/or mammographically. Questionnaire data were collected prior to biopsy diagnosis to blind subjects and interviewers. Histopathology showed 113 cases with mammary carcinoma (30 carcinoma in situ) and 278 controls with benign breast disease. NAT2 genotype was determined using allele-specific polymerase chain reaction amplification to detect slow acetylator mutations. Effects of passive and active tobacco smoke and of NAT2 genotype on breast cancer risk were examined with logistic regression controlling for known risk factors. Models first included all controls, and subsequently 107 with no or low risk (normal breast or no hyperplasia), and finally 148 with high risk (hyperplasia, atypical hyperplasia, complex fibroadenomas). Referents had no active or passive smoke exposure. We found no association between breast cancer risk and NAT2, smoking status (never, former, current), smoking duration, or cigarettes per day. There were no effects of passive exposure among never-smokers. Models were unchanged across control groups. There were no statistical interactions between tobacco smoke exposure and NAT2. The results were similar when restricting the analysis to invasive cancers. These findings do not support the hypothesis that NAT2 is a risk factor for breast cancer or that it alters susceptibility to tobacco smoke.

Adult↗
PubMed2000

Expression from the herpes simplex virus type 1 latency-associated promoter in the murine central nervous system.

Herpes simplex virus type 1 (HSV-1) establishes latency in neurones of both the central (CNS) and peripheral nervous system and can be used to drive long-term expression of the lacZ reporter gene by insertion of an encephalomyocarditis virus IRES-linked gene 1.5 kb downstream of the latency-associated transcript (LAT) start site. However, the kinetics of LAT promoter (LAP) activity, and its ability to function in all neuronal types within the CNS has not been studied in detail. In order to address these issues, mice were infected via the ear pinna with 2x10(6) p.f.u. of either SC16-LbetaA, which contains an IRES-linked lacZ under the control of LAP, or SC16-C3b, which expresses LacZ under the control of the human cytomegalovirus immediate early (HCMV-IE) promoter. Three to five animals from each group were sampled over a time-course from 5 days to 1 year post-infection (p.i.), and brainstem and spinal cord sections were examined histochemically for LacZ expression. We found that HCMV-IE promoter activity could be detected within distinct CNS regions from 5 to 15 days p.i. In contrast, LAP-driven LacZ expression was first detected at 7 days p.i. and persisted for at least 1 year. At times up to 34 days p.i., LAP activity was seen in similar regions of the CNS as those which were positive for HCMV-IE promoter activity during the acute stage of infection. After 34 days, however, the numbers of cells in which the LAP was active decreased and labelled motorneurones were predominantly detected in the facial and hypoglossal nuclei and occasionally also in the ventral spinal cord. These results suggest that following the establishment of latency in the CNS, the efficiency of long-term LAP-mediated gene expression may be influenced by the neuronal cell type in which latency is established.

Animals↗
PubMed2000

Molecular manifestations and molecular determinants of telomere capping.

Multiple interacting components of the telomere, together with telomerase (and sometimes recombination), determine whether a telomere will be functional, allowing cell proliferation. The various components reinforce each other, providing for a robust and resilient system of protection and replenishment of telomeres. A characteristic of a telomere is that its structural features elicit responses that allow it to be dynamically recapped. Eliciting a DNA damage response through uncapping of a telomere appears to be one way in which telomerase action at that telomere is stimulated. Thus, as long as a timely and appropriate recapping of the telomere is possible, regulated uncapping of a telomere appears to be not only normal, but even required for optimal telomere maintenance. Telomere length and the presence of telomerase provide an example of a pair of interacting components that determine telomere capping function. Telomerase is dispensable in cells with sufficiently long telomeres; but in cells with short telomeres lacking telomerase, cells lose the ability to proliferate, and in some cell types, telomere fusions are increased. However, expressing telomerase can make even very short telomeres functional. Many interesting questions remain as to the mechanisms of these biological effects.

Animals↗
PubMed2000

Structure of the nucleotide-binding domain of Plasmodium falciparum rab6 in the GDP-bound form.

Rab proteins are small Ras-like GTPases which play important roles in regulating intracellular vesicle trafficking. The nucleotide-binding domain of Rab6 from the malaria parasite Plasmodium falciparum was crystallized with GDP bound to the active site. The MAD phasing technique was used to determine the crystal structure to 2.3 A resolution. Comparisons of the structure of GDP-bound PfRab6 with the recently determined structures of Rab3A in complex with either a GTP analog or with GTP and Rabphillin present structural evidence supporting the traditional model for the molecular GTP/GDP switch in Rab proteins. PfRab6 residues homologous to those distinguishing human Rab6 isoforms, which differ in binding to Rabkinesin-6 in human cells, are located next to the recognized complementarity-determining region (CDR) and constitute a conceptual broadening of that domain. Despite significant observable differences in Golgi ultrastructure, the Rab6 core structure and switch mechanism appear highly conserved when compared with murine Rab3a structures. A significant difference between the PfRab6 and higher eukaryotic Rabs may be the lack of CDR features that allow binding interactions with Rabkinesin-type effectors.

Amino Acid Sequence↗
PubMed2000

The impact of nausea and vomiting on women: a burden of early pregnancy.

Nausea and vomiting are troublesome symptoms occurring in the first trimester of pregnancy. The aim of this study was to describe the impact these symptoms have on women in early pregnancy by interviewing, using a structured questionnaire, 593 pregnant women presenting with nausea and vomiting in the first trimester of pregnancy. The women were asked to complete the Rhodes index of nausea and vomiting and the MOS 36 Short Form Health Survey (SF-36). Symptoms of nausea and vomiting started early in pregnancy. Nausea was the most troublesome symptom experienced by women, both in its duration and intensity. Low scores for the SF-36 were found for all items, particularly physical functioning, energy and social functioning. The women described substantial effects on working, household duties and parenting activities. Findings from this study suggest nausea and vomiting in early pregnancy has a profound impact on women's general sense of well-being and day to day life activities.

Activities of Daily Living↗
PubMed2000

Effects of the salience of pitch and periodicity information on the intelligibility of four-channel vocoded speech: implications for cochlear implants.

Recent simulations of continuous interleaved sampling (CIS) cochlear implant speech processors have used acoustic stimulation that provides only weak cues to pitch, periodicity, and aperiodicity, although these are regarded as important perceptual factors of speech. Four-channel vocoders simulating CIS processors have been constructed, in which the salience of speech-derived periodicity and pitch information was manipulated. The highest salience of pitch and periodicity was provided by an explicit encoding, using a pulse carrier following fundamental frequency for voiced speech, and a noise carrier during voiceless speech. Other processors included noise-excited vocoders with envelope cutoff frequencies of 32 and 400 Hz. The use of a pulse carrier following fundamental frequency gave substantially higher performance in identification of frequency glides than did vocoders using envelope-modulated noise carriers. The perception of consonant voicing information was improved by processors that preserved periodicity, and connected discourse tracking rates were slightly faster with noise carriers modulated by envelopes with a cutoff frequency of 400 Hz compared to 32 Hz. However, consonant and vowel identification, sentence intelligibility, and connected discourse tracking rates were generally similar through all of the processors. For these speech tasks, pitch and periodicity beyond the weak information available from 400 Hz envelope-modulated noise did not contribute substantially to performance.

Cochlear Implants↗
PubMed2000

Functional consequences of a polymorphism affecting NF-kappaB p50-p50 binding to the TNF promoter region.

Stimulation of the NF-kappaB pathway often causes p65-p50 and p50-p50 dimers to be simultaneously present in the cell nucleus. A natural polymorphism at nucleotide -863 in the human TNF promoter (encoding tumor necrosis factor [TNF]) region provides an opportunity to dissect the functional interaction of p65-p50 and p50-p50 at a single NF-kappaB binding site. We found that this site normally binds both p65-p50 and p50-p50, but a single base change specifically inhibits p50-p50 binding. Reporter gene analysis in COS-7 cells expressing both p65-p50 and p50-p50 shows that the ability to bind p50-p50 reduces the enhancer effect of this NF-kappaB site. Using an adenoviral reporter assay, we found that the variant which binds p50-p50 results in a reduction of lipopolysaccharide-inducible gene expression in primary human monocytes. This finding adds to a growing body of experimental evidence that p50-p50 can inhibit the transactivating effects of p65-p50 and illustrates the potential for genetic modulation of inflammatory gene regulation in humans by subtle nucleotide changes that alter the relative binding affinities of different forms of the NF-kappaB complex.

Adenoviridae↗
PubMed2000

Massive hematuria in adults with Klippel-Trenaunay syndrome associated with vascular malformation of the bladder.

Although hematuria has been reported in children with Klippel-Trenaunay syndrome, it is a rare presentation in the adult population. Two cases of massive hematuria in adults with Klippel-Trenaunay syndrome are reported here. A unique feature was venous malformations of the bladder which were responsible for massive recurrent bleeding in 1 patient. The clinical presentation and management are discussed. Conservative endoscopic and arteriographic control seems to be appropriate as initial management in these patients.

Adult↗
PubMed2000

Treatment with nasal CPAP decreases automobile accidents in patients with sleep apnea.

We studied 50 consecutive patients to test the hypothesis that successful treatment of obstructive sleep apnea with nasal continuous positive airway pressure (nasal CPAP) will decrease automobile accidents in patients with sleep apnea. Thirty-six (72%) of the patients reported using nasal CPAP regularly during 2 yr. Fourteen patients reported they had not used CPAP during 2 yr. The patients with sleep apnea in this study had a higher automobile crash rate than all drivers in the state of Colorado (0.07 versus 0. 01 crash per driver per year, p < 0.02). Patients who were treated with nasal CPAP had a lower crash rate while being treated than before treatment (0.07 versus 0 crash per driver per year, p < 0.03). Untreated patients with sleep apnea continued to have a high crash rate (0.07 crash per driver before and after diagnosis). Drivers with sleep apnea were reluctant to report their automobile crashes, for the drivers in this study reported only one-third of the crashes in which they were involved. This is the first study to confirm with traffic records that patients with sleep apnea have fewer automobile crashes while being treated with nasal CPAP.

Accidents, Traffic↗
PubMed2000

Telepsychiatry evaluation in the north-west of England: preliminary results of a qualitative study.

A telepsychiatry referral service for patients suffering from anxiety and depression was evaluated from a user perspective. Low-cost video-phones linked a psychiatrist to two general practices in the north-west of England. Quantitative data were collected using a semistructured interview schedule. Twenty-two patients and 13 doctors were interviewed after a video-link consultation. Some users were very positive about the service and recognized its potential benefits, while others were more ambivalent. Patients saw the service as a means of obtaining additional 'expert' advice. General practitioners felt that the service might adversely affect the doctor-patient relationship in psychiatry. Both patients and clinicians recognized that the video-link modified normal interaction. Users need to adapt to this form of communication. An induction session is recommended for both patients and clinicians.

Anxiety↗
PubMed2000

(Re-) constructing pre-linguistic interpersonal processes to promote language development in young children with deviant or delayed communication skills.

BACKGROUND: Approaches to intervention with young children with delayed or deviant communication skills have tended to focus directly on the production and comprehension of linguistic forms. Research in developmental psychology, however, has highlighted the role of joint attention and action within a mutually negotiated frame in early communicative development. AIMS: An approach to intervention was developed which uses graded participation in such 'formats' to promote language development in 3- to 5-year-olds with significant delays or deviance in communication skills. This study was designed to evaluate this in comparison with a more conventional approach. SAMPLE: The sample comprised twenty 3- to 5-year-olds attending a diagnostic nursery or a speech and language support centre attached to a mainstream primary school. METHOD: In the intervention, developmentally ordered sequences of exchange games provided predictable ruled-based and structured joint contexts of action, within which verbal and non-verbal exchanges between an adult and child could be meaningfully used. In the control condition, participants received more conventional intervention focusing more directly on language per se. Level of participation in dyadic play was assessed in terms both of role and cognitive complexity, and for the present study language development was assessed using the verbal subtests of the WPPSI. The study entailed both a between- and a within-subjects design. RESULTS: Cross-sectional and longitudinal comparisons confirmed that this form of intervention was significantly more effective than the control condition in increasing children's level of participation in social game formats and in promoting their language development; moreover, these were significantly correlated. CONCLUSIONS: The results indicate that the development of language skills can be promoted more effectively through (re-) constructing the interpersonal framework of pre-linguistic communicative development than through conventional intervention focusing directly upon language per se.

Adult↗
PubMed2000

Empathy in the afternoon.

Empathy - the power of understanding and imaginatively entering into another person's feelings.

Adolescent↗
PubMed2000

The clinical enquiry service; benign intracranial hypertension.

Considering how uncommon the condition is (3.3 cases per 100 000 women aged 15 to 44 years) the CEU has received a surprising number of enquiries about contraceptive options for women with a diagnosis of idiopathic benign interacranial hypertension.

Adolescent↗