Biomedical subjects

J C Smith

Publications and source records attributed to J C Smith.

At least 91 records · Page 5Linked to original sources

PubMed2000

Respiratory rhythm generation in neonatal and adult mammals: the hybrid pacemaker-network model.

We review a new unified model of respiratory rhythm generation - the hybrid pacemaker-network model. This model represents a comprehensive synthesis of cellular and network mechanisms that can theoretically account for rhythm generation in different functional states, from the most reduced states in the neonatal nervous system in vitro to the intact adult system in vivo. The model incorporates a critical neuronal kernel consisting of a network of excitatory neurons with state-dependent, oscillatory bursting or pacemaker properties. This kernel, located in the pre-Bötzinger complex of the ventrolateral medulla, provides a rudimentary pacemaker network mechanism for generating an inspiratory rhythm, revealed predominately in functionally reduced states in vitro. In vivo the kernel is embedded in a larger network that interacts with the kernel via inhibitory synaptic connections that provide the dynamic control required for the evolution of the complete pattern of inspiratory and expiratory network activity. The resulting hybrid of cellular pacemaker and network properties functionally endows the system with multiple mechanisms of rhythm generation. New biophysically realistic mathematical models of the hybrid pacemaker-network have been developed that illustrate these concepts and provide a computational framework for investigating interactions of cellular and network processes that must be analyzed to understand rhythm generation.

Animals↗

PubMed2000

Microstructure of the rat's intake of food, sucrose and saccharin in 24-hour tests.

A detailed description of a method for collecting meal and drinking bout patterns for the rat over 24-h preference tests is presented. Both the hardware and software are described for data collection with a 6-s resolution. As an example of the value of knowing the details of ingestive patterns, data are presented describing the meal and drinking bout patterns during daylong preference tests between sucrose or saccharin vs. water. During these two-day tests at each of a wide range of concentrations, the intake of powdered Purina Chow, sucrose and saccharin were observed and quantified into meals or bouts. The analysis allowed for a comparison of sucrose and saccharin ingestion in terms of number of bouts, duration of bouts, rate of licking during bouts, the juxtaposition of eating and drinking and the day/night patterns of intake. Comparisons of drinking during bouts were made with electrophysiological and short-term taste test data. The usefulness of microstructure analysis is discussed.

Animals↗

PubMed2000

The check box: determining pregnancy status to improve maternal mortality surveillance.

OBJECTIVE: More than half of pregnancy-related deaths are not identified through routine surveillance methods. The purpose of this study was to evaluate the effectiveness of the pregnancy check box on death certificates in ascertaining pregnancy-related deaths. METHODS: Data derived from the Centers for Disease Control and Prevention's ongoing Pregnancy Mortality Surveillance System were used to identify states that included a check box on the death certificate in 1991 and 1992. Death certificates from those states were evaluated to determine the number and proportion of pregnancy-related deaths identified by a marked check box. Characteristics of death were also examined. RESULTS: Sixteen states and New York City included a check box or question specifically asking about pregnancy of the decedent. Of the 425 pregnancy-related deaths identified in the 17 reporting areas, 124 (29%) were determined to be pregnancy-related deaths only because of the pregnancy status information provided in the check box. The proportion of deaths identified only by a marked check box ranged from less than 5% for four states to 40% or more for seven states. CONCLUSIONS: The availability of pregnancy status information on death certificates is a simple and effective aid in ascertaining a pregnancy-related death, when no other indicators of pregnancy appear on the death certificate. Routine use of the pregnancy check box for all states would lead to substantially increased classification of maternal deaths and more accurate classification of the causes of and risk factors for maternal deaths.

Death Certificates↗

PubMed2000

A screen for targets of the Xenopus T-box gene Xbra.

Brachyury (T), a member of the T-box gene family, is essential for the formation of posterior mesoderm and notochord in vertebrate development. Expression of the Xenopus homologue of Brachyury, Xbra, causes ectopic ventral and lateral mesoderm formation in animal cap explants and co-expression of Xbra with Pintallavis, a forkhead/HNF3beta-related transcription factor, induces notochord. Although eFGF and the Bix genes are thought to be direct targets of Xbra, no other target genes have been identified. Here, we describe the use of hormone-inducible versions of Xbra and Pintallavis to construct cDNA libraries enriched for targets of these transcription factors. Five putative targets were isolated: Xwnt11, the homeobox gene Bix1, the zinc-finger transcription factor Xegr-1, a putative homologue of the antiproliferative gene BTG1 called Xbtg1, and BIG3/1A11, a gene of unknown function. Expression of Xegr-1 and Xbtg1 is controlled by Pintallavis alone as well as by a combination of Xbra and Pintallavis. Overexpression of Xbtg1 perturbed gastrulation and caused defects in posterior tissues and in notochord and muscle formation, a phenotype reminiscent of that observed with a dominant-negative version of Pintallavis called Pintallavis-En(R). The Brachyury-inducible genes we have isolated shed light on the mechanism of Brachyury function during mesoderm formation. Specification of mesodermal cells is regulated by targets including Bix1-4 and eFGF, while gastrulation movements and perhaps cell division are regulated by Xwnt11 and Xbtg1.

Amino Acid Sequence↗

PubMed2000

XSIP1, a Xenopus zinc finger/homeodomain encoding gene highly expressed during early neural development.

We have isolated a Xenopus homologue of the zinc finger/homeodomain-containing transcriptional repressor Smad-interacting protein-1 (SIP1) from mouse. XSIP1 is activated at the early gastrula stage and transcription occurs throughout embryogenesis. At the beginning of gastrulation, XSIP1 is strongly expressed in prospective neurectoderm. At the neurula stage, XSIP1 is highly expressed within the neural plate but weakly in the dorsal midline. At later stages of development transcripts are detected primarily within the neural tube and neural crest. In the adult, XSIP1 expression is detected at variable levels in several organs.

Amino Acid Sequence↗

PubMed2000

Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study.

BACKGROUND: Animal and in vitro data suggest that dyslipidemia plays an important role in the initiation and progression of chronic renal disease, but few prospective studies have been conducted in humans. METHODS: We studied the relationship of plasma lipids to a rise in serum creatinine of 0.4 mg/dL or greater in 12,728 Atherosclerosis Risk in Communities (ARIC) participants with baseline serum creatinine that was less than 2.0 mg/dL in men and less than 1.8 mg/dL in women. RESULTS: During a mean follow-up of 2.9 years, 191 persons had a rise in creatinine of 0.4 mg/dL or greater, yielding an incidence rate of 5.1 per 1000 person years. Individuals with higher triglycerides and lower high-density lipoprotein (HDL) and HDL-2 cholesterol at baseline were at increased risk for a rise in creatinine after adjustment for race, gender, baseline age, diabetes, serum creatinine, systolic blood pressure, and antihypertensive medication use (all P trends </=0.02). The adjusted relative risk for the highest versus lowest quartile of triglycerides was 1.65 (95% CI, 1.1, 2.5, P = 0.01) and for HDL was 0.47 (95% CI, 0.3, 0.8, P = 0.003). These associations were significant in participants with normal creatinine (defined as <1.4 mg/dL for men and <1.2 mg/dL for women), with diabetes, and without diabetes. The effect of high triglycerides was independent of plasma glucose, but was weaker and less consistent after further adjustment for fasting insulin in nondiabetics. CONCLUSIONS: High triglycerides and low HDL cholesterol, but not low-density lipoprotein cholesterol, predict an increased risk of renal dysfunction. The treatment of these lipid abnormalities may decrease the incidence of early renal disease.

Arteriosclerosis↗

PubMed2000

Prevalence of malnutrition on admission to four hospitals in England. The Malnutrition Prevalence Group.

AIMS: The primary objective was to estimate prevalence of malnutrition on admission to four hospitals. Secondary objectives included assessing the relationship between nutritional status and length of hospital stay, numbers of new prescriptions, new infections and disease severity. METHODS: We entered eligible patients according to predefined quotas for elective and emergency admissions to 23 specialties. We measured height, weight, Body Mass Index and anthropometrics, and recorded history of unintentional weight loss. Patients who had lost > or = 10% of their body weight, had a Body Mass Index <20, or had a Body Mass Index <20 with one anthropometric measurement <15th centile were considered malnourished. RESULTS: Of 1611 eligible patients, 761 did not participate; 269 were too ill; 256 could not be weighed; and 236 refused consent. Eight hundred and fifty were subsequently evaluated. Prevalence of malnutrition on admission was 20%. Length of stay, new prescriptions and infections and disease severity were significantly higher in the malnourished. CONCLUSIONS: One patient in every five admitted to hospital is malnourished. Although this figure is unacceptably high, it may underestimate true prevalence. Malnutrition was associated with increased length of stay, new prescriptions and infections. Malnutrition may also have contributed to disease severity.

Adolescent↗

PubMed2000

Time course and pattern of compensatory ingestive behavioral adjustments to lysine deficiency in rats.

We and others have demonstrated that rats deficient in an essential amino acid (EAA) will consume sufficient quantities of the lacking nutrient to produce repletion when it is made available in solution. In the current series of experiments, we made rats deficient in lysine (LYS) by limiting the level of this EAA in the diet. We then examined licking behavior during approximately 23-h two-bottle intake tests over 4 consecutive days. In three separate experiments, rats were presented with the following: 1) 0.1 mol/L LYS and water, 2) 0.2 mol/L threonine (THR) and water and 3) 0.1 mol/L LYS and 0.2 mol/L THR. Lysine-deficient (LYS-DEF) rats drink significantly more LYS than did nondepleted controls (CON) when this amino acid was available. Meal pattern analysis revealed that the enhanced intake of LYS occurred as a function of a greater number of ingestive bouts, not changes in bout size. A cumulative analysis of LYS intake between CON and LYS-DEF rats revealed that a potentiation of intake developed within 30 min of sampling the solution when LYS and water were available and within 90 min when LYS and THR were the contrasting choices. In conclusion, increased LYS intake in the deficient rats occurs relatively rapidly and appears to be at least somewhat specific. Moreover, LYS deficiency does not seem to enhance the palatability of the limiting amino acid as judged by behaviors such as lick rate and bout size. Instead, LYS-DEF rats relieve the deficiency by increasing the number of drinking episodes initiated.

Animals↗

PubMed2000

Structure of the Malpha2-3 toxin alpha antibody-antigen complex: combination of modelling with functional mapping experimental results.

Modelled structures of the acetylcholine receptor-mimicking antibody, Malpha2-3, both free and bound to its antigen, toxin alpha, are assessed in the light of new experimental mutational data from functional mapping of the paratopic region of Malpha2-3. The experimental results are consistent with the previously-predicted structure of the free antibody, and also demonstrate that structural particularities of the Malpha2-3 combining site that were identified in the models play a role in the protein association. The modelled conformations of the hypervariable loops are discussed in the context of recent new data and analyses. The new mutational data allow several previously-considered modelled structures of the complex to be rejected. Two quite similar models now remain.

Antibodies↗

PubMed2000

A population-based case-control study of farming and breast cancer in North Carolina.

We examined the role of farming and pesticide exposure among 862 cases and 790 controls in a population-based, case-control study of breast cancer conducted in North Carolina between 1993 and 1996. We obtained exposure information through personal interview. Increasing duration of farming was inversely associated with breast cancer risk; odds ratios (95% confidence intervals) were 1.2 (0.8-1.7), 0.8 (0.5-1.2), 0.7 (0.5-1.1), and 0.6 (0.4-0.9) for 1-10, 11-17, 18-23, and >23 years of farming, respectively, relative to nonfarmers. Inverse associations persisted when farming was restricted to calendar time periods of 2,2-bis(p-chlorophenyl)- 1,1,1-trichloroethane (DDT) use or to farming at ages 9-16. Among women who farmed, odds ratios (ORs) were elevated for those who reported being present in fields during or shortly after pesticide application (OR = 1.8, 95% CI = 1.1-2.8) and for those who reported not using protective clothing while applying pesticides (OR = 2.0; 95% CI = 1.0-4.3), but not among those who reported using protective clothing (OR = 0.8; 95% CI = 0.4-1.8). We conclude that residence or work on farms may be associated with a reduced risk of breast cancer. Nevertheless, our results suggest a possible increased risk of breast cancer among a subgroup of farming women who were most likely to be exposed to pesticides.

Adult↗

PubMed2000

Long-standing lateral neck mass as the initial manifestation of well-differentiated thyroid carcinoma.

OBJECTIVE: To analyze the presentation, evaluation, and treatment of a subset of patients with well-differentiated thyroid carcinoma who present with a lateral neck mass and no palpable disease in the thyroid gland. STUDY DESIGN: A retrospective review of all patients undergoing thyroidectomy for malignancy. METHODS: A database of all thyroidectomies performed for malignancy by the Vanderbilt University Department of Otolaryngology-Head and Neck Surgery from 1992 to 1997 was created. Patients who presented with an isolated neck mass without evidence of palpable disease in the thyroid were selected for the study population. RESULTS: There were 60 cases of thyroid malignancy, with 14 cases (23.3%) that presented as isolated lateral neck mass. The characteristics of this group (compared with the population of all thyroid malignancies) include younger age at presentation (37.7 +/- 15.2 y vs. 49.8 +/- 15.6 y; Student t test: P = .019) and long-standing presence of symptoms (27.4 +/- 39.6 mo vs. 3.6 +/- 3.9 mo; P = .023). These patients generally presented from a referring facility after having an excisional biopsy, which was 100% accurate. Fine-needle aspiration is becoming more useful and was 66.7% accurate. Histological examination revealed cancer in the thyroid gland in all patients, 11 cases of papillary carcinoma, 2 follicular carcinomas, and one medullary carcinoma The mean size of the primary focus was 10.9 +/- 8.7 mm, with 29% demonstrating bilateral disease and 14% demonstrating multifocal disease in the ipsilateral gland. The neck specimens revealed an average of 5.3 +/- 3.2 metastatic nodes in levels II-IV and 3.9 +/- 4.6 metastatic nodes in the paratracheal region. CONCLUSION: Based on this patient population, the long-standing lateral neck mass in the young patient should raise the physician's index of suspicion for thyroid carcinoma Fine-needle aspiration should be used in conjunction with judicious excisional biopsy. The bilateral and multifocal nature of otherwise occult primary disease argues for total thyroidectomy in this setting.

Adenocarcinoma, Follicular↗

PubMed2000

Change in backbone torsion angle distribution on protein folding.

Understanding protein folding requires the determination of the configurational space accessible to the protein at different stages in folding. Here, computer simulation analysis of small angle neutron scattering results is used to probe the change in the distribution of configurations on strong denaturation of a globular protein, phosphoglycerate kinase, in 4 M guanidine hydrochloride solution. To do this atomic-detail ensembles of the unfolded protein chain are modeled and their scattering profiles compared with the experiment. The local conformational statistics are found to strongly influence the experimental intensity at scattering vectors between 0.05 and 0.3 A(-1). Denaturation leads to a reduction in the protein atom-pair distance distribution function over the approximately 3-15 A region that is associated with a quantifiable shift in the backbone torsional angle (phi, psi) distribution toward the beta region of the Ramachandran plot.

Computer Simulation↗

PubMed2000

Effects of T'ai Chi training on function and quality of life indicators in older adults with osteoarthritis.

OBJECTIVE: To determine the effects of T'ai Chi training on arthritis self-efficacy, quality of life indicators, and lower extremity functional mobility in older adults with osteoarthritis. DESIGN: A prospective, randomized, controlled clinical trial. Intervention length was 12 weeks, with outcomes measured before and after intervention using blinded testers. Group (T'ai Chi vs Control) x time (2 x 2) mixed factorial ANOVA. SETTING: Allied Health Sciences Center at Springfield College, Springfield, MA PARTICIPANTS: A total of 33 community-dwelling participants (mean age 68) diagnosed with lower extremity osteoarthritis and having no prior T'ai Chi training longer than 2 weeks. INTERVENTION: T'ai Chi training included two 1-hour T'ai Chi classes per week for 12 weeks. MEASUREMENTS: Arthritis self-efficacy (Arthritis Self-Efficacy Scale), quality of life indicators (Arthritis Impact Measurement Scale), functional outcomes (one-leg standing balance, 50-foot walking speed, time to rise from a chair). RESULTS: T'ai Chi participants experienced significant (P < .05) improvements in self-efficacy for arthritis symptoms, total arthritis self-efficacy, level of tension, and satisfaction with general health status. CONCLUSIONS: A moderate T'ai Chi intervention can enhance arthritis self-efficacy, quality of life, and functional mobility among older adults with osteoarthritis. T'ai Chi training is a safe and effective complementary therapy in the medical management of lower extremity osteoarthritis.

Activities of Daily Living↗

PubMed2000

Augmentation of central arterial pressure in mild primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is associated with increased cardiovascular risk, although the mechanisms involved remain unclear. Recent evidence has shown increased pulse pressure to be a powerful predictor of cardiovascular events. As increases in pulse pressure are due largely to arterial stiffening, we measured arterial stiffness in 21 subjects with PHPT (18 women and 3 men; 46-71 yr old) and 21 age- and sex-matched healthy controls using pulse wave analysis, a technique that measures peripheral arterial pressure waveforms and generates corresponding central aortic waveforms. This allows determination of the augmentation of central pressure resulting from wave reflection and augmentation index, a measure of vessel stiffness. Metabolic parameters were also measured. The serum calcium level among PHPT subjects was (mean +/- SD) 2.74+/-0.14 mmol/L. pulse wave analysis showed that both augmentation and the augmentation index were significantly higher in the PHPT group vs. controls [16+/-5 vs. 10+/-4 mm Hg (P < 0.001) and 36+/-9% vs. 25+/-6% (P < 0.001)] despite comparable brachial systolic pressures between groups (136+/-13 vs. 134+/-18 mm Hg). Patients with PHPT had higher fasting serum insulin levels [median (range), 15.8 (7.4-39.4) vs. 11.6 (5.1-23) mU/L; P < 0.05] and triglyceride (1.6+/-0.6 vs. 1.2+/-0.4 mmol/L; P < 0.05), but lower high density lipoprotein cholesterol (1.4+/-0.4 vs. 1.6+/-0.3 mmol/L; P < 0.05). These data indicate that subjects with mild PHPT (calcium, <3.0 mmol/L) have increased arterial stiffness, as evidenced by higher augmentation of central aortic pressures. Enhanced vessel stiffness may arise from a combination of structural and functional vascular changes due to hypercalcemia and/or metabolic abnormalities. Increased vascular stiffness in subjects with PHPT may account in part for the increased cardiovascular risk in this group.

Aged↗

PubMed2000

Xwnt11 is a target of Xenopus Brachyury: regulation of gastrulation movements via Dishevelled, but not through the canonical Wnt pathway.

Gastrulation in the amphibian embryo is driven by cells of the mesoderm. One of the genes that confers mesodermal identity in Xenopus is Brachyury (Xbra), which is required for normal gastrulation movements and ultimately for posterior mesoderm and notochord differentiation in the development of all vertebrates. Xbra is a transcription activator, and interference with transcription activation leads to an inhibition of morphogenetic movements during gastrulation. To understand this process, we have screened for downstream target genes of Brachyury (Tada, M., Casey, E., Fairclough, L. and Smith, J. C. (1998) Development 125, 3997-4006). This approach has now allowed us to isolate Xwnt11, whose expression pattern is almost identical to that of Xbra at gastrula and early neurula stages. Activation of Xwnt11 is induced in an immediate-early fashion by Xbra and its expression in vivo is abolished by a dominant-interfering form of Xbra, Xbra-En(R). Overexpression of a dominant-negative form of Xwnt11, like overexpression of Xbra-En(R), inhibits convergent extension movements. This inhibition can be rescued by Dsh, a component of the Wnt signalling pathway and also by a truncated form of Dsh which cannot signal through the canonical Wnt pathway involving GSK-3 and (beta)-catenin. Together, our results suggest that the regulation of morphogenetic movements by Xwnt11 occurs through a pathway similar to that involved in planar polarity signalling in Drosophila.

Activins↗

PubMed2000

Hex is a transcriptional repressor that contributes to anterior identity and suppresses Spemann organiser function.

One of the earliest markers of anterior asymmetry in vertebrate embryos is the transcription factor Hex. We find that Hex is a transcriptional repressor that can be converted to an activator by fusing full length Hex to two copies of the minimal transcriptional activation domain of VP16 together with the flexible hinge region of the (lambda) repressor (Hex-(lambda)VP2). Retention of the entire Hex open reading frame allows one to examine Hex function without disrupting potential protein-protein interactions. Expression of Hex-(lambda)VP2 in Xenopus inhibits expression of the anterior marker Cerberus and results in anterior truncations. Such embryos have multiple notochords and disorganised muscle tissue. These effects can occur in a cell non-autonomous manner, suggesting that one role of wild-type Hex is to specify anterior structures by suppressing signals that promote dorsal mesoderm formation. In support of this idea, over-expression of wild-type Hex causes cell non-autonomous dorso-anteriorization, as well as cell autonomous suppression of dorsal mesoderm. Suppression of dorsal mesoderm by Hex is accompanied by the down-regulation of Goosecoid and Chordin, while induction of dorsal mesoderm by Hex-(lambda)VP2 results in activation of these genes. Transient transfection experiments in ES cells suggest that Goosecoid is a direct target of Hex. Together, our results support a model in which Hex suppresses organiser activity and defines anterior identity.

Animals↗

PubMed2000

Region-specific activation of the Xenopus brachyury promoter involves active repression in ectoderm and endoderm: a study using transgenic frog embryos.

Tissue specification in the early embryo requires the integration of spatial information at the promoters of developmentally important genes. Although several response elements for signalling pathways have been identified in Xenopus promoters, it is not yet understood what defines the sharp borders that restrict expression to a specific tissue. Here we use transgenic frog embryos to study the spatial and temporal regulation of the Xbra promoter. Deletion analysis and point mutations in putative transcription factor-binding sites identified two repressor modules, which exert their main effects at different stages during gastrulation. One module is defined by a bipartite binding site for a Smad-interacting protein (SIP1) of the deltaEF1 repressor family and acts to confine expression to the marginal zone early in gastrulation. The other module is defined by two homeodomain-binding sites and is responsible for repression in dorsal mesoderm and ectoderm at mid-gastrula stages. In addition, an upstream region of the promoter is necessary to repress expression in neural tissues later in development. Together, our results show that repression plays an important role in the restriction of Xbra expression to the mesoderm, and we suggest that similar mechanisms may be involved in the spatial regulation of other genes in early embryonic development.

Animals↗

PubMed2000

ABC relaxation theory and the factor structure of relaxation states, recalled relaxation activities, dispositions, and motivations.

ABC Relaxation Theory proposes 15 psychological relaxation-related states (R-States): Sleepiness, Disengagement, Physical Relaxation, Mental Quiet, Rested/Refreshed, At Ease/At Peace, Energized, Aware, Joy, Thankfulness and Love, Prayerfulness, Childlike Innocence, Awe and Wonder, Mystery, and Timeless/Boundless/Infinite. The present study summarizes the results of 13 separate factor analyses of immediate relaxation-related states, states associated with recalled relaxation activities, relaxation dispositions, and relaxation motivations on a combined sample of 1,904 individuals (group average ages ranged from 28-40 yr.). Four exploratory factor analyses of Smith Relaxation Inventories yielded 15 items that most consistently and exclusively load (generally at least .70) on six replicated factors. These items included happy, joyful, energized, rested, at peace, warm, limp, silent, quiet, dozing, drowsy, prayerful, mystery, distant, and indifferent. Subsequent factor analyses restricted to these items and specifying six factors were performed on 13 different data sets. Each yielded the same six-factor solution: Factor 1: Centered Positive Affect, Factor 2: Sleepiness, Factor 3: Disengagement, Factor 4: Physical Relaxation, Factor 5: Mental Quiet, and Factor 6: Spiritual. Implications for ABC Relaxation Theory are discussed.

Adult↗