Biomedical subjects
Publications and source records attributed to C A Williams.
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This study compared whether activation of muscle ergoreceptor afferents caused by isometric muscle contraction, activation of baroreceptor afferents induced by i.v. infusion of phenylephrine, or baroreceptor afferent inactivation, caused by carotid artery occlusion, elicit similar patterns of c-Fos induction in brainstem areas. Adult cats were anesthetized with alpha-chloralose, and in each case, the experimental intervention caused an increase in the arterial blood pressure. There were two sets of control experiments: in both, animals underwent the same surgical procedures but then either remained at rest for the entire study, or the tibial nerve was stimulated, as in the contraction group, following muscle paralysis with tubocurarine. Following the procedures, animals rested for 90 min to allow neuronal expression of c-Fos. Control cats showed very little c-Fos immunoreactivity (c-Fos-ir) in the brainstem. Muscle contraction induced c-Fos-ir expression mainly in the nucleus tractus solitarius, lateral reticular nucleus, lateral tegmental field, vestibular nucleus, subretrofacial nucleus, spinal trigeminal tract and in a lateral region of the periaqueductal grey (P 0.5-1.0). The majority of the c-Fos-ir was found in brainstem areas contralateral to the contracted muscle. In addition, muscle contraction induced c-Fos-ir in the dorsal horns of spinal segments L6-S1 on the ipsilateral side of the spinal cord. Phenylephrine infusion caused c-Fos-ir expression in the nucleus tractus solitarius, spinal trigeminal tract, solitary tract, and dorsal motor nucleus of the vagus. No c-Fos-ir was apparent in the periaqueductal grey. Carotid occlusions induced c-Fos-ir expression in the area postrema, nucleus tractus solitarius, solitary tract, and spinal trigeminal tract. Expression was bilateral. Areas that exhibited c-Fos-ir correspond to sites previously reported to release various neuropeptides in response to muscle contraction or carotid occlusions. These results indicate that the exercise pressor reflex and baroreflex activate similar, but not completely identical, sites in the brainstem.
Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are clinically distinct complex disorders mapped to chromosome 15q11-q13. They both have characteristic neurologic, developmental, and behavioral phenotypes plus other structural and functional abnormalities. However, the cognitive and neurologic impairment is more severe in AS, including seizures and ataxia. The behavioral and endocrine disorders are more severe in PWS, including obsessive-compulsive symptoms and hypothalamic insufficiency. Both disorders can result from microdeletion, uniparental disomy, or an imprinting center defect in 15q11-q13, although the abnormality is on the paternally derived chromosome 15 for PWS and the maternally derived 15 for AS because of genomic imprinting. Although the same gene may control imprinting for both disorders, the gene(s) causing their phenotypes differ. AS results from underexpression of a single gene, UBE3A, which codes for E6-AP, a protein that functions to transfer small ubiquitin molecules to certain target proteins, to enable their degradation. The genes responsible for PWS are not determined, although several maternally imprinted genes in 15q11-q13 are known. The most likely candidate is SNRPN, which codes for a small nuclear ribonucleoprotein, a ribosome-associated protein that controls gene splicing and thus synthesis of critical proteins in the brain. Animal models exist for both disorders. The genetic relationship between PWS and AS makes them unique and potentially highly instructive disorders that contribute substantially to the population burden of cognitive impairment.
Some of the recent advances in flavonoid research are reviewed. The role of anthocyanins and flavones in providing stable blue flower colours in the angiosperms is outlined. The contribution of leaf flavonoids to UV-B protection in plants is critically discussed. Advances in understanding the part played by flavonoids in warding off microbial infection and protecting plants from herbivory are described. The biological properties of flavonoids are considered in an evaluation of the medicinal and nutritional values of these compounds.
Acute S 22068 (24 mg/kg po) improved glucose tolerance and increased insulin sensitivity, assessed as the acute blood glucose response to exogenous insulin. The same acute dose did not stimulate insulin secretion or induce hypoglycemia in fed animals. Comparison of acute S 22068 to equipotent doses (with respect to effect on glucose tolerance) of gliclazide (2 mg/kg) and metformin (60 mg/kg) found S 22068 to be similar to metformin with respect to its effects on basal glucose levels (BGL) and insulin sensitivity. This also suggests that S 22068 acts by a mechanism which does not involve insulin release. Acute or sub-chronic S 22068 (14 days at 25 mg/day) had no effect on brown adipose tissue (BAT) or white adipose tissue (WAT) lipogenesis, an insulin-sensitive metabolic pathway. Sub-chronic treatment with S 22068 did not alter body weight (BW) or food intake, and resulted in tolerance to its effects on glucose metabolism and insulin sensitivity. These findings suggest that S 22068 is similar in effect to metformin, and is not insulinogenic, in contrast to the sulfonylureas or putative I(3) imidazoline site ligands.
Stress, pre-term labour and birth outcomes Preliminary studies have suggested that stress may be associated with the onset, treatment and outcomes of pre-term labour; however, a systematic comparison of the stress of women with and without pre-term labour has not been reported. Therefore, the purpose of this exploratory study was to compare the stress (daily hassles and mood states) and birth outcomes of black and white women who experienced pre-term labour (PTL) during pregnancy with those who did not. The convenience sample consisted of 35 pregnant women hospitalized in 1996-1997 for the treatment of PTL (24-35 weeks gestation) and 35 controls matched on age, race, parity, gestational age and method of hospital payment. Women in the PTL group had significantly higher tension-anxiety and depression-dejection on the Profile of Mood States (POMS), lower mean birthweight and mean gestational age, and a higher percentage of babies born <37 weeks and weighing 2500 g or less. Black women in the PTL group and white women in the control group had significantly higher scores on the fatigue sub-scale of the POMS and the work and future security sub-scales of the Daily Hassles Scale. Women in the PTL group whose babies weighed 2500 g or less had significantly higher scores on the health, inner concern and financial responsibility sub-scales of the Daily Hassles Scale. The findings from this study indicate the need for further exploration of the interaction of race and stress in understanding and preventing PTL and low birthweight and the need to examine the role of social support in preventing pre-term birth after an episode of PTL.
As the world's population ages, increasing numbers of people can anticipate spending their latter years in long-term care settings. Many of these nursing home residents will also present psychiatric illnesses as primary or secondary diagnoses. The resulting behavioral problems may present challenges to nursing staff that they are ill-prepared to meet. This article illustrates the application of the Blake and Mouton consultation model to a Veterans Administration (VA) nursing home situation by a team of psychiatric mental health nurse specialists. The consultation is described and interpreted in terms of the Blake and Mouton model. The focal conflicts addressed in the consultation included issues of morale/cohesion, power/authority, and norms/standards. Interventions used were acceptant, prescriptive, confrontation, and theories/principles. The model provided a useful structure for conceptualizing and organizing assessment and intervention in the consultation situation.
PURPOSE: The influences of age, body size, skin-fold thickness, gender, and maturation on the short-term power output of young people were examined using multilevel modelling. METHODS: Subjects were 97 boys and 100 girls, aged 12.2 +/- 0.4 yr at the onset of the study. Sexual maturity was classified according to Tanner's indices of pubic hair. Peak power (PP) and mean power (MP) were determined on two occasions 1 yr apart using the Wingate Anaerobic Test (WAnT). The data were analyzed using multilevel regression modelling. RESULTS: Initial models identified body mass and stature as significant explanatory variables with an additional positive effect of age, which was smaller for girls' MP. A significant gender difference was apparent for both power indices with girls achieving lower values than boys. A significant incremental effect of later maturity (stages 4 and 5 for pubic hair development) was identified for MP only. Subsequent incorporation of sum of two skin-fold thicknesses into the model yielded significant negative parameter estimates for PP and MP and negated both the stature effects and the maturation influence upon MP. CONCLUSION: There are gender differences in the longitudinal growth of performance on the WanT. Regardless of gender differences, body mass and skin-fold thicknesses appear to be the best anthropometric predictors of WAnT determined PP and MP in young people.
OBJECTIVE: To investigate the effects of two contrasting eight week training programmes on the aerobic performance of 39 prepubescent boys (mean age 10.1 years). METHODS: All boys were volunteer subjects from three city schools and the schools were matched by a health related behaviour questionnaire. All of the boys were assessed as Tanner stage one for genitalia and pubic hair development. Criterion laboratory tests included peak VO2 as assessed by an incremental discontinuous treadmill test to voluntary exhaustion. Submaximal measurements of heart rate, minute ventilation (VE) and VO2 were also recorded during the treadmill test. One of the schools provided the control group (n = 14), and boys from the other schools followed two contrasting training programmes. The first was a sprint interval running programme (n = 12) comprising 10 second and 30 second sprints, and the second a continuous cycle ergometer programme (n = 13) maintaining a heart rate in the range 80-85% of maximum for 20 minutes on a Monark cycle ergometer. After eight weeks training three times a week, the three groups were retested. RESULTS: There were no significant differences in peak VO2 (p>0.05) with training in either of the groups. Neither were there significant changes in any of the submaximal variables VO2, VE, or heart rate (p>0.05). CONCLUSION: The findings of this study indicate that neither eight week sprint interval running nor continuous cycle ergometer training programmes significantly improve maximal or submaximal indicators of the aerobic performance of prepubertal boys.
The purpose of the present study was to comprehensively examine oxygen consumption (VO(2)) kinetics during running and cycling through mathematical modeling of the breath-by-breath gas exchange responses to moderate and heavy exercise. After determination of the lactate threshold (LT) and maximal oxygen consumption (VO(2 max)) in both cycling and running exercise, seven subjects (age 26.6 +/- 5.1 yr) completed a series of "square-wave" rest-to-exercise transitions at running speeds and cycling power outputs that corresponded to 80% LT and 25, 50, and 75%Delta (Delta being the difference between LT and VO(2 max)). VO(2) responses were fit with either a two- ( LT) exponential model. The parameters of the VO(2) kinetic response were similar between exercise modes, except for the VO(2) slow component, which was significantly (P < 0.05) greater for cycling than for running at 50 and 75%Delta (334 +/- 183 and 430 +/- 159 ml/min vs. 205 +/- 84 and 302 +/- 154 ml/min, respectively). We speculate that the differences between the modes are related to the higher intramuscular tension development in heavy cycle exercise and the higher eccentric exercise component in running. This may cause a relatively greater recruitment of the less efficient type II muscle fibers in cycling.
Release of endomorphin (ENDO)-2 like substances from the dorsal horn of the isolated rat spinal cord was measured by the immobilized-antibody microprobe technique. Spinal cords were removed from anesthetized 4-6 week old rats and superfused with oxygenated Krebs solution at room temperature. Glass microprobes coated with ENDO-2 antibodies were inserted into the dorsal horn of the lumbar spinal cord 1.5 mm lateral to the midline to a depth 2.5 mm below the dorsal surface of the cord. Each probe remained in situ for 10 min periods before, during and after electrical stimulation applied to the dorsal root entry zone of the same spinal segment. There was no detectable basal release of immunoreactive endomorphin-2 like substance (irENDO) from the dorsal horns during the pre-stimulation, nor following the stimulation period. A significant release of irENDO was measured during the electrical stimulation. These results provide the first evidence of a irEndo release that is correlated spatially with the dorsal horn laminae I and II where ENDO-2-immunoreactive fibers are concentrated in the dorsal horn in response to electrical activation of primary afferent fibers.
The lipophilic flavonoids in leaf and flower of Tanacetum parthenium and T. vulgaris have been compared. While those of T. parthenium are methyl ethers of the flavonols 6-hydroxykaempferol and quercetagetin, the surface flavonoids of T. vulgare are methyl ethers of the flavones scutellarein and 6-hydroxyluteolin. Apigenin and two flavone glucuronides are surprisingly present in glandular trichomes on the lower epidermis of the ray florets of T. parthenium. The opportunity has been taken to revise the structures of the four 6-hydroxyflavonol methyl ethers of T. parthenium based on NMR measurements. These are now shown to be uniformly 6- rather than 7-O-methylated. Tanetin, previously thought to be a new structure, is now formulated as the known 6-hydroxykaempferol 3,6,4'-trimethyl ether. The vacuolar flavonoids of both plants are dominated by the presence of apigenin and luteolin 7-glucuronides; nine other glycosides were present, including the uncommon 6-hydroxyluteolin 7-glucoside in T. vulgare. When the major flavonol and flavone methyl ethers of the two plants were tested pharmacologically, they variously inhibited the major pathways of arachidonate metabolism in leukocytes. There were significant differences in potency, with the tansy 6-hydroxyflavones less active than the feverfew 6-hydroxyflavonols as inhibitors of cyclo-oxygenase and 5-lipoxygenase.
1. Acute SR 58611A (0.25 mg kg-1), was effective in reducing the blood glucose response to a glucose tolerance test (GTT) in normal lean (control) and spontaneously obese/diabetic CBA/Ca mice and to be equipotent to 1.25 mg kg-1 glibenclamide in lean mice. 2. Neither brown (BAT) nor white (WAT) adipose tissue lipogenesis was altered by acute SR 58611A (2 - 8 mg kg-1) in lean mice, but both increased significantly at the higher doses in the obese mice. 3. Acute SR 58611A produced a hypoglycaemia 40 min after dosing in lean and obese animals, the duration and potency of which was less than that of glibenclamide. Plasma insulin levels increased 20 min after acute SR 58611A and glibenclamide in lean and obese mice. 4. Chronic treatment (0.25 mg kg-1, 15 days) with SR 58611A increased its effectiveness in improving glucose tolerance, but did not affect the body weight (BW) or food intake of either lean or obese mice. 5. Acute and chronic SR 58611A prolonged the hypoglycaemic effect of exogenous insulin in lean but not obese mice. 6. In fed and fasted lean mice and in fasted obese mice chronic SR 58611A produced an acute hypoglycaemia 30 min post administration which was greater than after a single dose. 7. SR 58611A maintained its effectiveness in improving glucose tolerance in lean and obese mice over a dosing period of 15 days. The improvement in glucose tolerance was achieved at a dose less than that required to stimulate adipose tissue lipogenesis and which did not affect food intake or body weight.
A method is described for measuring the acute blood glucose response to an insulin challenge which requires only 6 samples of 20 microl of blood collected over a 4 hour period. This evaluation of sensitivity to insulin was validated by comparing the effects of gliclazide, metformin and a novel antidiabetic imidazoline compound (S22068) on the blood glucose response. The test distinguished between the insulin-secreting and hypoglycaemic action of gliclazide and the insulin-sensitizing actions of metformin and S22068. The test has the advantage that it can be repeated in the same animal after a period of recovery and thus enables the overall sensitivity to insulin to be compared before and after acute or chronic dose regimes.
Williams syndrome (WS) is considered a contiguous gene syndrome, with most patients having a 1.5-Mb deletion of chromosome 7q11.23 containing the elastin gene and flanking genes. Studies of the frequency, extent, and origin of these deletions are ongoing in many labs to discover ultimately the molecular and pathogenetic basis for WS. An analysis of 9 sporadic WS families with typical phenotypes was performed by genotyping polymorphisms in the region. This study revealed deletions in all 9 patients, with one showing a novel deletion extending much further centromeric than any other WS deletions yet reported.
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Deficiency of methylenetetrahydrofolate reductase (MTHFR) is associated with a variable phenotype that includes mental retardation, gait abnormalities, and seizures. Many of the same clinical findings are also seen in patients with Angelman syndrome. We report on a patient with MTHFR deficiency who was initially diagnosed as having Angelman syndrome. This case illustrates that MTHFR deficiency can mimic the phenotype of Angelman syndrome and that MTHFR deficiency should be excluded in patients with manifestations of Angelman syndrome whose molecular studies of chromosome 15 are normal.
Velo-cardio-facial syndrome, DiGeorge syndrome, conotruncal anomaly face syndrome, tetralogy of Fallot, and pulmonary atresia with ventricular septal defect are all associated with hemizygosity of 22q11. While the prevalence of the deletions in these phenotypes has been studied, the frequency of deletions in patients presenting with velopharyngeal insufficiency (VPI) is unknown. We performed fluorescence in situ hybridization for locus D22S75 within the 22q11 region on 23 patients with VPI (age range 5-42 years) followed in the Craniofacial Clinic at the University of Florida. The VPI occurred either as a condition of unknown cause (n=16) or as a condition remaining following primary cleft palate surgery (n=7). Six of sixteen patients with VPI of unknown cause and one of seven with VPI following surgery had a deletion in the region. This study documents a high frequency of 22q11 deletions in those presenting with VPI unrelated to overt cleft palate surgery and suggests that deletion testing should be considered in patients with VPI.