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Biomedical subjects

S A Jones

Publications and source records attributed to S A Jones.

At least 127 records · Page 7Linked to original sources

The interactions of desferrioxamine and hydroxypyridone compounds with haemoglobin and erythrocytes.

The iron chelator desferrioxamine has been applied in many studies of pathological states by several investigators. The resulting decreases in cellular and tissue damage have been interpreted as an indication of the involvement of iron-mediated radical species. Although the nature and location of the iron species have not been identified, the assumption has often been made that desferrioxamine is able to enter cells. This paper reports investigations of the ability of desferrioxamine to cross the erythrocyte membrane in comparison with that of specific hydroxypyridone iron chelators by assessing their interaction with haemoglobin.

Ascorbic Acid↗

Is it possible to "achieve a balance" and meet the "safety net"? Paediatric Advisory Subcommittee to the North West Thames Regional Health Authority.

The government's document Hospital Medical Staffing--Achieving a Balance--Plan for Action introduced the concept of a "safety net"--that is, a minimum safe level of staffing--of junior doctors in the acute specialties. The North West Thames Paediatric Advisory Group has therefore reviewed the implications and consequences of implementing the safety net in respect of children's services. The group found that if a reasonable safety net was to be provided that enabled the services to stay within the projected junior staffing levels, maintain a balance, meet training needs, and reduce junior doctors' hours of work, then changes in the organisation of the services would be required. Examining the options available showed that to achieve a safety net within the projected numbers of junior staff at least six paediatric units in the region would have to close. It is doubtful if there is the political will to support the very radical changes that would be needed in the distribution of services if the government's recommendations in Achieving a Balance were to be implemented. The profession, the Department of Health, and the public must be made aware that the proposed changes in medical staffing will cause a fundamental change in the traditional pattern of delivery of health care.

Child↗

Local stimulation of prostaglandin production by corticotropin-releasing hormone in human fetal membranes and placenta.

Corticotropin-releasing hormone is produced by the human placenta and fetal membranes, but its physiological significance is not established. We examined the possibility that CRH might affect prostaglandin output by these intra-uterine tissues. Primary cultures of amnion, chorion, decidua and placenta were established from tissue obtained from women at term elective cesarean section were maintained in the presence of increasing concentrations of synthetic hCRH. PG output at 48h was measured by radioimmunoassay. hCRH stimulated PGE2 output by amnion, chorion and placenta, but not by decidual tissue. PGF2 alpha output was stimulated in amnion, decidua and placenta but not chorion, whereas output of 13, 14-dihydro-15-keto PGF2 alpha was stimulated in all four tissues. We conclude that hCRH stimulates prostaglandin output by human placenta, decidua and the fetal membranes, raising the possibility of paracrine or autocrine interactions between CRH and prostaglandins in vivo.

Amnion↗

Vitamin D3 metabolites stimulate prostaglandin production by human fetal membranes and placenta in vitro.

In the present study we examined whether the vitamin D3 metabolites, 25-hydroxyvitamin D and 1-25-dihydroxycholecalciferol affected the production of the prostaglandins PGE2 and PGF2 alpha in human fetal membranes and placenta in vitro. Human amnion, chorion, decidual, and placental cells were maintained in primary monolayer culture. Treatment with the vitamin D3 metabolites resulted in an increase in PGE2 and PGF2 alpha production by amnion, decidua, and placental cells; however, these effects varied with time and were different between tissues. Although there was no significant increase in the production of PGE2 and PGF2 alpha by chorion cells in vitro, there was a significant increase in the production of prostaglandin F metabolites after treatment with the vitamin D3 metabolites. The data suggest that the vitamin D3 metabolites may increase free calcium availability and the conversion of arachidonic acid to the prostaglandins. The data do not, however, exclude the possibility that the vitamin D3 metabolites act at other points of arachidonic acid metabolism. These findings raise the possibility of a paracrine role for the vitamin D3 metabolites in the modulation of prostaglandin production within the human fetal membranes and placenta.

Calcitriol↗

Cardiovascular responses during feeding in newborn lambs.

We examined the cardiovascular responses to bottle feeding in newborn lambs. Feeding induced a persistent rise in blood pressure, from 76.3 +/- 1.9 mmHg to 114 +/- 3.8 mmHg, that lasted for the duration of the feeding episode. This was accompanied by a transient tachycardia that lasted for approximately 10 s at the beginning of each feeding episode. Vasoconstriction of the hindlimb circulation, the gastrointestinal tract, kidneys, and adrenal and thyroid glands contributed to the pressor response, whereas changes in skeletal muscle resistance were not statistically significant. Of tissues assessed, only those actively involved in feeding (tongue and esophagus) vasodilated. Feeding tachycardia was greatly inhibited or abolished by the beta-blocker propranolol but the alpha-blocker phentolamine caused only moderate inhibition of the pressor response. Furthermore, chemical sympathectomy with 6-hydroxydopamine delayed the onset of the pressor response but did not abolish the ultimate rise in pressure. These findings indicate that feeding causes a significant pressor response in newborn lambs that is only partially mediated by sympathetic innervation.

Animals↗

Heart rate variability analysis in full-term infants: spectral indices for study of neonatal cardiorespiratory control.

The heart rate and respirations of twenty healthy full-term infants between 30 and 60 h postnatal age were studied during quiet sleep with the objective of defining spectral indices which represent normal neonatal heart rate variability (HRV) characteristics. Total HRV power and the distribution of power across different frequency bands varied considerably among infants. Cluster analysis on the measured variables indicated that the population divided into two groups that represented significantly different patterns of HRV behavior. In one group (11 subjects), infants had lower breathing rates and HRV power in a band about the respiration frequency [respiratory sinus arrhythmia (RSA) band] was more than 20% of the total power (TP). Additionally, the ratio of low frequency band power to RSA band power was less than 4. The other group of neonates (nine subjects) had relatively higher breathing rates, RSA power less than 20% of total power, and low frequency to RSA power ratio greater than 4. Regression analysis of low frequency versus TP and RSA versus TP graphs gave strong support to the hypothesis that there were indeed two distinct patterns of HRV behavior. Separation of apparently normal neonates into two groups may be attributed partially to differences in respiratory rates and breathing patterns. However, it is possible that differences in the balance between sympathetic and parasympathetic nervous system control, perhaps related to autonomic maturation, also contribute to group separation. The indices developed from HRV spectral analysis in this investigation may be of value in the study of cardiorespiratory control in neonates.

Arrhythmia, Sinus↗

Steroids modulate corticotropin-releasing hormone production in human fetal membranes and placenta.

The levels of immunoreactive CRH are elevated in both maternal and fetal plasma in late gestation and labor, but fall precipitously after parturition. The major source of this peptide is thought to be the placenta. We determined if the placenta and also the amnion, chorion, and decidua produce CRH, whether this material has biological activity, and whether CRH output is modulated by glucocorticoids and progesterone. In an in vitro monolayer culture system CRH was produced by the fetal membranes and decidua. Media immunoreactive CRH concentrations averaged 625 +/- 45 (SE) pg/10(5) cells in amnion, 701 +/- 56 pg/10(5) cells in chorion, and 580 +/- 60 pg/10(5) cells in decidual tissue obtained at cesarean section. This output was similar to that by the placenta (906 +/- 121 pg/10(5) cells). These values increased in tissue obtained after spontaneous labor. A single peak of CRH immunoreactivity eluting at the same position as synthetic human CRH, and possessing biological activity, was found in all tissues. There was a dose-dependent increase in CRH output by all tissue types when cells were maintained in the presence of increasing concentrations of cortisol and dexamethasone. In contrast, increasing concentrations of progesterone decreased CRH output by all tissue types. We conclude that immuno- and biologically active CRH is produced not only in the human placenta, but also in the fetal membranes. CRH output by the placenta/fetal membranes is moderated by steroids, and changes with labor. These findings raise the possibility of a regulatory system similar to that of the hypothalamic pituitary axis, but residing within the placenta and fetal membranes.

Adrenocorticotropic Hormone↗

Controls of corticotrophin-releasing factor output by hypothalamic tissue from fetal sheep in vitro.

Corticotrophin-releasing factor (CRF) is thought to be an important physiological regulator of the pituitary-adrenal axis in fetal sheep and, as such, plays a fundamental role in the initiation of parturition in this species. However, little is known of the controls of CRF secretion from the fetal hypothalamus. We looked for the presence of CRF in fetal hypothalami, and examined whether the hypothalamic CRF concentration or molecular species changed in relation to gestational age. We established an in-vitro perifusion system to examine the release of CRF from perifused hypothalami taken from fetuses at day 100 and day 140 of pregnancy, under basal conditions and in response to potassium depolarization and/or dexamethasone administration. Immunoreactive CRF was present in fetal hypothalami as early as day 100 (2.42 +/- 0.99 (S.E.M.) micrograms/g protein, n = 9) and in similar concentrations at day 140 (2.31 +/- 0.69 micrograms/g protein, n = 9). There was a significant (P less than 0.05) increase in hypothalamic CRF content to 14.79 +/- 4.09 micrograms/g protein (n = 16) between day 122 and day 135 of gestation. Using Sephadex G-75 chromatography, hypothalamic extracts at day 100, days 122-135 and day 140 eluted with a single peak of immunoreactivity which corresponded to synthetic ovine CRF(1-41). The basal release of CRF from perifused hypothalami at day 140 (76.6 +/- 10.4 pg/fraction, n = 8) was significantly (P less than 0.05) greater than at day 100 (50.1 +/- 10.2 pg/fraction, n = 11). Dexamethasone significantly inhibited basal CRF release at day 140 of gestation but not at day 100.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of vibration on steady flow downstream of a stenosis.

A physical model was used to test the effects of vibrations on the position of transition to turbulence (zt) downstream of a constriction. Constrictions were inserted in a length of clear plastic (Tygon) tubing and vibrated. Water was the fluid medium and flow was visualized with India ink. The frequency and velocity of vibration were monitored. For a given constriction and flow velocity, there was a band of frequencies which caused zt to move upstream. This band corresponded to frequencies of flow disturbances as measured with a hot-film anemometer without vibration. Both flow-visualization and hot-film frequencies were correlated via a Strouhal number to the Reynolds number and contraction ratio of the flow. Values of zt decreased with increasing vibration amplitude. The critical Reynolds number for turbulence was also decreased by vibration. These results are of importance in the diagnosis of vascular disease and the design of physical models of stenotic flows.

Arterial Occlusive Diseases↗

NMR spectrometry. A new method for total stool fat quantification in chronic pancreatitis.

In the present investigation, suitability of nuclear magnetic resonance (NMR) spectrometry for total stool fat quantification in patients with normal or impaired exocrine pancreatic function (chronic pancreatitis) has been analyzed in comparison with a conventional chloroform-methanol extraction technique. Basic temperature-dependence studies of NMR spectrometry (90 degrees/180 degrees radiofrequency pulse sequence) on 21 chloroform-methanol extracted pure total stool lipid standards (weight range: 0.05-1.6 g) revealed significantly (P less than 0.05) improving correlations between NMR signal amplitudes and corresponding weights at increasing temperatures (r = 0.952/40 degrees C, r = 0.965/60 degrees C, r = 0.988/80 degrees C), thus indicating 80 degrees C as optimal temperature for NMR spectrometric total stool fat quantification. In subsequent comparative measurements of lyophilized stool samples, NMR spectrometry (at 80 degrees C) and conventional chloroform-methanol extraction provided significantly (P less than 0.001) correlated results with respect to total fecal fat contents/day of quantitatively collected and homogenized stools in 93 patients with known exocrine pancreatic function (secretin-pancreozymin test), irrespective of whether correlations were determined for all 93 patients (r = 0.983) or separately for patients with normal (N = 45; r = 0.867), moderately reduced (N = 31; r = 0.946), or highly reduced (N = 17; r = 0.992) exocrine pancreatic function and correspondingly increased total fecal fat excretions.

Celiac Disease↗

Analysis of break frequencies downstream of a constriction in a cylindrical tube.

Experiments were performed to correlate steady-flow power spectra downstream of a stenosis in a cylindrical tube with the flow geometry and velocity. The experiments were motivated by the need to improve quantitative phonoangiography. An objective break frequency (fb) was computed from spectra of velocity fluctuations, as measured with a hot film anemometer. Least squares fits with two independent variables were used to find an empirical relationship between a Strouhal number (S2), the contraction ratio (ds/D) and the Reynolds number (Re). The variables D and ds, are, respectively, the unobstructed tubing diameter and the inner diameter of the stenosis. The relationship found was S2 = Re 0.72(ds/D)0.26 The contraction ratio ds/D, can be found from the empirical relation in terms of known parameters. For the hot wire data the average error between the computed value of ds/D and the known value was 2.3%.

Arterial Occlusive Diseases↗

Nucleotide sequence analysis of the gene for protein A from Staphylococcus aureus Cowan 1 (NCTC8530) and its enhanced expression in Escherichia coli.

Nucleotide sequence analysis of the gene (spa) for staphylococcal protein A (SPA) from Staphylococcus aureus strain Cowan 1 (NCTC8530) shows that the sequence differs from previously reported SPA nucleotide sequences, especially in the number of repeat units in the cell-wall-binding region of the gene. Dot matrix comparison with streptococcal protein G and the macrophage receptor for the constant fragment (Fc) of immunoglobulins shows a limited but significant homology. The homology to the latter probably identifies the Fc-binding region in the immunoglobulin-binding domains of SPA. Enhanced production of SPA in Escherichia coli was achieved using the lac promoter immediately upstream from the spa gene.

Amino Acid Sequence↗

Effects of chronic infusion of porcine relaxin on oxytocin release in lactating rats.

The effects of chronic infusion of porcine relaxin on oxytocin release were studied in lactating rats. Infusion of relaxin (4.2 micrograms/h for either 4 or 6 days) suppressed reflex milk ejection and reduced litter weight gain for 48 h compared with saline-infused controls. After 2 days, neither the rate of growth nor the frequency of milk ejection were significantly different from controls. For 24 h after the infusion of relaxin ended, litters gained weight more quickly than controls but there was no difference seen in the frequency of milk ejection. The effects on oxytocin release of stopping an infusion of relaxin after 3 days were investigated. There was a significant (P less than 0.01) rise in plasma oxytocin (up to 90 pmol/l) 30 min after the infusion was stopped, followed by a sustained rise in intramammary pressure. Treatment of relaxin-infused rats with naloxone (0.1 mg/kg) when the infusion was halted caused a more rapid release of oxytocin (within 2 min), a greater release of oxytocin (up to 140 pmol/l) and a prolonged rise in intramammary pressure.

Animals↗

The subfornical organ and relaxin-induced inhibition of reflex milk ejection in lactating rats.

Experiments were carried out on anaesthetized, lactating rats to investigate the possible role of the subfornical organ in mediating relaxin-induced inhibition of reflex milk ejection. Milk ejection was judged by the behavioural response of the sucklings and by transient rises in intramammary pressure. Radiofrequency lesions of the subfornical organ, or control lesions in adjacent areas of the cerebrum, did not affect the pattern or the magnitude of intramammary pressure changes at reflex milk ejection. Purified porcine relaxin given by either i.v. (5 micrograms) or intracerebroventricular (50 ng) injection suppressed reflex milk ejection in intact, sham-lesioned and control-lesioned rats, but had no effect on either the pattern or magnitude of reflex milk ejection in rats with lesions of the subfornical organ. The subfornical organ, which is situated at the interface between the blood, brain and the cerebrospinal fluid appears to mediate, at least in part, the relaxin-induced inhibition of reflex milk ejection in the rat.

Animals↗