Search PubMed⌕ Search

Biomedical subjects

S Atkinson

Publications and source records attributed to S Atkinson.

At least 37 records · Page 2Linked to original sources

Monitoring of progesterone in captive female false killer whales, Pseudorca crassidens.

The present study describes progesterone profiles to enhance understanding of general reproductive patterns in three female captive false killer whales and analyzes potential relationships in progesterone concentrations between plasma, salivary, and ocular secretions. Plasma progesterone concentrations reflected ovarian activity for most of the year, with increased concentrations in the spring and summer, indicating that the two adult female false killer whales were spontaneous ovulators and seasonally polyestrus. Elevated progesterone concentrations were determined at intervals, for up to 10 consecutive months, in one female. There were also varying periods of no apparent ovarian activity from 3 to 10 consecutive months. Correlation coefficients between progesterone concentrations in plasma, salivary, and ocular secretions ranged between -0.23 and 0.16. It is concluded that blood collection should not be replaced by salivary or ocular secretion collection for the measurement of progesterone in the false killer whale.

Aging↗

p53 gene deletion and trisomy 12 in hairy cell leukemia and its variant.

The deletion or mutation of the p53 tumour suppressor gene on chromosome 17p13 is known to be associated with aggressive disease in several B-cell malignancies. The present study describes the p53 gene status in 20 cases of hairy cell leukemia (HCL) and in 12 cases of its morphological variant (HCL-V) by fluorescence in situ hybridization (FISH). A high incidence of p53 deletion was found in both diseases (75-100% of cases). However, a significant difference was observed between the proportion of cells with p53 deletion in HCL-V cases (mean 31%) and HCL cases (mean 12%) P value < 0.01. The observed difference correlates with the well known tendency for transformation and poor response to therapy in HCL-V and seven cases of HCL-V with greater than 22% of cells with p53 deletion showed features of disease progression and transformation. Trisomy 12 was present in 8.5% of the cells in one case of HCL-V and in 6-8% of cells in three cases of HCL.

Alleles↗

The referral process and urban health care in sub-Saharan Africa: the case of Lusaka, Zambia.

Much of the current reform of urban health systems in sub-Saharan Africa focuses upon the referral system between different levels of care. It is often assumed that patients are by-passing primary facilities which leads to congestion at hospital outpatient departments. Zambia is well advanced in its health sector reform and this case study from the capital, Lusaka, explores the patterns of health seeking behaviour of the urban population, the reasons behind health care choices, the functioning of the referral system and the users' evaluations of the care received. Data were collected across three levels of the system: the community, local health centres and the main hospital (both in- and out-patients). Results showed those who by-passed health centres were doing so because they believed the hospital outpatient department to be cheaper and/or better supplied with drugs (not because they believed they would receive better technical care). Few users were given information about their diagnosis or reason for referral. The most striking result was the degree of unmet need for health services and the large number of individuals who were self-medicating due to lack of money rather than the minor nature of their illness. The current upgrading of urban health centres into 'reference centres' may provide a capacity for unmet need rather than decongesting the hospital outpatient department as originally intended.

Adolescent↗

Premature infants fed mothers' milk to 6 months corrected age demonstrate adequate growth and zinc status in the first year.

The objective of this investigation was to describe zinc status to 12 months corrected age in premature infants fed their mother's milk in relation to nutritional management in hospital and post-hospital discharge. Twenty-five premature infants fed their mother's milk in hospital were randomized to receive either a multi-nutrient fortifier (MNF), providing protein, calcium, phosphorus and zinc (MM + MNF) or calcium and phosphorus alone (MM + CaGP). Twelve preterm infants fed a preterm formula (PTF) served as a comparison group. At 35 weeks post-menstrual age zinc retention was determined using the stable isotope tracer 70Zn. After hospital discharge infants in MM + MNF and MM + CaGP were designated to a mother's milk-feeding group to 6 months corrected age (Post-MM) or formula feeding group (Post-FF) based on parental choice of feeding practice. Anthropometry was performed at term, three, 6 and 12 months corrected age. At 6 and 12 months corrected age a hair sample was obtained to determine hair zinc concentrations. Preterm infants receiving supplemental zinc in hospital, as MNF, had significantly greater zinc retention in hospital compared to MM + CaGP but not greater hair zinc concentrations at 6 or 12 months corrected age. Despite significantly lower zinc intakes to 6 months corrected age, Post-MM had significantly greater hair zinc concentrations at 6 months compared to PTF (median[25-75th percentile]: 146[106-190] versus 85[54-91] microg/g, P < 0.05). Hair zinc in Post-FF (124[77-163] microg/g) was lower than Post-MM, but this was not significant (P = 0.09). Only in Post-MM were hair zinc concentrations above the median of reference values from term born infants at 12 months corrected age. Mean values of weight, length and head circumference of the preterm infants in Post-MM, Post-FF and PTF groups were between the 3rd and 97th percentiles derived from WHO reference growth standards for mother's milk-fed term infants. Our findings suggest that supplemental zinc either in hospital or post-hospital discharge does not appear to be required for preterm infants fed their mother's milk.

Analysis of Variance↗

Estrone and estradiol-17 beta concentration in tissue of the scleractinian coral, Montipora verrucosa.

Spawnings of scleractinian corals are affected by light, temperature, and other environmental cues, but no studies elucidate physiological mechanisms that regulate coral gametogenesis. We hypothesized that estrogens may act as bioregulators of coral reproduction. Estrone (E1) and estradiol-17 beta (E2) concentrations were measured in homogenates of tissue and skeleton from M. verrucosa. Tissue samples were collected monthly throughout the year, and more frequently in July and August around spawning. Steroids were extracted with diethyl ether, purified via celite chromatography and assayed with radioimmunoassay. Non-specific binding in coral tissue varied with sample weight and was elevated relative to standards. Monthly mean E1 ranged from 20-70 ng E1 g ash-free dry weight (AFDW)-1, with highest values in April. Smaller asynchronous peaks occurred in early July, prior to spawning. Monthly mean E2 ranged from 8-25 ng E2 g AFDW-1, with highest values in February and March. Peaks in E2 preceded peaks in E1, indicating metabolism of a pool of estrogen. E1 was positively correlated with protein concentration, which is consistent with a bioregulatory role of estrogens. Estrogen peaks in spring and prior to the July spawn corroborate our hypothesis that estrogens regulate coral gametogenesis and spawning.

Animals↗

Nutrient, fatty acid, amino acid and mineral analysis of natural prey of the Hawaiian monk seal, Monachus schauinslandi.

Proximate nutrients, gross energy content, mineral, amino acid and fatty acid composition were determined for teleost, cephalopod and crustacean prey of the Hawaiian monk seal. Crude protein was highest in the octopus, Octopus cyanea (80.0%), crude fat was highest in the Muraenid teleost, Gymnothorax eurostus (14.1%), whereas crude ash was highest in the lobster, Panulirus marginatus (11.6%). Gross energies ranged from 4.0 +/- 0.01 kcal g-1 in the Labrid teleost Bodianus bilulunatus to 6.0 +/- 0.12 kcal g-1 in the moray eel, Gymnothorax undulatus. Essential amino acids occurred in lower concentrations as a percentage of the total amino acids (35.8 +/- 2.6%) than non-essential amino acids (64.2 +/- 2.6%), but the ratio of individual amino acids to total amino acid concentrations were similar to those required by some monogastric terrestrial species and fingerling salmon. The fatty acid concentrations varied widely among species (range = 1.2-16.5 mg 100 mg-1); however, the teleosts had higher total fatty acids than the non-teleosts. This study indicates that, from a nutritional standpoint, some prey may be more beneficial to the Hawaiian monk seal; however, these prey are not necessarily the most abundant or available to some populations of the monk seal.

Amino Acids↗

A hierarchical quorum-sensing system in Yersinia pseudotuberculosis is involved in the regulation of motility and clumping.

In cell-free Yersinia pseudotuberculosis culture supernatants, we have chemically characterized three N-acyl homoserine lactone (AHL) molecules, N-octanoyl homoserine lactone (C8-HSL), N-(3-oxohexanoyl)homoserine lactone (3-oxo-C6-HSL) and N-hexanoyl homoserine lactone (C6-HSL). We have identified, cloned and sequenced two pairs of LuxR/I homologues termed YpsR/I and YtbR/I. In Escherichia coli at 37 degrees C, YpsI and YtbI both synthesize C6-HSL, although YpsI is responsible for 3-oxo-C6-HSL and YtbI for C8-HSL synthesis respectively. However, in a Y. pseudotuberculosis ypsI-negative background, YtbI appears capable of adjusting the AHL profile from all three AHLs at 37 degrees C and 22 degrees C to the absence of 3-oxo-C6-HSL at 28 degrees C. Insertion deletion mutagenesis of ypsR leads to the loss of C8-HSL at 22 degrees C, which suggests that at this temperature the YpsR protein is involved in the hierarchical regulation of the ytbR/I locus. When compared with the parent strain, the ypsR and ypsI mutants exhibit a number of phenotypes, including clumping (ypsR mutant), overexpression of a major flagellin subunit (ypsR mutant) and increased motility (both ypsR and ypsI mutants). The clumping and motility phenotypes are both temperature dependent. These data are consistent with a hierarchical quorum-sensing cascade in Y. pseudotuberculosis that is involved in the regulation of clumping and motility.

4-Butyrolactone↗

Mechanisms for pro matrix metalloproteinase activation.

The activation of pro matrix metalloproteinases (MMPs) by sequential proteolysis of the propeptide blocking the active site cleft is regarded as one of the key levels of regulation of these proteinases. Potential physiological mechanisms including cell-associated plasmin generation by urokinase-like plasminogen activator, or the action of cell surface MT1-MMPs appear to be involved in the initiation of cascades of pro MMP activation. Gelatinase A, collagenase 3 and gelatinase B may be activated by MT-MMP based mechanisms, as evidenced by both biochemical and cell based studies. Hence the regulation of MT-MMPs themselves becomes critical to the determination of MMP activity. This includes activation, assembly at the cell surfaces as TIMP-2 complexes and subsequent inactivation by proteolysis or TIMP inhibition.

Animals↗

Impact of age and cranial irradiation on radiographic skeletal pathology in children with acute lymphoblastic leukemia.

BACKGROUND: Symptomatic osteopenia is a common form of morbidity in children with acute lymphoblastic leukemia (ALL) before, during, and after treatment. A causal role for corticosteroids has been proposed, but other investigators have suggested that cranial irradiation is an important factor contributing to this disorder. PROCEDURE: In this study of children with ALL, all of whom received steroids, skeletal morbidity was assessed radiographically by an observer who was blinded to the ages of the children, their risk categorization (and related treatment), and the timing of the assessments with respect to the administration of therapy. DISCUSSION: Skeletal morbidity was most prevalent in older subjects who had been given cranial radiotherapy. However, there was no difference in the frequency of fractures in two groups of younger children (< or = 9 years of age), one irradiated and the other not. CONCLUSIONS: It is likely that corticosteroid therapy plays an important part in the pathogenesis of this disorder. The role played by cranial irradiation is much less certain.

Age Factors↗

Charged chelate-capillary electrophoresis of endogenous corticosteroids.

Separation of endogenous 17- or 18-hydroxylated corticosteroids (of the 21-hydroxylated 4-pregnen series) as charged chelates in capillary electrophoresis with borate as the ligand is demonstrated. Aldosterone, 18-hydroxycorticosterone, 18-hydroxy-11-deoxycorticosterone, cortisone, cortisol, and 11-deoxycortisol are separated and resolved by 400 mM borate buffer at pH 9.0. Separation characteristics of the corticosteroid charged chelates were examined by varying the separation buffer borate concentration, pH, ionic strength, and addition of organic modifiers. The borate ion [B(OH)4]- is identified as the critical buffer component. Corticosteroids chelate borate with proximal hydroxyls composed of either the 17- or 18-hydroxyl in combination with the 21-position hydroxyl. Corticosteroid/borate chelation as indicated by CE results is corroborated with 11B-nuclear magnetic resonance (11B-NMR) spectra. Chelation is a readily reversible process, with the strength of the resultant chelate, as opposed to the charge-to-mass ratio, predominantly determining analyte mobility in charged chelate - capillary electrophoresis (CC-CE).

18-Hydroxycorticosterone↗

Use of a GnRH agonist to suppress testosterone in wild male Hawaiian monk seals (Monachus schauinslandi).

A gonadotropin-releasing hormone (GnRH) agonist, d-Trp6-LHRH, was evaluated for its effectiveness in reducing circulating testosterone concentrations in wild Hawaiian monk seals (Monachus schauinslandi). Twenty-eight adult male seals were randomly divided into three groups: 10 were captured and treated with 7.5 mg of the GnRH agonist, 9 were captured but did not receive the agonist, and 9 were captured near the end of the study to serve as handling controls. Blood samples were taken from all 28 seals. From 14 to 58 days after initial capture, 8 of the treated seals and 8 of the untreated seals were recaptured and a second sample of blood was taken. For comparison, blood was also collected from 4 captive adult male seals during the same months as the field study. In the treated group, the agonist induced a significant decline in mean circulating testosterone concentrations, from 1.01 ng/ml (first sample) to 0.21 ng/ml (second sample, taken approximately 38 days later). In the untreated group, mean testosterone concentrations of the first and second samples were statistically indistinguishable (1.11 vs 1.16 ng/ml). The mean concentration of the untreated group (second sample) was also indistinguishable from the mean concentration of seals in the control group (1.16 vs 0.82 ng/ml). Also, mean testosterone concentration in the initial samples from the four captive seals was not statistically different from that of untreated wild seals (1.38 vs 1.11 ng/ml). These results suggest that (1) the GnRH agonist suppresses the production of testosterone in wild adult male Hawaiian monk seals, (2) a single handling of adult male seals does not affect their testosterone levels, and (3) testosterone concentrations in captive male seals appear to be consistent with concentrations in wild seals. Further evaluation of this GnRH agonist is necessary before it is used in the management of this endangered species, but these results suggest it may be a useful tool for reducing mortality of monk seals from adult male aggression related to reproduction and mating behavior.

Animals↗

A prospective, randomized, double-blind, controlled clinical trial of enteral immunonutrition in the critically ill. Guy's Hospital Intensive Care Group.

OBJECTIVE: To assess the effects of enteral immunonutrition (IMN) on hospital mortality and length of stay in a heterogeneous group of critically ill patients. DESIGN: Prospective, randomized, double-blind, controlled clinical trial with an a priori subgroup analysis according to the volume of feed delivered in the first 72 hrs of intensive care unit (ICU) admission. SETTING: A 13-bed adult general ICU in a London teaching hospital. PATIENTS: A total of 398 patients were enrolled and data from 390 patients (IMN = 193, control = 197) were used for an intention-to-treat analysis. There were 369 patients (IMN = 184, control = 185) who actually received some enteral nutrition, of whom 101 patients (IMN = 50, control = 51) received >2.5 L within 72 hrs of ICU admission. This latter group was defined as the successful "early enteral nutrition" group. INTERVENTIONS: Within 48 hrs of ICU admission, patients were randomized to receive either the IMN Impact (Novartis Nutrition), an enteral feed supplemented with arginine, purine nucleotides and omega-3 fatty acids, or an isocaloric, isonitrogenous control enteral feed. MEASUREMENTS AND RESULTS: There was no significant difference in hospital mortality rate between the two groups on an intention-to-treat analysis (Impact group 48%, control group 44%) nor in any other predefined subgroup analysis. However, patients randomized to receive the IMN had higher Acute Physiology and Chronic Health Evaluation II scores (20.1 +/- 7.1 vs. 18.7 +/- 7.1 [p = .07] intention-to-treat [n = 390]; 20.1 +/- 7.2 vs. 18.5 +/- 7.1 [p = .04] received feed [n = 369]). Of the 101 patients achieving early enteral nutrition, those patients fed with the IMN had a significant reduction in their requirement for mechanical ventilation compared with controls (median duration of ventilation 6.0 and 10.5 days, respectively, p = .007) with an associated reduction in the length of hospital stay (medians 15.5 and 20 days, respectively, p = .03). CONCLUSION: While the administration of enteral IMN to a general, critically ill population did not affect mortality, those patients in whom it was possible to achieve early enteral nutrition with Impact had a significant reduction in the morbidity of their critical illness.

APACHE↗

Combination of zolazepam and tiletamine as a sedative and anaesthetic for wombats.

OBJECTIVE: To assess the suitability of the combination of zolazepam and tiletamine for routine use as chemical restraint, sedative and anaesthetic in wild wombats. ANIMALS: Sixty common wombats, 25 southern hairy-nosed wombats and 40 northern hairy-nosed wombats. PROCEDURE: Wombats caught in cage-traps in the wild were given injections of the anaesthetic combination either intramuscularly or intraperitoneally. Anaesthesia was maintained for up to 4 h in some cases, and for 12 h in one case. All wombats were released after anaesthesia. RESULTS AND CONCLUSION: This drug combination is effective and apparently safe for the sedation or light anaesthesia of wombats. We did not observe adverse reactions or deaths and the dose range used (4 to 15 mg/kg) demonstrates a wide safety margin. The use of this anaesthetic combination was effective in reducing the stress to wombats from capture and handling.

Anesthetics, Combined↗

Fluid shear-induced mechanical signaling in MC3T3-E1 osteoblasts requires cytoskeleton-integrin interactions.

Mechanical stimulation of bone induces new bone formation in vivo and increases the metabolic activity and gene expression of osteoblasts in culture. We investigated the role of the actin cytoskeleton and actin-membrane interactions in the transmission of mechanical signals leading to altered gene expression in cultured MC3T3-E1 osteoblasts. Application of fluid shear to osteoblasts caused reorganization of actin filaments into contractile stress fibers and involved recruitment of beta1-integrins and alpha-actinin to focal adhesions. Fluid shear also increased expression of two proteins linked to mechanotransduction in vivo, cyclooxygenase-2 (COX-2) and the early response gene product c-fos. Inhibition of actin stress fiber development by treatment of cells with cytochalasin D, by expression of a dominant negative form of the small GTPase Rho, or by microinjection into cells of a proteolytic fragment of alpha-actinin that inhibits alpha-actinin-mediated anchoring of actin filaments to integrins at the plasma membrane each blocked fluid-shear-induced gene expression in osteoblasts. We conclude that fluid shear-induced mechanical signaling in osteoblasts leads to increased expression of COX-2 and c-Fos through a mechanism that involves reorganization of the actin cytoskeleton. Thus Rho-mediated stress fiber formation and the alpha-actinin-dependent anchorage of stress fibers to integrins in focal adhesions may promote fluid shear-induced metabolic changes in bone cells.

Actin Cytoskeleton↗

Membrane-type matrix metalloproteinases 1 and 2 exhibit broad-spectrum proteolytic capacities comparable to many matrix metalloproteinases.

Soluble proenzyme forms of the catalytic domains of membrane-type matrix metalloproteinases 1 and 2 (MT1-MMP and MT2-MMP) and a form of MT1-MMP containing the catalytic and hemopexin domains were expressed as soluble recombinant proteins. Purified, activated forms of the MT-MMP were shown to degrade fibronectin, tenascin, nidogen, aggrecan and perlecan. Only MT2-MMP showed activity against laminin. MT1-MMP retaining the hemopexin domain was able to specifically cleave native type-I and type-III collagens into the 3/4-1/4 fragments typical of the specific collagenases. The catalytic domain alone did not retain this activity. The MT-MMP did not degrade interleukin-1beta, but, similarly to many other MMP, could process a pro [tumor necrosis factor (TNF) alpha] fusion protein to release mature TNF. However, the latter was subsequently degraded into smaller fragments. These results demonstrate that, in addition to their ability to activate other MMP, such as progelatinase A/proMMP2 and procollagenase-3/proMMP13, MT-MMP degrade a number of extracellular matrix macromolecules. Their location at the surface of cells implies that they could play a significant role in the modulation of cell-matrix interactions.

Aggrecans↗

Reproductive biology of seals.

The reproductive biology of seals is fascinating in many aspects. As in most mammals, the time of onset of puberty in seals is variable. Once sexually mature, most but not all seals are seasonally mono-oestrous, with highly synchronized breeding seasons. They have evolved as either terrestrial or aquatic copulators, although a few species mate in a variety of habitats. Their mating strategies are diverse, ranging from serial monogamy to extreme polygyny. Gestation in seals is characterized by an embryonic diapause, which is obligate in most species. Reactivation of the blastocyst is followed by a placental gestation. All species of seal require a terrestrial (including ice floes) habitat for parturition. Lactation differs between the two seal families: phocid seals have an intense period of maternal investment, during which the mothers fast; otariid seals have a prolonged lactation during which intense bouts of suckling are interspersed by days of separation from their pups while the mother forages at sea. Although the anatomy and functional morphology of seals has been well described, less is known of the endocrinology of reproduction. This is due mainly to the logistical difficulties that researchers experience in collecting serial samples from a species that is relatively difficult to handle. This article reviews the basic anatomy and physiology, and our current understanding of the comparative aspects of reproduction in seals. Reproductive behaviours as well as the influences of environmental factors, such as photoperiod, nutrition and xenobiotics, are also discussed.

Animals↗