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Biomedical subjects

Peter Thomas

Publications and source records attributed to Peter Thomas.

At least 73 records · Page 4Linked to original sources
PubMed2004

Multiple rapid progestin actions and progestin membrane receptor subtypes in fish.

Progestin hormones exert rapid, nongenomic actions on a variety of target tissues in fish. The induction of oocyte maturation and the progestin membrane receptor (mPR) that mediates this action of progestins have been well characterized in fishes. Progestins also act on Atlantic croaker spermatozoa via an mPR to rapidly increase sperm motility. Preliminary results indicate that progestins can also exert rapid actions in the preoptic anterior hypothalamus (POAH) in this species to down-regulate gonadotropin-releasing hormone (GnRH) secretion. Recently, we reported the cloning, sequencing and characterization of a novel cDNA in a closely related species, spotted seatrout, that has the characteristics of the mPR involved in the progestin induction of oocyte maturation. Three distinct mPR subtypes, named alpha, beta, and gamma, have been identified in both fishes and mammals. The tissue distribution of the mPRalpha protein in seatrout suggests the alpha-subtype mediates progestin actions on GnRH secretion, sperm motility and oocyte maturation. However, mPRbeta antisense experiments in zebrafish oocytes suggest the beta-subtype also participates in the control of oocyte maturation in zebrafish.

Animals↗
PubMed2004

Opposite clear corneal incisions on the steep meridian in phacoemulsification: early effects on the cornea.

PURPOSE: To evaluate the effect of on-axis opposite clear corneal incisions (OCCIs) in phacoemulsification on reducing preoperative corneal astigmatism and to predict the astigmatic outcome of the incisions. SETTING: Royal Eye Infirmary, Dorset County Hospital, and Winterbourne Hospital, Dorchester, Dorset, and the Department of Ophthalmology, East Somerset Hospital, Yeovil, Somerset, United Kingdom. METHODS: This prospective study included all patients (n = 103) who had on-axis OCCIs as a part of routine phacoemulsification with foldable intraocular lens (IOL) implantation performed by 1 surgeon during 2000. Keratometry was done 6 to 8 weeks postoperatively. The differences in the preoperative and postoperative corneal astigmatism and corneal spherical equivalent (SE) were recorded. Surgically induced astigmatism (SIA) was calculated using vector analysis. RESULTS: The mean reduction in corneal astigmatism was 0.50 diopter (D) (P<.001). The mean SIA was 1.57 D (95% confidence interval [CI], 1.42 to 1.71). There was a weak association between the SIA and the patient's age and axis of preoperative astigmatism. The mean change in SE was +0.02 D (95% CI, -0.08 to +0.12). CONCLUSIONS: Results indicate that on-axis OCCIs are a reliable and practical way of reducing preexisting corneal astigmatism. The change in SE was negligible and thus can be ignored during biometry.

Aged↗
PubMed2004

Caffeine reduces cerebral blood flow in patients recovering from an ischaemic stroke.

BACKGROUND: Caffeine is present in a variety of beverages and food and is widely consumed. In a previous study of patients recovering from an acute ischaemic stroke using transcranial Doppler ultrasound we demonstrated a fall in middle cerebral artery blood velocity of 12% following ingestion of 250 mg caffeine. The aim of this study was to investigate if this velocity change reflected a change in cerebral blood flow. METHODS: The study used a randomised, double blind, cross-over design. Nineteen patients recovering from an acute ischaemic stroke in the middle cerebral artery territory and 10 controls attended two sessions, having abstained from caffeine for 48 hours previously. At each session cerebral blood flow was measured four times using xenon clearance, twice before the oral administration of 250 mg caffeine or matched placebo, and twice after. Similarly, three middle cerebral artery blood velocity readings using transcranial Doppler were made prior to administration and four after. RESULTS: The caffeine resulted in a significant fall in cerebral blood flow and middle cerebral artery blood velocity compared to placebo. CONCLUSIONS: Since caffeine is present in the diet of most patients recovering from an acute ischaemic stroke this effect may have adverse clinical consequences.

Aged↗
PubMed2004

Hepatic perfusion changes in mice livers with developing colorectal cancer metastases.

PURPOSE: To evaluate whether intrahepatic flow alterations occur during formation of hepatic colorectal cancer metastases and to identify possible causes of these alterations. MATERIALS AND METHODS: Intravital imaging of exteriorized livers was performed in 72 live mice. Three groups of mice were studied: a sham-operated control group (n = 24), a group with nonmetastasizing subcutaneous gliomas (n = 24), and a group with developing hepatic CX-1 colon cancer metastases (n = 24). Microvascular flow parameters, leukocyte-endothelial interactions, and wall shear stress were directly measured in hepatic sinusoids and postsinusoidal venules at 2-day intervals prior to and during the development of metastases. The Kruskal-Wallis test was used initially to test for overall equality of medians in each data group. Single posttest comparisons of independent samples were performed with the Mann-Whitney test, with an overall statistical significance of .05. RESULTS: Prior to the development of visible colorectal cancer metastases, significant (P <.05) reductions occurred in sinusoidal and postsinusoidal flow and wall shear rates, coupled with increased leukocyte rolling and adherence. With tumor growth, flow was further compromised in 92% of tumors larger than 0.5 mm in diameter by extrinsic compression of sinusoids and portal venules and narrowing caused by adherent leukocytes. CONCLUSION: Significant intrahepatic flow alterations occur in mouse livers prior to growth of visible metastases and provide a rational explanation for elevation in the Doppler perfusion index that occurs prior to tumor formation.

Animals↗
PubMed2004

Influence of caffeine on heart rate variability in patients with long-standing type 1 diabetes.

OBJECTIVE: The effect of caffeine on cardiovascular health remains controversial. Patients with long-standing type 1 diabetes are at risk of autonomic failure and sudden cardiac death. We investigated the effects of caffeine on autonomic dysfunction (as assessed by heart rate variability [HRV]) in this high-risk group and in a control population. RESEARCH DESIGN AND METHODS: Using a randomized blinded, placebo-controlled, crossover design trial, we examined 2 weeks of caffeine consumption (250 mg twice daily) on HRV in 20 type 1 diabetic patients and 10 matched healthy volunteers. RESULTS: Baseline HRV was blunted in the diabetic patients (P < 0.0005 vs. control subjects) and markedly increased by caffeine in both groups (+103% in the group with diabetes [P = 0.009] and +38% in control subjects [P = 0.002]). The caffeine-associated increase in HRV was not statistically different between the control and the type 1 diabetes groups (P = 0.16). CONCLUSIONS: Modest amounts of caffeine improved autonomic function in diabetic patients and healthy volunteers. For individuals with abnormal HRV, regular caffeine use may have the potential to reduce the risk of cardiovascular events.

Adult↗
PubMed2003

Is oral fluid analysis as accurate as urinalysis in detecting drug use in a treatment setting?

BACKGROUND: Technology for testing oral fluid (OF) for the presence of drugs is available for treatment services and is more attractive than urinalysis: its validity is not well established. AIMS: Compare the accuracy of methods of on-site testing of OF and urine. DESIGN: Comparison of the sensitivity and specificity of on-site testing of samples of OF and urine collected on the same occasion, using subsequent blind laboratory analysis of the same urine samples as the standard. SETTING: British addiction treatment service. PARTICIPANTS: 157 drug dependent persons, 89% with evidence of opiates, 73% male, and 85% aged between 20 and 35 years. MEASUREMENTS: Assessment of presence of four drugs using SYVA ETS urinalysis and Cozart Rapiscan OF Drug Test systems. Laboratory urinalysis using microplate enzyme-immunoassay technique. RESULTS: The sensitivity of OF tests and urinalysis were, respectively, for opiates 91 and 91%, methadone 91 and 94%, and benzodiazepines 6 and 72%. The specificity of OF tests and urinalysis were, respectively, for opiates 78 and 67%, methadone 90 and 95%, and benzodiazepines 95 and 96%. Amphetamine usage was rare. CONCLUSIONS: OF testing is as accurate as urinalysis in detecting the presence of opiates and methadone, and the absence of methadone and benzodiazepines.

Adult↗
PubMed2003

Surface expression of heterogeneous nuclear RNA binding protein M4 on Kupffer cell relates to its function as a carcinoembryonic antigen receptor.

Elevated concentrations of carcinoembryonic antigen (CEA) in the blood are associated with the development of hepatic metastases from colorectal cancers. Clearance of circulating CEA occurs through endocytosis by liver macrophages, Kupffer cells. Previously we identified heterogeneous nuclear ribonucleoproteins M4 (hnRNP M4) as a receptor (CEAR) for CEA. HnRNP M4 has two isoform proteins (p80, p76), the full-length hnRNP M4 (CEARL) and a truncated form (CEARS) with a deletion of 39 amino acids between RNA binding domains 1 and 2, generated by alternative splicing. The present study was undertaken to clarify any isoform-specific differences in terms of their function as CEA receptor and localization. We develop anti-CEAR isoform-specific antibodies and show that both CEAR splicing isoforms are expressed on the surface of Kupffer cells and can function as CEA receptor. Alternatively, in P388D1 macrophages CEARS protein has nuclear and CEARL has cytoplasmic localization. In MIP101 colon cancer and HeLa cells the CEARS protein is localized to the nucleus and CEARL to the cytoplasm. These findings imply that different functions are assigned to CEAR isoforms depending on the cell type. The search of 39 amino acids deleted region against the Prosite data base revealed the presence of N-myristylation signal PGGPGMITIP that may be involved in protein targeting to the plasma membrane. Overall, this report demonstrates that the cellular distribution, level of expression, and relative amount of CEARL and CEARS isoforms determine specificity for CEA binding and the expression of alternative spliced forms of CEAR is regulated in a tissue-specific manner.

Alternative Splicing↗
PubMed2003

Androgens inhibit estradiol-17beta synthesis in Atlantic croaker (Micropogonias undulatus) ovaries by a nongenomic mechanism initiated at the cell surface.

The presence of androgen receptors in the ovaries of several vertebrate species, including Atlantic croaker, suggests that androgens may have important roles in ovarian function. In the current study the effects of androgens on ovarian steroidogenesis in Atlantic croaker were investigated. Addition of 17beta-hydroxy-5alpha-androstan-3-one (DHT), 11-ketotestosterone (11-KT), or Mibolerone to ovarian incubations caused dose-dependent decreases in gonadotropin-stimulated in vitro estradiol production, which was not reversed by cotreatment with the antiandrogens, cyproterone acetate or 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene. Androgen treatment also caused significant decreases in estradiol production in the presence of 17-hydroxyprogesterone, which suggests that the site of androgen action is downstream of this steroid in the steroidogenic pathway. The mechanism of androgen action on ovarian steroidogenesis was also investigated. Coincubation with actinomycin D did not reverse the inhibitory effect of the androgens, which suggests that the mechanism of androgen action is nongenomic. An androgen conjugated to bovine serum albumin (DHT-BSA), which does not enter the cell, also caused inhibition of estradiol production in vitro, indicating that the androgen is acting at the cell surface. In addition, time course experiments revealed that the androgen action is rapid; 5-min exposure to DHT was sufficient to cause a significant reduction in estradiol production. Finally, preliminary evidence was obtained for the existence of a high-affinity, low-capacity androgen binding site in croaker ovarian plasma membranes. These studies suggest that androgens can down-regulate estrogen production in croaker ovaries via a rapid, cell surface-mediated, nongenomic mechanism.

Androgen Antagonists↗
PubMed2003

Cassini imaging of Jupiter's atmosphere, satellites, and rings.

The Cassini Imaging Science Subsystem acquired about 26,000 images of the Jupiter system as the spacecraft encountered the giant planet en route to Saturn. We report findings on Jupiter's zonal winds, convective storms, low-latitude upper troposphere, polar stratosphere, and northern aurora. We also describe previously unseen emissions arising from Io and Europa in eclipse, a giant volcanic plume over Io's north pole, disk-resolved images of the satellite Himalia, circumstantial evidence for a causal relation between the satellites Metis and Adrastea and the main jovian ring, and information on the nature of the ring particles.

Journal Article↗
PubMed2003

Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor.

Recently we discovered a previously uncharacterized gene with the characteristics of a membrane progestin receptor (mPR) in a fish model, spotted seatrout. Here, we report the identification, cloning, and characteristics of other members of this hitherto unknown family of putative mPRs from several vertebrate species, including human, mouse, pig, Xenopus, zebrafish, and Fugu, with highly conserved nucleotide and deduced amino acid sequences and similar structures to the spotted seatrout mPR. The 13 vertebrate genes identified seem to belong to an unknown gene family. Phylogenetic analysis indicates these cDNAs comprise three distinct groups (named alpha, beta, and gamma) within this gene family. Structural analyses of the translated cDNAs suggest they encode membrane proteins with seven transmembrane domains. The transcript sizes of the human alpha, beta, and gamma putative mPR mRNAs varied from 2.8 to 5.8 kb and showed distinct distributions in reproductive, neural, kidney and intestinal tissues, respectively. Recombinant human alpha, gamma, and mouse beta proteins produced in an Escherichia coli expression system demonstrated high affinity (K(d) = 20-30 nM) saturable binding for progesterone. Further analysis of binding to the gamma-subtype revealed binding was specific for progestins and was displaceable, with rapid rates of association and dissociation (t(1/2) = 2-8 min). These results suggest this is a new family of steroid receptors unrelated to nuclear steroid receptors, but instead having characteristics of G protein-coupled receptors.

Amino Acids↗
PubMed2003

Cloning, expression, and characterization of a membrane progestin receptor and evidence it is an intermediary in meiotic maturation of fish oocytes.

The structures of membrane receptors mediating rapid, nongenomic actions of steroids have not been identified. We describe the cloning of a cDNA from spotted seatrout ovaries encoding a protein that satisfies the following seven criteria for its designation as a steroid membrane receptor: plausible structure, tissue specificity, cellular distribution, steroid binding, signal transduction, hormonal regulation, and biological relevance. For plausible structure, computer modeling predicts that the protein has seven transmembrane domains, typical of G protein-coupled receptors. The mRNA (4.0 kb) is only detected in the brain and reproductive tissues on Northern blots. Antisera only detect the protein (40 kDa) in plasma membranes of reproductive tissues. The recombinant protein produced in an Escherichia coli expression system has a high affinity (K(d) = 30 nM), saturable, displaceable, single binding site specific for progestins. Progestins alter signal transduction pathways, activating mitogen-activated protein kinase and inhibiting adenylyl cyclase, in a transfected mammalian cell line. Inhibition of adenylyl cyclase is pertussis toxin sensitive, suggesting the receptor may be coupled to an inhibitory G protein. Progestins and gonadotropin up-regulate both mRNA and protein levels in seatrout ovaries. Changes in receptor abundance in response to hormones and at various stages of oocyte development, its probable coupling to an inhibitory G protein and inhibition of progestin induction of oocyte maturation upon microinjection of antisense oligonucleotides are consistent with the identity of the receptor as an intermediary in oocyte maturation. These characteristics suggest the fish protein is a membrane progestin receptor mediating a "nonclassical" action of progestins to induce oocyte maturation in fish.

Animals↗
PubMed2003

Changes in homologous and heterologous gap junction contacts during maturation-inducing hormone-dependent meiotic resumption in ovarian follicles of Atlantic croaker.

Homologous (granulosa cell-granulosa cell) gap junction (GJ) contacts increase in ovarian follicles of Atlantic croaker (Micropogonias undulatus) during the early (first) stage of maturation, but their profile during the second stage [i.e., during maturation-inducing hormone (MIH)-mediated meiotic resumption] is unknown. The profile of homologous GJ contacts during the second stage of maturation in croaker follicles was examined in this study and compared to that of heterologous (granulosa cell-oocyte) GJ, for which changes have been previously documented. Follicles were incubated with human chorionic gonadotropin to induce maturational competence (first stage), and then with MIH to induce meiotic resumption. The follicles were collected for examination immediately before and after different durations of MIH exposure until the oocyte had reached the stage of germinal vesicle breakdown (GVBD; index of meiotic resumption). Ultrathin sections were observed by transmission electron microscopy, and homologous and heterologous GJ contacts were quantified along a 100-microm segment of granulosa cell-zona radiata complex per follicle (three follicles/time/fish, n=3 fish). Relatively high numbers of both types of GJ were observed before and after the first few hours of MIH exposure (up to the stage of oil droplet coalescence). GJ numbers declined during partial yolk globule coalescence (at or near GVBD) and were just under 50% of starting values after the completion of GVBD (P<0.05). These results confirm earlier observations that GVBD temporally correlates with declining heterologous GJ contacts, and for the first time in teleosts show that there is a parallel decline in homologous GJ. The significance of the changes in homologous and heterologous GJ is uncertain and deserves further study.

Animals↗
PubMed2003

Reproductive seasonality of the male Florida gar, Lepisosteus platyrhincus.

The objective of this study was to characterize the reproductive seasonality of a wild population of male Florida gar, Lepisosteus platyrhincus. We measured the gonadosomatic index, reproductive stage of the testes, seminiferous tubule area, and plasma concentrations of testosterone and 11-ketotestosterone for each fish. A seasonal pattern was observed in the reproduction of male gar. Following a quiescent period in the summer, there was an increase in plasma testosterone concentration during the fall, which was associated with the onset of active spermatogenesis as indicated by an increase in seminiferous tubule area and gonadosomatic index. Plasma concentrations of 11-ketotestosterone remained basal during the summer and winter and then increased during the early spring. These data, taken together with data from female gar collected in a parallel study by our lab, suggest that spawning occurred during the early spring (February-March), followed by a general decrease in reproductive parameters to summer levels. Recognizing that peaks of hormone concentrations and spawning period could vary with annual seasonal variation, this study is important because it is the first characterization of the seasonal morphological and endocrinological reproductive pattern in a holostean species. Furthermore, it increases our understanding of the reproductive biology of semitropical fishes.

Animals↗
PubMed2003

[Systemic contact eczema against Balsam of Peru].

Balsam of Peru (PB; Myroxylon pereirae) is a natural product derived from resin of a tropical tree (MyroxyIon balsamum (L.) Harms var. pereirae (Royle) Baillon). Because of its antiseptic and aromatic properties PB or PB-components can be found worldwide not only in many health care and cosmetic products, but also in food items and semiluxury food. PB contains a wide variety of potent contact allergens leading to hypersensitivity reactions not only after topical application but also oral uptake. We report a 51-year-old brewer with chronic eczema of the hands who showed delayed-type patch test reactions against PB and fragrance-mix. Oral PB-challenge led to exacerbation of the eczema 5 and in a repeated test 2 days later. We here review this probably quite often overlooked disease and the therapeutic consequences which require profound knowledge about the wide distribution of PB when advising the patient about a PB-restricted diet. In addition, this unusual case report demonstrates that one has to consider marked delayed hypersensitivity reaction when investigating a systemic contact allergy.

Administration, Topical↗
PubMed2003

Antagonist-precipitated heroin withdrawal under anaesthetic prior to maintenance naltrexone treatment: determinants of withdrawal severity.

This study sought to characterize antagonist-precipitated heroin withdrawal during and immediately following anaesthesia and to identify the determinants of withdrawal severity and duration in 48 dependent heroin users. Objective withdrawal signs decreased significantly with each naloxone bolus administered under anaesthetic. The cost (amount) of the final heroin administration and the number of hours between last heroin use and commencement of anaesthesia were significant, independent predictors of the severity of withdrawal symptomatology. While 83% (40/48) of participants completed withdrawal according to objective criteria and commenced maintenance naltrexone treatment, almost half (22/48) were unable to commence naltrexone on the day of the procedure due to residual withdrawal signs. Fourteen of these 22 participants subsequently commenced naltrexone (median number of days between admission and commencement of naltrexone was 2, range 1 - 6) while eight left treatment prior to initiation of naltrexone. Significantly fewer of those with more severe withdrawal signs during anaesthesia commenced naltrexone (40% vs. 60%). While the severity and duration of withdrawal symptomatology may be moderated by encouraging participants to reduce (or cease) heroin use close to the time of withdrawal, for a substantial proportion of participants in this study, heroin withdrawal by this antagonist-precipitated procedure was neither rapid nor painless. [Ali R, Thomas P, White J, McGregor C, Danz,C, Gowing L, Stegink A, Athanasos P. Antagonist-precipitated heroin withdrawal under anaesthetic prior to maintenance naltrexone treatment: determinants of withdrawal severity.

Adolescent↗