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Biomedical subjects

D Peter

Publications and source records attributed to D Peter.

At least 19 recordsLinked to original sources
PubMed2003

Scintigraphy versus manometry in patients with suspected biliary sphincter of Oddi dysfunction.

INTRODUCTION: Sphincter of Oddi (SO) manometry is at present the "gold standard" investigation for patients with suspected biliary SO dysfunction. Non-invasive scintigraphy in cholecystectomised patients using a complex scoring system or the transit time from the hepatic hilum to the duodenum (HDTT) have been promoted as sensitive and specific alternatives. AIM: To evaluate the scintigraphic scoring system and HDTT in patients with suspected biliary SO dysfunction undergoing SO manometry. METHODS: Cholecystectomised patients undergoing SO manometry for persistent biliary-type pain, as defined by the Rome II criteria, for which all other causes had been excluded, were prospectively studied. Scintigraphy with cholecystokinin octapeptide infusion was performed within a month prior to manometry. Scoring of the scans and measurement of HDTT was performed by independent blinded observers. Manometry of the biliary sphincter was performed per-endoscopically and defined as abnormal if basal pressure was > or = 40 mm Hg. RESULTS: Thirty two patients were enrolled (30 females, mean age 45.1 years). Three patients were excluded from analysis because manometry from the bile duct was not technically possible. Eight patients had abnormal manometry. Scintigraphic scoring had a sensitivity of 25-38%, a specificity of 86-89%, positive predictive value (PPV) of 40-60%, and a negative predictive value (NPV) of 75-79%. The coefficient of variation for interobserver variation in scores was 0.72. HDTT sensitivity was 13%, specificity 95%, PPV 50%, and NPV 74%. CONCLUSIONS: Our findings indicate that scintigraphy using these methods of analysis correlates poorly with manometry in post cholecystectomy patients with suspected biliary SO dysfunction.

Adult↗
PubMed2002

Seasonal serum concentrations of melatonin in cycling and noncycling mares.

To determine whether secretory patterns of melatonin change throughout the seasons in mares, blood samples were drawn byvenipuncture from nine mares at noon and midnight for five successive days at monthly intervals from August through July at the University of Missouri in Columbia, MO. In addition, during September, December, March, and June, blood samples were drawn from indwelling catheters at 2-h intervals for 48 or 72 h. Mares were predominantly Quarter Horses weighing approximately 450 kg and ranged from 3 to 12 yr of age. Mares were housed in outdoor paddocks with three-sided run-in sheds for shelter. During the noon and midnight bleeding period, mares were placed in a larger open-sided barn with outside runs. Mares remained outdoors with the barn being used as a shelter in the event of inclement weather. All lights in the shed were converted to red light. Often, moonlight provided enough illumination to collect blood samples. Mares were returned to their normal paddock after each sampling period. For analysis of data, a mare was considered to be cycling if serum concentrations of progesterone were greater than 1 ng/ mL. For a mare to be classified as exhibiting a nocturnal rise of melatonin, serum concentrations of melatonin had to be at least two times greater at midnight than at noon. By month, a relationship did not exist (chi2; P > 0.05) among mares that were exhibiting estrous cycles and exhibiting nocturnal rises of melatonin. Likewise, examination of serum profiles of melatonin taken at 2-h intervals for 48 h revealed considerable variation among mares throughout the seasons. A nocturnal rise in serum melatonin was observed only in June (P < 0.02). In March and December, serum melatonin was greater in cycling mares than noncycling mares, but the elevation was not associated with light-dark periods (P < 0.01). Two of the mares exhibited estrous cycles throughout the seasons but melatonin secretion in these two mares were similar to that observed in the seven mares that demonstrated seasonal anestrous. From these results, it does not appear that changes in serum concentrations of melatonin are used as a cue to regulate cyclic activity in the mare throughout the seasons.

Anestrus↗
PubMed2000

Endogenous morphine.

It is now well accepted that endogenous morphine is present in animals, both in invertebrates and vertebrates. It is a key signaling molecule that plays an important role in downregulating physiological responses, such as those in the immune system, including immune elements in the CNS. It has been demonstrated that a specific mu-opiate-receptor subtype, mu3, mediates these downregulatory effects through release of NO. This article examines morphine as an endogenous signaling molecule, in terms of its role in neural and immune regulation.

Animals↗
PubMed2000

Determination of N,N-dimethylaminoethyl chloride and the dimethylaziridinium ion at sub-ppm levels in diltiazem hydrochloride by LC-MS with electrospray ionisation.

An LC-MS method is described for the determination of the synthetic reagent N,N-dimethylaminoethyl chloride (DMC) in the drug substance diltiazem hydrochloride, for which the permissible limit is not more than 1 ppm (microgram g-1). The N,N-dimethylaziridinium ion (DMA), the reactive intermediate formed by cyclisation of DMC, is also detected. A column switching arrangement is used: diltiazem hydrochloride is trapped on a reversed-phase HPLC column, and the polar analytes are separated by ion exchange chromatography. Ionisation is effected by positive-ion electrospray, and the quadrupole filter mass spectrometer is operated in the selected ion recording mode. The detection limit (peak height-to-baseline noise ratio = 3) for DMC varies from day to day in the range < 0.05 to 0.1 ppm. The response for DMC is linear (r > 0.999) over the concentration range 0.2-10 ppm, and the repeatability is better than 7% (relative standard deviation) at 1.0 ppm. Concentrations of DMC in diltiazem hydrochloride from the manufacturing facility under study ranged from undetectable to about 0.07 ppm. An indirect TLC method has been published for the determination of DMC in mepyramine maleate, but it lacks the necessary sensitivity and specificity. The LC-MS method presented is direct, straightforward and suitable for routine use.

Alkylating Agents↗
PubMed2000

The low dose ACTH stimulation test is less sensitive than the overnight metyrapone test for the diagnosis of secondary hypoadrenalism.

OBJECTIVE: The 1 microgram ACTH stimulation test has been advocated as a sensitive indicator of the integrity of the hypothalamic-pituitary-adrenal axis in patients with suspected hypopituitarism. The aim of our study was to define the normal response to 1 microgram ACTH stimulation in a control population and to study the sensitivity and specificity of the test in a group of patients with suspected pituitary disease. DESIGN: A prospective analysis of the performance of the 1 microgram ACTH stimulation test in a group of patients with pituitary disease. PATIENTS: The cortisol response to 1 microgram ACTH was evaluated in 21 normal subjects and 65 patients with pituitary disease. The patients with pituitary disease were divided into two groups according to the 11-deoxycortisol response to overnight metyrapone: normal (11-deoxycortisol > 200 nmol/l) and subnormal ACTH secretory status (11-deoxycortisol < 200 nmol/l). MEASUREMENTS: In both controls and patients, blood was sampled for cortisol at - 15, 0, + 20, + 30, + 40 and + 60 minutes after intravenous administration of 1 microgram synthetic ACTH (Synacthen(R)). The overnight metyrapone test was performed only in the subjects with pituitary disease. Metyrapone (30 mg/kg) was administered orally at 2300 h and blood was sampled at 0830 h the following morning for 11-deoxycortisol. RESULTS: The 65 patients with pituitary disease were categorized according to the 11-deoxycortisol response to metyrapone as follows: 53 normal (11-deoxycortisol > 200 nmol/l) and 12 subnormal (< 200 nmol/l). The 12 patients who failed the metyrapone test had a significantly impaired cortisol response to low dose ACTH stimulation at all time points when compared with both the control group and the pituitary patients with a normal response to metyrapone (P < 0.001). Comparing the pituitary patients who had a normal response to metyrapone and the control subjects, there was no significant difference in the cortisol response to ACTH (P > 0.05). The minimum cortisol response at 30 minutes in the 21 control subjects was 414 nmol/l and this was defined as the minimum normal cortisol response to 1 microg ACTH. Using this criterion, six of the 12 patients with a subnormal response to metyrapone had a normal cortisol response to low dose ACTH stimulation. Empirically increasing the cortisol cut-off to 600 nmol/l increased the sensitivity of the low dose ACTH test to 83%, although the specificity was reduced from 100% to only 58%. CONCLUSIONS: The normal cortisol response to low dose ACTH stimulation in 50% of the patients with ACTH deficiency proven on metyrapone testing suggests that the 1 microgram ACTH stimulation test, like the 250 microgram-test, lacks sensitivity for the diagnosis of ACTH deficiency.

Adult↗
PubMed2000

Dynamics of discourse: a case study illuminating power relations in mental retardation.

In this paper, a discourse analysis of a single case, I examine the text of the case file of an individual labeled as having mental retardation. The focus is on exploring some of the power dynamics that underpin services and our understanding of mental retardation. Using Foucault's treatise on discipline as an analytic tool, I sought to unravel some of the mechanisms through which a defective identity is constructed, thereby legitimizing social control.

Adult↗
PubMed2000

Human vascular and cardiac endothelia express mu opiate receptor transcripts.

Pharmacologic and immunologic evidence suggests that nitric oxide-coupled mu-subtype opiate receptors are expressed in human vascular endothelium. In this study, we present molecular evidence of mu opiate receptor expression. Using primers derived from the human neuronal mu1 opiate receptor, we used RT-PCR to detect expression of mu transcripts from human endothelia. Sequence analysis of the RT-PCR products revealed 100% identity with the neuronal human mu1 receptor. We further show that pretreatment of human internal thoracic artery and cardiac atrial endothelium with the proinflammatory cytokines interleukin-1-alpha and -beta led to a significant increase in both the expression of the mu transcript and in morphine-stimulated nitric oxide release measured amperometrically. Taken together, these studies provide molecular evidence that mu-type opiate receptors are expressed in human vascular endothelia and that their expression can be upregulated by proinflammatory cytokines.

Base Sequence↗
PubMed1999

Mu3 opiate receptor expression in lung and lung carcinoma: ligand binding and coupling to nitric oxide release.

The mu3 opiate receptor subtype is expressed in human surgical specimens of both normal lung and non-small-cell lung carcinoma. Nitric oxide (NO) release is mediated through the mu3 receptor, and in lung carcinoma, morphine-stimulated NO release is significantly higher and prolonged than in normal lung. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis we show that specific mu opioid receptor transcripts are present in lung carcinoma and other cells with the mu3 profile. Our findings identify a unique role for the mu3 opiate receptor in opiate-mediated NO release and suggest that endogenous opiates, through their release of NO, may play a role in cancer progression.

Dihydromorphine↗
PubMed1999

[Rotational digital subtraction angiography of carotid bifurcation stenosis].

PURPOSE: A prospective study was designed to evaluate, whether multiplanar imaging with rotational digital subtraction angiography (R-DSA) could improve assessment of carotid artery bifurcation stenosis. PATIENTS AND METHODS: 45 patients with suspected stenosis of the ICA were examined with DSA in standard projections (0 degree-(45 degrees)-90 degrees) and additional R-DSA of each ICA from 0-90 degrees in 10 degrees steps. We compared imaging quality and degree of stenosis as well as exposure of the patients to radiation and contrast media. RESULTS: 79/82 R-DSA (96%) were suitable for evaluation of stenosis, 58/82 (70%) matched the quality standard of single projection DSA. Specificity and sensitivity of the R-DSA to diagnose high grade ACI stenosis were 100% and 94%, respectively. 7/79 R-DSA revealed a higher and 3/79 a lower degree of stenosis than the corresponding DSA. Regarding the degree of stenosis there was no significant difference between the two modalities (p > 0.05), but R-DSA detected 4 stenoses greater than 60% that were estimated to be lower than 60% by DSA. Radiation dose for R-DSA was equivalent to one DSA run (170 cGycm2). The average amount of contrast media (25 ml) was slightly higher than for 2-3 single-projection DSA (19.8 ml). CONCLUSIONS: R-DSA provides high quality imaging of the carotid bifurcation with multiplanar projections facilitating exact grading of vessel stenosis. The number of cases (n = 2) is to small to judge the value of R-DSA as to (tandem-) stenosis of the distal ICA. Still, diagnostic value and low radiation exposure justify the use of R-DSA as additional series to standard protocols.

Adult↗
PubMed1999

Behaviour of migrating birds exposed to X-band radar and a bright light beam

Radar studies on bird migration assume that the transmitted electromagnetic pulses do not alter the behaviour of the birds, in spite of some worrying reports of observed disturbance. This paper shows that, in the case of the X-band radar 'Superfledermaus', no relevant changes in flight behaviour occurred, while a strong light beam provoked important changes. Large sets of routine recordings of nocturnal bird migrants obtained using an X-band tracking radar provided no indication of differing flight behaviour between birds flying at low levels towards the radar, away from it or passing it sideways. Switching the radar transmission on and off, while continuing to track selected bird targets using a passive infrared camera during the switch-off phases of the radar, showed no difference in the birds' behaviour with and without incident radar waves. Tracking single nocturnal migrants while switching on and off a strong searchlight mounted parallel to the radar antenna, however, induced pronounced reactions by the birds: (1) a wide variation of directional shifts averaging 8 degrees in the first and 15 degrees in the third 10 s interval after switch-on; (2) a mean reduction in flight speed of 2-3 m s-1 (15-30 % of normal air speed); and (3) a slight increase in climbing rate. A calculated index of change declined with distance from the source, suggesting zero reaction beyond approximately 1 km. These results revive existing ideas of using light beams on aircraft to prevent bird strikes and provide arguments against the increasing use of light beams for advertising purposes.

Journal Article↗
PubMed1997

Phosphorylation of a vesicular monoamine transporter by casein kinase II.

The vesicular monoamine transporters (VMATs) package monoamine neurotransmitters into secretory vesicles for regulated exocytotic release. One isoform occurs in the adrenal gland (VMAT1) and another in the brain (VMAT2). To assess their potential for regulation, we have investigated the phosphorylation of the VMATs. Using heterologous expression in Chinese hamster ovary, PC12, and COS cells, we find that rat VMAT2, but not VMAT1, is constitutively phosphorylated. Phosphoamino acid analysis indicates that this phosphorylation occurs on serine residues, and the analysis of VMAT1-VMAT2 chimeras and site-directed mutagenesis localize the phosphorylation sites to serines 512 and 514 at the carboxyl terminus of VMAT2. Since these residues occur in an acidic region, we tested the ability of the acidotropic kinases casein kinase I (CKI) and casein kinase II (CKII) to phosphorylate bacterial fusion proteins containing the carboxyl terminus of VMAT2. Purified CKI and CKII phosphorylate the wild-type carboxyl terminus of VMAT2, but not a double mutant with both serines 512 and 514 replaced by alanine. The protein kinase inhibitor CKI-7 and unlabeled GTP both block in vitro phosphorylation by cell homogenates, indicating a role for CKII and possibly CKI in vivo. Both kinases phosphorylate the VMAT2 fusion protein to a much greater extent than a similar fusion protein containing the carboxyl terminus of VMAT1, consistent with differential phosphorylation of the two transporters observed in intact cells. These results provide the first demonstration of phosphorylation of a vesicular neurotransmitter transporter and a potential mechanism for differential regulation of the two VMATs.

Adenosine Triphosphate↗
PubMed1996

Vesicular monoamine transporter 2 expression in enteric neurons and enterochromaffin-like cells of the rat.

The cellular localization of the vesicular monoamine transporter 2 (VMAT2) in the rat digestive tract was investigated with immunohistochemistry. VMAT2-immunoreactivity (IR) was localized to neurons and fibers of enteric and pancreatic ganglia, to processes supplying the gut wall, the pancreas and blood vessels, and to enterochromaffin-like (ECL) cells in the gastric corpus, which contained calbindin-IR. Few VMAT2-IR cells were also found in the gastric antrum, but they did not contain gastrin-IR. VMAT2-IR was expressed in extrinsic sympathetic fibers as demonstrated by the elimination of a portion of VMAT2-IR processes by sympathectomy. The VMAT2-IR pattern is consistent with the overall distribution of biogenic amine cell groups in the digestive tract. Our results provide further evidence that VMAT2 is the vesicular amine transporter responsible for accumulation of monoamines into secretory vesicles of monoaminergic neurons and ECL cells.

Animals↗
PubMed1996

Chimeric vesicular monoamine transporters identify structural domains that influence substrate affinity and sensitivity to tetrabenazine.

The vesicular monoamine transporters (VMATs) 1 and 2 show close sequence similarity but substantial differences in apparent substrate affinity and drug sensitivity. To identify structural domains that determine these functional characteristics, chimeric transporters were constructed and their properties were analyzed in a heterologous expression system. The results implicate multiple regions in the recognition of serotonin and histamine and the sensitivity to tetrabenazine. Two domains of VMAT2, one extending from transmembrane domain (TMD) 5 to the beginning of TMD8 and the other from the end of TMD9 through TMD12, increase the affinity for serotonin and histamine as well as the sensitivity to tetrabenazine but only in the context of more C-terminal and more N-terminal VMAT2 sequences, respectively. In addition, the extreme N terminus of VMAT2 alone suffices to confer a partial increase in substrate affinity and tetrabenazine sensitivity. Despite these similarities among the interactions with serotonin, histamine, and tetrabenazine, the region of VMAT2 from TMD3 through TMD4 increases serotonin affinity but not histamine affinity or tetrabenazine sensitivity, and whereas the region from TMD5 to TMD8 of VMAT2 increases serotonin affinity in the context of more C-terminal VMAT2 sequences, the region encompassing TMD5 through TMD7 reduces serotonin but not histamine affinity or tetrabenazine sensitivity in the context of more N-terminal VMAT2 sequences. Thus, the chimeric analysis also reveals differences between serotonin recognition and the recognition of both histamine and tetrabenazine that may account for the observed differences in their interaction with the transport protein.

Animals↗
PubMed1996

A molecular analysis of vesicular amine transport.

To package classical neurotransmitters into vesicles so that their release can be regulated by activity, neuronal cells express a set of specific vesicular transport proteins. We have used selection in MPP+ to clone the cDNAs encoding two vesicular monoamine transporters, the first members of this novel gene family that now also includes the vesicular transporter for acetylcholine. The sequences show similarity to several bacterial antibiotic resistance proteins, further supporting a role in detoxification and possibly Parkinson's disease. The two vesicular amine transporters show differences in their affinity for substrates, their turnover number and their pharmacology. In particular, the proteins differ in their interactions with the potent inhibitor tetrabenazine and with amphetamines, accounting for several classic pharmacological observations. Since the subcellular localization of the transport proteins determines the site of monoamine storage and the site of monoamine storage appears to differ from other classical transmitters, we have also raised polyclonal antibodies to the transporters and used these to demonstrate localization in dense core vesicles rather than synaptic vesicles. In addition to the implications for monoamine release, these observations also indicate a vesicular amine transporter as the first integral membrane protein restricted to the regulated secretory pathway.

Animals↗
PubMed1996

Reserpine affects differentially the density of the vesicular monoamine transporter and dihydrotetrabenazine binding sites.

We have studied the effect of a single injection of reserpine (5 mg/kg, s.c.) on the synaptic vesicle monoamine transporter (VMAT) density in the rat striatum, using two labelling procedures: radioimmunolabelling with an antibody against VMAT, and binding of the specific ligand [(3)H]dihydrotetrabenazine ([(3)H]TBZOH). In the rostral and medial striatum, the distribution of VMAT immunoreactivity displayed the highest density in the lateral subregions. In the caudal part of the striatum, VMAT immunoreactivity showed increasing density from dorsal to ventral subregions. The VMAT immunoreactivity was not altered 2 and 30 days after the reserpine injection, whereas [(3)H]TBZOH binding site density, measured on adjacent slices, showed a dramatic decrease at day 2 and a moderate recovery at day 30, suggesting that despite a persistent blockade of [(3)H]TBZOH binding sites, VMAT protein density was unchanged.

Animals↗