Search Results - (Author, Cooperation:R. D. Gordon)

2012-01-24

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Amino Acid Sequence ; Animals ; Base Sequence ; Blood Pressure/genetics ; Carrier Proteins/chemistry/*genetics ; Cohort Studies ; Cullin Proteins/chemistry/*genetics ; Electrolytes ; Exons/genetics ; Female ; Gene Expression Profiling ; Genes, Dominant/genetics ; Genes, Recessive/genetics ; Genotype ; Homeostasis/genetics ; Humans ; Hydrogen-Ion Concentration ; Hypertension/complications/*genetics/physiopathology ; Male ; Mice ; Models, Molecular ; Molecular Sequence Data ; Mutation/*genetics ; Phenotype ; Potassium/metabolism ; Pseudohypoaldosteronism/complications/*genetics/physiopathology ; Sodium Chloride/metabolism ; Water-Electrolyte Imbalance/complications/*genetics/physiopathology

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Preparations of structurally preserved cerebellar perikarya (cells) were found to express high-affinity transport systems for glutamate but not for certain putative transmitter substances (including monoamines, glycine and taurine) and non-transmitter amino acids. The characteristics of the high-affinity glutamate transport system were similar to those of other preparations of brain tissue: [3H]glutamate uptake by the cells was Na+-dependent and was inhibited competetively by other acidic amino acids. The rank order of apparent affinities of the carrier for acidic amino acids was L-aspartate 〉 L-glutamate 〉 D-aspartate ≫ D-glutamate (the affinity for D-glutamate being over two orders of magnitude lower than for the other three amino acids). Comparison of high-affinity [3H]glutamate uptake in preparations enriched in different cell types showed that although the affinities are similar (2-4 fiM), the rate is outstandingly high in astrocytes (Vmax 18 nmol/min per mg protein). Significantly, uptake into the putatively glutamatergic granule cells was very low. These observations were supported by autoradiographic findings which showed that the predominant sites of [3H]glutamate uptake in cerebellar cultures enriched in interneurones are the astrocytes. Furthermore, the Vmax in cultures enriched in astrocytes was as high as that in separated astrocytes. Thus, it seems that the principal cell type involved in acidic amino acid uptake in the cerebellum is the astrocyte, and this must be taken into consideration when high-affinity uptake is used as a marker for glutamatergic transmitter systems. Furthermore, the selective cellular distribution of glutamate transport sites, together with the uneven distribution of enzymes related to glutamate metabolism observed previously, indicates that a metabolic interaction takes place between the different cell types, supporting the current hypothesis on metabolic compartmentation in the brain.

Electronic Resource

1089-7690

AIP Digital Archive

Physics

Chemistry and Pharmacology

The 18 373 cm−1 band in the fluorescence excitation spectrum of jet-cooled CrO2F2 has been recorded with 0.007 cm−1 linewidth. The stronger lines have been assigned to a type c transition, consistent with a B1←A1 vibronic transition analogous to that in CrO2Cl2. Ground-state rotational constants, A″=0.148, B″=0.130, and C″=0.120 cm−1, agree well with electron diffraction predictions. The B1 excited state is significantly perturbed. Evidence includes (i) a decreasing fluorescence yield with increasing J′, such that signals were not observed for J′〉3, (ii) the appearance of "extra'' lines in the spectrum, leading to perturbing levels strongly mixed with levels of the B1 state, and (iii) anomalous effective rotational constants for the B1 state.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract: The effect of anoxia and ischemia on the release of amino acid transmitters from cerebellar slices induced by veratridine or high [K+] was studied. Synaptic specificity was tested by examining the tetradotoxin (TTX)-sensitive and the Ca2+-dependent components of stimulated release. Evoked release of endogenous amino acids was investigated in addition to more detailed studies on the stimulated efflux of preloaded [14C]GABA and d-[3H]aspartate (a metabolically more stable anologue of acidic amino acids).[14C]GABA release evoked by either method of stimulation was unaffected by periods of up to 35 min of anoxia and declined moderately by 45 min. In contrast, induced release of d-[3H]Asp increased markedly during anoxia to a peak at about 25 min, followed by a decline when anoxia was prolonged to 45 min. Evidence was obtained that the increased evoked efflux of d-[3H]Asp from anoxic slices was not due to impaired reuptake of the released amino acid and that it was completely reversible by reoxygenation of the slices. Results of experiments examining the evoked release of endogenous amino acids in anoxia were consistent with those obtained with the exogenous amino acids. Only 4 of the 10 endogenous amino acids studied exhibited TTX-sensitive veratridine-induced release under aerobic conditions (glutamate, aspartate, GABA, and glycine). Anoxia for 25 min did not affect the stimulated efflux of these amino acids with the exception of glutamate, which showed a significant increase. Compared with anoxia, effects of ischemia on synaptic function appeared to be more severe. Veratridine-evoked release of [14C]GABA was already depressed by 10 min and that of d-[3H]Asp showed a modest elevation only at 5 min. Stimulated release of d-Asp and labelled GABA declined progressively after 5 min. These findings were compared with changes in tissue ATP concentrations and histology. The latter studies indicated that in anoxia the earliest alterations are detectable in glia and that nerve terminals were the structures by far the most resistant to anoxic damage. The results thus indicated that evoked release of amino acid transmitters in the cerebellum is compromised only by prolonged anoxia in vitro. In addition, it would appear that the stimulated release of glutamate is selectively accentuated during anoxia. This effect may have a bearing on some hypoxic behavioral changes and, perhaps, also on the well-known selective vulnerability of certain neurons during hypoxia.

Electronic Resource

1440-1681

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

1. This study sought to assess the incidence of primary aldosteronism in 199 hypertensives who were normokalaemic and in whom the question of primary aldosteronism had never been raised.2. The screening test applied was the aldosterone to renin ratio in plasma, which was raised in 40 and normal in 159 patients. A second ratio was normal in 14 of these 40.3. Twenty-two patients with two further raised ratios required fludrocortisone suppression testing. This has been completed in 17, and failure to suppress led to a diagnosis of primary aldosteronism in all.4. A dexamethasone suppression test (DST) excluded ACTH-dependent hyperaldosteronism and laterality of aldosterone production was determined by adrenal vein sampling.5. Unilaterality in five patients led to adrenalectomy in four and spironolactone in one. Bilaterality in six patients led to spironolactone.6. This study so far provides a proven (minimum) incidence for primary aldosteronism of 8.5%, a probable incidence of 12.0% (including two raised ratios) and a possible (maximum) incidence of 13.0% (leaving out those with second ratio normal). Exclusion of hypokalaemic hypertensives will lead to an underestimation of the true incidence of primary aldosteronism.7. Based on this and other evidence, it is estimated that the incidence of primary aldosteronism in the ‘essential hypertensive’ population is between 5 and 15%, and is probably around 10%.

Electronic Resource

1440-1681

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

1. A significant positive correlation was found between changes in circulating noradrenaline (NA) levels and changes in atrial natriuretic peptide (ANP) levels during NA infusion and clonidine administration.2. A significant positive correlation was also found between changes in arterial blood pressure and changes in ANP level during infusion of angiotensin II and of NA.3. Two patients with very high circulating NA levels due to phaeochromocytoma, but receiving α-and β-blockade, did not have clearly elevated ANP. A third not receiving medications and aged 73 years had elevated levels.4. Atrial natriuretic peptide response to NA and angiotensin II may be mediated by changes in blood pressure levels or increased noradrenergic and angiotensinergic receptor activity in the atria or both. Atrial natriuretic peptide may have a role in blood pressure regulation in both normotensive and hypertensive man.

Electronic Resource

1440-1681

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

1. Plasma levels of ANP were measured in normal subjects and in three conditions associated with disturbed volume homeostasis.2. Levels of ANP were appropriately raised in seven patients with primary aldosteronism, and fell to normal following removal of an aldosterone-producing adenoma in six and dexamethasone treatment in one patient with glucocorticoid-suppressible hyperaldosteronism.3. The level of ANP in one patient with Gordon's syndrome (a condition associated with plasma volume expansion) was lower than in the patients with primary aldosteronism, both before and after saline infusion. This is consistent with reduced ANP responsiveness in this condition.4. Levels of ANP were inappropriately elevated in three patients with Bartter's syndrome (a condition with plasma volume contraction) and rose further during saline infusion. This is consistent with primary hypersecretion of ANP.

Electronic Resource

1440-1681

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

1. Both resting and stimulated (straight-leg raising and head-up tilt) levels of arterial and venous plasma noradrenaline were significantly higher during low-dose adrenaline infusion in five mild hypertensive and four normotensive patients with one adrenal.2. Repeat adrenaline infusions in the five hypertensive patients while measuring noradrenaline clearance (3H-noradrenaline constant infusion) achieved similar levels of plasma adrenaline, and similar increases in plasma noradrenaline, within five min of achieving target infusion rate. Increased plasma noradrenaline was not explained by reduced clearance.3. These results are consistent with the hypothesis that physiological concentrations of adrenaline are capable of facilitating noradrenaline release in man.

Electronic Resource

1440-1681

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

1. In 14 hypertensive patients aldosterone/cortisol ratio was always lower in a peripheral vein or low IVC than in either adrenal vein. In four patients with a right-sided aldosterone-producing adenoma (APA), the aldosterone/cortisol ratio in peripheral vein was always higher than in the left adrenal vein. If only the left adrenal vein is cannulated, right-sided APA can still be diagnosed with certainty.2. In three patients with glucocorticoid-suppressible hyperaldosteronism, urinary excretion of both 18-oxocortisol and 18-hydroxycortisol was elevated. In four patients with APA excretion of 18-oxocortisol was elevated. In two of three patients with bilateral adrenal hyperplasia (BH), excretion of both steroids was normal.3. 75Se-selenomethylcholesterol scanning correctly lateralized five APA, but falsely lateralized a patient with BH. Results with CT scans were often misleading.

Electronic Resource

1440-1681

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

1. The ratio of aldosterone to renin in plasma was measured in samples collected from 79 hypertensive patients.2. Eighteen patients with primary aldosteronism had ratios ranging from 25 to 677 (mean 183) when measured on 34 occasions, while 16 normal subjects had ratios of 3.3–21 (mean 11.3).3. Of the remaining 61 patients with ratios ranging from 1.8 to 184, 15 patients have ratios greater than 25 and are under investigation for primary aldosteronsim, which appears highly likely in five and has been excluded in two.4. The aldosterone/renin ratio appears promising as a screening test for primary aldosteronism. Consistency and the effects of sodium and potassium balance and of antihypertensive medications require further study.

Electronic Resource

1440-1681

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

1. In patients with primary aldosteronism due to angiotensin-responsive and andotensin-unresponsive aldosterone-producing adenomas, no differences in the coding region of the angiotensin II type 1 (AT1) receptor gene were observed compared to normal subjects in peripheral blood leucocyte DNA.2. Furthermore, no differences in the AT1 receptor gene were observed in DNA extracted from tumour tissue of either subgroup.3. Genotypic and allelic frequencies for an RFLP detected in the coding region of the AT1 receptor gene were not significantly different between normal subjects and patients with aldosterone-producing adenomas as a group, nor between normal subjects and patients of either subgroup when compared with each other.4. In those patients heterozygous in peripheral blood at the RFLP site, tumour DNA showed the same allelic pattern.5. In patients with aldosterone-producing adenomas either responsive or unresponsive to the renin-angiotensin system, no differences were detected using SSCP analysis in the coding region of the AT1 receptor gene in peripheral blood or tumour tissue.

Electronic Resource

1440-1681

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

1. Saline infusion was performed in normal subjects, in essential hypertensives and in patients with aldosterone-producing adenoma (APA), with serial measurements of plasma aldosterone, cortisol and atrial natriuretic peptide (ANP). The effect of recumbency alone was also observed in the normal subjects.2. Plasma aldosterone after saline infusion was less than 7 ng per 100 ml in the essential hypertensives and normal subjects, but greater than 9 ng per 100 ml in the patients with APA.3. The aldosterone/cortisol ratio in normal subjects and in essential hypertensives was unchanged or fell during saline infusion, but rose in five of eight patients with APA.4. Thus, an increase in aldosterone/cortisol ratio after saline infusion appears to be diagnostic of APA, but its absence does not exclude it.

Electronic Resource

1440-1681

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

1. Two males with glucocorticoid-suppressible hyperaldosteronism had hyperaldosteronism, hypertension and hypokalaemia corrected by continuous administration of physiological doses of dexamethasone for more than a year.2. During long-term dexamethasone treatment:(a) Plasma renin activity increased from subnormal to high normal levels, with normal posture-mediated increases;(b) Plasma aldosterone became responsive to angiotensin infusion, a new observation;(c) A fall in plasma aldosterone between 0800 h (recumbent) and 1000 h (upright) was replaced by a rise;(d) Plasma aldosterone became suppressible with salt loading.3. These findings are consistent with a shift to more normal control of aldosterone by renin-angiotensin, once abnormal responsiveness to ACTH has been nullified.

Electronic Resource

1440-1681

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

1. Renal venous renin ratio (RVRR) was measured in twenty hypertensive patients before removal of a kidney for unilateral, parenchymal renal disease. They were then followed for 1.3–9 y.2. Hypertension was cured or improved in six of eight patients with positive unstimulated and stimulated ratios, in none of five whose ratios became positive only on stimulation, and in one of seven with all ratios negative.3. Patients improved or cured by surgery had a significantly shorter duration of hypertension and a significantly lower serum creatinine after nephrectomy.4. Unstimulated RVRR was a reliable predictor of the effect of unilateral nephrectomy on blood pressure level.

Electronic Resource

1440-1681

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

1. A subgroup of patients with aldosterone-producing adenoma (APA) have been identified who lack many of the biochemical features regarded as characteristic of APA and used to distinguish APA from bilateral adrenal hyperplasia.2. In these patients, aldosterone is responsive to infused angiotensin II (angiotensin-responsive APA), which explains their uncharacteristic responses to upright posture, saline infusion and fludrocortisone acetate administration.3. The angiotensin-responsiveness of these patients may derive from the contra-lateral adrenal gland, since renin levels are less completely suppressed in angiotensin-responsive APA than in angiotensin-unresponsive APA.4. However, while the excretion of 18-oxo-cortisol was consistently increased in angiotensin-unresponsive APA, it was normal in angiotensin-responsive APA, consistent with biochemical and biosynthetic distinctiveness residing in the tumours.5. Angiotensin-responsive APA should always be considered as an alternative diagnosis to bilateral hyperplasia causing primary aldosteronism.

Electronic Resource

1440-1681

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

1. Normokalaemic primary aldosteronism (PA) masquerades as ‘essential hypertension', and 50% of patients with aldosterone-producing adenoma (APA) are normokalaemic at presentation to this unit.2. Angiotensin-responsive (AII-R) APA is as common as angiotensin-unresponsive (AII-U) APA, and requires adrenal venous sampling for differentiation from bilateral adrenal hyperplasia (BAH).3. From 1981 to 1992, 55 patients with APA underwent unilateral adrenalectomy and were followed up for at least 12 months postoperatively. Hypertension was cured in 55% and improved in the remainder.4. Cure rate was lower (P〈0.001) in males (11/32, 34%) vs females (19/23, 83%), lower (P〈0.005) in patients over 45 years of age (13/33, 39%) vs those 45 years or younger (17/22, 77%), lower (P〈0.05) in AII-R APA (11/28, 39%) vs AII-U APA (19/27, 70%) and tended to be lower (not significant) in normokalaemic APA (7/17, 41%) vs hypokalaemic APA (23/38, 61%).5. A higher proportion (P〈0.001) of AII-R APA patients were males (23/28, 82%) vs AII-U APA (9/27, 33%), and a higher proportion were from the older age group (AII-R APA 20/28, 71%vs AII-U APA 13/27, 48%; P〈0.05). Females with AII-U APA who were hypokalaemic had a very high cure rate (16/17, 94%).6. Since unilateral adrenalectomy cures or improves blood pressure in normokalaemic and AII-R as well as in hypokalaemic and AII-U patients, all hypertensives should be screened for PA, and AII-R APA differentiated from BAH in proven PA.

Electronic Resource

1432-1211

Springer Online Journal Archives 1860-2000

Biology

Medicine

Abstract The secondary cytotoxic responses to the male-specific antigen (H-Y) in mice showH-2 restriction so that the cytotoxic female cell must share the K- and/or D-end antigen with the male target cells. The association with the K and/or D end varies with differentH-2 haplotypes,e.g., H-2 b cytotoxic cells require the H-2Db antigen(s) on the target cells, while cytotoxic cells fromH-2 b/H-2 d F1 mice sensitized toH-2 d male cells kill only male targets having H-2Kd antigen(s). This association of H-Y with appropriate K/D antigens seems to be needed also in the induction of the cytotoxic response. Of the independent haplotypes, onlyH-2 b strains are capable of making secondary anti-H-Y responses and this trait seems to be dominant,i.e., the F1 strains with oneH-2 b parent are able to produce anti-H-Y cytotoxic cells against both theH-2 b parent and the nonresponder parent. The mating of the two nonresponder strains may produce F1 mice which are responders, thus suggestingIr gene complementation. Mapping data indicates that at least one of these complementary genes is located in theI-C region fork/s complementation.

Electronic Resource

1432-2277

Human orthotopic liver transplantation ; Complications ; Biliary tract ; Primary sclerosing cholangitis ; Recurrent disease ; Rejection

Springer Online Journal Archives 1860-2000

Medicine

Abstract One of 55 patients transplanted for sclerosing cholangitis during the cyclosporin-steroid era (March 1980–June 1986) developed intrahepatic biliary strictures in the absence of allograft rejection within the 1st year posttransplantation. Although many causes underlie biliary pathology in the postoperative period (i.e., arterial injury, ischemia, chronic rejection, cholangitis), recurrent disease remains a possibility.

Electronic Resource

0377-0486

Chemistry ; Analytical Chemistry and Spectroscopy

Wiley InterScience Backfile Collection 1832-2000

Chemistry and Pharmacology

Physics

Raman and infrared spectra of tetramethylcyclobutane-1, 3-dithione (TMCBDT) and the fully deuteriated derivative (TMCBDT-d12) have been recorded. A reasonably complete set of vibrational frequencies and assignments are presented for the two molecules. The symmetric C=S stretching mode was observed at 1328 cm-1 for TMCBDT and at 1352 cm-1 for TMCBDT-d12. The antisymmetric C=S stretching mode occurs at lower frequencies of 1167 cm-1 for TMCBDT and 1158 cm-1 for the deuteriated molecule. This is consistent with previous observations for tetramethylcyclobutanedione. Ground-state vibrational frequencies of several modes involved in progressions in the n→ π* electronic absorption spectra have been located.

4 Ill.

Electronic Resource