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Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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%.