A novel genetic locus for low renin hypertension: familial hyperaldosteronism type II maps to chromosome 7 (7p22)

Familial hyperaldosteronism type II (FH-II) is caused by adrenocortical hyperplasia or aldosteronoma or both and is frequently transmitted in an autosomal dominant fashion. Unlike FH type I (FI-I-I), which results from fusion of the CYP11B1 and CYP11B2 genes, hyperaldosteronism in FH-II is not glucocorticoid remediable. A large family with FH-II was used for a genome wide search and its members were evaluated by measuring the aldosterone:renin ratio. In those with an increased ratio, FH-II was confirmed by fludrocortisone suppression testing. After excluding most of the genome, genetic linkage was identified with a maximum two point lod score of 3.26 at theta =0, between FH-II in this family and the polymorphic markers D7S511, D7S517, and GATA24F03 on chromosome 7,a region that corresponds to cytogenetic band 7p22. This is the first identified locus for FH-II; its molecular elucidation may provide further insight into the aetiology of primary aldosteronism.

Exposure of rats to a high but not low dose of ethanol during early postnatal life increases the rate of loss of optic nerve axons and decreases the rate of myelination

Visual system abnormalities are commonly encountered in the fetal alcohol syndrome although the level of exposure at which they become manifest is uncertain. In this study we have examined the effects of either low (ETLD) or high dose (ETHD) ethanol, given between postnatal days 4-9, on the axons of the rat optic nerve. Rats were exposed to ethanol vapour in a special chamber for a period of 3 h per day during the treatment period. The blood alcohol concentration in the ETLD animals averaged similar to 171 mg/dl and in the ETHD animals similar to 430 mg/dl at the end of the treatment on any given day. Groups of 10 and 30-d-old mother-reared control (MRC), separation control (SC), ETLD and ETHD rats were anaesthetised with an intraperitoneal injection or ketamine and xylazine, and killed by intracardiac perfusion with phosphate-buffered glutaraldehyde. In the 10-d-old rat optic nerves there was a total of similar to 145000-165000 axons in MRC, SC and ETLD animals. About 4 % of these fibres were myelinated. The differences between these groups were not statistically significant. However, the 10-d-old ETHD animals had only about 75000 optic nerve axone (P < 0.05) of which about 2.8 % were myelinated. By 30 d of age there was a total of between 75000 90000 optic nerve axons, irrespective of the group examined. The proportion of axons which were myelinated at this age was still significantly lower (P < 0.001) in the ETHD animals (similar to 77 %) than in the other groups (about 98 %). It is concluded that the normal stages of development and maturation of the rat optic nerve axons, as assessed in this study, can be severely compromised by exposure to a relatively high (but not low) dose of ethanol between postnatal d 4 and 9.

Characterization of peroxisome proliferator-activated receptor alpha in normal rat mammary gland and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced mammary gland tumors from rats fed high and low fat diets

Normal Sprague-Dau ley rat mammary gland epithelial cells and mammary gland carcinomas induced by 2-amino-1 -methyl-6-phenylimidazo[4,5-b]pyridine, a carcinogen found in the diet, were examined for the expression of peroxisome proliferator-activated receptor alpha (PPAR alpha). PPAR alpha mRNA and protein was detected in normal and tumor tissue by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. By quantitative RT-PCR, carcinomas had a 12-fold higher expression than control mammary glands, a statistically significant difference. PPAR alpha expression was examined in carcinomas and normal tissues from rats on high fat (23.5/% corn oil) and low fat (5% corn oil) diets. Although neither carcinomas, nor control tissues showed statistically significant differences between the two diet groups, PPAR alpha expression was the highest in carcinomas from rats on the high fat diet. The expression of PPAR alpha in normal mammary gland and its significant elevation in mammary gland carcinomas raises the possibility of its involvement in mammary gland physiology and pathophysiology. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.

Semisolid casting of AlSi7Mg0.35 alloy produced by low-temperature pouring

AlSi7Mg0.35 alloy was cast into permanent moulds using different pouring temperatures (725 to 625degreesC). As the pouring temperature decreased, the as-cast microstructure changed from a coarse dendritic structure, through fine equiaxed grains to fine rosette-like grains. The as-cast materials were then partially remelted and isothermally held at 580degreesC prior to semisolid casting into a stepped die. The feedstock material cast from a high temperature filled only half the die, with severe segregation and other defects. The low-temperature-poured material completely filled the die with negligible porosity. The quality of semisolid castings is significantly affected by the microstructure of the semisolid feedstock material that arises from a combination of as-cast and subsequent thermal treatment conditions. The paper describes (a) the influence of pouring temperature on the microstructure of feedstock; (b) microstructure evolution through remelting and (c) the quality of semisolid castings produced with this material. For A17Si0.35Mg alloy, low temperature pouring in the range of 625-650degreesC followed by suitable isothermal holding treatment can result in good quality semisolid casting.

Review of stress corrosion cracking of pipeline steels in "low" and "high" pH solutions

This paper reviews the current understanding of the mechanisms of stress corrosion cracking of pipeline steels. The similarities, the differences and the influencing factors are considered for the high pH stress corrosion cracking caused by a concentrated bicarbonate-carbonate solution, and for the low pH stress corrosion cracking due to a diluter solution. For high pH stress corrosion cracking, it is well accepted that the mechanism involves anodic dissolution for crack initiation and propagation. In contrast, it has been suggested that the low pH stress corrosion cracking is associated with the dissolution of the crack tip and sides, accompanied by the ingress of hydrogen into the pipeline steel. But the precise influence of hydrogen on the mechanism needs to be further studied. (C) 2003 Kluwer Academic Publishers.

Low-affinity neurotrophin receptor with targeted mutation of exon 3 is capable of mediating the death of axotomized neurons

1. In vivo studies have shown that the low-affinity 75 kDa neurotrophin receptor (p75NTR) is involved in axotomy-induced cell death of sensory and motor neurons. To further examine the importance of p75NTR in mediating neuronal death in vivo , we examined the effect of axotomy in the p75NTR-knockout mouse, which has a disrupted ligand-binding domain. 2. The extent of sensory and motor neuron loss in the p75NTR-knockout mouse following axotomy was not significantly different to that in wild-type mice. This suggests that disruption of the ligand-binding domain is insufficient to block the cell death process in axotomized neurons. 3. Immunohistochemical studies showed that axotomized neurons continue to express this mutant receptor with its intracellular death-signalling moiety intact. 4. Treatment with antisense oligonucleotides targeted against p75NTR resulted in significant reduction in the loss of axotomized neurons in the knockout mouse. 5. These data suggest that the intracellular domain of p75NTR is essential for death-signalling and that p75NTR can signal apoptosis, despite a disrupted ligand-binding domain.

Low symbiont diversity in southern Great Barrier Reef corals, relative to those of the Caribbean

The specific identity of endosymbiotic dinoflagellates (Symbiodinium spp.) from most zooxanthellate corals is unknown. In a survey of symbiotic cnidarians from the southern Great Barrier Reef (GBR), 23 symbiont types were identified from 86 host species representing 40 genera. A majority (>85%) of these symbionts belong to a single phylogenetic clade or subgenus (C) composed of closely related (as assessed by sequence data from the internal transcribed spacer region and the ribosomal large subunit gene), yet ecologically and physiologically distinct, types. A few prevalent symbiont types, or generalists, dominate the coral community of the southern GBR, whereas many rare and/or specific symbionts, or specialists, are found uniquely within certain host taxa. The comparison of symbiont diversity between southern GBR and Caribbean reefs shows an inverse relationship between coral diversity and symbiont diversity, perhaps as a consequence of more-rapid diversification of Caribbean symbionts. Among clade C types, generalists C1 and C3 are common to both Caribbean and southern GBR symbiont assemblages, whereas the rest are regionally endemic. Possibly because of environmental changes in the Caribbean after geographic isolation through the Quaternary period, a high proportion of Caribbean fauna associate with symbiont taxa from two other distantly related Symbiodinium clades (A and B) that rarely occur in Pacific hosts. The resilience of Porites spp. and the resistance of Montipora digitata to thermal stress and bleaching are partially explained by their association with a thermally tolerant symbiont type, whereas the indiscriminant widespread bleaching and death among certain Pacific corals, during El Nino Southern Oscillation events, are influenced by associations with symbionts possessing higher sensitivity to thermal stress.

Recruitment of single human low-threshold motor units with increasing loads at different muscle lengths

We investigated the recruitment behaviour of low threshold motor units in flexor digitorum superficialis by altering two biomechanical constraints: the load against which the muscle worked and the initial muscle length. The load was increased using isotonic (low load), loaded dynamic (intermediate load) and isometric (high load) contractions in two studies. The initial muscle position reflected resting muscle length in series A, and a longer length with digit III fully extended in series B. Intramuscular EMG was recorded from 48 single motor units in 10 experiments on five healthy subjects, 21 units in series A and,27 in series B, while subjects performed ramp up, hold and ramp down contractions. Increasing the load on the muscle decreased the force, displacement and firing rate of single motor units at recruitment at shorter muscle lengths (P < 0.001, dependent t-test). At longer muscle lengths this recruitment pattern was observed between loaded dynamic and isotonic contractions, but not between isometric and loaded dynamic contractions. Thus, the recruitment properties of single motor units in human flexor digitorum superficialis are sensitive to changes in both imposed external loads and the initial length of the muscle. (C) 2003 Elsevier Ltd. All rights reserved.