Reduced renal sodium excretion in primary hypertensive patients after an oral glucose load

This study was designed to determine urinary sodium excretion in response to an oral glucose load in hypertensive patients. Fifteen hypertensive patients and eighteen normotensive subjects were studied after an overnight fast and for 4 h after the ingestion of 100 g glucose. A subgroup of untreated, nonobese, primary hypertensive patients (five of the 15 hypertensive patients) became hyperinsulinemic (total area under the insulin curve [TAUC]: 33,080 +/- 3348 microU ml(-1) 120 min-1) in response to an oral glucose load compared to normotensive subjects (TAUC: 3670 < 13.731 < 23,693 microU ml(-1) 120 min-1) or to be other subgroup of normoinsulinemic hypertensive individuals TAUC: 10,221 +/- 1615 microU ml-1 120 min-1) despite a similar serum glucose concentration in both groups. A significant decrease in renal sodium excretion in the entire hypertensive group (47.1 +/- 4.7%, P < 0.019) compared to the normotensive (20.0 +/- 10.5%) subjects was also observed during the oral glucose tolerance test. Decreased renal sodium excretion was followed by a transient increase in urinary acid excretion. We speculate that the increase in insulin secretion may be responsible for the sodium-dependent increase in intracellular Ca2+, cellular H+ output and blood pressure in a subgroup of salt-sensitive patients with hypertension. New studies should be designed to identify the precise mechanisms involved in the interaction between hypertension, serum insulin-glucose levels and the magnitude of the renal tubule reabsorption abnormality.     

Comparative antagonism of kainate-activated kainate and AMPA receptors in hippocampal neurons

Native kainate receptors expressed by cultured hippocampal cells were studied in the whole-cell configuration of the patch-clamp technique by using a fast perfusion system. About 80% of the neurons expressed kainate receptors independently of the time in culture (0-4 days), which coincided with the number of cells immunoreactive for a monoclonal antibody against the GluR5/6/7 subunits. Three types of cells were considered: neurons in which the rapid application of kainate induced a rapidly desensitizing current, cells in which kainate induced a more slowly rising, non-desensitizing, response and those in which a mixture of both responses was apparent. Steady responses induced by 300 microM kainate were inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in a dose-dependent manner (IC50 = 0.92 microM). CNQX was less potent in blocking transient kainate-induced responses (IC50 = 6.1 microM). Responses to kainate, whether steady or transient, were also inhibited by NS102, showing poor selectivity for the transient response (IC50 = 4.1 and 2.2 microM respectively). The new alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) receptor antagonist NS394 was very potent in inhibiting steady kainate-induced currents (IC50 = 0.45 microM), but was even more effective in preventing peak responses (IC50 = 0.13 microM). In contrast, cyclothiazide did not affect transient kainate-induced responses but did potentiate current induced by activation of AMPA receptors by AMPA or kainate. These results demonstrate the lack of complete selectivity amongst some available competitive antagonists for AMPA and kainate receptors, and indicate that kainate receptors expressed by hippocampal cells lack the cyclothiazide modulatory site present at AMPA receptors. In addition, the present data support the idea that low-affinity kainate binding sites in the brain correspond to receptor channels selectively activated by kainate.     

Molecular structures and conformational studies of triarylcyclopropyl and related nonsteroidal antiestrogens

Molecular structures and conformational characteristics of a series of 1,1-dichloro-2,2,3-triarylcyclopropanes (DTACs), which were reported previously to be distinctly antiestrogenic and inhibitors of the estrogen-receptor-positive MCF-7 human breast cancer cells in culture, are reported. In addition, structural and conformational features of the DTACs were compared to the first-known nonsteroidal antiestrogen, MER25, and the clinically useful antiestrogen Tamoxifen. The molecular structures of four DTAC compounds were determined by X-ray diffraction. Crystallographic structures show that the DTAC molecules have nearly the same relative conformation for the three aryl rings which is designated as a "nonpropeller" conformation in contrast to the observed "propeller" conformation for the three rings in all known triarylethylenes. Systematic conformational searches were performed to find the conformational preferences of DTACs, MER25, and Tamoxifen using idealized model compounds built from their respective crystal structure. Energy-minimization and conformational-search studies demonstrated that all DTAC molecules have a common, single global minimum energy conformer for their central core containing the dichlorotriarylcyclopropyl system, which is similar to that found in their crystal structures. Conformational search of MER25 showed that the molecule can assume a number of low-energy conformers of which two, one anti (A1) and one gauche (G1A), have about the same energy. The anti conformation is similar to the one observed in its crystal structure and resembles the estrogenic E-isomer of Tamoxifen, while the lowest energy gauche conformer of MER25 resembles more closely the antiestrogenic Z-isomer of Tamoxifen. NMR spectroscopic analysis of MER25 showed that the molecule exists predominantly in the anti conformation in solution. A comparative review of the structural features and bioactivities of Tamoxifen, DTACs, and MER25 provides a possible explanation for their low estrogen receptor binding affinity which is common to these compounds together with their antiestrogenic activity.     

Haemoglobins of the shark, Heterodontus portusjacksoni II. Amino acid sequence of the alpha-chain

The amino acid sequence of the alpha-chain of the principal haemoglobin from the shark, H. portusjacksoni has been determined. The chain has 148 residues and is acetylated at the amino terminal. The soluble peptides obtained by tryptic and chymotryptic digestion of the protein or its cyanogen bromide fragments were isolated by gel filtration, paper ionophoresis and paper chromatography. The amino acid sequences were determined by the dansyl-Edman procedure. The insoluble "core" peptide from the tryptic digestion contained 34 residues and required cleavage by several prosteases before the sequence was established. Compared with human alpha-chain there are 88 amino acid differences including the additional seven residues which appear on the amino terminal of the shark chain. There is also one deletion and one insertion. The chain contains no tryptophan but has four cysteinyl residues which is the highest number of such residues recorded for a vertebrate globin. In the alpha1beta1 contact sites there are four changes in the oxyhaemoglobin form and six deoxy form. Nine of the 16, alpha1beta1 contact sites show variation while three of the haem contact sites have changed in comparison to the residues known to be involved in these interactions in horse haemoglobin alpha-chain. Use of the sequence data to estimate a time of divergence of the shark from the main vertebrate line yielded the value of 410 +/- 46 million years. The data, in general, support the palaeontological view that bony fishes arose before the elasmobranchs.     

Molecular-beam epitaxial growth of HgCdTe infrared focal-plane arrays on silicon substrates for midwave infrared applications

Molecular beam epitaxy has been employed to deposit HgCdTe infrared detector structures on Si(112) substrates with performance at 125K that is equivalent to detectors grown on conventional CdZnTe substrates. The detector structures are grown on Si via CdTe(112)B buffer layers, whose structural properties include x-ray rocking curve full width at half maximum of 63 arc-sec and near-surface etch pit density of 3–5 × 10⁵ cm⁻² for 9 μm thick CdTe films. HgCdTe p⁺-on-n device structures were grown by molecular beam epitaxy (MBE) on both bulk CdZnTe and Si with 125K cutoff wavelengths ranging from 3.5 to 5 μm. External quantum efficiencies of 70%, limited only by reflection loss at the uncoated Si-vacuum interface, were achieved for detectors on Si. The current-voltage (I-V) characteristics of MBE-grown detectors on CdZnTe and Si were found to be equivalent, with reverse breakdown voltages well in excess of 700 mV. The temperature dependences of the I-V characteristics of MBE-grown diodes on CdZnTe and Si were found to be essentially identical and in agreement with a diffusion-limited current model for temperatures down to 110K. The performance of MBE-grown diodes on Si is also equivalent to that of typical liquid phase epitaxy-grown devices on CdZnTe with R₀A products in the 10⁶–10⁷ Θ-cm² range for 3.6 μm cutoff at 125K and R₀A products in the 10⁴–10⁵ Θ-cm² range for 4.7 μm cutoff at 125K.     

A 210-GHz fT SiGe HBT with a non-self-aligned structure

A record 210-GHz f_T SiGe heterojunction bipolar transistor at a collector current density of 6-9 mA/μm² is fabricated with a new nonself-aligned (NSA) structure based on 0.18 μm technology. This NSA structure has a low-complexity emitter and extrinsic base process which reduces overall thermal cycle and minimizes transient enhanced diffusion. A low-power performance has been achieved which requires only 1 mA collector current to reach 200-GHz f_T. The performance is a result of narrow base width and reduced parasitics in the device. Detailed comparison is made to a 120-GHz self-aligned production device     

The link between ethnic diversity and scientific impact: the mediating effect of novelty and audience diversity

Scientometrics - Understanding the nature and value of scientific collaboration is essential for sound management and proactive research policies. One component of collaboration is the composition...