Mutations of respiratory syncytial virus attachment glycoprotein G associated with resistance to neutralization by primate polyclonal antibodies.

The respiratory syncytial (RS) virus attachment glycoprotein G is a type II transmembrane glycoprotein and an important target of the host immune response. Antigenic variability of the G protein is postulated to contribute to the ability of the virus to evade established immune responses. A glycoprotein G monospecific polyclonal antiserum from a nonhuman primate was used to select for an antibody resistant RS virus. The mutant virus was resistant to neutralization by the selecting antiserum and by the sera from three other G-protein immunized primates. G-protein amino acid changes were found at residues 61 (Phe to Leu), 174 (Ser to Cys), and 183 (Trp to Leu). Thus the mutant protein had amino acid changes in the transmembrane domain (61) and the central ectodomain (174 and 183). The change at amino acid 174 resulted in five rather than the usual four Cys found in the conserved central region of the ectodomain. These data demonstrate that an RS virus with resistance to neutralization by polyclonal antibodies can be selected readily in cell culture. In addition, only a limited number of amino acid changes is required to produce the resistant phenotype.

A comparative study of atenolol/nifedipine and atenolol/diuretic in hypertension.

A prospective, randomized, double-blind between-patient study was carried out to compare the efficacy and tolerance of atenolol with nifedipine and atenolol with diuretic. Ninety-eight hypertensive patients inadequately controlled after 1-month's treatment with 100 mg atenolol alone once daily received, in addition, either 20 mg nifedipine twice daily or 5 mg amiloride plus 50 mg hydrochlorothiazide once daily for a further 8 weeks. The results of blood pressure measurements in the lying and standing positions showed that the mean reduction in standing blood pressure from atenolol baseline was 28/12 mmHg for atenolol/diuretic and 18/13 mmHg for atenolol/nifedipine. The only significant difference between treatments in blood pressure control was in lying systolic blood pressure favouring atenolol/diuretic and a trend in favour of this combination for standing systolic blood pressure. Both regimens were reasonably well tolerated, although 19 patients withdrew during the course of the trial because of side-effects (2 on atenolol alone, 10 on atenolol/diuretic and 7 on atenolol/nifedipine).

Atenolol and chlorthalidone in combination in the management of older hypertensive patients: a randomized clinical trial.

In a double-blind, crossover study in 100 elderly hypertensive patients, the hypotensive effect of a fixed combination of atenolol (50 mg) with chlorthalidone (12.5 mg) was compared with that of each of its component drugs given alone. Patients were allocated at random into two groups: one group received treatment for 4 weeks with either the combination or atenolol alone before being crossed over to the alternative medication for a further 4 weeks; the other group received either the combination or chlorthalidone alone and followed the same treatment pattern. Dosage was a single tablet per day given in the morning. Blood pressure and pulse rate were measured approximately 24 hours after dosing at the end of each treatment period. The results showed that significantly lower blood pressures were achieved, both in the standing and lying positions, with the combination than with either atenolol or chlorthalidone used alone. Combination treatment was well tolerated, few side-effects being reported and there was no significant disturbance of plasma electrolytes.

Randomized comparison of atenolol and placebo in the treatment of anxiety: a double-blind study.

In a randomized double-blind prospective between-patients trial in patients presenting with primary anxiety, atenolol significantly improved mean values on the Hamilton rating scale at two and four weeks when compared with placebo. There was also a significant improvement in affective symptoms at 28 days for atenolol when compared with placebo.

Allelic variation at α-Amylase loci in hexaploid wheat.

A study of α-amylase isozyme patterns from gibberellin-induced endosperms from more than 200 wheat genotypes has revealed allelic variation at five of the six α-Amy-1 and α-Amy-2 structural loci. These differences will find application as genetic markers and in varietal identification. The α-Amy-B1 locus on chromosome 6B was most variable and displayed eight distinct allelic forms. The nature of the allelic phenotypes, observations of segregating populations and the number of in vivo translation products of mRNAs from the α-Amy-1 and α-Amy-2 loci indicated that the individual loci are multigenic, each consisting of tightly linked subunits which produce several different isoforms.

Intracellular mannitol, a product of glucose metabolism in staphylococci.

Mannitol (Mtl), not previously reported as an intracellular component of bacteria, although it has been found as an extracellular end product of anaerobic carbohydrate metabolism, accumulated within strains of all 10 staphylococcal species tested after aerobic incubation of washed cell suspensions in phosphate-buffered 1% glucose for 2 h. Phenol extracts of the cells, before and after incubation, were analyzed for Mtl content by periodate utilization and paper chromatography and for Mtl 1-phosphate content, with Mtl 1-phosphate dehydrogenase. In Staphylococcus aureus Towler, the content of Mtl increased from a 0-h value of less than 2.4 to 16 mumol/g (dry weight) after incubation, and the level of Mtl 1-phosphate increased from a 0-h value of 1 to 8 mumol/g. The identification of Mtl was confirmed as the per-O-acetyl ester by gas-liquid chromatography and as the per-O-methyl ether by mass spectrometry. Also tested were 5 additional S. aureus strains and 32 coagulase-negative staphylococcal strains. All strains accumulated Mtl, even those strains that could not utilize exogenous Mtl during aerobic growth, usually in the range 4 to 25 mumol/g. Furthermore, three strains accumulated very high Mtl levels. Bacteria from several other genera were tested, and some were found to accumulate low to moderate levels of Mtl under similar incubation conditions. The metabolic conversion of glucose to intracellular Mtl, probably via Mtl 1-phosphate, is a common feature of staphylococci and also occurs in some other bacteria.