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The aim of the study was to investigate endothelium-dependent vasodilator responses in the forearm vasculature of patients with systemic vasculitis. We studied 10 patients with systemic vasculitis and 16 healthy control subjects using forearm venous occlusion plethysmography to assess changes in forearm blood flow in response to acetylcholine (ACh). NG-monomethyl-L-arginine (L-NMMA), was also used to assess the contribution of endothelium derived relaxing factor/nitric oxide (EDRF/NO) to the vasodilator responses to acetylcholine. A significantly greater vasodilator response to ACh was seen in the patient group at all doses infused (p < 0.01). After pre-infusion of L-NMMA, the differences in ACh dilator responses were no longer significant. There was a greater magnitude of inhibition of ACh responses by L-NMMA in the patient group. The enhanced vasodilator response to ACh observed was in part abolished by L-NMMA, suggesting that EDRF/NO is produced in excess in systemic vasculitis. The precise role played by EDRF/NO in the pathogenesis of systemic vasculitis requires further study.

For studies on the regulation of myocardial protein metabolism, isolated adult cardiomyocytes were introduced as an experimental model about a decade ago. When used shortly after isolation, this model represents a tool for studying the properties of normal and diseased myocardium on the cellular level. The influence of various peptide hormones, neurotransmitters, and mechanical stimulation on protein synthesis and degradation in isolated cardiomyocytes has been studied. It has been demonstrated, for example, that alpha 1-adrenoceptor stimulation increases protein synthesis in newly isolated cardiomyocytes, independently of any mechanical effects. Other potential growth stimuli require appropriate conditions to induce cellular responsiveness. Neuropeptide Y, for example, does not stimulate cellular protein synthesis in newly isolated cells, whereas it does so in cells that have been cultured for a week in the presence of serum. Mechanical stretch also represents a growth stimulant. It seems that its signal transduction involves an autocrine loop. Thus different mechanisms, by which exogenous influences can modify cellular protein synthesis and degradation, have been identified on the cellular level, with the use of isolated adult cardiomyocytes.

1. The alpha- and beta-adrenoceptor antagonist activity of carvedilol, a beta-adrenoceptor antagonist with vasodilating properties, and labetalol were investigated in 10 healthy male subjects. They received infusions with serially increasing concentrations of isoprenaline and phenylephrine before and after single oral doses of carvedilol 6.25, 12.5 and 25 mg, labetalol 400 mg and placebo at weekly intervals in a double-blind randomised manner. An exercise step test was performed at the end of the infusions. 2. The dose of isoprenaline required to increase heart rate by 25 beats min-1 (I25) and the dose of phenylephrine required to increase systolic and diastolic blood pressure by 20 mm Hg (PS20 and PD20) were calculated using a quadratic fit to individual dose-response curves. Comparisons were made with placebo and P < 0.05 was considered significant. 3. The I25 was increased by carvedilol 25 mg and labetalol 400 mg (P < 0.05). The dose ratios at I25 were: carvedilol 6.25 mg 2.1 +/- 1.6, carvedilol 12.5 mg 3.1 +/- 1.9, carvedilol 25 mg 6.4 +/- 4.9 and labetalol 400 mg 8.8 +/- 4.4. 4. The PS20 was increased by labetalol 400 mg (P < 0.05). The dose ratios at PS20 were: carvedilol 6.25 mg 1.0 +/- 0.2; 12.5 mg, 1.2 +/- 0.2; 25 mg, 1.3 +/- 0.4 and labetalol 400 mg 2.2 +/- 0.8. 5. The PD20 was increased by labetalol 400 mg (P < 0.05). The dose ratios at PD20 were: carvedilol 6.25 mg 1.1 +/- 0.3; 12.5 mg, 1.3 +/- 0.3; carvedilol 25 mg 1.3 +/- 0.4 and labetalol 400 mg 2.1 +/- 0.8.(ABSTRACT TRUNCATED AT 250 WORDS)

The endothelium plays a pivotal role in modulating the reactivity of vascular smooth muscle through the formation of several vasoactive substances. We examined the effects of endothelium-dependent and independent vasodilators on forearm blood flow in 29 patients with Type 2 (non-insulin-dependent) diabetes mellitus and in 21 control subjects, using venous occlusion plethysmography. Via a brachial artery cannula, increasing amounts of acetylcholine and glyceryl trinitrate were infused in doses of 60, 120, 180 and 240 mmol per min and 3, 6 and 9 nmol per min respectively. NG monomethyl-L-arginine, a stereospecific inhibitor of endothelium derived relaxing factor, was infused to inhibit basal and stimulated release of this dilator substance. Reactive hyperaemic forearm blood flow did not differ between groups. Forearm blood flow responses to each dose of acetylcholine were significantly greater in control than diabetic subjects (p less than 0.01 for all doses). NG monomethyl-L-arginine attenuated forearm blood flow from maximal stimulated values when responses were compared with the natural decline to acetylcholine in forearm flow in both control and diabetic subjects (p less than 0.05 for both groups), but had no effect on basal blood flow responses. Forearm blood flow responses to each dose of glyceryl trinitrate were significantly greater in control than diabetic subjects (p less than 0.05 for all). These data provide evidence for endothelial and smooth muscle dysfunction in diabetes which may have important therapeutic implications.

The potency of neuropeptide Y (NPY) to cause negative and positive contractile responses in rat ventricular cardiomyocytes was investigated. In these cells, NPY was found to activate the transient outward K+ current (Ito) and the slow inward Ca2+ current (Isi). As reported before (H. M. Piper, B. C. Millar, and J. R. McDermott, Naunyn Schmiedeberg's Arch. Pharmacol. 340: 333-337, 1989), NPY attenuated the increase in the contractile response induced by isoprenaline (10(-7) M). This effect of NPY could be abolished by 1) the presence of the inhibitor of Ito, 4-aminopyridine (4-AP, 0.5 mM); 2) pretreatment of the cells with pertussis toxin (1 microgram/ml for 6 h); and 3) the presence of the 19-amino acid COOH-terminal fragment of NPY, NPY-(18-36) (10(-6) M). In the absence of isoprenaline, but in the presence of 4-AP, NPY exerted a stimulatory effect on the cardiomyocytes. This effect could be abolished 1) by using the inhibitor of the Isi, verapamil (10(-8) M), but not 2) by pretreatment with pertussis toxin, nor 3) by coincubation with NPY-(18-36). The results indicate that in the rat the antiadrenergic negative contractile effect of NPY results from its action on the Ito. Blockade of this current by 4-AP unmasks a positive contractile effect of NPY that is related to activation of the Isi.

Intermedin (IMD) is a novel peptide related to calcitonin gene-related peptide (CGRP) and adrenomedullin (AM). Proteolytic processing of a larger precursor yields a series of biologically active C-terminal fragments, IMD(1-53), IMD(1-47) and IMD(8-47). IMD shares a family of receptors with AM and CGRP composed of a calcitonin-receptor like receptor (CALCRL) associated with one of three receptor activity modifying proteins (RAMP). Compared to CGRP, IMD is less potent at CGRP(1) receptors but more potent at AM(1) receptors and AM(2) receptors; compared to AM, IMD is more potent at CGRP(1) receptors but less potent at AM(1) and AM(2) receptors. The cellular and tissue distribution of IMD overlaps in some aspects with that of CGRP and AM but is distinct from both. IMD is present in neonatal but absent or expressed sparsely, in adult heart and vasculature and present at low levels in plasma. The prominent localization of IMD in hypothalamus and pituitary and in kidney is consistent with a physiological role in the central and peripheral regulation of the circulation and water-electrolyte homeostasis. IMD is a potent systemic and pulmonary vasodilator, influences regional blood flow and augments cardiac contractility. IMD protects myocardium from the deleterious effects of oxidative stress associated with ischaemia-reperfusion injury and exerts an anti-growth effect directly on cardiomyocytes to oppose the influence of hypertrophic stimuli. The robust increase in expression of the peptide in hypertrophied and ischaemic myocardium indicates an important protective role for IMD as an endogenous counter-regulatory peptide in the heart.

Endothelin (ET)-1 is a potent positive inotropic agent, the effects of which are mediated by increases in cytosolic Ca(2+) in the myocardium. The object of this study was to examine 1) the influence of ET(A) and ET(B) receptor subtypes, and 2) the role of the phospholipase C (PLC) pathway in mediating ET-1-induced contraction. Left ventricular cardiomyocytes were isolated from the hearts of New Zealand White rabbits (2-2.5 kg) by the use of Langendorff perfusion with collagenase. Cardiomyocyte function was examined during unloaded, electrically stimulated (0.5 Hz) contractions with a video-edge detection system. ET-1 increased cell shortening with greater potency than ET-3: mean EC(50) values were 1.1 x 10(-11) and 2.6 x 10(-10) M, respectively. With the same order of potency, ET-1 and ET-3 increased (P.05) velocity of cell shortening. The ET(A) receptor-selective antagonist ABT-627 shifted the ET-1-induced cell shortening response curve to the right with a pA(2) value of 10.3. The ET(B) receptor-selective antagonist A-192621 (10(-8)-10(-7) M) did not alter the concentration-response of ET-1. Moreover, the ET(B) receptor-selective agonist sarafotoxin 6c did not have any effect on cell shortening over the concentration range of 10(-11) to 10(-7) M. ET-1 in the presence of the PLC inhibitor U-73122 did not alter the contractile amplitude. However, ET-1 in the presence of the protein kinase C inhibitor bisindolylmalemide increased cell shortening. These findings indicate that 1) the ET(A) receptor subtype, and not the ET(B) receptor subtype, mediates the positive inotropic effect of ET-1, and 2) the response of ET-1 is mediated by a PLC pathway, but not through protein kinase C, in ventricular cardiomyocytes isolated from rabbit myocardium.

Enhanced expression of IGF-1 occurs in left ventricular hypertrophy (LVH) associated with systemic hypertension. Cardiac dysfunction accompanied by LVH is also observed in hyperthyroidism.to assess the relative contributions of de novo protein synthesis and attenuated protein degradation to increased protein mass associated with cardiomyocyte hypertrophy elicited by IGF-1 and thyroid hormones (tri-iodo thyronine T3, and l-thyroxine T4), respectively.total mass of protein, and both the incorporation, and removal of previously incorporated l-U-14C-phenylalanine, indices of protein synthesis and degradation, respectively, were assessed in quiescent adult rat ventricular cardiomyocytes maintained in short-term culture, and corrected for DNA content, as a index of cell number.IGF-1 (1 pM-100 nM) increased cell protein significantly, maximally at 1 nM and by 38% above basal value after 24 h. T3 (10 pM-2 microM) and T4 (10 pM-2 microM) increased cell protein significantly maximally at 1 microM and by 33.2 and 30.5%, respectively, above basal value. IGF-1 (or = 10 pM), T3 (10 pM-2 microM) and T4 (10 pM-2 microM) did not increase incorporation of l-U-14C-phenylalanine above basal values. IGF-1 (100 pM-100 nM) increased incorporation of radiolabel significantly maximally at 100 nM and by 56%. T4 (100 pM) and IGF-1 (10 pM), concentrations that did not stimulate de novo protein synthesis, attenuated the degradation of radiolabelled protein by 13.6 and 11.8%, respectively, compared to control values after 48 h.These data indicate that the acute hypertrophic response to (i) thyroid hormones cannot be attributed to initiation of de novo protein synthesis; (ii) IGF- 1 comprises two components; the response elicited by IGF-1 (10 pM) is independent of, while the response elicited by IGF-1 (100 pM) is due to de novo protein synthesis.

1. D-myo inositol 1,2,6 trisphosphate (alpha-trinositol, pp56), an isomer of the second messenger substance, D-myo inositol 1,4,5 trisphosphate, has an interesting pharmacological profile that includes anti-inflammatory and analgesic effects and antagonism of neuropeptide Y (NPY)-mediated cellular responses. 2. However, not all responses elicited by this neuropeptide are sensitive to antagonism by pp56. Evidence is emerging, at least in certain tissues, that other receptor populations, in addition to those for NPY, are also sensitive to inhibition by pp56. 3. A direct or allosteric interaction of pp56 at receptors for NPY is now considered unlikely and it is more probable that pp56 might interfere at some point in the phosphatidylinositol signaling pathway, possibly at the level of the plasmalemmal inositol 1,3,4,5, tetrakisphosphate receptor. 4. Full realization of the therapeutic potential of this novel compound, however, must await a thorough characterization of the cellular mechanism(s) associated with the various pharmacological effects of pp56.

The purpose of this study was to establish whether specific receptor subtypes are responsible for mediating the effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) on the L-type calcium current (ICa) using a number of receptor-selective antagonists, including PD155080 (ETA), BQ-788, RES-701 and IRL-1038 (ETB) and the ETA/ETB receptor-non-selective antagonist PD145065. Ventricular cardiomyocytes were isolated from adult New Zealand White rabbits using Langendorff perfusion with collagenase. ICa was recorded using a whole-cell patch-clamp technique. ET-1 decreased, whereas ET-3 increased, ICa at equimolar concentrations of 10 nM. The decrease in ICa produced by ET-1 was completely blocked by PD155080 and PD145065 (1 and 10 microM); however, ICa was increased upon washout of PD155080. Although the decrease in ICa produced by ET-1 was partially blocked by BQ-788 (1 and 10 microM), ET-1 in combination with either RES-701 (1 and 10 microM) or IRL-1038 (1 microM) produced a decrease in ICa similar to that produced by ET-1 alone. The increase in ICa by ET-3 was completely abolished by either BQ-788 or IRL-1038 (1 microM). These data indicate that the decrease in ICa produced by ET-1 in rabbit ventricular cardiomyocytes is mediated by the ETA receptor subtype, because PD155080 completely inhibited this response. The ETB receptor-selective antagonists RES-701 and IRL-1038 did not alter the decrease in current produced by ET-1, although the response was partially sensitive to BQ-788, which may lack receptor-subtype selectivity in these cells. In contrast, the increase in ICa produced by ET-3 was mediated by the ETB receptor subtype, because BQ-788 and IRL-1038 abolished this response.

1. D-Myo inositol 1,2,6 trisphosphate (alpha-trinositol, pp56), an isomer of the second messenger substance, inositol 1,4,5 trisphosphate, has an interesting pharmacological profile that includes antagonism of a number of neuropeptide Y (NPY)-mediated cellular processes. The ability of pp56 to inhibit selectively the myocardial contraction mediated by NPY in relation to the responses to other cardioactive peptides, including endothelin-1, calcitonin gene-related peptide (CGRP), secretin and vasoactive intestinal peptide (VIP), was assessed. In order to investigate the possible interaction of pp56 with mechanisms of inositol phosphate signalling generated in heart muscle cells by activation of the beta-isoenzyme of phospholipase C (PLC beta), noradrenaline was used as a positive control, and isoprenaline and forskolin were included as negative controls. 2. Ventricular cardiomyocytes, isolated from the hearts of adult rats, were stimulated to contract at 0.5 Hz in the presence of calcium ion (2 mM). The concentrations of agonists used were in the region of their maximally effective concentrations for myocyte contraction and the concentration of pp56 was in the range of 1-100 microM. Contractile activity was monitored by video microscopy and maximum shortening determined by image analysis. 3. In the absence of agonist, contractile amplitudes following 20 min preincubation with pp56 were not different from that observed in the absence of pp56. Pp56 (1-100 microM) inhibited significantly the positive contractile response to noradrenaline (5 microM) in the presence of propranolol (500 nM), such that the response was almost completely attenuated at the highest concentration of the inhibitor. Pp56 did not inhibit the positive contractile responses to forskolin (40 microM) or isoprenaline (100 nM). 4. NPY alone does not influence the basal level of contraction of cardiomyocytes, but can attenuate isoprenaline-stimulated contraction and can increase contractile amplitude from basal when the transient outward current is blocked with 4-aminopyridine. In the presence of isoprenaline (100 nM), the negative response to NPY (100 nM) was attenuated significantly by pp56 (1-100 microM). With 4-aminopyridine, the positive contractile response to NPY (200 nM) was decreased by pp56, although this was not statistically significant. 5. Pp56 inhibited the positive contractile responses to CGRP (1 nM) and endothelin-1 (20 nM) completely, but did not affect the responses to secretin (20 nM) or VIP (20 nM). 6. In conclusion, these data challenge the previously obtained selectivity of pp56 as an antagonist of NPY-mediated cellular processes, since responses to CGRP and endothelin-1 were at least equally sensitive. Furthermore, as pp56 discriminated clearly in its inhibition of responses to alpha-adrenoceptor by comparison with beta-adrenoceptor/adenylate cyclase stimulation, it appears that pp56 may be a useful pharmacological agent with which to distinguish between PLC beta-dependent and PLC beta-independent coupling mechanisms. On this basis, further evidence has been obtained that, in rat cardiomyocytes, the contractile responses to NPY, CGRP and endothelin-1 are attributable to the activation of PLC beta-dependent pathways, whereas the responses to secretin and VIP are mediated by PLC beta-independent pathways.

The aim of the study was to investigate endothelium-dependent vasodilator responses in the forearm vasculature of patients with systemic vasculitis. We studied 10 patients with systemic vasculitis and 16 healthy control subjects using forearm venous occlusion plethysmography to assess changes in forearm blood flow in response to acetylcholine (ACh). NG-monomethyl-L-arginine (L-NMMA), was also used to assess the contribution of endothelium derived relaxing factor/nitric oxide (EDRF/NO) to the vasodilator responses to acetylcholine. A significantly greater vasodilator response to ACh was seen in the patient group at all doses infused (p0.01). After pre-infusion of L-NMMA, the differences in ACh dilator responses were no longer significant. There was a greater magnitude of inhibition of ACh responses by L-NMMA in the patient group. The enhanced vasodilator response to ACh observed was in part abolished by L-NMMA, suggesting that EDRF/NO is produced in excess in systemic vasculitis. The precise role played by EDRF/NO in the pathogenesis of systemic vasculitis requires further study.

Decreased release of nitric oxide from damaged endothelium is responsible for the impaired endothelium-dependent vasodilator responses found in animal models of vascular disease. Dietary supplementation with fish oils has been shown to augment endothelium-dependent relaxations, principally by improving the release of nitric oxide from injured endothelium. Using forearm venous occlusion plethysmography we studied vascular responses to 60, 120, 180 and 240 nmol/min of acetylcholine (an endothelium-dependent vasodilator) and 3, 6 and 9 nmol/min of glyceryl trinitrate (an endothelium-independent vasodilator) infused into the brachial artery in 23 patients with Type 2 (non-insulin-dependent) diabetes mellitus. NG monomethyl-L-arginine was employed to inhibit stimulated and basal release of nitric oxide from the endothelium. On completion of the baseline studies patients randomly received either fish oil or matching olive oil capsules in a double-blind crossover fashion for 6 weeks followed by a 6-week washout period and a final 6-week treatment phase. Studies, identical to the initial baseline studies, were performed at the end of the active treatment periods at 6 and 18 weeks. Fish oil supplementation significantly improved forearm blood flow responses to each dose of acetylcholine when compared to the vasodilator responses recorded at baseline and after olive oil administration (p < 0.01). Neither fish oil nor olive oil supplementation produced any significant changes in forearm blood flow to the incremental infusions of glyceryl trinitrate when compared with responses recorded during the baseline studies.(ABSTRACT TRUNCATED AT 250 WORDS)

The mechanism of action of NPY to produce contractions of adult rat ventricular myocytes was investigated. Positive effects were mediated through an L-type Ca2+ channel. Negative effects, linked through an inhibitory G-protein to a transient outward K+ channel, could be antagonised by NPY-(18-36).

After an 8-week placebo period, 73 patients whose diastolic blood pressures were between 90 and 110 mmHg were randomly assigned to receive 125 micrograms (low dose) or 500 micrograms of cyclopenthiazide (standard dose) for a period of one year. Blood pressure was measured in the patient's home by the same observer at two-weekly intervals during an 8-week placebo run-in period, every 4 weeks for a further 12 weeks and at 24, 36 and 52 weeks thereafter. Serum potassium, urate, glucose, glycosylated haemoglobin, total and HDL cholesterol, and apolipoproteins were measured at the end of the placebo period and at 4, 8, 24 and 52 weeks of active treatment. Twelve of the 73 patients had an inadequate antihypertensive response--five on the higher dose and seven on the lower dose. One patient receiving 500 micrograms was withdrawn because of adverse effects. In the remaining 60 patients, systolic and diastolic blood pressures were significantly reduced when compared with pretreatment values in both treatment groups throughout the one year period. The decreases in blood pressure were not significantly different from each other (p greater than 0.65). Three patients on 500 micrograms required potassium supplements. Maximum decreases in the serum potassium of 0.52 mmol/l (500 micrograms dose) and 0.14 mmol/l (125 micrograms dose) were observed at 24 weeks of treatment in the remaining 57 patients. The differences between the two doses at this time were statistically significant (p less than 0.05), as were the increases in serum urate observed at 4, 8 and 24 weeks (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

A low dose atenolol/bendrofluazide combination in patients with mild to moderate hypertension

Endothelin-1 (ET-1), is a 21 amino-acid peptide with potent inotropic and chronotropic actions in the heart. Relatively little is known about the underlying electrophysiological effects of the peptide. In this study the effects of ET-1 on the acetylcholine-activated potassium current (IK(Ach)) were investigated in the absence and presence of the receptor-selective antagonists, PD155080 (ETA receptor-selective) and RES-701 (ETB receptor-selective) in atrial cardiomyocytes. Cells were obtained from New Zealand White rabbits (2·5–3 kg) by enzymatic dissociation using collagenase. Potassium currents were recorded, in the presence of nifedipine (5 μM), using the whole cell ruptured patch-clamp technique. Low resistance electrodes (1–3 MΩ) were filled with potassium gluconate solution (pH 7·2). Cells were superfused with a modified Tyrode's solution. Following stabilization, control recordings were made using standard pulse protocols, and drugs were applied using a gravity fed microperfusion system. Data were expressed as mean±standard error, and comparisons were made using Friedman's ANOVA and Wilcoxon's Signed Ranks tests; p

Subjective quality ratings of pcm coded speech were obtained with the aims of (i) determining the effects of certain coder parameters and their interactions on speech quality, (ii) finding objective measures for predicting perceived distortions, and (iii) providing guidelines for optimizing coder design. Coders with various combinations of four clipping levels, seven step sizes, four bandwidths, and three logarithmic companding laws were simulated. The coders were rated for quality on a 10-point scale by 48 listeners who heard male and female speech processed by the coders. The ratings depended strongly on clipping level and step size, but only weakly on bandwidth. None of the coder parameters interacted strongly with another. Clipping noise power grossly overestimated the extent of perceived overload distortion; instead, clipping percentage is proposed as a much more realistic predictor. Signal-to-granular-noise ratio was a good predictor of perceived granular noise. For a given bit rate, the coder with the highest quality rating was not the coder with minimum total clipping and granular noise power, contrary to traditional wisdom.

Permutation of speech segments is frequently utilized in scramblers for analog speech privacy. This paper discusses a “sequential” permutation procedure that has better segment-separation properties than the well-known procedure of “block” permutation, where contiguous segments are arranged in blocks of appropriate size, and permuted within such blocks. It further proposes the application of the sequential procedure to a novel technique for simultaneous permutations in time and frequency. The paper also presents results of a subjective experiment where we measured residual speech intelligibility at the output of scramblers using permutations in time [time segment permutation (TSP)], or permutations in time and frequency [time-frequency segment permutation (TFSP)]. The experiment included examples of block TSP, sequential TSP, and sequential TFSP. We measured spoken-digit-intelligibility as a function of the communication delay introduced by the scrambling operation. We found that even with a delay of 512 ms, the residual intelligibility in a TSP scrambler is no lower than about 50 percent; however, a sequential TFSP scrambler can realize an average digit intelligibility in the order of 20 percent with a delay of 256 ms. A companion paper discusses the implementation of the sequential TFSP scrambler, and the quality of descrambled speech in the context of real-channel operation.

Recent studies in this laboratory have been directed at investigating the cellular and subcellular metabolism of RNA in leukemic cells which have been characterized with respect to their degree and type of sensitivity/resistance to specific chemotherapeutic agents. In the present report, electrophoretic patterns on several types of SDS-polyacrylamide gels are presented using total cellular RNA preparations from a subline of L1210 mouse leukemia found to be resistant to cytosine arabinoside (L1210/Ara-C). These studies have been facilitated by using a computerized-spectrophotometric system for quantitative and qualitative comparisons of these profiles. The results suggest that patterns of RNA metabolism may be a useful biochemical test in leukemia.

Listeners judged the loudness of speech processed by 22 different circuits, including both linear and nonlinear distortions. Listeners heard pairs of sentences, each processed by a different circuit, and indicated which of the pair sounded louder. The analysis produced solutions in one through eight dimensions. A χ2 test for goodness of fit showed that the data were not satisfied by a unidimensional solution. The analysis showed that the loudness of circuits with added noise is ambiguous and that listeners differed in their interpretation. Listeners also differed in their judgments about some of the nonlinear distortions. Additional dimensions representing the attributes of these two types of circuits accounted for most of the residual variability. The results of this analysis are compared to those of a previous experiment, which indicated that loudness is a major factor influencing preference judgments of the same circuits.

Although a great deal has been learned about how speakers are verified, both by humans and by machines, several factors have not yet been studied. One of these factors is the effect of the transmission system (over which the message is communicated) on the accuracy with which verification is achieved. This factor is potentially an important one for digital communications problems over telephone lines where the transmission system could vary from one which gives a high-quality coded representation of the signal (e.g., log PCM) to a low-bit-rate vocoder. The purpose of this paper is to demonstrate the effects of three speech transmission systems on verification accuracy by human listeners. It is shown that the false alarm rate (i.e., a customer is rejected) is significantly higher when the test and reference utterances are transmitted by different systems than when transmitted by the same system. The miss rate (i.e., an imposter is accepted) is not significantly different for similar comparisons except for one of the conditions. The overall conclusion of this experiment is that speaker verification by human listeners cannot be performed as accurately over mixed speech transmission systems as over the same transmission system.

A subjective experiment was carried out to assess the effect of spelling context on the ability of listeners to identify spoken letters of the alphabet. Individual letters, spoken by a male talker and a female talker, were concatenated to form strings of up to ten letters representing the spelling of a last name (surname) and one or two initials. Three spelling contexts were observed. First, real names were selected at random from the 20 000‐entry Bell Labs telephone directory. Second, strings were constructed using trigram statistics for letter sequences tabulated from the same directory. Third, letters were selected at random to form strings. In addition, three masking noise conditions were observed: no noise, low‐level, and high‐level broadband additive masking noise. The results show that the listeners made fewer errors identifying letters imbedded in real name or trigram strings than in random letter strings. The effect is especially pronounced in the presence of masking noise. Confusions among the spelled letters are also tabulated.

Similarity, preference, and loudness judgments were obtained for all possible pairs of 22 voice‐communication circuits, including both linear and nonlinear distortions. Each set of judgments was analyzed, using multidimensional techniques. The analyses indicate that each type of judgment has some factors in common. The interrelationship of these factors and their influence on judgments of circuit quality is discussed.