Dynamic correction of dual-energy x-ray absorptiometry images improves chain speed prediction of lamb composition in abattoirs.

A prototype, on-line Dual Energy X-ray Absorptiometer (DXA) has shown high precision of the prediction of carcass composition for the purpose of improved sheep meat grading in the Australian lamb supply chain, albeit with small inaccuracies over time. These inaccuracies were present across hours, and more significantly across days, which were unacceptable for any accreditation of this device as an objective carcass measurement tool in Australia. This inaccuracy demanded the creation of a novel image-processing algorithm for the prototype DXA. This DXA was tested for repeatability of predictions of lamb carcass composition over minutes, hours, and days, using two developed image processing algorithms. There was high immediate repeatability for both algorithms when predicting lean muscle % in 40 lamb carcasses, with a maximum CV of 0.65% over five repeated scans. There was a decrease in the CV of the prediction of lean muscle % of 30 lambs scanned three times over a 48-h period from 5.93 to 1.19% when the superior algorithm was used. The inaccuracies of lean muscle % predictions were associated with increases in the unattenuated space pixel values in DXA images. Improvements of the current algorithm are required to demonstrate repeatability over time for the purpose of accreditation within the Australian sheep meat industry, and for possible expansion of this technology into international supply chains.

A prototype rapid dual energy X-ray absorptiometry (DEXA) system can predict the CT composition of beef carcases.

The development of a novel rapid dual energy X-ray absorptiometry (DEXA) system provides the opportunity to improve measurement of beef carcase composition. A prototype rapid DEXA system was built in a shipping container to scan 51 beef carcases selected for a wide range in weight and fatness. One side of each carcase was spray chilled and the other conventionally chilled overnight before being quartered for DEXA scanning and then being cut into 16 pieces for CT scanning to determine carcase composition. Spray chilling did not impact DEXA prediction of CT composition, with the DEXA system describing 89%, 95%, and 87% of the variation in beef carcase CT lean %, fat % and bone %, with a root mean square error of prediction of 2.31 lean %, 2.15 fat %, and 1.12 bone % units. These results demonstrate that the novel rapid DEXA system has excellent capacity to predict CT composition in beef carcases.

Dual energy X-ray absorptiometry precisely and accurately predicts lamb carcass composition at abattoir chain speed across a range of phenotypic and genotypic variables.

Dual energy X-ray absorptiometry (DEXA) is an imaging modality that has been used to predict the computed tomography (CT)-determined carcass composition of multiple species, including sheep and pigs, with minimal inaccuracies, using medical grade DEXA scanners. An online DEXA scanner in an Australian abattoir has shown that a high level of precision can be achieved when predicting lamb carcass composition in real time. This study investigated the accuracy of that same online DEXA when predicting fat and lean percentages as determined by CT over a wide range of phenotypic and genotypic variables across 454 lambs over 6 kill groups and contrasted these results against the current Australian industry standard of grade-rule (GR) measurements to grade carcasses. Lamb carcasses were DEXA scanned and then CT scanned to determine CT Fat % and CT Lean %. All phenotypic traits and genotypic information, including Australian Sheep Breeding Values, were recorded for each carcass. Residuals of the DEXA predicted CT Fat % and Lean %, and the actual CT Fat % and Lean % were calculated and tested against all phenotypic and genotypic variables. Excellent overall precision was recorded when predicting CT Fat % (R2 = 0.91, RMSE = 1.19%). Small biases present for sire breed, sire type, dam breed, hot carcass weight and c-site eye muscle area could be explained by a regression paradox; however, biases among kill group (-0.73% to 1.01% for CT Fat %, -1.48% to 0.76% for CT Lean %) and the Merino sire type (0.36% for CT Fat %, -0.73% for CT Lean %) could not be explained by this effect. Over the large range of phenotypic and genotypic variation, there was excellent precision when predicting CT Fat % and CT Lean % by an online DEXA, with only minor biases, showing superiority to the existing Australian standard of GR measurements.

Application and biomolecular monitoring of psychrophilic anaerobic digestion.

Thirteen anaerobic hybrid expanded granular sludge bed-anaerobic filter bioreactors were used for psychrophilic (15-18 degrees C) anaerobic digestion of a variety of synthetic and non-synthetic wastewaters, including: food-processing, dairy, aromatic- and aliphatic-containing and brewery discharges. Specific methanogenic activity assays were employed to assess temporal physiological activity dynamics. Terminal restriction fragment length polymorphism genetic fingerprinting and fluorescent in situ hybridization were used to monitor shifts in the structure of the microbial communities in the bioreactors in response to operating conditions. Treatment efficiencies obtained were comparable to previous mesophilic (37 degrees C) trials. Methanogenic activity developed under psychrophilic conditions and putative psychrophilic populations were detected within otherwise psychrotolerant mesophilic communities. Shifts in the population structure of archaeal (methanogenic) communities were more indicative of process disruption than bacterial communities. Biomolecular techniques were demonstrated as valuable tools for anaerobic wastewater treatment plant monitoring.

Developing performance indicators that reflect an expanded view of health: findings from the use of an innovative methodology.

BACKGROUND: The increasing presence of managed health care in the United States has been accompanied by the widespread use of performance indicators to assess health plans along various dimensions of quality. Current performance indicator sets virtually ignore psychosocial and behavioral factors in the prevention and management of illness, especially chronic illness, in spite of documented evidence in the medical literature of the importance of these factors. Instead, current indicator sets focus primarily on biomedical interventions to prevent, treat, and manage illness. METHODOLOGY: In a novel method for developing performance indicators--the use of a storytelling methodology--eight interdisciplinary panels, composed of health care experts at the community, state, and national levels, each completed two stories about patients with chronic illnesses. The first story described experiences a patient might have in the health care system as it is today; the second story retold the events that might transpire if attention to psychosocial and behavioral factors were integrated into the health care system. FINDINGS: Differences between the two sets of stories developed by the panels revealed common themes and specific areas where indicator development might prove fruitful. Performance indicators were identified from these themes, and work is underway to operationalize them; to identify barriers and opportunities for their inclusion in indicator sets; and to further document their potential health and cost-effectiveness. DISCUSSION: Although not scientifically rigorous, the storytelling method was found to provide consistent results and may be applied to many aspects of the health care planning process, health education, and quality improvement efforts.

Enhanced Th2-like responses in IL-1 type 1 receptor-deficient mice.

IL-1 has a number of effects on T cell growth but a specific role for IL-1 in T cell responses in vivo has not been elucidated. In this study the role of IL-1 in Th1/Th2 responses was examined in mice deficient for the IL-1 type 1 receptor (IL-1RI-/-) during cutaneous Leishmania major infection or following immunization with keyhole limpet hemocyanin (KLH). After inoculation of L. major stationary phase promastigotes into the hind footpad, both IL-1RI-/- and wild-type (WT) mice developed small lesions which resolved spontaneously. Lymph node cells from infected IL-1RI-/- mice produced significantly more IL-4 and IL-10 than those from WT mice following antigenic stimulation in vitro. Splenocytes from IL-1RI-/- and WT mice showed similar levels of antigen-induced proliferation. In contrast, splenocyte cultures from the IL-1RI-/- mice contained significantly more IL-4 than those from WT mice. Similar results were also obtained after immunization with KLH. While lymph node cells from both IL-1RI-/- and WT mice displayed similar levels of KLH-specific proliferation, those from IL-1RI-/- mice produced significantly more IL-4 than those from WT mice. Conversely, antigen-stimulated lymph node cells from WT mice secreted significantly greater amounts of IFN-gamma as compared with those from IL-1RI-/- mice. These data indicate that while IL-1 is not required for mounting an immune response or antigen-dependent proliferation, it appears to be required for normal regulation of Th1/Th2 responses and may function to negatively regulate IL-4 expression.

Design, synthesis, and pharmacological evaluation of conformationally constrained analogues of N,N'-diaryl- and N-aryl-N-aralkylguanidines as potent inhibitors of neuronal Na+ channels.

In the present investigation, the rationale for the design, synthesis, and biological evaluation of potent inhibitors of neuronal Na+ channels is described. N,N'-diaryl- and N-aryl-N-aralkylguanidine templates were locked in conformations mimicking the permissible conformations of the flexible diarylguanidinium ion (AS+, AA+, SS+). The resulting set of constrained guanidines termed "lockamers" (cyclophane, quinazoline, aminopyrimidazolines, aminoimidazolines, azocino- and tetrahydroquinolinocarboximidamides) was examined for neuronal Na+ channel blockade properties. Inhibition of [14C]guanidinium ion influx in CHO cells expressing type IIA Na+ channels showed that the aminopyrimidazoline 9b and aminoimidazoline 9d, compounds proposed to lock the N,N'-diarylguanidinium in an SS+ conformation, were the most potent Na+ channel blockers with IC50's of 0.06 microM, a value 17 times lower than that of the parent flexible compound 18d. The rest of the restricted analogues with 4-p-alkyl substituents retained potency with IC50 values ranging between 0.46 and 2.9 microM. Evaluation in a synaptosomal 45Ca2+ influx assay showed that 9b did not exhibit high selectivity for neuronal Na+ vs Ca2+ channels. The retention of significant neuronal Na+ blockade in all types of semirigid conformers gives evidence for a multiple mode of binding in this class of compounds and can possibly be attributed to a poor structural specificity of the site(s) of action. Compound 9b was also found to be the most active compound in vivo based on the high level of inhibition of seizures exhibited in the DBA/2 mouse model. The pKa value of 9b indicates that 9b binds to the channel in its protonated form, and log D vs pH measurements suggest that ion-pair partitioning contributes to membrane transport. This compound stands out as an interesting lead for further development of neurotherapeutic agents.

Financing pediatric education in community settings.

Increasingly, hospital-based pediatric outpatient departments are recognized as settings that attempt to combine two critical, but not always compatible, mandates: (1) education of medical students and pediatric residents in outpatient pediatrics, and (2) service, often with inadequate resources, to a socially highrisk population with a disproportionately high prevalence of social, family, and psychological dysfunction. Coexistence of these two mandates has raised a number of concerns, because pediatric ambulatory care education and training have historically been based almost exclusively in a hospital setting. Trainees often get a false impression of the types of problems they will be dealing with in pediatric primary care and of how an efficient pediatric practice is managed. In addition, they often are supervised by full-time faculty who have little if any experience in community settings and who practice only part time or not at all. These problems have led to a widespread desire to train pediatric residents outside the hospital, in settings that more closely approximate the places in which they will practice in the future. Residency programs that address this issue also provide residents with the opportunity to be trained by seasoned practitioners whose primary professional responsibility is the outpatient care of children. To date, little has been written about the cost or the financing of such educational efforts. This article summarizes what is known about the costs. We also attempt to specify the costs that should be anticipated for the various components and steps involved in devising and implementing pediatric community-based educational programs and to describe potential sources of funding for such programs.

Reduced incidence and severity of collagen-induced arthritis in interleukin-12-deficient mice.

Collagen-induced arthritis (CIA) is an animal model for rheumatoid arthritis. The disease is elicited by immunization of genetically susceptible DBA/1 mice with type II collagen, resulting in a debilitating arthritis characterized by inflammation and involvement of multiple joints. We investigated the role of endogenous interleukin (IL)-12 in the pathogenesis of this disease by undertaking an analysis of IL-12-deficient mice on the DBA/1 genetic background after immunization with type II collagen. Both the incidence and severity of disease were significantly reduced in mice unable to produce biologically active IL-12. Concomitant decreases were observed in serum levels of pathogenic, collagen-specific IgG2a antibodies and collagen-induced secretion of interferon-gamma by immune splenocytes in vitro, consistent with an impaired T helper-1 response. There were, however, a few animals which developed severe disease in a single paw in spite of this highly diminished Th1 response. Taken together, these results demonstrate an important role for IL-12 in the pathogenesis of CIA, although it is not absolutely required for disease development.

Interleukin-12 antagonist activity of mouse interleukin-12 p40 homodimer in vitro and in vivo.

Mo(p40)2 is a potent IL-12 antagonist that interacts strongly with the beta 1 subunit of the IL-12R to block binding of moIL-12 to the high-affinity mouse IL-12R. Mo(p40)2, alone or in synergy with the 2B5 mAb specific for the moIL-12 heterodimer, blocked IL-12-induced responses in vitro, Mo(p40)2 was thus used alone or with 2B5 mAb to examine the role of IL-12 in vivo, Mo(p40)2 caused a dose-dependent inhibition of both the rise in serum IFN-gamma levels in mice injected with endotoxin and the Th1-like response to immunization with KLH. Treatment with mo(p40)2 plus 2B5 anti-moIL-12 mAb also suppressed DTH responses to methylated bovine serum albumin but not specific allogeneic CTL responses in vivo. In each of these models, responses seen in mice treated with mo(p40)2 +/- 2B5 anti-moIL-12 mAb were similar to those observed in IL-12 knockout mice. Thus, mo(p40)2 can act as a potent IL-12 antagonist in vivo, as well as in vitro, and is currently being used to investigate the role of IL-12 in the pathogenesis of some Th1-associated autoimmune disorders in mice.

IL-12-deficient mice are defective but not devoid of type 1 cytokine responses.

Interleukin-12 (IL-12) has been described as a pivotal molecule in the immune response based in part on its ability to influence the differentiation of T helper (Th) cells into a type 1 (Th1) phenotype. This event is crucial in that appropriate differentiation of naive T cells can determine susceptibility or resistance to given pathogens by influencing the balance between cellular and humoral immunity. In order to further delineate the role of IL-12 in the immune response, we generated mice deficient for this cytokine. IL-12 knockout mice were viable, fully fertile, and displayed no obvious developmental abnormalities. Upon immunological analysis, these mice demonstrated an impaired ability to effect a Th1 response as well as an impaired ability to produce interferon-gamma in response to endotoxin in vivo. These data establish an essential role for IL-12 in the generation of optimal Th1 responses in vivo, but weak responses can occur independently of IL-12.

IL-12-deficient mice are defective in IFN gamma production and type 1 cytokine responses.

IL-12 is a cytokine that can exert regulatory effects on T and NK cells and promote Th1 responses. To delineate further the physiologic role of IL-12 in immunity, mice deficient for this cytokine were generated. IL-12-deficient mice were impaired but not completely lacking in the ability to produce IFN gamma following endotoxin administration and to mount a Th1 response in vivo, as measured by antigen-induced IFN gamma secretion by immune lymph node cells in vitro. In contrast, secretion of IL-4 was enhanced, while proliferation and secretion of IL-2 and IL-10 were normal following antigen stimulation. DTH responses were significantly reduced in IL-12-deficient mice, but no defect in allogeneic CTL responses was observed. These results indicate that IL-12 plays an essential role in regulating IFN gamma production and in facilitating normal DTH responses. However, other phenomena associated with Th1 responses and cell-mediated immunity, i.e., IL-2 secretion and CTL generation, were not compromised in the absence of IL-12.

Monoclonal antibody 2D10 recognizes a novel T cell costimulatory molecule on activated murine B lymphocytes.

We have developed a panel of rat mAbs against dibutyryl cAMP-activated 5C2 cells. In this panel, one mAb, 1G10, recognized murine B7. Another mAb designated 2D10 did not bind to murine B7 but could recognize a surface molecule expressed only on dibutyryl cAMP-activated 5C2 mouse B lymphoma cells or on LPS-stimulated splenic B cells. This new molecule is referred to as early T cell costimulatory molecule-1 (ETC-1). From both activated 5C2 cells and splenic B cells, mAb 2D10 immunoprecipitated a 59- to 60-kDa protein, which was different from the 47- to 55-kDa murine B7 protein precipitated from the same cell populations. FACS analysis showed that, in contrast to B7, the expression of ETC-1 on 5C2 cells was induced by lower concentrations of dibutyryl cAMP and displayed a faster kinetics. LPS-stimulated splenic B cells expressed relatively low levels of B7 and much higher levels of ETC-1. Importantly, in an Ag presentation assay using activated 5C2 cells as APC, the secretion of IL-2 by C8A3 T hybrids was partially inhibited by mAb 2D10 alone and completely blocked by combination use of mAbs 2D10 and 1G10 in a dose-dependent and synergistic fashion. In a one-way primary MLR, mAb 2D10 alone at 0.1 to 1 microgram/ml inhibited T cell proliferation by 19 to 56%. However, an additive blocking effect (up to 76%) was observed when two mAbs were added in combination. Thus, our data have demonstrated that a novel T cell costimulatory molecule is present on activated murine B cells, which, in cooperation with B7, may play a critical role in optimal T cell activation.

Expression and functional analysis of murine B7 delineated by a novel monoclonal antibody.

The B cell surface molecule designated B7 has been shown to be expressed by activated human B cells and monocytes and to be a ligand for the CD28 and CTLA-4 molecules on T cells. B7/CD28 interactions can provide a second signal to T cells (in addition to occupancy of the T cell antigen receptor) that is needed for T cell activation. COS cells transfected with the mouse homologue of B7 have been demonstrated to provide a stimulatory signal to murine and human T cells. In this report we describe a rat anti-mouse B7 mAb designated 1G10. Scatchard and/or FACS analyses utilizing 1G10 demonstrated that B7 was not expressed on resting splenic T cells or B cells, but could be induced at high levels on B cells cocultured with a syngeneic I-Ak-restricted autoreactive T cell hybridoma. Furthermore, activation of B cells with dibutyryl-cAMP (db-cAMP), a second messenger for class II MHC signaling, or with LPS induced the expression of B7 and the two agents showed additive effects. In contrast to B cells, freshly isolated mouse peritoneal macrophages constitutively expressed B7. Antibody-blocking experiments indicated that anti-B7 antibody partially inhibited T cell proliferative responses to primary antigenic stimulation but had no effect on the responses of previously activated T cells to antigenic restimulation.

Administration of recombinant IL-12 to normal mice enhances cytolytic lymphocyte activity and induces production of IFN-gamma in vivo.

IL-12 is a heterodimeric cytokine that has been shown to enhance natural killer (NK) and cytotoxic T lymphocyte (CTL) responses, and to induce IFN-gamma production in vitro. In this study, we have examined the effects in vivo of administering purified murine rIL-12 to normal mice. Daily injections of rIL-12 i.p. (1 ng to 10 micrograms/day) caused dose-dependent enhancement of NK cell lytic activity in the spleens and livers of treated mice. Histologic examination of the livers of IL-12-treated mice revealed focal mononuclear cell infiltrates, and flow cytometry studies indicated that the livers of IL-12-treated mice contained increased numbers of NK cells, CD8+ T cells, and monocytes. Liver and splenic lymphoid cells from IL-12-treated mice, unlike liver and splenic lymphoid cells from control mice, spontaneously secreted IFN-gamma in vitro, suggesting that they had been induced by IL-12 to produce IFN-gamma in vivo. Consistent with this, IFN-gamma could be detected in the serum of IL-12-treated mice. In mice which had been immunized by footpad injection of allogeneic splenocytes, daily administration of rIL-12 i.p. was shown to enhance the specific CTL response in the draining lymph nodes. Thus, these studies demonstrate that IL-12 can enhance NK and CTL activity and induce IFN-gamma production in vivo, as well as in vitro, and suggest possible mechanisms by which IL-12 may exert therapeutic effects in the treatment of some tumors and infectious diseases.

Investigations of the subtype of alpha 2-adrenoceptor mediating contractions of the human saphenous vein.

1. We have examined the effects of a series of alpha 2-adrenoceptor antagonists against isometric contractions to noradrenaline in human saphenous vein, and correlated these potencies with affinities for the alpha 2A-ligand binding site of human platelet and the alpha 2B-ligand binding site of rat kidney. 2. The alpha 2B-selective adrenoceptor antagonists, prazosin, ARC 239 and HV 723 showed high, and the alpha 2A-selective antagonist BRL 44408 showed low, potency in human saphenous vein. 3. Potency in human saphenous vein correlated better with affinity for the alpha 2B-ligand binding site (r = 0.71, n = 12, P less than 0.01) than with affinity for the alpha 2A-ligand binding site (r = 0.56, n = 12, non significant). 4. It is concluded that the postjunctional alpha 2-adrenoceptor of human saphenous vein resembles an alpha 2B-ligand binding site more than an alpha 2A-ligand binding site.

Investigations of prejunctional alpha 2-adrenoceptors in rat atrium, vas deferens and submandibular gland.

We have examined the effects of a series of alpha 2-adrenoceptor antagonists on the stimulation-evoked release of tritium from rat atrium, vas deferens and submandibular gland pre-incubated with [3H]noradrenaline, and correlated these potencies with affinities for the alpha 2A-ligand binding site of human platelet and the alpha 2B-ligand binding site of rat kidney. The alpha 2B-selective adrenoceptor antagonists prazosin and ARC 239 showed significantly higher, and the alpha 2A-selective antagonist BRL 44408 showed significantly lower, potency in atrium than in vas deferens and submandibular gland. Yohimbine and BDF 8933 failed to distinguish between prejunctional alpha 2-adrenoceptors or between ligand binding sites. It is concluded that the prejunctional alpha 2-adrenoceptor of rat atrium resembles the alpha 2B-ligand binding site, and differs from the prejunctional alpha 2-adrenoceptors of rat vas deferens and submandibular gland, which resemble the alpha 2A-ligand binding site.

Actions of 8-hydroxy-2-(N-dipropylamino) tetralin (8-OH-DPAT) at alpha 2-adrenoceptors.

1 We have examined the actions of the 5-HT1A-receptor ligand 8-OH-DPAT at alpha 2-adrenoceptor ligand binding sites in human platelet and rat kidney membranes and at functional pre- and postjunctional alpha 2-adrenoceptors in rat atrium and human saphenous vein, respectively. 2 8-OH-DPAT had low affinity for the alpha 2A ligand binding site of human platelet but showed 10 times higher affinity for the alpha 2B ligand binding site of rat kidney (K1 of 6.41, -log M). 3 In functional studies, 8-OH-DPAT had low potency as an antagonist of noradrenaline-induced contractions in human saphenous vein, with a KB of 5.40 (-log M). 4 In rat atria preincubated with [3H]-noradrenaline, 8-OH-DPAT potentiated stimulation-evoked overflow of tritium with an EC30 (concentration producing 30% increase in the stimulation-evoked overflow) of 6.37 (-log M). 5 It is concluded that 8-OH-DPAT shows selectively for the alpha 4B ligand binding site of rat kidney and for the functional prejunctional alpha 2-adrenoceptor of rat atrium, which resembles the alpha 2B ligand binding site.

Functional evidence for heterogeneity of peripheral prejunctional alpha 2-adrenoceptors.

1. We have examined the potencies of a series of alpha 2-adrenoceptor antagonists in functional studies of prejunctional alpha 2-adrenoceptors in rat atrium and vas deferens, and compared potencies with affinities for the alpha 2A-ligand binding site of human platelet and the alpha 2B-site of rat kidney. 2. Antagonist potency in rat atrium was expressed as an EC30 (concentration producing 30% increase in the stimulation-evoked overflow of tritium in tissues pre-incubated with [3H]-noradrenaline). Antagonist potency in rat vas deferens was expressed as a pA2 or KB at antagonizing the inhibition by the alpha 2-adrenoceptor agonist xylazine of the isometric twitch to a single stimulus, or as an EC30. 3. In ligand binding studies, Ki values were obtained for the displacement by alpha-adrenoceptor antagonists of [3H]-yohimbine binding to human platelet or rat kidney membranes. 4. In functional studies, three antagonists (ARC 239, prazosin and chlorpromazine) distinguished between prejunctional alpha 2-adrenoceptors of rat atrium (EC30) and rat vas deferens (pA2) and showed 49, 12 and 7 times higher potency in rat atrium, respectively. ARC 239 was also 17 times more potent in rat atrium than rat vas deferens when EC30 values were compared. 5. The correlation of affinity for the alpha 2A-site of human platelet was better with prejunctional potency in rat vas deferens than rat atrium. 6. The correlation of affinity for the alpha 2B-site of rat kidney was better with prejunctional potency in rat atrium than rat vas deferens. 7. It is concluded that prejunctional alpha 2-adrenoceptors of rat vas deferens and rat atrium differ, and these receptors may resemble the alpha 2A- and alpha 2B-ligand binding sites, respectively.

No evidence for differences between pre- and postjunctional alpha 2-adrenoceptors in the periphery.

1. We have compared prejunctional alpha 2-adrenoceptors in rat and guinea-pig vas deferens and rat and guinea-pig atria with postjunctional alpha 2-adrenoceptors in human saphenous vein and human platelets employing the antagonists yohimbine and SK&F 104078 and other alpha 2-adrenoceptor antagonists. 2. Yohimbine was approximately 10 times more potent prejunctionally than SK&F 104078 at antagonizing the inhibition by the alpha 2-adrenoceptor agonist xylazine of stimulation-evoked contractions in rat and guinea-pig vas deferens, and at increasing stimulation-evoked release of tritium in rat and guinea-pig atria pre-incubated with [3H]-noradrenaline. 3. Yohimbine was approximately 10 times more potent postjunctionally than SK&F 104078 at antagonizing contractions to noradrenaline in human saphenous vein and at displacing [3H]-yohimbine binding in human platelet membranes. 4. For the antagonists yohimbine, SK&F 104078, prazosin, phentolamine, CH 38083 and urapidil, there was a significant correlation between prejunctional potency in rat vas deferens atrium and postjunctional potency in human platelet, although the correlation was improved by the omission of prazosin. 5. We have no evidence for differences between functional pre- and postjunctional alpha 2-adrenoceptors in the periphery, although these functional receptors may differ from the ligand binding site in the human platelet.