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At least 19 recordsLinked to original sources

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

PubMed1983

In vitro analysis of the cellular interactions between unprimed lymphocytes responsible for determining the class of response an antigen induces: specific T cells switch a cell-mediated response to a humoral response.

Unprimed murine spleen cells, when cultured at different densities but in the presence of the same concentration of antigen, are induced to mount different classes of response. Three modes of behavior are found. A low density does not support the induction of any response, a medium density supports a transient IgM and substantial delayed-type hypersensitivity (DTH) response, and a high density only supports a sustained IgM response. This in vitro system has been used to show that a low density of cells, when complemented with irradiated specific T cells, can mount a DTH response, and thus behave as a medium density of cells. These observations show that the induction of DTH requires helper T cells, and that a medium density, in contrast to a low density, allows sufficient collaboration to obtain a DTH response. The observation that a high density only mounts a sustained humoral response suggests that the formation of more helper T cell-dependent signals than the number generated at a medium density may be required to induce a sustained humoral response as well as the suppression of DTH. This hypothesis is supported by the findings that the response by a medium density of cells is dramatically affected by the addition of irradiated antigen-specific helper T cells; the DTH response is specifically suppressed and a sustained humoral response is observed. These results show that the induction of a humoral response is more T cell dependent than the induction of a cell-mediated response and provides an in vitro means for switching a cell-mediated response to a humoral one in an antigen-specific manner. Observations are also presented to show that the production of antibody by a high density of cells is not a prerequisite for the suppression of DTH reactivity.

Animals↗

PubMed1984

LPS regulation of the immune response: Bacteroides endotoxin induces mitogenic, polyclonal, and antibody responses in classical LPS responsive but not C3H/HeJ mice.

Recent studies have suggested that lipopolysaccharide (LPS) derived from gram-negative organisms such as Bacteroides, which are not members of the Enterobacteriaceae, stimulate B cells from the classic LPS-hyporesponsive C3H/HeJ mouse. In the present study, purified, phenol-water-extracted LPS from Bacteroides fragilis ATCC 25285 (B-LPS) was tested for its ability to induce in vivo and in vitro responses in classic LPS-responsive C3H/HeN, LPS-hyporesponsive C3H/HeJ, and (C3H/HeN X C3H/HeJ)F1 hybrid mice. B-LPS induced mitogenic responses in both C3H/HeN and C3H/HeJ spleen cell cultures when cells were cultured under standard conditions, i.e., 8 X 10(5) cells/well. Interestingly, when lower spleen cell numbers were tested with B-LPS, a typical responsive-nonresponsive pattern developed in which good mitogenic responses were induced by B-LPS in C3H/HeN cultures and in which low responses in C3H/HeJ spleen cell cultures were evident. In vivo immunization of mice with B-LPS resulted in high antibody responses in C3H/HeN, intermediate responses in F1, and low responses in C3H/HeJ mice. When purified splenic B cells were incubated with B-LPS, both mitogenic responses and polyclonal immunoglobulin M (IgM) synthesis occurred in C3H/HeN cultures, whereas intermediate responses were noted in F1 cultures and no response was seen in B cell cultures from C3H/HeJ mice. Furthermore, in vitro TNP-B-LPS responses were induced in C3H/HeN spleen cells or purified B cell cultures, and intermediate anti-TNP PFC responses occurred in F1 spleen cells or purified B cell cultures. The toxicity of B-LPS was tested in galactosamine-sensitized mice. The LD50 values for B-LPS in classic LPS-responsive C3H/HeN and C57BL/6J mice were 0.6 microgram and 1.1 microgram, respectively; F1 hybrid mice were approximately 15-fold more resistant, whereas C3H/HeJ mice gave an LD50 of 1650 micrograms. This study shows that phenol-water preparations of B-LPS are biologically active and induce responses in the classic LPS-responsive but not in the LPS-hyporesponsive C3H/HeJ mouse strain.

Animals↗

PubMed1991

Time-response and dose-response to acetazolamide in the WB/ReJ and C57BL/6J mouse strains: genetic interaction in the ectrodactyly response.

The WB/ReJ and C57BL/6J strains were compared in their time and dose responses to acetazolamide administered in a single subcutaneous injection regime. WB/ReJ has a genetically determined, high-frequency, transient fetal edema that has maximum expression on day 14 and is resolved by day 18. Acetazolamide, at 1,000 mg/kg, appears to induce edema in WB/ReJ with a time of response on days 9 and 10, and the induced edema follows the same time course of appearance and disappearance as the spontaneous trait. The dose-response analysis is not interpretable in the WB/ReJ and C57BL/6J strains and their reciprocal F1 fetuses because there was significant response only at the highest dose (2,000 mg/kg) used in this study. The time of ectrodactyly response is maximal on day 9 in both WB/ReJ and C57BL/6J strains. The dose-response analysis demonstrates that, for the usual measure of total fetuses with ectrodactyly (or penetrance), the Wb/ReJ and C57BL/6J strains and the WB/ReJ x C57BL/6J F1 (WB.B6F1) have the same slope of the dose-response curve and the strain difference in response can be interpreted as a difference in dosage tolerance. The tolerance of WB/ReJ is twofold greater than that of C57BL/6J. This overdominance of relative resistance to acetazolamide ectrodactyly supports the general finding of directional dominance of relative resistance among genetically different strain pairs. The median effective dose for penetrance of the ectrodactyly response of the reciprocal B6.WBF1 embryo is similar to the WB.B6F1, but the slope of the dose-response curve is significantly different, and a different teratogenic mechanism of response may be involved. Ectrodactyly was predominantly right sided in all genotypes, and, in bilaterally affected fetuses, the right forelimb was more severely affected. An unexpected difference between WB/ReJ and C57BL/6J was found when the laterality of ectrodactyly was analyzed further. There is a significant increase with dosage in bilaterally affected fetuses (a measure of expressivity) in C57BL/6J but not in WB/ReJ, even though the dose-response of total affected fetuses (penetrance) is similar in both strains. In C57BL/6J, the left and right forelimbs are correlated in their responses with the left, requiring approximately a threefold greater dose. The left and right forelimbs are symmetrical in response, and the difference can be interpreted in terms of a developmental (or teratogenic) gradient. In WB/ReJ, the right forelimb has the same dose response as C57BL/6J and requires a twofold greater dose than the right forelimb of C57BL/6J, but the left forelimb has a very flat slope and is not correlated with the response of the right.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Drug-Induced↗

PubMed2002

Influence of practice on response-selection and response-implementation processes involved in the response-interference effect.

In a choice reaction-time task, the response-interference effect is an increase in reaction times when the two possible responses are from the same hand compared to when the two possible responses are from different hands [Psychonomic Science 2 (1965) 55-56; Human Motor Control, Academic Press, San Diego, CA, 1991]. Although the influence of practice on other reaction-time effects (i.e., the complexity effect and precuing) has been examined, research evaluating the influence of practice on the response-interference effect is limited. Therefore, two experiments were conducted to determine the influence of practice on the response-interference effect. In Experiment 1, a bilateral transfer task was used to assess the influence of practice on the response-selection processes associated with the response-interference effect. The practice results indicated decreased reaction times, but did not influence the response-interference effect. In Experiment 2, a priming task was used to assess the influence of practice on response-implementation processes associated with the response-interference effect. The reaction time results indicated a change in the response-interference effect. The results of these two experiments suggest that with only two fingers on response keys, practice alters the mechanical constraints affecting the response-implementation processes and thereby decreases the response-interference effect.

Adult↗

PubMed1993

The effects of response cost and response restriction on a multiple-response repertoire with humans.

In two experiments a multiple-response repertoire of four free-operant responses was developed with university students as subjects using monetary gain as reinforcement. Following baseline, one of the responses was reduced either by making monetary loss contingent upon it (response cost) or by removing it from the repertoire (response restriction). In Experiment 1 a multielement baseline design was employed in which baseline and restriction or response-cost contingencies alternated semirandomly every 3 minutes. In Experiment 2 a reversal design was employed (i.e., baseline, restriction or response cost, then baseline), and each response required a different amount of effort. Both experiments had the following results: (a) The target response decreased substantially; (b) most nontarget responses increased, and the rest remained near their baseline levels; and (c) no support was found for Dunham's hierarchical, most frequent follower, or greatest temporal similarity rules. For several subjects, the least probable responses during baseline increased most, and the most probable responses increased least. Furthermore, in Experiment 2, responses with the lowest frequency of reinforcement increased most (for all 7 subjects), and those with the greatest frequency of reinforcement increased least (for 5 subjects).

Journal Article↗

PubMed1979

Development of antigen-induced proliferative responsiveness by murine lymph node cells. I. Identification of differences in the in vitro proliferative responses during a first and a second period of responsiveness.

The development and course of antigen-induced proliferative responsiveness by murine lymph node cells (LNC) was observed for 16 weeks post-immunization. The initial phase of responsiveness was characterized by antigen-induced proliferative responsiveness in vitro which reached a maximum 3-5 weeks post-immunization and then declined to low levels by 6-8 weeks. Without injection of additional antigen, the initial phase of responsiveness was followed by the development of a second phase of antigen-induced proliferative responsiveness 10-12 weeks post-immunization. These findings suggest that the in vivo development of lymph node lymphocytes capable of a proliferative response to antigen is under some type of modulation which is maximal 6-8 weeks post-immunization. Early in the first phase the proliferative responses to higher concentrations of antigen peaked early in the culture period (days 3-4), whereas responses to the lower concentrations of antigen were optimal after 5-6 days of culture. During the latter half of the first phase, however, peak proliferative responses were made to all the concentrations of antigen on the same day of culture (day 6). In contrast, the responses detected at the beginning and throughout the second phase of responsiveness were characterized by maximum proliferation to all the concentrations of antigen late in the culture period (day 7). These results delineate the temporal requirements for maturation of antigen-induced proliferative responsiveness of murine LNC post-immunization and indicate the time interval when optimal responses may be detected.

Animals↗

PubMed1991

Response rates, duration of response, and dose response effects in phase I studies of antineoplastics.

Over a period of 14 years, 7,960 patients were treated in 228 phase I trials. In these patients, there were 75 complete and 432 partial responses for an overall objective response rate of 6%. Complete responses lasted a median of six months (range 1-18), while partial responses lasted a median of three months (range 1-17). Of note is that no drug has made it to the market which has not had a response in phase I trials. Responses were noted in very diverse histologic types of tumors. Although there were responses at doses which were as low as 3-5% of the recommended dose for phase II trials, the majority of responses did occur at 80-120% of the dose recommended for phase II trials. Although the response rate in phase I trials is indeed low, responses do occur. This response rate information should help the clinician provide facts for the patient considering a phase I trial with new anticancer agents. These findings also emphasize that although phase I trials are characteristically dose-finding studies, if no responses are noted in phase I studies, it is unlikely the drug will be used routinely in the clinic.

Antineoplastic Agents↗

PubMed2005

Stimulus-response compatibility and response preparation: effects on motor component of information processing for upper and lower limb responses.

The effects of stimulus-response compatibility and response preparation on the motor component of the information processing system were investigated by analyzing the fractionated reaction time for the upper and lower limbs. The reaction time was divided into two periods with respect to the onset of electromyographic activity, premotor and motor times. The response preparation was manipulated by the probability that the locations of the precue and subsequent imperative stimulus corresponded. On a stimulus-response compatible task, subjects were required to release a key on the same side as an imperative stimulus, irrespective of the precued side. On an incompatible task, subjects were required to act in the reverse manner. The upper and lower limb responses were measured during both tasks. A repeated-measures design was used with 12 male university students. Analysis of the reaction and premotor times indicated that the stimulus-response compatibility effect became larger as response preparation decreased. The analysis of motor time yielded significant interactions between stimulus-response compatibility and limb and between response preparation and limb. These findings indicated that the motor component of information processing for the lower limb response is affected by both stimulus-response compatibility and response preparation.

Adolescent↗

PubMed1976

In vitro immune response to the 2,4,6-trinitrophenyl determinant in aged C57BL/6J mice:changes in the humoral immune response to, avidity for the TNP determinant and responsiveness to LPS effect with aging.

An in vitro anti-TNP response of the spleen cells from aged C57BL/6J mice showed approximately 4-fold less PFC than did that from young adult mice. Anti-theta serum-treated young spleen cells gave an anti-TNP response that was definitely greater than the response of the anti-theta serum-treated aged spleen cells in the presence of the exogenous activated thymus cells as helper cells. These results suggest that the deficits in B cells may be partly responsible for the imparied anti-TNP response of the aged spleen cells. To examine further the capacity of stem cells in the bone marrow to generate B cells responsible for anti-TNP response in the spleen, we injected i.v. 1.5 to 2.0 times 10(7) bone marrow cells from young or aged mice into lethally irradiated syngeneic recipients that had previously been thymectomized. Four to 6 weeks later, 10(7) spleen cells from the two groups of these recipient mice were immunized with TNP-SRBC in the presence of the exogenous activated thymus cells and assayed for anti-TNP PFC. The response of the aged marrow-derived B cells was approximately one-half of that of the young marrow-derived B cells. The avidity for TNP determinant of the antibodies produced by the PFC was determined by the plaque-inhibition technique. The avidity of the antibodies produced by the aged mice was approximately 33 times lower than that by the young mice. Anti-TNP response of the young spleen cells were markedly enhanced by the addition of LPS to the cultures, whereas no or little enhancement of the response was induced in the aged spleen cells even in the presence of high concentration of LPS. In contrast, DNA synthesis of both the young and aged spleen cells was comparably stimulated by 1 mug/ml and 10 mug/ml of LPS, however, it was rather less in the aged spleen cells at a concentration of 100 mug/ml. Mechanisms responsible for the changes in avidity and responsiveness to LPS with aging are discussed.

Aging↗

PubMed1997

Dopamine-beta-hydroxylase activity is necessary for hypothalamo-pituitary-adrenal (HPA) responses to ether, and stress-induced facilitation of subsequent HPA responses to acute ether emerges as HPA responses are inhibited by increasing corticosterone (B).

To determine a role of norepinephrine (NE) in stress-induced HPA function, young male rats were treated with diethyldithiocarbamide (DDC) which inhibits dopamine-beta-hydroxylase, the enzyme that synthesizes NE from dopamine (DA). DDC injected 5 h prior to ether stress stimulated ACTH and corticosterone (B) during this time, and there was no further HPA response to ether. To control for elevated B feedback in DDC effects on HPA responses to ether, rats were adrenalectomized (Adx) and replaced with no (0% B), moderate (40% B) and high (80% B) levels of steroid 5 d prior to DDC or saline with ether stress 5 h later; Sham-Adx rats were included. In Adx rats increasing B inhibited thymus weight, median eminence CRF content, pituitary and plasma ACTH. In saline-treated rats, ether 5 h later caused increased CRF content and plasma ACTH in Sham-Adx and Adx, 0% B, increased ACTH in Adx, 40% B, and no response in Adx, 80% B. B treatment did not alter catecholamine content, and DDC treatment reduced NE content in the paraventricular nuclei by 50-60% in all groups. 5 h after DDC, pituitary ACTH was decreased in all rats with B and plasma ACTH was increased in sham-Adx and Adx, 40% B; thus DDC caused significant, prolonged stress which should facilitate subsequent HPA responses to acute stress. There was no HPA response to ether in Sham-Adx, Adx, 0% or 40% B groups, but there was a marked ACTH response to ether in the Adx, 80% B group treated with DDC. We conclude that: 1) the HPA response to ether stress is probably mediated by catecholamines; 2) DDC does not stimulate responses in the HPA axis in the absence of B; and, 3) facilitation of HPA responses to acute stress depends on increased steady-state B signals. Facilitated responses are probably not mediated by catecholamines. The consequence of facilitation is that under conditions of chronic stress and elevated B concentrations, as in depression or anorexia nervosa in man, or adjuvent-induced arthritis in rats, the HPA axis is continually responsive to new stimuli.

Adrenalectomy↗

PubMed1983

Mechanism of the water response in carp gustatory receptors: independent generation of the water response from the salt response.

The carp gustatory responses to various salts and those to distilled water after adaptation of the receptors to the salts were recorded from the palatine nerve under varying conditions. (a) As far as Na4Fe(CN)6 solution prepared freshly was used, any peak in the dose-response curve was not observed, while the solution stored overnight induced a large peak response at the low concentration region as Konishi reported. The magnitude of the water response after adaptation to the stored solution was practically equal to that after adaptation to the fresh solution, suggesting that the receptor site for the water response is different from that for the dilute salts. (b) The responses to salts depended largely on the species of both cations and anions of the salts. The responses were deceased with an increase in the lyotropic number of the anions and increased with an increase in the number above 11. The response to distilled water was practically independent of the species of both monovalent cations and anions of the salts used for the adaptation. The pH dependence of the response to 10 mM NaCl was largely different from that to distilled water after adaptation to 10 mM NaCl. (c) The water response was suppressed by the presence of electrolytes in stimulating solution; the data obtained with different species of salts were described by a single curve as a function of the ionic strength. (d) The mechanism to explain how distilled water leads to depolarization of the taste cell was discussed in terms of the electric double-layer potential.

Animals↗

PubMed2004

The costs of changing the representation of action: response repetition and response-response compatibility in dual tasks.

In 5 experiments, the authors investigated the costs associated with repeating the same or a similar response in a dual-task setting. Using a psychological refractory period paradigm, they obtained response-repetition costs when the cognitive representation of a specific response (i.e., the category-response mapping) changed (Experiment 1) but benefits when it did not change (Experiment 2). The analogous pattern of results was found for conceptually similar (i.e. compatible) responses. Response-response compatibility costs occurred when the cognitive representations of the compatible responses were different (Experiments 3A & 3B), but compatibility benefits occurred when they were the same (Experiment 4). The authors interpret the costs of repeating an identical or compatible response in terms of a general mechanism of action selection that involves coding the task-specific meaning of a response.

Adult↗

PubMed2003

Effects of response eccentricity and relative position on orthogonal stimulus-response compatibility with joystick and keypress responses.

When unimanual left-right movement responses are made to up-down stimuli, performance is better with the up-right/down-left mapping when responding in the right hemispace and with the up-left/down-right mapping when responding in the left hemispace. We evaluated whether this response eccentricity effect is explained best in terms of rotational properties of the hand (the end-state comfort hypothesis) or asymmetric coding of the stimulus and response alternatives (the salient features coding hypothesis). Experiment 1 showed that bimanual keypresses yield a response eccentricity effect similar to that obtained with unimanual movement responses. In Experiment 2, an inactive response apparatus was placed to the left or right of the active response apparatus to provide a referent. For half of the participants, the active and inactive apparatuses were joysticks, and for half they were response boxes with keys. For both response types, an up-right/down-left advantage was evident when the relative position of the active response apparatus was right but not when it was left. That bimanual keypresses yield similar eccentricity and relative location effects to those for unimanual movements is predicted by the salient features coding perspective but not by the end-state comfort hypothesis.

Functional Laterality↗

PubMed1977

Genetic control of the immune response to staphylococcal nuclease. III. Time-course and correlation between the response to native nuclease and the response to its polypeptide fragments.

The progression of the Ir gene-controlled antibody response to staphylococcal nuclease in mice with repeated immunizations has been examined. H-2-linked control of the response to a single immunization with 100 mug of nuclease in complete Freund's adjuvant was confirmed. However, among strains of the high responder H-2a haplotype, the response of the A/J mice was about 10-fold higher than that of the B10.A, indicating additional non-H-2-linked control. In addition, the low responder C57BL/10 (H-2b) strain produced antibody levels as high as or higher than those of the congenic high responder B10.A (H-2a) strain when both strains were repeatedly immunized, indicating complexity even in the H-2-linked control of the response to this small monomeric protein. Polypeptide fragments of nuclease were also studied as immunogens. The antibody response to one fragment (residues 99-149) was found to follow the same pattern among five strains tested as that to whole nuclease. However, in this case the C57BL/10 was found to be a nonresponder rather than a low responder, failing to develop a response despite repeated immunizations. In contrast, the C57BL/10 showed a low but significant response to another fragment (residues 1-126) of nuclease. These results suggest that the apparent H-2-linked control of the response to whole nuclease is a reflection of the ability to recognize a determinant(s) in the region from residues 99 to 149, and that the eventual response of the C57BL/10 strain after hyperimmunization reflects the recognition of other determinants. If these observations reflect the common recognition of a determinant on native nuclease and on a random-conformation fragment, they have implications about the conformational specificity of the receptors, or the flexibility of the determinants, involved in H-2-linked Ir-gene control. In addition, evidence is presented for a possible second H-2-linked gene (or genes) controlling the response to other determinants of nuclease expressed on the polypeptide fragments.

Animals↗

PubMed1975

Avoidance response, house response, and wind responses of the sporangiophore of Phycomyces.

Avoidance response: An object placed 1 mm from the growing zone of a Phycomyces sporangiophore elicits a tropic response away from the object. The dependence of this response on the size of the object and its distance from the specimen is described, as well as measurements which exclude electric fields, electromagnetic radiation, temperature, and humidity as avoidance-mediating signals. This response is independent of the composition and surface properties of the object and of ambient light. House Response: A house of 0.5- to 10-cm diameter put over a sporangiophore elicits a transient growth response. Avoidance responses inside closed houses are slightly smaller than those in the open. Wind responses: A transverse wind elicits a tropic response into the wind, increasing with wind speed. A longitudinal wind, up or down, elicits a transient negative growth response to a step-up in wind speed, and vice versa. It is proposed that all of the effects listed involve wind sensing. This proposal is supported by measurements of aerodynamic effects of barriers and houses on random winds. The wind sensing is discussed in terms of the hypothesis that a gas is emitted by the growing zone (not water or any normal constituent of air), the concentration of which is modified by the winds and monitored by a chemical sensor. This model puts severe constraints on the physical properties of the gas.

Fungi↗

PubMed1995

Contribution of response kinetics to the response pattern: studies of responses to thyrotropin-releasing hormone in Xenopus oocytes.

In Xenopus oocytes injected with total rat pituitary GH3 cell RNA, thyrotropin-releasing hormone (TRH) causes the activation of the inositol lipid transduction pathway and the induction of chloride conductance via calcium-activated channels (Oron et al., 1987, Mol. Endocrinol., 1:918-925). This response exhibits characteristic prolonged latency (Oron et al., 1988, Proc. Natl. Acad. Sci. U.S.A., 85:3820-3824; Lipinsky et al., 1993, Pflugers Arch., 425:140-149). We examined the role of agonist diffusion in the extracellular medium in the generation of latency and the determination of response amplitude. An increase in the viscosity of the medium markedly prolonged the latency and decreased the amplitude of the response. Moreover, an increase in the viscosity of the medium in the immediate vicinity of the oocyte had a major effect on both the latency and the amplitude of the response, which appeared to be a result of desensitization rather than restricted diffusion of chloride to the medium. Extrapolation to [TRH] infinity yielded a diffusion-dependent latency value of 0 and a diffusion-independent latency value of 4 seconds. In low viscosity medium, at all TRH concentrations, diffusion contributed less than 2% to the latency of the response. This implied that events distal to ligand binding are responsible for a major part of latency. Analysis of the dependence of latency and amplitude of the response on [TRH] yielded Hill coefficients markedly smaller than unity, suggesting postreceptor negative modulation of the response. Preincubation of cells with a specific inhibitor of protein kinase C, chelerythrine, increased the Hill coefficients to unity and changed the shape of the Hill plot of response amplitudes. Our results suggest that at low agonist concentrations, even in a low viscosity medium, the prolonged latency allows negative effects on both latency and amplitude by a simultaneous activation of a protein kinase C.

Alkaloids↗

PubMed2002

Not another questionnaire! Maximizing the response rate, predicting non-response and assessing non-response bias in postal questionnaire studies of GPs.

BACKGROUND: Non-response is an important potential source of bias in survey research. With evidence of falling response rates from GPs, it is of increasing importance when undertaking postal questionnaire surveys of GPs to seek to maximize response rates and evaluate the potential for non-response bias. OBJECTIVES: Our aim was to investigate the effectiveness of follow-up procedures when undertaking a postal questionnaire study of GPs, the use of publicly available data in assessing non-response bias and the development of regression models predicting responder behaviour. METHOD: A postal questionnaire study was carried out of a random sample of 600 GPs in Wales concerning their training and knowledge in palliative care. RESULTS: A cumulative response rate graph permitted optimal timing of follow-up mailings: a final response rate of 67.6% was achieved. Differences were found between responders and non-responders on several parameters and between sample and population on some parameters: some of these may bias the sample data. Logistic regression analysis indicated medical school of qualification and current membership of the Royal College of General Practitioners to be the only significant predictors of responders. Late responders were significantly more likely to have been qualified for longer. CONCLUSIONS: This study has several implications for future postal questionnaire studies of GPs. The optimal timing of reminders may be judged from plotting the cumulative response rate: it is worth sending at least three reminders. There are few parameters that significantly predict GPs who are unlikely to respond; more of these may be included in the sample, or they may be targeted for special attention. Publicly available data may be used readily in the analysis of non-response bias and generalizability.

Adult↗