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PubMed1989

HIV-induced immunodeficiency. Relatively preserved phytohemagglutinin as opposed to decreased pokeweed mitogen responses may be due to possibly preserved responses via CD2/phytohemagglutinin pathway.

We studied the proliferative response of PBL to the mitogens PHA and PWM and Candida albicans Ag in 301 HIV seropositive homosexual men, of whom 55 had AIDS. The responses to PHA were reduced only in the clinically ill HIV seropositive subjects. In contrast, the responses to PWM were profoundly reduced in most HIV seropositive subjects including the asymptomatic group. Further analysis of 16 HIV seropositive subjects showed that the proliferative responses were reduced in both CD4 and CD8 T cell subsets. A total of 15 HIV seropositive individuals with low responses to PWM, of whom seven had AIDS and eight controls were chosen for the following studies. Expression of T3, Ti, delta receptors, and CD2 was investigated and showed an increased percentage of CD2 receptors positive cells in HIV seropositive subjects without AIDS. The proliferative responses of PBL to stimulation with PHA, PWM, antibodies to CD3, or antibodies to CD2 were investigated and showed significant correlation in controls, whereas in contrast, only the responses to PHA and CD2ab correlated in patients with AIDS. The proliferative responses to CD2ab and CD3ab in controls were larger than the responses to both PHA and PWM. In patients, these responses were less suppressed than the responses to PWM indicating that stimulation with mitogens is more complex than a simple stimulation of Ti/T3 and CD2 receptors. Further investigations were done on resting T cells, i.e., lymphocytes depleted of macrophages and pre-activated cells. Addition of PHA to these cells resulted in preactivation with expression of IL-2R (CD25) but not in proliferation. In contrast, addition of PHA plus SRBC, which bind to the CD2 receptors caused IL-2R expression, IL-2 production, and proliferation. Addition of PWM + SRBC did not result in proliferation. A comparison of the responses to PHA + SRBC of resting T cells from 26 HIV seropositive individuals, of whom seven had AIDS and 12 seronegative controls, showed that these responses were normal or only slightly decreased in the 19 seropositive men without AIDS whereas it was decreased in AIDS patients. Nevertheless, all AIDS patients showed clear-cut responses in this assay. Thus, the discrepancy between responses to PHA and PWM may be explained by an at least partially preserved function of the PHA/CD2-dependent pathway. We suggest that the defect induced by the HIV infection primarily concerns T3/Ti-induced responses.

Acquired Immunodeficiency Syndrome↗

PubMed1984

Agglutinin responses to Salmonella pullorum in Japanese quail selected for plasma cholesterol response to adrenocorticotropin and a model describing the dynamics of the response.

Japanese quail from the S16 generation of lines selected for high (HR) and low (LR) plasma cholesterol response to adrenocorticotropin (ACTH), and the randombred control line (C) from which the selected lines had been derived, were immunized with a heat-killed Salmonella pullorum antigen. Plasma from blood samples taken at 0,5,8, and 12 days postimmunization was titered for total agglutinin levels. A quadratic equation and its first derivative, calculated for each bird, produced mean values by line for maximum titers, mean day of maximum titer, and rate of titer decline. Results indicated that the LR line had significantly lower titers than the HR or C lines but that the HR line reached maximum titer later than the LR line. The rate of titer decline was fastest in the C line.

Adrenocorticotropic Hormone↗

PubMed1981

A genetic locus responsible for salmonella susceptibility in BSVS mice is not responsible for the limited T-dependent immune responsiveness of BSVS mice.

BSVS mice are known to be highly susceptible to salmonella infection. We have shown that the bulk of the difference in susceptibility between BSVS and salmonella-resistant A/J mice is the result of a genetic difference at a single locus not closely linked to H-2, Igh-C, or Hbb, and not X-linked. We have backcrossed the A/J allele at this locus into BSVS mice for 8 successive generations and have demonstrated that the salmonella resistance afforded by this allele is not the result of a restoration of the generalized poor T-dependent responsiveness of BSVS mice. The salmonella resistance locus we have examined with these 2 strains is probably the same as the Ity locus described by others.

Animals↗

PubMed2005

Involvement of the cannabinoid CB1 receptor in the opioid inhibition of the response to cholecystokinin and acute withdrawal response.

Numerous recent studies have reported major functional interactions between cannabinoid and opioid systems. These interactions can be studied in the myenteric plexus-longitudinal muscle isolated preparations. We had previously shown that in the guinea-pig ileum (GPI), the opioid acute withdrawal response is under the inhibitory control of several systems; mu-opioid agonist exposure indirectly activates the kappa-opioid system; conversely, exposure to a kappa-opioid agonist indirectly activates the mu-system; the indirectly activated opioid system inhibits the withdrawal response. The adenosine A1 system is also indirectly activated by opioids and it inhibits the withdrawal response. We had also shown that indirect activation is prevented or antagonized by cholecystokinin (CCK-8). In GPI preparations briefly exposed to the mu-agonist, dermorphine (DERM) and then challenged with naloxone (NL), the cannabinoid CB1 antagonist, SR141716 (SR), increased the withdrawal responses to NL, but only did so in presence of a kappa-opioid and an adenosine A(1) antagonist. Under similar experimental conditions, SR also enhances the kappa-opioid withdrawal response. In opioid agonist/CCK-8/NL tests, SR antagonized the inhibition of the tissue response to CCK-8 induced by the mu- or kappa-opioid agonist and increased the kappa-withdrawal response, but not the mu-withdrawal response. However, the dose-response curve against dermorphine inhibition of the response to CCK-8 was bell-shaped and the highest SR concentration also significantly decreased the mu-withdrawal response. In preparations exposed to dermorphine or to the kappa-agonist, U-50,488H, the cannabinoid agonist WIN 55,212-2 increased the opioid-induced inhibition of the tissue response to CCK-8 and decreased the NL-induced responses. These results show that opioid exposure may also activate the cannabinoid CB1 system, which leads to an inhibition of the opioid acute withdrawal response. This phenomenon and the antagonistic effect of SR on the opioid-induced inhibition of the response to CCK-8 suggest that reciprocal interaction between opioid and cannabinoid systems are operating in the enteric nervous system.

Acute Disease↗

PubMed2007

On modelling response propensity for dwelling unit (DU) level non-response adjustment in the Medical Expenditure Panel Survey (MEPS).

Non-response is a common problem in household sample surveys. The Medical Expenditure Panel Survey (MEPS), sponsored by the Agency for Healthcare Research and Quality (AHRQ), is a complex national probability sample survey. The survey is designed to produce annual national and regional estimates of health-care use, expenditures, sources of payment, and insurance coverage for the U.S. civilian non-institutionalized population. The MEPS sample is a sub-sample of respondents to the prior year's National Health Interview Survey (NHIS) conducted by the National Center for Health Statistics (NCHS). The MEPS, like most sample surveys, experiences unit, or total, non-response despite intensive efforts to maximize response rates. This paper summarizes research on comparing alternative approaches for modelling response propensity to compensate for dwelling unit (DU), i.e. household level non-response in the MEPS.Non-response in sample surveys is usually compensated for by some form of weighting adjustment to reduce the bias in survey estimates. To compensate for potential bias in survey estimates in the MEPS, two separate non-response adjustments are carried out. The first is an adjustment for DU level non-response at the round one interview to account for non-response among those households subsampled from NHIS for the MEPS. The second non-response adjustment is a person level adjustment to compensate for attrition across the five rounds of data collection. This paper deals only with the DU level non-response adjustment. Currently, the categorical search tree algorithm method, the chi-squared automatic interaction detector (CHAID), is used to model the response probability at the DU level and to create the non-response adjustment cells. In this study, we investigate an alternative approach, i.e. logistic regression to model the response probability. Main effects models and models with interaction terms are both evaluated. We further examine inclusion of the base weights as a covariate in the logistic models. We compare variability of weights of the two alternative response propensity approaches as well as direct use of propensity scores. The logistic regression approaches produce results similar to CHAID; however, using propensity scores from logistic models with interaction terms to form five classification groups for weight adjustment appears to perform best in terms of limiting variability and bias. Published in 2007 by John Wiley & Sons, Ltd.

Family Characteristics↗

PubMed2006

Response bias induced in rats by response effects.

Two experiments examined whether response choice in rats is affected by the presentation of response-produced stimuli. Rats were first trained to emit two different responses, with each response producing a unique auditory stimulus. Subsequently, the former response-produced stimuli were presented while the two response options were freely available. Presentation of a former response-produced stimulus caused the rats to choose more frequently the response option that had previously produced that specific stimulus over the other response option. However, although statistically significant, this response-biasing effect was numerically weak and was only apparent when the stimuli no longer had a general response-activating effect. Moreover, in the case of relatively short presentations of the stimuli, the response-biasing effect was only present if, during testing, the responses continued to produce the auditory stimuli according to the response-effect mapping used during training. These results were discussed in terms of possible underlying associations and were contrasted with previous results from analogous human studies on action control by response-produced stimuli.

Analysis of Variance↗

PubMed1988

Response of vestibular neurons to head rotations in vertical planes. II. Response to neck stimulation and vestibular-neck interaction.

1. We have studied the responses of neurons in the lateral and descending vestibular nuclei of decerebrate cats to stimulation of neck receptors, produced by rotating the body in vertical planes with the head stationary. The responses to such neck stimulation were compared with the responses to vestibular stimulation produced by whole-body tilt, described in the preceding paper. 2. After determining the optimal vertical plane of neck rotation (response vector orientation), the dynamics of the neck response were studied over a frequency range of 0.02-1 Hz. The majority of the neurons were excited by neck rotations that brought the chin toward the ipsilateral side; most neurons responded better to roll than to pitch rotations. The typical neck response showed a low-frequency phase lead of 30 degrees, increasing to 60 degrees at higher frequencies, and a gain that increased about threefold per decade. 3. Neck input was found in about one-half of the vestibular-responsive neurons tested with vertical rotations. The presence of a neck response was correlated with the predominant vestibular input to these neurons; neck input was most prevalent on neurons with vestibular vector orientations near roll and receiving convergent vestibular input, either input from both ipsilateral vertical semicircular canals, or from canals plus the otolith organs. 4. Neurons with both vestibular and neck responses tend to have the respective orientation vectors pointing in opposite directions, i.e., a head tilt that produces an excitatory vestibular response would produce an inhibitory neck response. In addition, the gain components of these responses were similar. These results suggest that during head movements on a stationary body, these opposing neck and vestibular inputs will cancel each other. 5. Cancellation was observed in 12 out of 27 neurons tested with head rotation in the mid-frequency range. For most of the remaining neurons, the response to such a combined stimulus was greatly attenuated: the vestibular and neck interaction was largely antagonistic. 6. Neck response dynamics were similar to those of the vestibular input in many neurons, permitting cancellation to take place over a wide range of stimulus frequencies. Another pattern of interaction, observed in some neurons with canal input, produced responses to head rotation that had a relatively constant gain and remained in phase with position over the entire frequency range; such neurons possibly code head position in space.

Animals↗

PubMed2002

Clinical response after intradermal immature dendritic cell vaccination in metastatic melanoma is associated with immune response to particulate antigen.

Metastatic melanoma is poorly responsive to treatment, and immunotherapeutic approaches are potentially beneficial. Predictors of clinical response are needed to identify suitable patients. We sought factors associated with melanoma-specific clinical response following intradermal vaccination with autologous melanoma peptide and particulate hepatitis B antigen (HBsAg)-exposed immature monocyte-derived dendritic cells (MDDC). Nineteen patients with metastatic melanoma received a maximum of 8, 2-weekly vaccinations of DC, exposed to HBsAg in addition to autologous melanoma peptides. A further 3 patients received an otherwise identical vaccine that did not include HBsAg. Patients were assessed 1-2 monthly for safety, disease volume, and cellular responses to HBsAg and melanoma peptide. There was no significant toxicity. Of 19 patients receiving HBsAg-exposed DC, 9 primed or boosted a cellular response to HBsAg, and 10 showed no HBsAg response. HBsAg-specific responses were associated with in vitro T cell responses to melanoma peptides and to phytohemagglutinin (PHA). Zero out of 10 non-HBsAg-responding and 4/9 HBsAg-responding patients achieved objective melanoma-specific clinical responses or disease stabilization - 1 complete and 2 partial responses and 1 case of stable disease ( P=0.018). Development of melanoma-specific cellular immunity and T cell responsiveness to mitogen were greater in the group of patients responding to HBsAg. Therefore stimulation of an immune response to nominal particulate antigen was necessary when presented by melanoma peptide-exposed immature DC, to achieve clinical responses in metastatic melanoma. Since general immune competence may be a determinant of treatment response, it should be assessed in future trials on DC immunotherapy.

Adjuvants, Immunologic↗

PubMed2000

The pattern of response to interferon alpha (alpha-IFN) predicts sustained response to a 6-month alpha-IFN and ribavirin retreatment for chronic hepatitis C. TVVH Study Group.

BACKGROUND/AIMS: In chronic hepatitis C, interferon-alpha (alpha-IFN) and ribavirin combination therapy improves sustained response compared to alpha-IFN monotherapy, both in naive patients and in previous alpha-IFN relapsers, but the efficacy of such therapy remains limited in non-responder cases. The aim of this study was to assess whether the pattern of response to alpha-IFN alone may predict sustained response to combination therapy during retreatment. METHODS: Fifty previous alpha-IFN relapsers and 50 previous alpha-IFN non-responders were retreated with a high alpha-IFN dose (6 MU/thrice weekly for 2 months; induction phase) and then randomised to continue with alpha-IFN alone (3 MU/thrice weekly) or to receive combination therapy (3 MU/thrice weekly of alpha-IFN and 1000-1200 mg/daily of ribavirin) for an additional 6 months according to the biochemical response to alpha-IFN shown after the induction phase. All patients were also evaluated for virological and histological response. RESULTS: Eleven of 25 (44%) relapsers treated with combination therapy and 4/25 (16%) treated with alpha-IFN alone achieved a sustained response. The corresponding figures among non-responders were 1/25 (4%) and 0/25, respectively. Among 26 patients with a complete ALT and HCV-RNA response after 2 months of alpha-IFN, sustained response was seen in 11/14 (79%) treated with combination therapy and in 4/12 (33%) treated with alpha-IFN alone (p=0.05). On the other hand, of 74 cases still HCV-RNA positive after 2 months of alpha-IFN alone, biochemical and virological end of therapy response was better with combination therapy (11/36; 30.5%) compared to alpha-IFN alone (4/38; 10.5%), but only one patient developed a sustained response (1/36; 3%). CONCLUSIONS: The retreatment with a 6-month combination therapy was associated with a high rate of sustained response only in patients showing a complete biochemical and virological response to alpha-IFN alone. Longer retreatment with combination therapy may be needed to achieve a sustained response in patients without a prompt virological response to alpha-IFN.

Adult↗

PubMed2003

EMG responses evoked by the termination of galvanic (DC) vestibular stimulation: 'off-responses'.

OBJECTIVE: Vestibular responses in soleus electromyography (EMG) evoked by the sudden onset of galvanic (DC) stimulation ('on-responses') have been described in detail previously. The aim of the present study was to describe responses in soleus triggered by the termination of galvanic stimulation ('off-responses'). METHODS: In 10 healthy human subjects, we studied responses to transmastoid (bilateral) stimuli of 200 ms and 2 s average duration and 3 or 4 mA intensity. We obtained both on- and off-responses using the same raw data. EMG activity was recorded onto tape while current pulses of systematically varying duration were delivered. Averaged on-responses were obtained by triggering from the beginning of the current pulses. Averaged off-responses were obtained by triggering from the termination of the current pulses. RESULTS: Short-latency (SL) and medium latency (ML) off-responses were both obtained in all but one study. The SL and the ML components of the off-responses were present and had similar latencies and amplitudes, but opposite excitability, to the on-responses obtained with the same stimuli. CONCLUSIONS: Off-responses to galvanic vestibular stimulation can be recorded from soleus EMG. Our findings imply that vestibular SL and ML reflex responses in the legs are dependent on the change in the rate of vestibular nerve discharge, not its absolute level. Both on- and off-responses have properties appropriate to a role in maintaining body stability.

Adult↗

PubMedDate not supplied

Agonist concentration-dependent differential responsivity of a human platelet purinergic receptor: pharmacological and kinetic studies of aggregation, deaggregation and shape change responses mediated by the purinergic P2Y1 receptor in vitro.

Platelet shape change (SC), aggregation and deaggregation responses are integral components of hemostasis that are elicited and modulated in vivo by the simultaneous activation of several membrane receptors. Selective activation of the purinergic P2Y1 receptor in vivo elicits a sustained SC and a small, transient aggregation response that is reversed rapidly by a robust deaggregation response (Platelets 2003; 14: 89). Using a kinetics-based turbidimetric approach to study the modulation of these concurrent components of human platelet responses, we demonstrate that these P2Y1 receptor-related responses and a number of their kinetic and steady-state characteristics are differentially elicited and modulated. P2Y1 receptor agonist concentrations that elicited aggregation (pEC50 for ADP, 2-MeSADP; 5.88, 6.69) were 10-fold greater than those that elicited SC (7.33, 7.67). The magnitude of the aggregation response was agonist concentration-dependent, saturable and was associated with an agonist concentration-dependent deceleration of the deaggregation response. Gi-coupled receptor (alpha 2A-adrenoceptor, EP3 and P2Y12 receptors) agonists also enhanced aggregation through deceleration of the deaggregation response, and an inhibitor of PI3K activity (wortmannin) inhibited aggregation through acceleration of the deaggregation response. Neither treatment affected the extent or the kinetics of the SC response. The aggregation but not the SC response was rapidly desensitized by P2Y1 receptor activation by ADP. The affinity of the presence of a single P2Y1 receptor subtype. The differential characteristics and modulation of the SC and aggregation responses by a single receptor support the idea that different signaling pathways activated at different occupancy states of the same receptor underlie the two responses. P2Y1 receptor-mediated platelet aggregation and SC responses provide a convenient model for studying the phenomenon of agonist-directed signaling by differential occupancy of the same membrane receptor.

Adenosine Diphosphate↗

PubMed1997

Dopaminergic responses in the Fischer 344 rat heart: preserved chronotropic and dromotropic responses with aging.

BACKGROUND: Marked decreases in cardiac responses to beta-adrenergic stimuli have been found in cellular, animal, and human models of physiologic aging. As another probe of receptor-regulated cardiovascular changes with aging, responses to dopamine were studied. Responses were studied with and without depletion of myocardial catecholamines to eliminate effects secondary to myocardial catecholamine release. METHODS: Responses of heart rate (A-A intervals), atrioventricular conduction (AV intervals and AV Wenckebach block cycle length) to 0-50 microM dopamine were studied in Langendorff perfused hearts from 10 mature (6.2 +/- 0.8 mo, mean +/- SD) and 9 senescent (23.6 +/- 0.7 mo) Fischer 344 rats and in hearts from 10 mature (5.3 +/- 0.4 mo) and 8 senescent (23.9 +/- 0.8) Fischer 344 rats after myocardial catecholamine depletion by reserpine (0.25 mg/kg i.p. x 5 days). RESULTS: Dopamine decreased A-A (p < .0001) and AV conduction intervals (p < .0001) and increased peak developed pressure (p < .0001) and dP/dt (p < .001) in hearts from nonreserpine treated mature and senescent rats. Greater decreases in A-A intervals and AV conduction were seen in senescent compared to mature hearts (p < .0001). Contractile responses were greater in mature hearts (p < .001). After reserpine, A-A interval and paced AV conduction dose vs response relationships shifted rightward (p < .0001), but peak responses and age-related differences in responses were not significantly affected. In contrast, increases in peak developed pressure were greatly reduced in mature hearts (p < .0001) and age-related differences in contractile responses to dopamine were eliminated in hearts from reserpine-treated rats. CONCLUSIONS: (a) A-A interval and AV conduction responses to dopamine were greater in senescent hearts even after catecholamine depletion, suggesting age-related differences in sinus and AV nodal responses to direct dopaminergic stimuli exist. (b) Age-related differences in contractile responses to dopamine were eliminated by reserpine suggesting basal age-related differences in response were secondary to age-related differences in responses to myocardial catecholamine release.

Aging↗

PubMed1983

Slope of the dose-response curve: usefulness in assessing bronchial responses to inhaled histamine.

The value of determining the slope of the histamine dose-response curve, in addition to the histamine provocation concentration producing a 20% reduction in FEV1 (PC20-FEV1), was assessed by analysis of histamine dose-response curves in 40 patients selected as having a wide range of increased non-specific bronchial responsiveness to inhaled histamine. The histamine dose-response curves were found to be fit the linear curve (dose v response, mean r2 = 0.97) better than the logarithmic curve (log dose v response, mean r2 = 0.93), the difference being significant (p less than 0.001). There was a strong negative correlation between the PC20-Fev1 and the slope (r = -0.98, p much less than 0.001) and a weak negative correlation between the PC20-FEV1 and the log-dose-response slope (r = -0.38, p greater than 0.05). Sixteen normal subjects and 16 asthmatic patients were compared on the basis of histamine dose-response curves measuring fal in sGaw. In this study there was no difference between r2 for the linear determination and for the logarithmic determination (0.91 v 0.90, p less than 0.05). The PC35-sGaw showed a strong negative correlation with the dose-response slope (r = -0.95, p much less than 0.01) and no correlation with the log-dose-response slope (r = 0.09, p greater than 0.05). In the two studies there appeared to be little information gained from the determination of either the dose-response slope or the log-dose-response slope. The slope and the PC20-FEV1 were equally reproducible, duplicate determinations showing less than a two-fold difference in 14 of 15 paired PC20 measurements and in 13 of 15 paired slope measurements. In summary, the slope of the histamine dose-response curve appears to fit the linear model better than the logarithmic model. It is feasible to calculate it from the results of a standardised histamine inhalation test; determination of either the slope or the log-dose-response slope, however, appears to add little useful information. It is recommended that bronchial provocation test results should be expressed in terms of a threshold concentration such as the PC20-FEV1 or the PC35-sGaw.

Adult↗

PubMed2006

Angiotensin-(1-7) potentiates responses to bradykinin but does not change responses to angiotensin I.

Angiotensin-(1-7) (Ang-(1-7)), a bioactive peptide in the renin-angiotensin system, has counterregulatory actions to angiotensin II (Ang II). However, the mechanism by which Ang-(1-7) enhances vasodepressor responses to bradykinin (BK) is not well understood. In the present study, the effects of Ang-(1-7) on responses to BK, BK analogs, angiotensin I (Ang I), and Ang II were investigated in the anesthetized rat. The infusion of Ang-(1-7) (55 pmol/min i.v.) enhanced decreases in systemic arterial pressure in response to i.v. injections of BK and the BK analogs [Hyp3, Tyr(Me)8]-bradykinin (HT-BK) and [Phe8psi (CH2-NH) Arg9]-bradykinin (PA-BK) without altering pressor responses to Ang I or II, or depressor responses to acetylcholine and sodium nitroprusside. The angiotensin-converting enzyme (ACE) inhibitor enalaprilat enhanced responses to BK and the BK analog HT-BK without altering responses to PA-BK and inhibited responses to Ang I. The potentiating effects of Ang-(1-7) and enalaprilat on responses to BK were not attenuated by the Ang-(1-7) receptor antagonist A-779. Ang-(1-7)- and ACE inhibitor-potentiated responses to BK were attenuated by the BK B2 receptor antagonist Hoe 140. The cyclooxygenase inhibitor sodium meclofenamate had no significant effect on responses to BK or Ang-(1-7)-potentiated BK responses. These results suggest that Ang-(1-7) potentiates responses to BK by a selective B2 receptor mechanism that is independent of an effect on Ang-(1-7) receptors, ACE, or cyclooxygenase product formation. These data suggest that ACE inhibitor-potentiated responses to BK are not mediated by an A-779-sensitive mechanism and are consistent with the hypothesis that enalaprilat-induced BK potentiation is due to decreased BK inactivation.

Angiotensin I↗

PubMed2001

Do the acute platelet responses of patients with immune thrombocytopenic purpura (ITP) to IV anti-D and to IV gammaglobulin predict response to subsequent splenectomy?

The acute platelet response to Intravenous Gammaglobulin (IVIG) has been reported to predict response to subsequent splenectomy of patients with ITP. The current study was undertaken to determine if the platelet response to IV anti-D (Winrho-SDF) predicts response to subsequent splenectomy. The 61 HIV-uninfected children and adults in this study had taken part in the pre-licensing studies of IV anti-D and were all those who not only had evaluable platelet responses to IV anti-D but also had undergone splenectomy and had information available describing its 1-year outcome. Results of treatment with IVIG were available in 38 of these 61 patients. Neither response to the initial infusion of IV anti-D, nor response to the initial or last IVIG, predicted the response in either children or adults to subsequent splenectomy. However, response to the last anti-D infusion in adults was strongly correlated (P = 0.003) to response to subsequent splenectomy as was hemolysis >/=2.0 gm/dl after IV anti-D (P = 0.03). There was no overall relationship between response to IV anti-D or IVIG, and response to subsequent splenectomy. However, a good platelet response in adults to the last IV anti-D and a hemoglobin decrease >/=2.0 gm/dl both appeared to predict response to subsequent splenectomy.

Adolescent↗

PubMed1986

Electrophysiological differences between bone cell clones: membrane potential responses to parathyroid hormone and correlation with the cAMP response.

Electrophysiological measurements on three clonally derived bone cell populations showed a positive correlation between longer-term hyperpolarizing membrane potential responses to parathyroid hormone (PTH) and an intracellular cAMP response to PTH. One clone (RCJ 1.20) had no sustained electrophysiological response and no cAMP response to PTH. Another clone (ROS 17/2.8) had both a sustained hyperpolarizing response and a cAMP response to PTH. The third clone (RCB 2.2) initially had both an electrophysiological response and a cAMP response to PTH, but both responses were lost after prolonged growth in culture. Application of dibutyryl cAMP to RCJ 1.20 and ROS 17/2.8 cells produced both transient and sustained hyperpolarizing responses. Application of isobutylmethylxanthine produced a sustained hyperpolarization. These results suggest that the hyperpolarizing response to PTH is related to a cAMP-mediated increase in Ca2+ conductance, which leads to an increase in Ca2+-activated K+ conductance. The pronounced membrane potential spikes and fluctuations that occur in some of the clonal lines were shown to be unrelated to the hyperpolarizing response to PTH. This was demonstrated by the lack of correlation between the occurrence of the spikes or fluctuations and the occurrence of the hyperpolarizing response to PTH in the various cell lines, by the lack of effect of PTH on the spikes and fluctuations, and by the lack of effect on the hyperpolarizing response to PTH of verapamil and quinine, both of which significantly reduce the spikes and fluctuations.

Bone and Bones↗

PubMed1981

H-2 effects on cell-cell interactions in the response to single non-H2 alloantigens. IV. Variations in the proliferative response to H-Y and H-3.

Individual mice were tested for their proliferation T-cell response to H-Y- and H-3-incompatible stimulator cells in secondary mixed lymphocyte culture. Responders expressing the H-2b haplotype were restricted in their response to stimulators presenting H-Y and H-3 in the context of H-2b. Lymphocytes from individual B10 females proliferated in response to H-Y presented with I-Ab and Db. The ratio of I-Ab/Db-restricted responses varied between individual responders, indicating significant qualitative variation between genetically identical responders. The majority of the proliferative response in all tested mice was restricted to the entire H-2b haplotype suggesting complementation of I-Ab- and Db-region genes in presenting the H-Y antigen. Similar observations were made in the response of individual B10.LP mice to the H-3 antigen. H-3-specific, proliferating T cells were restricted to H-3 antigen presented with KbAb and Db with significant variation between individuals in proliferative response to H-3 plus KbAb and Db. In contrast to the response to H-Y, the proliferative response to H-3 plus H-2b could be accounted for by the summation of the proliferative responses to H-3 plus KbAb and Db. These observations demonstrate that the proliferative response to non-H-2H antigens in the context of I-region determinants is not a sine qua non for the T-cell response to these antigens. Further, the individual qualitative and quantitative variation observed with individual genetically identical mice has strong implications for our knowledge of intrastrain variation in immune responsiveness and the characterization of inbred strains for immune responsiveness.

Animals↗

PubMed1992

Auditory response properties and spatial response areas of single neurons in the pontine nuclei of the big brown bat, Eptesicus fuscus.

Using free-field acoustic stimulation conditions, we studied the response properties and spatial sensitivity of 146 pontine neurons of the big brown bat, Eptesicus fuscus. The best frequency (BF) and minimum threshold (MT) of a pontine neuron were first determined with a sound broadcast from a loudspeaker placed ahead of the bat. A BF sound was delivered from the loudspeaker as it moved across the frontal auditory space in order to locate the response center at which the neuron had its lowest MT. Then the basic response properties of the neuron to a sound delivered from the response center were studied. As in inferior collicular and auditory cortical neurons, pontine neurons can be characterized as phasic responders, phasic bursters and tonic responders. They have both monotonic and non-monotonic intensity-rate functions. However, most of them are broadly tuned as are cerebellar neurons. Auditory spatial sensitivity was studied for 144 pontine neurons. In 9 neurons, variation of MT with a BF sound delivered from several azimuthal and elevational angles along the horizontal and vertical planes crossing the neuron's response center was measured. In addition, variation in the number of impulses with several stimulus intensities at 10 dB increments above a neuron's MT delivered from each angle was also studied. The auditory spatial sensitivity of other pontine neurons was studied by measuring the response area of each neuron with stimulus intensities at 3, 5, 10, 15 or 40 dB above its lowest MT. The response areas of pontine neurons expanded asymmetrically with stimulus intensity, but the size of the response area was not correlated with either MT or BF. In half of the pontine neurons studied, the response area expanded greatly and eventually covered almost the entire frontal auditory space. The response areas of the other half of the pontine neurons only expanded to a restricted area of frontal auditory space. Two possible neural mechanisms underlying these two types of response areas are hypothesized. The response centers of all 144 neurons were located within a small area of the frontal auditory space. The locations of response centers of these neurons are not correlated with their BFs. The distribution pattern of these response centers is comparable to that of superior collicular and cerebellar neurons but is different from that of inferior collicular and auditory cortical neurons. The results of our study suggest that auditory information is integrated in the pontine nuclei before being further sent into the cerebellum.

Acoustic Stimulation↗