Extension of Rapid Phase-Contrast Magnetic Resonance Imaging Using BRISK in Multidirectional Flow

We developed BRISK–CON–VPS, a rapid phase-contrast cine approach that is a hybrid of the BRISK–VPS (Block Regional Interpolation Scheme for k-space) and conventional (CONV–VPS) scanning employing k-space views per segment (VPS). BRISK–CON–VPS allows data acquisition approximately four times faster than CONV–VPS imaging and has the advantage compared to BRISK–VPS that it can potentially be incorporated into real-time applications. In BRISK–CON–VPS contiguous regions of k-space are sampled using a views per segment factor that is varied as a function of distance from the k-space center. Computational fluid dynamics (CFD) data were used to simulate CONV–VPS, BRISK–VPS, and BRISK–CON–VPS. BRISK–CON–VPS was simulated by incrementing the VPS progressively with increasing distance from the k-space origin while BRISK–VPS was simulated using a uniform VPS applied to the sparse sampling scheme. Simulations showed that up to a base VPS of 5, both BRISK–CON–VPS and BRISK–VPS retained excellent axial-velocity accuracy. Secondary in-plane velocity flow fields were well represented with BRISK–CON–VPS and BRISK–VPS up to a base VPS of 3. CONV–VPS, BRISK–CON–VPS, and BRISK–VPS were applied in vivo and shown to provide comparable quantitative flow data. BRISK–CON–VPS accomplishes breath-hold acquisitions as efficiently as BRISK–VPS, but without requiring data interpolation or under-sampling k-space.     

Role of 4-1BB in immune responses

4–1BB is an inducible T cell surface receptor which belongs to the tumor necrosis factor receptor superfamily, a group of cysteine–rich cell–surface molecules. Both human and mouse 4–1BB recently received HLDA nomenclature. Naive T cells lack 4–1BB, which is not only induced upon T cell activation, but also remains on activated T cells. The natural ligand for 4–1BB, 4–1BBL is also induced and is found on activated antigen–presenting cells. Cross–linking of the 4–1BB molecule by agonistic antibody transmits a distinct and potent co–stimulatory signal leading to the activation and differentiation of CD4⁺and CD8⁺cells. 4–1BB transmits signals through the TRAF2–NIK pathway and activates NF–κB. Signals relayed through 4–1BB inhibit activation–induced cell death and rescue the immune system during the post–CD28 phase. Antibodies to the 4–1BB molecule can increase GVHD, accelerate the rejection of cardiac allograft and skin transplants, and eradicate established tumors. Interference with the 4–1BB–4–1BBL pathway may be of therapeutic use in the treatment of HIV infection. 4–1BB–deficient mice show dysregulated immune responses and mount elevated Ig responses to T–dependent antigens.     

Antigenic relationships among the 47 human adenoviruses determined in reference horse antisera

Summary Reference equine antisera to all 47 serotypes of human adenoviruses presently described have been prepared and evaluated by reciprocal neutralization and hemagglutination-inhibition tests. All tests were carried to endpoint dilutions a minimum of five times in each direction to give accurate values for homologous and heterologous antibody titers. Significant cross-reactions in the horse antisera were compared to similar data obtained from rabbit antisera. Using this analysis, major antigenic relationships exist among types 12–18–31 of subgenus A, types 7–11–14 and 34–35 of subgenus B, types 8–9–10, 10–19–37, 13–38–39, 15–22–42, 20–47, 24–32–33–46, and 29–45 of subgenus D, types 16-4 between subgenera B and E, and types 40–41 of subgenus F. Across all subgenera, types 8, 10, 13, 15, 17, 19, 26, 29, 39, 40, and 43 have antigenic moieties found most frequently in other types, averaging 12 heterologous reactions per type when summing both tests in both directions. Types 20, 30, 32, and 45 exhibit shared determinants slightly less often, with a mean of 8 heterologous reactions per type.     

An in vitro investigation of aorta and corpus cavernosum from eNOS and nNOS gene-deficient mice

In order to ascertain the relative contribution of the endothelial and neuronal nitric oxide (NO) synthase isoforms on NO-dependent vascular and nerve function in vitro, aorta and corpus cavernosum from mice deficient in their expression (eNOS–/– and nNOS–/–) were isolated in organ baths for tension measurements. Agonist or electrical field stimulation (EFS) evoked nerve-mediated responses were compared against wild-type controls. In aortas from nNOS–/– mice, contraction responses to phenylephrine were increased. Conversely, endothelium-dependent relaxation (EDR) to acetylcholine (ACh) was decreased. In contrast, eNOS–/– aortas showed decreased sensitivity to phenylephrine and developed a flurbiprofen-sensitive contraction to ACh, and sensitivity to the NO-donor sodium nitroprusside was increased. In cavernosum from eNOS–/– and nNOS–/– mice, maximum contractions to phenylephrine and EFS, and relaxation responses to nitroprusside, were increased. As in aorta, ACh addition led to a contractile response in eNOS–/– cavernosum. Maximum EFS induced non-adrenergic, non-cholinergic (NANC) nerve-mediated relaxation was increased in eNOS–/–, whilst being decreased in nNOS–/– cavernosum. These data suggest that whilst NO-dependent vascular function is primarily eNOS mediated, and nerve function nNOS mediated, aorta function may be at least partially reliant on nNOS-related mechanisms. In addition, mechanisms of physiological compensation were observed, which require further study.     

Human basophils as effectors and immunomodulators of allergic inflammation and innate immunity

Abstract Basophils have often stood in the shadow of their tissue–fixed mast cell counterparts which share some, common features, such as high–affinity IgE receptor expression and the ability to release histamine. That rodent mast cells produce a variety of pro–allergic and inflammatory cytokines has further added to the deception that basophils only play a minor role in allergic inflammation. Surprisingly, in humans, basophils, but not mast cells, appear to be the prime early producers of the Th2–type cytokines IL–4 and IL–13, which perform several crucial functions in initiating and maintaining allergic responses. This putative immunomodulatory role of basophils is supported further by their ability to express CD40 ligand, which, together with IL–4 and IL–13, serve as inductors of B–cell proliferation and class switching to IgE and IgG4. Moreover, human basophils are the main cellular source for rapid IL–4 generation, a mandatory requirement for the development of Th2 responses. Recent specific staining techniques have localised basophils in various tissues affected by allergic diseases and it appears likely, but remains to be proven, that the interaction of basophils, T cells and B cells at these sites propagate pro–allergic immune responses. Additionally, basophil activation is not restricted to antigen–specific IgE crosslinking but can be caused in non–sensitised individuals by parasitic antigens, plant lectins and viral superantigens binding to non–specific IgEs. Finally, the presence of novel IgE–independent receptor targets that cause trafficking and Th2 cytokine release from basophils further underlines their potential role in innate as well as adaptive immunity.     

Autoantibodies against bactericidal/permeability–increasing protein (BPI–ANCA) in cystic fibrosis patients treated with azithromycin

Abstract Autoantibodies against bactericidal/permeability- increasing protein (BPI-ANCA) were found in patients with cystic fibrosis (CF). It is speculated that they represent a marker of the chronic endobronchial infection and sustained inflammatory response in CF. Our aim was to evaluate whether azithromycin (AZM), through its antiinflammatory effect, could affect the level of BPI–ANCA in CF patients. Eighteen patients with CF aged 5.5–36.3 years (median 15.1) were enrolled in a randomised, double– blind, placebo–controlled trial of AZM (250 mg twice a week to 10 patients) or placebo (8 patients) for 12 weeks. BPI–ANCA levels were recorded pre– and post–treatment and compared to a group of 18 matched healthy controls. Chi–square analysis, Kruskal–Wallis and Mann–Whitney tests were used to compare between the groups. Pre– and post–treatment values were compared using the Wilcoxon Signed–Ranked test. BPI–ANCA was found in 12 CF patients (67%) and four (22%) healthy subjects (P<0.001). The mean BPI–ANCA level was 3.94±6.15 U/ml (mean±SD) in healthy subjects and 38.11±42.34 U/ml in CF patients (P=0.023). The mean BPI–ANCA level was higher in patients with Pseudomonas aeruginosa compared to those without (64±35 U/ml and 25±41 U/ml respectively, P=0.032). No change in BPI–ANCA levels occurred in the AZM–treated patients [35 (0–127) U/ml (median (range) and 30 (0–120) U/ml, respectively] or in the placebo group [10 (0–66) U/ml and 13 (0–83) U/ml, respectively]. BPI–ANCA levels are significantly higher in patients with CF compared to healthy controls. BPIANCA levels are higher among patients colonised with P. aeruginosa. Twelve weeks of AZM therapy did not lower the BPI–ANCA level in patients with CF.     

Synthesis and antitumor activity of doxorubicin conjugated stearic acid-g-chitosan oligosaccharide polymeric micelles

Doxorubicin conjugated stearic acid-g-chitosan oligosaccharide polymeric micelles (DOX–CSO–SA) was synthesized via cis-aconityl bond between the anticancer drug doxorubicin (DOX) and stearic acid grafted chitosan oligosaccharide (CSO–SA) in this paper. The CSO–SA micelles had been demonstrated faster internalization ability into tumor cells. Here, the CSO–SA with 6.47% amino substituted degree (SD%) was used to synthesize DOX–CSO–SA. The critical micelle concentration (CMC) was about 0.14 mg mL⁻¹. The micelles with 1 mg mL⁻¹ CSO–SA concentration had 32.7 nm number average diameter with a narrow size distribution and 51.5 mV surface potential. After conjugating with doxorubicin, CMC of DOX–CSO–SA descended; the micellar size increased; and the zeta potential decreased. The DOX–CSO–SA micelles indicated pH-dependent DOX release behavior. The release rate of DOX from DOX–CSO–SA micelles increased significantly with the reductions of the pH for release medium from 7.2 to 5.0. In vitro antitumor activity tests of DOX–CSO–SA micelles against human breast carcinoma (MCF-7) cells and their multi-drug resistant (MCF-7/Adr) cells presented the reversal activity against DOX resistance MCF-7 cells (MCF-7/Adr). The in vivo antitumor activity results showed that DOX–CSO–SA micelles treatments effectively suppressed the tumor growth and reduced the toxicity against animal body than commercial doxorubicin hydrochloride injection.     

Anti-inflammatory properties of zinc protoporphyrin disodium (Zn−PP−2Na)

Anti-inflammatory properties of zinc protoporphyrin disodium (Zn–PP–2Na) were studied. Zn–PP–2Na exhibits anti-allergic action against type III and IV reactions (passive Arthus reaction in rats and tuberculin-induced footpad reaction in mice), but does not affect type I and II reactions (homologous passive cutaneous anaphylaxis in mice and reversed cutaneous anaphylaxis in rats). Zn–PP–2Na also clearly inhibits type II collagen-induced arthritis in mice. The agent inhibits general arthritis symptoms, anti-type-II collagen antibody production and type II collagen-induced delayed type hypersensitivity (DTH) in arthritic mice. Zn–PP–2Na, however, did not affect carrageenin-induced paw edema and histamine- and serotonin-induced skin reactions in rats. Zn–PP–2Na inhibits IL-1-induced mouse lymphocyte proliferation, but does not affect PMA-induced O ₂ ^– generation from guinea-pig neutrophil. These results indicate that Zn–PP–2Na inhibits type II collagen-induced arthritis in mice due to the antagonism of IL-1 activity and the inhibition of DTH against type II collagen.     

Comparison of the central and peripheral antihistamine effects of dimethindene maleate (Fenistil?) and its enantiomers

The H₁ histamine receptor antagonist activity and sedative effects of dimethindene maleate racemate (DIM +/–) (FENISTIL^®) and the individual enantiomers (DIM+ and DIM–) were monitored in parallel in a double-blind, placebo-controlled, cross-over study in 9 healthy subjects. Peripheral antihistamine activity (histamine-induced wheal and flare planimetry) and central effects (electroencephalography (EEG) and self-evaluation on a visual analogue scale (SEVS)) were measured after oral administration of a single dose of DIM+/– (4 mg), DIM+ (2 mg), DIM– (2 mg) and placebo.DIM+/–, DIM+ and DIM– induced decreased SEVS scores. EEG pattern modifications indicative of a sedative effect appeared comparable for DIM+/– and DIM–, especially 2 h after drug intake, whereas DIM+ exhibited spectral differences more marked at 5.5 h. Moreover, DIM+/– and DIM– significantly inhibited the cutaneous reaction to histamine, whereas DIM+ activity was not different from that of placebo, demonstrating that the peripheral antihistamine activity of DIM+/– resided mainly in the DIM– enantiomer.     

Ascorbate–apatite composite and ascorbate–FGF-2–apatite composite layers formed on external fixation rods and their effects on cell activity in vitro

Ascorbate–apatite and ascorbate–fibroblast growth factor-2 (FGF-2)–apatite composite layers were successfully formed on anodically oxidized Ti rods clinically used for external fixation by a one-step procedure at 25 °C, using a metastable supersaturated calcium phosphate solution supplemented with l-ascorbic acid phosphate magnesium salt n-hydrate (AsMg) and FGF-2. The AsMg–apatite and AsMg–FGF-2–apatite composite layers were evaluated in vitro using fibroblastic NIH3T3 and osteoblastic MC3T3-E1 cells. The AsMg–FGF-2–apatite composite layer markedly enhanced the NIH3T3 cell proliferation and procollagen type І gene expression. Without FGF-2, the AsMg–apatite composite layer whose ascorbate content was 3.64 ± 1.27 μg cm⁻² obviously enhanced osteoblastic proliferation and differentiation. However, the AsMg–FGF-2–apatite composite layers whose FGF-2 contents were from 0.15 ± 0.03 to 0.31 ± 0.04 μg cm⁻² inhibited osteoblastic differentiation in vitro. Thus, the AsMg–FGF-2–apatite composite layer should be precipitated on the surface of external fixators attached to skin and soft tissue. On the other hand, the AsMg–apatite composite layer should be precipitated at the part attached to bone tissue.     

Immunogenicity of free synthetic peptides corresponding to T helper epitopes of the influenza HA 1 subunit

Summary Four linear synthetic peptides corresponding to residues 12–29, 50–67, 121–138 and 131–147 of the HA 1 subunit of H 3 subtype influenza virus (NT/60/68) were tested for their capacity to elicit in vivo peptide-specific CD 4⁺ T cells cross reacting with whole virus.By studying the in vitro peptide proliferative response of lymph node cells from mice sensitized in vivo with free peptides emulsified in complete or incomplete Freund adjuvant, it was found that region 12–29 could be recognized by CD 4⁺ T lymphocytes in the context of H-2^k and H-2^b, region 50–67 in association with H-2^b and region 121–138 in the context of H-2^d MHC molecules. Outbred OF 1 mice could recognize regions 50–67 and 121–138.Peptides 50–67 and 121–138 are of potential interest for synthetic vaccine design since they induced in BALB/c (peptide 121–138) and OF 1 (both peptides) mice a CD 4⁺ T cell population that cross reacted with whole virus. The region 50–67 is of particular interest since only few substitutions have been found in this area in natural variants of the H 3 virus subtype.     

Action of the SP2–11 and SP3–11 fragments of substance P on rat peritoneal mast cells

The ability of the SP fragments SP_2–11 and SP_3–11 to release histamine from rat peritoneal mast cells has been compared with that of the whole peptide. SP_1–11 was found to be about 3.4 times more active than SP_2–11 and about 10.4 times more active than SP_3–11. The substance P antagonist [D-Pro⁴, D-Trp^7,9,10] SP_4–11 was equally effective at antagonizing the histamine releasing action of SP_1–11, SP_2–11 and SP_3–11. Benzalkonium chloride was found to be a competitive antagonist of SP and SP_3–11: the dissociation constants for the benzalkonium chloride-receptor interaction being about the same when either SP_1–11 or SP_3–11 was used as the agonist.     

Diurnal variations of serum erythropoietin at sea level and altitude

This study tested the hypothesis that the diurnal variations of serum-erythropoietin concentration (serum-EPO) observed in normoxia also exist in hypoxia. The study also attempted to investigate the regulation of EPO production during sustained hypoxia. Nine subjects were investigated at sea level and during 4 days at an altitude of 4350 m. Median sea level serum-EPO concentration was 6 (range 6–13) U·l^–1. Serum-EPO concentration increased after 18 and 42 h at altitude, [58 (range 39–240) and 54 (range 36–340) U·l^–1, respectively], and then decreased after 64 and 88 h at altitude [34 (range 18–290) and 31 (range 17–104) U·l^–1, respectively]. These changes of serum-EPO concentration were correlated to the changes in arterial blood oxygen saturation (r = –0.60,P = 0.0009), pH (r = 0.67,P = 0.003), and in-vivo venous blood oxygen half saturation tension (r = –0.68,P = 0.004) but not to the changes in 2, 3 diphosphoglycerate. After 64 h at altitude, six of the nine subjects had down-regulated their serum-EPO concentrations so that median values were three times above those at sea level. These six subjects had significant diurnal variations of serum-EPO concentration at sea level; the nadir occurred between 0800–1600 hours [6 (range 4–13) U·l^–1], and peak concentrations occurred at 0400 hours [9 (range 8–14) U·l^–1,P = 0.02]. After 64 h at altitude, the subjects had significant diurnal variations of serum-EPO concentration; the nadir occurred at 1600 hours [20 (range 16–26) U·l^–1], and peak concentrations occurred at 0400 hours [31 (range 20–38) U·l^–1,P = 0.02]. This study demonstrated diurnal variations of serum-EPO concentration in normoxia and hypoxia, with comparable time courses of median values. The results also suggested that EPO production at altitude is influenced by changes in pH and haemoglobin oxygen affinity.     

Cyclo-DfKRG peptide modulates in vitro and in vivo behavior of human osteoprogenitor cells on titanium alloys

The first aim of the present study was to investigate the capacity of a cyclo-DfKRG-coated hydroxyapatite–titanium alloy (Ti–HA–RGD) to activate in vitro human osteoprogenitor cells adhesion and differentiation. The second purpose was to examine in vivo the role of a autologous cell seeding on cyclo-DfKRG-functionalized materials to provide bone repair after implantation in femoral condyle of rabbits.Our in vitro results have demonstrated that both titanium alloy functionalized with hydroxyapatite (Ti–HA–RGD and Ti–HA) contributed to higher cell adhesion than titanium alloy alone respectively 85 and 55% vs 15% compared to tissue culture polystyrene after one hour of cell seeding.As for differentiation, after 3 days of culture, Ti–HA presented the highest increase of ALP mRNA of all surfaces studied. Ti–HA–RGD showed an intermediate value about half as high as Ti–HA. Moreover after 3 days, both Ti–HA and Ti–HA–RGD surfaces showed the highest increase of cbfa1 mRNA expression.Two weeks following implantation, in vivo findings revealed that percentage of lacunae contact observed with pre-cellularized Ti–HA–RGD samples remains significantly lower than with Ti–HA group (10.5 ± 9.6 % vs 33.7 ± 11.5 %, P < 0.03). Meanwhile, RGD peptide coating had no significant additional effect on the bone implant contact and area. Moreover, histomorphometry analysis revealed that implantation of pre-cellularized RGD coated materials with ROP cells increased significantly peri-implant fibrous area (24 ± 11.6% vs 3 ± 1.7% for Ti–HA–RGD, P < 0.02). RGD coatings demonstrated osteoblastic adhesion, differentiation and in vivo bone regeneration at most equivalent to HA coatings.     

The effects of food additives and aflatoxin B1 on histamine release from human mast cells

The effects of the food additives tartrazine, biphenyl, sorbic acid and the mycotoxin contaminant aflatoxin B₁ were studied in mechanically isolated human adenoidal mast cells. Tartrazine inhibited the spontaneous histamine release in the concentration range of 10^–9 to 10^–5 M and the concanavalin A (Con A)-induced histamine release dose-dependently at 10^–11–10^–5 M [10.3%–31.6%]. Biphenyl [10^–9–10^–6 M] neither influenced the spontaneous nor the stimulated histamine release. Sorbic acid [10^–7–10^–4 M] slightly inhibited the Con A-induced release at the highest concentration tested. Aflatoxin B₁ [10^–10–10^–7 M] did not influence mediator release after a preincubation time of 5 min. Extension of the preincubation period inhibited the histamine release slightly. In summary, none of the tested substances enhanced histamine release from human adenoidal mast cells. Tartrazine even had an inhibitory effect.     

The effect of acetylcholine on chloride transport across the mouse lacrimal gland acinar cell membranes

The mechanisms of Cl^– transport and the effects of acetylcholine (ACh) and electrochemical Cl^– potential changes across the basolateral plasma membrane on intracellular Cl^– activity in the acinar cells of isolated mouse lacrimal glands were studied using double-barreled Cl^–-selective microelectrodes. In the resting state, the basolateral membrane potential (V _m) was about –40 mV and intracellular Cl^– activity was about 35 mmol/l. Addition of ACh (10^–910^–6 mol/l) hyperpolarizedV _m and decreased the Cl^– activity in a dose-dependent manner. ACh (10^–6 mol/l) hyperpolarizedV _m by 20 mV and decreased the cytosolic Cl^– activity with an initial rate of 16.0 mmol/l · min. Reduction of the perfusate Cl^– concentration to 1/9 control depolarizedV _m and decreased cytosolic Cl^– activity at a rate of 1.9 mmol/l · min. AV _m hyperpolarization of 20 mV produced by DC injection to the adjacent cell decreased Cl^– activity at a rate of 4.6 mmol/l · min. DIDS (1 mmol/l) hyperpolarizedV _m by 8 mV with little change in Cl^– activity and increased the input resistance of the cells by 25%. DIDS decreased the rate of change in Cl^– activity induced by low-Cl^– Ringer to 35% of control, but had no effect on the ACh-evoked decrease in the Cl^– activity. Furosemide (1 mmol/l) slightly hyperpolarizedV _m and decreased Cl^– activity at a slow rate but affected Cl^– movements induced by ACh or low-Cl^– Ringer only slightly. Cl^– uptake into the cells was inhibited partially by furosemide. The present results showed that ACh induces an increase in the Cl^– permeability across the luminal plasma membrane and that the basolateral membrane possesses a DIDS-sensitive Cl^– conductance pathway and a furosemide-sensitive Cl^– uptake mechanism.     

Interaction of Histamine and Glucocorticoids with Neural Structures of the Respiratory Tract

The effects of dexamethasone on the actions of histamine on isolated tissue and large bronchus preparations and the interactions of these substances with intramural neural structures were studied. Low histamine concentrations (10^–12–10^–8 g/ml) decreased muscle responses induced by stimulation of preganglionic nerve fibers, while high concentrations (10^–7–10^–4 g/ml) increased these responses. Dexamethasone at concentrations of 10^–7–10^–6 g/ml decreased muscle responses, while concentrations of 10^–5–10^–6 g/ml produced biphasic changes in responses. Dexamethasone decreased the effects of histamine at high concentrations. Atropine eliminated the effects of simultaneous application of histamine and dexamethasone on respiratory tract preparations; hexamethonium blocked the effects of substances associated with decreased responses and had virtually no effect on those potentiating responses. Novocaine eliminated the actions of histamine at low and high concentrations and the dilatory effect of dexamethasone. These experimental results led to the conclusion that changes in the responses of muscles from the rat respiratory tract induced by stimulation of preganglionic nerve fibers were modified by low concentrations of histamine and dexamethasone and that these modifications were associated with interactions of these substances with tracheobronchial receptors.     

Changes in bone marrow hemopoiesis in donor rabbits

Summary It was shown in an experiment on 17 rabbits that animals from which bone marrow had been extracted in amounts of 10–20 ml one time, 2–3 times at intervals of 4–5 months or 7–8 times at intervals of 1–1.5 months were in good condition during the entire experiment and even put on weight. Four animals from which bone marrow was taken in large quantities (25–50 ml 3–4 times at 4–5 months intervals) developed anemia of a hyporegenerative character 12–16 months after the beginning of the experiment, which was followed by a septic conditions with multiple abscesses in the visceral organs. Hence, repeated extractions of large quantities of bone marrow may bring about severe disorders in hemopoietic processes and a reduction in the body resistance.(Presented by Active Member AMN SSSR A. F. Tur) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 60, No. 8, pp. 43–46, August, 1965     

Interactions of morphine with PGE1, isoproterenol,dopamine and aminophylline in rat mast cells; their effect on IgE-mediated14C-serotonin release

The formaldehyde method was used to examine the interactions of morphine with PGE₁, isoproterenol, dopamine and aminophylline in rat mast cells by their effects on IgE-mediated¹⁴C-serotonin release. PGE₁ (2×10^–8–2×10^–5 M), isoproterenol (10^–10–10^–8 M), dopamine (4×10^–8–4×10^–6 M) and aminophylline (6×10^–6–6×10^–4 M) caused dose-related inhibition of the mediator release 1 min after an antigen challenge, and propranolol (10^–7 M) blocked the inhibition by isoproterenol (10^–8 M) but not that by dopamine (4×10^–6 M), while haloperidol (4×10^–6 M) blocked that by dopamine (4×10^–6 M) but not that by isoproterenol (10^–8 M). Morphine (3×10^–7–3×10^–5 M) reversed the inhibitory effects of PGE₁ (2×10^–6 M), isoproterenol (10^–8 M) and dopamine (4×10^–6 M) dose-dependently and stereospecifically; naloxone (2×10^–4 M) antagonized these reversing actions of morphine (3×10^–5 M). Morphine (10^–6–10^–4 M) did not reverse the inhibitory action of aminophylline (6×10^–4 M). These results suggest that the inhibitory responses of mast cells to PGE₁, isoproterenol and dopamine but not to aminophylline in immunological mediator release were reversed by morphine through opioid receptors, and that the inhibition of adenylate cyclase in mast cells is one of the biochemical actions of morphine.     

Uncoupling of Na+H+ from Cl−HCO 3 − exchange under some steady state conditions in rabbit gallbladder

The transapical Cl^– influx and transepithelial Na⁺ transport were measured in rabbit gallbladder. Only 11.7% of the transported Na⁺ was found to be accompanied by HCO ₃ ^– . 10^–4 M SITS eliminated the HCO ₃ ^– dependent fraction of Cl^– influx (50%) but did not significantly alter intracellular Na⁺ activity and Na⁺ transport. Exposure to HCO₃-free salines or to 10^–4 M acetazolamide about halved Cl^– influx and Na⁺ transport. 25 mM SCN^– reduced Cl^– influx to zero, decreased intracellular Na⁺ activity, but only halved Na⁺ transport which under these conditions was abolished only in the absence of HCO ₃ ^– . Exposure to a Cl^–-free saline produced effects similar to those caused by SCN^–. These resuits suggest that when Cl^–/HCO ₃ ^– exchange is inhibited at the apical membrane, Na⁺/H⁺ exchange and transepithelial Na⁺ transfer are unmodified if HCO ₃ ^– is available for transport. The permanent uncoupling of the exchangers and the elevated transepithelial transport of Na⁺ are not due to an increased activity of the parallel Na⁺–Cl^– cotransport but to a redirection of HCO ₃ ^– flux toward the basolateral side.