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J W Wells

Publications and source records attributed to J W Wells.

At least 37 records · Page 2Linked to original sources
PubMed1995

Magnetization transfer and high-dose contrast in early brain infection on magnetic resonance.

RATIONALE AND OBJECTIVES: The authors studied the effect of contrast dose, use of magnetization transfer (MT), and temporal delay on the visualization of contrast enhancement with gadoteridol (Gd HP-DO3A) in a canine brain abscess model. METHODS: Alpha streptococcus brain abscesses were studied in five dogs at 1.5 tesla (T) 1 and 5 days after implantation. Scans were performed 1, 11, and 21 minutes after contrast was administered, using an initial dose of 0.1 mmol/kg. A supplemental contrast injection of 0.2 mmol/kg was given (for a cumulative dose of 0.3 mmol/kg), with scans repeated at 31, 41, and 51 minutes. RESULTS: Lesion conspicuity on day 1 was greater at high-contrast doses (0.3 mmol/kg) compared with standard doses (0.1 mmol/kg), regardless of whether imaging was performed without (0.89 +/- 0.02 compared with 0.26 +/- 0.08) or with (0.97 +/- 0.04 compared with 0.28 +/- 0.06) MT. High-dose, MT, and a delay after contrast was injected all produced a statistically significant improvement. On blinded review of films obtained 11 and 14 minutes after injection, enhancement of the lesion could not be identified with certainty in two of five dogs at a dose of 0.1 mmol/kg, regardless of whether MT was used. Enhancement was seen consistently in all lesions at 0.3 mmol/kg. On day 5, results were comparable, with greater absolute enhancement. CONCLUSIONS: In early brain infection, high-contrast doses (0.3 mmol/kg), MT, and a moderate delay after injection all improve visualization of lesion enhancement.

Animals↗
PubMed1995

Detectability of early brain meningitis with magnetic resonance imaging.

RATIONALE AND OBJECTIVES: The ability of high-field (1.5 T) magnetic resonance imaging (MRI) to detect early brain meningitis was evaluated in a canine model. Contrast dose, timing postinjection, and imaging technique (specifically the use of magnetization transfer) were assessed. METHODS: Imaging of five canines was performed at 1.5 T 24 hours after injection of Cowans staphylococcus into the cisterna magna. Two control animals also were imaged using the same protocol, with one animal receiving a cisternal injection of nutrient broth only and the other no injection. Contrast doses of 0.1, 0.3, and 0.8 mmol/kg gadoteridol (Gd HP-DO3A or Pro-Hance) were compared. Scans were performed at 2, 12, and 22 minutes after an initial injection of 0.1 mmol/kg. At each time point, paired T1-weighted scans with and without magnetization transfer (MT) were acquired. Thirty minutes after the initial injection of contrast, a supplemental dose of 0.2 mmol/kg was given (for a cumulative dose of 0.3 mmol/kg). Scans were then repeated at 2, 12, and 22 minutes after this dose was administered. A second supplemental contrast injection of 0.5 mmol/kg (for a cumulative dose of 0.8 mmol/kg) was given at 70 minutes, and immediate postinjection scans with and without MT were acquired. RESULTS: In the animals receiving a cisternal injection of bacteria, the degree of meningeal enhancement was greatest at 0.8 mmol/kg, intermediate at 0.3 mmol/kg, and least at 0.1 mmol/kg. These conclusions were constant whether imaging was performed with or without MT. Scans in control studies did not demonstrate abnormal meningeal enhancement. High-contrast dose, MT, and acquisition of immediate postcontrast scans all resulted in statistically significant improvement. On masked film review, abnormal meningeal enhancement was noted in only 2 of 5 experimental dogs at a dose of 0.1 mmol/kg (regardless of the use of MT) compared with all animals at a dose of 0.3 mmol/kg. In 18 of 37 dogs (paired scans with and without MT), when abnormal enhancement was noted, the use of MT improved the visualization of abnormal meningeal enhancement. CONCLUSIONS: In early brain meningitis, high-contrast dose (0.3 mmol/kg), MT, and scanning immediately after injection improve detection of abnormal meningeal enhancement, thus facilitating the diagnosis of meningitis. Of these factors, contrast dose is the most important.

Animals↗
PubMed1995

Update: safety, new applications, new MR agents.

In the last decade, i.v. contrast media use in magnetic resonance imaging (MRI) of the central nervous system has become well established. Three agents are currently available in the United States: gadopentetate dimeglumine (Magnevist), gadodiamide (Omniscan), and gadoteridol (ProHance). At a dose of 0.1 mmol/kg, for which all three agents are approved, the contrast effect is equivalent. The agents differ on the basis of stability in vivo, osmolality, and charge. A single agent (ProHance) is approved for high-dose administration (0.3 mmol/kg). The basis of this approval is due in part to the high stability of the agent and thus lower potential for toxicity from long-term heavy metal deposition. Clinical experience, combined with new developments in MR technology, continue to expand applications for these agents. Improved detection of metastatic disease to the brain has been demonstrated in multiple clinical trials with high-dose contrast administration. High dose may also play an important role in brain infection and infarction, providing improved recognition of blood-brain barrier disruption and thus disease activity. First-pass studies make possible the evaluation of regional cerebral blood volume with high intrinsic spatial resolution. The availability of new instrumentation, together with the use of high contrast dose, have improved the quality and clinical utility of these studies. Research is ongoing in the development of new agents, both with greater tissue selectivity and improved safety profile. Chelates of dysprosium, in addition to gadolinium, are receiving attention for potential clinical application in first-pass imaging.

Animals↗
PubMed1994

Management of pterygium with surgery and radiation therapy. The North Florida Pterygium Study Group.

PURPOSE: To compare our results in the management of pterygium using a higher total dose with other reported results. METHODS AND MATERIALS: Between 1971 and 1991, 690 patients were treated with complete surgical excision followed by beta irradiation for primary or recurrent pterygium. Of these patients, 129 had two or more areas involving both eyes for a total of 825 lesions treated. Only 17 patients (2%) had temporal lesions with the rest of the patients having nasal pterygia. All patients underwent complete surgical resection of the pterygium before undergoing radiation therapy. One hundred forty-nine patients had undergone previous surgical resection alone but developed recurrence. After surgical excision, all patients were treated with Strontium-90 applicators starting immediately within 24 hr of surgery. Our standard policy was six weekly applications, each delivering a surface dose of 1000 cGy. The total dose delivered was 6000 cGy. Minimum follow-up was 1 year with a median of greater than 8 years. RESULTS: There were only fourteen recurrences (1.7%) out of a total of 825 lesions treated. Nine of the fourteen patients received suboptimal therapy undergoing less than five applications of Strontium-90. There were no major complications. CONCLUSION: The combination of surgical excision followed by adequate Strontium-90 applications is highly effective in the management of pterygium. The optimal total dose appears to be in the range of 2000 cGy to 6000 cGy.

Adult↗
PubMed1994

Magnetic resonance imaging of an experimental model of intracranial metastatic disease. A study of lesion detectability.

RATIONALE AND OBJECTIVES: The detectability of brain metastases was evaluated in a rabbit model, with attention to magnetic resonance contrast dose and timing of image acquisition after injection of contrast medium. METHODS: Five New Zealand white rabbits were studied at 1.5 T 6 to 7 days and 11 to 12 days after surgical implantation of an adenocarcinoma tumor nidus. T1- and T2-weighted spin-echo images (0.9 x 0.9 x 2 mm3 voxel size) were obtained before administration of contrast medium. T1-weighted images were repeated 5, 15, and 30 minutes after intravenous injection of 0.1 mmol/kg gadoteridol. At 40 minutes, a supplemental dose of 0.2 mmol/kg (0.3 mmol/kg cumulative dose) was administered, with T1-weighted images repeated at 5, 15, and 30 minutes after the second injection. RESULTS: Six to 7 days after tumor implantation, lesion enhancement (percent change, with normalization to baseline and equilibrium values) was 42 +/- 9% at 5 minutes, 48 +/- 9% at 15 minutes, and 42 +/- 10% at 30 minutes after administration of 0.1 mmol/kg gadoteridol. After administration of 0.3 mmol/kg gadoteridol, lesion enhancement was 111 +/- 13% at 5 minutes, 116 +/- 8% at 15 minutes, and 100% at 30 minutes. On film review, 2 of 5 lesions were not detectable at 6 to 7 days after tumor implantation with 0.1 mmol/kg gadoteridol. Administration of 0.3 mmol/kg gadoteridol provided for lesion identification in each instance. Eleven to 12 days after tumor implantation, one lesion was not detectable with 0.1 mmol/kg gadoteridol. Administration of 0.3 mmol/kg gadoteridol again provided for lesion identification in all cases. Mean lesion enhancement increased from 39 +/- 15% to 104 +/- 10%. CONCLUSIONS: The administration of 0.3 mmol/kg gadoteridol (high dose) compared with 0.1 mmol/kg gadoteridol (conventional dose) improves metastatic lesion detectability in the brain. The lesions identified only at high dose were confirmed by histopathology. Smaller lesions were not detected at a dose of 0.1 mmol/kg.

Adenocarcinoma↗
PubMed1994

Visualization of blood-brain barrier disruption on MR images of cats with acute cerebral infarction: value of administering a high dose of contrast material.

OBJECTIVE: The detection of blood-brain barrier disruption in patients with cerebral infarction by means of contrast-enhanced MR images improves the specificity of diagnosis, enables lesion dating, and on occasion improves lesion detection. Accordingly, we performed a study to determine the extent of visualization of disruption of the blood-brain barrier on contrast-enhanced MR images, with specific attention to contrast dose, in a cat model of acute cerebral infarction. We used doses of 0.1 and 0.3 mmol/kg of a gadolinium chelate, gadoteridol, which is characterized by extracellular distribution and renal excretion, and was approved by the Food and Drug Administration for clinical use at these doses. MATERIALS AND METHODS: Blood flow in the middle cerebral artery was occluded unilaterally in seven cats for 1 hr, followed by 4 hr of reperfusion. T2- and T1-weighted MR images were obtained before the injection of contrast material. After injection, the time course of enhancement was observed for 1 hr by repeated sequential acquisition of T1-weighted images. Five cats received an initial injection of 0.1 mmol/kg of contrast material, supplemented 33 min later by 0.2 mmol/kg (cumulative dose, 0.3 mmol/kg). Two cats received a single injection of contrast material, either 0.1 or 0.3 mmol/kg. The images were reviewed in a prospective fashion by a single observer, who was blinded to the dose of contrast material and the timing of image acquisition, in order to detect abnormal contrast enhancement. Changes in single intensity were quantified by region-of-interest measurements. RESULTS: Enhancement at 4 and 13 min, respectively, after injection of contrast material was 25 +/- 10% and 38 +/- 7% with 0.1 mmol/kg, vs 80 +/- 12% and 100 +/- 15% with 0.3 mmol/kg (n = 5). The difference between doses was statistically significant (p < .002) for all time points. Abnormal contrast enhancement was visible in three of six cats that received 0.1 mmol/kg and in all cats that received 0.3 mmol/kg. By 13 min after injection, enhancement had peaked with a dose of 0.1 mmol/kg and was within 20% of maximum with a dose of 0.3 mmol/kg. CONCLUSION: Detection of disruption of the blood-brain barrier in acute cerebral infarction in cats is improved when high doses (0.3 mmol/kg) of contrast material are used. Disruption may not be visualized when 0.1 mmol/kg, the currently accepted standard dose, is used.

Animals↗
PubMed1994

Magnetic resonance contrast agents in neuroimaging. New agents and applications.

Of the four gadolinium chelates in clinical use worldwide, only three are available in the United States: gadoteridol, gadodiamide, and gadopentetate dimeglumine. Although gadopentetate dimeglumine is still administered in many clinical practices, a consequence of being the first agent developed (1988) and until recently the only agent available, gadoteridol demonstrates a higher index of safety--at least on theoretical grounds. With linear chelates such as gadopentetate dimeglumine and gadodiamide, greater release of free gadolinium ion occurs in vivo owing to lower thermodynamic and kinetic stability. The concern with respect to demetallation and resultant increased chronic deposition of gadolinium ion in marrow and liver is greater with gadodiamide. Drug safety appears not to be an issue at high dose for gadoteridol, the only agent approved in this regards. The safety of the other chelates at high dose has yet to be established. The nonionic character of the two newer agents (gadoteridol and gadodiamide) is not of great importance in current clinical practice, in which most examinations are still performed with a dose of 0.1 mmol/kg given as a slow infusion. The non-ionic nature of the newer MR contrast agents may become clinically important in the future, with more common application of bolus injection and high dose. High contrast dose (0.3 mmol/kg) is advocated in routine MR clinical practice for the evaluation of intracranial metastatic disease. Only with prior evidence for multiple metastases and in patients for whom the detection of additional lesions would not influence therapy can the use of standard dose (0.1 mmol/kg) be justified.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed1993

Vitreous surgery for macular holes.

BACKGROUND: To surgically treat patients with macular holes, the authors previously reported both anatomic (re-attachment) and visual success (2 lines of improvement) in a series of 52 eyes. They now have operated on an additional 118 eyes using similar techniques, for a total of 170 eyes. METHODS: After ophthalmologic examination and history, the authors operated on suitable patients. The surgical objectives included relief of all tangential traction and retinal tamponade with intraocular gas. All eyes were followed for at least 6 months postoperatively. RESULTS: In the total population of 170 eyes, anatomic success was achieved in 73% and vision improved at least two lines in 55%. Twenty-nine percent (49/170) of patients had a visual acuity of 20/40 or better at last examination. Patients with symptoms of less than 6 months' duration managed better than those with symptoms of longer duration (P = 0.3001). In the former group of 66 eyes, anatomic success was achieved in 80% (n = 53), whereas visual acuity improved at least two lines in 68% (n = 45) and at least four lines in 55% (n = 36). CONCLUSIONS: The authors suggest that macular hole surgery may provide meaningful improvement in visual acuity in most patients, especially in those whose symptoms are of less than 6 months' duration.

Aged↗
PubMed1993

Assessment of cerebral perfusion by first-pass, dynamic, contrast-enhanced, steady-state free-precession MR imaging: an animal study.

OBJECTIVE: The purpose of this study was to determine whether cerebral perfusion could be assessed with a conventional 1.5-T MR imaging system by applying a steady-state free-precession (SSFP) technique during bolus IV injection of contrast material (gadoteridol). Normal and abnormal perfusion states and the effect of the dose of contrast material were studied in cats. MATERIALS AND METHODS: Nine healthy anesthetized cats were imaged after administration of 0.5 mmol/kg (n = 5), 0.25 mmol/kg (n = 2), and 0.1 mmol/kg (n = 2) of gadoteridol. Six cats with an acute infarct of the middle cerebral artery (five cats 10 min after and one cat 1 hr after vessel occlusion) were evaluated at a dose of 0.5 mmol/kg. The middle cerebral artery was ligated in each instance by use of a snare placed around the vessel during surgery, which was performed via a transorbital approach. Each animal was imaged with spin-echo T2-weighted (3000/45,90 [TR/TE]) and T1-weighted (500/10) techniques before contrast material was injected. SSFP images (12/18, 80 degrees tip angle) were acquired sequentially (each with a 1-sec acquisition time and no interimage delay) immediately before and for 45 sec after IV injection of a bolus of gadoteridol. RESULTS: The first-pass effect in both normal gray and white matter was dose dependent, with a greater magnitude of change seen at higher doses of contrast material. A 55% decrease in signal intensity of normal peripheral gray matter was observed during the first pass after bolus injection of 0.5 mmol/kg gadoteridol, compared with a 23% decrease and a 17% decrease at doses of 0.25 and 0.1 mmol/kg, respectively. High temporal (one image per second) and spatial (1.5 x 1.5 x 6.0 mm) resolution was achieved, with sufficient sensitivity that both visual and statistical differentiation of normal and abnormal gray and white matter was possible. Ten minutes after vessel occlusion, the change in signal intensity during the first pass was 45 +/- 5% and 27 +/- 9% for normal central gray and white matter, respectively, as compared with 20 +/- 2% and 11 +/- 5% for ischemic central gray and white matter, respectively. CONCLUSION: Cerebral perfusion can be assessed on conventional 1.5-T MR imaging systems by combining high-dose IV bolus injection of contrast material (in this instance, using gadoteridol) with dynamic SSFP imaging.

Animals↗
PubMed1993

G protein-linked receptors labeled by [3H]histamine in guinea pig cerebral cortex. II. Mechanistic basis for multiple states of affinity [corrected].

Tritiated histamine labels multiple states of guanine nucleotide-binding protein-linked receptors in washed membranes from guinea pig cerebral cortex. The effects of guanylylimidodiphosphate identify the radioligand as an agonist, but the Hill coefficients can be as low as 0.78 for H2 and H3 agonists and 0.66 for antagonists. To examine the mechanistic basis of the binding patterns, the inhibitory behavior of 14 histaminergic ligands has been measured at 1.4 nM and 11 nM [3H]histamine. In such experiments, the radioligand is both a second independent variable and an internal control; it is therefore possible to differentiate among mechanistic schemes for binding at equilibrium. When the data are analyzed in terms of distinct and independent sites, the relative capacities and the inferred affinities of [3H]histamine differ significantly from ligand to ligand. Because the discrepancies persist for any degree of heterogeneity, the model can be rejected unequivocally. Several lines of evidence argue against the notion of a ligand-regulated equilibrium between two states of mutually independent sites. In particular, antagonists reveal a paradoxical arrangement in which the ligand appears to increase the relative number of sites in the state to which it binds more weakly; also, the Hill coefficients estimated at 1.4 nM [3H]histamine are 1.54 for the H2 agonist pyridylethylamine and 1.26 for the antagonist SK&F 93479 [Mol. Pharmacol. 43: 569-582 (1993)]. High values of nH suggest that one equivalent of bound ligand affects the affinity of the next, and a model based on cooperative interactions can predict most of the effects that are anomalous in the context of other schemes. H2 agonists can be distinguished empirically from antagonists on the basis of their inhibitory behavior at two concentrations of [3H]histamine. The trend includes two compounds that are H2 agonists but H3 antagonists, and the labeled sites therefore reveal an element of H2 specificity.

Animals↗
PubMed1993

Enhanced liver MR: contrast agents and imaging strategy.

Contrast enhancement in liver MR can be achieved by a variety of fundamentally different strategies. The published clinical literature regarding Gd DTPA (gadopentetate dimeglumine), Gd HP-DO3A (gadoteridol), Gd BOPTA (gadobenate dimeglumine), Mn DPDP, and AMI-25 is reviewed, followed by a brief discussion of two new iron particulate agents currently in preclinical trials. Different imaging techniques also must be used for visualization of contrast enhancement depending on the specific type of agent utilized. With both gadolinium and manganese chelates, T1 weighted sequences are used to visualize the effect of the contrast agent. There is positive enhancement (an increase in signal intensity) of normal liver parenchyma post-contrast due to enhanced T1 relaxation. With iron particulate agents, T2 weighted sequences are used. In this instance, there is negative enhancement (a decrease in signal intensity) of normal liver post-contrast due to enhanced T2 relaxation. Clinical use at present is limited to the extracellular gadolinium chelates, with bolus injection and dynamic imaging improving efficacy. Current research also supports the use of a high dose (0.3 mmol/kg) for improved lesion detectability, a finding now clinically relevant due to the recent approval of Gd HP-DO3A at both standard and high doses.

Contrast Media↗
PubMed1993

G protein-linked receptors labeled by [3H]histamine in guinea pig cerebral cortex. I. Pharmacological characterization [corrected].

Binding of histamine to washed membranes from guinea pig cerebral cortex can be described empirically as two classes of distinct and independent sites (log IP1 = -8.45 +/- 0.02, R1;t = 98 +/- 6 pmol/g of protein; log KP2 = -6.34 +/- 0.22, R2.t = 990 +/- 60 pmol/g of protein). At 1.4 nm [3H]histamine, the kinetics of association and dissociation are biexponential. The values of k-Pj/k+Pj calculated for parallel one-step processes agree well with the corresponding values of KPj. Both k-p1 and k-P2 are increased by 0.1 mM guanylylimidodiphosphate; apparent capacity at equilibrium is reduced for both classes of sites, with little or no change in KP1 or KP2. Twenty-six H2 and H3 agonists and antagonists block access of [3H]histamine to the same sites, and the binding patterns reveal either one or two hyperbolic terms [i.e., sigma nj = 1 F' jKj/(Kj+[L])]. Two terms are required for six agonists and six antagonists, and F'2 varies widely from ligand to ligand. Also, the quantity log (K2/K1) is correlated with F'1 among agonists but with F'2 among antagonists (K1 < K2). The pharmacological selectivity is suggestive of both H2 and H3 receptors. An H2 specificity emerges from the appropriate values of Kj for 12 H2 agonists (i.e., K1 when n = 1 and K2 when n = 2; p = 0.00045), although a specificity distinct from that of H2 receptors is found with H2 antagonists. An H3 specificity emerges from the inhibitory potencies (IC50) of eight H3 agonists (p = 0.00025) and eight H3 antagonists (p = 0.0019); also, the sites labeled by [3H]histamine resemble H3 receptors reportedly labeled by N alpha-[3H]methylhistamine and (R)-alpha-[3H]methylhistamine. Ligand-dependent differences in F'2 are inconsistent with the notion of distinct and independent sites, and the tendency of antagonists to promote the sites of weaker affinity (F'2) argues against a ligand-regulated equilibrium between two states. The physical significance of the binding parameters is therefore unclear. The failure to identify an unambiguous pharmacological specificity may reflect the failure to assess binding in the correct mechanistic context.

Animals↗
PubMed1992

Effects of adenyl nucleotides and carbachol on cooperative interactions among G proteins.

Muscarinic agonists and adenyl nucleotides are noncompetitive modulators of sites labeled by [35S]GTP gamma S in washed cardiac membranes from Syrian golden hamsters. Specific binding of the radioligand and its inhibition by either GTP gamma S or GDP reveals three states of affinity for guanyl nucleotides. In the absence of adenyl nucleotide, carbachol promotes an apparent interconversion of sites from higher to lower affinity for GDP; the effect recalls that of guanyl nucleotides on the binding of agonists to muscarinic receptors. In the presence of 0.1 mM ATP gamma S, the binding of [35S]GTP gamma S is increased at concentrations up to about 50 nM and decreased at higher concentrations. At a radioligand concentration of 160 pM, binding exhibits a bell-shaped dependence on the concentration of both ATP gamma S and AMP-PNP; with ADP and ATP, there is a second increase in bound [35S]GTP gamma S at the highest concentrations of adenyl nucleotide. ATP gamma S and AMP-PNP also modulate the effect of GDP, which itself emerges as a cooperative process: that is, binding of the radioligand in the presence of AMP-PNP exhibits a bell-shaped dependence on the concentration of GDP; moreover, the GDP-dependent increase in bound [35S]GTP gamma S is enhanced by carbachol. The interactions among GDP, GTP gamma S, and carbachol can be rationalized quantitatively in terms of a cooperative model involving two sites tentatively identified as G proteins. Both GTP gamma S and GDP exhibit negative homotropic cooperativity; carbachol enhances the homotropic cooperativity of GDP and induces or enhances positive heterotropic cooperativity between GDP and [35S]GTP gamma S. An analogous mechanism may underlie the guanyl nucleotide-dependent binding of agonists to muscarinic receptors. The data suggest that the binding properties of G proteins and their associated receptors reflect cooperative effects within heterooligomeric arrays; agonist-induced changes in cooperativity may facilitate the exchange of GTP for bound GDP and thereby constitute the mechanism of G protein activation in vivo.

Adenine Nucleotides↗
PubMed1992

Interaction of domoic acid and several derivatives with kainic acid and AMPA binding sites in rat brain.

We have determined the inhibitory potencies of domoic acid and a series of derivatives of domoic acid at kainic acid and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) binding sites in rat forebrain membranes. These derivatives of domoic acid differed in the configuration, stereochemistry, and degree of saturation of the side chain attached to C-4 of the prolyl ring. The binding data were analyzed in terms of one or two classes of sites as appropriate. Domoic acid and kainic acid displayed similar inhibition constants at [3H]kainic acid sites (IC50 = 5 and 7 nM, respectively). At both kainic acid and AMPA binding sites, all of the compounds tested were less potent than domoic acid itself. At high affinity [3H]kainic acid sites, the derivatives could be categorized into two groups; those with nanomolar affinity and those with micromolar affinity. All members of the former group possessed a side chain with the first double bond intact and in the Z (cis) configuration. The more distal atoms present in the extended side chain of domoic acid did not appear to contribute to the high affinity interaction with the kainic acid receptor. Although all the compounds tested were weaker inhibitors of [3H]AMPA binding compared to [3H]kainic acid binding, there was a high correlation between the rank order of potency of the seven domoic acid derivatives at [3H]kainic acid and at [3H]AMPA binding sites. The inhibition data for kainic acid at [3H]AMPA binding sites were described adequately in terms of a 1-site model, whereas the data for domoic acid required two classes of sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Inefficient muscarinic transduction in cardiomyopathic Syrian hamsters.

Regulation of cyclic AMP (cAMP) production and muscarinic binding were studied in highly washed left ventricular membranes from spontaneously cardiomyopathic Syrian hamsters (TO strain). Basal production of cAMP was decreased relative to that in random-bred (RB) controls, with proportionally similar decreases in stimulated production elicited by 7 beta-deacetyl-7 beta-(gamma-N-methylpiperazino)-butyryl forskolin and by the beta-adrenergic agonist isoproterenol. GTP-stimulated production of cAMP was inhibited fully by the muscarinic agonist carbachol in tissue from controls, but only partially in tissue from TO hamsters. Total muscarinic binding, as revealed by N-[3H]methylscopolamine, was similar in the two strains. Competition between carbachol and the radioligand revealed at least three classes of sites for the agonist, the apparent affinities of which were insensitive to the disease. Upon the addition of guanylyl imidodiphosphate (GMP-PNP, 0.1 mM), there was a disease-dependent redistribution such that the sites appeared to be predominantly of low affinity for the agonist in RB tissue and predominantly of medium affinity in TO tissue. The potency of GMP-PNP in mediating the change in carbachol binding apparently was unaffected by the disease. The loss of muscarinic regulation of cAMP production in TO left ventricular tissue appears to reflect a disease-related change in the coupling of muscarinic receptors to inhibitory GTP-binding proteins.

Adenylyl Cyclases↗
PubMed1990

The sexual vocabularies of heterosexual and homosexual males and females for communicating erotically with a sexual partner.

This study explored what terminology constitutes an erotic or arousing language for male and female, heterosexual and homosexual, and the extent to which that language is used with a sexual partner. Five sexual references were included: male genitalia, female genitalia, lovemaking/coitus, oral-genital contact, and hand-genital contact. Respondents consisted of 120 urban midwestern university students, 30 in each gender and sexual orientation category. Sexual orientation was as powerful a predictor as gender for language that was considered erotic. Lesbians and gay males more often than heterosexual females and males used erotic or arousing vocabulary with a spouse or lover. Gay males more often used slang with a spouse or lover than did heterosexual males and heterosexual females. Implications for sexual arousal based upon communication are discussed.

Adult↗