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Biomedical subjects

J W Wells

Publications and source records attributed to J W Wells.

At least 55 records · Page 3Linked to original sources

Sexual language usage in different interpersonal contexts: a comparison of gender and sexual orientation.

Previous investigators have demonstrated that gender differences exist in the use of sexual language in various interpersonal contexts. However, sexual orientation has not been addressed in any study regarding sexual language usage. This investigation examined the use of sexual language for female and male in different interpersonal contexts based upon sexual orientation. Respondents were 440 university students: 202 heterosexual female, 30 lesbian, 173 heterosexual male, and 35 gay male. Findings indicate that differences in sexual language usage in interpersonal contexts is significant for gender as well as for sexual orientation. Conjecture is made for the implications this may have on intimate relationships.

Adult↗

Expanded indications for pneumatic retinopexy.

The Collaborative Pneumatic Retinopexy Study evaluated retinal detachments (RDs) secondary to one break or group of breaks no larger than 1 clock hour located within the superior 8 clock hours of the fundus. Eyes with prominent proliferative vitreoretinopathy (PVR) were excluded. Forty eyes which exceed these criteria and were treated with pneumatic retinopexy have been retrospectively evaluated to determine what preoperative conditions limit the application of pneumatic retinopexy. Multiple breaks in multiple quadrants, large tears up to 2.5 clock hours in size, and RDs associated with a moderate degree of PVR were successfully managed with pneumatic retinopexy. The greatest number of failures were due to inferior breaks. The overall success rate for pneumatic retinopexy was 75%. New breaks occurred in 12.5% of eyes, but all of these were successfully managed.

Humans↗

Role of glucosinolates in the causation of liver haemorrhages in laying hens fed water-extracted or heat-treated rapeseed cakes.

Glucosinolates were removed from whole rapeseed by a hot-water extraction procedure or depleted by heat treatment. When laying hens were maintained for three months on diets containing about 300 g kg-1 of these rapeseed cakes, the incidence of liver haemorrhages detected at post mortem examination was similar to that in birds maintained on 300 g kg-1 commercial rapeseed meal and significantly greater than in control birds fed soya-based diets. The effectiveness of glucosinolate extraction or depletion was determined by chemical analysis and by histological examination of the thyroid glands. Histologically the haemorrhages were similar after feeding extracted and commercial rapeseed meals. Diets containing mixtures of nitriles and glucosinolates severely depressed food intake and egg production but did not cause a greater incidence of haemorrhages than the other rapeseed products tested. Mortality from causes other than liver haemorrhage was higher with the diets containing rapeseed and this suggests that rapeseed has a more generalised effect on the body's defence mechanisms. These observations suggest that other factors in rapeseed meal, alone or acting with glucosinolates, may be responsible for inducing liver haemorrhages in laying hens.

Animal Feed↗

Pneumatic retinopexy. A collaborative report of the first 100 cases.

The preliminary experience of one surgeon, using pneumatic retinopexy for 20 consecutive cases of rhegmatogenous retinal detachment, was previously reported. The collaborative experience of six surgeons using pneumatic retinopexy for 100 cases is now reported. This series includes cases with pseudophakia, aphakia, macular detachment, macular breaks, vitreous hemorrhage, trauma, and old detachments. Initially, 91% were reattached, but seven recurrences yielded a 6-month follow-up cure rate of 84% with pneumatic retinopexy. With subsequent scleral buckling, 98% were reattached. Postoperative complications included proliferative vitreoretinopathy (3%), macular pucker (3%), and new/missed retinal breaks (7%). A review of the literature disclosed postoperative new/missed retinal breaks in nine series: 21, 3, 8, 4, 9, 7, 5, 4, and 13%. There were no cases of glaucoma, cataract, subretinal gas, endophthalmitis, or extension of the detachment into a previously attached macula. Pneumatic retinopexy offers the advantages of reduced tissue trauma, fewer complications, no hospitalization, and less expense. The major disadvantage is the need for postoperative positioning.

Cryosurgery↗

Assessment of mechanistic proposals for the binding of agonists to cardiac muscarinic receptors.

N-[3H]Methylscopolamine has been used to characterize muscarinic receptors in crude homogenates prepared from hearts of Syrian golden hamsters. The Hill coefficient is one for specific binding of the radioligand itself and for its inhibition by muscarinic antagonists; markedly lower values are obtained for its inhibition by muscarinic agonists. The binding patterns of agonists have been analyzed in terms of a mixture of sites differing in affinity for the drug and reveal the following. All agonists discern at least two classes of receptor in atrial and ventricular homogenates. The number of classes and the relative size of each differ for different agonists in the same region and for the same agonist in different regions. Atrial and ventricular affinities are in good agreement for some agonists but differ for others. Guanylyl imidodiphosphate (GMP-PNP) is without effect on the specific binding of the radioligand but alters the binding of carbachol via an apparent redistribution of receptors from one class to another; the apparent affinity at either class remains unchanged. Carbachol reveals two classes of sites in ventricular preparations, and the nucleotide mediates an interconversion from higher to lower affinity; three classes are revealed in atrial preparations, and the nucleotide eliminates the sites of highest affinity with a concomitant increase in the number of sites of lowest affinity. Taken together, the data are incompatible with the notion of different, noninterconverting sites; rather, there appear to be several possible states of affinity such that the equilibrium distribution of receptors among the various states is determined by the tissue, by the agonist, and by neurohumoral modulators such as guanylyl nucleotides. The effects of agonists and GMP-PNP cannot be rationalized in terms of a ternary complex model in which the low Hill coefficients arise from a spontaneous equilibrium between receptor (R) and G protein (G) and in which agonists bind preferentially to the RG complex.

Animals↗

Assessment of a ternary model for the binding of agonists to neurohumoral receptors.

A frequently cited variant of the "mobile receptor" hypothesis has been examined for its ability to describe the binding of agonists at neurohumoral receptors that operate via a guanylyl nucleotide binding protein. The model involves a reversible association between the receptor (R) and the G protein (G). Agonists (A) bind with different affinity to R and to the RG complex; similarly, G differentiates between R and the AR complex. Theoretical binding curves calculated according to the model have been analyzed in terms of the Hill equation and as a mixture of independent and noninteracting sites. The model is shown to be compatible in some respects with reported data on the binding of agonists to the beta-adrenergic receptor but not to the muscarinic cholinergic or D2 dopaminergic receptors. It is difficult to reconcile with the reported effects of guanylyl nucleotides, magnesium, and N-ethylmaleimide on the binding of agonists at any neurohumoral receptor.

Animals↗

Liver haemorrhages induced by rapeseed meal: incidence in adult male and female fowls.

Adult cockerels of a commercial egg-producing strain did not develop liver haemorrhages when maintained for 12 weeks on a diet containing 400 g rapeseed meal/kg food. Haemorrhages occurred in 43% of laying hens of the same strain as the cockerels and 33% of laying hens of another strain maintained on the same diet for the same period. Oestrogenisation of the male birds did not influence the incidence of haemorrhage.

Animal Feed↗

H2 histaminic receptors in rat cerebral cortex. 1. Binding of [3H]histamine.

Saturable binding of [3H]histamine in equilibrium with homogenates of rat cerebral cortex reveals Hill coefficients between 0.4 and 1.0, depending upon the conditions. Data from individual experiments are well described assuming one or two classes of sites. Only the sites of higher affinity (KP1 = 3.9 +/- 0.5 nM) are observed when binding is measured by isotopic dilution at a low concentration of the radioligand (less than 1.5 nM) in the presence of magnesium or by varying the concentration of the radioligand. The sites of lower affinity (KP2 = 221 +/- 26 nM) appear during isotopic dilution at higher concentrations of the radioligand or at lower concentrations either upon the addition of guanylyl imidodiphosphate (GMP-PNP) or upon the removal of magnesium. Estimates of the second- and first-order rate constants for association and dissociation of [3H]histamine agree well with KP1. Apparent capacities corresponding to KP1 and KP2 are of the order of 100 ([R1]t) and 1300 pmol/g of protein ([R2]t), respectively. Simple interconversion cannot account for the changes in binding that occur upon adding GMP-PNP or removing magnesium, since the increase in [R2]t exceeds the decrease in [R1]t. Moreover, the apparent amount of high-affinity complex exhibits a biphasic dependence on the concentration of [3H]histamine; an increase at low concentrations is offset by a decrease that occurs at higher concentrations. The latter appears to be positively cooperative and concomitant with formation of the low-affinity complex. These and other observations indicate that the binding of histamine is inconsistent with models commonly invoked to rationalize the binding of agonists to neurohumoral receptors. GMP-PNP and magnesium reciprocally alter capacity at the sites of higher affinity, however, and the reduction caused by GMP-PNP reflects a substantial increase in the rate constant for dissociation at the sites that appear to be lost. The sites labeled by [3H]histamine thus reveal the properties of neurohumoral receptors linked to a nucleotide-specific G/F protein.

Animals↗

H2 histaminic receptors in rat cerebral cortex. 2. Inhibition of [3H]histamine by H2 antagonists.

Sites labeled by [3H]histamine in homogenates of rat cerebral cortex reveal a pharmacological specificity typical of H2 receptors. Fourteen H2 antagonists inhibit the specific binding of the radioligand to the same level; Hill coefficients are near or equal to one for five compounds and markedly lower for nine. The binding patterns of individual antagonists (A) are well described by the empirical expression Y = F1K1/(K1 + [A]) + F2K2/(K2 + [A]), in which F1 and F2 sum to 1; F2 is 0 for those drugs that reveal a Hill coefficient of 1. Concentrations of A that reduce specific binding by 50% (IC50) correlate well (r = 0.991; P less than 0.00001) and show good numerical agreement with potencies reported for inhibition of the response to histamine in H2-mediated systems. The correlation is poorer when IC50 is replaced by either K1 (r = 0.973) or K2 (r = 0.921) for those antagonists that reveal both; the antihistaminic activity of the drug thus appears not to be associated preferentially with one or other class of sites. Since F2 varies from 0.16 to 0.60 among those antagonists that discern heterogeneity, the antagonist appears to determine the distribution of sites between the two classes. Moreover, a correlation among antagonists between values of K1 and K2 (r = 0.975; P = 0.00001) suggests that the apparent heterogeneity reflects different conformers within an otherwise homogeneous population. H2 antagonists appear to be noncompetitive with respect to each other and to the radioligand: one antagonist has relatively little effect on the values of K1, K2, and F2 revealed by another; also, estimates of K1 and K2 are independent of the concentration of [3H]histamine between 1.3 and 10 nM, although the radioligand exhibits an apparent dissociation constant of 3.9 nM [Steinberg, G. H., Eppel, J. G., Kandel, M., Kandel, S. I., & Wells, J. W. (1985) Biochemistry (preceding paper in this issue)].

Animals↗

H2 histaminic receptors in rat cerebral cortex. 3. Inhibition of [3H]histamine by H2 agonists.

The binding of [3H]histamine to H2 receptors in homogenates of rat cerebral cortex is inhibited by 11 H2 agonists in a characteristic and unique manner. At low concentrations of the radioligand (less than 1.5 nM), the inhibitory profiles of individual agonists (A) are distinctly biphasic; specific binding is well described in most cases by the empirical expression Y = F1K1/(K1 + [A]) + F2K2/(K2 + [A]), in which F1 and F2 sum to 1. Maximal inhibition is the same for all agonists. Since values of F2 vary from 0.42 to 0.90, the agonist appears to determine the equilibrium distribution of receptors between two states of affinity. Ratios of apparent affinity (K2/K1) vary from 204 to 3 090 000, and there is no correlation between values of K1 and K2. Compounds lacking H2 activity, including structural analogues of histamine and dimaprit, reveal a Hill coefficient of 1 and inhibit the radioligand only weakly. For six agonists, values of K2 agree and correlate well (P = 0.00047) with H2 pharmacological potency (EC50) in the guinea pig right atrium; for the others, K2 is less than EC50 by 15-61-fold. Four observations suggest that the inhibition corresponding to F1 is allosteric and cooperative: the dissociation constant of the radioligand appears to vary in the presence of an unlabeled agonist, absolute levels of binding corresponding to F1, as defined by dimaprit, decrease at higher concentrations of [3H]histamine, F1 for dimaprit is reduced from 0.48 to 0.32 by 2-methylhistamine (F1 = 0.27) at a concentration of 20 nM (approximately K1(0.5) K2(0.5) for 2-methylhistamine), but the increase in K1 for dimprit is at least 100-fold less than expected from competitive effects, and 1 equiv of some agonists appears to preclude access of [3H]histamine to more than 1 equiv of receptors, with no evidence that an appreciable fraction of the unlabeled drug is bound. Noncompetitive effects also may account in part for the inhibition corresponding to F2.

Animals↗

Detection of gonadotrophic hormones on isolated thecal interstitial cells of the domestic hen, Gallus domesticus, by an immunohistochemical method.

An immunohistochemical method was used to demonstrate the presence of gonadotrophins in isolated ovarian interstitial cells. The cells were obtained by collagenase digestion of large ovarian follicles after removal of the yolk and the granulosa layer. Using a peroxidase-labelled anti-rabbit serum with anti-chicken follicle stimulating hormone (FSH) serum raised in rabbits, a strong positive reaction was obtained. Anti-human FSH serum also produced a positive result but the reaction was weaker. There was no apparent difference in the staining reaction of cells which had been preincubated with ovine FSH serum. Treatment with anti-ovine luteinizing hormone (LH) resulted in a faintly positive reaction. The viability of the cells was tested by the Trypan Blue method and they were identified as steroid-producing cells by the histochemical demonstration of their 3 beta-hydroxysteroid dehydrogenase activity.

Animals↗

Comparison of the response in vivo to luteinizing hormone and follicle stimulating hormone of the granulosa of six follicles from the ovarian hierarchy in the chicken (Gallus domesticus).

A function test was used to compare the response of the granulosa from the six largest preovulatory follicles. F1-F6, of laying hens to ovine LH (40 micrograms), ovine FSH (1200 micrograms), and PMSG (800 micrograms). The progesterone content of these granulosa which were dissected out exactly 45 min after the injection, was measured by radioimmunoassay. With each of the three gonadotropin preparations, the amount of progesterone accumulating in the F1-F3 granulosa always exceeded that of F4 and F5. The values were two to six times greater than those obtained in tissue from control hens injected with 1% bovine serum albumin (BSA). The levels in the smallest F6 granulosa did not differ from those of BSA-treated controls. LH had the greatest stimulatory effect on the granulosa response. The results indicate that the production of progesterone by the granulosa of the F1-F5 follicles in vivo may be controlled mainly by LH, rather than FSH. The observed changes induced by the FSH and PMSG preparations could be attributed to their LH content. The granulosa of the F1 and F2 follicles are the major contributors to the circulating progesterone in the blood plasma of the laying hen.

Animals↗

Elevated bile acids in the plasma of laying hens fed rapeseed meal.

A simple procedure was developed for the estimation of bile acid taurine conjugates in fowl plasma. Laying hens fed a diet containing rapeseed meal (RSM) (400 g kg-1) for 12 weeks had higher bile acid levels (154 mumol litre-1) than hens fed a control soyabean diet (116 mumol litre-1) (P less than 0.01). The incidence of liver haemorrhages was higher (34.8 per cent) in RSM-fed hens than in controls (21 per cent), but the severity of the lesions did not correlate with the bile acid concentration in affected birds. Histological examination of sections from livers of RSM-fed birds did not reveal significant hepatocyte degeneration outside the immediate vicinity of the haemorrhage. Canalicular bile plugs were never seen. The incidence of liver haemorrhages (13 per cent) and plasma bile acids (85 mumol litre-1) were lower in hens fed a diet containing beta-aminopropionitrile (0.5 g kg-1), a known lathyrogen. Acute treatment of hens with the hepatotoxin alpha-naphthyl isothiocyanate over four days induced necrosis of hepatocytes and resulted in elevated bile acid concentrations (262 mumol litre-1) compared with controls (73 mumol litre-1) given arachis oil. It was concluded that laying hens fed high levels of RSM develop cholestasis but the toxic principle is not known.

Animal Feed↗

Dopamine receptor parameters detected by [3H]spiperone depend on tissue concentration: analysis and examples.

The binding of lipophilic radioligands to homogenized tissue was investigated with the help of a simple, two-component model: a specific component reflects binding to a single and uniform population of sites; a nonspecific component reflects partitioning into the membrane and the entrapment of some drug present in the aqueous phase prior to separation of the particulate fraction. The results indicate that the capacity and the affinity of the receptor may be underestimated when the data are analyzed in terms of total rather than free radioligand. Errors in capacity arise when for a significant fraction of the radioligand access to the receptor is blocked by an unlabelled drug and this appears as nonspecific binding. This is most likely to occur when the partition coefficient is such that the free radioligand is located predominantly in the particulate phase. Errors in affinity reflect the tendency of the membrane to reduce the free concentration of a lipophilic drug in the aqueous phase. A further complication arises when a significant fraction of the total radioligand binds to the receptor. [3H]Spiperone binds to dopamine D2 receptors with a dissociation constant of about 50 pM and partitions into the particulate phase of brain homogenates with a membrane/buffer partition coefficient of 410. As expected, both capacity and affinity can appear to depend on the concentration of tissue used in the assay. If the partition coefficient is known, corrected estimates of both parameters can be obtained knowing only the total concentration of radioligand; if the partition coefficient is not known, the free concentration of radioligand in the aqueous phase must be measured independently. The former procedure requires that the aqueous and particulate components of the system be separated by centrifugation; with filtration, the removal of an indeterminate amount of radioligand from the membrane during washing precludes any correction based on the partition coefficient. For the specific example of [3H]spiperone in human brain, the artifacts become negligible at concentrations of protein below 0.1 mg/ml of incubate. The capacity per unit of original tissue is best determined using unwashed preparations, since about 30% of the total protein and a comparable percentage of the receptors are lost on washing.

Brain↗

Detection of gonadotrophic hormones on isolated granulosa cells of the domestic hen, Gallus domesticus, by an immunohistochemical method.

Two immunohistochemical methods were used to detect the presence of luteinizing hormone (LH) on the cells of chicken granulosa. Using a peroxidase-labelled anti-rabbit serum together with anti-chicken LH serum raised in rabbits, a strong positive response was obtained with granulosa cells from small and large pre-ovulatory follicles obtained from the mid-cycle. Similarly, by using an available antiserum to human follicle stimulating hormone (FSH), a slightly weaker response was obtained with cells from both large and small follicles. After incubating cells with ovine LH, ovine FSH and ovine prolactin, there was no detectable difference with the method used in reaction with their respective antisera to cells which had received no incubation, implying that chicken gonadotrophins were displaced only partially from their receptors by mammalian gonadotrophic hormones. Pre-incubation of the cells with human chorionic gonadotrophin gave negative results with anti-hCG serum. Using a fluorescent-labelled antibody method, similar results were obtained except that the distribution of the receptors on the granulosa cell for LH or FSH appeared to be different. With the LH, the fluorescence formed a halo around the cell in contrast to the overall fluorescence with FSH.

Animals↗

Effect of luteinizing hormone on progesterone production by the follicular granulosa in the ovarian hierarchy of the domestic fowl (Gallus domesticus).

A LH function test was used to assess the effect of a previously administered dose of ovine LH on the granulosa from the four largest preovulatory follicles, F1-F4, of laying hens. At intervals of 1, 3, and 6 hr after intravenous ovine LH (40 micrograms; a dose previously shown to cause atresia) or carrier solution (1% bovine serum albumin solution, BSA), a second dose of LH or carrier was injected. The progesterone contained in the dissected granulosa of the F1-F4 follicles 45 min after the second injection was measured by radioimmunoassay. With birds injected with BSA, the mean basal levels ranged from 17 to 59 ng progesterone per granulosa, irrespective of the follicular type. In short-term experiments, i.e., 45 min after LH, the mean progesterone contents of F1 (262 ng) and F2 (137 ng) were significantly higher than their controls, whereas those of F3 (59 ng) and F4 (21 ng) did not change. The response per cell was greater in the F1 granulosa than in that of F2-F4; other evidence is presented to support a hypothesis that the F1 granulosa contains a larger LH receptor population. The effect of LH over a longer period (6 hr) was shown by a decline in the steroidogenic response of the F1 granulosa only. The kinetics of this decline (estimated t1/2 13.7 hr) resembled that previously reported for adenylate cyclase activity in granulosa cells from postovulatory follicles (POF) (t1/2 about 14.4 hr).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Variations in the number of nucleoli in the granulosa cells of the domestic fowl during follicular growth.

1. The proportions of granulosa cells containing one, two, or more nucleoli were determined in ovarian follicles of the domestic fowl (Gallus domesticus). Follicles ranged in size from 5 to 37 mm diameter. 2. The greatest proportion of cells (65%) contained one nucleolus. Cells containing two nucleoli were fewer (29%) and those containing more than two were rare (6%). 3. There was a tendency for the proportion of multinuclear cells to decrease with increasing size of the follicle. Conversely there was a similar tendency for the proportion of cells with single nucleoli to increase with size of the follicle. These relationships are curvilinear. 4. Suitable linear models confirmed these observations (P less than 0.005). 5. These results may provide an explanation for the previously reported progressive decrease in cellular DNA as the follicle increases in size.

Animals↗