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C J Wallis

Publications and source records attributed to C J Wallis.

9 recordsLinked to original sources
PubMed1992

Characterization of calcium binding to brain spectrin.

Brain spectrin alpha and beta chains bind 45Ca2+, as shown by the calcium overlay method. Flow dialysis measurements revealed eight high affinity binding sites/tetramer that comprise two binding components (determined by nonlinear regression analysis). The first component has one or two sites (kd = 2-30 x 10(-8) M), depending on the ionic strength of the binding buffer, with the remaining high affinity sites in the second component (kd = 1-3 x 10(-6) M). In addition, there is a variable, low affinity binding component (n = 100-400, kd = 1-2 x 10(-4) M). Magnesium inhibits calcium binding to the low affinity sites with a K1 = 1.21 mM. Proteolytic fragments from trypsin or chymotrypsin digests of brain spectrin bind 45Ca2+ if they include alpha domain IV, alpha domain III, or the amino-terminal half of the beta chain (but more than 25 kDa from the amino-terminal). These data suggest that calcium ions bind with high affinity to the putative EF-hands in alpha domain IV and to one site in the amino-terminal half of the beta chain that is associated with alpha domain IV in the native dimer. The localization is consistent with a direct calcium modulation of the spectrin-actin-protein 4.1 interaction. In addition, there appears to be one high affinity site near the hypersensitive region of alpha brain spectrin. All four proposed binding sites occur near probable calmodulin-binding or calcium-dependent protease cleavage sites.

Animals↗
PubMed1990

Pathophysiological actions of thromboxane A2 and their pharmacological antagonism by thromboxane receptor blockade with GR32191.

With a growing general conviction that thromboxane A2 does have a pathological role in occlusive vascular disease, there is a current debate on the ideal type of drug treatment needed. The more widely accepted view now seems to be that drugs that antagonize the actions of thromboxane A2 by blocking its receptors have greater clinical potential than those that block its synthesis. However, this premise has yet to be proven clinically. The historical development of thromboxane receptor blockers as a new class of medicines and, in particular, that of GR32191, are described here. The clinical evaluation of GR32191 should determine the importance of thromboxane A2 in cardiovascular disease.

Animals↗
PubMed1985

Hormonal evaluation in patients with osteosarcoma.

Aspects of growth regulation were studied in patients with osteosarcoma to ascertain if hormonal imbalance is associated with this disease. Thirty-nine evaluated patients were of normal height for their ages. During the oral glucose tolerance test, carbohydrate intolerance was demonstrated in seven of 18 patients, while growth hormone was slightly elevated in four of 17 patients. Serum somatomedin activity (SMA) was elevated in seven of nine patients. In one untreated patient in whom SMA was measured across the tumor bed, significant gradient of SMA was found; gel filtration of the sera at pH 2.4 revealed a typical SMA profile in the arterial serum and an additional high SMA peak in the venous serum. Among needle biopsy specimens incubated for 48 hours, SMA was released by the histologically viable tumors but not by the nonviable specimens. The data suggest that young patients with osteosarcoma have elevated SMA.

Adolescent↗
PubMed1975

Stimulation of male and female sexual behavior in gonadectomized rats with estrogen and androgen therapy and its inhibition with concurrent anti-hormone therapy.

In the first experiment gonadectomized male rats were injected daily with various combinations of vehicle (V), estradiol benzoate (E), dihydrotestosterone (D) and/or the anti-androgen cyproterone acetate (CA). The eight treatment combinations consisted of V, E, D, CA, E + D, E + CA, D + CA and E + D + CA. Only those males treated with both E and D were found to display ejaculations. Concurrent treatment with CA completely blocked ejaculatory behavior and it significantly reduced both mount and intromission frequencies. Examination of peripheral androgen target tissues indicated that following stimulation with D, CA effectively reduced seminal vesicle and penile weights, and penile lengths, but it did not reduce penile spines. In the second experiment gonadectomized female rats were treated with two daily injections of E, E + CA or E + the anti-estrogen CI-628. A second set of gonadectomized females received three daily injections of testosterone (T), T + CA or T + CI-628. On the day after completion of these injections all females received progesterone and were tested for sexual receptivity three hours later. Both E and T treated females were found to display the lordotic posture in response to mounting stimulation while both CI-628 and CA were found to block this behavior. In E treated females, CI-628 and CA were also found to reduce uterine weight. Thus, CA was shown to have anti-estrogenic as well as anti-androgenic properties. These results were discussed in terms of the aromatization and 5alpha reduction theories of testosterone action in sexual behavior.

Androgens↗
PubMed1975

Maintenance of male sexual behavior by combined treatment with oestrogen and dihydrotestosterone in CD-1 mice.

After castration, adult male sexually experienced CD-1 strain mice were treated with dihydrotestosterone (200 mug/day, DHT), oestradiol benzoate (1 mug/day, OB) or DHT (200 mug/day) plus OB (1 mug/day). Oestradiol benzoate and the combined treatment DHT + OB maintained male sexual behaviour at levels comparable to a group of intact control mice, while DHT m maintained behaviour at a lower level. Having all hormone dosages resulted in a decrease in the number of OB-treated animals mating and a complete loss of mating in the DHT-treated animals. The decrease in dosage did not result in any change in the behavior of the mice receiving both hormones. Adrenalectomy was found to have no effect on the mating behaviour of the OB-treated and untreated animals, but it did reduce the number of DHT+ OB-treated animals mating. Thus, both OB alone and combined DHT+OB treatment can maintain male mating behaviour in castrated CD-1 strain mice and these effects do not appear to be due to the effects of oestradiol on the adrenal.

Adrenal Glands↗
PubMedDate not supplied

Effects of septal lesions and chronic estrogen treatment on dopamine, GABA and lordosis behavior in male rats.

Septal lesions (SL) in female rats result in an increased sensitivity to the behavioral effects of acute estradiol benzoate (ACUTE-EB; 2 microgram/day X 3) treatment as measured by the lordosis quotient (LQ: number of lordotic responses X 100/number of mounts). Male rats, intact or castrated, do not show this enhanced behavioral response to ACUTE-EB unless they are treated with EB (2 microgram/day) for 2--4 weeks immediately following the production of SL. The present study was undertaken to examine possible neurochemical alterations which could account for the enhanced behavioral sensitivity to ACUTE-EB seen in the SL male rat treated chronically with EB during the postlesion period (SL-EB). Three groups, normal males, SL-EB and SL males chronically treated with oil (SL-oil), were subdivided and treated with ACUTE-EB or oil and decapitated. The brains were removed, frozen and stored at -50 degrees C prior to dissection and assay. Tyrosine hydroxylase (TH) activity was assayed in the dopamine (DA) rich areas of the forebrain (striatum, STR, nucleus accumbens septi, ACB; and olfactory tubercle). The TH activity was significantly suppressed in both the STR and ACB of the SL-EB males treated with ACUTE-EB. The glutamic acid decarboxylase (GAD) activity in both the substantia nigra and ventral tegmentum was significantly increased in the SL-EB males given ACUTE-EB relative to that of all other groups. In summary, SL-EB males given ACUTE-EB show (1) an enhanced LQ, (2) decreased TH activity in the region of DA terminals, and (3) increased GAD activity in the region of DA cell bodies. The increase in GAD activity is suggested to be a result of an altered neuronal feedback because of plastic changes that occur during chronic EB treatment following production of SL. This probable increase in inhibitory tone in the region of the DA cell bodies may explain the observation that the SL-EB male exhibits decreased DA turnover following ACUTE-EB treatment. Moreover, since DA may be inhibitory to the display of lordosis behavior, the SL-EB males may show an enhanced LQ, at least partially, because of this reduction in DA activity.

Animals↗