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Biomedical subjects

C G Smith

Publications and source records attributed to C G Smith.

At least 73 records · Page 4Linked to original sources
PubMed1982

Response of rhesus monkey lymphocytes to short-term administration of THC.

Four Rhesus monkeys were subjected to daily administration of 2.5 mg of tetrahydrocannabinol (THC)/kg body wt, after establishing the norms for complete blood count, T- and B-cell concentrations, and the dose response of thymidine incorporation after PHA stimulation. THC was administered daily for 3 weeks, the treatment was stopped, and then the animals were allowed to recover for 4 weeks. Cellular responses, incorporation studies and fibrinogen levels were determined during the treatment and recovery phases. Compared to 4 vehicle-treated animals, the THC-treated animals experienced significant augmentation of both their total white cell and their neutrophil counts during the recovery phase which returned to normal levels during the recovery phase. There was no alteration in total lymphocyte count or T- or B-cell concentrations. Fibrinogen levels of the THC-treated animals during the treatment phase were also elevated compared to controls, and the levels diminished to the same values as the vehicle-treated animals during recovery phase. Possible mechanisms for the response of Rhesus monkeys to short-term administration of THC are discussed.

Animals↗
PubMed1982

Use of monoclonal antibody to increase sensitivity and specificity in quantitative immunodiffusion assays.

A mouse monoclonal antibody has been produced which recognizes human liver gamma-cystathionase, Radioiodination of the monoclonal antibody facilitated its use in combination with non-specific precipitating rabbit antisera in classical immunodiffusion assays. The technique may have broad applicability in the detection and quantitation of rare antigens which are difficult to purify but easily recognizable in immunodiffusion assays. It may also be used for the initial detection of monoclonal antibodies to unique antigens of interest.

Animals↗
PubMed1982

Fibronectin has a dual role in locomotion and anchorage of primary chick fibroblasts and can promote entry into the division cycle.

Fibronectin (FN), which is already known to be a natural factor for fibroblast spreading on substrata, has now been shown to be essential for two distinct types of adhesion with different biological functions in chick heart fibroblasts, namely adhesion directed toward locomotion and toward stationary anchorage for growth. Manipulation of culture conditions and the use of antisera of differing specificities has demonstrated that both exogenous and cell-derived FN are important in each process. The organization of the fibronectin-containing matrix differs between the two states. Immunoelectron microscopy with a colloidal gold marker reveals the presence of small membrane-associated plaques of fibronectin in motile cells with associated submembranous specialization. A fibrillar matrix containing fibronectin is dominant in nonmotile, growing fibroblasts. The development of focal adhesions for stationary anchorage can be dramatically enhanced by addition of cell-derived FN at an appropriate stage, and this promotes entry into the growth cycle. New macromolecular synthesis in addition to FN is necessary for focal adhesion development but not for locomotion.

Animals↗
PubMed1982

Effects of porcine follicular fluid on gonadotropin concentrations in rhesus monkeys.

The administration of steroid-free charcoal-treated porcine follicular fluid to long term castrated female rhesus monkeys lowered basal serum concentrations of FSH and had almost no effect on serum LH. Treatment with porcine follicular fluid before the administration of exogenous LRH inhibited the release of FSH, but also affected the release of LH. This inhibition was especially striking on the suppression of the peak of release of both FSH or LH at 20 min. These findings suggest that an inhibin-like material present in follicular fluid could play an important role in the secretion of FSH and LH in rhesus monkeys.

Animals↗
PubMed1982

Modified schema for classifying positive-pressure tympanograms.

Tympanograms with peaks located in the high-positive air pressure range (greater than or equal to 50 mm H2O) are infrequently recorded in clinical practice and have been little discussed in the literature. Such tympanograms accounted for 1.2% of a series of 8,011 tympanograms recorded at various times from 1,556 subjects ranging in age from 7 months through 12 years. Correlations between otoscopic diagnoses and tympanometric findings in the case of 65 of the high-positive air pressure tympanograms form the basis of the present report. Of the 65 high-positive air pressure tympanograms, 51 showed relatively high compliance (less than or equal to 5.5 Madsen units), and of these 46 (90%) were associated with ears considered normal otoscopically. Fourteen of the high-positive air pressure tympanograms showed low compliance (greater than 5.5 Madsen units), and of these, six (43%) were associated with ears considered normal, six (43%) with ears showing signs of acute infection, and two (14%) with ears in which the presence of effusion seemed probable. A previously presented zonal schema for classifying tympanograms has been modified on the basis of these findings.

Acoustic Impedance Tests↗
PubMed1982

Luteolytic effect of azastene in the nonhuman primate.

The ability to block steroidogenesis with 4,4,17-alpha-trimethylandrost-5-eno[2,3,-d]isoxazol-17-ol (azastene) was studied in 3 different models. Oral administration of 500 mg to rhesus monkeys on different days of their luteal phase induced marked depression of circulating progesterone concentrations, and in some cases early onset of menses. Simultaneous administration of human chorionic gonadotropin (hCG) during the midluteal phase did not overcome the luteolytic effect of azastene. Concentrations of 50 micrograms/ml of azastene inhibited testosterone secretion by decapsulated mice testes in vitro in response to hCG [controls, 1165 +/- 196 ng/ml, azastene, 306 +/- 40 ng/ml (P less than .01)]. Production of progesterone by dispersed luteal cells from rhesus monkey corpora lutea was markedly inhibited by the presence of 25 and 50 micrograms/ml azastene in the incubation media (P less than .05 and less than .01, respectively). The availability of a compound that blocks in vivo and in vitro gonadal steroidogenesis opens a new approach to postcoital contraception in primates because of its luteolytic and interceptive activity. The possible mechanisms of action of azastene are discussed.

Abortifacient Agents↗
PubMed1981

Human chorionic gonadotropin blocks the estrogen-induced luteinizing hormone release in long-term castrated rhesus monkeys: evidence for an ultrashort-loop negative feedback.

We studied the effects of human chorionic gonadotropin (hCG) administration on the biphasic response of luteinizing hormone (LH) to estrogen challenge in long-term castrated, female rhesus monkeys. Estradiol benzoate (EB), 400 micrograms, was administered to all animals at time zero; hCG, 2000 IU, was administered either concomitantly or 12 hours after EB. Blood samples were obtained every 6 hours for 58 hours, and then at 72 and 82 hours. Control animals received EB alone. Serum LH and beta hCG were determined by radioimmunoassay. Control animals showed a typical biphasic response to EB: an initial decrease in LH levels, 50% to 70% of baseline, from +6 hours until +30 hours; then a large increase, 150% to 190% of baseline, at +48 hours. Animals treated with hCG at time zero showed an initial decrease in LH, 40% to 70% of baseline, but LH returned to basal levels at +42 hours. Animals treated with hCG 12 hours after EB showed an initial decrease in LH, 45% to 55% of baseline, but LH returned to basal levels at +36 hours. These results suggest that an LH ultrashort-loop negative feedback may exist in the nonhuman primate.

Animals↗
PubMed1981

Effects of delta 9-tetrahydrocannabinol during the follicular phase of the rhesus monkey (Macaca mulatta).

It is well documented in the literature that delta 9-tetrahydrocannabinol (THC) decreases serum concentrations of pituitary gonadotropins in several species. To study its effects in the menstrual cycle of regularly cycling rhesus monkeys, 2.5 mg/kg THC were administered to five animals from days 1-18 of the cycle [ovulation day in our colony, 15 +/- 1 day (mean +/- SD)]. Controls received vehicle (Tween 80 and saline) in an identical protocol. Animals were bled daily or every other day, and serum total estrogens, LH, PRL, and progesterone were determined by RIA. Serial laparoscopies were performed to visualize ovulation. Whereas animals treated with vehicle presented normal cycle lengths (26, 26, 29, 30, and 34 days), those treated with THC presented abnormal lengths (145, 76, 22, 94, and 59 days). All vehicle-treated cycles were ovulatory, while four of five THC cycles were anovulatory (P < 0.02). Five THC-treated animals were anovulatory in the posttreatment cycle. To determine the site of action of THC-induced anovulation, five animals received THC, human menopausal gonadotropin, and hCG simultaneously. All ovulated normally, as determined by laparoscopic visualization of stigma. Normal luteal phases were evidenced by normal luteal phase lengths and serum progesterone concentrations. These findings are of clinical relevance, since they were achieved with doses of THC that produce blood concentrations similar to those found in heavy marijuana users.

Animals↗
PubMed1981

Luteolytic effect of D-Trp6-luteinizing hormone-releasing hormone in the rhesus monkey (Macaca mulatta).

A potent agonist of luteinizing hormone, D-Trp6-LRH, was administered at different stages during the luteal phase of rhesus monkeys (Macaca mulatta). Luteolysis, evidenced by short luteal phases and decreased serum progesterone concentrations, was consistently induced when the analog was injected on days 3 or 5 post ovulation; however, no effect was observed when it was given on day 7 post ovulation. Increasing doses of hCG administered from days 6-10 post ovulation prevented the luteolytic effect of D-Trp6-LRH. The possible mechanisms of action and the potential uses of LRH analogs as contraceptive agents are discussed.

Animals↗
PubMed1981

Reduced gamma-cystathionase protein content in human malignant leukemia cell lines as measured by immunoassay with monoclonal antibody.

A murine hybrid cell line has been produced which secretes immunoglobulin G2b with specificity for human gamma-cystathionase (EC 4.2.1.15). The antibody has been iodinated and used in combination with quantitative immunoelectrophoresis in an assay which is capable of detecting as little as 1.5 ng enzyme protein. Human lymphoblastic leukemia cell lines CEM and Laz-221 contain undetectable enzyme protein, corresponding to their behavior as cysteine auxotrophs. In contrast, nonmalignant lymphoblastoid lines contain easily detectable enzyme protein which correlates with their behavior as cysteine prototrophs. Other malignant leukocyte cell lines contained detectable but variable amounts of enzyme protein, suggesting that the enzyme may be a useful marker of cellular differentiation.

Antibodies↗
PubMed1979

Inhibition of gonadotropin by delta9-tetrahydrocannabinol:mediation by steroid receptors?

Competition assays for estradiol receptors in cytosol preparations of uteri from rhesus monkeys and humans showed that delta9-tetrahydrocannabinol (THC) does not compete with estradiol for intracellular estrogen recptors. Although isotopically labeled THC bound to macromolecules in uterine cytosol from the rhesus monkey, the binding was not displaced by unlabeled THC, diethylstilbestrol, estradiol, progesterone, cortisol, or 5 alpha-dihydrostestosterone. Scatchard analyses indicated that high-affinity saturable binding of THC to cytosol did not occur. Thus the inhibitory effect of THC on gonadotropin and steroid secretion in primates is not mediated by the interaction of THC with intracellular steroid hormone receptors.

Animals↗
PubMed1979

Effect of tetrahydrocannabinol on the hypothalamic-pituitary axis in the ovariectomized rhesus monkey.

Single doses of delta9-tetrahydrocannabinol (THC) (5.0, 2.5, 1.25, or 0.625 mg/kg) can decrease the levels of both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the ovariectomized rhesus monkey. The inhibition of gonadotropins (50% to 88%) lasts for 6 to 24 hours depending upon the dose of THC. There are no great differences in the responses of the two gonadotropins to THC. The inhibition of gonadotropin levels by THC appears to be at the level of the hypothalamus, since both LH and FSH are released from the pituitary gland in response to LH- releasing factor in the presence of THC.

Animals↗
PubMed1979

Acute decreases in serum prolactin concentrations caused by delta 9-tetrahydrocannabinol in nonhuman primates.

The acute effects of single injections of delta 9-tetrahydrocannabinol (THC) on serum prolactin (PRL) concentrations were studied in oophorectomized female and intact adult male rhesus monkeys. Some animals were challenged with thyrotropin-releasing hormone (TRH) to determine whether THC influences pituitary responsiveness to releasing hormone. THC markedly suppresses serum PRL concentrations in animals of both sexes. TRH injections resulted in normal PRL release when administered simultaneously with or 30 minutes after THC administration. These results suggest that the serum prolactin-lowering effect of THC occurs principally at a suprapituitary level.

Animals↗
PubMed1979

Effects of delta 9-tetraphydrocannabinol administration on gonadal steroidogenic activity in vivo.

The effects of delta 9-tetrahydrocannabinol (THC) administration on gonadal steroidogenic activity in vivo were studied in two animal models: (1) luteal function of the rhesus monkey and (2) periovulatory steroid concentrations of rabbits treated with human chorionic gonadotropin (hCG). THC-treated monkeys demonstrated progesterone concentrations and luteal phase lengths which were not different from those in untreated controls. THC did not impair the normal pattern of response of the corpus luteum to increasing doses of hCG as measured by serum progesterone concentrations and luteal phase lengths. Rabbits treated with THC manifested normal periovulatory steroidal patterns (progesterone, testosterone, and dihydrotestosterone). These data suggest that THC does not significantly inhibit steroidogenesis by a direct action on the ovary. Its effect may be mediated by a central mechanism of action.

Animals↗