Hypoxemia unassociated with anatomic shunting in pulmonary disease.
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Biomedical subjects
Publications and source records attributed to G L Jackson.
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An initial liver/spleen scan performed on a patient with blunt abdominal trauma was negative 3 days following the accident. A follow-up scan 7 days later showed definite evidence of splenic rupture, proved surgically. The authors conclude that, in such cases, spleen scans may be negative initially because of delayed splenic ruptures.
In the first experiment, the influence of synthetic gonadotropin-releasing hormone (GnRH) on the time course of [3H]glucosamine ([3H]GA) and [14C]alanine ([14C]A) incorporation into LH by quartered rat anterior pituitary glands and the sequence of release of radiolabeled and total immunoreactive LH (IR-LH) was investigated. Radiolabeled LH was measured by immunoprecipitation and total IR-LH was measured by RIA. After lag periods of 5 and 20 min, respectively, incorporation of [14C]A and [3H]GA into tissue LH increased linearly for 4 h. GnRH stimulated incorporation of [3H]GA only. The ratio of [14C]A-LH to [3H]GA-LH (14C:3H ratio) in the tissue decreased significantly with time and with GnRH treatment. In the second experiment, replenishment of GnRH in the medium every 0.5 h elevated the release rate (release during each sequential 0.5 h) of both [3H]GA and [14C]A-labeled LH within 1.5 h. The release rate of radiolabeled LH increased linearly until 3.5 h. The 14C:3H ratio in LH released during each time interval was reduced by GnRH. The release rate of IR-LH increased linearly with time, plateaued by 1.5-3 h, and started to decline. In other experiments, cycloheximide blocked synthesis of [14C]A-LH and greatly reduced the GnRH-induced synthesis and release of [3H]GA-LH, but reduced release of IR-LH by only 25%. Actinomycin D had no effect on GnRH-induced synthesis and release of LH at 2 h, but significantly reduced both at 4 h. These data suggest that 1) the time course for the release of preexisting IR-LH differs from that for newly synthesized LH, 2) the newly synthesized LH released in response to high levels of GnRH has more sugar residues than that released under basal conditions, 3) the GnRH-induced LH release can occur under conditions in which LH synthesis has been blocked, and 4) synthesis of messenger RNA is not required for GnRH-induced LH release or short term LH synthesis but seems to be required for continued synthesis and subsequent release of LH.
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The influence of estrogen on uptake of [3H]glucosamine and [14C]alanine and their incorporation into LH and total protein was investigated. Ovariectomized rats were sacrificed 22 h after injection with either oil or estradiol benzoate (EB, 50 microng/rat). Quartered anterior pituitary glands were incubated for 4 h with radioactive precursors in the presence or absence of 3.6 X 10-8M synthetic gonadotropin-releasing hormone (GnRH). Labeled LH was isolated by immunoprecipitation with specific anti-LH-beta serum. Both EB and GnRH significantly elevated the amount of [3H]glucosamine-LH appearing in the medium, the tissue, and the total system (medium + tissue), but they increased the amount of [14C]alanine-LH only in the medium. There was a significant positive interaction between EB and GnRH on the amounts of [3H]glucosamine-LH and [14C]alanine-LH in the medium and of [3H]glucosamine-LH in the tissue and total system. EB enhanced [3H]glucosamine uptake and incorporation into total protein, but GnRH had little or no effect on these parameters. In time course studies rats were injected with either oil or EB at 22, 11, or 5.5 h prior to sacrifice. At all times EB significantly increased synthesis and release of [3H]-glucosamine-LH and release of total immunoreactive LH (IR-LH) by pituitaries incubated with GnRH. The amounts of labeled and IR-LH released into the medium increased linearly with time after EB injection, but the amount of labeled LH in the total system plateaued at 5.5 h after EB injection. In another study, estradiol (E2, 5 microng/rat) dissolved in 1% ethanol-saline was injected at 0.5, 1.0, 2.0, or 4 h prior to sacrifice. Incorporation of [3H]glucosamine into tissue protein and release of [3H]glucosamine-LH was stimulated within 2 h after E2 injection. However, incorporation of [3H]glucosamine into LH was not stimulated until 4 h after E2 injection. These results suggest that estrogen and GnRH regulate LH synthesis at different sites, and that the effect of estrogen is non-specific compared to that of GnRH. The synthesis of the carbohydrate moiety of LH appears to be subjected to hormonal regulation more readily than the synthesis of the polypeptide moiety.
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The capability of pregnant mare serum (PMS) and human chorionic gonadotropin (HCG) to induce estrus and ovulation was tested in mature, anestrous bitches. The PMS was given for 10 consecutive days in 1 of 3 regimens: 500 IU/day (experiment 1), 250 IU/day (experiment 2), or 20 IU/kg/day (experiment 3). The HCG was given as a single 500-IU dose on experimental day 10. Controls were given saline solution. Vaginal smears were collected on days 1, 3, 5, 7, 9, and 12 by jugular venipuncture, and the plasma was assayed for progesterone concentration by radioimmunoassay. On day 13, the bitches were euthanatized, ova were flushed from the uterine tubes (oviducts), and the ovaries were collected and prepared for microscopic examination. Fourteen of 25 bitches treated with PMS and HCG showed estrus and ovulated. Proestrus (vaginal bleeding) commenced between experimental days 7 and 10. Estrus commenced on day 9 or 10. Progesterone increased from approximately 1 ng/ml on day 1 to more than 6 ng/ml on day 12. Numbers of ovulation sites on both ovaries were 4.7 +/- 1.1 and 4.6 +/- 0.5 (mean +/- SEM) in those given the daily doses of 500 and 250 IU of PMS and 9.8 +/- 1.5 in experiment 3 bitches. Eleven hormone-treated dogs and 7 saline-treated dogs did not show any detectable response. Neither cystic nor unovulated, luteinized follicles appeared on the ovaries.
The influence of synthetic gonadotropin-releasing hormone (GnRH) on incorporation of glucosamine and amino acids into LH and total protein was investigated. Rat pituitaries were incubated in vitro with radioactive precursors for 4 h at 37 C. Labeled LH was isolated by immunoprecipitation with specific anti-LH-beta serum. Total LH in the medium and pituitary glands was measured by radioimmunoassay. GnRH significantly stimulated incorporation of [3H]glucosamine into LH in pituitaries from immature male, intact female, and ovariectomized rats. Pituitaries from ovariectomized rats synthesized more [3H]glucosamine-labeled LH than those from intact adult rats. GnRH enhanced release of [3H]glucosamine-LH into medium in pituitaries of both adult intact and ovariectomized rats. The response to GnRH was greatly reduced when pituitaries were exposed to cold shock before the 4 h incorporation period. In contrast to its effect on incorporation of [3H]glucosamine into LH, GnRH had either no or little effect, depending on experimental conditions, on uptake of [3H]glucosamine by pituitaries. Incorporation of [3H]glucosamine into total protein was not affected by GnRH treatment. GnRH increased release of either [3H]leucine- or [3H]alanine-labeled LH into medium, but had no significant effect on incorporation of labeled amino acids into total LH in the system. GnRH modified neither uptake nor incorporation of amino acids into total protein. GnRH significantly stimulated the release of cold LH into medium under all conditions, but the total amount of immunoassayable LH in the system was not detectably modified by GnRH treatment.
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Implants of cocoa butter (CB) or CB and actinomycin D (AD) were placed in the hypothalamus, amygdala, or anterior pituitary gland of testosterone-pretreated ovariectomized rats. The animals were then given an injection of 2.5 mg progesterone (P) at 11.00 h and sacriviced at approximately 16.30 h. Serum LH was determined by radioimmunoassay. Implants of AD placed in or near the arcuate nucleus and in other sites in the ventromedial hypothalamus blocked p-induced LH release, but those placed in the preoptic area or ventrolateral hypothalamus were only partially effective. Implants of AD in the amygdala or anterior pituitary gland had no detectable effect on LH release. Approximately 70 percent of the radioactivity in implants of 3H-AD diffused from the implant site within 8 h. of that recovered, most was found within 1 mm of the implant site. These results suggest that the ventromedial hypothalamus is one site at which AD acts to block P-induced LH release.
These experiments tested the effects of reserpine on estrogen-induced LH release and the effects of estrogen on gonadotropin-releasing hormone-induced LH release in ovariectomized ewes. Injection of 50, 200, or 500 mug of estradiol benzoate (EB) into progesterone-treated ewes, or of 50 mug of EB into non-treated ewes induced a large surge in serum LH levels approximately 15 h later. Injection of 5 mg/ewe of reserpine 6 h prior to the EB, blocked the LH surge. Reserpine reduced, but did not block the release of LH induced by injection of 20 mug or 40 mug of synthetic gonadotropin-releasing hormone (GnRH). Injection of graded doses (5, 10, or 20 mug) of GnRH into progesterone-treated ewes that had been treated with reserpine, induced increases in serum LH levels that were proportional to the logarithm of the dose. In the final series of experiments both progesterone-treated and non-treated ewes were injected with reserpine and then with either EB or oil. Fifteen hours after receiving EB or oil they were injected with either GnRH or the diluent. GnRH elevated serum LH levels significantly higher in ewes given EB than in those given oil. LH levels in ewes given oil and diluent were not elevated. These data suggest that reserpine blocked EB-induced LH release by an action on the central nervous system and that EB acted directly on the anterior pituitary to increase the response to GnRH.
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