Search PubMed⌕ Search

Biomedical subjects

G L Jackson

Publications and source records attributed to G L Jackson.

At least 91 records · Page 5Linked to original sources

Synthesis and release of luteinizing hormone in vitro: manipulations of Ca2+ environment.

We determined if luteinizing hormone (LH) synthesis is Ca2+ dependent and coupled to LH release. We monitored LH synthesis when LH release was stimulated either by specific [gonadotropin-releasing hormone (GnRH)] or nonspecific stimuli (50 mM K+ and 2 or 20 microM Ca2+ ionophore A23187) and inhibited by Ca2+-reduced medium. LH synthesis was estimated by measuring incorporation of [3H]glucosamine (glycosylation) and [14C]alanine (translation) into total (cell and medium) immunoprecipitable LH by cultured rat anterior pituitary cells. Both GnRH (1 nM) and 50 mM K+ significantly stimulated LH release and glycosylation, but had no effect on LH translation. A23187 also stimulated LH release, but significantly depressed glycosylation of LH and total protein and [14C]alanine uptake. Deletion of Ca2+ from the medium depressed both GnRH-induced LH release and glycosylation. Addition of 0.1 mM EGTA to Ca2+-free medium not only inhibited GnRH-induced release and glycosylation of LH but also uptake of precursors and glycosylation and translation of total protein. Thus glycosylation and release of LH are Ca2+ dependent. Whether parallel changes in LH release and glycosylation reflect a cause and effect relationship remains to be determined.

Alanine↗

Effect of frontal hypothalamic deafferentation on photoperiod-induced changes of luteinizing hormone secretion in the ewe.

These experiments were conducted sequentially in two parts. In the first, we examined the effect of frontal hypothalamic deafferentation (FHD) on photoperiod-induced changes in luteinizing hormone (LH) concentration in ovariectomized ewes ('steroid-independent' changes). In the second we placed Silastic implants of estradiol-17 beta in these same ewes and examined the effect of FHD on photoperiod-induced changes in the LH concentration in the presence of estradiol ('steroid-dependent' changes). 15 ovariectomized Suffolk ewes were subjected either to FHD (n = 10) or sham FHD (n = 5). They were placed in a photochamber and exposed to the following lighting regimens. In the first part, two trials of alternating lighting periods were used: trial 1 = 120 days of 8 h light (L):16 h dark (D) followed by 90 days of 16L:8D; trial 2 = 90 days of 8L:16D followed by 60 days of 16L:8D. In the second part, three lighting periods of alternating daylengths were used: 65 days of 16L:8D, followed by 60 days of 8L:16D and by 60 days of 16L:8D. Blood samples were collected from the jugular vein at 20-min intervals for 3 or 4 h during the last day of each lighting period. Data on mean LH concentrations were obtained. The location of the FHD was verified histologically. In the absence of gonadal steroids, 16L:8D increased, whereas 8L:16D decreased the LH concentration (p less than 0.001) in both sham FHD and FHD ewes.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Synthesis and release of luteinizing hormone in vitro by rat anterior pituitary cells: effects of gallopamil hydrochloride (D600) and pimozide.

We compared the role of Ca2+ in regulating GnRH-induced LH synthesis and release from cultured rat pituitary cells. LH synthesis and release were measured after a 4-h treatment of cells with gallopamil hydrochloride (D600; 1 and 100 microM), a Ca2+ channel blocker, or pimozide (0.5 and 5.0 microM), a calmodulin inhibitor, with or without 1 nM GnRH. LH translation and glycosylation were monitored by measuring incorporation of [14C]alanine and [3H]glucosamine, respectively, into total (cell and medium) immunoprecipitable LH. GnRH significantly (P less than 0.01) increased total [3H]LH (glycosylation), but had no effect on total [14C]LH (translation). D600 significantly (P less than 0.01) depressed (1 microM) and completely blocked (100 microM) GnRH-induced LH glycosylation and release of [3H]LH, [14C]LH, and immunoreactive LH. D600 (100 microM) also reduced (P less than 0.05) total basal synthesis of [14C]LH. Neither dose of D600 altered uptake of [3H]glucosamine, but 100 microM D600 significantly (P less than 0.01) depressed its incorporation into total protein. D600 (100 microM) significantly (P less than 0.01) depressed [14C]alanine uptake and incorporation into total protein. Pimozide significantly (P less than 0.01) reduced, in a dose-related manner, GnRH-induced LH glycosylation, and release of immunoreactive LH, [3H]LH, and [14C]LH. Pimozide did not alter LH translation or uptake of radiolabeled precursors or their incorporation into total protein. These results demonstrate that D600 and pimozide inhibit both GnRH-induced LH glycosylation and release. Thus, the actions of GnRH on LH glycosylation and release are both mediated by similar Ca2+-dependent pathways.

Alanine↗

Long term superfusion of rat anterior pituitary cells: effects of repeated pulses of gonadotropin-releasing hormone at different doses, durations, and frequencies.

We investigated the temporal release of LH by rat pituitary cells superfused with repeated pulses of GnRH at different doses (amplitudes), frequencies, and pulse durations. Anterior pituitary (AP) cells prepared from ovariectomized rats were cultured on bio-beads and then placed in columns and superfused. The cells were stimulated intermittently for 24 h with synthetic GnRH given as pulses of 6-, 10-, or 15-min duration at frequencies of one pulse per 30, 60, or 90 min. In the first experiment we tested the temporal response of cells exposed to different doses of GnRH. At all doses, the first pulse of GnRH stimulated greater LH release than subsequent pulses. The response to subsequent pulses varied with dose. At low doses (1 and 5 X 10(-10)M) of GnRH, the AP cells stabilized and released similar amounts of LH in response to each sequential identical GnRH pulse for up to 24 h. In contrast, at high doses (10(-8) and 10(-6)M) of GnRH, the AP cells gradually released less LH with each pulse. During the initial pulses, the dose-response curves of LH release were linear between doses of 5 X 10(-10) to 1 X 10(-6) M GnRH. Thereafter, the maximum response was diminished, and the slope of the dose-response curve was reduced. In subsequent experiments we found that the decline in responsiveness with time was not due to either degradation of GnRH in the medium or loss of cell viability. The low responsiveness to high GnRH pulses at the end of the superfusion period could be overcome temporarily by further increasing the dose of GnRH. In the presence of high doses, changing GnRH pulse frequency from one 6-min pulse per h to one 6-min pulse per 1.5 h or changing duration from one repeated 10-min pulse per h to one repeated 6-min pulse per h had no detectable effect on the temporal pattern of LH release. These results suggest that, similar to constant infusion, pulsatile delivery of GnRH at high doses to AP cells can induce cell refractoriness to GnRH. This loss of responsiveness probably involves factors in addition to depletion of GnRH receptors and the releasable LH pool. In contrast, pulsatile delivery of low doses of GnRH appears to maintain LH release at a relatively constant level for up to 24 h.

Animals↗

Effect of frontal hypothalamic deafferentation on photoperiod-induced changes in the secretion of prolactin in the ewe.

The purpose of these experiments was to determine the effect of frontal hypothalamic deafferentation (FHD) between the suprachiasmatic-preoptic region and the mediobasal hypothalamus on diurnal, seasonal, and photoperiod-induced changes in PRL secretion in ewes. In Exp 1, intact cycling ewes were subjected to either FHD or sham FHD. They were kept outdoors, and sequential hourly blood samples were taken for either 24 or 36 h during two breeding seasons and one nonbreeding season. Mean plasma PRL concentrations were higher (P less than 0.01) during the nonbreeding season than during the breeding season in both FHD and sham FHD ewes. Although FHD did not block the seasonal changes, it reduced (P less than 0.05) the 24-h mean concentration and diurnal peak concentration during the nonbreeding season. During the breeding seasons, there was no consistent diurnal pattern of PRL concentrations. In Exp 2, ovariectomized ewes were placed in a photochamber. After adaptation to an 8-h light, 16-h dark (8L:16D) photoperiod, they were subjected to either FHD or sham FHD. Sequential hourly blood samples were collected on the last day of exposure to each of three sequential lighting periods (120 days 8L:16D, 90 days 16L:8D, and 90 days 8L:16D). The 24-h mean plasma PRL concentrations were higher (P less than 0.01) after exposure to 16L:8D than after exposure to 8L:16D in both FHD and sham FHD ewes. FHD did not affect the 24-h mean concentrations. In both groups, there was a distinct diurnal pattern of plasma PRL after exposure to 16L:8D, but not after exposure to 8L:16D. FHD did not alter the diurnal pattern, but significantly (P less than 0.05) reduced the magnitude of the nocturnal elevation under 16L:8D. In summary, FHD reduced, but did not block, seasonal changes in PRL secretion in intact ewes and did not alter photoperiod-induced changes in 24-h patterns and 24-h mean concentrations of plasma PRL in ovariectomized ewes. These results suggest that direct neural pathways between the supra-chiasmatic-preoptic region and the mediobasal hypothalamus play a relatively minor role in mediating photoperiod-induced changes in PRL secretion in sheep.

Animals↗

Long-term superfusion of rat pituitary cells: interaction of 17 beta-estradiol with pulses of gonadotropin-releasing hormone on luteinizing hormone release.

In a series of four experiments, the temporal development of acute inhibitory and delayed stimulatory effects of 17 beta-estradiol (E) on luteinizing hormone (LH) release by superfused rat anterior pituitary cells pulsed with gonadotropin-releasing hormone (GnRH) was studied. Dispersed anterior pituitary cells from ovariectomized rats were cultured on Bio-Beads for 3 days and then placed in columns and superfused for up to 24 hr. During superfusion, the cells were exposed to GnRH pulses (3 X 10(-9) M, one 6-min pulse/hr). Cells treated with E (3 X 10(-10) M) either before (only 24 hr prior to superfusion) or before and during superfusion released significantly (P less than 0.05) more LH in response to the first few pulses of GnRH than cells treated with diluent. In contrast, cells treated with E only during superfusion initially released less GnRH-induced LH than cells treated with diluent. In a subsequent experiment, the inhibitory effect of E reached a maximum by 1.5 hr (P less than 0.01), and then gradually disappeared after 4.5 hr. Cells superfused simultaneously with E and fixed "low"-dose GnRH (5 X 10(-10) M) pulses did not exhibit enhanced LH responses with time to that dose of GnRH. However, E-superfused cells responded more than diluent-superfused cells to subsequent stimulation with a higher-dose GnRH pulse. Superfusion of cells with E for 16.5 hr in the absence of GnRH pulses also did not increase release of LH to low-dose (5 X 10(-10) M) pulses of GnRH, yet did cause a transitory increase to subsequent high-dose (10(-8) M) GnRH pulses. In conclusion, these results demonstrate the direct biphasic inhibitory then stimulatory effects of E on GnRH-induced LH release by superfused rat anterior pituitary cells. Expression of the stimulatory effect of E is related to the dose of GnRH.

Animals↗

Results of surgery alone and surgery combined with postoperative radiotherapy in the treatment of cancer of the parotid gland.

Seventy-seven patients with primary malignant parotid tumors were studied and the various factors relative to their disease, as well as their treatment, were analyzed. Because of the retrospective nature of this study, no attempt was made to compare surgery alone with surgery and postoperative radiation, but it was interesting to reflect on the relative and absolute indications for the use of combined treatment versus surgery alone. The above-clavicle control in this group of patients was excellent, and the relatively low incidence of distant metastases reflect that optimal local control was closely correlated with survival. Sacrifice of the facial nerve should not be routinely based on the histologic characteristics of the tumor but rather on the findings at the time of surgery. Elective regional node dissection was indicated as a staging adjuvant and to provide extra exposure and soft tissue margins of excision in large tumors without producing any significant additional morbidity.

Combined Modality Therapy↗

Plasma catecholamines in the chronically cannulated sheep fetus: predominance of L-dihydroxyphenylalanine.

Dihydroxyphenylalanine (Dopa) and catecholamines (CA) concentrations were determined in plasma collected from chronically cannulated fetal and maternal sheep from days 125-140 of gestation. Dopa was measured by a radioenzymatic assay, followed by ion exchange chromatography and high performance liquid chromatography. The assay was linear to 2.5 ng Dopa, and its sensitivity was 35-45 pg. Dopamine (DA), norepinephrine, and epinephrine were determined simultaneously by the same radioenzymatic incubation procedure, followed by solvent extraction and two-dimensional thin layer chromatography. The Dopa level in the fetal circulation was 10-25 times higher than that of DA, 5-10 times higher than that of norepinephrine, and 100 times higher than that of epinephrine. Furthermore, Dopa was the only CA that was significantly (P less than 0.05) higher in fetal (3.5-4.5 ng/ml) than in maternal plasma (1-1.5 ng/ml). The data indicate that Dopa is the predominant circulating CA in the sheep fetus. While the physiological importance of this observation is unknown at the present time, fetal Dopa might serve as the source of free DA in fetal urine and/or amniotic fluid.

Animals↗

Synchronous bilateral neck dissection.

The type of treatment used to control evident or possible metastatic cancer in the cervical region remains in dispute. When clinically positive lymph nodes are present in both sides of the neck, treatment to both sides is mandatory. If surgery is elected as the primary treatment, the neck dissection can be done bilaterally, either in one or two stages. Synchronous bilateral radical neck dissection has been associated with a high morbidity rate. It was the purpose of this paper to report the indications, complications, and results in a series of 179 synchronous bilateral neck dissections done between 1967 and 1979. In all except one instance, the internal jugular vein was saved on one or both sides. The mortality rate was 3.4 percent. Patients with histologically positive lymph nodes that were present bilaterally were found to have a reasonable prospect for cure. The rate of recurrence was related more to the inability to control the primary cancer than to treatment failure in the neck.

Carcinoma↗

Simultaneous measurement of luteinizing hormone-releasing hormone and luteinizing hormone release in unanesthetized, ovariectomized sheep.

The push-pull perfusion technique was used in combination with a sequential bleeding schedule to estimate simultaneously the release patterns of LHRH and LH in unanesthetized ovariectomized sheep and to determine the temporal relationship between the release of these two hormones. Ovariectomized (greater than 30 days) ewes received unilateral push-pull cannula (PPC) implants (od, 0.85 mm) into the median eminence. After at least 6 days of recovery, each ewe was fitted with an indwelling jugular catheter. For push-pull perfusion, a stylette was removed from the outer PPC, and an inner cannula assembly (od, 0.40 mm) was inserted. Artificial cerebrospinal fluid was pushed through the inner cannula and pulled up between the cannulae at 20 microliters/min. Continuous 10-min perfusate fractions were collected, acidified, and stored at -20 C for LHRH RIA. Blood samples were obtained every 10 min via the jugular catheter, each being drawn 5 min after the start of a perfusate collection interval. Plasma LH levels were determined by RIA. The duration of the sampling was 3-7 h. LHRH output was distinctly pulsatile, occurring at a frequency of approximately one pulse every 30-40 min (n = 5 sheep). LHRH pulse amplitude and frequency remained relatively constant throughout each perfusion. Plasma LH values also were pulsatile, and all LH peaks occurred either during the same interval or during the interval after a LHRH pulse. LH pulses always were accompanied or directly preceded by LHRH pulses, but LHRH pulses were not always followed by LH pulses. The amplitudes of LH pulses and corresponding LHRH pulses were highly correlated (r = 0.81; P less than 0.01). Histological examination revealed that detection of LHRH in perfusates depended upon the placement of the PPC tip into either the zona externa of the central median eminence or adjacent areas. These experiments demonstrate that 1) hypothalamic LHRH release in the Ovx ewe occurs in discrete pulses, with a mean interpulse interval of 38.7 +/- 1.5 min, 2) LH pulses invariably are preceded or accompanied by LHRH pulses, and 3) LH pulse amplitude is highly correlated with LHRH pulse amplitude.

Animals↗

Intracavitary chromic phosphate (32P) colloidal suspension therapy.

Two-hundred-eighty-nine patients received treatment with chronic phosphate (32P) colloidal suspension (CPCS) 346 times since 1963. One-hundred-seventy-eight patients received 200 intraperitoneal treatments. One-hundred-fifteen patients received 144 intrapleural treatments. Six patients received both intraperitoneal and intrapleural treatments. Two patients received two intrapericardial treatments. Results of therapy were evaluated three months later and then at yearly intervals. In those patients who survived three months, the referring physician observed improvement in 85% of intraperitoneal treatment and in 75% of intrapleural treatments.

Brachytherapy↗

Hypercalcemia in patients with breast cancer. Osseous metastases, hyperplastic parathyroid tissue, or pseudohyperparathyroidism?

Breast cancer is the malignant neoplasm most commonly associated with hypercalcemia. At the University of Texas M. D. Anderson Hospital, Houston, during the fiscal year 1977 to 1978, of 16,887 patients having calcium determinations, 7.8% had hypercalcemia. From 1969 to 1979, 13 patients had proved and three had presumed primary hyperparathyroidism associated with breast cancer. Two other patients had pseudohyperparathyroidism. Selective neck vein catheterization was used in 17 of the 18 patients and helped localize and confirm the diagnosis of primary hyperparathyroidism. Chloride-phosphate ratios were elevated in 13 of the 14 patients with proved or presumed primary hyperparathyroidism. This condition may mimic osseous metastases by producing brown tumors or compression fractures. In patients with breast cancer and hypercalcemia, particularly without osseous metastases, a careful diagnostic evaluation is warranted to rule out primary hyperparathyroidism.

Adenoma↗

Role of parotidectomy for skin cancer of the head and neck.

Involvement of the parotid gland or periparotid nodes by direct extension from a skin cancer or metastasis from a present or previously treated skin cancer is an uncommon but potentially disastrous event. Aggressive surgery with sacrifice of necessary structures but preservation of the facial nerve and surrounding structures when feasible results in satisfactory local and regional control. The overall local or regional control rate was 70.9 percent. Isolated metastases to the parotid gland in patients with successfully treated nonbasal cell skin cancers are controlled locally or regionally in 84.2 percent of the 57 patients reviewed. The addition of radiotherapy should be considered in patients when warranted by the pathologic findings and clinical condition of the patient, however, it is not without complications.

Adult↗

Effects of GnRH and drugs that affect cAMP levels on LH synthesis and release.

We examined basal and gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release and synthesis in response to drugs that raise intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels. Anterior pituitaries from ovariectomized rats were incubated with or without drugs in the presence of GnRH and [3H]glucosamine. Neither 8-bromo-cAMP (8-Br-cAMP) (10 mM), cholera toxin (10 micrograms/ml), nor phosphodiesterase inhibitors [theophylline, 2 and 8 mM; 3-isobutyl-1-methylxanthine (MIX), 0.2 mM] had any detectable effect on release of immunoreactive LH (IR-LH) when used alone. However, 8-Br-cAMP and the inhibitors potentiated (P less than 0.01) GnRH-induced release of IR-LH. Total radiolabeled LH in the system was elevated (P less than 0.01) by either GnRH, 8-Br-cAMP for cholera toxin, but reduced (P less than 0.01) by 8 mM theophylline and unaffected by MIX or 2 mM theophylline. 8-Br-cAMP did not alter the effect of GnRH on radiolabeled LH in the total system, whereas MIX and 2 mM theophylline reduced (P less than 0.05) it. These results suggest that 1) cAMP does not effect LH release directly, but may interact with GnRH to potentiate it, 2) GnRH and cAMP have a similar mode of action on LH glycosylation, and 3) phosphodiesterase inhibitors have additional actions that interfere with LH glycosylation.

1-Methyl-3-isobutylxanthine↗

Differential effects of cyclic nucleotide analogues and GnRH on LH synthesis and release.

We compared the effects of gonadotropin-releasing hormone (GnRH) and cyclic nucleotides on biosynthesis and release of luteinizing hormone (LH) by rat anterior pituitary glands (APs). APs from ovariectomized rats were incubated in the presence of test compounds, [3H]glucosamine, and [14C]alanine. GnRH significantly (P less than 0.01) increased both incorporation of [3H]glucosamine into LH (glycosylation) and release of immunoreactive LH (IR-LH) and [3H]LH. None of the cyclic nucleotides alone at 5 mM significantly stimulated release of IR-LH. Adenosine 3',5'-cyclic monophosphate (cAMP), N6,O2'-dibutyryl cAMP (DBcAMP), and 8-bromo-adenosine 3',5'-cyclic monophosphate (8-Br-cAMP) stimulated (P less than 0.01) glycosylation, whereas 8-Br-AMP, 8-bromoguanosine 5'-monophosphate (8-Br-GMP), cGMP, and 8-Br-cGMP had no detectable effect. Release of [3H]LH was increased by GnRH, 8-Br-cAMP, and DBcAMP, but not by other nucleotides. None of the cyclic nucleotides elevated [14C]LH, whereas GnRH elevated it (P less than 0.01) in the medium. Dose-response curves for glycosylation in response to 8-Br-cAMP and GnRH were parallel. In contrast, dose-response curves for release of both [3H]LH and IR-LH were nonparallel. It appears that cAMP can mimic the action of GnRH on LH glycosylation, but may have little direct effect on LH release.

8-Bromo Cyclic Adenosine Monophosphate↗