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Biomedical subjects

L L Anderson

Publications and source records attributed to L L Anderson.

At least 127 records · Page 7Linked to original sources

Characterization of the circulating form of porcine relaxin: biological activity and terminal amino acids.

Relaxin is structurally related to insulin, and it induces pregnancy-related changes in the reproductive tract of several mammalian species. Relaxin isolated from the ovaries of pregnant sows has been used for primary structure determination, for much of the biological characterization of the hormone, and for the development of RIAs. Immunoreactive (IR) relaxin is found in peripheral blood during pregnancy in pigs and other species, but it has not been established that the substance identified by RIA is structurally or biologically equivalent to the native ovarian hormone. IR relaxin was, therefore, isolated from peripheral plasma of late pregnant gilts (days 112-114) for bioassay and determination of terminal amino acid residues. IR relaxin was monitored by a specific homologous RIA during fractionation of plasma by gel filtration, cation exchange, and hydrophobic binding to octadecysilica. IR relaxin circulates unbound and is equipotent with ovarian relaxin in the mouse pubic ligament bioassay. Amino acids released from IR relaxin by pyroglutamic aminopeptidase and carboxypeptidase-Y were converted to their 4-dimethylamino-azo-4'-sulfonyl derivatives for identification by HPLC. The B-chain of IR relaxin had an amino-terminal pyroglutamic acid. Amino acids sequentially released from the carboxy-terminal indicated a chain length of 28-30 amino acids, suggesting a heterogeneity reminiscent of that of ovarian relaxin isolated by other methods. Arginine was released from the free amino-terminal by dimethylaminozaobenzene-isothiocyanate degradation, indicating an intact A-chain of 22 amino acids. Blood immunoreactive relaxin in pigs is, therefore, a secreted biologically active form of relaxin with an amino acid composition similar to that of the form stored in the corpus luteum.

Amino Acids↗

Relaxin regulates oxytocin secretion in late-pregnant beef heifers.

The effects of porcine relaxin (3000 units/mg) on oxytocin (OT) and progesterone secretion were studied in beef heifers on Day 274 (10 days before expected parturition). Heifers (n = 11) were randomly assigned to three treatments: relaxin iv infusions combined with im injection (RLX-INF, 9000 units), relaxin im injection (RLX-im, 6000 units), and phosphate-buffered saline-treated controls (PBS). RLX-INF heifers received infusions of PBS and 1000 units of relaxin for 165 min, followed by 2000 units of relaxin im and finally 2000 units of relaxin infusion followed by 4000 units of relaxin im. Endogenous relaxin (immunoreactive) in the PBS-treated group was 0.2-0.9 ng/ml peripheral plasma. For the RLX-im group, peak relaxin was 81 +/- 12 ng/ml (+/- SE) at 45 min after treatment. There were two peaks of relaxin, 18 +/- 5.3 ng/ml and 74 +/- 7.5 ng/ml, 3.5-4.5 hr apart in the RLX-INF group. Significant peak releases of OT were evident in the relaxin-treated heifers. For the RLX-im group, an OT peak (42 +/- 16 pg/ml) occurred within 30 min after relaxin treatment. For the RLX-INF heifers, 2000 and 4000 units of relaxin were associated with major peaks of 14 +/- 0.5 and 43 +/- 1.7 pg/ml OT, respectively. Basal OT plasma levels in the PBS group were 2.5-3.1 pg/ml. Mean plasma progesterone for all heifers was 6.2 +/- 2.11 ng/ml before treatment. There was a significant decrease in progesterone (-2.5 ng/ml) in the RLX-im group within 60 min after relaxin treatment and 45 min after peak OT secretion. The maximum decrease in progesterone (-3.2 +/- 0.68 ng/ml) occurred 135 min after treatment in the RLX-im group. In the RLX-INF group, 2000 units of relaxin infusion combined with 4000 units of relaxin im significantly decreased progesterone (-3.2 +/- 1.59 ng/ml) in peripheral plasma. These results clearly indicate that relaxin causes an acute peak release of oxytocin within 30 min, followed by a marked decrease in plasma progesterone concentration in late-pregnancy cattle.

Animals↗

Relaxin and progesterone secretion as affected by luteinizing hormone and prolactin after hysterectomy in the pig.

Plasma levels of relaxin and progesterone in hysterectomized and pregnant gilts were determined from days 100-120 to evaluate the effects of purified porcine (p) LH and pPRL on the secretory activity of the aging corpora lutea. Gilts were bred on the second observed estrus or were hysterectomized between 6-8 days after estrus (estrus = day 0) and were assigned randomly to one of three treatment groups; saline-treated control, im injections of pLH, and iv injections of pPRL from days 110-120. In control, pLH-treated, and pPRL-treated animals, average gestation lengths were 114 +/- 0.8, 116 +/- 1.9, and 115 +/- 0.5 days (+/- SE), respectively. The relaxin level in mated gilts on day 100 was less than 2 ng/ml; it began to increase after day 110 and peaked in control animals on day 113 (66 ng/ml), whereas in pLH- and pPRL-treated animals, prepartum peak values were greater (P less than 0.01) and occurred on days 113 (104 ng/ml) and 114 (117 ng/ml), respectively. Relaxin dropped to basal levels (less than 1 ng/ml) by day 115 in controls and by day 116 in both pLH- and pPRL-treated gilts. Although pLH and pPRL treatments markedly accentuated peak relaxin secretion, they did not significantly accelerate or delay parturition or delay the abrupt demise of the corpora lutea immediately postpartum. In hysterectomized gilts, relaxin began to increase after day 110, peaked in control animals on day 113 (27 ng/ml), and decreased abruptly thereafter to less than 4 ng/ml. In contrast, pLH caused an immediate release of relaxin on day 111 (23 ng/ml) and sustained elevated levels (P less than 0.01) of relaxin until day 118, but the original corpora lutea regressed. Relaxin in pPRL-treated animals increased steadily after day 110, reaching peak values by day 115 (29 ng/ml), and remained consistently elevated (P less than 0.01) until day 120. Progesterone secretion was maintained in the pPRL-treated hysterectomized gilts from days 110-120 by the original corpora lutea and with no luteinization of follicles or formation of new corpora lutea. It is evident from this study that administration of pPRL starting on day 110 enhanced and prolonged the preprogramed release of relaxin and maintained progesterone secretion by aging corpora lutea in hysterectomized animals until day 120.

Animals↗

Growth hormone-releasing factor on growth hormone secretion in prepubertal calves.

The effects of iv administration of growth hormone-releasing factor (GRF) on growth hormone (GH) release and on nitrogen metabolism were measured in prepubertal calves. Crossbred beef heifers (111 kg) were used in a Latin square design to test the effects of 0, 0.01, 0.033, 0.067, and 0.1 microgram human pancreatic (hp) GRF [hpGRF (1,40)OH]/kg body wt on plasma GH concentrations. When they were given doses of 0.067 and 0.1 microgram hpGRF/kg body wt, plasma GH increased (P less than 0.05) within 5-15 min, compared with injections of control buffer, and then returned to preinjection concentrations. The response to 0.067 microgram hpGRF/kg body wt every 3 hr for 42 hr was studied in five heifers (137 kg body wt). The animals responded to 50% of the GRF injections with an increase in plasma GH during every 6-hr period measured. Nitrogen retention, hormone concentrations, and weight gain were measured in five bull calves (90 kg body wt) administered 0 or 0.067 microgram Nle rat hypothalamic GRF (1,29)NH2/kg body wt every 4 hr for 10 days. Metabolic parameters were interpreted to indicate an anabolic response to GRF even though increases of 16% in nitrogen retention, 23% in plasma somatomedin C concentrations, and 36% in weight gain with pulsatile GRF treatment were variable and statistically similar to those of controls. These results indicate that GRF induces peak GH secretion within 15 min in prepubertal calves and that calves can respond to multiple injections of GRF with an increase in plasma GH.

Animals↗

Effects of growth hormone-releasing factor and somatostatin on growth hormone secretion in hypophysial stalk-transected beef calves.

The effects of growth hormone-releasing factor (GHRF) on growth hormone (GH) secretion were studied in beef calves after hypophysial stalk transection (HST). Peripheral GH concentration during surgery was elevated for 60 min after the initiation of anesthesia to 15 ng/ml, which was greater than plasma levels after HST and during the recovery period (0-30 hr mean, 3 ng/ml; P less than 0.05). Episodic GH secretion normally seen in sham-operated controls (SOC) was abolished after HST. Before HST, calves responded to 80% of the GHRF challenges, whereas after HST calves responded to every challenge of GHRF with an increase in plasma GH. A dose of 0.067 microgram human pancreatic (hp) hpGHRF(1-40)OH/kg body wt 3 days after HST increased plasma GH to 55 ng/ml from a control period mean of 5 ng/ml (P less than 0.04). On Day 8, HST calves received two injections of 0.067 microgram hpGHRF/kg body wt at 3-hr intervals, with feeding 70 min after the first injection. During two preinjection control periods, basal GH averaged less than 4 ng/ml and increased to 17 (P less than 0.02) and 9 (P less than 0.04) ng/ml immediately after the first and second injection of hpGHRF, but the response declined over the 8-day period after surgery. On Days 19 and 20, the HST calves were infused iv with 0.033 and 0.067 microgram somatostatin(SS)-14 (SRIH)/kg body wt, during which a pulse injection of 0.067 microgram hpGHRF/kg body wt was administered. GH increased to 9 and 5 ng/ml during the 0.033- and 0.067-microgram SRIH infusions after GHRF; no somatotropic rebound was observed after the SRIH was discontinued as was seen in the animals while the hypothalamic-hypophysial connections were intact. Five and six months after HST the responses to two analogs of rat hypothalamic GHRF were similar to those in SOC calves. These results indicate that HST calves responded to exogenous GHRF with an abrupt increase in plasma GH, but GH response to GHRF during SRIH infusion was greatly inhibited.

Animals↗

Early effect of myo-inositol deficiency on phosphatidylinositol metabolism in rat liver.

Young rats (100 g) were fed either a myo-inositol-deficient or supplemented (control) diet for up to 14 days following a 12 h fast. At various times during this period animals were killed, livers were removed, and a microsomal fraction was prepared and assayed for CDPdiacylglycerol inositol transferase activity and for phosphatidylinositol-inositol exchange activity. Within 2 days after beginning the regimen, rats consuming the deficient diet had a 40% lower activity of the transferase than rats consuming the control diet. This difference was maintained throughout the feeding period and developed simultaneously with the accumulation of triacylglycerol in the deficient livers. In contrast, the specific activity of the exchange enzyme was unchanged by feeding the deficient diet.

Animals↗

Induction of parturition, progesterone secretion, and delivery of placenta in beef heifers given relaxin with cloprostenol or dexamethasone.

Sixty primiparous beef heifers from a crossbreeding study were used to examine the effects of inducing parturition with relaxin (3,000 U/mg) combined with cloprostenol (500 micrograms, i.m., n = 30) or dexamethasone (20 mg, i.m., n = 30) at Day 273, 10 +/- 1 days before expected parturition (Day 283). Heifers were assigned at random within cloprostenol and dexamethasone groups to receive relaxin (1 mg, n = 5/treatment), i.m. or in the cervical os (OS), at 0 h (the same time as cloprostenol and dexamethasone) or 24 h later. Eleven and six first-calving heifers and sixteen and nine second-calving cows also received cloprostenol + relaxin and cloprostenol + phosphate-buffered saline, respectively. Radioimmunoassay of daily plasma samples indicated an abrupt decrease in progesterone with time (p less than 0.001), from 7.5 +/- 0.50 to 1.0 +/- 0.30 ng/ml (mean +/- SE) within 48 h for all groups. The mean rate of progesterone decrease (ng/ml in 24 h) was accelerated (p less than 0.01) in relaxin-treated heifers (5.3 +/- 0.36), in contrast to dexamethasone- and cloprostenol-treated control heifers (2.8 +/- 0.40). Relaxin combined with cloprostenol or dexamethasone shortened the calving period in these heifers by reducing the interval between treatment and calving (33 vs. 56 h; p less than 0.01). The incidence and duration of retained placenta were reduced by 22 vs. 75% and 14 vs. 34 h for relaxin combined with cloprostenol or dexamethasone as compared with cloprostenol- or dexamethasone-treated controls, respectively (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Lung tumors: percutaneous implantation of I-125 sources with CT treatment planning.

Seven patients with lung tumors underwent percutaneous implantation of iodine-125 sources into the tumor. Needle placement and seed implantation were effected with biplane fluoroscopy and a computer planning model based on computed tomography. No complications were encountered. Five of the seven patients underwent the procedure at the outpatient center and were discharged the same day. Follow-up radiologic evaluations were available for six patients; in all six the examination demonstrated tumor shrinkage, and in four tumor shrinkage was essentially complete.

Adenocarcinoma↗

Acute decrease in progesterone and increase in estrogen secretion caused by relaxin during late pregnancy in beef heifers.

Purified porcine relaxin (3000 U/mg) was administered im (RLX-IM; 1 mg; n = 2) and in the cervical os (RLX-OS; 1 mg; n = 2) on day 273 (approximately 10 days before parturition normally occurs) of gestation to determine the profiles of immunoreactive relaxin and its effects on progesterone, estrone (E1), and 17 beta-estradiol (17 beta-E2) secretion in peripheral blood plasma of beef heifers. Controls received either 0.01 M PBS (1 ml, im; n = 2) or 0.01 M gel-PBS (gel; 1 ml, os; n = 2) in cervical os. One relaxin-treated (im) heifer calved at 4 h and 36 min after treatment; thus, data from this heifer were not included in subsequent analysis. Relaxin-treated heifers showed an acute elevation in relaxin, a precipitous decrease in progesterone, and a significant (P less than 0.05) elevation of E1 and 17 beta-E2. Plasma relaxin levels were 4.95, 1.5, and 0.24 ng/ml at 0.5 h in RLX-IM, RLX-OS, and control animals, respectively. Peripheral plasma relaxin peaked between 23-31 ng/ml 1-2.5 h before returning to less than 0.5 ng/ml 5-12 h after treatment. Relaxin administration accounted for 70%, 73%, and 58% of the progesterone, E1, and 17 beta-E2 variability between treatments, respectively. An abrupt decrease (P less than 0.01) in progesterone preceded the rises (P less than 0.05) in E1 and 17 beta-E2 at 1.5, 2-2.5, and 2-3.5 h, respectively. Maximum progesterone deviations from the pretreatment mean concentration were -5.43, -3.05, and -0.92 ng/ml for RLX-IM, RLX-OS, and controls. Progesterone rebounded from 36% to 61% and 62% to 79% of respective pretreatment means for RLX-IM and RLX-OS. Peak elevation of E1 was 407.3, 306.5, and 71.5 pg/ml and that of 17 beta-E2 was 82.2, 35.8, and 7.8 ng/ml for RLX-IM, RLX-OS, and controls, respectively. These results provide strong evidence that a pharmacological dosage of relaxin induces an acute depression of progesterone secretion beginning within 90 min in beef heifers during late pregnancy. We suggest that these early and marked luteolytic effects of relaxin on progesterone secretion in cattle could be by direct or indirect actions via mechanisms that are yet unknown.

Animals↗

Limb preservation and tumor control in the treatment of popliteal and antecubital soft tissue sarcomas.

Soft tissue sarcomas of the antecubital and popliteal space often involve the neurovascular bundle and are prone to recurrence after surgical resection. Amputation has frequently been performed for control of these tumors. A multimodality treatment program consisting of limb-sparing resection, tumor-bed radiation using temporary iridium 192 implants, and adjuvant chemotherapy for high-grade lesions, has yielded satisfactory preservation of limb function and no local tumor recurrence in ten patients after a median follow-up time of 5 years. Eight of the ten patients are still alive, five of whom beyond 5 years; six of the eight survivors had high-grade tumors. These results are superior to those of 14 patients with similar tumors treated earlier by surgery alone: seven by amputation and seven by soft part resection; four of the latter resulted in local recurrence and all of the seven who had high-grade sarcoma died of disease. Multimodality treatment including limb-sparing resection merits consideration in the management of antecubital and popliteal soft tissue sarcomas.

Adolescent↗

On a method of dosimetry planning and implantation of 125I for interstitial irradiation of malignant gliomas.

Utilizing a treatment concept geared to the cell cycle of the glioma, a CT determined tumor volume and boundaries, 125I dosimetry data and a reference probe template system, it is now feasible to produce a volume implant of an intracranial mass based on prospective planning with accurate postimplant correspondence. The cell cycle oriented treatment plan is felt perhaps to be more beneficial in the treatment of the highly malignant glioblastoma, considering its wide range of cell cycle times, large irregular volumes and large dormant segment, than would be a similar isotope source delivering a high-dose rate, but short-term course irradiation. Seeds are contained within Lexan tubes, thereby allowing accurate assessment of postoperative dosimetry planning, negating seed migration and possible 'cold spots' within a volume implant as would be noted with unrestrained seeds. The implant described in this communication is designed to remain in place for approximately 20 months, a period of time well beyond the life expectancy of any group of failed glioma patients. Although ultimately the system may prove most beneficial in newly diagnosed glioblastomas, the current trial in patients having previously undergone 5-6000 rads of external beam therapy is not considered hazardous to surrounding brain.

Brachytherapy↗

Pelvic development as affected by relaxin in three genetically selected frame sizes of beef heifers.

Purified porcine relaxin was administered into the cervical os on Day 278 of gestation to determine its effects on pelvic development in three genetically selected frame sizes of primiparous beef heifers. Heifers were categorized as small, medium and large frame based upon their genetic composition. Pelvic height, pelvic width and cervical dilatation were determined from Day 270 to 2 days postpartum. On Day 270, heifers were assigned at random to one of three treatments: vehicle control, n = 16; relaxin once (3,000 U), n = 14; and relaxin twice (2 times 3,000 U 12 h apart), n = 17. Each heifer-frame size was represented in each treatment. Relaxin caused marked increases in pelvic height and width, as well as in the rate of linear increase (cm/day) of these parameters (p less than 0.05). These linear increases in pelvic height were 510, 264 and 204%, and pelvic width, were 280, 213 and 204% of the respective pretreatment rates for small, medium and large heifers. The rate of linear increase in pelvic width was greater than pelvic height in all heifers, but maximal in small-frame heifers; relaxin attenuated these intrinsic differences. For small heifers, the rate of linear increase in pelvic width was 121 and 145% of increases for medium and large heifers, respectively, before treatment, and 160 and 200% after treatment. The rate of postpartum involution of pelvic width was -0.03, -0.36 and -0.50 cm/day and, for pelvic height, -0.02, -0.27 and -0.29 cm/day in small, medium and large heifers, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hypothalamic deafferentation and luteinizing hormone-releasing hormone effects on secretion of luteinizing hormone in prepubertal pigs.

The control of luteinizing hormone (LH) secretion was investigated in ovariectomized, prepubertal Yorkshire pigs by comparing the effects of anterior (AHD), complete (CHD), and posterior (PHD) hypothalamic deafferentation to sham-operated controls (SOC). Gilts (n = 16) were assigned randomly to treatments, fitted with an indwelling jugular catheter, and ovariectomized 2 days before deafferentation or sham-operation (Day 0). Blood for radioimmunoassay (RIA) of LH was collected sequentially at 20-min intervals for a period of 2 h before and 24, 48, 72, and 96 h after hypothalamic deafferentation or SOC. Episodic LH release after AHD or CHD was abolished (p less than 0.01), but not after PHD or SOC. Concentrations of serum LH in AHD and CHD dropped (p less than 0.01) at 24 and 48 h after surgery. Levels of LH before and after surgery in PHD and SOC were similar (p greater than 0.05). Infusion of 25 micrograms LH-releasing hormone (LHRH) i.v. at 72 and 96 h after hypothalamic deafferentation and SOC increased (p less than 0.01) serum LH to peak levels within 15 min. after infusion; LH returned to basal levels 60-80 min later. By 96 h after surgery, LH response to LH-releasing hormone (LHRH) was less in AHD and CHD as compared with the response at 72 h postinjection. Concentrations of LH in PHD and SOC were similar (p greater than 0.05) at 72 and 96 h, respectively. The results from this study clearly indicate that neural stimuli originating or traversing the neural areas rostral to the median eminence are required for secretion of LH in the pig.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Relaxin on induction of parturition in beef heifers.

Purified porcine relaxin (3000 U/mg) was administered into the cervical os of primiparous beef heifers on day 278 of gestation (approximately 5 days before parturition normally occurs) to determine its effects on the induction of parturition, changes in progesterone, estrone (E1), 17 beta-estradiol (17 beta-E2), cervical dilation, and pelvic relaxation. Heifers were assigned randomly to 1 of 3 treatments: relaxin-double (two infusions of 3000 U, 12 h apart; n = 17), relaxin-single (3000 U; n = 14), and PBS-gel vehicle (n = 16). Relaxin induced marked earlier calving (P less than 0.002) than PBS-gel vehicle. The intervals between the administration of relaxin or the PBS-gel vehicle and calving were 2.0, 2.5, and 5.3 days for heifers given relaxin-double, relaxin-single, and PBS-gel vehicle, respectively. The duration of gestation was significantly reduced (P less than 0.002) in relaxin-treated heifers compared with that in control heifers. A precipitous decrease in progesterone (7.1 ng/ml) occurred in peripheral blood plasma within 24 h after relaxin treatment. Coincident with a decline in levels of progesterone, E1 and 17 beta-E2 increased by 1700 and 400 pg/ml, respectively, an increase of 35% compared with the 12% increase in these steroids in control heifers. Mean deviations of cervical dilation increased 643%, 526%, and 11% in heifers given relaxin-double, relaxin-single, and PBS-gel vehicle, respectively. Relaxin induced maximum pelvic opening between 12-36 h after treatment. Although relaxin induced significantly earlier calving, there was no incidence (0 of 31 heifers) of retained placenta. We conclude from this study that purified relaxin administered intracervically to primiparous beef heifers during late pregnancy induced premature parturition. Marked shifts of progesterone, E1, 17 beta-E2, pelvic canal expansion, and cervical relaxation reflect the premature parturition induced by relaxin.

Animals↗