Excessive alpha-fetoprotein concentrations in hepatocellular carcinoma.
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Biomedical subjects
Publications and source records attributed to W F White.
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Long-term administration of [D-Leu6, des-Gly-NH210, Pro-ethylamide9]-GnRH, an analog of gonadotropin releasing hormone, caused regression of neoplastic tissue in a rat bearing a spontaneous mammary adenocarcinoma and in rats in which tumors had been induced by treatment with dimethylbenzanthracene (DMBA). During two separate treatment periods with the analog, the tumor in the single animal regressed although it had previously grown spontaneously. After a third period of growth, ovariectomy also induced regression, suggesting endocrine dependency of the tumor. These observations were confirmed in the DMBA-induced tumor system, where tumor regression in the analog-treated rats was comparable to that observed in the ovariectomized rats, and in both cases the tumor regression was significant when compared to untreated controls.
The projection from the contralateral entorhinal cortex to the dentate gyrus is shown to exert a monosynaptic excitatory action. Stimulation of the contralateral entorhinal cortex evokes unitary granule cell discharges in the dentate gyrus. This evoked activity is followed by a period of inhibition lasting about 50 msec. Laminar analyses of field potentials generated by contralateral medial entorhinal stimulation localize the synaptic activity to the middle portion of the granule cell dendrites. This localization is consistent with the termination site of the contralateral entorhinal projection as previously shown anatomically. Earlier studies have indicated that the entorhinal cortex excites only the ipsilateral dentate gyrus. These findings now demonstrate that the cortical input to the dentate gyrus is bilateral in normal rats. However, the contralateral projection appears to be much less efficacious than the ipsilateral input.
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Studies were performed in immature and mature female rats to determine the effects of chronic administration of [D-Leu6,des-Gly-NH210, Pro-ethylamide9]-gonadotropin-releasing hormone (GnRH) upon maturation and maintenance of reproductive function. Treatment of immature rats inhibited normal overian growth and maturation as evidenced by arrest of uterine growth, delay of vaginal opening, and absence of normal cycling. The primary responses in the mature animal were cessation of cycling, atrophy of the ovaries to a "prepuberal" size, and uterine weight regression. In both groups termination of treatment was followed by prompt restoration of normal ovarian mass and function, including support of breeding processes. The results presented here suggest that chronic administration of the GnRH analog inhibits ovarian steroid output either by direct action of the analog on the ovary or indirectly through qualitative or quantitative changes in levels of luteinizing hormone and follicle-stimulating hormone.
Ss were 46 preschool boys and girls, ages three, four, and five years, in a child and family development center. Each child, his mother, father, and teacher were administered, separately, 18 select items from the primary factor in the I Feel-Me Feel self-concept inventory. Results indicated that the childrens' self/social constructs scores were very stable but did not correlate with scores of mother, father, and teacher. The adult percepts of the child's self-concept were highly correlated ( less than .05) among themselves, but they were not in the same system of relationships with the children.
1. Brain synaptosomal fractions released both endogenous and exogenously loaded noradrenaline and gamma-aminobutyric acid (GABA) in response to calcium. Elevation of magnesium concentrations in the release media decreased the calcium-dependent release. 2. The release of noradrenaline and GABA occurred within 250 msec following the application of calcium. Following the initial response to calcium, release progressively decreased with continued application of calcium. GABA release declined more rapidly than noradrenaline release, consistent with a noradrenaline distribution having greater accessibility to the release process. 3. Sodium was required for the loading of noradrenaline and GABA into pools released by calcium. On the other hand, the presence of sodoium was not required for release from previously loaded pools. 4. Microsomal fractions did not exhibit calcium-dependent release of noradrenaline or GABA. Furthermore, exogenously loaded lysine was not released from synaptosomal fractions in response to calcium. 5. Barium and strontium, but not magnesium, stimulated noradrenaline and GABA release in the absence of calcium. The ordering of alkaline earth efficacies was barium greater than strontium greater than calcium. 6. Manganese inhibited calcium-dependent release of noradrenaline and GABA to a greater extent than magnesium. 7. Release, in response to 1 mM calcium, increased linearly with the log. [K+]0, suggesting that a voltage-dependent calcium inophore limits release. The slope of release vs. log. [K+]0 was greater for noradrenaline than for GABA. 8. For a given [K+]0 less than 55 mM, increases in external calcium concentration above 1 mM increased noradrenaline release but decreased GABA release. These data suggest that calcium can decrease its own permeation and that differences in the release process may exist for different neurotransmitters. 9. In the presence of the artificial calcium ionophore, A23187, both noradrenaline and GABA release increased linearly with the log. [Ca2+]0. The slope for noradrenaline release was greater than that for GABA release. 10. Stimulus-secretion coupling in brain is suggested to be regulated at the level of a voltage dependent calcium permeation mechanism. However, basic differences in the interaction of calcium with the release process may exist between the noradrenaline and GABA systems.
A synthetic analog of gonadoliberin (gonadtropin-releasing factor of luteinizing hormone/follicle-stimulating hormone-releasing hormone), designated A-43818, was evaluated for its ability to effect regression of carcinogen-induced mammary tumors in the Sprague-Dawley rat. This analog, specifically (D-leuyl6, desglycyl-NH210, prolyl ethylamide9), gonadoliberin, is a potent synthetic luteinizing hormone/follicle-stimulating hormone-releasing hormone at low dose levels but, at the higher dose levels used in these studies, the effect appears to be that of a potent gonadoliberin antagonist. Administration of 5 or 20 mug of A-43818 per day to tumor-bearing rats was essentially as effective as ovariectomy in causing mammary tumor regression. At least 80% of the tumors in the A-43818-treated animals underwent regression; about one-half of the regressing tumors disappeared in the 6-week period of continuous treatment, and, unlike the 0.9% NaCl solution control group, no new tumors appeared during the treatment period. A subsequent 4-week period of drug withdrawal resulted in the regrowth of palpable tumors and the appearance of new tumors, most of which again regressed on further A-43818 administration.
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30 Ss scoring between 125 and 139 and 30 (out of 100) from 79 to 112 on the California Short-form Test of Mental Maturity were significantly different on the 16 PF only on Factors B and H (p = .05) and not on the California F scale. Significant comparisons appeared to be chance effects.
The ovulation-inducing and gonadotropin-releasing activities of [d-Leu-6, des-Gly NH2-10, Pro-ethylamide-9]-GnRH (II), were evaluated in rats, rabbits, and sheep. A sc dose of 3.4 ng/100 g body wt of the analog was equal to 160 ng/100 g body wt of GnRH in causing ovulation in the diestrous rat. At these dose levels, the integrated LH release was 1.9 times greater for the analog. Both the time of increase and maximum serum concentrations of LH were delayed after injection of the analog. Oral administration of II and GnRH to the proestrous rat resulted in an ED50 for ovulation of 0.92 and 54 mug/100 g body wt,respectively. Serum levels of LH and FSH were highly variable for the various treatment groups when both releasing substances were administered orally. The intense ovulating activity of II was also evident in the estrous rabbit as indicated by an activity 31 times greater than that of GnRH. Additionally, the analog was at least 50 times more active than GnRH in releasing LH in both the mid-luteal and anestrous ewe. From our experiments with the cycling rat it appears that the intense ovulation-inducing activity of II can be accounted for by the intrinsic LH-releasing activity of the nonapeptide, rather than by a prolonged release stimulus.
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