Human Y-chromatin : I. Dispersion and condensation

The fluorescent Y-body was observed to manifest striking variations in morphology in interphase lymphocyte and fibroblast nuclei. These variations appeared to be largely independent of the specific fixation or hypotonic treatment. The Y-chromatin body ranged from a highly condensed mass to a constellation of smaller discrete particles. Dispersion of Y-chromatin was not seen in mitotically inactive cells from buccal mucosa and hair root sheaths. Comparison of uncultured and cultured lymphocytes confirmed a higher proportion of dispersed Y-bodies in cultured cells, particularly those with a relatively large mean nuclear diameter. In serially cultured lymphocytes, the frequency of Y-body dispersion showed a direct relationship to the time in culture. Mean nuclear diameter also increased directly with time in culture. In cultured fibroblasts dispersion of the Y-body increased during the logarithmic phase of growth and declined during the post-logarithmic phase.     

Plasma 13, 14-dihydro-15-keto-PGF2 (PGFM) in pregnant and nonpregnant heifers prior to and during surgery and following intrauterine injection of PGF2

On day 17 postestrus or postmating, heifers were given intrauterine injections of saline (2 pregnant, 2 non-pregnant) or 200 μg PGF₂α (7 pregnant, 6 nonpregnant) through cannulae installed surgically into the uterine horn ipsilateral to the corpus luteum bearing ovary. Jugular blood samples were collected prior to the laparotomy at which the cannulae were installed during surgery, and for 90 min following the intrauterine injection. Plasma was assayed for progesterone and 13,14-dihyro-15-keto-PGF₂α )PGFM). Laparotomies were reopened to confirm proper cannula placement and to determine if blastocysts were present in mated heifers. Concentrations of PGFM were higher in pregnant compared to nonpregnant heifers during the presurgery (68 26 24 26 pg/ml; P < 0.25) and surgery (186 47 65 17 pg/ml; P < .05) periods. Pregnancy status did not alter the mean concentrations of PGFM (pregnant, 554 70 pg/ml; nonpregnant, 422 81 pg/ml) or the half-life of its decline in concentration (18 min) following intrauterine injection of PGF₂α. Pregnancy at 17 days in cattle does not appear to influence PGF₂α transport from the uterine lumen or its metabolism in the uterus or elsewhere in response to an acute intrauterine injection.     

The effect of prostaglandin I2 on the contractility of the term pregnant human myometrium

Small myometrial strips were dissected from the upper and lower segments of the term pregnant human uterus. The specimens were superfused in organ chambers and contractile activity was recorded isometrically.In strips from the upper segment, prostacyclin (PGI₂), induced an initial excitatory response followed in the majority of experiments by transient inhibition. In the lower segment the response was generally the same although direct inhibition without initial stimulation occurred in some cases.During the period of inhibition the specimens were refractory to iterated exposure to PGI₂. Furthermore, during this period of PGI₂-induced inhibition the muscle strip was also refractory to PGE₂ but responded to PGF_2α and oxytocin by stimulation.After inhibition of spontaneous contractile activity induced by indomethacin PGI₂ induced an excitatory response.The results do not indicate any critical change in the myometrial responsiveness of the upper uterine segment to PGI₂ during labor. In strips from the lower segment obtained before labor there tended to be a dominance of non-responders and inhibition only as compared to the results during labor. Nevertheless, whether or not PGI₂ under physiological or pharmacological conditions has any significant influence on the contractility of the term pregnant human uterus, still remains obscure.As judged from earlier reports from our laboratory and the present study it is evident that the uterine vessels are considerably more sensitive to the action of PGI₂ than the myometrium.     

Dopamine inhibition of anterior pituitary adenylate cyclase is mediated through the high-affinity state of the D2 receptor

The diterpinoid forskolin stimulated adenylate cyclase activity (measured by conversion of [³H]-ATP to [³H]-cAMP) in anterior pituitary from male and female rats. Inhibition of stimulated adenylate cyclase activity by potent dopaminergic agonists was demonstrable only in female anterior pituitary. The inhibition of adenylate cyclase activity displayed a typically dopaminergic rank order of agonist potencies and could be completely reversed by a specific dopamine receptor antagonist. The IC₅₀ values of dopamine agonist inhibition of adenylate cyclase activity correlated with equal molarity with the dissociation constant of the high-affinity dopamine agonist-detected receptor binding site and with the IC₅₀ values for inhibition of prolactin secretion. These findings support the hypothesis that it is the high-affinity form of the D₂ dopamine receptor in anterior pituitary which is responsible for mediating the dopaminergic function of attenuating adenylate cyclase activity.     

Kinetic study of reduction of [Tc(V)OBr5]2− in concentrated HBr

Pertechnetate is rapidly reduced in concentrated (8.7 M) HBr to Tc(V). Subsequently reduction to give TcBr₆^2? is a slow process. The kinetics of this last process have been investigated. They indicated a combination of first and zero order reactions in the presence of the high HBr concentration. The first order rate constant was 4.8 × 10^?2 h^?1, and the zero order process constant was 6.0 × 10^?6 mol l^?1 h^?1.     

Quantitation of submandibular proteins resolved from normal individuals and children with cystic fibrosis

Submandibular secretions collected from children with cystic fibrosis (CF) showed increased protein concentration (milligrams/milliliter) and increased amylase specific activity (units/milligram of protein) relative to normal secretions. These differences between normal (N) and CF secretions were as follows: protein, 1.25 ± 0.51 (N), 1.75 ± 0.35 (CF) (P < 0.02); and amylase, 58 ± 18 (N), 80 ± 19 (CF) (P < 0.001). To determine the basis for elevated protein in CF saliva, several major proteins resolved by polyacrylamide disc gel electrophoresis were quantitated by densitometry. These included four phosphoproteins (PP), serum albumin, an acid phosphatase-containing fraction, amylase, and an unidentified protein referred to as PI-7.1. Together, these proteins comprise greater than 75% of the total protein in the secretion. Differences in individual protein concentrations (milligrams/milliliter) resolved from normal and CF secretions, respectively, were as follows: PP₂, 0.02 ± 0.01, 0.03 ± 0.02 (NS, not significant); PP₃, 0.06 ± 0.04, 0.05 ± 0.03 (NS); acid phosphatase fraction, 0.06 ± 0.04, 0.12 ± 0.07 (P < 0.05); amylase, 0.09 ± 0.04, 0.27 ± 0.16 (P < 0.01); and pI-7.1, 0.04 ± 0.02, 0.13 ± 0.08 (P < 0.02). Amylase, the most significant contributor to the elevated protein, comprised 26% of the total protein of normal secretions and 38% of the total protein of CF secretions. Thus, our results do not support the concept of a generalized increase in all organic components in CF submandibular secretions but, rather, increases in specific proteins, namely amylase, component pI-7.1, and an acid phosphatase-containing fraction.     

Ovulation and implantation in montane voles (Microtus montanus) as a function of varying amounts of copulatory stimulation

Estrous female voles (Microtus montanus) received (a) no copulation, (b) one ejaculatory series, (c) two ejaculatory series, or (d) more than two series. Copulation was shown to be essential for ovulation, and increasing amounts of copulatory stimulation were demonstrated to increase the probability of ovulation. Only 25% of females receiving one ejaculatory series ovulated, whereas 100% of those receiving more than two series ovulated. Thus, multiple ejaculations play an important role in successful reproduction in this species.     

A study of three vasodilating agents as selective inhibitors of thromboxane A2 biosynthesis

Three clinically efficacious vasodilatory drugs were found to be selective inhibitors of thromboxane A₂ biosynthesis. Hydralazine, dipyridamole, and diazoxide inhibited platelet aggregation at 1 × 10^?4 M, 1.75 × 10^?4 M, and 2 × 10^?3 M respectively. Their relative inhibitory potencies on thromboxane B₂ production in human platelet microsomes were examined and found to be similar to that observed for their inhibition on human platelet aggregation. At 10^?3 M, hydralazine, dipyridamole, and diazoxide inhibited thromboxane B₂ formation by 65 percent, 27 percent and 18 percent respectively. These compounds were examined in the sheep vesicular gland system, and they were shown not to be inhibitors of the cyclooxygenase enzyme. Thus, the inhibition of thromboxane A₂ biosynthesis by these three drugs in human platelet microsomes appeared to be specific at the thromboxane synthetase level.     

The effect of 7-oxa-13 prostynoic acid on the mechanism of action of bradykinin in human synovial fibroblasts

Bradykinin, a potent inflammatory mediator, induces an increment in intracellular cyclic AMP concentrations of human synovial fibroblasts and evokes the synthesis and release of ³H-arachidonic acid and ³H-E prostaglandins from these cells pre-labeled in their phospholipids. Fetal calf serum in the media also stimulates the synthesis and release of these labeled lipids from pre-labeled human synovial fibroblasts and potentiates the bradykinin-induced cyclic AMP response. The PGE₁ analogue, 7-oxa-13 prostynoic acid, completely abrogates both the bradkinin-induced cyclic AMP response and the bradykinin- and fetal calf serum-evoked release of labeled E-prostaglandins from pre-labeled cells. In serum-free media, the prostaglandin antagonist stimulated the release of ³H-arachidonic acid from pre-labeled human synovial fibroblasts and did not inhibit the bradykinin-induced release of this lipid.     

The binding of [3H]nitrendipine to receptors for calcium channel antagonists in the heart,cerebral cortex,and ileum of rats

The binding properties of the calcium channel antagonist, [³H]nitrendipine, were investigated in homogenates of the rat cerebral cortex, heart and ileum. The specific component of [³H]nitrendipine binding was consistent with mass-action behavior and was characterized by a high affinity dissociation constant in the range of 0.1 ? 0.3 nM. A variety of other calcium channel antagonists inhibited the binding of [³H]nitrendipine with K_i's that agree generally with the ability of these drugs to block contractions of cardiac and smooth muscle. The inhibition of [³H]nitredipine binding by other dihydropyridines was consistent with competitive antagonism whereas the inhibition caused by verapamil and D600 resembled negative heterotropic cooperativity. Consistent with this latter postulate was the observation that the kinetics of [³H]nitrendipine binding are altered by verapamil, with both the association rate and the dissociation rate being increased. La⁺³ and several divalent cations caused an inhibition of [³H]nitrendipine with the rank order of potency being Cd⁺² > La⁺³ > Ni⁺² > Co⁺² ? Mn⁺² > Mg⁺² ? Ba⁺² > Ca⁺².     

Specific in vivo binding of 77Br-p-bromospiroperidol in rat brain: A potential tool for gamma ray imaging

The binding of the gamma labeled neuroleptic, ⁷⁷Br-$\text{p}$-bromosprioperidol, in the rat brain was examined $\text{in vivo}$. This binding parallels the binding of ³H-spiroperidol, in that binding is especially high in dopaminergically innervated areas, is saturable, and is displaced by high doses of unlabeled spiroperidol (1–5). Thus, ⁷⁷Br-$\text{p}$-bromospiroperidol is a suitable ligand for use in gamma ray imaging techniques for $\text{in vivo}$ monitoring of receptor binding.     

An analysis of sandbathing and grooming in the kangaroo rat (Dipodomys merriami)

The sandbathing and grooming behaviour of ten kangaroo rats (Dipodomys merriami) were recorded on sand and woodchip substrates after periods of 0,1,5 and 10 days without sand. Sandbathing is restricted to the sandy substrate. Grooming occurs on both, but with a higher frequency on sand. Increases in both grooming and sandbathing occur with increasing sand deprivation, but the temporal patterning does not change. D. merriami tends to alternate sandbathing components in contrast to other Dipodomys species. Lipid on the pelage increases noticeably with sand deprivation and decreases during a sandbathing bout; sand appears to be removed from the pelage by shaking and grooming. These findings suggest a three-process system for care of the body surface.     

Pharmacologic identification of muscarinic receptors in the pylorus of the cat by binding of [3H]-quinuclidinyl benzilate

Muscarinic receptors in the smooth muscle of the cat pylorus (pyloric sphincter) were identified by binding of the ligand (±) [³H]-quinuclidinyl benzilate ([³H]-QNB). Receptor related binding of [³H]-QNB reached steady-state in thirty minutes at 37°C, was saturable, showed pharmacologic specificity and was stereoselective. An apparent equilibrium dissociation constant, K_D, of 1.9 ± 0.3 nM and maximum receptor concentration of 122 ± 13 femtomoles per mg of protein (means ± S.E.M.) were determined from Scatchard plots of [³H]-QNB binding. Hill coefficients of 0.99 and 1.01 indicated the absence of cooperative interactions. The muscarinic antagonists atropine and propantheline inhibited binding with IC₅₀ values in the nanomolar range, whereas bethanechol was over four orders of magnitude less potent. Noncholinergic agents had little or no effect on [³H]-QNB binding. The $\text{levo}$ isomer of QNB was about seventy times more effective at inhibiting binding than its $\text{dextro}$ isomer while $\text{dextro}$ benzetimide was greater than two thousand fold more active than $\text{levo}$ benzetimide. The isomers of another anticholinergic compound, tropicamide, also competed for [³H]-QNB binding sites in a stereoselective manner, the $\text{levo}$ isomer being eighty-five times more potent than the $\text{dextro}$ isomer.     

Increased queen-like behaviour of workers in large colonies of the sweat bee Lasioglossum zephyrum

Observations were made on Lasioglossum zephyrum colonies containing from one to 17 workers. In experiment I, the most dominant workers in larger colonies exhibited more queen-like characteristics in their interactions with nestmates than did those in smaller colonies. In experiment II, a higher proportion of workers in large than in small colonies were willing to mate with males. These results are consistent with the hypothesis that the queen's ability to suppress queen-like behaviour in workers declines with increasing colony size.     

Quantitation and interaction of glycosaminoglycans with Alcian blue in dimethyl sulfoxide solutions.

An improved method is described for the quantitation of glycosaminoglycans separatedon cellulose acetate, stained with Alcian blue, and dissolved in a dimethyl sulfoxide solution. Standard curves are shown for all eight glycosaminoglycans. It is shown that absorption at the Alcian blue orthochromatic E_max is depressed under conditions which favor formation of dye-glycosaminoglycan complexes. The interaction between Alcian blue and the eight glycosaminoglycans was studied in dimethyl sulfoxide solutions of varying composition. It was shown that the extent of complex formation depends both on the glycosaminoglycan and the composition of the dimethyl sulfoxide solution. A dimethyl sulfoxide solution which contains 0.094 m H₂SO₄ is described which maximizes dye-glycosaminoglycan dissociation and thus the absorbance. Also, an improved staining method is described which improves dye uptake by the glycosaminoglycans and consequently increases the sensitivity of glycosaminoglycan quantitation.     

Interaction of poly(l-lysine) and Ca2+ with stearic acid monolayers

Interaction of poly(l-lysine) and Ca²⁺ with stearic acid monolayers is studied at pH 9.1, 9.9 and 10.7. The competition between the condensation effect of Ca²⁺ and the expansion effect of the protein on the monolayer is seen to depend on surface pressure as well as pH. Ca²⁺ is much less effective in the competition when the poly(l-lysine) penetration into the monolayer is stabilized by electrostatic interactions.     

Selective retention of T cell precursors in bone marrow. Cell populations after filtration through anti-immunoglobulin columns.

Lethally irradiated mice transplanted with normal syngeneic bone marrow have restored their immunocompetence 2–4 weeks after transplantation. During regeneration T cells seem to develop more slowly than B cells. We have studied the impact of anti-Ig column fractionation of bone marrow cells on their subsequent development into T cells. The results showed that in mice grafted with anti-Ig column-passed bone marrow cells (a) the number of θ-positive cells which develop was very much reduced, and (b) the development of GVH reactive cells and helper cells was much delayed when compared with mice grafted with normal unpassed bone marrow cells. In contrast, the development of B cell function and of the hematopoietic system was always normal. It was concluded that one possible explanation for such findings was the existence of immunoglobulin on T cell precursors.     

Reversal of social deficits produced by isolation rearing in monkeys

A major body of research has clearly demonstrated that rearing monkeys for at least the first 6 months of life in total social isolation from conspecifics produces profound psychopathology, including both massive social deficits and ideosyncratic self-directed behaviors rarely seen in normal monkeys. Previously, isolation-induced psychopathology was thought to be permanent, and various theoretical explanations, e.g. critical periods and “emergence trauma” were posited to account for such phenomena. Recent research at Wisconsin has indicated that the isolation syndrome in monkeys is, in fact, reversible, rendering the above theoretical positions inadequate. In this paper, the procedures for successful rehabilitation of isolate-reared monkeys are described and an alternative theoretical explanation presented. Implications of the theory and data are discussed.