Electrocardiographic signs in experimental myocardial ischemia and infarction. Epicardial ECG signs have been studied in 26 anesthetized and thoracotomized dogs in an attempt to follow the progress of tissue damage during regional myocardial ischemia. Epicardial ECG's were recorded before and during 15 min, 1 and 5 h of severe left anterior descending coronary artery narrowing. Epicardial ST segment elevation followed a complicated natural history. An analysis of variance showed the significant effects of respiration, heart rate and changes in time during myocardial ischemia. Regional epicardial R waves showed a transient increase in amplitude following coronary narrowing. There was no loss of electrically active myocardium following 15 min of ischemia. Irreversible loss of R waves were noted at between 30 and 45 min and progressed to full development within 5 h following coronary artery narrowing. The loss of electrically active myocardium (R loss plus Q waves) at 5 h was closely related to the myocardial depletion of creatine kinase activity (mu/mg DNA-1) at 24 h in each dog. The early manifestation of myocardial ischemia (ST segment elevation at 17 min) was closely related in the later evidence of cell death (R loss plus Q waves) in each dog. These relationships were less precise when the results were combined and this showed the variability between dogs in heart size and infarct size. The study suggested that the individual complete natural history of these ECG signs must be studied before they can be used to assess the extent and progress of myocardial ischemia and cell death.


The impact of computers on electrocardiography. The development of the electrocardiograph was the culmination of a scientific effort aimed at perfection of a device conceived for the elucidation of a physiologic phenomenon. The development of the digital computer was the culmination of a scientific effort aimed at perfection of warfare. Both of these fairly recent innovations of modern technology have been moderately successful in their initial objectives. Electrocardiography has had a profound influence on the practice of medicine. On the global scene, computers have so far had an insignificant influence on the practice of electrocardiography. In North America, however, computer interpretation of ECGs has already made a modest impact, perhaps more in terms of commercial gains rather than producing a substantial benefits to health care. The introduction of computers into clinical electrocardiography has not resulted in any widespread application of improved diagnostic criteria. The automation of ECG interpretation has not resulted in reduction of the cost of health care, on the contrary, in general it has increased the cost. Perhaps the most dismal failure has been the negligible use of computers in epidemiologic studies and heart disease prevention efforts. Palmistry, astrology, the art of palpation of the pulse, auscultation and acupuncture have had a more profound influence on the practice of medicine than computer analysis of the electrocardiogram. On the positive side, one of the beneficial effects of the use of computers has been the increasing awareness of the limited diagnostic accuracy of currently used ECG criteria, and the recognition of the fact that a substantial improvement is warranted; if such improvement can not be achieved in the foreseeable future, electrocardiography will lose much of its current clinical utility. Computers have had a profound influence on research in electrocardiology, and although a very few tangible concrete results have thus far diffused into clinical electrocardiography, their impact can be expected during the last two decades of this century. Computers will produce at least containment of costs if not actual net cost reduction in clinical electrocardiography. Computer analysis will rapidly antiquate the present primitive visual ECG classification in epidemiologic studies and clinical heart disease intervention trials. Computer analysis will enhance the diagnostic accuracy of the electrocardiogram. However, a radical departure from the current ECG display and interpretation practice will be mandatory before any substantial breakthrough can be materialized. All these anticipated evolutionary and perhaps even revolutionary changes will require a continuing intensive research effort, a change in the professional attitude of practicing electrocardiographers and a considerable effort in professional education. Finally, the elucidation and exploration of the full diagnostic and predictive value of the ECG remains the challenge of first magnitude in electrocardiography...


Endocardial and His bundle electrocardiograms. Endocardial electrocardiograms permit the analysis of auricular depolarization and contribute to the study of ventricular activation. Direct recording of auriculograms from the right atrium and indirect recording of the left auriculograms through the coronary sinus and pulmonary artery, show the different auricular activation pathways in common atrial flutter, atrial tachycardia and in case of retrograde atrial depolarization (via the AV node, septal or parietal accessory pathway). His bundle electrograms obtained via the femoral vein or, less easy, via the brachial vein, has introduced an essential mark in the analysis of intracardiac activation enabling us to precisely locate lesions of the AV conduction system, making easier differential diagnosis between aberrant ventricular conduction and ventricular ectopic rhythms and contributing to the study of ventricular preexcitation. Endocavitary stimulation at increasing rate and by the single extrastimulus technique is the complement of intracardiac electrocardiography in evaluating sinus node function, conduction times and refractory periods at different levels, electrophysiological properties of accessory pathways and studies of the antiarrhythmic drugs. Programmed stimulation allows the recognition of reentry as the mechanism of many tachyarrhythmias. The recording of monophasic action potential by the suction--electrode technique is another step in the intracavitary electrophysiological investigation.


Advances in the understanding of conduction disturbances. The interest towards intraventricular conduction defects started some 10 yr after the introduction of the string galvanometer by Einthoven. As early as 1910, it was known that conduction blockade could occur along either branch of the intraventricular conducting pathway. It took some 20 yr to identify properly the electrocardiographic manifestations of right and left bundle branch blocks. A further 30 yr were needed to obtain a sound correlation between these functional disorders and the presence of anatomical lesions. The more recent introduction of the concept of left hemiblocks further improved our understanding of intraventricular conduction defects. The latter concept is based on the hypothesis of the anatomical and functional bifascicularity of the left bundle branch, a hypothesis which cannot be accepted without some reservations. Later developments indicated that left hemiblocks associated with right bundle branch block represent manifestations of bilateral conduction disturbances (incomplete bilateral bundle branch block). Such an association may constitute a forerunner of complete atrioventricular block, or an indicator of the possibility of sudden death. Whether these complications occur frequently or unfrequently in the setting of incomplete bilateral bundle branch block remains an unsettled question.


Immune responses to weakly immunogenic virally induced tumors. II. Suppressive effects of the in vivo carried tumor YAC. Unprimed spleen cells from A and C57BL/6 mice could not produce cytotoxic responses to their syngeneic tumors: a Moloney virus-induced in vitro subline YAC-1 and a Rauscher virus-induced in vitro subline RBL5, respectively. Spleen cells from A and C57BL/6 mice immunized with YAC-1 OR RBL5 (which cross-react serologically) generated significant syngeneic cytotoxicities after cultivation in vitro. The in vivo carried tumor of A mice, unlike the in vitro sublines, could not stimulate a priming effect. In contrast, YAC stimulated the formation of suppressor cells in both A and C57BL/6 mice. The suppressor cells abrogated the priming effect of the syngeneic tumors, but not the priming effect of the allogeneic tumors. Furthermore, YAC did not suppress normal allogeneic anti-tumor responses. The theoretical and the practical implications of these studies are discussed.


Intrathymic pathogenesis of myasthenia gravis: transient expression of acetylcholine receptors on thymus-derived myogenic cells. Differentiation of myogenic stem cells from undifferentiated thymic stem cells is thought to play a critical role in the pathogenesis of myasthenia gravis. The expression of membrane acetylcholine receptor (AChR) on the membranes of developing muscle clones in cultures of murine thymus reticulum was followed and found to be transient. AChR are first expressed shortly after fusion of myotubes. In subsequent stages of myogenic development, the density of homogenously distributed AChR is strongly increased, and, in addition, concentrated "hot spot" AChR areas appear. During further maturation, membrane AChR are lost. Highly mature myotubes (3 months in culture) lack substantial amounts of homogenous AChR, as well as hot spots.


Rat macrophage-mediated toxicity to cancer cells; effect of endotoxins and endotoxin inhibitors contained in culture media. The cytotoxic effect of normal or BCG-activated rat macrophages on a syngeneic line of cancer cells was compared in media containing rat or bovine sera. Normal macrophages were usually cytotoxic to cancer cells in fetal or newborn bovine serum; however, they enhanced cancer cell growth in normal rat serum. BCG- activated macrophages were toxic to cancer cells regardless of the serum used in the assay. Many cell culture media or sera obtained commercially were found to be contaminated by bacterial endotoxins. When endotoxin-free reagents were used in the toxicity assay, different results were observed: normal macrophages were not cytotoxic, but rather, they often enhanced cell growth even in fetal bovine serum; toxicity of activated macrophages was significantly reduced in normal rat serum. These results suggest that endotoxin and endotoxin inhibitors play a role in the modulation of macrophage-mediated cytotoxicity. These results emphasize the importance of monitoring endotoxin contamination in cell culture reagents used in assays involving macrophages.


Expression of HLA-A, but not of HLA-B, in mouse-human somatic cell hybrids carrying the region p21 leads to pter of human chromosome 6. Mouse-human somatic cell hybrids containing human chromosome 17 carrying the region p21 leads to pter of human chromosome 6 and no other human chromosomes, were found to express HLA-A but not HLA-B. Counterselection of the hybrid cells in medium containing 5-bromodeoxyuridine resulted in the growth of hybrid cells that have concordantly lost the expression of HLA-A and the human translocation chromosome.


Effects of single and multiple doses of desipramine (DMI) on endogenous levels of 3-methoxy-4-hydroxyphenylglycol-sulfate (MOPEG-SO4) in rat brain. A single administration of desipramine (DMI) (10 mg/kg, i. p.) decreased brain levels and probenecid-induced accumulation rate of 3-methoxy-4-hydroxyphenylglycol-sulfate (MOPEG-SO4) in rats. To investigate the mechanism of this action, the interaction of DMI with NA receptor blockers and its effects on electrical stimulation were evaluated. It was found that phenoxybenzamine (20 mg/kg) or chlorpromazine (10 mg/kg) completely prevented the DMI-induced decrease in MOPEG-SO4 brain levels. On the other hand, DMI did not antagonize the increase in MOPEG-SO4 induced in the cortex-hippocampus by stimulation of the locus coeruleus. These observations indicate that the effect of DMI on MOPEG-SO4 is more likely to be due to a reduction of neuronal impulse flow mediated by a negative feed-back mechanism resulting from impairment of reuptake than to a direct effect on NA catabolism. In contrast to the effect of a single dose, the repeated administration of DMI (10 mg/kg, twice a day for 3 days) did not significantly reduce the rate of probenecid-induced accumulation of MOPEG-SO4. This development of tolerance to the metabolite-decreasing effects of DMI indicates that complex adaptive changes occur in the NA system upon repeated DMI administration.


Electrophysiological and inotropic effects of natural amino-deoxyglyco-cardenolides. The electrophysiological, inotropic and chronotropic effects of the two first natural amino-dexoyglyco-cardenolides, mitiphylline and holarosine B, were studied. Mitiphylline has qualitatively the same properties as those of common cardiac glycosides but is more potent; holarosine B has a similar action on cardiac electrophysiological parameters of the guinea pig heart but is less potent. The difference in activity between these two compounds could be attributed to the configuration in 5-and 17-positions of the genins. Holarisone B has the particularity of increasing the action potential plateau amplitude and its duration in rat heart; this could be part of the role of the aminosugar moiety.


The effect of gamma-acetylenic GABA, an enzyme-activated irreversible inhibitor of GABA-transaminase, on dopamine pathways of the extrapyramidal and limbic systems. gamma-Acetylenic GABA (100 mg/kg i.p.) inhibited GABA-transaminase activity and caused a several-fold increase in the concentration of GABA in rat brain. This increased GABA concentration was associated with a decreased rate of dopamine depletion following alpha-methyl-p-tyrosine treatment and a decrease in homovanillic acid in extrapyramidal and limbic structures suggesting a decrease in dopamine turnover in both pathways. In addition, gamma-acetylenic GABA injected into the ventral mesencephalic tegmentum decreased dopamine turnover in the mesolimbic forebrain. These results are consistent with a modulatory function of GABAergic neurons on extrapyramidal and limbic dopamine pathways. Inhibitory effects on dopaminergic functions of the extrapyramidal and limbic systems were also indicated by the amphetamine and apomorphine-induced ipsilateral turning after unilateral substantia nigral injections of gamma-acetylenic GABA and by the attenuation of dopamine-induced hypermotility after bilateral injections of gamma-acetylenic GABA into the nucleus accumbens.


Effects of neurotensin on isolated intestinal smooth muscles. The effects of neurotensin were investigated in intestinal smooth muscle preparations. Neurotensin relaxed the rat ileum, and contracted the guinea-pig ileum and taenia. Neurotensin induced a biphasic response (relaxation followed by contraction) in the contracted guinea-pig ileum. In all systems, half-maximal effects were obtained with 4--5 nM neurotensin and maximal responses with 30--60 nM; tachyphylaxis occurred with higher concentrations. Tetrodotoxin did not affect the responses to neurotensin in the rat ileum and the guinea-pig taenia. Tetrodotoxin abolished the contraction or the contraction phase (but not the relaxation phase) of the biphasic response induced by neurotensin in the guinea-pig ileum. Atropine partially inhibited the Neurotensin-induced contraction in the guinea-pig ileum. These results suggest that neurotensin acts on intestinal smooth muscle both directly (relaxation of the rat and guinea-pig ileum, and contraction of the guinea-pig taenia) and through a nerve-mediated, partly cholinergic, process (contraction of the guinea-pig ileum).


The role of calcium in supersensitivity to the inotropic effects of norepinephrine. Experiments using electrically stimulated rabbit left atria have demonstrated that supersensitivity to the inotropic effects of norepinephrine can be induced by either chronic reserpine pretreatment or hypothermia (lowering the temperature of the bathing medium). These two experimental conditions for inducing supersensitivity were not additive implying that they shared a common mechanism of action. Norepinephrine had no significant effect on the amplitude of a potentiated contraction of the rabbit atrium when the temperature was reduced from 37 to 30 degrees C or following pretreatment with reserpine (30 or 37 degrees C). Under these same conditions the ED50 of norepinephrine on the normal contraction was reduced. It is concluded that both reserpine pretreatment and hypothermia induce supersensitivity to the inotropic effects of norepinephrine by enhancing the cellular store of activator calcium while not affecting the ability of norepinephrine to release activator calcium.


Muscarinic modulation of acetylcholine release evoked by dimethylphenylpiperazinium and high potassium from guinea-pig myenteric plexus. The effects of oxotremorine and atropine on the ACh release evoked from the guinea-pig myenteric plexus by dimethylphenylpiperazinium (DMPP) or by high potassium were investigated. DMPP caused an output of ACh by stimulating nicotine receptors that are probably situated on the soma-dendritic part of the cholinergic neuron. The DMPP-induced release of ACh was dose-dependently inhibited by oxotremorine and increased by atropine. The ACh output evoked by either 45 or 108 mM potassium was enhanced by atropine. Oxotremorine did not affect the ACh release by high potassium but prevented the facilitatory effect of atropine. It is concluded that the inhibitory muscarinic mechanism modulates similarly the ACh release evoked by DMPP or high potassium and the release caused by electrical stimulation. From the experiments with high potassium it is concluded that the inhibitory muscarine receptors are localized at the site of ACh release.


Effect of imidazole on prostaglandin and thromboxane accumulation in urate arthritis. High concentrations of prostaglandins E2 and F2alpha and much lower concentrations of thromboxane B2 occurs in joint washes of chicken 1--3 h after intra-articular injection of urate crystals. Pretreatment with 200 mg/kg imidazole i.v. reduced the concentration of prostaglandins and of thromboxane B2 in the joint washes significantly. Simultaneously, leucocyte invasion was delayed and development of oedema was inhibited. The results suggest that in urate crystal arthritis the effect on prostaglandin and thromboxane accumulation at the site of inflammation contributes to the anti-inflammatory activity of imidazole.


The effects of delta1-tetrahydrocannabinol on mammary gland growth, enzyme activity and plasma prolactin levels in the mouse. DELTA1-tetrahydrocannabinol (delta1-THC), a highly lipid soluble and active principle of cannabis, was injected each day (25 mg/kg) s.c. in mice from the estimated 13th day of pregnancy. Delta1-THC-treated mice showed no increase in the wet weight or DNA content of their mammary glands during the period of investigation from before parturition until the 12th day post-partum. A marked increase in mammary-gland lipoprotein lipase activity w,s found in control mice at parturition and this was suppressed by delta1-THC. Prolactin rose to a peak level in plasma earlier in lactation in the control mice than in the delta1-THC-treated mice. This delayed rise in plasma prolactin due to delta1-THC may account for the depression of mammary gland growth and development by the drug and for the delay in the appearance of high activities of lipoprotein lipase until later in lactation.


Responses of central neurones to piribedil and 2-bromo-alpha-ergocryptine: comparison with dopamine and apomorphine. The effects of two putative dopamine receptor agonists, piribedil and 2-bromo-alpha-ergocryptine were studied by means of microiontophoresis. Their effects were compared with those of dopamine and apomorphine on neurones of the frontal cortex and of the caudate nucleus both of which are rich in dopaminergic terminals. Piribedil and S. 584, its dihydroxyphenyl derivative, displayed a potent dopamine-like inhibition in both these areas. 2-Bromo-alpha-ergocryptine exerted significant inhibition on cortical neurones which were spontaneously active but only weak or negligible inhibition on cortical and caudate glutamate-driven units. These observations raise the possibilities that 2-bromo-alpha-ergocryptine (1) mediates its inhibitory effect via a predominant presynaptic action; (2) acts preferentially on cortical neurones.


Precise location within the preoptic area where noradrenaline produces hypothermia. Noradrenaline (5 microgram in 0.5 microliter) was microinjected into 87 different sites within the preoptic anterior hypothermic area of cat brain to determine the anatomical location most sensitive to the hypothermic action of the amine. At 26 of these sites noradrenaline produced a hypothermia greater than 0.5 degrees C. Such falls in body temperature were invariably accompanied by vasodilation and sometimes by a marked increase in respiratory rate. During the hypothermia most animals appeared sedated. Histological analysis of the sites where hypothermia was produced indicated that the site of maximum sensitivity occurred between the optic chiasm and the anterior commissure at A 15.0, L 2.5, H--2.5. The results are discussed in terms of the physiological control of body temperature.


Effects of cold or restraint on incidence of gastric ulceration induced in rats by ulcerogenic drugs. Exposure to cold (4degreesC) or restraint increased the incidence and severity of gastric ulceration induced after i.p. injection of phenylbutazone, aspirin and indomethacin but not of histamine. Oral administration of cimetidine, an H2-receptor blocker, 30 min before drug injection, prevented the occurrence of gastric lesions.


Transient effect of intracellular dantrolene on E--C coupling in skeletal muscle. The effect of dantrolene-Na (DAN) on electrical and mechanical responses was investigated to single fibers of frog semitendinosus. Twitch tension was potentiated over 2--4 min by intracellular application of DAN and was rapidly decreased thereafter. Extracellular DAN depressed the tension with all dosages used. Although DAN had no effect on membrane potential, it exerted a biphasic action on membrane excitability. From these results, a mechanism is postulated for the release of trigger Ca2+ from T-tubules.


Clozapine concentrations in brain regions: relationship to dopamine metabolite increase. Levels of clozapine in rat striatum and tuberculum olfactorium were quantitated by a gas chromatographic technique. The relationship of the increase in 3,4-dihydroxyphenylacetic acid (DOPAC) in these regions produced by clozapine to the concentration of clozapine was explored. One hour after 10, 20 or 40 mg/kg clozapine i.p. the concentration of drug increased in proportion to the dose and at each dose was similar in striatum and T.O. The percent increase in DOPAC in both areas was related to the clozapine concentration in a typical dose--response manner and was greater in the striatum than the T.O. A relatively high concentration of clozapine (40 micron) was required to produce a half-maximal elevation of DOPAC. Striatal clozapine levels were similar in acutely and chronically treated animals. The concentrations of clozapine in striatum and T.O. reflect the dose injected and do not account for its atypical properties.


Yohimbine blockade of ionic channels in myocardial cells. The effects of yohimbine, an alkaloid shown to have local anesthetic properties on nerve, were determined in isolated perfused chick embryonic (19--21-day-old) hearts. Effects on the fast Na+ channels were studied in hearts perfused with normal Ringer solution by using the maximal upstroke velocity (+Vmax) as an index of the inward current flowing during the rising phase of the normal action potential. Yohimbine (10(-5)--10(-4) M) depressed +Vmax and overshoot and prolonged the action potential. At 5 x 10(-4) M, yohimbine completely blocked the fast Na+ channels, since this dose abolished the action potential when Mn2+ (2 mM) was present to eliminate the slow Ca2+ current. Effects on the slow channels were studied in hearts in which the fast Na+ channels were voltage-inactivated by partial depolarization to about--40 mV with an elevated (25 mM) K+-Ringer solution or blocked by tetrodotoxin (TTX), resulting in loss of excitability. Isoproterenol (10(-6) M) restored excitability by inducing a slowly rising overshooting electrical response (the "slow response") that was accompanied by contractions. At low concentrations (10(-5)--10(-4) M), yohimbine enhanced the isoproterenol-induced slow response; yohimbine induced the slow response in the absence of isoproterenol, even in the presence of a beta-adrenergic blocker. In contrast, at high concentrations (10(-3) M), yohimbine markedly depressed or blocked the slow response. Consistent with this dual action, yohimbine exerted a small positive inotropic action at low doses in hearts perfused with normal Ringer solution and exerted a considerable negative inotropic action at high doses, causing complete blockade of the contractions within 20 min. Cultured reaggregated cells obtained from chick embryo (15--17 day-old) ventricles showed a similar response to yohimbine in that both the normal action potentials and the slow responses were abolished. It is concluded that yohimbine exerts a local anesthetic-like action on myocardial cells, since both fast and slow channels were blocked, but the fast channels were more sensitive to yohimbine.


The in vivo binding of [3H]-desipramine and [3H]-chlorpromazine to areas in the rat brain. The distribution of [3H]-desipramine (DMI) and of [3H]-chlorpromazine (CPZ) in rat brain was determined by the incorporation of radioactivity into various regions of the brain and by autoradiography of transverse cryostat sections. The label from [3H]-DMI was rapidly distributed in all brain regions, reaching peak levels within 30 min and considerably decreasing 1--4 h after injection. Following the selective destruction of catecholaminergic nerve terminals by intracerebral administration of 6-hydroxydopamine, a marked reduction in the incorporation of DMI, but not of CPZ, was evident in all brain areas investigated. The autoradiographed sections clearly demonstrated a preferential uptake of both drugs by the caudate nucleus. These findings suggest that DMI might be largely bound to presynaptic dopamine and norepinephrine terminals, while the CPZ binding involves postsynaptic sites.


Altered state of cardiac sympathetic nerves during immunologically induced anemia. Cardiac norepinephrine (NE) levels exhibit a marked reduction in rats suffering from hemolytic anemia induced with antibodies against rat red blood cells. Administration of antiserum via tail vein resulted in a highly reproducible 70% drop in hemoglobin levels by 72 h. At 96 h cardiac NE levels were decreased by 67%; NE levels in vas deferens and submaxillary gland were not decreased. Within 10 days, both hemoglobin and cardia NE returned to near control levels. Hearts from anemic rats showed a 68% decrease in their ability to accumulate 3H-NE administered in tracer doses at 72 h of anemia. Cardiac NE turnover rates were increased 88% in 72 h anemic animals. These results are consistent with an anemia-induced activation of cardiac sympathetic nerves. Cardiac monoamine oxidase and dopamine-beta-hydroxylase activities in whole heart homogenates were similar in control and anemic animals at 72 h. These results suggest that NE depletion is not the result of decreased synthetic capacity of the nerves or degeneration of existing terminals. The data suggest that cardiac NE depletion during anemic stress is associated with the combined effects of increased NE release and a decrease in the effective NE uptake or binding capacity of sympathetic nerves. Anemia-induced depletion may, therefore, be different from the depletion associated with other forms of cardiovascular stress.


Increased adenylate cyclase activity and rapid weight loss following intraseptal injection of cholera toxin. Cholera toxin, stereotaxically injected into the medial septal nucleus of the rat, leads within 24 h to a dramatic decrease in body weight and an increase in septal adenylate cyclase activity. Toxin-treated rats drink one-third the water of vehicle-treated animals while excreting two-and-one half times the urine. Food intake over the 24-h period is depressed to 13% of control but feces production was normal. The dramatic increase of urinary output suggests that cholera toxin activates a septal adenylate cyclase system which supressess the release of antidiuretic hormone. Cholera toxin injection into the septum may be a unique alternative to electrical stimulation for investigating septal involvement in the regulation of neuronal and metabolic processes.


Interaction of serotonin and deslanoside on cardiac rhythm in the cat. The present study was performed to determine whether increases in the tissue content of serotonin creatinine SO4 in the periphery would influence the arrhythmogenic effect of deslanoside. This was accomplished by infusing serotonin into anesthetized cats exposed to a subarrhythmic dose of deslanoside, determining doses of deslanoside required to produce ventricular tachycardia and ventricular fibrillation, and determining ventricular pacemaker rate (obtained during vagal-induced sinus node suppression). It was found that animals receiving serotonin creatinine SO4 plus deslanoside exhibited a greater increase in ventricular rate during sinus node suppression than with 5-HT infusion alone. No corresponding increase in ventricular pacemaker rate during sinus node suppression was observed with creatinine SO4 plus deslanoside. In addition, the dose of deslanoside to produce ventricular fibrillation in these animals was significantly correlated with the increase in ventricular pacemaker rate seen during th 5-HT infusion in the presence of deslanoside. Studies were also performed to determine whether the arrhythmogenic interaction of serotonin with deslanoside was associated with alterations in either cardiac tissue, blood or plasma levels of serotonin and 5-hydroxyindoleacetic acid. The data revealed a significant correlation between serotonin content in the left ventricle and the dose of deslanoside required to produce ventricular fibrillation. These results suggest that exogenous serotonin interacts with deslanoside to enhance the arrhythmogenic action of deslanoside.


Release of beta-endorphin from rat pituitary in vitro. The rate of release of beta-endorphin immunoreactivity from the anterior lobe of the rat pituitary in vitro increased in respone to potassium-induced depolarization in a calcium-dependent manner. Potassium-induced depolarization did not, however, change the rate of release from intermediate/posterior lobe. These findings provide support for the view that beta-endorphin may have a humoral function and suggest that beta-endorphin stores in discrete pituitary areas are regulated by different release mechanisms.


Integration in descending motor pathways controlling the forelimb in the cat. 5. Properties of and monosynaptic excitatory convergence on C3--C4 propriospinal neurones. Recording was made in the C3--C4 segments from cell bodies of propriospinal neurones identified by their antidromic activation from more caudal segments. Monosynaptic excitatory effects from descending motor pathways and primary afferents were investigated by electrical stimulation of higher motor centres and peripheral nerves in the forelimb and neck. The cell bodies were located mainly laterally in Rexed's layer VII. Threshold mapping for single axons showed that they descend in the lateroventral part of the lateral funicle. Antidromic stimulation at different spinal cord levels showed that some neurones terminated in the forelimb segments, others in the thoracic cord or in the lumbar segments. Terminal slowing of the conduction velocity suggested axonal branching over some segments. Monosynaptic EPSPs were evoked in the neurons by stimulation of the contralateral pyramid, red nucleus and dorsal tegmentum-superior colliculus. It is concluded that corticospinal, rubrospinal and tectospinal fibres project directly to both short and long propriospinal neurones. There was marked frequency potentiation in tectospinal synapses. Convergence from two descending tracts was common and in half of the tested cells all three tracts contributed monosynaptic excitation. Experiments with collision of descending volleys and antidromic volleys from the brachial segments demonstrated that the corticospinal and rubrospinal monosynaptic projection to the propriospinal neurones is by collaterals from fibres continuing to the forelimb segments.


Diminution and reversal of eye movements induced by local stimulation of rabbit cerebellar flocculus after partial destruction of the inferior olive. After the dorsal cap and adjacent ventrolateral outgrowth regions of the inferior olive had been chronically destroyed in the rabbits, the eye movements evoked by local stimulation of the flocculus were reduced in amplitude and reversed in direction, indicating that the inhibition by flocculus Purkinje cells of vestibulo-ocular relay neurons could no longer be actuated by the stimulation.


Reduction of the cerebellar stimulus effect on rat Deiters neurons after chemical destruction of the inferior olive. After the inferior olive of the rats had been destroyed by administration of 3-Acetylpyridine, the inhibitory effect of cerebellar stimulation on Deiters neurons was substantially reduced, indicating impairment in functions of Purkinje cells and/or their axons after deprivation of climbing fiber afferents from the cerebellum.


The response of horizontal semicircular canal afferents to sinusoidal rotation in the cat. Dynamic characteristics of primary vestibular afferents innervating the horizontal semicircular canal were studied in decerebrate, unanesthetized cats. Activities of individual afferent fibers were recorded intracranially by glass micropipettes. Frequency of sinusoidal rotation was varied from 0.014 Hz to 0.42 Hz, and phase and gain properties were examined. All of the fibers recorded fired spontaneously, and their firing rate ranged from 7 to 128 spikes/sec. Regularity of firing, phase lags, and gains were calculated in individual fibers. There was a tendency that the units with high spontaneous firing rates showed regular firing, larger phase lags, and lower gains that the units with low spontaneous firing rates. The transfer function of the system (firing rate of the primary afferent per angular acceleration of the head) was (formula: see text). A high frequency phase lead component was needed to account for the data obtained, indicating a slight deviation from the relationship predicted by the torsion pendulum model. The present phase properties were compared with those of vestibular nucleus neurons reported previously. It was suggested that a group of vestibular nucleus neurons transmits fairly faithfully the phase properties of primary afferents, and that another group of vestibular nucleus neurons receive additional influences from central structures, exhibiting larger phase lags than primary afferents.


Visuomotor restriction of one eye in kittens reared with alternate monocular deprivation. It is known that kittens reared in ways that restrict movement while visual stimulation is received exhibit deficits in visually guided behavior. Presumably, the behavioral dysfunction is due to a lack of sensorimotor coordination during visual exposure. The current investigation was undertaken to study this effect both physiologically and behaviorally. Two groups of kittens were normally reared until they were nearly 4 weeks old. They were then placed in a darkroom and exposed daily for 1--2 hours while one eye was occluded. On alternate days, alternate eyes were covered. One group was restrained in a body cast while a given eye was exposed, but the kittens were free to move about while the other eye received visual experience. A second control group was alternately occluded, but freely mobile during all exposures. An additional cat was also unrestrained during daily rearing periods and neither eye was ever occluded. Behavioral tests showed clear deficits when the "passive" eye of the restrained-unrestrained group was used. Deficiencies were found in visually guided paw placing, pursuit eye movements, and jumping behavior to a platform. Responses of single cells were studied in area 17 of the visual cortex. Ocular dominance distributions showed marked reductions in binocularity for alternated occluder cats. The eye that had received exposure while animals were active in the restrained-unrestrained group also tended to predominate but the difference was not statistically significant.


Systems-matching by degeneration. I. A quantitative electron microscopic study of the generation and degeneration of retinal ganglion cells in the chicken. The total number of optic nerve fibers of the chicken was determined at twenty sequential developmental stages from incubation day 5 to 104 days after hatching. It was found that the total number of optic nerve fibers increases from 4400 on incubation day 5 to about 4.0 million on incubation days 10 and 11. Thereafter, it decreases to a final value of about 2.4 million by incubation day 18 and remains constant from that time on until adulthood. Thus, 40% of optic fibers degenerate. Degenerating ganglion cells in the retina are first detectable by incubation day 9. Initially degenerating cells are located mainly in the central retina, but on subsequent days they can be found predominantly in peripheral zones. It is postulated that cell death occurs because of competition for adequate arborization space. If more retinal afferent fibers arrive than tectal termination sites are available, supernumerary fibers may degenerate. By degeneration the two systems retina and optic tectum, are matched in size.


The effect of pentobarbital, chloralhydrate, ether and protoveratrine on the distribution of synaptic vesicles in rat cortical synaptosomes. Rat cortical synaptosomes were incubated in a saline medium. On the addition of pentobarbital, chloralhydrate, ether and protoveratrine a redistribution of synaptic vesicles was revealed by electron microscopy. The anaesthetics decreased the number of synaptic vesicles attached to the presynaptic membrane while protoveratrine increased them. It is assumed that these agents affect the mechanism of vesicle reformation from the synaptosomal membrane and/or vesicle migration towards the synaptic cleft.


Short-term increase and long-term reversion of striatal cell activity after degeneration of the nigrostriatal dopamine system. The spontaneous activity of neurons in the head of the striatum was studied in rats 3 days and more than 1 year after a 6-hydroxydopamine-induced lesion of the nigrostriatal dopamine system in comparison to unlesioned animals. Cells were detected and tracked by stimulating the excitatory corticostriatal pathway. In unlesioned animals striatal cells discharged at very low frequencies, with a median of 0.04 impulse/second. The activity was increased to 0.28 impulses/second 3 days after the lesion. This increase was related to the degree of dopamine depletion. More than 1 year after the lesion, the frequency had decreased to a level indistinguishable from that measured in unlesioned animals, with a median of 0.03 impulses/second. Cells in 3-day lesioned animals discharged a higher number of bursts at shorter intervals as compared to unlesioned animals, while in long-term denervated animals the bursting pattern was similar to that in unlesioned animals. This demonstrates that removal of the dopaminergic input results in increased activity only during an initial phase and that adaptive processes subsequently occur. The data from this Parkinsonian model suggest that symptoms of this disease cannot simply be related to an increased striatal cellular activity. The fact that the initially increased spontaneous activity adapted indicates that functional effects of a lesion can only be evaluated when studying the resulting changes throughout a time course.


The control of rapid limb movement in the cat. I. Response latency. A versatile tracking task has been developed to assess the competence of feline subjects in using sensory information to initiate and guide limb movement. In the present study we investigated the response latency and the factors which affect it in order to define temporal constraints on the underlying processing of information. The paradigm makes use of an electromechanical display of the difference between the output of transducers in a manipulandum (controlled by the cat) and a target level (controlled by the experimenter). Because of inertia and friction, a step change in target level required 230 msec to fully shift the display. The animals were trained to match the position of the manipulandum (or the force they applied to it isometrically) to the target level for a food reward. Target perturbations elicited rapid position or force adjustments of appropriate direction and magnitude at short latency. Under isometric conditions, the latency of the response was an inverse function of the extent of display motion and of the peak rate of force change attained during the adjustment. Asymptotic values of the response time, measured from the perturbation to the first change in force applied to the lever, were typically between 50 and 70 msec. Since the motor responses were invariably initiated while the display was still moving, the animals must have used information contained in the derivatives of its motion. In the absence of visual cues, deflection of the vibrissae by the sudden motion of the dispaly provided two of the four animals with sufficient information to initiate and guide their movements without changes in response latency. When vision was allowed, section of the vibrissae produced a persistent increase in response times of 15-20 msec. This difference in latency is compatible with the delays due to retinal transmission. The short time interval elapsing between stimulus and response strongly suggests that the topography and the metrics of the underlying transformations are adjusted by gating and/or biasing processes which precede the stimulus. It is concluded that sensory information can generate purposeful movements through pathways which include only a small number of central relays in series, independently of its modality.


The control of rapid limb movement in the cat. II. Scaling of isometric force adjustments. In the previous study it was shown that cats were capable of making rapid and accurate adjustments in the force they applied to a lever in accord with information provided by a compensatory display. In the present study, isometric responses were examined in greater detail to determine 1. if a general control policy (or model) governing responses of different magnitudes could be inferred from the relations among output parameters and 2. if the earliest output measures were scaled to the preceding sensory events. The force adjustments elicited by the sudden motion of the display showed a linera relation between the peak force and the peak of its first derivative, dF/dt. Similarly, the peak d2F/dt2 was a linear function of dF/dt. By contrast, the times required to achieve the peak force and the peak dF/dt were largely independent of their magnitudes. These adjustments were produced by a burst of EMG activity in agonist muscles which coincided with the rising phase of dF/dt. The observations suggest that such motor outputs are determined by a pulse-step control policy. The amplitude of the pulse would control the rate of rise of dF/dt (and therefore also the peak force since the rising phase of dF/dt was of constant duration), and the step would control the level of the terminal steady state force. Both the peak force and the preceding peak dF/dt were highly correlated with the amplitude of the perturbation. Changes in display gain, which altered the required relation between input and output magnitudes, resulted in a gradual readjustment of the output parameters. It was concluded that the motor outputs were scaled from their inception to requirements dictated by the initial sensory information. The selection by the cat of the appropriate scaling function was contingent upon its previous experience with the device.


Cutaneous fiber groups involved in the inhibition of fictive locomotion in the rabbit. Decorticate, paralyzed unanaesthetized rabbit preparations can display motoneuron discharges (spontaneous or elicited through various somatic stimulations) which are related to locomotion. These activities are suppressed when manual pressure is exerted on the dorso-lumbar skin. The present study indicates that: (1) locomotor discharges can also be inhibited through repetitive electrical stimulation of one of the skin nerves belonging to dorsal dermatomes (TH5 to L5); (2) other skin nerves, especially those of the limbs, do not present the same inhibitory properties; (3) among the various fiber groups composing these dorsal skin nerves, only A delta are inhibitory; other groups, on the contrary, display moderate (A alpha and A beta) or strong (unmyelinated C fibers) excitatory actions; (4) the inhibitory action of A delta fibers counteracts the excitatory action of C fibers, when both groups are stimulated together. The relationship between this form of motor inhibition and the well known phenomenon of "reflex immobility" is briefly considered.


The karyotypes of the Corsican and Sardinian mountain salamanders, Euproctus montanus and E. platycephalus (Urodela: Salamandridae). The chromosomes of Euproctus montanus and E. platycephalus were studied by means of the C-banding method and the AS-SAT technique which are useful for identifying the single pairs of the complement and for recognizing nucleolar organizer regions. According to the morpho-structural characteristics shown by the specific karyotypes, it has been possible to draw some cytotaxonomic deductions concerning the karyological evolution within the insular group.


Cytochemical localization of surface carbohydrates on mycoplasma membranes. Surface carbohydrate structures, containing alpha-D-glucosyl or sterically closely related residues, were visualized on mycoplasma membranes by cytochemical staining procedure with concanavalin A and iron-dextran complexes.


Two new polyploid Xenopus species from western Uganda. 2 new species of the anuran genus Xenopus have been found in western Uganda: X. ruwenzoriensis sp.n. with the hexaploid chromosome number of 108 in the Semliki Valley, west of the Ruwenzori, and X. species nova with the tetraploid chromosome number of 72 in and near lake Bunyoni.


Reoxidation of reduced hen egg white lysozyme fragment 1-123. The reactivation of reduced lysozyme, whose 6 COOH-terminal amino acid including cysteine 127 were cut off, was studied. The results show that the disulfide bridge I-VIII as well as the COOH-terminal hexapeptide do not play a decisive role in the acquisition of the native 3-dimensional structure of the enzyme.


Microbiological oxidation of the pentyl side chain of cannabinoids. Syncephalastrum racemosum ATCC 18192 and Mycobacterium rhodochrous ATCC 19067 partially degrade the n-pentyl side chain of cannabidiol, cannabinol, delta8-tetrahydrocannabinol and delta9-tetrahydrocannabinol. Carboxylic acid and alcohol side chain derivatives are major metabolites.


Successful cryopreservation of auricle fragments from rat hearts at -196 degrees C. The influence of electrolyte composition and glucose concentration of a cryoprotective medium on the survival of auricle fragments from adult rat hearts after storage at -196 degrees C was investigated. Using a K+-, Mg++-, Ca++-rich solution with increased glucose concentration, a high rate of surviving fragments was found after cryopreservation.


Increased blood pressure in the SHR is not related to a deficit in renomedullary PGE2. Synthesis of prostaglandin E2 by renal medulla from SHR and WKY rats was compared during early postnatal development. Although arterial blood pressure was significantly higher in SHR as early as 6 weeks of age, no difference in renal medullary prostaglandin synthesis was observed.


Effect of exercise training on the chronotropic response of isolated rat atria to atropine. Atria isolated from rats after 7 weeks of exercise training beat at a slower rate than did atria from sedentery controls. Atria from exercised rats showed a significant acceleration in response to atropine.


Seasonal changes in the levels and the turnover of brain serotonin and noradrenaline in the European hamster kept under constant environment. Seasonal changes in the content and the turnover of noradrenaline and serotonin are shown in various parts of the brain of the European hamster kept under constant conditions of light and temperature.


Induction of electrical excitability in crustacean muscle by 4-cyclopentene-1,3-dione. 4-Cyclopentene-1,3-dione induces electrical activity in inexcitable crustacean muscle. This effect is blocked by previous treatment with p-chloromercuribenzoic acid. These results suggest that crustacean muscle becomes excitable when certain -CH2-SH side chains are converted to thioethers having carbonyl groups.


Proteoglycans in ovine brain.

Proteoglycans in ovine brain. Sulphated proteoglycans were isolated using a dissociative method of extraction. Cerebrum accounted for the major portion of proteochondroitin sulphate in brain, whereas the brain stem fraction contained over half the proteoheparan sulphate. Chemical characterization studies demonstrated that heparan sulphate from cerebellum contain more N-sulphate glucosamine residues.


Radioautographic identification of serotonergic neurones in Aplysia. Radioautography shows that 3H 5-HT specifically labels metacerebral and 2 other serotonergic cell bodies in Aplysia cerebroid ganglia as well as 5-HT terminals in close contact with giant neurone membrane in buccal ganglia.


Cerebellar decussation of fibres from the nucleus reticularis tegmenti pontis in the brain of the albino rat. The existence of a cerebellar decussation of fibres from the medial portion of each nucleus reticularis tegmenti pontis (Rtp) of the albino rat is indicated. Definite cell loss in the medial aspect of the most rostral third of Rtp is detectable after cerebellar hemisection involving parts or the entire depth of sublobule VIb. Cell loss in the medial aspect of the caudal half of Rtp is evident as a consequence of experimental lesions which damage both sublobules IIb and III.


Selective activation of noradrenergic neurons in the brainstem and spinal cord of young spontaneously hypertensive rats. In young spontaneously hypertensive rats (SHR), dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) activities were examined in the brainstem nuclei. Activation of noradrenergic neurons in the locus coeruleus, A2 and spinal intermediolateral cell areas, resulting in enhanced sympathetic nervous activity in the periphery, initiates hypertension. Adrenergic neurons, unchanged in these and A1 cell areas of young SHR, are not involved in the development of hypertension in SHR.


The effects on thermoregulation of intracerebroventricular injections of L-aspartic acid in the sheep. L-Aspartic acid was injected into a lateral cerebral ventricle of the sheep at ambient temperatures between 0 degrees and 40 degrees C. Doses of 100 or 500 nmoles-kg-1 caused a rise in heat production and/or a decrease in heat loss; rectal temperature rose. Atropine sulphate attenuated or prevented these effects.


Interaction of chlorpromazine with organic solvents and fatty acids as studied by UV-spectrophotometry. The magnitude of the UV-spectral change of chlorpromazine increases in the presence of increasing concentrations of alcohols or fatty acids and with increasing chain length. A maximum is reached with 14.0- or 16.0-fatty acids. The differential spectrum is still larger with unsaturated fatty acids, a maximum effect being obtained with one cis-double bond. The spectral change is abolished by chaotropic and enhanced by antichaotropic agents.


Anti-phalloidine and anti-alpha-amanitine action of silybin in comparison with compounds similar to structural parts of silybin. Silybin significantly antagonises the lethal poisoning of mice with alpha-amanitine or phalloidine. In the same test, taxifolin, coniferyl alcohol, fisetin and (+)-catechin were not effective.


Current(I)-voltage(V) relationships of the neuromembrane of an identifiable giant neurone of an African giant snail (Achatina fulica Férussac) in the presence of an inhibitory tripeptide, L-Lys-L-Phe-L-Tyr. An inhibitory tripeptide, L-Lys-L-Phe-L-Tyr, caused membrane hyperpolarization of the TAN (tonically autoactive neurone) resulting in an elevated firing level. The tripeptide, however, did not markedly affect either the TAN I-V curve or the firing pattern obtained by transmembrane triangular current injection.


Protective role of brain ascorbic acid content against lipid peroxidation. The high ascorbic acid concentration in the brain inhibits lipid peroxidation induced by various agents in rat brain microsomes. The physiological importance of the fact is discussed.


Monoamine oxidase activity in tissues of spontaneously hypertensive rats. Monoamine oxidase (MAO) activity was assayed both in central and peripheral blood vessels of spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKR). The activity of MAO in the brain and peripheral vasculature was essentially the same in both SHR and WKR. It can therefore be concluded that central and peripheral vascular MAO activity is not altered in the genetically hypertensive animals.


The effect of urethane and pentobarbital anaesthesia and hepatic portal vein catheterization on liver blood flow in the rat. The effect of urethane and pentobarbital anaesthesia and hepatic portal vein catheterization on liver blood flow was investigated in the rat. Liver blood flow with pentobarbital anaesthesia was 40% greater than with urethane. Hepatic portal vein catheterization had no effect under pentobarbital anaesthesia whereas it produced an 18% fall in liver blood flow with urethane.


Chemical and photooxidation of thiothixene (Navane): structure of the thiothixene fluorophor. The spontaneous photooxidation of thiothixen (Navane) to 2-(N,N-dimethyl-sulfonamido)-9-thioxanthone is described. The corresponding sulfoxide is demonstrated to be the fluorescent species obtained upon permanganate oxidation of thiothixene in the fluorometric assay procedure of Mjörndal and Oreland.


Inhibitory effect of tiaramide on ADP-induced aggregation in rabbit platelets. Tiaramide in 10(-4) or 10(-5) M depressed the ADP-induced aggregation of rabbit platelets using the turbidimetric method. In modified Chandler's loop method, tiaramide in the same concentration accelerated the restoration of the time course of disaggregation.


Carcinogenic activation of benzo(a)pyrene by iodine and ferric chloride in the respiratory tract of Syrian golden hamsters. Benzo(a)pyrene (0.5 mg), in itself weakly carcinogenic, when given in combination with ferric chloride (0.16 mg) or iodine (0.2 mg), alone noncarcinogen, induced a number of tumors of different parts of the respiratory tract of Syrian golden hamsters.


Nerves and taste-buds degeneration in the cat-fish Ictalurus melas. After nerve transection, external taste-buds remain apparently normal for more than 3 weeks, become round, then disappear. Cryonecrosis of the cranial ganglia V and VII induces a loss of polarity of the buds, which, though keeping up their form for 50 and even 150 days, are progressively deprived of sensory cells. This shows a dissociation of the actions of nerve factors.


[Ultrastructural study of the cytological changes in the adenohypophysis of the male quail submitted to long daily photoperiods (author's transl)]. The collective data obtained at the ultrastructural level in anterior pituitaries of male Chinese quails submitted to long daily photoperiods, confirm the cytological changes observed earlier in, at least, 2 types of cells of the gland. This cellular types may be the source of avian LH and FSH.


Changes in cellular noradrenaline fluorescence in the denervated rat superior cervical ganglion. The microfluorimetrical investigation showed that in the principal perikarya of the rat superior cervical ganglion, after inhibition of noradrenaline-synthesis and unilateral preganglionic axotomy, the fluorescence of newly synthesized noradrenaline was most intense at the periphery of the perikarya of the intact side.


Giant pigment granules in dermal melanocytes of rat scrotal skin. Giant melanosomes, ellipsoidal (1.5 micron X 1.3 micron) or spherical (1.1 micron-1.4 micron in diameter) exist in the scrotal skin of the black pelted Long Evans rat. They are longer and wider than normal stage IV melanosomes (0.7 micron X 0.4 micron) found in these dermal melanocytes.


Lack of synaptic reorganization in inner plexiform layer (IPL) of retina following ganglion cell degeneration. Ganglion cell degeneration in the rat retina following optic nerve lesion does not induce the formation of new synapses even after 1 year of postoperative recovery.


Lamprey biliary atresia: first model system for the human condition? Degeneration of the bile ducts and gallbladder occurs during metamorphosis of the lamprey. Morphological aspects of this process suggest a similarity to human biliary atresia.


Ocular involvement in hamsters transplanted with a human leukemic T-cell line. A leukemic T-cell line (TALL-1) was serially transplanted for 5 passages into newborn hamsters treated with antilymphocyte serum. This cell line was derived from a leukemic patient with clinical evidence of ocular involvement. I.p. implantation of 1--3 X 10(7) cells resulted in disseminated growth of tumors in all 15 recipients after 23--41 days and 8 of them showed leukemic infiltration of the uveal tract of one or both eyes.


Studies of autoimmune induction in the rat lacrimal gland. Induction of autoimmunity in the rat lacrimal gland was presently assessed. Antibodies to lacrimal gland extract were detectable in 58% of the immunized rats. Skin tests were positive at 4 week postimmunization in 70% of the animals. Histological observations revealed the presence of mononuclear cell infiltrates surrounding the ductal and acinar epithelium at 2--6 weeks.


Plasma triiodothyronine, thyroxine and thyrotrophin levels in germfree rats. Plasma T3, T4 and TSH levels in developing germfree rats were high, low and normal as compared with those in conventional counterparts. The high T3/T4 ratio in germfree rat plasma was lowered by cholestyramine feeding.


[Effects of reserpine on development of Oedipoda coerulescens L. (Acrididae, Orthoptera) (author's transl)]. Inhibitory  effects of reserpine on ecdysis and chromatic adaptation in Oedipoda appear to be linked with changes observed in both neural and neuro-endocrine regulating systems.


Effect of acute administration of triiodothyronine in chicken. Liver glycogen depletion and amino acid incorporation to proteins. Single injections of thyroid hormone (T3) produce liver glycogen depletion in chickens. This effect cannot be suppressed by protein synthesis inhibitors and is previous to the hormone-induced increase in protein synthesis.


An anatomical study of the microcirculation in the rabbit femur. A technique is described which will allow a study of the microcirculation to a long bone such as the femur. It involves use of a silicone rubber compound (Microfil) in combination with the Spalteholz clearing technique. Preliminary results in the normal rabbit skeleton suggest that this technique can be used to study the changes in vascularity which occur under various pathological conditions.


The determination of extracellular space using hemoglobin. The ECS of guinea-pig atria and frog sartorii can be determined using hemoglobin. For guinea-pig atria an ECS of (32.2 +/- 2.6)% wet wt for frog sartorii an ECS of (12.4 +/- 1.0)% wet wt can be measured.


Pentagastrin induction of acetylcholinesterase activity in cerebral cortex of rats. A single injection of pentagastrin (500 microgram kg-1) produced an immediate (within 15 min) and pronounced increment (about 50%) in the activity of acetylcholinesterase (AChE) in the cerebral but not in the cerebellar region of the brain. Pretreatment of rats with either actinomycin-D or cycloheximide did not fully abolish the pentagastrin-mediated stimulation of cerebral AChE activity.


Cross-linked arabinogalactan: a new affinity matrix for the purification of Ricinus communis lectins. Arabinogalactan has been cross-linked to give a new high capacity affinity matrix for the purification of Ricinus communis lectins. It shows a capacity which is 50 times greater than that of the conventional affinity matrices.


Cysteine oxidase and cysteine sulfinic acid decarboxylase in developing rat liver. The patterns of development of cysteine oxidase (CO) and cysteine sulfinic acid decarboxylase (CSD) in rat liver are not similar. It was observed that CO is not under sex control as CSD is. The results obtained agree with the idea that, in liver, as well as in brain, CSD is the limiting factor for the regulation of taurine biosynthesis.


Acid and alkaline phosphatase heterogeneity in liver, heart and intestine of the adult chick. The molecular heterogeneity of acid and alkaline phosphatase from chick liver, intestine and heart is demonstrated by polyacrilamide disc gel electrophoresis. Liver and heart show the same number of molecular forms of acid and alkaline phosphatases. In contrast, the intestine homogenate shows electrophoretic bands different in number and in gel position from those of the liver and of the heart.


Glutathione peroxidase in erythrocytes and plasma of rats during pregnancy and lactation. The glutathione peroxidase activity in the plasma of rats on the 20th day of pregnancy was found to be 50% lower than in nulliparous control animals. During lactation, the level rose again but was still significantly different from that of the control rats on the 20th day post partum. The erythrocyte enzyme activity remained unchanged.


Glutamate decarboxylase activity in preoptic and hypothalamic nuclei of the rat. Freeze-dried samples were used for the determination of glutamate decarboxylase activity in discrete preoptic and hypothalamic nuclei. The activity showed marked regional variation in distribution.


Activity of phospholipases A and some lysosomal enzymes in rat testes at different stages of hypervitaminosis A. Excess of vitamin A induces decrease of neutral phospholipase A1 and A2 activity in rat testes homogenates on the 4th day, and increase of beta-galactosidase activity on the 8th day of treatment. It is suggested that phospholipase A activity decrease is of great importance in development of testicular disorders, caused by disbalance of vitamin A.


[Inhibition of adjuvant arthritis by oxonate: influence of uricemia (author's transl)]. Adjuvant arthritis in rat is inhibited by an oxonate diet, which increases uricemia. The inhibition is proportional to blood uric acid level and not to oxonate concentration in the diet. Oxonate alone does not exert an inhibitory effect.


Remarks on the karyotype of the Polypteriformes. The chromosomes of Polypterus delhezi, P. endlicheri congicus and P. palmas. The chromosomes of 3 species of bikirs (Polypterus delhezi, P. endlicheri congicus and P. palmas) were studied in somatic metaphases. The diploid number was found to be 2 n = 36 in all the species and a basic morphological identity of the karyotype emerges from karyogram comparison not only in the 3 species described herein, but also in the other Polypteriformes already studied.


Contraceptive use in the United States, 1973--1976. The pill and sterilization were the main methods used by U.S. married couples in 1976 to prevent pregnancy. In 1973 the poor were more likely than the more affluent, and blacks as likely as whites, to use the most effective methods. By 1976 this was no longer true, because more blacks turned to traditional and folk methods and the sterilization increase was largely limited to more affluent whites.


Abortion in the United States, 1976--1977. In 1976, about 1.2 million, and in 1977 some 1.3 million, abortions were performed in the U.S. More than half a million women were without the abortion services that they wanted. Poor, rural, young and black women were disporportionately represented among those not yet served.


Does your mother know...?

Does your mother know...? Many teenagers inform their parents when they come to a family planning clinic. Most of those who do not, however, would stop coming to the clinic if their parents were told of their attendance, and a substantial proportion would have sex without using any birth control method.


Family therapy and drug abuse: a national survey. The following report describes the results of a national study of the role of family therapy in the drug abuse field. Characteristics of agencies that work with families are described, as well as the demographic characteristics and psychological problems of the clients most apt to be treated in family therapy. The study also looks at the role and structure of family therapy in the ecological system of the treatment institutions. A profile of the family therapists who are responsible for providing services to families is presented. An attempt was made to assess agencies' level of development with regard to family therapy by using an instrument, The Progress Index for Family Therapy Programs. Generally, findings indicated that there is considerable variation in expertise. More extensive training in family therapy techniques was of major concern, particularly among clinics with a heroin addict population.


Deterioration in marital and family therapy: empirical, clinical, and conceptual issues. Recent empirical evidence of deterioration during both nonbehavioral and behavioral marital and family therapy is presented. While the frequency of patient worsening in marital-family therapy does not appear to exceed that previously found for individual psychotherapy, the acceptability of the evidence for negative effects in the treatment of systems may be greater than that which exists for individual treatment. After examining the empirical evidence of negative effects in family therapy and some of the factors that influence their occurrence, the authors discuss some conceptual issues relevant to a definition of worsening in marital and family therapy and present some methodological guidelines for the assessment of deterioration in therapy with family systems. It is concluded that the study of deterioration processes in family therapy may aid the understanding of family change processes more generally.


The Slovak-American "swaddling ethos": homeostat for family dynamics and cultural continuity. This paper explores the systemic relationships among cultural ethos, family dynamics, personality configuration, and child-rearing patterns among multigeneration Slovak-Americans. The "swaddling ethos" is posited to serve as a homeostat whose regulatory function can be discerned through the analysis of family structure and process, in particular through the explication of values, affective patterns, roles, boundaries, and structural units within the family. The core of the ethos is a dependency-security complex that attaches the individual to an extended family network of obligation, indebtedness, and reciprocity (ethnic, Slovak); induces rebellion against such attachment (mainstream American); and undermines efforts toward separation-individuation, resulting in the perpetuation of an ethnic tradition.


The family life cycle: developmental crises and their structural impact on families in a community mental health center. A typology for troubled families was developed based on the configuration of family members and the position of the identified patient within the family structure. This typology was investigated by surveying the demographic and clinical characteristics of 110 families of patients treated in a day hospital. Four types or "constellations" were found in the sample population. The families in the four Constellations differed significantly from one another in the gender, age, and diagnoses of the identified patient and the income level of the families. The Constellations thus appeared to constitute distinct clinical entities in the population studied. The reasons for the differences among Constellations are discussed in terms of the stress families experience during developmental crises involving structural change.


Susan smiled: on explanation in family therapy. The contemporary psychotherapist is exposed to a variety of conceptual models and paradigms. These are usually presented as opposing truths in different doctrinal schools, but actually they are all valid from one point of view or another. And accordingly, they are all tactically useful at some point or another. I thought it was important to say this, but I did not want to write a dry, academic paper on the subject. So I will tell a clinical story that weaves the threads into a fabric.


Some notes on the use of family sculpture in therapy. Therapists learning to use family sculpture as a tool often find difficulty in exploiting the technique to its fullest. This article, designed to encourage therapists to take the risks involved in using a technique new to them, describes how the author and his cotherapists used sculpture in three cases in different ways. In each case, the author explains how the therapists made the choices involved in directing the therapeutic process. He suggests that even when a sculpture itself seems to have failed to produce useful information, it can elicit from clients signals that will indicate opportunities for effective use of other techniques and that a sculpture, once used, can be restaged to reinforce client behavior change.


How many children do couples really want? Program workers and policy makers may be seriously misled if they put too great a reliance on statements about preferred family size. Underlying biases toward more or fewer children than the stated number affect the timing and effectiveness of contraceptive practice, and may help explain discrepancies between desired and achieved family size.


A multi-method investigation of two family constructs. Two family constructs--prominence and interpersonal distance--are examined. Their origins are traced in the experimental and theoretical literature. The validity of each construct is investigated using data obtained from 15 families with a symptom-bearing child. Validity is supported in both cases through the occurrence of significant correlations among different measures of the same construct. It is suggested that the current distress of the families being studied may have increased the clarity of the prominence hierarchies and dyadic distances that emerged.


[Effect of ether and fluorothane on higher nervous activity]. Tests conducted with dogs by using Pavlov's method of conditioned reflexes (salivation procedure) showed fluothane to act on the central nervous system 3 times as strong as does ether. This is confirmed by a longer time necessary for the higher nervous system to normalize. Thus, awakening of the animals after the ether anesthesia, the re-establishment of the conditioned reflex activity supervened by the 7th day on the average, whereas, after the fluothane anesthesia, this occurred only on the 24th day.


[Action of morphine and amidopyrine against a background of mineralocorticoid hormone and its antagonist]. The effect of morphine and amidopyrine, used against the background of a mineralocorticoid hormone or its antagonist excess (multiple administration of desoxycorticosteron acetate or verospiron), is mitigated. The pain-allaying effect of analgesics and their influence on the behavioral reactions are less marked in both models than it is in intact animals and their toxocity is down.


[Action of fentanyl, droperidol and diazepam on the contractile function of the isolated human myometrium]. The action of the analgesic phenthanyl, neuroleptic-droperidol and tranquilizer--diazepam on the contractile function of an isolated human myometrium was investigated. Phenthanyl (5.10(-8)--5.10(-7) g/ml) produced a stimulating influence on the contractility of an isolated human myometruim. When in relatively low concentrations (5.10(-7)--2.10(-6) g/ml) droperidol caused a stimulating effect and in higher concentrations (8.10(-6)--2.10(-5) g/ml) it exerted a biphasic action on the contractile function of an isolated myometrium, viz. first stimulation and then--inhibition. Diazepam (1.10(-12))--5.10(-8) g/ml suppressed the spontaneous periodic activity of an isolated human myometrium.


[Effect of adrenaline, noradrenaline, histamine and acetylcholine on the blood flow in the vascular bed of the bone marrow]. Medullary circulation in the tibia and effect produced on it by microinjections of epinephrine (1.4.10(-5) and 2.7.10(-5) M), norepinephrine (0.2.10(-4) M), histamine (0.9.10(-4) and 1.8.10(-4) M) and acetylcholine (2.2.10(-4) were studies in acute tests on Wistar rats by using the 133Xe clearance method. The study agents significantly changed the circulation rate in the medullary vascular bed. Phasic changes of hemodynamics in the bone marrow occurring under the effect of the mentioned vasoactive substances point to the presence of alpha- and beta-adrenoreceptors and H1- and H2-receptors in the medullary vascular bed.


[Evaluation of the arrhythmogenic activity of adrenergic and cholinergic agents in calcium chloride arrhythmia]. Under conditions prevailing in an experimental chlorocalcium arrhythmia in rats an anti-arrhythmic action of the sympatholytic-rausedyl, the gamma-adrenolytic-dihydroergo toxin, the beta-adrenolytic--obsidan, the M-cholinolytics--atropine and benactyzine was ascertained. The N-cholinolytics tropacin and hexamethonium had no effect on the parameters and the outcome of the chlorocalcium arrhythmia, whereas the M-cholinomimetic-- carbacholine potentiated the arrhythmogenic action of calcium chloride. The mechanism of the chlorocalcium arrhythmia development the authors attribute to an intensified discharge of epinephrine from the functional depot of the sympathetic nerve endings and to sensitization of the alpha- and beta-adrenoreceptors of the myocardium to the mediator. In the genesis of arrhythmia the participation of M-cholinoreceptors of the myocardium is presumed.


[Pharmacology of calenduloside B, a new triterpene glycoside from the roots of Calendula officinalis]. Calendulozide B--trioside of oleanolic acid, isolated from rhizomes of Calendula officinalis, Fam. Compositae, used perorally in doses of 5, 10, 20 and 50 mg/kg exerted an antiulcerous action in 3 experimental ulcer models of different genesis (caffein-arsenic, butadion and induced by ligation of pylorus) and also displayed a certain antiphlogistic and sedative action. It did not have any effect on the cardiovascular system, the tone of intestinal smooth muscles, diuretic renal function and electrolytes excretion with urine or on the biligenic function of the liver. The drug is devoid of locally irritation properties, manifests a relatively low hemolytic activity (15000 after Kofler) and an insignificant toxicity both with its one-time and chronic administration.


[Effect of amidine and guanidine derivatives on thrombocyte aggregation]. The capacity of 25 different amidines, guanidines and biguanidines to suppress the thrombocytes aggregation, induced by adenosinodiphosphate, was studied. Good prospects of a search for antiaggregation agents in this series of compounds are shown. N-benzyl-N1-propionylguanidine was found to reduce by more than 4 times the induced adhesiveness of the blood platelets.


[Change in the gastrointestinal tract and liver functions of animals due to dithiocarbamic acid derivatives]. The TMTD does not change the secretory activity of the dogs' stomach with its one-time administration by mouth in doses of 0.5--10 mg/kg. With its multiple introduction (10 mg per kg once a day for a space of consecutive 30 days) the secretion of juice increases, while the pepsin content in the juice of dags diminishes. The DEDCS, EEDMDCA, TMTD and EBDCC (singly into the stomach in a dose of 1l5LD50 per kg) bring down the glycogen-forming and secretory function of the liver in rats and inhibit the propulsive activity of the intestines in mice, stimulated with 5-oxytryptophan. The mechanism of the intestinal motor activity inhibition is caused by the inhibition of oxytryptophandecarboxylase (CP 4.1.1.28) in the intestines of the animals with the DTCA derivatives.


[K-strophanthin-beta complexing with calcium, magnesium and dysprosium ions]. Nuclear magnetic resonance, microcalorimetry and the use of the ion-selecting electrode evidenced that k-strophanthine-beta forms complexes with the calcium, magnesium and disprosium ions. Changes in the position of the k-strophanthine-beta carbohydrate parts and aglycones signals bear witness to their participation in the complexing.


[Effect of neocompensan (haemodesum) on the course of experimental myocardial infarct with arrhythmias in rabbits]. In rabbits with experimental myocardial infarction (EMI) complicated by arrhthmias the antiarrhythmic action of neocompensan (haemodesum) was ascertained for the first time. In the acute period of EMI no electrolytes shifts in the blood serum of the animals were disclosed and this justified the antiarrhythmis effect of neocompensan, occurring during the first 24 hours of the experiment, to be attributed to the influence of polyvinylpyrrolidine. Besides, the drug produced in rabbits with EMI deceleration of the total blood coagulation. Following administration of neocompensan (haemodesum) no arrhythmias were recorded. Thus, neocompensan (haemodesum) displays antiarrhytmic action, has a beneficial effect on the blood coagulation system and as a result reduces the lethality among rabbits with EMI, complicated by arrhythmias.


[Resistance to hypoglycemic sulfanilamides and biguanidines and its immune genesis]. In blood of patients with diabetes mellitus receiving bucarban or adebit antibodies to these drugs were discovered. Patients medicated with bucarban demonstrated an elevated content of antibodies to insulin. The appearance of specific antibodies occurred in rabbits and rats following introduction of bucarban, glucophage or adebit per se or when mixed with adjuvants. An increased production of antibodies to endogenous insulin was observed in all animals reveiving bucarban. Introduction to rats of inactivated (at 56 degrees C for 30 minutes) serum of patients with diabetes mellitus that contained antibodies to bucarban or adebit as well as immune rabbit sera greatly mitigated the hypoglycemic effect of the latter. Introduction to rats of the blood serum taken in patients reveiving bucarban allso attenuated the effect of exogenous insulin. These findings suggest that, possessing neutralizing properties, these antibodies to bucarban, adebit and glucophage cause habituation to these substances. Accumulation in the blood of autoantibodies to insulin following introduction of bacarban reduces the sensitivity to the exogenous hormone and manifests the existence of an immune mechanism securing the preservation of chemical homeostasis in the organism.


["System of recognition" (or "system of preference") for corticosteroids in the hepatocyte plasmatic membrane]. By using fluorescent probes it was shown that hydrocortisone, cortisone and estron decrease the constant of the probe binding with dimethylaminochalcone in the lipid membranes proportional to the distribution coefficient of steroids in the system lipids-water. It is only hydrocortisone and, to a lesser extent, cortisone which produce such an effect in the plasmatic membranes of the hepasytes. The presence of a "preference system" for corticosteroids is presumed in the membranes.


[Effect of an estrogen-progestin contraceptive preparation on the enzymatic acitivity of the pentosephosphate carbohydrate metabolic pathway and nucleic acid metabolic indices]. The effect of a long-term (14 days) combined introduction of mestranol and noiethinodrel in contraceptive doses on the activity of pentosophosphate routes enzymes of the carbohydrates metabolism, that of acid and basic ribonucleases and on the level of summary nucleinic acids in the uterus and liver in sexually mature female-rats was studied. It was found that the concentration of summary nucleinic acids in the tissues increases under the effect of the drug, the oxidative reactions enzymes become more active, while the activity of non-oxidative reactions enzymes of the pentosophosphate route and of acid and basic endoribonucleases in inhibited.


[Biochemical mechanisms of the action of cimetidine on the development of experimental stomach ulcers in rats]. In tests on rats with the use of the atom-absorption spectrophotometry a direct relation between the number of ulcerative lesion in the stomach, caused by immobilization, and the Ca2+ and Na+ content in the tissues of this organ was noted. The Ca2+ level declined propotrionally to the duration of the stress, viz. after a 1-hour long action-down to 76 per cent (9.9  micron/g) m after 4 hours-down to 65 per cent (7.7 micron/g) and with the calcium level in controls--11.8 micron/g. The Na+ content then increased, viz. after a 4-hour long immobilization is comprised 116 per cent (0.169 mM/g). The drug cimetidine prevented the development of lesions in the stomach and averted shifts in the content of ions in the tissues. The authors conclude that the fall of the Ca2+ ions in the tissues bears proof to a disturbed energy exchange in the cells and in this way contributes to the development of ulcerative lesions.


[Effect of wolfram, molybdenum, copper and arsenic on intrauterine fetal development]. Experients showed tungsten, molibdenum, copper and arsenic employed in doses producing no general toxic effect on the organism with their prolonged introduction to act adversely on the embryogenesis. Tungsten  copper and arsenic were found to increase the embryonal lethality and tungsten and molebdenum to inhibit the processes of bones ossification in fetuses. The authors presume that the embryotoxic effect of the study elements is due to their direct action on the developing organism. Tungsten molibdenum and copper amass in the organism of test fetuses without being arrested in the placenta. A possible embryotoxic effect should be taken account of in chosing biogenic doses of trace elements.


[Effect of the antifolic preparation, tomizin, that possesses antitumor activity, on thyroid gland function]. Experimental investigations and clinical observations on the use of alkylating antineoplastic agents demonstrated these to influence the thyroid function. It is worthwhile to assess the effect of the antimetabolite tomizine, displaying antineoplastic properties, on the function of this organ. Tests conducted on rats with sarcoma M-1 disclosed the maximally tolerated doses of tomizine to produce a marked inhibition of the thyroid function. The latter is attended by a reduced accumulation of introduced 131I in the iron. Structural changes in the thyroid occurring under the effect of tomizine are characterized by the lowering of the thyroid epithelium height, increased dimensions of the follicles and a diminished volume of the insular tissue. This also points to depression of the thyroid function. Disturbances in this organ taking place under the effect of a single introduction of tomizine may be reversible. Multiple administration of the drug produces persistent functional disorders in the organ.


[Effect of quinolaline di-N-oxide derivatives on the DNAse and plasmocoagulase of Staphylococcus aureus]. The effect of the di-N-oxide quinoxaline on the activity and biosynthesis of DNA-ase and plasmocoagulating properties of the Staphylococcus aureus, strain Zhaev, was studied. The highest action in respect to DNA-ase of the Staphylococcus is shown to display dioxydine (1,4-di-N-oxide of 2,3-dioxymethylquinoxaline). Under its effect there takes place a significant fall of the DNA-ase activity and the plasmocoagulating properties of the staphylococcus. In cultures treated with dioxydine or its biologically active analogues the ability to biosynthetize DNA-ase with subsequent cultivationon on a medium containing no compounds is not restored. A possible mechanism of action produced by the study drugs is suggested.


Parathyroid hormone biosynthesis: structure and function of biosynthetic precursors. Investigations over the past several years have uncovered new information concerning the processes involved in the cellular formation of parathyroid hormone (PTH). Studies of parathyroid hormone biosynthesis in vitro using intact cell preparations as well as cell-free systems have led to: identification and characterization of a biosynthetic pathway for the formation of PTH involving successive proteolytic cleavages of the hormone from a larger polypeptide precursor; identification of the subcellular locations where the proteolytic processing of the precursors takes place; isolation of the messenger RNA for the hormone; and, finally, synthesis of functionally active gene copy of the parathyroid mRNA. It is now generally recognized that biosynthetic precursors and their post-translational modifications by proteolytic cleavages are characteristic of the biosynthetic processes involved in the formation of most if not all secretory proteins, not only parathyroid hormone and other polypeptide and protein hormones, but such diverse proteins as immunoglobulins, enzymes, and albumin. Furthermore, it is now evident that these biosynthetic precursors belong to two distinct classes, preproteins and proproteins, based on several criterions, including i) the time that elapses between synthesis of the precursor and the proteolytic conversion to the product, ii) the subcellular site at which the cleavages occur, iii) the specificity of the enzymic cleavage, and iv) the characteristics of the primary structures of the precursors.


Relationship between vitamin K-dependent carboxylation and vitamin K epoxidation. It has been postulated that the liver microsomal conversion of vitamin K hydroquinone to its 2,3-epoxide (epoxidase activity) is coupled in some obligatory fashion to the vitamin K-dependent carboxylation (carboxylase activity) event also occurring in microsomes. This hypothesis is supported by the observations that the requirements for the two reactions are similar and that conditions that promote increased carboxylation increase the epoxidase activity. It has now been shown that both of these reactions are localized in the rough microsomal fraction of a cellular homogenate, and that both activities appear to be located on the luminal rather than the outer surface of microsomal membrane vesicles. The epoxidase activity has been found to be enriched as the microsomal carboxylase activity is fractionated, and a microsomal inhibitor of the carboxylase activity had been shown to also inhibit the epoxidase activity. The enzyme glutathione peroxidase inhibits both of these activities, suggesting that a hydroperoxide of the vitamin might be an intermediate for both reactions. The organic hydroperoxide t-butyl-OOH has also been shown to have weak vitamin K-like activity in an in vitro system. These data strengthen the hypothesis that these two reactions are related, perhaps through a common intermediate, but do not provide a definite molecular role for this interrelationship.


Nature of the vitamin K-dependent CO2 fixation in microsomal membranes. Vitamin K is a component of a membrane-bound enzyme complex which catalyzes the posttranslational carboxylation of peptide-bound glutamate to form the gamma-carboxyglutamate (Gla) residues of prothrombin. The reaction requires reduced vitamin K, bicarbonate, oxygen, and a carboxylase, and does not require ATP. In a Triton X-100 solubilized carboxylase system, it was found that the naphthoquinone ring structure is essential for activity, as is the 2-methyl group. Menaquinone homologs from MK-1 to MK-4 all had carboxylase activity, whereas menadione was inactive. However, dithiothreitol and other thiols form thioethers with menadione, which restores considerable carboxylation activity to the provitamin. Hydrogenation of the beta-gamma double bond in phylloquinone reduced its activity only slightly. The active species of "CO2" utilized in this carboxylation is CO2 and not bicarbonate. Ribosomes contain Gla residues and are labeled with CO2 when whole microsomes are incubated with CO2 in the presence of NADH and vitamin K. About 25% of the activity is releasable with puromycin, suggesting that Gla residues are formed on both the nascent chains and the structural proteins of ribosomes. The deoxycholate-solubilized carboxylase system can be dialyzed to yield membranous vesicles with enhanced carboxylase activity. The warfarin-binding protein from normal rats, but not that from warfarin-resistant rats, further enhances the carboxylase activity of these reformed vesicles.


Properties and biosynthesis of a vitamin K-dependent calcium binding protein in bone. Bone, whether of endochondral or intramembranous origin, contains the vitamin K-dependent calcium binding amino acid residue gamma-carboxyglutamic acid (Gla) in a small, anionic protein we have named osteocalcin. This protein, which constitutes 0.5 to 1.0% of the total bone proteins and about 20% of the noncollagenous protein, is extractable by EDTA, and contains at least 90% of bone Gla. Analysis of purified osteocalcin from chicken bone and independent sequence studies of an analogous bovine bone protein show no apparent homology to the Gla-containing region of prothrombin. Chicken osteocalcin specifically binds 2 moles of calcium ions per 6,500 g protein. Employing coumarin drugs and vitamin K-deficient diets, vitamin K-dependent osteocalcin biosynthesis has been demonstrated in the chick before and after hatching. Organ cultures of embryonic chick bone show de novo synthesis of osteocalcin, and microsomal preparations of embryonic bone also exhibit vitamin K-dependent carboxylase activity. In addition to the presence of osteocalcin in bone, a Gla-protein of unknown function is present in normal nonmineralized kidney cortex. Furthermore, in various pathological calcifications such as hard atheromatous plaque, renal calculi, and subcutaneous ectopic calcifications other Gla-proteins are found, thus implicating such proteins and vitamin K in many facets of calcium metabolism.


Interactions of vitamin K-dependent proteins with calcium ions and phospholipid membranes. The calcium-dependent interaction of vitamin K-dependent proteins with membranes is a complex process that minimally consists of 1) calcium binding to the protein and an essential calcium-dependent protein transition, 2) an essential calcium-membrane interaction, and 3) formation of the protein-membrane complex. Below about 5 mM calcium, the protein-membrane complex binds more calcium than the sum of the components but at higher concentrations protein-membrane binding is not accompanied by additional cation binding. These protein-menbrane interactions function in blood coagulation by increasing the binding affinity of the active site. The increased affinity results from the additive effects of protein-membrane (e.g., prothrombin-, factor Xa- and factor V-membrane) interactions and protein-protein (e.g., factor Xa- factor V and prothrombin-factor V) interactions. The prothrombinase complex can be viewed kinetically as a dissociable three-component enzyme (factor Xa, factor V, and phospholipid) acting on the soluble substrate, prothrombin.


The cell-to-cell channel.

The cell-to-cell channel. Cells of most organized tissues are interconnected at their junctions by aqueous membrane channels, shown in one instance to be at least 14--16 A in diameter. During junction formation, nascent channels are detected as quantal steps in cell-to-cell conductance, growing progressively in number. The channels detected are stable. Elevation of cytoplasmic free Ca2+ concentration can cause graded closure of channels.


Synaptic actions of acetylcholine: problems for future research. Acetylcholine is currently believed to act on postsynaptic membranes by binding to a specific membrane receptor protein and inducing a conformational change that opens a channel for ion fluxes. This conformational change is viewed as rate limiting, with the agonist binding-dissociation step being very fast. The open channel has a conductance of 27 pS, and the gating molecule responsible for the channel opening and closing undergoes a dipole moment change of 50 D in making the open-closed transition. Although this picture accounts quantitatively for many aspects of acetylcholine action, certain of the underlying assumptions are untested, and the view is incomplete or unsatisfactory in several other ways. Four goals for future research, then, are: 1) To determine whether conformational change or agonist dissociation is the rate limiting step; present interpretations assume the conformation change is rate limiting, but available data are equally consistent with the alternative assumption. 2) To discover the nature and significance of direct anticholinesterase actions on the channel gating process; evidence is available that some direct actions occur, but these have not yet been studied. 3) To fit the process of desensitization into the present picture of acetylcholine actions. 4) To merge the pictures of acetylcholine-receptor interactions that are being developed concurrently by physiologists and biochemists. Achieving this goal should eventually lead to an understanding of how intrinsic proteins regulate membrane ionic fluxes.


Tolerance to alloantigens of the A and B systems in chickens. Tolerance to alloantigens of the A and B systems in chickens has been induced by multiple injections of RBC and tested by the elimination of 51Cr-labelled RBC of the same specificity. Three doses consisting of at least 108 RBC each in the B system and 107 RBC in the A system were needed to induce tolerance in newly hatched chicks. Futhermore, it was found that large doses, 109 RBC, in both systems induced tolerance in 100% of week-old and 50% of 14-day-old chickens. With doses of 109 RBC, tolerance to the B antigen disappeared at 8 days in the absence of RBC, whereas in the case of the A antigen it disappeared after more than 50 days, and with the 107 cell doses after 35 days. The elimination of A-incompatible RBC was proportional to the amount of anti-A antibodies present in the recipient's circulation, whereas a minimal amount of antibodies was capable of considerably accelerating the elimination of B-incompatible RBC.


Transfer to chick embryos of incompatible DNA. After the transfer of chicken DNA to chick embryos incompatible at the B locus a retardation of growth was observed. Retarded differentiation of muscle fibres was histochemically detected in hatched chicks by the demonstration of enzymatic activities. The manifestations of apparent weakness of the dorsal muscles resembled a "myasthenia-like" syndrome. Infection with Marek's disease virus was not responsible for the damage caused by transferred DNA.


The interaction of migration, income, and employment in Sweden. A common approach in migration studies is to explain interregional migration by single-equation models. Such models are likely to suffer from simultaneous-equation bias when used in studies attempting to analyze migration over a long period of time.  In this study, a simultaneous-equation appraoch is applied, which takes account of the interdependence between migration and income and employment changes. The four-equation model is estimated for 70 labor market areas in Sweden.


Recent net alien immigration to the United States: its impact on population growth and native fertility. Estimates of the size and structure of recent alien immigration to the United States are made. Substituting these revised estimates in the Series II projections of the U.S. Bureau of the Census implies a future U.S. population smaller than that implied by the Census Bureau's estimates of immigration. The analysis of Coale (1972)--which calculates the decline in native-born fertility required to accommodate immigration and, at the same time, maintain a stationary population--is replicated, using both the Census Bureau's estimates and the revised estimates reported here. The revised estimates indicate a smaller reduction in native fertility and a smaller ultimate size of the stationary population than are implied by the Census Bureau's immigration estimates. The importance of age structure in all of these calculations is demonstrated.


Residential mobility on skid row: disaffiliation, powerlessness, and decision making. Individual-level models of residential mobility emphasize (a) the stabilizing effects of various social, demographic, and housing characteristics and (b) the important mediating role played by decision-making variables. Data from a sample of skid row residents are analyzed to determine if these models retain their accuracy under conditions of disaffiliation and powerlessness. The findings indicate that, while older age, employment, and other characteristics may encourage residential stability on skid row, such factors influences mobility behavior in a direct fashion rather than through the intervening decision variables of residential evaluation and mobility expectation. In general, persons with weakened social attachments and little control over their lives and resources find it difficult to engage in the calculated, long-term type of decision-making process implied by mobility theory.


Toward a general theory of fertility: a causal modeling approach. A general theory of fertility is derived hypothesizing that the demand for children is primarily an outcome of social psychological processes within the family, subject to certain socioeconomic constraints. Two broad social psychological processes are posited as determinants of fertility. The first suggests that the attitudes or tastes of family members influence the demand for children. The second maintains that the nature of the husband-wife interaction (in terms of power, conflict, decision making, and marital satisfaction) determines family size. Socioeconomic variables, in the form of the normative social structure and social stratification, and economic constraints, such as income and price, are hypothesized to influence fertility through their impact on social psychological processes within the family. The overall theory is tested on two independent samples--one in Ankara, Turkey, the second in Mexico City, Mexico--using a structural equation methodology.