Pre-emption of human cell-mediated lympholysis by a suppressive mechanism activated in mixed lymphocyte cultures. The regulation of B-cell and T-cell immune responses has been extensively examined and in the experimental animal appears to involve regulatory or "suppressor" T cells (1-4). The limitations of in vitro experimentation have made comparable study of nonpathological human suppression quite difficult (5). We report here an in vitro method that generates and quantitates suppressor activity in man after antigen-specific activation in mixed leukocyte culture (MLC). The one-way MLC induces both a proliferative response (6) and the generation of cytotoxic T lymphocytes (CTLs) (7). Both of these responses are mediated by antigen-specific T-cell subpopulations (8,9) and have been correlated with recognitive and destructive phases of allograft rejection. Recent reports have examined the antigen reactivity of mouse (10,11), rat (12), or human (13,14) lymphocytes obtained after proliferation in MLC. In all cases, after the primary MLC proliferative peak, the recovered lymphocytes rapidly differentiate upon re-exposure to the initial stimulating population, but do so only weakly when exposed to a presumably noncross-reactive third-party stimulating population. Velocity sedimentation separation studies have shown that the blast cells produced in a primary MLC revert to small lymphocytes that rapidly differentiate into proliferating and/or cytotoxic T lymphocytes upon restimulation with the initial antigen (15). These findings demonstrate that positive selection for the responding population in primary MLC does exist and may account for at least part of the specificity of the secondary response. However, this positive selection does not preclude possible involvement of a suppressor mechanism. In fact we have detected suppressor activity in primary MLC sensitization cultures at a time when the proliferation responsible for positive selection does not preclude possible involvement of a suppressor mechanism. In fact we have detected suppressor activity in primary MLC sensitization cultures at a time when the proliferation responsible for positive selection in not yet significant, suggesting that suppression may be overriding importance in the specificity of MLC-activated secondary responses.


Concanavalin A potentiates syngeneic response in murine lymphocytes. In an attempt to modulate the recognition processes that occur on lymphocyte membranes in mixed lymphocyte culture, responding cortisone resistant thymocytes or stimulating spleen cells (treated with mitomycin C) were pretreated with native concanavalin A (N-Con A) or succinyl-Con A (S-Con A). Highly significant cell proliferation was observed in syngeneic combinations when either the responding cells or the stimulating cells were so treated with Con A, although Con A pretreatment alone was never mitogenic. In allogeneic combinations the proliferative response with Con A pretreatment of either partner on day 3 was five to seven times higher than in the normal mixed lymphocyte reactions. The triggering of proliferation was dependent on two factors: (a) The presence of spleen cells as the stimulating cells (thymocytes were much less effective). (b) The binding of Con A molecules to either one of the partners, the effect being abrogated by the specific inhibitor of Con A, alpha-mannopyranoside. The optimal concentration of S-Con A was about twice that of N-Con A. Even more striking was the observation that cultures in which either one of the partners was pretreated with Con A in allogeneic combinations showed a strong suppression (60-80% inhibition) in the subsequent generation of the cytotoxic lymphocytes (CL). The Con A concentration required to trigger a proliferative response corresponded to that for suppressing the generation of CL. Con A pretreatment did not result in a cytotoxic activity toward syngeneic tumor cells.


Purification and molecular properties of the (sodium + potassium)-adenosinetriphosphatase and reconstitution of coupled sodium and potassium transport in phospholipid vesicles containing purified enzyme. Recent work in our laboratory on the purification and characterization of the (sodium + potassium)-activated adenosinetriphosphatase (NaK ATPase) has been reviewed. Two enzymes have been purified, that from the rectal salt gland of the spiny dogfish, Squalus acanthias and that from the electric organ of the electric eel, Electrophorus electricus. The enzyme appears to consist of two catalytic subunits of molecular weight of about 95,000 and one glycoprotein with a molecular weight of about 50,000. The amino acid composition, N-terminal amino acids, and the carbohydrate composition of these subunits have been determined. The phospholipid composition of the holoenzyme has also been determined. The protein component shows very little variation with evolution, but the carbohydrate and phospholipid components show considerable variation. It has been possible to form vesicles from the purified enzyme from Squalus acanthias and to demonstrate the ATP-dependent, ouabain inhibitable, coupled uphill transports of Na+ and K+. The properties of these transports are very similar to those observed previously in intact erythrocytes or resealed erythrocyte ghosts with respect to asymmetries of binding sites, stoichiometries of Na+ and K+ transported, Na+-Na+ exchange, and K+-K+ exchange. It is concluded that the NaK ATPase is the molecular machine for effecting Na+ and K+ transport in the intact cell membrane.


Hepatic morphology in Huntington's chorea. Liver biopsy specimens from six patients with Huntington's chorea were examined locally and referred with clinical information to three colleagues abroad experienced in the interpretation of liver biopsy specimens. The minor and inconsistent abnormalities reported upon were of non-specific character. The suggested interrelation between damage to cerebral neurones and hepatocytes in Huntington's chorea was not substantiated by this study.


Human muscle spindles: fine structure of the primary sensory ending. The primary sensory innervation of muscle spindles obtained by muscle biopsy of normal human volunteers was studied with the light and electron microscopes. The parent IA sensory fibre branched 4-6 times, became unmyelinated for 25-30 mum, then formed sensory terminals on each nuclear bag and chain intrafusal muscle fibre. The first 4--5 mum of the unmyelinated segment is believed to be an encoder zone because the plasmalemma was undercoated by a dense granular layer similar to that under other membranes where action potentials originate. A reconstruction from micrographs of serial longitudinal sections showed that the primary sensory ending on a nuclear bag fibre is an irregular coil with branches and varicose swellings. The terminals contain central aggregates of microfilaments often surrounded by mitochondria, small numbers of vesicles, cisterns and tubular profiles. The latter merge with the plasma membrane. Junctional complexes between the plasma membranes of the terminals and intrafusal muscle resemble fascia adherns and are postulated to act as attachment plaques. These could contribute to the transduction process by incresing the degree of distortion of the terminal's membrane when stretch is applied to the spindle. A mechanism is described which could account for some of the differences in sensitivity of the primary and secondary sensory endings.


Remyelination by Schwann cells of axons demyelinated by intraspinal injection of 6-aminonicotinamide in the rat. Focal areas of primary demyelination were produced in the spinal cords of rats by means of local injections of 6-aminonicotinamide. Both astrocytes and oligodendrocytes underwent degeneration in the demyelinated area. Nearly all the demyelinated axons were remyelinated by Schwann cells; only a very small number of axons located adjacent to normally myelinated axons were remyelinated by oligodendrocytes. The glial limiting membrane was reconstituted around the ecge of the area remyelinated by Schwann cells. This experiment offers further evidence for an important role of astrocytes in controlling Schwann cell invasion of the central nervous system, and in addition suggests that astrocytes are also needed for oligodendrocyte remyelination to take place.


The selective in vivo incorporation and metabolism of radioactive putrescine in the adult male rat. Putrescine (1,4, diaminobutane), a known precursor of the polyamines, spermine, and spermidine, was studied as a possible vehicle for a radioisotope scan of the prostate and other tissues rich in polyamines. Male Sprague-Dawley rats received intravenous injections (2.3 muCi/100 gm) of 3H putrescine dihydrochloride (specific activity, 107 muCi/muM). One hour after injection the ventral prostate and pancreas showed uptake of radioactivity that was three and four times greater than that of the liver, respectively. The ratio of the amount of radioactivity in the ventral prostate compared with that of abdominal wall musculature was 8:1. The pancreas-to-muscle ratio was 10:1. At 1 hr the ventral prostate contained 0.6% (0.9%/gm wet wt) of the total injected radioactivity and the pancreas, 0.5% (1.2%/gm wet wt) of the injected dose. More than 90% of the radioactivity in the rat ventral prostate, 6 hr after intravenous injection of 14C-putrescine dihydrochloride, was found to be in the form of spermine and spermidine, thus confirming previous in vitro biosynthetic studies.


Impulse activity and receptor potential of primary and secondary endings of isolated mammalian muscle spindles. 1. An isolated muscle spindle preparation from a tail muscle of cat is described. The afferent response to a ramp-and-hold stretch was recorded in individual axons from identified primary and secondary endings. 2. Primary endings exhibit a prominent dynamic response, including an initial burst. They also show a well-maintained static discharge. Secondary endings also show a well-sustained static discharge but generally have a much lower dynamic sensitivity. The response of primary and secondary endings of the isolated spindle are similar to the typical responses seen in vivo in groups Ia or group II afferent fibres respectively. 3. Following  impulse blockade by tetrodotoxin, the receptor potential was recorded from primary and from secondary endings in response to ramp-and-hold stretch. 4. During the dynamic phase the receptor potential of primary endings consists of a depolarization which has two components. (a) An initial component occurs early during ramp stretch, depends in rate of rise and amplitude on velocity of stretch and is reduced on repetitive stretch; it appears to be responsible for the initial burst. (b) A late dynamic component, which follows, is also dependent on stretch velocity and produces the late dynamic discharge. At the end of ramp stretch the receptor potential falls, and may undershoot, the static level. There is a subsequent adaptive fall during hold stretch, then a maintained static level of receptor potential. On release from stretch the membrane is hyperpolarized. 5. Secondary endings usually show a smaller dynamic response, lacking the initial component seen in primary endings. They also generally lack an undershoot following the ramp and have less of a post-release hyperpolarization. 6. Static levels of receptor potential in both primary and secondary endings are related to amplitude of stretch. 7. The receptor potentials of primary and secondary endings account for the major features of the impulse responses of these endings to ramp-and-hold stretch. In primary endings the dynamic frequencies may also depend upon a sensitivity of the impulse initiating site to rate of change of receptor current.


Effect of insulin upon membrane-bound (Na+ + K+)-ATPase extracted from frog skeletal muscle. 1. Insulin stimulates the activity of membrane-bound ATPase isolated from frog skeletal muscle and from rat brain. The increase in activity of the membrane-bound ATPase system isolated from frog ranged from 9-8 to 53% at concentrations of Na+ (25 mM), K+ (10 mM), and ATP (2 mM) similar to those in in vivo experiments conducted previously (Moore, 1973). The increased activity of the membrane-bound ATPase is, therefore, at least as great as the insulin-induced increase in Na efflux (10-38%) from intact cells (Moore, 1973). If the concentration of Na+ is lowered to 4 mM and that of ATP lowered to 0-5 mM albumin, and 10(6) M, the increase in ouabain-inhibitable ATPase activity can reach as high as 400%. 2. Ouabain, at a concentration (10(-3) M) sufficient to inhibit stimulation of the frog ATPase by increasing Na from 4 to 25 mM, completely blocked the stimulation of ATPase activity due to insulin. 3. At 2 mM-ATP, 100 mM-Na+, and 20 mM-K+, conditions which maximally activate the (Na+ + K+)-ATPase, insulin did not increase the ATPase, activity. Stimulation was consistently seen at 10 mM-K+, 0-5 mM-ATP, and either 4 mM or 25 mM-Na+. 4. The finding that insulin does not stimulate the ATPase activity in conditions in which the (Na+ + K+)-ATPase component is maximally activated and especially the fact that ouabain can reproducibly inhibit insulin stimulation of the membrane-bound ATPase activity strongly suggest that interaction of insulin with its receptor upon the plasma membrane somehow stimulates the (Na+ + K+)-ATPase system (ouabain sensitive; ATP phosphohydrolase, EC (3.6.1.3). These results are consistent with previous studies of the effect of insulin upon Na efflux from intact cells (Moore, 1973) and support the previous conclusion that the component of Na efflux stimulated by insulin is active. The evidence suggests that insulin probably does not affect Vmax of the (Na+ + K+)-ATPase system, but may increase the affinity of the enzyme system to one or more effectors, most likely Na+, ATP, and perhaps K+. 5. Oxidized glutathione (2-7 X 10(-6) M), 10(-6) M, 10(-7) M, and 10(-8) M cyclic AMP did not affect the ATPase activity 10(-6)Malbumin, and . 6. The results are consistent with the view that the Na pump, (Na+ + K+)-ATPase, is intimately involved with the physiological action of insulin and may be transducer between the binding of insulin to its receptor on the plasma membrane and the cellular actions of insulin.


Mouth-operated devices for handicapped persons. A mouth-operated device designed for paralyzed persons was described. This device enables invalid persons to perform simple, everyday actions. The uses and advantages of the instrument as compared to other types were discussed.


The lives of patients before presentation with pain in the neck or back. More significant events occurred in the lives of patients during the three months before presentation in general practice with pain in the neck or back than in a control group of symptomless patients.These findings were obtained by the completion by patients of a short questionnaire and their significance is discussed.


Genetic and endocrine studies of the pregnancy-blocking pheromone of mice. Secretion of the pregnancy-blocking pheromone was stimulated by injection of depo-testosterone cypionate into females and males of inbred strains of mice which do not normally secrete the pheromone. Testosterone treatment of SJL males altered pheromone secretion so that pregnancies were blocked when the stud male was of the same inbred strain; an event that does not normally occur. Injection of epiandrosterone, androstenedione, androsterone or testosterone significantly increased pheromone secretion in SJL females, but progesterone and dehydroepiandrosterone were ineffective. Kidney weights were significantly increased by administration of androgen metabolites and the possibility of the kidney being the site of pheromone synthesis is discussed. The preputial gland can be excluded as the site of pheromone synthesis since males which are hemizygous for the Tabby-J gene and have no preputial glands blocked pregnancies as effectively as their normal littermates. Preliminary results are also presented concerning the isolation of the pregnancy-blocking pheromone from urine. Urine was analysed by gas chromatography and a peak was observed whose concentration could be correlated with secretion of the pheromone, although the compound(s) has not been identified or tested for biological activity.


Excess electrical noise during current flow through porous membranes separating ionic solutions. Spectral analysis of electrical noise from various artificial membrane systems suggests that excess noise of an f-n spectral form, where n is approximately unity, is not primarily a bulk phenomenon simply dependent on the number of charge carriers. Measurements from aqueous and nonaqueous electrolytic resistors, comprised of several different ionic species, show only flat power density spectra under applied currents, even at extreme dilutions. Excess noise of f-n form is observed under applied d-c current in single pore membranes, as previously reported, but is also seen in multipore and polymer mesh membranes. Calculations based on single pore membrane noise data are in significant variance with the bulk charge carrier model proposed by Hooge. These observations suggest that such excess noise occurs in conjunction with anisotropic constraints to ion flow.


The use of a registry case load survey in predicting trends in rehabilitative needs for the handicapped. A special follow-up study of handicapped children was carried out to determine the level of residual disability in the caseload of the British Columbia Health Surveillance Registry. A total of 10,689 cases, aged seven or fourteen years were surveyed. Sixty-eight per cent of seven-year-olds and sixty-five per cent of fourteen-year-olds had a residual handicap. Of 3,131 seven-year-olds with a residual handicap, four per cent were not attending a school of any kind. Three per cent of the 4,094 fourteen-year-olds with a residual handicap were not attending school. These figures, along with prevalence statistics obtained through other Registry procedures provide useful minimal data for planning rehabilitative facilities for handicapped persons.


Banding identification of chromosomal abnormalities in four patients: ring (6), translocation (2q-;15q+), translocation (21q;21q) and deletion (22q-). Four children with mental deficiency and different chromosomal errors, previously reported, have been restudied with the use of the G-banding technique. The errors include ring-6, t(2q-; 15+), t(21q;21q) and 22q-.


The nature of the colour retention deficit in Down's syndrome. In Sinson and Wetherick (1973) the authors reported evidence that Down's syndrome children show a deficit in short-term retention of colour information not shown by matched S.S.N. controls. The experiments were conducted in good daylight illumination. Repetition in blue weak artificial light showed that retention of green, red and purple was much improved but that the other colours were not affected. Implications of the finding are considered for theories of colour vision and short-term retention and for educational technology.


Thymineless bacteriophage induction in Staphylococcus aureus. I. High-frequency transduction with lysates containing a bacteriophage related to bacteriophage phi 11. A thymine-requiring mutant of Staphylococcus aureus, strain 8325 (PI258)thy, undergoes prophage induction and lysis after thymine starvation. Four different phages were isolated from the lysate in low titers, among which was a phage designated phi 14, which differs from phage phi 11 in its immunity locus. The thymineless induced lysates of strain 8325(PI258)thy transduce the penicillinase plasmid at high frequency (10(-1), whereas transduction of chromosomal markers is inefficient. A plasmic-cured derivative of strain 8325(PI258)thy is also lysed by thymine starvation and be used for high-frequency transduction of other plasmids. Reconstitution of a strain of S. aureus that responds to thymine starvation was only partially successful, but this system can effectively be used to transduce plasmids or plasmid derivatives.


Thymineless bacteriophage induction in Staphylococcus aureus. II. Specific transduction of constitutive and inducible erythromycin resistance. Specific transduction of inducible (eroA) and constitutive (eroB) erythromycin resistance is mediated by thymineless induced lysates from derivatives of Staphylococcus aureus strain 8325(N)thy. Both loci can coexist in the same cell but segregate by transduction or transformation. The gene(s) is probably integrated in the recipient chromosome and excised at thymine starvation.


Observations on epizootiology and distribution of Elaeophora schneideri in Montana ruminants. Seventy-four moose, 111 elk, 20 mule deer, 8 white-tailed deer, 26 prong-horn antelope, 42 domestic sheep and 3 bighorn sheep from Montana or northwestern Wyoming were examined post-mortem for evidence of Elaeophora schneideri infection in 1973-74. Fifteen percent of the mule deer and four percent of the moose were positive for adult arterial worms. This constitutes the first report of E. schneideri in mule deer in Montana. No gross signs of blindness or other neurologic disorder were evident in the infected animals. Potential horsefly intermediate hosts collected in the enzootic area included Hybomitra rhombica osburni, H. tetrica, H. metabola, Chrysops noctifer pertinax and Atylotus incisuralis.


Echocardiographic observations in hypertension. Ultrasoundcardiograms (UCG) and radiocardiograms (RCG) were obtained from 50 patients with essential hypertension. They were classified into four groups according to the severity index of Veterans Administration Hospital. These echocardiograms were compared with those obtained from 20 normal individuals. Of the 50 patients with hypertension, ten had abnormal patterns of mitral valve echogram: two had shoulder formation of the A wave (A-A'), three had increased amplitude of the A wave (A greater than E), and five had systolic anterior movement (SAM) of the anterior mitral leaflet toward the ventricular septum. The former two groups were considered to have impairment of left ventricular (LV) function proven by UCG and RCG, however, the SAM group was considered to have hyperfunction with concentric hypertrophy of the left ventricle with thickened ventricular septum simulating that of idiopathic hypertrophic subaortic stenosis (IHSS). This was supported by the fact that SAM increased after inhalation of amyl nitrite and decreased after injection of propranolol. The descent rate of the anterior mitral valve decreased and the thickness of the ventricular septum increased with the severity of hypertension, indicating the LV compliance decreases as the severity of hypertension advances. A significant positive correlation was noted between stroke index (SI) obtained by UCG and RCG. There were no significant differences of LV dimensions and function indices measured by UCG and RCG among the groups classified according to the severity index of hypertension. This suggests that such factors as myocardial ischemia might play an important role in LV function as well as the grade of afterload due to hypertension.


[Contractile myocardial proteins in patients with acquired heart defects]. The ATP-ase activity of myosin; the level of SH-groups and the concentration of myosin were studied in various clinical groups of patients with mitral, mitral-aortic and mitral-aortic-tricuspid valve defects. Proceeding from the duration of the history of the disease, the mitral cases were grouped in the following way: Group 1 -- heart disease of under 10-years duration; Group 2 -- under 20 years; Group 3 -- over 20 years; Group 4 -- three patients with combined heart diseases; Group 5 -- four lethal cases due to postoperative cardiovascular failure. The papillary muscle was taken for biochemical tests in all surgical procedures for mitral valve replacement. The conducted investigations demonstrated that the ATP-ase activity of myosin was the lowest in those dying after surgery of cardiovascular failure. The earliest sign of the deteriorating structure of the contractile proteins in lasting mitral heart disease is the growing content of thiol compounds of myosin.


[Certain changes in the water-electrolyte metabolism in desoxycorticosterone acetate salt hypertension in rats adapted to high altitude hypoxia]. In the course of the development of desoxycorticosterone-acetate-salt hypertension the animals were noted to display high appetite of sodium chloride, a considerable increase of the weight of the heart, kidneys and adrenal glands, of the diameter of the glomeruli and the surface of the cortical and medullar zones of the kidneys, a decrease of the sodium and potassium gradient in the renal tissue. Adaptation to hypoxy is noted so cause a decrease in the interventricular factor, in the width of the glomerular zone of the adrenal glands, in the sodium concentration in the erythrocytes, an increase in the mass of the medullar layer of the kidneys, and an increase in the sodium and potassium gradients. When adaptation to hypoxy is combined with the effect of desoxycorticosterone-acetate-salt, hypertension develops to a lower degree than in non-adapted animals.


An activation mechanism for ATP cleavage in muscle. Evidence for a proposed activation mechanism is summarized. The low rate of ATP cleavage in the resting state of muscle is considered to result from the formation of a stable ring structure involving the two essential sulfhydryl groups on each myosin head and MgATP. Activation is thought to occur by interaction of actin in the vicinity of one of the essential sulfhydryl groups. Thus opening the stable ring leading to rapid dissociation of split products. This idea is consistent with the kinetic scheme of ATP cleavage developed recently by other workers and allows a prediction of the shift in population of intermediate states with changes in solvent conditions. It is also supported by our recent studies on the spatial geometry of the ring. The possibility that other nucleophilic groups may replace the sulfhydryl groups in other contractile systems is considered. The relevance of the ring structure to the tension generating event is discussed on the basis of recent measurements of the rate of contraction of modified (SH1-blocked) actomyosin threads. Results indicate the ability to form the ring structure is an essential requirement of the contractile process in these systems, and, moreover, that single, modified heads of myosin can act independently to produce the same rate of contraction as native myosin. This latter finding suggests that the myosin duplex exhibits some type of negative cooperativity in the contractile process.


Structural changes in myosin during contraction and the state of ATP in the intact frog muscle. The reactivity of myosin to [14C]-labeled N-ethylmaleimide ([14C]NEM) or to tritium was determined in functionally different frog muscles. The incorporation of [14C]NEM into myosin decreased during isotonic or isometric contractions, as compared to resting muscle. The cysteine residues which were protected during contraction were not involved in the ATPase activity or the actin-binding ability of myosin. Peptide mapping revealed that several residues were protected simultaneously. The incorporation of tritium into the peptide N-H groups of myosin was also decreased during muscle activity. These data support the idea that activation and subsequent contraction of muscle are correlated with structural changes in the myosin molecule. The reactivity of myosin to [14C]NEM was increased when the muscle was stretched to 140% rest length and treated with iodoacetate to deplete ATP. Based on in vitro experiments and on literature data, it is suggested that in the resting muscle myosin contains bound MgATP which decreases the rate of incorporation of [14C]NEM into myosin and that upon the irreversible loss of ATP the rate increases. 31P nuclear magnetic resonance signals from a number of phosphates were detected in the intact frog muscle. The data indicated that the minimum concentration of ATP in the muscle is 3 mM, a value which agrees with that of chemical determination. The characteristic chemical shifts, coupling constants, and line widths of ATP in the muscle were considerably altered from that of either free ATP in aqueous solutions or ATP in perchloric acid extracts of muscle.


The bound nucleotide of actin.

The bound nucleotide of actin. The extent of actin polymerization has been studied for samples in which the bound nucleotide of the actin was ATP, ADP, or an analog of ATP that was not split (AMPPNP). The equilibrium constants for the addition of a monomer to a polymer end were determined from the concentration of monomer coexisting with the polymer. An analysis of these results concludes that the bound ATP on G-actin provides little energy to promote the polymerization of the actin. AMPPNP was incorporated into F-actin and the interaction of F-actin - AMPPNP with  myosin was studied. F-actin - AMPPNP activated the ATPase of myosin to the same extent as did F-actin - ADP. However, the rate of superprecipitation was slower in the case of F-actin - AMPPNP than in the control.


Isotopic probes of catalytic steps of myosin adenosine triphosphatase. A new approach to the direct estimation of the value of the off constant for dissociation of ATP from myosin subfragment 1 (S1) has been developed. From measurements of the extremely slow rate of release of [32P] - ATP formed from 32P(i) by S1 catalysis and the amount of rapidly formed [32P] - ATP tightly bound to S1, the value of the off constant is approximately 2.8 X 10(-4) sec -1 at pH 7.4. The concentration dependencies for P(i) in equilibrium H18 OH exchange and for (32)P(j) incorporation into myosin-bound ATP give direct measurements of the dissociation constant of P(i) from S1. Both approaches show that the enzyme has a very low affinity for P(i), with an apparent K(d) of greater than 400 mM. Measurement of the average number of water oxygens incorporated into P(i) released from ATP by S1-catalyzed hydrolysis in the presence of Mg2+ suggests that the hydrolytic step reverses an average of at least 5.5 times for each ATP cleaved. With the Ca2+ -activated hydrolysis, less than one oxygen from water appears in each P(i) released. This finding is indicative of a possible isotope effect in the attack of water on the terminal phosphoryl group of ATP.


Time-dependent fluorescence depolarization and lifetime studies of myosin subfragment-one in the presence of nucleotide and actin. Time-dependent fluorescence depolarization and lifetime studies have been made on myosin subfragment 1 to obtain information about mobility changes and dye environment changes when different nucleotides are added. Data are reported for static and actively hydrolyzing systems containing G- and F-actin. Preliminary data indicate that myosin labeled with the fluorophore 1, 5 IAEDANS and treated with DTT preserves its actin-activated Vmax. S1 prepared in this manner gives lifetime changes which are nearly identical for all systems studied. S1 labeling without DTT addition gives a pattern of lifetimes similar, though not identical to ESR work. Either type of labeling produces no observable change in the polarization decay, and we set an upper limit of 15% length change for the elongate S1. An unusually long fluorescence decay lifetime for the S1-Mg++ ATP-G-actin system is found which may indicate a new acto-S1 state stabilized by G-actin. The method for obtaining the bound fraction of S1's in the presence of actin is presented and applied to the S1-F-actin-Mg++ ATP system. Qualitative agreement is obtained with other methods.


The binding of Mn2+ and ADP to myosin.

The binding of Mn2+ and ADP to myosin. The metal ion requirement of myosin-ADP binding was investigated by use of Mn2+. Mn2+ binds to two sets of noninteracting sites on myosin which are characterized by affinity constants of 10(6) and 10(3), M(-1) at 0.016 M KCl concentration. The maximum number of sites is 2 for the high affinity and 20-25 for the low affinity set. Binding of Mn2+ to the high affinity sites increases the affinity of ADP binding to myosin. F-actin inhibits ADP binding (Kiely, B., and Martonosi, A., Biochim. Biophys. Acta 172: 158-170 [1969]), but even at F-actin concentrations much higher than that required to saturate the actin binding sites of myosin or its proteolytic fragments, significant ADP binding remained. The actin insensitive portion of ADP binding was inhibited by 10(-4) M inorganic pyrophosphate or ATP. The results are discussed on the basis of a model in which actin and ADP bind to myosin at distinct but interacting sites.


Interaction of myosin and paramyosin.

Interaction of myosin and paramyosin. The interaction of myosin and paramyosin was investigated by enzymological and ultrastructural techniques. The actin-activated Mg+2 ATPase of rabbit skeletal muscle myosin can be inhibited by clam adductor paramyosin. Both proteins must be rapidly coprecipitated to form filaments for this inhibition. Slowly formed cofilaments are fully activatable by F-actin. In both cases, the cofilaments possess unique structural characteristics when compared to homofilaments. The mode of inhibition appears to be competitive when different concentrations of paramyosin and F-actin are compared. The apparent affinity of the myosin heads for actin is reduced by the presence of paramyosin within rapidly reconstituted thick filaments. These results suggest that paramyosin may serve as part of a relaxing mechanism within invertebrate muscles. It is unlikely that paramyosin plays a role in the initiation and maintenance of catch within specialized molluscan muscles.


Calcium regulation of cardiac myofibrillar activation: effects of MgATP. In 2 mM MgATP, 0.08 ionic strength and 1 mM free Mg++ cardiac myofibrils bound 3.5 nmoles Ca/mg protein at maximal ATPase activation. Significant amounts of Ca were also bound to cardiac myosin with these same conditions. By subtraction of this myosin-bound Ca we obtained an estimate of 4 moles Ca bound per mole of myofibrillar troponin at maximal ATPase. We found, however, that Ca activation of myofibrillar ATPase could be estimated assuming that only two of troponin's Ca-binding sites are engaged in regulation of crossbridge activity. Increases in MgMTP from 0.3 to 5.0 mM raised the free Ca, giving half-maximal isomteric tension or ATPase. Although part of this shift is most probably due to changes in the number of rigor (nucleotide-free) actin-myosin linkages, the rightward shift of the free Ca++-activation relation with increase in MgATP from 2 to 5 mM appears to be due to effects of active (nucleotide-containing) actin-myosin linkages.


Effect of essential phospholipids on the properties of ATPases of isolated rat liver plasma membranes of young and old animals. "Essential" phospholipids (EPL), rich in dilinoleyl-phosphatidylcholine were given orally to young and 780-800 day-old rats. The double-labelled (14C/32P) dilinoleyl-phosphatidylcholine was incorporated in plasma membranes and the amounts incorporated into different organs investigated. Old animals incorporated higher radioactivity than young. The 14C/32P ratio however decreased in comparison with the substance administered. The amount of (Na+-K+)-ATPase in rat liver plasma membranes of old animals increased after pretreatment with EPL. The thermostability of ATPases was increased in plasma membranes of EPL treated old animals. In old animals EPL significantly lowered the cholesterol content. The membrane fluidity increased. The role of EPl in structural and functional properties of aged plasma membranes is discussed.


Characterization of age-associated kidney disease in Wistar rats. Kidney disease was studied patho-histologically, electron microscopically and immunologically in Wistar rats ranging in age from 2 weeks to 24 months. Glomerular lesions characterized by adhesion of podocyte foot processes were first detected at 3 months of age. The kidney lesions became more pronounced with age, as manifested by an increase of mesangial matrix, basement membrane thickening, crescent formation and hyalinization of glomeruli, and tubular degeneration. Evidence for the deposition of immune complexes in the kidney was obtained by immunofluorescence and electron microscopy, as well as by immuno-electrophoretic analysis of kidney elutions. Tests with antiserum reagent against Moloney leukemia virus antigen revealed its presence in some but not all glomeruli. The presence of other viruses in Moloney leukemia virus negative glomeruli was not ruled out. Serum autoantibody against an array of rat tissues could not be detected. Therefore, it would appear that autoimmune mechanism may not be the primary underlying cause of pathogenesis of the disease. Accordingly, the disease could be referred to as chronic immune complex glomerulonephropathy with nephrotic syndrome, but sources of the antigens in the complex were mostly unknown, althougn virus could be one portion of them. The possibility that diet antigens may also be present in the complex seems unlikely because attempts to demonstrate serum antibodies against diet pellet in old rats were unsuccessful.


[Echography in sinus diseases (author's transl)]. With high frequency echography (8 MHz) rhinogenic processes can be examined after they have penetrated the bony wall. Thus extension and form of bony defects can be determined and the degree of soft tissue involvement in the orbit can be evaluated. A scan echography provides tissue differentiation; it is a safe method bearing no risk for the patient and can be repeated any time. Whenever orbital involvement in cases of sinusitis is suspected, a scan echography of the orbit and adjacent sinuses is recommended.


[X-Ray and clinical study of the nose, sinuses and maxilla in patients with severe iron deficiency disease (author's transl)]. A definite relation between ozaena and iron deficiency disease could not be verified. However, the examination of 88 patients with severe iron deficiency disease, mostly of juvenile age, revealed that X-ray pictures of the nose and the paranasal sinuses showed abnormal alterations indicating the existence of a non-inflammatory process. There were few symptoms from the nose and the neighbouring structures as well as insignificant clinical findings by inspection of these structures. The increased opacity of the maxillary sinuses on the roentgenograms and some other changes are considered to be partially due to the insufficient pneumatisation which is related to the retarded development and maturation of juvenile patients with iron deficiency disease. Furthermore, it is caused by the enlargement and thickening of the facial bones resulting from the expansive growth of the hyperplastic and hypertrophic red marrow filling completely the cancelous substance. The space of the maxillary sinuses is narrowed in many cases, the penetration power of the X-ray diminished and the clearing effect of the air containing cavities decreased.


ATP-atp.

ATP-atp. It has been known for some years that intra-arterial application of ATP as well as the only treatment with hyperbaric Oxygen is able to influence favorably a sudden hearing loss. In this study the combined application of both agents was used optimally. Up to now only few cases could be treated. The three above mentioned patients have shown remarkable results. A patient with a long lasting sensorineural hearing loss is especially interesting and this is the reason why we now publish the results gathered up to now.


[Varicositiy formation in the parotid gland (author's transl)]. First known case report of the a single large varicosity formation in the parotid gland. Assuming a benign tumer, a parotidectomy was performed and the diagnosis made histologically.


[Lymphogranulomatosis of the larynx (author's transl)]. It is reported the case of a 50 year old man with Hodgkin's disease. The first symptom was growing dyspnea and histological problems of Hodgkin's disease in the larynx are discussed.


[A "hairy polyp" of the throat causes larynx occlusion in a newborn (author's transl)]. A case of "polyp with hair" in the throat is reported. It's occurence is extremely seldom. It is the simplest form of an epignathus. The birth defect is considered as an uncomplete dual formation, it is more often found in female than in male newborns. The left palate is the preferred place of occurence. Because it is anchored with a pedicle, the tumor may change it's position resulting in an occlusion of the larynx, as it was in this case. Recurrence after surgery is not known.


["Central Recruitment" with unilateral conductive deafness (author's transl)]. Feldmann described a recruitment with conductive deafness using simultaneous tones for loudness-balancing. On 20 patients with unilateral conductive deafness a loudness-balance-test was performed in 4 different ways. The results were strongly method-influenced: 1 There was a substantial hysteresis between ascending and descending loudness-balancing. 2 The choice of the reference ear, i.e. the ear on which the intensity steps are fixed, appeared to be very important. Different results were obtained when the intensity steps were fixed on the good ear (and thus adapting for equal loudness on the bad ear) compared to the results when the intensity steps were fixed on the other ear.- With continuous tones, and when fixing the intensities on the good ear, a recruitment can be measured with conductive deafness, but it is only method-depending. For a reliable recruitment-diagnosis with the Fowler-test strictly defined test-conditions, considering method-depending influences, are necessary.


[The behaviour of the post-stimulatory acoustic response trigger threshold during experiments and with noise workers (author's transl)]. The findings on impedance jump responses after experimental and professional exposure to noise are presented and discussed. It can be shown that the trigger threshold of the impedance jump is raised only slightly by the development of a temporary shift of the threshold of audibility (TTS). By sealing the acoustic duct with ear-plugs (made of cotton and wax) however, the trigger threshold shifts by the same amount in decibel which originated through the sound attenuation itself. Furthermore, the impedance jump can be triggered more and more rarely with increasing exposure to noise during the working years under noise of noise workers. This can be explained by the additional increasing degeneration of the ganglion cells and the auditory nerve.


[The fowler test (author's transl)].

[The fowler test (author's transl)]. On 20 patients with unilateral recruitment-positive deafness (Morbus Meniere) 4 variations of the loudness-balancing test were performed: A. Two methods with alternate tones:1st method (Jerger): alternate tones, affected ear as reference ear. Loudness on the good ear was adapted for loudness balancing(= "affected ear fixed"), 2nd method (Hood): alternate tones, "good ear fixed". B. Two methods with continuous tones: 3rd method: continuous tones on both ears, "affected ear fixed", 4th method: continuous tones on both ears, "good ear fixed". Results were compared with the corresponding data obtained with recruitment-negative patients. Statistical analysis showed that separation between recruitment-positive and negative patients was equally excellent with both methods with alternate tones. With Jerger's method (method 1) the tendency to recruitment is less pronounced. Overrecruitment does practically not exist. Under our testing conditions the standard values for positive, and also for negative recruitment (reference point 110 dB lower with method 1 (Jerger) as compared to method 2 (Hood). The different values with method 1 and method 2 were due to the choice of the affected or good ear as "fixed ear" (reference ear). Method 1 (Jerger) can be recommended for clinical use as there is less overrecruitment (unfavourable testing technique) and as an audiometer with 5 dB intensity-steps can be used.


Lipogenesis by intact hepatocytes from normal and diabetic rats. Intact hepatocytes isolated from livers of diabetic rats demonstrate the characteristic decreased lipogenic capacities as compared to normal. Administration of insulin to diabetic rats restores these capacities to near normal levels. The results emphasize the potential that the hepatocyte system has for the study of hormonal regulation of lipogenesis.


Faucial bonorrhoea.

Faucial bonorrhoea. Nine hundred patients (250 females and 650 males) attending the Clinic for the Treatment of Venereal Diseases had throat swabs taken as a routine; 1-1% (1-6% of females and 0-92% of males) were found to have faucial gonorrhoea. This figure appears to be similar to that found by Odegaard and Gunderson (1973) in Norway. The treatment regime used in the clinic in Perth appeared to be satisfactory, as there were no failures. It is stressed that all patients suspected of suffering from venereal disease should have their throats swabbed as a routine. Information as to whether or not oral sex is practised should be obtained.


Pyrimidine biosynthesis in Aspergillus nidulans. Isolation and characterisation of mutants resistant to fluoropyrimidines. Mutants resistant to 5-fluorouracil, 5-fluorouridine and 5-fluorodeoxyuridine have been selected in Aspergillus nidulans. Growth tests combined with genetic analysis showed that mutations conferring resistance to fluoropyrimidines could occur in at least seven genes. Three of these fulE, fulF and furA were concerned with either the uptake of pyrimidines or their conversion to uridine monophosphate. The other four genes did not affect these functions. Mutations in fulA probably confer resistance by lowering ornithine transcarbamoylase, thereby making the normally arginine-specific carbamoyl phosphate pool available for increased uracil synthesis. Mutations in fulD may make the arginine-specific carbamoyl phosphate synthetase insensitive to inhibition or repression by arginine, and so lead to increased carbamoyl phosphate pool sizes, and increased uracil synthesis. Both fulA and fulD mutants suppress pyrA mutants which lack the uracil-specific carbamoyl phosphate synthetase. Mutations in fulB and fulC do not suppress pyrA, and so may act more directly to increase uracil synthesis. The synthesis of aspartate carbamoyl transferase in fulB7 strains is not repressed by uracil. fulC mutants are closely linked to the pyrA, B, C, N region which codes for the first two enzymes of pyrimidine biosynthesis, and may result in these enzymes being less sensitive to inhibition by uracil.


Membrane bound and soluble adenosine triphosphatase of Escherichia coli K 12. Kinetic properties of the basal and trypsin-stimulated activities. Basal and trypsin-stimulated adenosine triphosphatase activities of Escherichia coli K 12 have been characterized at pH 7.5 in the membrane-bound state and in a soluble form of the enzyme. The saturation curve for Mg2+/ATP = 1/2 was hyperbolic with the membrane-bound enzyme and sigmoidal with the soluble enzyme. Trypsin did not modify the shape of the curves. The kinetic parameters were for the membrane-bound ATPase: apparent Km = 2.5 mM, Vmax (minus trypsin) = 1.6 mumol-min-1-mg protein-1, Vmax (plus trypsin) = 2.44 mumol-min-1-mg protein-1; for the soluble ATPase: [S0.5] = 1.2 mM, Vmax (-trypsin) = 4 mumol-min-1-mg protein-1; Vmax (+ trypsin) = 6.6 mumol-min-1-mg protein-1. Hill plot analysis showed a single slope for the membrane-bound ATPase (n = 0.92) but two slopes were obtained for the soluble enzyme (n = 0.98 and 1.87). It may suggest the existence of an initial positive cooperativity at low substrate concentrations followed by a lack of cooperativity at high ATP concentrations. Excess of free ATP and Mg2+ inhibited the ATPase but excess of Mg/ATP (1/2) did not. Saturation for ATP at constant Mg2+ concentration (4 mM) showed two sites (groups) with different Kms: at low ATP the values were 0.38 and 1.4 mM for the membrane-bound and soluble enzyme; at high ATP concentrations they were 17 and 20 mM, respectively. Mg2+ saturation at constant ATP (8 mM) revealed michealian kinetics for the membrane-bound ATPase and sigmoid one for the protein in soluble state. When the ATPase was assayed in presence of trypsin we obtained higher Km values for Mg2+. These results might suggest that trypsin stimulates E. coli ATPase by acting on some site(s) involved in Mg2+ binding. Adenosine diphosphate and inorganic phosphate (Pi) act as competitive inhibitors of Escherichia coli ATPase. The Ki values for Pi were 1.6 +/- 0.1 mM for the membrane-bound ATPase and 1.3 +/- 0.1 mM for the enzyme in soluble form, the Ki values for ADP being 1.7 mM and 0.75 mM for the membrane-bound and soluble ATPase, respectively. Hill plots of the activity of the soluble enzyme in presence of ADP showed that ADP decreased the interaction coefficient at ATP concentrations below its Km value. Trypsin did not modify the mechanism of inhibition or the inhibition constants. Dicyclohexylcarbodiimide (0.4 mM) inhibited the membrane-bound enzyme by 60-70% but concentrations 100 times higher did not affect the residual activity nor the soluble ATPase. This inhibition was independent of trypsin. Sodium azide (20 muM) inhibited both states of E. coli ATPase by 50%. Concentrations 25-fold higher were required for complete inhibition. Ouabain, atebrin and oligomycin did not affect the bacterial ATPase.


The cervical locking mechanism. Its contribution to the cervical spine stability and to the vertebral artery and spinal cord safety. An anatomical study. Investigations were conducted with macerated cervical vertebrae and human cadavers. During extension, lateral flexion, and rotation of the neck, the cervical transverse process engages to the top of the upper articular process of the subjacent vertebra, thus embodying the locking mechanism which plays an important role in the stabilization of the cervical spine and the protection of the integrity of vertebral arteries, spinal cord, and nerve roots. A deficiency of this locking mechanism may cause a vertebrobasilar insufficiency or a cervical myelopathy.


Osteomyelosclerosis. A histopathological study of osteomedullary lesions on 32 cases. The pathological features of the osteomyleoproliferative syndrome development were studied by trephine biopsy on 32 cases out of which 28, lesionally characterized by myeloproliferation, reticulin hyperplasia, intravascular hematopoiesis, myelofibrosis, myeloslerosis, and osteosclerosis, were interpreted as primary osteomyelosclerosis. Dynamic relationships between the myelogenous tissue and the osteogenous one are emphasized in the development of disease.


Cardiac tumour in infant.

Cardiac tumour in infant. A case of an eighteen-month-old-infant who died in narcosis following an aortic obstruction by myxomatous tumour of the left ventricle is reported. Since his birth the infant exhibited cyanosis fits and cerebral manifestations due to an intermittent occlusion of the aorta. The result of the post-mortem examination pleads for including the cardiac myxoma amongst the true tumours.


A comparative study of allogenic "first set" and "second set" skin rejection in mice. In our case, where the difference between donor WHT/Ht(H--2d) and recipient C57B1/6 (H--2b) was at the H--2 locus of histocompatibility, the FSg rejection occurred between the 6th and the 10th day, while the SSg rejection was two days earlier. The morphological study emphasized that the cellular infiltrate in the FSg is predominantly lymphocytic, while in the SSg it is predominantly granulocytic. The vascularization settles on the second day postgrafting in the FSg as well as in the SSg, but is scarce and quickly destroyed in the SSg, thus being explained the scanty supply of lymphocytes in the latter graft type. The histochemical reactions demonstrated an increase of the NMPS in skin allograft from the moment of settling till the end of the rejection and a decrease of AMPS, till the complete disappearance, in the rejected graft. Little morphological differences were found between colateral draining nodes and contralateral ones during the reaction to the graft. An important feature described is the presence at the bed graft level of some cells morphologically identical to the IB encountered in great number in the TDA of lymph nodes in the allograft-bearing mice.


Ultrastructural investigations on the lysosomal system of lymph node lymphocytes in transplantation immunity. Activation of the lysosomal system in T lymphocytes is demonstrated in connexion with immune stimulation, by electron microscopic study of the lymph nodes draining skin allografts. The development of primary lysosomes from enlarged Golgi apparatus, their fusion with autophagic and secretory vacuoles forming secondary lysosomes, of the cytolysome and crinophagosome type, were identified by the ultrahistochemical acid phosphatase reaction, suggesting the involvement of these organelles either in blastic transformation or in the effector function of lymphocytes, in connexion with the elaboration of active factors and cytotoxic events.


Morphogenesis and pathogenesis of chronic lung diseases. vii. Kinetics of alkaline phosphatase active cells during the development of experimental lung granulomas. The circulating cells arriving at the formation site of the experimentally induced lung granuloma were quantitatively and qualitatively determined during their development by estimation of alkaline phosphatase active free cells. These represent 32 per cent the 2nd day and 27 per cent the 4th, of all the lung granuloma cells, and rapidly decrease to 8 per cent the 8th day, to 4 per cent the 11th and to only 1.5 per cent the 15th day. The participation of alkaline phosphatase circulating cells appears to be important only the first days, the process becoming by proliferation and differentiation a histiocytic, epithelioidic, and lympho-plasmocytic structure under the influence of antigenic and non-antigenic components of the used immunologic adjuvant.


Microautoradiographic study of cell proliferation in compensatory renal growth. DNA synthesis in the renal parenchyma was studied by electron microscopic autoradiography 48 and 72 hours after unilateral nephrectomy in mice and weanling rats. The proportion of labelled nuclei belonging to the epithelium, endothelium, interstitial areas, or circulating cells was evaluated. Most of cells showing DNA synthesis were epithelial but many belonged to stroma. All the nephron segments were found to participate in compensatory hyperplasia, with a greater contribution, however, of the proximal convoluted tubules. DNA synthesis by the capillary endothelial cells occurred later than the peak epithelial mitotic activity. The site of DNA synthesis in nuclei was the euchromatin, the silver grains being uniformly distributed throughout the nuclear areas with condensed chromatin, and more seldom in the nuclear envelope areas or that of the perinucleolar satellites.


National gonorrhea therapy monitoring study: treatment results. To monitor the efficacy of the 1972 United States Public Health Service recommended treatment regimens for uncomplicated gonorrhea, we studied 9008 patients who were randomly assigned either to aqueous procaine penicillin G, 4.8 million units intramuscularly plus 1 g of oral probenecid, or to one of the three other recommended regimens. Among the 3871 patients re-examined within three to seven days after therapy, the penicillin-probenecid regimen was successful in 96.8 per cent, whereas the cure rates of the ampicillin-probenecid, tetracycline, and spectinomycin regimens were 92.8, 96.2, and 94.8 per cent, respectively. In clinics comparing the regimens, penicillin G-probenecid was as effective as tetracycline, but more effective than ampicillin-probenecid (P less than 0.05) and spectinomycin (P less than 0.01). However, in patients re-examined three to 14 days after treatment, only the ampicillin-probenecid regimen was significantly less effective than penicillin probenecid (P less than 0.01). Despite these differences in results, all four regimens recommended by the Public Health Service provided effective therapy for uncomplicated gonorrhea.


National gonorrhea therapy monitoring study: in vitro antibiotic susceptibility and its correlation with treatment results. To monitor temporal trends and regional differences in antibiotic susceptibility, we measured the minimum inhibitory concentrations for penicillin G, ampicillin, tetracycline, and spectinomycin of 4405 pre-treatment gonococcal isolates from patients with uncomplicated gonorrhea. As compared to isolates studied in 1970-1971, recent United States isolates appeared equally sensitive to penicillin G and more sensitive to tetracycline. Relatively resistant strains were found throughout the country. We also studied 1974 patients, treated for uncomplicated gonorrhea according to the 1972 regimens recommended by the United States Public Health Service, to determine the relation between pretreatment minimum inhibitory concentrations and treatment results. For patients receiving the procaine penicillin-probenecid and ampicillin-probenecid regimens, minimum inhibitory concentrations to the treatment drugs were significantly higher in patients not cured than in those cured (P less than 0.01 fr penicillin and P less than 0.05 for ampicillin). In contrast, spectinomycin-treatment results appeared to be independent of the isolate's susceptibility to spectinomycin and other antibiotics.


Renal gluconate excretion after 6-aminonicotinamide. After application of 6-aminonicotinamide, an increasing amount of gluconate was found in the urine. No correlation with the renal excretion of electrolytes could be established.


Monozygotic twins with Huntington's disease in a family expressing the rigid variant. A set of male monozygotic twins concordant for Huntington's disease is described. The monozygosity of the twins and the diagnosis of Huntington's disease are well established. The twins are now age 30, and although the severity of their chorea differs, they have a similar degree of mental deficit. This family is of additional interest because the daughter of one of the twins has childhood Huntington's disease, and the mother of the twins had the adult-onset rigid variant of the disease. Such unusual families afford some insight into the variability of the clinical manifestations of this hereditary disease.


[Akinetic zones of the left ventricle in aortic insufficiency. Treatment]. 22 cases of aortic valvular insufficiency treated by prosthesis and in which the acinetic areas of the left ventricle were eliminated at the same time are reported. Only one postoperative death (ventricular fibrillation) was encountered; one after 1 year (emboly as a result of endocarditis) and one as a result of an unknown cause. Emphasis is laid upon the frequency of this associated complication, its seriously negative incidence on ventricular haemodynamics, the need for surgical treatment, and its favourable immediate and long-term results.


[Value of the esophageal ECG].

[Value of the esophageal ECG]. The Authors examined 20 patients suffering from anginose symdrome, whose standard ECG did not show remarkable alterations. In the same patients, oesophagus ECG did show clear signs of sub-epicardium lesion as well as necrosis, which interested the upper part of left ventricle's posterior wall; such zone is not explorable by traditional ECG. Hemodynamic poligraphic examinations were made as well, and thus also a reduction of cardiac inotropism was found out.


Sjogren's syndrome and drug reaction to practalol. A case is reported of a patient who developed exfoliative dermatitis while being treated with practalol for angina pectoris. The patient also had trigeminal neuropathy, renal impairment and keratoconjunctivitis sicca. The antinuclear factor was diffusely positive but other antibodies were negative. At post mortem the patient was found to have acute pancreatitis, and peritonitis. It is postulated that the patient has antecedent Sjogren's syndrome and on introduction of practalol therapy developed a drug reaction with a generalised exfoliative dermatitis and exacerbation of keratoconjunctivitis sicca leading to bilateral corneal ulceration. The association of similar conditions in patients receiving practalol therapy is reviewed.


[Analysis of a "movement epilepsy" bearing a rolandic focus in a monkey]. Several observations in Man as well as in animals have stressed the importance of specific afferents in triggering some focal cortical fits. The authors report an analysis of the role of various afferents on the activity of a precentral focus in the monkey. The chronic focus was created on one adult female monkey by subpial injection of alumina cream in the motor area of the left foot. Typical seizures were clonic and local. The most striking feature was that movement or, more generally, proprioceptive afferents from the concerned leg could elicit and maintain these motor fits. This assumption was verified by curaryzing the animal with succinyl-choline. In this condition, the number of attacks was strongly reduced. Since there was no lowering of excitability at the central level, as shown by direct stimulation of the perifocal area, this decrease seems to result from the lack of triggering mechanisms. If this is the case, one should be able to elicit seizures by proprioceptive afferent volleys coming from the concerned leg. In fact, although passive motion was not very effective (the reason probably being the decrease of the back-ground activity of stretch receptors under curare), direct electrical intramuscular stimulation was always followed by an attack. Similar stimulation of the opposite leg was ineffective. These results are discussed. The role of the "motor cortex proprioceptive feedback" in jacksonian progression of motor seizures is debated. The same concept is applied to "startle epilepsy", for which a physiological hypothesis is purposed.


Peripheral steroid levels in a patient with virilizing adrenal adenoma. The peripheral levels of pregnenolone (delta5-P), 17-hydroxypregnenolone (17-delta5-P), progesterone (P), 17-hydroxyprogesterone (17-P), testosterone (T), 5alpha-dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone (DHEA), its sulfate (DHEA-S), estrone (E1), estradiol-17beta (E2), and cortisol (F) were measured prior to and 1 1/2 and 9 months after removal of a right adrenal "compact cell" adenoma in an amenorrheic patient with a virilizing adrenal adenoma, under the following conditions: 1) control for 2 days, 2) dexamethasone, 0.5 mg, every 6 hours for 2 days, and 3) dexamethasone, 2 mg, every 6 hours for 2 days. Except for E1, E2, and F, the control levels of all steroids measured were elevated, markedly so for delta5-P, 17-delta5-P, DHEA, A, and DHEA-S. Dexamethasone treatment had no detectable effect on the steroid levels. Following removal of the adrenal adenoma, the levels of all steroids returned to normal. The patient became eumenorrheic, with marked improvement of her hirsutism and virilization.


Peripheral arterial and venous concentrations of various androgens in patients with and without hirsutism. The mean peripheral arteriovenous difference for dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), testosterone (T), 5ALPHA-dihydrotestosterone (DHT), and 17-hydroxyprogesterone (17-P) has been calculated in 7 nonhirsute and 9 hirsute women. No significant difference was found between peripheral artery and vein concentrations for all steroids measured in both groups of women studied. Since steroid concentrations in peripheral arterial samples are not expected to differ from those from ovarian and adrenal arteries, it is concluded that peripheral venous steroid levels adequately represent the steroid concentrations of arterial blood delivered to steroid-producing tissue.


Hysteroscopic removal of occult intrauterine contraceptive device. Dilatation and curettage or hooking an occult intrauterine contraceptive device (IUD) may fail to recover the device on occasion. Theoretically, endoscopic observation should enable the controlled removal of this type of device. Of 200 patients who underwent hysteroscopic examination, 10 had an occult IUD. In 8 cases, the device was visible through the hysteroscope, and in 6 patients a successful removal was accomplished with this endoscopic technic. Failures and problems are discussed, and the importance of adequate preoperative study is stressed. Hysteroscopy is an effective procedure in the recovery of the occult intrauterine contraceptive device in selected nonpregnant patients.


Comparison of lymphocyte reactivity in patients with cancer, systemic lupus erythematosus and renal allografts. The PHA and MLC reactivity of lymphocytes from patients with cancer, SLE or renal allografts was comparatively tested in the presence of autologous and of normal homologous serum. Sera from patients with advanced cancer, active SLE or chronic allograft rejection strongly inhibited the MLC reactivity of autologous lymphocytes. It is suggested that serum inhibitory factors might be antibodies which are directed against modified antigenic determinants of the major histocompatibility complex, and are capable of blocking T lymphocyte receptors.


Effect of 2-methylcitrate on citrate metabolism: implications for the management of patients with propionic acidemia and methylmalonic aciduria. 2-Methylcitrate was tested in vitro on enzymes which interact with citrate and isocitrate. It was found to inhibit citrate synthase, aconitase, the NAD+- and NADP+-linked isocitrate dehydrogenase. This inhibition was competitive in nature except in the case of aconitase, and the Ki for all the enzymes was in the range of 1.5-7.6 mM. Phosphofructokinase was also inhibited by 2-methylcitrate with 50% inhibition achieved at 1 mM. ATP-citrate lyase and acetyl-CoA carboxylase were not inhibited by this compound. 2-Methylcitrate was not a substrate for ATP-citrate lyase. Acetyl-CoA carboxylase was activated by 2-methylcitrate with a Ka of 2.8 mM. The apparent Km (3.3 mM) for 2-methylcitrate for the mitochondrial citrate transporter was about 10-fold higher than the apparent Km (0.26 mM) for citrate. The tricarboxylase carrier can also be inhibited by low concentrations (0.2 mM) of 2-methylcitrate when the concentration of citrate is close to the apparent Km. Accumulation of 2-methylcitrate inside the mitochondrion, therefore, might lead to inhibition of enzymes in the citric acid cycle and thereby contribute to the ketogenesis and hypoglycemia seen under these conditions.


[Monogenea and fishes of some fresh water reservoirs of the Kol'sk peninsula]. 25 species of Monogenea were found in the basins of the Ponoi, Pjalitsa and Varzuga rivers. The belonging to faunistic complexes is indicated for 29 species of monogeneans known at present for water bodies of the Kola peninsula. On the basis of the distribution of Monogenea in the Ponoi and due to its hydrological regime and geological past the introduction of freshwater fauna into this water body via the Varzuga river is suggeste.


Increased erythrocyte Ca2+ content in hereditary spherocytosis. The Ca2+ content of red blood cells (RBC) appears to correlate inversely with the Ca2+-ATPase activity of the red cell membrane (Fig. 1). When hereditary spherocytosis (HS) cells and normal control erythrocytes are compared, the dependence of Ca2+ content upon ATPase activity is similar. The Ca2+ content of HS red cells is increased compared with appropriate control erythrocytes matched for cell age (Fig. 2). Splenectomy has a different effect upon HS cells than upon normal cells (Fig. 2). Erythrocytes of splenectomized patients with HS seem to contain less Ca2+ than do those of presplenectomy patients with HS, whereas the reverse appears to pertain in normal subjects.


Complex saccharide metabolism in cystic fibrosis fibroblasts. There are several reports of secretory and other abnormalities present in cultured fibroblasts from patients with cystic fibrosis (CF). We have, therefore, investigated aspects of complex saccharide synthesis and secretion by such cells compared with fibroblasts derived from heterozygous (HZ) parents and from normal (N) children. The main glycosaminoglycans produced by skin fibroblasts  during in vitro culture were hyaluronic acid, heparan sulfates, and dermatan sulfate-like materials. Using double-label experiments with D-[3H]- or [14c]glucosamine and analyzing the products by ion exchange chromatography, it was shown for five CF, two HZ, and four N lines that these polysaccharides were secreted into the medium in approximately similar proportions to each other. Moreover, experiments in which three CF, nine HZ, and three N lines were grown in log phase for up to 5 days in the presence of [35S]sulfate and [3H]glucosamine indicate that, during such a period, CF fibroblasts do not secrete complex carbohydrates at rates significantly different from N or HZ cells. Neither do such cells shown an abnormal intracellular accumulation of complex carbohydrates. The latter observation was further confirmed by preparing whole cell autoradiographs during growth of six CF, two HZ, and three N lines in the presence of D-[3H]glucosamine and, subsequently, after addition of unlabeled medium.


Renal proximal tubular buffer-(glycodiazine) transport. Inhomogeneity of local transport rate, dependence on sodium, effect of inhibitors and chronic adaptation. Using the stop flow microperfusion technique with simultaneous capillary perfusion the secretory rate of H+ ions in the proximal tubule was evaluated by measuring the level flow reabsorption as well as the static head concentration difference of 3H labeled glycodiazine. At ambient glycodiazine concentration of 21 mmol/l the level flow reabsorption is in the same range as that of bicarbonate. In the early proximal loops the reabsorption is 20% greater than in the late proximal loops. The carbonic anhydrase inhibitors acetazolamide and 3,4-methylene-dioxyphenyl-sulfonamide (both 10(-4) M) as well as furosemide (10 (-3) M) inhibit the glycodiazine reabsorption 43%, 27% and 22% respectively. Thiocyanate (2-10(-2) M), however, exerted only an insignificant inhibition (12%). When Na+ in the ambient perfusion solutions was replaced by Li+ or choline+ the glycodiazine transport was strongly reduced. Ouabain (5-10(-2) M) inhibited too, but amiloride (10(-3) M) had no effect on glycodiazine transport. The glycodiazine transport was 28% reduced in metabolic alkalosis and to a smaller although significant extent (17%) in metabolic acidosis; it was unchanged in chronic hypercapnia. In chronic K+ depletion the glycodiazine reabsorption was accelerated by 12% only in the early proximal loops. Chronic parathyroidectomy as well as acute substitution with parathyroid hormone had no effect on the glycodiazine absorption. The main conclusions are: Proximal H+ transport proceeds with suitable buffers. Although independent of HCO3- and carbonic anhydrase, it could be partially inhibited by CA inhibitors. H+ transport is supposed to proceed as countertransport with Na+ ions. In chronic alkalosis the H+ transport is reduced.


[Round-table discussion on the weak back problem. Misunderstood backache patients, a challenge to medical care]. "Pain in the back" is one of the most common reasons for consultations, sick-leaves, and invalid pensions. In the Nordic countries, back trouble costs thousands of millions of kronor each year in terms of lost working days alone. Yet, the information to the doctors on problems connected with this disorder is generally sparse, and the primary doctors give too little time to the backache patients. The latter are often misunderstood - but most of those who seek medical advice for "pain in the back" really suffer pain. The failing care of backache patients was discussed at a round-table conference held by Nordisk Medicin in Oslo in October, 1975. A programme of action was outlined.


Counseling parents of infants with Down's syndrome. The primary objective in counseling parents of a child with Down's syndrome is to secure realistic goals and an accepted place in the family for the child. A nurturing environment gives the child the best chance to reach full potential.


Changes of renal ATPase enzymes in different types of kidney preservation. After 24-hr storage of canine kidneys with extracellular or intracellular (Ursol) solutions, the cortical and medullary renal ATPase enzymes (total Na+ + K+ and Mg-ATPase, Na+ + K+ -ATPase, and Mg-ATPase) were examined. It was found that storage with extracellular solution decreased all cortical enzymes. This was not the case with intracellular solution or in kidneys cooled and stored without any solution. A decrease in the potassium concentration of the Ursol solution decreased cortical (Na+ + K+)-ATPase enzymatic activity. The medullary enzymatic changes were similar in the different groups, and lower than in unstored controls. It appears that the changes on the level of the ATPase enzyme system which is related to the cation transport system might play a significant role in explaining the different results seen in clinical or experimental renal preservation systems. These changes can be related to the injury of preservation due to environmental effects of the cation concentrations and to a lesser degree to the damage of the enzyme system which provides the energy for cation transport.


Influence of an aggregated multienzyme system on transient time: kinetic evidence for compartmentation by an aromatic-amino-acid synthesizing complex of Neurospora crassa. The aromatic complex of Neurospora crassa is an aggregated multienzyme system which catalyzes five consecutive reactions in the central pathway leading to the biosynthesis of the aromatic amino acids. In an attempt to understand the physiological importance of this complex in particular, as well as the importance of cellular organization of enzyme systems in general, we have isolated the complex and have begun to characterize its catalytic properties. Optimum conditions for the assay of the overall 5-step reaction catalyzed by the partially purified complex have been determined. An analog computer was programmed to represent an unaggregated system of five enzymes with rate constants identical to those found for the constituent enzymes of the complex. By direct comparison, it was shown that the lags (transient times) obtained for the overall reaction were 10-15 times longer for the hypothetical unaggregated system than for the complex. We conclude from these data that the aggregated multienzyme system compartmentalizes intermediate substrates during the course of the overall reaction. We suggest that, in addition to "channeling" intermediates of competing pathways, reduction of the transient time may be an important consequence of the containment of intermediates within a physically associated enzyme sequence. The fact that the aromatic complex exhibits a second catalytic property unique to aggregated enzyme systems, "coordinate activation" [Welch, G.R. & Gaertner, F.H. (1975) Arch. Biochem. Biophys., in press] indicates that the physical association of these enzymes may have more than one physiological function.


Viability of Escherichia coli treated with colicin K. Conditions permitting survival (colony formation) of E. coli after treatment with colicin K have been found. Survival required K+ and Mg2+ at concentrations high enough to replace the intracellular ions lost from colicintreated cells. Either glucose minimal medium or broth could support survival. Survival was still observed after colicin-promoted efflux of Rb+ and decline in ATP levels had occurred, and after the period during which treatment with trypsin could rescue the cells on media containing low concentrations of K+. In an adenosinetriphosphate (ATP phohsphohydrolase, EC 3.6.1.3) deficient (uncA) mutant, survival after colicin treatment was observed at lower Mg2+ concentrations than those required by the wild type, and Rb+ could replace K+. Cells treated with colicin E1 (but not with colicin I2, E3, or Ib) also survived under conditions permitting survival of colicin K.


Effect of trinitrophenylation on the correlation between ATPase activity and superprecipitation of skeletal actomyosins. The results of this work have shown that the actin-induced increase of the presteadystate extraphosphate production is depressed in the case of the trinitrophenylated myosin A. At the same time the onset of superprecipitation is delayed and the rate of turbidity change of the trinitrophenylated synthetic actomyosins is depressed significanylt. The results of these experiments failed to demonstrate any correlation between the steadystate ATPase activity of myosin A or actomyosin enzyme and the onset and rate of the superpricipitation reactions. The results of this study seem to indicate that the time resolution of the instruments used to monitor the turbidity changes during the superprecipitation reaction may be an important factor in the proper evaluation of the experimental results.


Vectorcardiographic analysis of the QRS loop in hypertensive heart disease. The authors made a quantitative and qualitative vectorcardiographic analysis (Frank lead system) in 47 patients with hypertensive heart disease compared with a control group of 16 normal subjects. The magnitude and the angle of the maximum QRS vector, the sense of rotation of the QRS loop, the magnitude of the maximum posterior deflection (Sz), of the anterior maximum one (Rz), of the maximum leftward one (Rx), and of the maximum rightward one (Qx), the length (L) and the width W) of the QRS loop, as well as the angle of the maximum T vector were measured. A significant difference, in all planes of the maximum QRS magnitude between the normals and the AHT was found, while the maximum QRS angle was not significantly different. The quantitative analysis of the veg made in the horizontal plane revealed significant differences for the Sz, Rx, L, and the relation Rz/Sz. The quantitative analysis made according to Varriale et al. (1966) revealed a prevalence of the cases of type I A (72.3%) and I B (21.3%).


Monoaminergic mechanisms in aversive brain stimulation. In these experiments we have examined the role of brain monoamines in the fearlike aversive responses produced by the electrical stimulation of the dorsal midbrain tegmentum (DMT). Chronic bipolar stimulating  electrodes were bilaterally implanted into the DMT of 77 rats. Electrical stimulation via 34 of these electrodes produced fearlike, escape seeking responses. These animals were then trained for stable stimulus escape using a decremental bar pressing paradigm. In this paradigm, each bar press reduced the stimulation current by a predetermined fraction (5 percent) of the initial current level. Perceived aversive strength of the initial stimulus current was thereby represented by an increasing function of the number of bar presses to escape. Administration  of the catecholamine depleting drug alpha-methyl-para-tyrosine yielded no change in bar pressing relative to saline-injected controls. However, the serotonin depleting drub para-chlorophenylalanine produced a marked increase in decremental bar pressing compared to saline-injected controls. These results suggest that fearlike responses to DMT stimulation may be dependent upon brain serotonin levels and relatively insensitive to levels of brain catecholamines.


Influence of age on orthostatic changes in plasma renin activity and urinary catecholamines in man. The authors studied plasma renin activity (PRA), urinary epinephrine, norepinephrine and dopamine excretion and their mutual relationships in 54 healthy subjects under basal (recumbent) conditions and age-related orthostatic changes in these parameters. The test subjects were divided into six 10-years groups, according to their year of birth (1901-1910 to 1951-1960). In the oldest groups (1901-1910 and 1911-1920), both basal PRA values and norephrine and epinephrine excretion and their postural increase were smaller than in younger subjects. Conversely, urinary dopamine excretion and the dopamine/norepinephrine and epinephrine ratio rose with advancing age. There were no significant differences between the plasma sodium and potassium concentrations in the various groups. Urinary aldosterone excretion was slightly higher in the oldest group than in the others, but was still within the control value limits. The intravenous administration of  Inderal reduced both resting PRA values and the orthostatic increase in the youngest age groups, so that their PRA approached the values in older subjects. Higher norepinephrine and epinephrine excretion and the lower dopamine/norepinephrine and epinephrine in young subjects may play a role in their higher PRA, especially in the orthostatic reaction. Diminution of sympathetic activity, with lower norepinephrine and epinephrine excretion and relatively high dopamine excretion, may have a direct bearing on the lower PRA values in older subjects. The diminished capacity of older subjects for catecholamine mobilization and raised renin secretion during an orthostatis stress may be related to the higher incidence of orthostatic forms of hypotension in old age.


Effect of thyroxine administration to the mother on postnatal radioiodine uptake by the thyroid of partially thyroidectomized rats. The experiment was carried out on 35 litters of infant rats aged 4-17 days. The animals in each litter were always divided into two groups: control (sham operation) and experimental (hemithyroidectomy). Starting with the day on which the young were operated on, the mothers received daily subcutaneous injections of either saline or of thyroxine in doses of 50, 100 or 200 mug. At the end of the experiment, the young were injected intraperitoneally with 1 muCi 131I. One hour later they were decapitated and the radioactivity in their thyroid was expressed as the percentage of the administered dose per mg thyroid. The following age groups were used, according to the interval between thyroidectomy and decapitation: 4 to 8, 9 to 13, 13 to 15 and 15 to 17 days. 131I uptake by the residue of the thyroid in partially thyroidectomized animals was always compared with the values in the animals from the same litter subjected to sham operation. The results showed that partial thyroidectomy significantly stimulated 131I uptake in all age groups in which the mother was only given saline. In the 4- to 8-day-old group, the administration of 50 or 100 mug thyroxine to the mother inhibited this compensatory increase. In the 9- to 13-day-old group, inhibition occurred only after a dose of 100 mug thyroxine. In animals with an interval from the 13th to the 15th days old the dose of thyroxine administered to the mother had to be raised to 200 mug/day to achieve an inhibitory effect. In the last group (interval 15th to 17th day), not even administration of the maximum thyroxine dose to the mother from the 13th postnatal day succeeded in inhibiting the significant increase in 131I uptake. These results show that thyroxine administered to lactating female rats can be transmitted via the milk to the organism of the young in amounts which can be demonstrated in a physiological tests.


The effect of constant light and chemical sympathectomy on the development of serotonin, n-acetyltransferase and monoamine oxidase activities in the rat epiphyses. The daytime activity of N-acetyltransferase per mg epiphysis decreased to 1/10 the newborn level by the age of 13 days, and subsequently remained unchanged. The night activity was equal to the day activity at the age of 3 days, was higher at the age of 6 days and was 20 X that of the day level at the age of 40 days. Keeping animals in constant light after birth depressed the development of these diurnal differences in N-acetyltransferase activity and slowed down the decrease in enzyme activity after birth. Sympathectomy with 6-hydroxydopamine after birth abolished the development of the diurnal rhythm in N-acetyltransferase in 12-day-old rats in two experiments out of five and only decreased the night activity without abolishing the rhythm in three experiments. Monoamine oxidase activity (MAO) per mg epiphysis, which is the same in newly born and in adult animals, decreased to half the original value for 6 days after birth and then increased again. Constant light after birth did not influence MAO activity, but sympathectomy with 6-hydroxydopamine decreased activity in the epiphysis in 12-day-old animals.


Glycogen metabolism in white and red muscle or normal and diabetic rats. The glycogen concentration and glycogen synthesis from glucose. The amount of glycogen and its synthesis from glucose was studied in white muscle (extensor digitorum longus -- EDL) and red muscle (soleus -- SOL) of normal rats and rats with alloxan diabetes by the anthrone method. The amount of glycogen was higher in the white muscle of normal rats, both after a 24 hours' fast (0.37+/-0.02 mg/g as against 0.29+/-0.01 mg/g in the SOL) and with feeding ad libitium (0.72+/-0.05 mg/g as against 0.58+/-0.03 mg/g in the SOL). After a 24 hours' fast, the glycogen content of both muscles was non-significantly higher in alloxan-diabetic rats than in normal animals, whereas in diabetic animals fed ad libitum it was significantly lower than in normal rats fed in the same manner (0.54+/-0.07 mg/g in the EDL and 0.33+/-0.03 mg/g in the SOL). The difference between the glycogen content of the white and red muscle of diabetic rats was also in favour of the white muscle. Muscle glycogenesis from intragastrically administered glucose was higher in the red muscle in all the experimental groups. In normal fed ad libitum the glycogen content of the EDL did not change after glucose administration, but in the SOL it rose from 0.58+/-0.03 to 0.83+/-0.05 mg/g. In fasting (24 hours) normal rats it rose sharply in both muscles, from 0.037+/-0.02 to 0.57+/-0.03 mg/g in the EDL and from 0.29+/-0.01 to 0.87+/-0.06 mg/g in the SOL. In fasting (24 hours) diabetic animals, the glycogen content rose after glucose in the SOL only, from 0.36+/-0.01 to 0.66+/-0.06 mg/g. The differences found in glycogen synthesis in the white and red muscle of normal and diabetic rats are discussed mainly from the aspect of the existence of a relationship between the glycogen concentration and glycogen synthetase activity.


Glycogen metabolism in white and red muscle or normal and diabetic rats. Degradation of glycogen by adrenaline. The author studied the effect of adrenaline (500 mug/kg s.c.) on the glycogen content of white (extensor digitorum longus -- EDL) and red (soleus -- SOL) muscle of normal and alloxan-diabetic rats. In normal rats, whose nutritional state varied at the time of adrenaline administration (after a 24 hours' fast, fed ad libitum or given 5 g glucose/kg as a 20% solution intragastrically 2 hours before injecting adrenaline), no marked post-adrenaline differences were found between the size of the decrease in the amount of glycogen in white and red muscle. In addition, no significant differences were found between the three groups of animals in glycogen concentration in the EDL (0.3+/-0.05, 0.35+/-0.03 and 0.26+/-0.02 mg/g) or in the SOL, apart from one exception (0.23+/-0.02, 0.2+/-0.01, and 0.51+/-0.03 mg/g), after adrenaline. The glycogen concentration in the white and red muscle of diabetic rats fed ad libitum fell to values similar to those in normal rats after adrenaline (0.32+/-0.05 mg/g in the EDL and 0.18+/-0.02 mg/g in the SOL). These results supoort the view of authors who hold that glycogenolysis is possible without pre-activation of phosphorylase; they also support the idea, expressed by Krebs, of the existence of a reciprocal relationship between phosphorylase activity and the glycogen concentration, according to which glycogen itself may influence its own degradation.


Effect of pyruvate and oleate on respiration of frog skeletal and heart muscle. The authors studied the effect of pyruvate and oleate on O2 consumption of the frog sartorius and heart ventricle. 10 mM pyruvate raised O2 consumption of both tissues by over 100%, but only in the winter. Raised O2 consumption was only partly associated with glycogen synthesis from pyruvate. 0.1 mM oleate reduced O2 consumption in both tissues. A marked drop in O2 consumption was observed in the ventricle (up to 50%). Lecithin had a similar effect on O2 consumption. The addition of pyruvate plus oleate led to an 8-fold increase in O2 consumption of the ventricle, i.e. to maximum oxidation capacity of the tissue, but the addition of lecithin inhibited the pyruvate-induced increase in O2 consumption. It is assumed that both pyruvate and oleate influence resting metabolism in a specific manner which cannot be attributed solely to raised availability of substrate for resting energy metabolism requirements.


Effect of glucagon on glucose and fatty acid metabolism in goats. Adult goats of a white breed were injected i.v. with glucagon in doses of 6.25--25 mug/kg. The blood sugar curve rose relatively slowly after the injection after the injection and the maximum increase, which attained 360--400% of the resting value was usually recorded 20-30 min after glucagon administration. The non-esterified fatty acid (NEFA) level rose immediately after injecting glucose. Within 10 min it returned to the initial value and then fell abruptly. No concentration correlation was found between the glucagon dose and the size of the metabolic response.


Ontogenetic patterns of frequency-power spectra elicited by flickering light in children: a comparative study of evoked and background EEGs. Frequency-power spectra of the EEG evoked by repeptitive photic stimulation and of the background EEG were studied during childhood in 43 awake subjects aged between 2 months and 14 years. EEG activity was recorded from the middle parieto-occipital region with the aid of a 1-channel analyzer Lysograf-Alvar, analysing 16 frequencies in the range from 2 to 28 c/sec. The responsiveness of the central nervous system to flickering light improved in the course of childhood in parallel with the significant decline of delta activity and with the prominent increase of alpha intensity in the resting EEG. The 4th month of life appeared to be a marked turning point in the development of evoked and background EEGs. From that age, the bioelectric power at the flash rate corresponding to photic "driving" began to increase together with the highest and optimal driving frequencies. The flash rate, at which evoked potentials changed into the "driven" rhythm, also shifted towards higher frequencies. Subsequently, the amount of energy in the resting EEG increased significantly within the theta, alpha and beta bands and, on the contrary, a prominent decline was observed in the delta range. Marked ontogenetic changes at this age closely coincided with the rapid development of exogenous fibres in the occipital cortex, including the thalamo-cortical conncetions, and fibres of the neuropil in cortical layer I, which might play an important role in the genesis of background and "driven" in the occipital region.


A quantitative model of venous stasis thrombosis in rats. A quantitative model of stasis-type of venous thrombosis in rats is described. The ligated bowel loop was used after provocation by an injection of kaolin. The mesenteric vessels of the loop were cut in a dish filled with distilled water and the extinction of escaped haemoglobin was measured photometrically. Heparin was highly effective in this model. Vessel wall lesion may be used or inducing thrombosis instead of kaolin.


Adjuvant arthritis in Lewis and AVN inbred strain of rats. The authors analysed the manifestations of adjuvant arthritis in inbred Lewis and AVN rats and in subsequent generations (F1, F2, B1, B2), using a subjective (scoring system) and an objective criterion (paw volume). The results obtained were in good correlation. Marked variability of the systemic symptoms of the disease was found not only in the parent generation but also in the subsequent generations.


Lung function in acute paraquat intoxication. Functional and morphological examination of the lungs was performed in rats 48 hours after intratracheal injection of 0.5 mg/kg of the herbicide paraquat. Pronounced tachypnoea was observed (235+/-20 c/min), which also persisted under urethane anaesthesia (210+/-18 c/min). In control rats the mean breathing rate was 115+/-11 and 90+/-9 c/min in wake and anaesthetized rats respectively. The rate of breathing decreased to comparable values in experimental and control rats after bilateral cervical vagotomy. The functional residual lung capacity was significantly increased in experimental rats. After vagotomy also this increase of functional residual capacity became normalized. Histologically the disease was characterized by focal formation of hyaline membranes and oedema with occasional haemorrhages and signs of inflammation. The significant role fo vagal function in lung pathology is demonstrated.


Dynamic characteristics of a metabolic reaction of mice with different responses to irradiation. The course of the reaction of mice placed in a metabolic chamber and afterwards irradiated with an exposure dose of 610 R was studied by assessing total oxygen consumption and the size of its fluctuation. Fluctuation was greater in non-survivors than in survivors in the initial phase of the metabolic reaction only (P is less than 0.05), while the mean oxygen consumption values for the two groups were the same, In the distribution of the individual values there were more non-survivors in the frequency class with a high fluctuation level and, conversely, more survivors in the low level class (P is less than 0.01). Fluctuation during the studied reaction was more variable in survivors, despite its lower level, than in non-survivors. The reciprocal relationship between the size and fluctuation of oxygen consumption, determined for the whole series of experimental mice at given stages of the metabolic reaction, is linear. Attention is drawn to the association between changes measured in the metabolic rate and motor activity and to the possibility that it is determined by the individual's type of nervous activity.


[Parameters of digitally averaged potentials of individual motor units]. Of sixty normal subjects of different age six different muscles each were examined electromyographically. The activity pattern was recorded for moderate voluntary innervation and superposed digitally. The parameters of digitally averaged summation action potentials were compared with those of manually assessed potentials. The two methods gave identical results: The duration of potentials was between 5 and 10 ms. It increased in the younger and older age groups and showed only slight changes in middle-aged persons. Only minor differences were found between the muscles of one age group, an exception being the orbicularis oris muscle. The results obtained are compared with values reported in the literature.


Involvement of brain monoamines in the stimulant and paradoxical inhibitory effects of methylphenidate. The significance of central noradrenergic, dopaminergic and serotonergic neural systems for the locomotor stimulant effects of methylphenidate was investigated in the rat. In order to study the role of brain catecholamines, rats were pretreated with reserpine (2.5 mg/kg) followed 24 hrs later by treatment with alpha-methyltyrosine (25 mg/kg) or U-14,624 (75 mg/kg), a dopamine-beta-hydroxylase inhibitor. In these experiments, methylphenidate stimulated motor activity was antagonized by alpha-methyltyrosine and enhanced after treatment with U-14,624, suggesting that release of newly synthesized dopamine is important to a locomotor stimulant action of methylphenidate. Evidence implicating brain serotonin in the actions of methylphenidate was obtained in rats pretreated with pargyline or p-chlorophenylalanine (PCPA). Administration of pargyline 1 hr prior to methylphenidate was found to reduce the locomotor activity induced by methylphenidate and this was antagonized by pretreatment with low doses of PCPA. Higher doses of PCPA caused a significant elevation of methylphenidate induced activity which could be reduced by 5-hydroxytryptophan. Destruction of serotonergic neurons with 5,7-dihydroxytryptamine also potentiated methylphenidate induced locomotion. These latter findings suggest that serotonergic fibers have an inhibitory function in brain. These results are discussed in relation to the possible mechanism by which methylphenidate may act in hyperkinesis.


Afterload mismatch and preload reserve: a conceptual framework for the analysis of ventricular function. A two-dimensional framework can be used for considering the characteristics of left ventricular ejection in terms of the appropriateness of the matching between afterload and the level of inotropic state, as modulated by the preload reserve. An afterload mismatch (reduced velocity and extent of shortening) can be induced acutely in the normal heart under controlled conditions if the preload is not allowed to compensate for an increased afterload, or if the limit of preload (Frank-Starling) reserve has been reached. In the intact circulation the normal heart is sensitive to some degree to acute changes in afterload, perhaps due to impaired venous return; but under basal resting conditions the ejection phase measures (such as the ejection fraction and the mean velocity of circumferential fiber shortening or VCF, corrected for heart size) encompass a relatively narrow range. This finding, and the lack of change in ejection phase measures after the normal heart has adapted to a chronic pressure or volume overload, provides justification for the use of ejection phase indices for detecting depressed inotropic state under basal conditions. When there is mild depression of myocardial inotropic state, with or without accompanying mechanical overload, enhanced preload may allow full compensation, but acute pressure loading may allow early detection of a less than normal preload reserve. When the inotropic state is substantially reduced, however, a mismatch between afterload and contractility (a reduction in mean VCF) will become evident even in the basal state (venous return being presumed to be adequate under these conditions). The concept of afterload mismatch with limited preload reserve provides an explanation for the value of ejection phase indices compared to isovolunic phase measures in assessing the basal level of inotropic state: the former may be more reliable because they are sensitive to afterload. The effects and implications of therapeutic afterload reduction as modulated by the preload also are understood within this framework.