Myoglobin of the shark Heterodontus portusjacksoni: isolation and amino acid sequence.

Myoglobin isolated from red muscle of the shark H. portusjacksoni was purified by ion-exchange chromatography on sulfopropyl-Sephadex and gel-filtration. Amino acid analysis and sequence determination showed 148 amino acid residues. The amino terminal residue is acetylated as shown by mass spectrographic analysis of N-terminal peptides. There is a deletion of four residues at the amino terminal end as well as one residue in the CD interhelical area relative to other myoglobins. The complete amino acid sequence has been determined following digestion with trypsin, chymotrypsin, pepsin and staphylococcal protease. Sequences of the purified peptides were determined by the dansyl-Edman procedure. The amino acid sequence showed approximately 85 differences from mammalian, monotreme and bird myoglobins. The date of divergence of the shark H. portusjacksoni from these other orders was estimated at 450 +/- 16 million years, based on the number of amino acid differences between species and allowing for multiple mutations during the evolutionary period. This estimate agrees well with similar estimates made using alpha- and beta-globin sequences, in contrast to widely differing estimates of dates of divergence for monotremes using the same three globin chains. Compared with myoglobins from species previously studied, there are many more differences in amino acid sequences, and in many positions residues are found that are more characteristic of alpha- and beta-globins, suggesting a conservation of residues over a long period of evolutionary time. There are fewer stabilizing hydrogen bonds and salt-linkages than in other myoglobins.


Relationship between protein synthesis and secretion in liver cells and the state of the adenine nucleotide system.

Adenine nucleotide levels could be precisely and reproducibly adjusted in liver cell suspensions by partially depleting the ATP pool with D-fructose or glycerol. Thus, it was possible to quantitatively correlate rates of protein synthesis and secretion with intracellular levels of ATP and with derived parameters, such as the adenylate energy charge. Half the maximum rate of incorporation of leucine into protein was observed at an energy charge of 0.80, a ratio of ATP to ADP of 2.6, and an ATP level of 1.05 mumol per g of wet cells. Proteins were secreted with half the maximum rate at an energy charge of 0.85, a ratio of ATP to ADP of 3.1 and an ATP concentration of 1.1 mumol per g of wet cells. Protein secretion did not depend on continued synthesis. Inhibitors of oxidative phosphorylation inhibited protein secretion in addition to protein synthesis, in contrast to observations by other authors on liver slices.


Cell proliferation and cortical cell production in relation to wool growth.

The relationship of wool growth to cell proliferation in the follicle bulb and to the subsequent migration and growth of the fibre cortical cells was investigated in 10 Peppin Merino sheep. These sheep had been maintained on a low, medium or high level of nutrient intake to ensure a wide range in wool growth. The number and mitotic activity of the germinal cells in the follicle bulb were determined after administration of colchicine. Cortical cell size was measured following isolation of the fibre cells by acid-treatment of wool. The average fibre production of the follicle varied from 4.1 x 10(4) to 13.2 x 10(4) micron3/day in these sheep. There were also substantial differences between sheep in the mitotic activity of the germinal cells in the bulb, the rate of cell proliferation being highly correlated with the average daily fibre production of the follicle (r = + 0.88, n = 10). However, the size of the germinal cell population differed from sheep to sheep and was not closely related to the level of fibre production (r = + 0.48, n = 10). The average turnover time of these cells was inversely related to fibre production and varied from 41.6 to 19.4 h (r = -0.82, n = 10). Multiple regression analysis of the data showed that the average daily fibre production of the follicle was largely determined by the number of germinal cells present in the bulb and their rate of proliferation (R = +0.95, n = 10). Variations in cell turnover time and in cortical cell size were not significant in influencing the rate of fibre production. In these sheep, the average cortical cell varied in size from 658 to 1279 micron 3 and the positive correlation (r = + 0.83, n = 10) found between cell size and fibre production is considered to merely reflect an allometric relationship. The proportion of germinal cells contributing to the fibre cortex was found to be small and variable, ranging from 9.4 to 17.8%. Furthermore, this proportion was not related to the nutritional level of these sheep, and it is thought that the variability in the distribution of cells to the fibre may be attributed to genetic differences between sheep.


Acute effects of lithium on central dopamine and serotonin activity reflected by inhibition of prolactin and growth hormone secretion in the rat.

The acute administration of lithium chloride significantly inhibits both prolactin and growth hormone secretion in the rat. In terms of known neuroendocrine relationships this finding indicates that lithium administration alters both dopamine (DA) and serotonin (5-HT) activity in the hypothalamus. The data suggest that DA activity is increased (inhibiting prolactin release) and 5-HT activity is decreased (reducing growth hormone stimulation). The data are in agreement with fluorescent histological studies on the effects of chronic lithium administration and suggest that endocrine parameters may be used to provide neuropharmacological information about compounds which alter brain monoamine activity.


A simple procedure for the assay of brain biogenic amines by selected-ion monitoring: its application to the elucidation of the mechanism of prolactin release induced by 3-iodo-L-tyrosine.

A simple method for the assay of brain biogenic amines by selected-ion monitoring was applied to examination of the effects of 3-iodo-L-tyrosine on the hypothalamic-median eminence concentrations of dopamine, noradrenaline and serotonin in the rat. Thirty minutes after its administration iodotyrosine (50 mg/kg) caused a highly significant (P less than 0.0005) rise in serum prolactin and a highly significant (P less than 0.0025) fall in the concentration of dopamine in the hypothalamus and median eminence where the levels reached 50% of control levels. Less marked but significant falls were also observed in the hypothalamic (P less than 0.05) and median eminence (P less than 0.0025) concentrations of noradrenaline after iodotyrosine administration. Serotonin concentration was significantly reduced (P less than 0.025) in the median eminence but not in the hypothalamus after iodotyrosine administration. These findings suggest that iodotyrosine exerts its prolactin stimulating effect by blockage of dopamine synthesis rather than by receptor blockade.


Plasma insulin concentrations during infusions of potassium and sodium chloride solutions into conscious splenectomized sheep.

Haematocrit values, plasma osmolality and the plasma concentrations of sodium, potassium, chloride and insulin were measured in carotid arterial blood before, during and after intravenous infusion of NaCl (0.5 mol 1-1) and KCl (0.5 mol 1-1) at 2 ml min-1 for 105 min into six conscious splenectomized sheep. Hypertonic NaCl infusion was associated with a fall in haematocrit of 1.30 +/- 0.10% (P less than 0.001) and no consistent change in plasma insulin concentration occurred during this infusion. Hypertonic KCl infusion caused the haematocrit to increase by 1.70 +/- 0.39% (P less than 0.001) and the plasma insulin concentration to increase by 60.0 +/- 16.3 mu U ml-1 (P less than 0.01). It was concluded that this increase in insulin concentration was caused by elevation of the plasma potassium concentration and was not due to coincident increases in plasma chloride concentration or osmolality. Shrinkage of the extracellular fluid volume during KCl infusion made no major contribution to the increase in insulin concentration which was probably the result of increased release from the pancreas.


Foetal and placental growth in the mouse after pre-implantation development in vitro under oxygen concentrations of 5 and 20%.

Blastocysts which developed from two-cell mouse embryos in culture tubes containing an atmosphere with 20% oxygen had approximately 20% fewer blastomeres than blastocysts which developed under an oxygen concentration of 5%. When these smaller blastocysts were transferred to the uteri of pseudopregnant foster mothers, the foetuses developing were as viable as those developing from blastocysts cultured under 5% oxygen, indicating their ability to regulate for a lower blastomere number by at least day 17 of development. The transfer operation itself had no adverse effect on foetal or placental growth. However, culture of blastocysts in vitro did depress foetal though not placental growth, suggesting that the inner cell mass is more susceptible than the trophectoderm to culture in vitro. Foetal but not placental growth was lower following the transfer of blastocysts to a day-3 rather than a day-4 uterus. Four cases of placental fusion were found. In one case, the foetuses were contained within the same embryonic sac and may have been twins.


Variations in plasma thyroxine concentrations throughout one year in penned sheep on a uniform feed intake.

Plasma total thyroxine (T4) concentrations were measured by radioimmunoassay throughout one year in 10 sheep maintained indoors under natural light and consuming a constant amount of feed. Plasma T4 concentrations varied throughout the year, the highest and lowest values occurring in the spring and autumn months respectively. The mean of all observations was 5.4 +/- 0.1 microgram/dl. The changes observed did not appear to correlate with changes in ambient temperature, day length or with reported changes in wool growth.


Studies on metatherian sex chromosomes. IX. Sex chromosomes of the greater glider (Marsupialia: Petauridae).

The greater glider, currently but incorrectly known as Schoinobates volans, is widely distributed in forested regions in eastern Australia. All animals studied from six different localities had 20 autosomes but there were four chromosomally distinct populations. At Royal National Park, N.S.W., all female greater gliders studied had 22 chromosomes including two large submetacentric X chromosomes with subterminal secondary constrictions in their longer arms. This form of X chromosome occurred also at Bondo State Forest, Myall Lakes and Coff's Harbour, N.S.W., and at Eidsvold, Qld. At Coomooboolaroo, Qld, the X chromosome was also a large submetacentric but a secondary constriction occurred in the shorter arm. Two chromosomally distinct types apparently occur in Royal National Park, one with XY males as in all other populations, and one with XY1Y2 males. Y or Y1, but not Y2, chromosomes were eliminated from the bone marrow in all populations but were present in spermatogonia, primary spermatocytes and cultured fibroblasts. Animals from Bondo State Forest had three or more acrocentric or metacentric supernumerary chromosomes.


Conceptual frameworks and the philosophical foundations of general living systems theory.

The continued expansion and fragmentation of biological disciplines impede education, communication, and efficient advance of biological research. Reversing these trends may require a unification of theories and concepts from all levels of biological organization. One form of this unification is the statement of generalizations that apply to all living systems. We explore the philosophical foundations of general theories of living systems by analyzing conceptual frameworks as they apply to biology. This analysis examines the relation of empirical observation, theories, and conceptual frameworks within the context of an individual scientist's conceptual continuum. Also presented are a small set of translevel generalizations that articulate our conceptual framework of living systems in terms of organismic system organization, the environmental system-organismic system dyad, system capacity, and system incorporation. A set of procedural rules are stated which suggest minimum criteria for the evaluation of the explanatory adequacy of biological theories. The relation of this work to other similar analyses and syntheses of biological knowledge is discussed.


Is thiamine pyrophosphatase a reliable marker of the neuronal Golgi apparatus? A critical analysis.

The thiamine pyrophosphatase histochemical technique is believed to be a suitable approach to the selective staining of the Golgi vesicles of all animal cells, icluding the neuron. However, during the past decade a considerable number of data have been published, suggesting that the TPPase is in general a membrane-associated enzyme in the brain, which can be found in subcellular fractions other than Golgi lamellae. It has therefore become necessary to reconsider the view that thiamine pyrophosphatase is an exclusive marker enzyme of the Golgi apparatus.


Effects of moderate coronary stenosis on myocardial flow reserve in man and in the dog.

The influence of coronary stenosis on resting blood flow (201Tl-uptake) and myocardial flow reserve (bicycle ergometry) is studied in 18 patients with coronary disease. Severe coronary stenosis of 75--90% caused a reduced 201Tl-uptake both at rest and peak exercise. In contrast to this group patients with a 50--60% stenosis have a normal scintigram at rest but focal defects of 201Tl-uptake at peak exercise. Results are compared with experimental data obtained after acute coronary constriction and simultaneous coronary dilatation (myocardial flow reserve, MFR) in 12 dogs. 60% coronary constriction causes a 37% decrease of poststenotic MFR measured with tracer microspheres. Changes of transmural flow distribution (endo/epi ratio) are minor in the left ventricular free wall but significant in the poststenotic septum (endo/epi = .84). It is concluded that even a moderate coronary stenosis of 60% not affecting resting blood flow becomes "critical" under conditions of high flow velocities.


Measurement of flow velocity in the model circulation by videodensitometry. Methodological investigations.

The relation between videodensitometrically measured front velocity and electromagnetically assessed flow was examined in a circulatory model with continuous as well as pulsatile flow (89 experiments). The diameter of the tubes in the videodensitometric measuring section was 0.305 to 0.518 cm. A linear correlation was proved in flow velocities up to Reynold's number Re = 225. The exact flow, measured electromagnetically, was overestimated in continuous flow by 21% (r = 0.99, Syx = +/- 14.5 ml/min) and in pulsatile flow by 24% (r = 0.98, Syx = +/- 20.8 ml/min). In view of these results the phasic and average flow can be calculated accurately using videodensitometric techniques.


Newly built facilities for ballistocardiography at the Polytechnic of Turin.

The role of recent research started in Italy, funded by the National Research Council, is stressed. The newly built Bcg facilities at the Polytechnic of Turin are concisely described. Current experimental research concerns the evaluation of a new type of concave-convex Bcg bed. Results from three healthy male individuals are shown and briefly discussed.


Morphological alterations of non-varicose and varicose veins. (A morphological contribution to the discussion on pathogenesis of varicose veins).

Venous valves do not play a role in pathogenesis of primary varicose veins. Their number remains constant during life time. In varicose veins their insufficiency is secondary. Intimal fibrosis is no prerequisite for the development of varicose veins. It is a frequent finding in non-varicose veins of all age groups. Fibrosis of media and adventitia is no early morphological alteration in varicose veins. Fibrotic replacement of smooth muscles represents a late stage of varicosis. Degenerative lesions of deep leg veins are rare even at old age. The deep veins are not influenced by sclerotic lesions of the adjacent arteries. Preexisting intimal fibrosis in autogenous graft veins may be one of several factors which induce an overshooting intimal proliferation. Degenerative alterations (fibrotic lesions of the wall layers, insufficiency of the valves) are secondary phenomena in pathogenesis of varicose veins which follow a functional deficiency of the smooth musculature.


Comparative recording of the heart beat by ultralow frequency and direct body methods with evidence of their basic clinical identity.

An attempt has been made to validate the d-v-a modification of the direct body electromagnetic shin bar in the ballistocardiographic evaluation of cardiac function. Its essential mirror reflections of body movements recorded with Ulf have been amply illustrated. A plea is made for a resumption of interest in its wider clinical application within a rigid correlative framework.


Ballistocardiographic correlation with invasive and noninvasive characteristics of cardiac ejection and designation of the initial point.

Noninvasive Bcg, ACG, ECC, CP and PCG were correlated simultaneously or by superimposition with the intraventricular and intra-aortic pressure pulse curves. Corresponding alterations in terms of one another have been demonstrated. These made possible delineation of the three phases of initial ejection by marking the points of initial and full opening of the aortic valve cusps (phase 2) in the Bcg, ACG and PCG. Possible prolongation of the interval between them may be seen in the severely diseased, dyskinetic heart which may perhaps be attributed to a 'sinusoidal' Bcg with prolonged H ejection time. The relation of S4 and S3 to mitral leaflet motion and their reflection in the Bcg has been emphasized.


Minimum average configuration for a set of 'n' independent Bcg events.

Since the analysis of the Bcg signal in the time domain is conveniently performed on a one-heartbeat block obtained by averaging a number of such blocks extracted from a continuous recording, the problem exists of which is the best relative phasing of the blocks before averaging. Supposing that each block has been expanded in a truncated Fourier series, an algorithm is found that allows one to determine the relative phase shift of the blocks; this is done by imposing the requirement that the integral variance over the period be a minimum. The influence of this procedure is tested on the width of confidence limits of a measure of signal dispersion of two different Bcg beds.


Up-to-date access to cardiovascular problems.

The regulatory systems that control the pump function of the heart are the mechanisms that modulate the level of myocardial contractility and the lenght-tension relationship. The Frank-Starling relationship is important in balancing -- beat-to-beat -- the outputs of both ventricles. More drastic changes in circulatory dynamics, as during exercise and in old age, are accompanied by changes in myocardial contractility. The young heart normally becomes smaller during exercise, even though the cardiac output is markedly increased. The increased myocardial contractility and the normal distensibility make it possible that the length-tension curve moves to the left and upward. The old heart and the failing heart tend to a relative dilation, even though the cardiac output is markedly decreased. Because of the diminished myocardial contractility in combination with the decreased distensibility, the length-tension curve is moved to the right and downward.


Clinical and physiological findings when the cardiac contraction is incoordinate compared with those found in matched cases with well-coordinated hearts.

A group of patients in whom the Bcg, the pulse derivative and the ventriculogram all agreed that cardiac incoordination was present has been compared with another group in which the same three tests agreed that the heartbeat was well coordinated. By pairing the cases we have demonstrated that those with cardiac incoordination showed significantly more angina pectoris, more coronary arteriosclerosis, more abnormal electrocardiograms, a slowed pulse rate and a smaller ejection fraction than did the corresponding cases. The other physiological functions measured were not significantly different in the two groups. Evidently, incoordination of the cardiac contraction is associated with other evidences of severe coronary heart disease. One can regard it as the physiological consequences of the irregular interruptions of coronary blood supply which characterize the pathological anatomy of this disease, and can expect it to appear late in its course.


Studies on the Bcg signal in infants.

In this report, we studied the relationship between respiratory and cardiac rates derived from a modified Bcg and for comparison from the thermistor and the ECG in infants from a new-born baby to a 13-year-old boy. The results with fair correlation coefficients support us in our opinion that this method is worth taking into consideration. Although the number of disturbances is not negligible, this indirect method offers a harmless control of vital parameters in childhood and adolescence. It gives reliable data without any trouble to the patients. In a period of increasing malpractice accusations, it could be of some interest to have a monitoring device working without any direct contact with the patient.


The value of echocardiography in assessing the severity of mitral stenosis.

In a group of 24 patients having pure mitral stenosis, the relation between the echo parameters of the mitral valve and pressures in the pulmonary circulation was studied. On the basis of the authors' results, it was concluded that the sensitivity of one-dimensional echocardiography for the assessment of the severity of mitral stenosis can be further improved by measuring not only the widely accepted parameters, such as the diastolic closing velocity and the motion amplitude of the AML, but also by taking into account the echodiameter of the mitral orifice. Besides, careful observation of the motion pattern of the PML might be of use for distinguishing between a mild and moderate degree of mitral stenosis.


Cardiac dynamics during the work load as studied by polycardiography.

Changes in systolic time intervals during the work load point to the differences in their control mechanisms. The exponential decay of the parameters shows sinusoidal oscillations. The number of oscillations is short in cycle length and isometric contraction time; it is the greatest in the ejection period.


Sphygmographic assessment of arterial distensibility in patients at risk of degenerative arterial disease.

The paper deals with the application of carotid resonance electrosphygmography (CRESG) to primary arterial hypertension (PAH) and primary hyperlipoproteinaemia (PHLP). On a group of 145 patients with PAH (and a control group of 63 healthy persons) aged 20--50 years and on a group of 30 patients with PHLP (plus a control group of 43 healthy persons) aged 30--60 years, the records were taken bilaterally. In both groups significant quantitative differences in the sphygmograms were found which are indicative for reduced distensibility and indirectly for the degeneration of the arterial wall. It is concluded that an effective follow-up of the progress of degenerative changes can be made by CRESG.


Early diastole in mitral valve disease.

Noninvasive findings from the study of early diastole in patients with mitral stenosis or mitral regurgitation are reported. Isovolumic relaxation time and the opening phase of the mitral valve are the main subintervals of early diastole. In mitral stenosis, a 3rd subinterval, the ECHO X-E phase, is described. Also, the effect of the cardiac cycle length on these intervals is studied, as well as the relationship between the opening snap, the O point of the apexcardiogram and the mitral echographic curve in early diastole.


Dynamic characteristics of the thorax connected with the heart action.

We determined the indices of local vibrations (resonance frequency, damping coefficient, stiffness constant, extinction time) and transfer function H(s) . 10(-6) for three somatotypes and three respiratory positions on 88 points of the thorax. The examinees were males (age 21 years). We found the resonance frequencies of 36.86--54.75 cps, damping coefficient (delta) 0.121--0.217. This means the damping is less than critical (delta = 1). We applied shocks (a force of 2 N) with a reflex hammer on 88 points of the thorax. The force diminished from the exciting place (say ictus) to the recording place (accelerometer on the sternum) from 2 to 0.2 N. The athletic type has the highest resonance frequency and stiffness constant; the leptosomic type has the highest damping; the longest extinction time belongs to the pyknic type. The pyknic type has also the highest value of the transfer function. The respiratory position (quiet respiration, Valsalva and Müller experiment) influences the values of the indices of local vibrations and of the transfer function. The influence is evident especially on the intercostal points: the transfer of the oscillations is alleviated at a higher stiffness of the thorax (Valsalva; the value of H(S) . 10(-6) rises from 7.00 to 9.39 sec2), it deteriorates at a small stiffness of the thorax (in Müller's experiment falls to 2.78 sec2). With the fall in the intrathoracic pressure the damping in the intercostal points decreases. On the basis of experiments the conclusion was made that a short testing of the thorax of an examinee will give the dynamic characteristics of the thorax (indices of local vibrations and transfer functions) of the individual. This procedure will alleviate the quantitative use of noninvasive mechanical methods in the assessment of the cardiovascular function.


Evaluation of the pulse contour method in beat-to-beat determination of the cardiac output in small laboratory animals.

The pulse contour method was used for determining beat-to-beat stroke volume in small laboratory animals. A good correlation was found between stroke volume values determined by the pulse contour method and figures obtained by dye dilution. The pressure volume proportionality factor KA from Bourgeois' formula for the pulse contour determination of stroke volume was less stable under changing haemodynamic conditions compared with the results of other authors obtained from larger laboratory animals.


Comparative examination of the pulse of both right and left carotid arteries.

The technique of CRESG secured on both arteries simultaneously is applied as a noninvasive diagnostic tool. A group of 42 persons (healthy and patients, 7 females and 35 males) aged 19--66 years was examined. In 14 of them X-ray angiography and in 5 of these 14 cases the additional surgical procedure confirmed the diagnosis. A difference of less than or equal to 10% between left and right upstroke time is shown in all subjects with decreased distensibility and signifies a generalized atherosclerotic process in all central arteries. Greater asymetry in bilateral CRESG is caused by a local more pronounced left/right arterial lesion. It is concluded that simultaneous left/right CRESG help to differentiate between generalized and localized arterial lesions.


Influence of diastolic fibre orientation on the left ventricular power generation.

A mathematical model is described which in a simplified way, without directly taking into account the elastic properties of the heart wall, describes the EDV which corresponds to the experimental data. The model further describes the power generation of the left ventricle at high EDV. The volume density of power is expressed with a product of three factors (1) average density of the CE, (2) a factor which contains the inotropic properties of a single CE and (3) a form factor, which involves structural changes in the heart wall at various EDV.


Further observations on modelling of the cardiovascular function in the electrical model.

In 1976 the fourth type of the electrical model of the cardiovascular function was constructed, showing formal and electronic changes: inverting system, hysteresis comparator (for the valve function), simulation of the insufficiency and the stenosis of the valves. The analog values were established but they are not yet definitive. The important values are: pressure 100 mm Hg = 100mV; flow 100 ml/sec = 137 microA. The action of the heart is given by changing capacity; the contractility is characterized by systolic capacity (CS). The diastolic capacity (CD) is not yet variable (CD = 4,000 microF) and consequently the diastolic pressure is always near to zero. The pressure curves of the left ventricle and of the aorta of cardiac patients with aortic valve disease were simulated. For comparison purposes only two clinical records and electrical model simulation records are given in this paper. In the patients (only aortic stenosis is given here) left heart catheterization was carried out. A case of coronary heart disease is also shown. The curves (simulated) are satisfactory and reflect the events in the compression chamber. The values of the parameters, which were used in the stimulation, represent the analysis of the clinical curves and a functional characterization of the situation. Besides these simulations the effect of valve changes on the pressure in the left ventricle, aorta and large arteries was also studied. With the aim of extending the integrative view of the use of the electrical model, an attempt of comparing the time course of capacity changes and the time course of inner surface changes of the left ventricle was made. The cinecardioangiographic data, obtained in an invasive way, were used for the purpose of obtaining the inner surface of the left ventricle. From pressure and surface data the cardiac forces (isometric, average and also total force per minute) were calculated and compared with the normal state, taken from the literature. The total force per minute includes the sum of systolic durations per minute and characterizes the energy expenses of the heart. Further data must be obtained by different cardiographic techniques in order to obtain a solid basis for the use of indirect methods, where the electrical model would be helpful as a noninvasive integrative tool in the assessment of the cardiovascular function.


Ballistocardiography: past, present and future.

In this paper, an analysis is given of the present state of ballistocardiography. It is concluded that several aspects of the method have to be improved before successful application in medicine can follow. These aspects are, for example, (a) physiological backgrounds of the method, and (b) signal analysis of the ballistocardiogram. Recent developments on these items are discussed and some preliminary results are given. Research on ballistocardiography is worthwhile to be continuing, since the method offers good perspectives for application in preventive medicine (early detection of coronary heart disease) and in clinical medicine.


Direct body ballistocardiography: a 25 year survey. Landmarks in its representation of cardiac dynamics.

The direct body Bcg has been shown to reflect various expressions of the known physiological principles of cardiac dynamics. Emphasis has been placed on the identification and characteristics of the individual segment rather than on gross pattern variability for proper Bcg pattern evaluation. Its sensitivity in the detection of early myocardial infarction with particular attention to its initial HI forces has been described. The significance of the simple Master two-step test (double) in eliciting the amplification or deterioration of these forces as a measure of myocardial integrity has also been emphasized. With this proposed definitive direction, there is call for widely organized attempts to clarify its potential as an important adjuvant in the study of clinical heart disease.


Kinetocardiography: past and present.

Kinetocardiography (KCG) records the absolute displacement of several points of the precordium. KCG utilizes only the low frequency motions (0--30 Hz). Computer availability allows for many improved methods of KCG evaluation. Amplitude and time normalization make averaging of curves more meaningful. Determining the mean of many KCGs of patients with the same disease offers a useful means of comparison. Of more recent interest is the possibility of comparing preoperative to postoperative curves of patients undergoing coronary artery surgery. Greatly increased total systolic retraction is evidenced in patients with improved clinical findings.


Clinical application of carotid electrosphygmography.

A short historical review of sphygmography and a description of the contour together with the genesis of the arterial pulse wave is given. An own procedure of quantitative analysis of the carotid sphygmogram is described. The scope of these investigations was an attempt to determine sphygmographic criteria for arterial distensibility, showing the degeneration of the arteries. First it is reported about the original technique of the carotid resonance electrosphygmography (CRESG), then the advantages resulting from long-term investigations (especially with arterial atheriosclerotic patients compared with normal subjects) are stressed. Secondly, the practical value of CRESG, substantiated with X-ray aortography, pathological findings and experiments on dogs is shown. In two groups (70 healthy subjects and 221 patients with reduced distensibility of the arterial wall) a significant correlation between PWV in the aorta and quantitative sphygmographic data could be shown. Thirdly, the usefulness of CRESG as a noninvasive method in the quantitative assessment of arterial damage is concluded especially for the case of atherosclerosis and hypertension. The further development of this original method in evaluating arterial ageing, the arterial changes in hypertensive patients and in different other pathological situations may promote a broader clinical application of CRESG.


Genesis of the sphygmogram from the kinetocardiogram.

The functional uniformity of the heart and vessels is studied. The idea of the genesis of the carotid sphygmogram from the kinetocardiogram (GS-KCG) was developed on the basis of the analysis of the KCG and carotid-sphygmographic (CSG) pattern obtained in 10 young healthy adults. Two of these examinees were additionally examined under the influence of a s.c. injection of adrenaline (A) and noradrenaline (NA). Two kinds of transducers for the displacement of the chest wall and of the carotid region were used (photoelectric and resonance receiver). They did not touch the skin and were placed in four positions on the thorax; three of them are routine auscultatory positions (ictus, ERB, aorta), one was the carotid artery pulse position. Amplitude and time intervals at rest and under the influence of catecholamines were determined and their interrelationship studied. The amplitudes are more variable than the intervals. The genesis of the waves was studied on the basis of the records in four positions. On this basis, a uniform hypothesis about the genesis of the KCG and CSG waves is derived. From this hypothesis and from the existence of a reflection wave starting at the aorta, the concept of the genesis of the sphygmogram from the kinetocardiogram was developed: the deformation starts at the aorta, is directed to the apex, is there reflected and propagated to the carotid artery. The validity of this concept of the GS-KCG is proved on the basis of experiments with adrenaline and noradrenaline. The quantitative data of peaks and waves from four positions show a stability of the KCG and CSG pattern despite the influence of catecholamines. A comparison is made between the apex cardiogram (ACG) and KCG and determinants of the characteristic pattern of chest movements are given. It was further concluded that the technique of measuring reflection wave velocity (=intracardiac velocity) and pulse wave velocity (=vascular, mixed) can be used as a test for individual reactivity of the cardiovascular system. The wave velocities and the carotid amplitude can help in detecting a disposition towards coronary disease.


Nutritional requirement and its assessment, with special reference to energy, protein and calcium.

If food is plentiful the requirement for energy is met by an accurate system of control so that intake balances expenditure. Energy requirements are therefore often assessed by measuring energy intakes. Intakes of protein, however, are no measure of protein requirements and the amounts customarily taken in Western diets are considerably more than man needs. The requirements for calcium are difficult to assess, for they are affected not only by age, but by other constituents of the diet, by the time of year, by individual peculiarities and by the previous intake. There is a physiological loss of calcium from the body starting in middle age which is not prevented by a high calcium intake.


Relevance of a borderline vitamin deficiency in relation to the question of vitamin requirement.

A definition is given for the terms of latent and borderline vitamin deficiency, and the vitamin requirement and optimal vitamin supply, respectively, are discussed in relation to these two terms. The upper limit of the latent vitamin deficiency status can be used to define the optimal intake of vitamins, whereas the lower limit indicates the minimum requirement. The impact on health of a latent vitamin deficiency lies in the risk of falling into a manifest vitamin deficiency during sudden stress, whereas, in borderline vitamin deficiency status, some health functions are affected so that a problem of public health may arise and countermeasures should be taken.


Fortification of foods in industrial and developing countries.

Sophisticated consumers of the future will not only feed themselves better; they will be far less prone to the victims of ignorance, the misplaced enthusiasm of the food faddist, the hucksterism of the charlatan, and the malice of those who inflate their egos, and earn their living by alarming others. There is much to be concerned about in the years ahead and our efforts should be expended on the right points -- and one of these right points will be an orderly and intelligent expansion of the concept of food fortification. The rationale for this is because too many of us, and far more in other parts of the world, do not consume, or have the opportunity to consume, a variety of foods that provide in adequate amounts the some 50 nutrients known to be necessary for good nutrition. A proper variety of foods, when available and when consumed, will provide the best nutrition each of us can obtain genetically. Intelligent fortification of certain key foods will assist in obtaining this adequate nutrition by those who do not or cannot consume this desired and proper variety of foods.


Studies on sex-organ development. Changes in the oestrogenic response of the chick Müllerian duct as measured by chromatin template and ribonucleic acid initiation capacity.

Assays of transcription in vitro, with Escherichia coli RNA polymerase or wheat-germ RNA polymerase II, were used to characterize chromatin templates isolated from the left Müllerian duct of the chick embryo during normal development, and during development in the presence of diethylstilboestrol. Control Müllerian-duct template capacity with E. coli RNA polymerase decreased from 6.42% on day 10 to 4.34% by day 15 of development. Similar results were found with wheat-germ RNA polymerase II. In the presence of rifampicin and heparin, the prokaryotic enzyme transcribed a number-average RNA chain of 670 nucleotide residues, at an average rate of 110 nucleotide residues/min, from Müllerian-duct chromatin of all developmental stages. From day 10 to day 15 there was a 44% decrease in the number of initiation sites for E. coli RNA polymerase on Müllerian-duct chromatin. A 47% decline was observed when these chromatins were transcribed with excess RNA polymerase II in the presence of rifamycin Af/013. Signs of increasing responsiveness to oestrogen developed between days 10 and 16. Embryos exposed to maximally responsive doses of diethylstilboestrol for 2 days showed increases in Müllerian-duct chromatin template capacity, RNA-chain initiation sites, wet weight, protein and RNA. The changes seen in the oviduct of the 1-week-old chick injected for 2 days with diethylstilboestrol were defined as 100% responses. By comparison, the Müllerian duct, after exposure to diethylstilboestrol from day 10 to day 12, from day 13 to day 15 or from day 16 to day 18, showed a 15%, 39% and 72% template response respectively, and a 42%, 56% and 85% initiation-site change respectively. A similar developmental trend was observed in all parameters. It is concluded that oestrogenic responsiveness in the developing Müllerian duct increases from day 10 to nearly maximal values by day 16 of development, and that this transition is paralleled by a progressive restriction of genomic activity.


Studies on sex-organ development. Prenatal effect of oestrogenic hormone on tubular-gland cell morphogenesis and ovalbumin-gene expression in the chick Müllerian duct.

The effects of diethylstilboestrol on morphogenesis and cyto-differentiation of the chick-embryo left Müllerian duct were examined. Embryos were treated at different stages of development with maximal-responsive doses of diethylstilboestrol over a 5-day interval. The shell gland and magnum regions of the Müllerian duct were then assayed for growth and histological morphogenesis. The results were correlated with diethylstilboestrol-induced ovalbumin-gene expression as measured by ovalbumin-mRNA (mRNAov) accumulation and the relative rate of ovalbumin synthesis. Treatment of the embryo from day 10 to day 15 of incubation induces morphogenesis of tubular-gland cells in the Müllerian-duct magnum. Although these cells constitute 10% of the total cell population and contain an average of 8000 molecules of mRNAov per cell, ovalbumin synthesis is only 0.85% of total magnum protein synthesis. The Müllerian-duct magnum of embryos treated from day 13 to day 18 of incubation contains about 30% tubular-gland cells, which have accumulated an average of 7000 molecules of mRNAov per cell, but ovalbumin synthesis is only 3.25% of total magnum protein synthesis. The Müllerian-duct magnum of embryos treated from day 16 to day 21 of incubation contains about 50% tubular-gland cells, which have accumulated an average of 6500 mRNAov molecules per cell, and ovalbumin synthesis is 10% of total magnum protein synthesis. Oestrogen responsiveness develops simultaneously in the Müllerian-duct magnum and shell-gland regions. Compared with the rate of diethylstilboestrol-induced oviduct growth, the relative rate of diethylstilboestrol-induced Müllerian-duct growth increases with embryonic age, from 20-fold lower in the 10-day embryo to only 3-fold lower in the 16-day embryo. All results are discussed in comparison with the responses to oestrogen of the immature chick oviduct, and in terms of the ontogeny of hormone-competent epithelial and stromal components of the Müllerian duct. It is concluded that the development of oestrogenic competence in the embryonic Müllerian duct is a multiphasic phenomenon. A dramatic increase in hormone responsiveness in the Müllerian duct occurs between days 10 and 16 of development, and a less dramatic final maturation of oestrogen responsiveness occurs between day 16 of development and 1 week after hatching.


Lactose synthesis in the rat, and the effects of litter size and malnutrition.

1. The rate of lactose synthesis per g of mammary tissue, measured in vivo by a radioisotopic technique, rose 13-fold between parturition and day 16 of lactation in the rat, but was unaffected by wide variation in litter size. 2. The increase reflected a greater tissue content of galactosyltransferase (EC 2.4.1.22), and was augmented by a rise in the total weight of mammary tissue. Superimposed on this were unpredictable changes in the functional efficiency of the enzyme. 3. Lactose synthesis in 14-day-lactating rats, permitted only 76% of the food intake of paired control rats over the previous 3 weeks, showed a pronounced diurnal variation at an overall rate markedly below that in control rats. 4. Such nutritional deficiency did not affect the tissue content of galactosyltransferase, but impaired its functional efficiency in a manner reversed by renewed feeding or by the preparation and incubation of acini in vitro. 5. Plasma insulin concentrations decreased at parturition and with increasing litter size, and remained relatively unchanged during lactation and malnutrition.


Studies on the isolation and properties of renin granules from the rat kidney cortex.

The present study was undertaken to isolate and investigate some physicochemical properties of renin granules from the rat kidney cortex. Two preparations of subcellular organelles were used: a primary-granule fraction, which allowed the properties of lysosomes to be compared simultaneously with those of renin granules, and a semi-purified preparation of the latter. The specific activity of renin in the primary-granule preparations was about 4-fold higher than in the original homogenate; that of the semi-purified renin-granule preparation was about 18-fold higher than in the homogenate, and consisted mainly of electron-dense granules but some mitochondria were also observed. Renin and acid phosphatase release from the primary-granule preparation was increased by lowering osmolality, by a low-molecular-weight solute (glucose) and by Triton X-100 or digitonin. Enzyme release was decreased by lowering the incubation temperature (4 degrees C) or the presence of CaCl2. Renin release from the partially purified granule preparation was not affected by cyclic AMP, cyclic GMP and ATP.


Endocytosis of lysosomal enzymes by non-parenchymal rat liver cells. Comparative study of lysosomal-enzyme uptake by hepatocytes and non-parenchymal liver cells.

Cultured non-parenchymal rat liver cells internalize human urine alpha-N-acetylglucosaminidase, human skin beta-N-acetylglucosaminidase and pig kidney alpha-mannosidase. Different heat-stabilities of endocytosed and endogenous alpha-mannosidase activity provided indirect evidence that the increase in intracellular activity resulted from uptake. The high efficiency and the saturation kinetics of uptake indicated that these enzymes become internalized by adsorptive endocytosis. Competition experiments with glycoproteins bearing known carbohydrates at their non-reducing terminals, with mannans, methyl glycosides and monosaccharides, established that the uptake of these three lysosomal enzymes is mediated by the binding to cell-surface receptors that recognize mannose and N-acetylglucosamine residues. The decreased uptake after treatment of these enzymes with either beta-N-acetylglucosaminidase or alpha-mannosidase was in accordance with the results of the inhibition experiments. Removal of oligosaccharides of the high-mannose type by treatment with endoglucosaminidase H inhibited uptake almost completely, suggesting that the sugars recognized by cell-surface receptors of non-parenchymal liver cells are located in the outer core of these oligosaccharides. A comparison of the uptake of these three lysosomal enzymes by parenchymal and non-parenchymal rat liver cells indicates that infused alpha-N-acetylglucosaminidase is taken up preferentially by hepatocytes, whereas alpha-mannosidase and beta-N-acetylglucosaminidase are localized predominantly in non-parenchymal rat liver cells.


Biosynthesis of skin collagens in normal and diabetic mice.

Synthesis of collagens in vitro was studied on minced mouse skins incubated with [3H]-proline in organ-culture conditions. A comparative study was carried out on genetically diabetic mice (KK strain) and control mice (Swiss strain). After incubation, neutral-salt-soluble and acid-soluble collagens were extracted. The insoluble dermis was digested by pepsin and type I and type III collagens separated by differential precipitation in neutral salt solutions. Type I and Type III collagens were characterized by ion-exchange and molecular-sieve chromatography, amino acid analysis and by the characterization of CNBr peptides. In diabetic-mouse skin, the relative proportion of type III collagen was significantly higher than in control-mouse skin. The incorporation of radioactively labelled proline into hydroxyproline of type III collagen was significantly faster in diabetic-mouse skin than in control-mouse skin. No significant modifications in the total collagen content of the skin or of their rates of synthesis were observed between the two strains. Alteration in the ratio of type III to type I collagen in the diabetic-mouse skin can be interpreted as a sign of alteration of the regulation of collagen biosynthesis and may be related to the structural alterations observed in the diabetic intercellular matrix.


4-Methyl-2-oxopentanoate oxidation by rat skeletal-muscle mitochondria.

1. Oxidative decarboxylation of 4-methyl-2-oxopentanoate (2-oxoisocaproate) by mitochondria of rat skeletal muscle showed biphasic kinetics. Two apparent Km values of 9.1 micronM and 0.78 mM were established. In broken mitochondria the rate of oxidation was lower and only the higher apparent Km value was found. 2. Isovalerylcarnitine inhibited 4-methyl-2-oxopentanoate oxidation in the presence and absence of carnitine, but isovaleryl-CoA had no inhibitory effect. 3. Addition of ADP enhanced 4-methyl-2-oxopentanolate oxidation. Malate, succinate and 2-oxoglutarate additionally increased the rate of oxidation, but in the absence of ADP succinate and 2-oxoglutarate inhibited. 4. Addition of rotenone and simultaneous addition of carbonyl cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP) and valinomycin markedly decreased 4-methyl-2-oxopentanoate oxidation. 5. These observations indicate that the branched-chain 2-oxo acid dehydrogenase complex is situated on the inner side of the mitochondrial inner membrane. 6. In mitochondria and homogenates CO2 was only produced by oxidative decarbosylation of 4-methyl-2-oxopentanoate. In intact muscle oxidation of this oxo acid proceeds more to completeness. 7. The physiological significance of intermediate formation during oxidation of branched-chain amino acids is discussed.


Activation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in homogenates of developing rat brain.

The specific activity of 3-hydroxy-3-methylglutaryl-CoA reductase increases when homogenates of developing rat brain are incubated at 37 degrees C or kept on ice. This increase is completely blocked by the addition of F- to the homogenization medium and the assay mixture. The capacity for activation of the reductase is greatest during the early postnatal period and declines as brain maturation proceeds. The data suggest that catalytic modification of the reductase may play a role in the regulation of cholesterol synthesis in the developing brain.


Effect of calcipenia on proteoglycan metabolism and aggregation in normal articular cartilage in vitro.

Glycosaminoglycan synthesis in normal adult dog knee cartilage cultured in medium containing 0, 0.3 MM- and 0.9 mM-Ca2+ was 52, 67 and 78%, respectively, of that in cartilage from the same joints cultured in a normal concentration of Ca2+, i.e. 1.8 mM. Pulse-chase experiments indicated that the rate of degradiation of glycosaminoglycans in cartilage cultured in the absence of Ca2+ was similar to that of glycosaminoglycans in cartilage cultured in 1.8 mM-Ca2+. Although [35S]sulphate incorporation into glycosaminoglycans was decreased in the presence of calcipenia, [3H]leucine incorporation into protein was unaffected. The average hydrodynamic size of newly synthesized proteoglycan aggregates and purified disaggregated proteoglycans from cartilage cultured in the absence of Ca2+ was similar to that of aggregates and disaggregated proteoglycans from cartilage cultured in 1.8 mM-Ca2+.


Effects of antimycin A and 2-deoxyglucose on secretion in human platelets. Differential inhibition of the secretion of acid hydrolases and adenine nucleotides.

1. Shape change, aggregation and secretion of dense-granule constituents in platelets differ in their dependence on cellular energy metabolism. The possibility that such a difference also exists between secretion of dense-granule constituents and acid hydrolases was investigated. 2. Human platelets were incubated with [(14)C]adenine in plasma, and then washed and resuspended in salt solutions. The effects of incubating the cells with antimycin A and 2-deoxyglucose on the concentrations of [(14)C]ATP, ADP, AMP, IMP and inosine plus hypoxanthine and on thrombin-induced secretion of ATP plus ADP and acid hydrolases were studied. The metabolic inhibitors only affected (14)C-labelled nucleotides, whereas thrombin only liberated unlabelled ATP and ADP. 3. The extent of secretion decreased progressively with time during incubation with the metabolic inhibitors. At any time the secretion of acid hydrolases, beta-N-acetylglucosaminidase, beta-glucuronidase and beta-galactosidase was inhibited to a greater extent than secretion of ATP plus ADP (dense-granule secretion). 4. Incubation with the metabolic inhibitors shifted the log (dose)-response relationship to higher thrombin concentrations, and with a greater shift for acid hydrolase secretion than for dense-granule secretion. 5. Antimycin, when present alone, caused a marked decrease in the rate of acid hydrolase secretion, but had no effect on dense-granule secretion. 6. These results further support the view that acid hydrolase secretion and dense-granule secretion are separate processes with different requirements for ATP energy. Acid hydrolase secretion, but not dense-granule secretion, appears to depend on a simultaneous rapid generation of ATP, which can be accomplished by oxidative, but not by glycolytic, ATP production.


Role of insulin receptors in the changing metabolism of adipose tissue during pregnancy and lactation in the rat.

Changes in the volume, the rates of fatty acid synthesis and synthesis of the glycerol moiety of acylglycerols, the activity of lipoprotein lipase, and the number and affinity of insulin receptors of adipocytes, and concentrations of serum insulin, prolactin and progesterone were determined in virgin rats and in rats at various stages of pregnancy and lactation. Changes in the metabolic activities of adipose tissue appeared to be synchronized and primarily comprised a marked decrease in anabolic activity around parturition. In contrast, the number of insulin receptors (Kd 1.5 nM) per adipocyte doubled during pregnancy before returning to normal values around parturition. It is postulated that the increase in the number of insulin receptors is an adaptation to counteract the effects of insulin-antagonistic hormones during pregnancy and that the decrease in the number of receptors is primarily responsible for the loss of anabolic activity around parturition.


Isoepoxydon, a new metabolite of the patulin pathway in Penicillium urticae.

A patulin-negative mutant (J1) of Penicillium urticae (N.R.R.L. 2159A) was known to accumulate about 100mg per litre quantities of the 5,6-epoxygentisyl quinone, (-)-phyllostine and another metabolite (UIII). Both were derived from acetate and hence were polyketides. Purified UIII (m.p. 53 degrees C, [alpha](32) (D)+206 degrees , lambda(methanol) (max.) 240nm; epsilon 3806 litre.mol(-1).cm(-1)) was characterized as a partially reduced derivative of (-)-phyllostine and was found to be a diastereoisomer of the known phytotoxin, (+)-epoxydon. Hence its designation as (+)-iso- or epi-epoxydon. From (1)H n.m.r. and c.d. data the stereochemistry of the epoxide ring in (+)-isoepoxydon was determined to be identical with that in (+)-epoxydon (i.e. R,R) but the configuration of the secondary alcohol at C-4 was S rather than R as in (+)-epoxydon. Isoepoxydon (compound UIII) is therefore (4S,5R,6R)-5,6-epoxy-4-hydroxy-2-hydroxymethylcyclohex-2-en-1-one. The boat conformation in which the C-4 hydroxy group is axial is preferred. In the range of 1mm to 5mm, the antibiotic activity of (+)-isoepoxydon against Bacillus subtilis sp. was 56% of that obtained with patulin. Over a period of 1 to 3h, [(14)C]isoepoxydon was efficiently converted into patulin by a shake culture of the parent strain of P. urticae. The precursor relationship of isoepoxydon to patulin was confirmed by feeding unlabelled isoepoxydon (1mm) to a washed-cell suspension of a mutant (J2) in which, over a period of 3 to 5h, a better than 60% conversion into patulin was attained. The enzymic relationship between isoepoxydon and phyllostine and their positions in the late portion of the patulin biosynthetic pathway are discussed.


Kinetics of 3-O-methyl-D-glucose transport in isolated rat hepatocytes.

3-O-Methyl-D-glucose transport across the plasma membrane of isolated rat hepatocytes was followed for net entry of the sugar into sugar-free cells (zero trans entry), net exit of sugar into sugar-free medium (zero trans exit) and for unidirectional entry and exit fluxes when cells had been equilibrated with sugar in the extracellular medium (equilibrium exchange entry and exit). These measurements were performed at 20 degrees C and pH 7.4 by the use of simple manual methods. Initial rates of transport showed a Michaelis--Menten dependency on the sugar concentration at the cis side of the membrane over the range of concentrations tested (100 microM to 100 mM). Transport was found to be symmetrical with no evidence of substrate stimulation of transport from the trans side of the membrane. Parameters (mean values +/- S.E.M.) of transport were estimated as Vmax. 86.2 +/- 9.7 mmol/litre of cell water per min and Km 18.1 +/- 5.9 mM for exchange entry, Vmax. 78.8 +/- 5.3 mmol/litre of cell water per min and Km 17.6 +/- 3.5 mM for exchange exit, Vmax. 84.1 +/- 8.4 mmol/litre of cell water per min and Km 16.8 +/- 4.6 mM for zero trans exit.


Calcium ions and cell fusion. Effects of chemical fusogens on the permeability of erythrocytes to calcium and other ions.

1. Fusogenic and non-fusogenic chemicals were tesetd for their ability to allow 45Ca2+ and 3H2O to enter hen and human erythrocytes. 2. The ratio of 45Ca2+/3H2O in treated cells to that in untreated cells is referred to as the entry ratio. 3. Within 1 min at 37 degrees C both water-soluble and lipid-soluble fusogens increased the value of the entry ratio, which reached maximum values in 5--10 min. 4. Values of the entry ratio in the range of 4--12 were found under conditions that led to cell fusion. 5. Closely related but non-fusogenic chemicals did not significantly alter the entry ratio. 6. The entry ratios for 86Rb+, 22Na+ and 35SO42- were also significantly increased by both lipid-soluble and water-soluble fusogens, though the increases were not as large as those for 45Ca2+. 7. It is suggested that fusogenic compounds increase the permeability of biological membranes to ions, and that an increase in the concentration of intracellular Ca2+ initiates or facilitates events that lead to the chemically induced fusion of erythrocytes.


Metabolism of glucose in hyper- and hypo-thyroid rats in vivo. Glucose-turnover values and futile-cycle activities obtained with 14C- and 3H-labelled glucose.

1. A trace amount of glucose labelled with 14C uniformly and with 3H at position 2, 3 or 6 was injected intravenously into starved rats to measure the turnover rate of blood glucose. 2. Reliable estimates were made based on the semilogarithmic plot of specific radioactivity of the glucose contained in whole blood samples taken from the tail vein. 3. Glucose turned over more rapidly in hyperthyroid and more slowly in hypothyroid than in euthyroid rats. The percentage contribution of glucose recycling (determined from the difference in replacement rates between [U-14C]glucose and [6-3H]glucose) to the glucose utilization increased on induction of hyperthyroidism. 4. Futile cycles between glucose and glucose 6-phosphate (determined from the difference between replacement rates of [2-3H]glucose and [6-3H]glucose) were activated and inactivated by induction of hyperthyroid and hypothyroid states respectively. 5. The hepatic content of glycogen was much lower in hyper- and hypo-thyroid than in euthyroid rats. The enhanced glucose production in hyperthyroid rats resulted from not only activationof hepatic gluconeogenesis but also diversion of the final product of gluconeogenesis from liver glycogen to blood glucose. In hypothyroidism, the inhibition of gluconeogensis led to suppression of both glucose production and glycogenesis in the liver.


Metabolism of glucose in hyper- and hypo-thyroid rats in vivo. Minor role of endogenous insulin in thyroid-dependent changes in glucose turnover.

1. Rates and rate coefficients of glucose utilization and replacement (glucose turnover) as well as its recycling were determined in rats by using [U-14C]- and [2-3H]-, [3-3H]- or [6-3H]-glucose. 2. In euthyroid rats, the blood concentration of glucose was 1.5 times and its turnover rate was 2 times as high in the fed state as in the starved state; consequently the rate coefficient, a measure of the capacity of rats to utilize blood glucose, was also higher in the former than in the latter. 3. Induction of mild diabetes by streptozotocin exerted little influence on the content and turnover of blood glucose in the starved state, whereas it caused hyperglycaemia and a decrease in the rate coefficient after feeding. 4. Induction of hyperthyroidism caused increases in rates and rate coefficients of glucose turnover to substantially the same extent whether or not the plasma concentration of insulin was lowered by treatment with streptozotocin or injection with anti-insulin serum. 5. It is concluded that thyroid hormones are capable of enhancing glucose turnover in the starved state independently of endogenous insulin, which plays a significant role in increasing glucose utilization in the fed state.


Metabolism of glucose in hyper- and hypo-thyroid rats in vivo. Relation of catecholamine actions to thyroid activity in controlling glucose turnover.

1. In euthyroid rats, treatment with reserpine of 6-hydroxydopamine, which deprived neuronal terminals of catecholamines, resulted in increases in rates and rate coefficients for blood glucose turnover in the starved states as determined by decay of [U-14C,6-3H]-glucose. Conversely, the injection of adrenaline or noradrenaline into starved euthyroid rats caused a marked decrease in rate coeeficients for glucose turnover. There was no change in the percentage glucose recycling under these conditions. 2. Adrenaline and noradrenaline caused more pronounced hyperglycaemia in hyperthyroid than in euthyroid rats owing to the greater activation of hepatic glucose production. 3. The increase in glucose turnover characteristics of hyperthyroidism was observed even after treatment with an alpha- or beta-adrenergic antagonist, showing the insignificant role of the balance between alpha- and beta-adrenergic receptors in the thyroid-dependent metabolic changes. 4. Rate coefficients for glucose turnover were not affected by reserpine treatment or catecholamine injections when rats had been rendered hyperthyroid. 5. Thus catecholamines are direct determinants of glucose-turnover rates in the starved state, and depend to some extent on the prevailing thyroid state.


Interactions in vivo between oxidation of non-esterified fatty acids and gluconeogenesis in the newborn rat.

Metabolic interactions between fatty acid oxidation and gluconeogenesis were investigated in vivo in 16h-old newborn rats under various nutritional states. As the newborn rat has no white adipose tissue, starvation from birth induces a low rate of hepatic fatty acid oxidation. Hepatic gluconeogenesis in inhibited in the starved newborn rat when compared with the suckling rat, which receives fatty acids through the milk, at the steps catalysed by pyruvate carboxylase and glyceraldehyde 3-phosphate dehydrogenase. These inhibitions are rapidly reversed by triacylglycerol feeding. Inhibition of fatty acid oxidation by pent-4-enoate in the suckling animal mimics the effect of starvation on the pattern of hepatic gluconeogenic metabolites. It is concluded that, in the newborn rat in vivo, hepatic fatty acids oxidation can increase the gluconeogenic flux by providing the acetyl-CoA necessary for the reaction catalysed by pyruvate carboxylase and the reducing equivalents (NADH) to displace the reversible reaction catalysed by glyceraldehyde 3-phosphate dehydrogenase in the direction of gluconeogenesis.


Hydrolysis of membrane phospholipids by phospholipases of rat liver lysosomes.

(1) The hydrolysis of (32)P- or myo-[2-(3)H]inositol-labelled rat liver microsomal phospholipids by rat liver lysosomal enzymes has been studied. (2) The relative rates of hydrolysis of phospholipids at pH4.5 are: sphingomyelin>phosphatidylethanolamine>phosphatidylcholine> phosphatidylinositol. (3) The predominant products of phosphatidylcholine and phosphatidylethanolamine hydrolysis are their corresponding lyso-compounds, indicating a slow rate of total deacylation. (4) Ca(2+) inhibits the hydrolysis of all phospholipids, though only appreciably at high (>5mm) concentration. The hydrolysis of sphingomyelin is considerably less sensitive to Ca(2+) than that of glycerophospholipids. (5) Analysis of the water-soluble products of phosphatidylinositol hydrolysis (by using myo-[(3)H]inositol-labelled microsomal fraction as a substrate) produced evidence that more than 95% of the product is phosphoinositol, which was derived by direct cleavage from phosphatidylinositol, rather than by hydrolysis of glycerophosphoinositol. (6) This production of phosphoinositol, allied with negligible lysophosphatidylinositol formation and a detectable accumulation of diacylglycerol, indicates that lysosomes hydrolyse membrane phosphatidylinositol almost exclusively in a phospholipase C-like manner. (7) Comparisons are drawn between the hydrolysis by lysosomal enzymes of membrane substrates and that of pure phospholipid substrates, and also the possible role of phosphatidylinositol-specific lysosomal phospholipase C in cellular phosphatidylinositol catabolism is discussed.


Identification of isobutyronitrile and isobutyraldoxime O-methyl ether as volatile microbial catabolites of valine.

G.l.c.--mass-spectral analysis of headspace above cultures of Aeromonas and Moraxella spp. indicates the presence of isobutyronitrile, isobutyraldoxime O-methyl ether, methacrylonitrile and possibly methacrylaldoxime O-methyl ether. Accumulation of these catabolites is maximal under low oxygen concentrations and is enhanced by enrichment of the medium with valine. Isobutyraldoxime O-methyl ether is established as the compound observed but not identified in previous studies with other bacterial species involved in spoilage of meat and chicken.


Composition and spectral properties of a cytochrome-enriched fraction obtained from chloroplasts by digitonin treatment.

A cytochrome-enriched fraction obtained from chloroplasts after treatment with the detergent digitonin contained cytochromes f, b-559LP and b-563 in the approximate proportions 1:1:2, close to those observed in unfractionated chloroplasts. The spectrum of cytochrome b-563 at temperature of liquid N2 showed a single asymmetrical alpha-band with a maximum at 561 nm.


The maximum activities of enzymes that are involved in substrate cycles in liver and muscle of obese mice.

The maximum activities of some dehydrogenases and enzymes involved in substrate cycles are increased in both liver and muscle of obese mice. This suggests that endocrine control rather than maximum capacity of the activities of enzymes constituting such cycles is impaired in obese mice.


Glycosylation of exogenous protein by endoplasmic-reticulum membranes from castor-bean (Ricinus communis) endosperm.

Endoplasmic-reticulum membranes isolated from the endosperm tissue of 3-day-old castor-bean (Ricinus communis) seedlings catalysed the enzymic transfer of the sugar moiety from an oligosaccharide--lipid to a chemically unfolded form of ribonuclease A.


Inhibition of protein synthesis in vitro by a lectin from Momordica charantia and by other haemagglutinins.

Protein synthesis by a rabbit reticulocyte lysate is inhibited by the haemagglutinating lectins from Momordica charantia and Crotalaria juncea seeds and from the roe of Rutilus rutilus, and by a commercial preparation of the mitogenic lectin from Phytolacca americana. The haemagglutinins from the seeds of Ricinus communis and of Vicia cracca acquired inhibitory activity after their reduction with 2-mercaptoethanol.


Approach to the study of the role of sex hormones in autoimmunity.

Investigators from this laboratory have been studying sex hormones in normal and autoimmune mice for the past 10 years. We have found that immune responses to DNa are influenced by sex hormones. Androgens reduce and estrogens increase both spontaneous and immunization-induced antibodies to single-stranded DNA in NZB X NZW, NZB X C3H, NZB X CBA, NZB X DBA mice. Treatment of female NZB/W mice with testosterone or 5 alpha dihydrotestosterone retards the progress of autoimmunity. Castration is not necessary for this effect. In contrast, danazol has no favorable effect on the disease process. Estrogens cause a marked acceleration of autoimmunity and a reduction in thymus weight. During the course of these studies, we found that a number of problems or variables arise in studying sex hormone effects, including: 1) X-linked genes, 2) metabolism of testosterone to estrogens, 3) dose of hormone, 4) age at which administration is initiated, 5) differential effects of sex hormones on different autoantibodies and various immune responses.


Alterations of estrogen metabolism in systemic lupus erythematosus.

Estradiol metabolism in 10 patients with systemic lupus erythematosus (SLE) and 29 normal controls was studied by measurement of urinary metabolites after injection of labeled 3H-estradiol. Patients with SLE manifested increased 16-hydroxylation of estrone. Diseases men differed from diseases women to the extent that only 16 alpha-hydroxyestrone was elevated in men, whereas women had elevations of both 16 alpha-hydroxyestrone and estriol. These data suggest that patients with SLE have abnormal patterns of estradiol metabolism, leading to increased estrogenic activity.


The role of the endocrine thymus in female reproduction.

Neonatal thymectomy in mice induces ovarian disturbances, indicating some relationship between the thymus and the ovaries. The mechanism of the relationship, however, is not fully understood. One approach to elucidating the complex relationship has been to measure circulating hormone levels in thymectomized animals and those with small thymus glands, and compare these levels with those found in control animals. The data indicate that a thymus-pituitary-ovarian axis exists and that thymus disturbances may hasten the aging processes of the ovaries.


Sex differences in response to hepatitis B virus. I. History.

Sex differences related to responses to hepatitis B infection are reviewed. In most human populations there is a higher prevalence of chronic carriers of hepatitis B virus (persistently HBsAg+) among males than females. Females are more likely than males to produce anti-HBs in response to infection. Diseases associated with increased frequencies of carriers are more prevalent among males. The response of parents to hepatitis B virus (HBV) infection appears to affect the sex ratio at birth of their offspring. Couples in which either parent is a carrier have higher sex ratios (higher proportion of males) compared with couples in which neither parent is HBsAg+. Couples in which the mother is anti-HBs+ have children with lower sex ratios than either carriers or uninfected couples.


The antiatheromatous action of silicon.

Silicon is a constituent of connective and elastic tissues. Administered intravenously or per os in rabbits, it inhibits experimental atheromas normally induced by an atheromatous diet, making atheromatous plaques much rarer and lipid deposits more superficial. Though the mechanism of silicon's antiatheromatous action remains shadowy, the impermeability's rise of the arterial wall is probably not the only influencing factor, because the arterial walls of animals under silicon do show a higher lipid concentration with respect to control animals. The preservation of the structure of elastic fibers, as well as of ground substance, and the absence of an increase in oleic acid in the aortic wall may also explain the rareness of atheromatous plaques.


Fibrin and atherogenesis--a hypothesis.

It has recently been found that endothelial cells exhibit an unusual change in cellular behavior in response to contact with fibrin. The possible implications of this finding with regard to the mechanism of atherogenesis are discussed. It is proposed that mural fibrin in vivo may produce a disorganized endothelium which can act as a nidus for further fibrin deposition and platelet aggregation. In the presence of inadequate fibrinolysis, a prolonged endothelial lesion could occur which may eventually result in atheromatous plaque formation. This view of atherogenesis requires reduced fibrinolytic activity as a prerequisite for plaque formation, a requirement which is in agreement with currently known data associating atherogenic risk factors with inhibited fibrinolysis.


Effects of increasing concentrations of minocin on the motility of bovine spermatozoa processed in various extenders.

The effect of minocycline hydrochloride (Minocin) on bovine spermatozoa was studied in eggyolk-citrate, Tris buffer and whole milk extenders. Each of the extenders contained penicillin, streptomycin, lincomycin-spectinomycin and four levels of minocin (10, 260, 510 and 760 mug/ml). Split ejaculates from Holstein sires were diluted in each of the extenders. This was followed by microscopic evaluation for progressive motility after initial dilution at 32 degrees C, after cooling at 5 degrees C and complete dilution, immediately after freezing and after 14 days of storage in liquid nitrogen. Under the experimental conditions employed, a decrease in the percent progressive motility was observed in the eggyolk-citrate and Tris buffer extenders with increasing concentration of minocin. Little or no difference in the percent progressive motility in the whole milk extender, either before or after freezing was observed when the minocin concentration was elevated.


A computer-based obstetric data retrieval system.

A computer-based obstetric patient data retrieval system is described which permits physicians with no prior computer knowledge or experience to access a patient data base. The advantages are minimal physician instruction, opportunity to examine maternal and neonatal outcome of defined diagnostic or therapeutic subsets of the data base, and rapid recall of individual patients' data, without need for continuous assistance from computer specialists. Disadvantages are the costs and our inability to interface our medical information with hospital business office data. Two brief examples of use of the system are provided.


Eosinophilc polymyositis.

A case of eosinophilic polymyositis is reported. Tender muscle swelling was followed by proximal weakness, creatinine kinase elevation, and electromyographic features typical of polymyositis. Severe myocarditis, pericarditis and heart failure were present. Muscle biopsy specimen showed active myositis with eosinophil infiltrate. Unlike previous cases, blood eosinophils count was normal. The clinical response to corticosteroids was excellent, and a relapse occurring as steroid dose was lowered responded rapidly to an increased dose of prednisolone. Eosinophilic polymyositis may be a component of a general systemic illness with prominent cardiac involvement.


Reproductive toxicity of caffeine in Musca dosmestica.

Marked changes in fecundity were noticed in houseflies fed caffeine in the diet. Partial treatment of male and female flies with caffeine also altered the oviposition pattern. Hatchability of the eggs was reduced significantly by caffeine. Concomitant with the oviposition effect, ovarian growth was retarded, resulting in abnormal ovaries and malformed eggs. Histological studies of growth-inhibited ovaries revealed that differentiation of the oocytes was blocked. Caffeine-fed female flies showed an accumulation of hemolymph portein. In contrast, caffeine-fed male flies showed a decrease in hemolymph protein compared with controls. Several changes in the electropherogram of hemolymph protein was observed in caffeine-treated flies. Biochemical analyses of ovaries isolated from caffeine-fed flies showed that they had less RNA and protein than controls.


Correlates of broad MMPI categories.

Investigated behavioral correlates of MMPI profiles of 363 male psychiatric Ss, classified by the Goldberg system and by two systems based on Welsh's factor scales A and R. For each profile category, frequency of occurrence for 81 behavioral descriptors from an adjective check-list was compared with frequency in the remaining categories. Two of the systems were compared with classification by code-type. Categories were not differentiated strongly on the basis of behavioral descriptors, although some trends were indicated. This study supports the position that interpretive systems that provide relatively few classification alternatives are of limited value in the interpretation of individual profiles. The results are discussed in terms of category heterogeneity.


[Specific activity and release of norepinephrine in isolated and perfused rabbit hearts under various oxygen pressure].

The incorporation of 3H-tyrosine into norepinephrine of rabbit hearts perfused with Krebs-Henseleit solution containing 11 mM glucose and gassed with 95% O2 - 5% CO2 (control) or 80% O2 - 5% CO2 15% N2 (hypoxic) or 95% N2 - 5% CO2 (anoxic), was studied. In the control hearts a constant specific activity of norepinephrine without any release of catecholamine into coronary effluent was measured after 5, 15, 30, 60 minutes. The hypoxic perfusion while not causing any release of norepinephrine, produced a significant increase in tyrosine incorporation into norepinephrine. The specific activity of norepinephrine and its release into coronary effluent were increased by anoxic perfusion; this effect was most evident when the glucose was replaced with a solution containing 11 mM mannitol. These results suggest that the synthesis of norepinephrine in isolated hearts, lacking of sympathetic innervation, may be affected by different condition of oxygen supply.


[Enzymatic exonuclease poly(A) degradation activity in liver nucleus and cytoplasm of rats].

Poly(A) degrading activities are detectable in nuclear, nucleoplasmic, cytoplasmic extracts and chromatin preparations from rat liver. More than 75% of the activity has been found within the nucleus; most of the nuclear activity is chromatin bound. Poly(A) degradation appears to occur largely via exonucleolitic cleavage.


[Separate extraction of 2 fractions of Mn++-dependent poly-A polymerase activity in liver cell nuclei of rats].

Part of the Mn++-dependent poly(A) polymerase activity of rat liver nuclei leaks out of the organelles when they are suspended in isotonic sucrose. With 0.5 ml/g fresh tissue of medium or more no increase in enzyme leaking out occurs after 30 min. Three repeated isotonic suspensions yelded all the activity thus obtainable (about 25% of total). Increasing the ionic strength of the suspension medium causes dramatic inactivation of the residual activity both in the extracted fraction and in the remaining one. It is confirmed that the bound activity is attached to chromatin.


Innate behaviour of mice studied in a double Y maze.

A test to study mice innate behaviour was realized. Groups of mice ran a double Y maze and chose one of the four possible exits. The results showed with a high probability level that mice had a very clear preference for a choice rather than the other ones.


Internal and external factors which modify the innate behaviour of the mouse in the double Y maze.

A test to study an innate behaviour of mice was standardized and the factors which could modify the results were examined. A track left by a mouse had effect upon the choices of the next one, the homogeneity of light at the exits was important, whereas orientations of the maze were not relevant and finally the significance of the test was increased when a maze with floating single-directional doors was used.


Effect of mescaline on an innate behaviour of mice.

The action of mescaline on mice innate behaviour was studied. In the first experiment the drug modified the innate behaviour of mice. The dose-effect curve was obtained by the second. The results pointed out that, in the range of doses examined, there was one for which the disruptive action of mescaline reach the maximum so that mice behaviour became completely casual.


[Artificial pancreas: study methods and control of glycemia equilibrium in diabetic patients].

The artificial endocrine pancreas or artificial beta cell, consists of a continuous blood glucose monitoring system, a computered set-up which responds to glycemia and the hormone delivery system. This system provides a technique which can completely normalize blood glucose concentration in diabetic patients, during both food assumption and after. This paper deals with the characteristics of the artificial beta cell, its possible applications and its limits.


[Biochemical and clinical studies of 2 new Italian cases of Hb G-Ferrara heterozygosis].

The Authors report the data concerning a family coming from Ficarolo (Rovigo). The father and one son were found hematologically healthy, but resulted carriers of Hb G-Ferrara. This is an unstable rare pigment with a replacement in the beta 57 (E-1) helicoidal position. The type and site of the mutation explain the "in vitro" molecular instability; on the other hand, this latter doesn't seem to cause any hematological disorder, even if an increased met-Hb production was found when affected blood was incubated at 37 degrees C for two hours in sterile conditions.


[Analysis of cerebellar proteins and glycoproteins in adult cattle. I. Con A positive glycoproteins].

The cerebellar glycoproteins of bovine have been separated by affinity chromatography on Con A-Sepharose and analyzed by poliacrylamide gel electrophoresis. Some soluble Con A binding glycoproteins are common to the insoluble (membrane bound) glycoproteins suggesting a relationship between the two classes of molecules. The data support the hypothesis that some of the soluble glycoproteins can be considered precursors of the insoluble.


[Early changes of liver microsomal lipids in acute thiobenzamide poisoning].

The administration to rats of Thiobenzamide, a new liver toxin, induces the early appearance of conjugated dienes among microsomal lipids. Along with an increased malonic dialdehyde "in vitro", the finding suggests lipid peroxidation to occur.


Increase in the preneoplastic liver lesions by thioacetamide followed by repeated partial hepatectomy.

Thioacetamide administration at low dose induces minimal changes in rat liver. Following withdrawal of the drug, the extent of the subsequent cholangiofibrosis and hyperplastic hepatocyte proliferation is strongly enhanced by partial hepatectomies performed monthly on the same animal.


[Effects of catecholamine treatment on UDPG levels in white and red skeletal muscle].

Adrenaline causes of 5 fold increase of glucose-6-phosphate and of glucose-1-phosphate both in the white extensor digitorum longus and in the red soleus (where the levels of the two sugar phosphates are significantly lower). On the other hand, UDPG levels--which are similar in the two muscles--are significantly decreased after adrenaline. It has been concluded that the levels of glucose-1-phosphate and of UDPG in muscle are not bound to change together.


[Modifications in glycogen following white and red muscle denervation in rats].

Native glycogen was prepared from intact and 12 and 36 h denervated white and red rat muscles, ultracentrifuged on a sucrose density gradient (3) and the fractions stained by the iodine method (4). An increase of the optical density of the fractions showing a relatively high density was observed, which may be related to the well known changes of muscle glycogen levels after denervation.


[Changes in lactate dehydrogenase isoenzyme patterns of human lymphocytes before and after blast formation].

The lactate dehydrogenase isoenzyme pattern of human lymphocitic cells has been determined in several people before and after stimulation by mitogenic lectins at different times after the start of the culture. A very significant change take place in the LDH 5 which can reach a greater concentration towards the other isoenzymes at the 72 h from the mitogenic stimulus, even if it starts from a smaller concentration.


[Effects of stereochemically different fatty acids on blood cholesterol in rats].

In the present study some observations about the effects of stereochemically different fatty acids on cholesterolaemia are reported. It is well known that high in EFA diets are useful for cholesterol metabolism: in fact cholesterol is preferably esterificated by EFA. Because of the increasing intake of fats, as high in hydrogenated EFA margarines, it has been verified whether such a technological process, inducing structural modifications, affects or not the ipocholesterolemic effect of EFA, particularly linoleic acid. Actually this research has shown such an effect to fail in presence of trans fatty acids and has pointed out some implications of lipid metabolism which are related to the different stereochemical configurations.


Total fasting and postprandial serum bile acids determination by 3 alpha-hydroxysteroid dehydrogenase in normal subjects.

Total serum bile acids (SBA) have been evaluated in 28 healthy subjects by an enzymatic-fluorimetric method using the enzyme 3 alpha-hydroxysteroid dehydrogenase. The healthy subjects showed a value of 2.78 +/- 1.84 microM/1 (mean +/- SD), ranging 0.5 to 4.7 microM/1. In addition, two hours postprandial evaluation of SBA was carried out in five of the above subjects. The mean value of SBA before and after the meal was 2.58 +/- 1.4 and 8.73 +/- 1.7 microM/1 respectively and the postprandial increase was found statistically significant (P less than 0.001). The present method for quantitative determination of SBA seems to be sensitive, reliable and useful as a routine clinical aid.


Tachyphylactic action of high doses of pentagastrin.

The study of the human LES was performed with manometrical methods for atropine action on gastrine tachyphylaxis. Our study points out that there is a complex self regulating neuronal circuit in the LES contraction. We discuss some hypothesis for the LES control. In particular ACh could activate an inhibitory adrenergic muscarinic receptor.


Response to nor-epinephrine, isoprenaline and spironolactone derivatives in normal and hypertensive rats.

In normal as well as in experimentally hypertensive rats the Blood Pressure and Heart Rate response-time curves are investigated following administration of nor-epinephrine, isoprenaline, spironolactone and K-canrenoate. The results stress the pharmacological effect dependence on integrity of homeostatic blood pressure mechanisms. alpha and beta receptor systems, as well as renine-angiotensine-aldo sterone system show different response-kinetic in mononefrectomized and mononefrectomized plus controlateral renal stenosis rats (Grollmann's model), in comparison with normal. While in normal rats the spironolactones evoke an hypertensive effect in experimentally renal hypertensive rats they reduce pressure to normal values.


[Influence of desoxycorticosterone on the reaction of isolated segments of coronary arteries to noradrenaline in the presence of pyrogallol].

The effect of the desoxycorticosterone on the noradrenaline-induced relaxation of coronary arteries waw studied in vitro, after a known inhibitor of COMT, pyrogallol. Relaxation induced by noradrenaline was enhanced by desoxycorticosterone. Relaxation in response to noradrenaline was increased by desoxycorticosterone. Pyrogallol potentiated the responses of coronary strips to noradrenaline and also reduced or abolished the enhancing effects of desoxycorticosterone. It is concluded that desoxycorticosterone enhances the reponse of coronary smooth muscle to noradrenaline by inhibiting and enzymatic pathway for the inactivation of catecolamines.


[Influence of bioflavonoid (4-methylesculetin) on the reaction of isolated calf hepatic artery to serotonin].

The effect of 4-metilesculetin on strips of calf hepatic arteries was investigated. 4-metilesculetin antagonizes the contraction induced by 5-HT probably through activation of the synthesis of vasodilator prostaglandins.


[Inhibitory effect of methergoline on serotonin induced contraction of isolated strips of coronary arteries].

Metergoline (antiserotonin drug) prevents the contraction induced by serotonin on strips of isolated coronary arteries. Moreover when metergoline is added at the maximal contraction, it induces relaxation of the vascular smooth muscle preceeded by a brevious phase of contraction.


[Shore species varieties in Lake Piediluco ((Umbria: Terni). Food and degree of parasitism of lake fish].

Lake Piediluco is a small natural lake in Umbria, Italy, which is regulated by hydroelectricity demands. Two artificials tributaries flow into it at the north end and create a lotic zona. The lake is rich in algae and hydrophytes. There are many sponge colonies and a great number of rheophil and limnophile caddis flies (40 species), gasteropods and bivalves. In the intestinal content of fishes the trichoptera larvae are very numerous. The fishes, which have been carefully investigated for parasites, are not seriously damaged.


[Mechanisms of detecting organic cholephilic anions in man: comparative studies on plasma depuration of rifamycin-SV. Interference of nicotinic acid and phenobarbital].

We have studied plasmatic half-life of R-SV administered alone and in association with nicotinic acid, before and after treatment with phenobarbital, in 10 normobilirubinaemic subjects and in 10 patients Gilbert's syndrome, used like controls. Ouer results confirm the existence of some alterations of drug-metabolism produced by associated administration of other drugs, in both healthy and hyperbilirubinaemic subjects, and in these one even more.


[Air embolism due to limited high grade barometric depression as evidenced in vivo].

The Authors supply documentary evidence for the aeroembolism of auricular lobe vessels photographed in transillumination of living albino rabbits exposed to high grade barometric depression (850 g/cm2) limited on the top of the head.


[The temporary occlusion of middle cerebral artery in cats--the correlation between the rCBF and the histological changes (author's transl)].

The correlation between the changes of regional cerebral blood flow (rCBF) and the histological changes were examined using the middle cerebral arterial (MCA) occlusion model in cats. A total of 24 adult cats were tracheostomized and anesthetized by inhalation of halothane. The right MCA was clipped by the transorbital approach. Two hours after the application, the clip was removed and the brain was recirculated for two hours. Then, the brain was perfusion-fixated and the histological studies were carried out. The animals were separated into two groups according to the severity of histological damages using light and electron microscope. Severe cortical damage was present in 8 cats (Group A). In the remaining 16 cats, little or no cortical damage was found (Group B). The averaged rCBF values before occlusion were 45.4 +/- 2.3 ml/100 gm/min in group A and 46.5 +/- 1.6 in group B, showing no statistically significant difference. Between these two groups, however, there was a statistically significant difference in the averaged rCBF values during the ischemic period. In group A, the averaged rCBF values during MCA occlusion was only 6.8 +/- 0.9 and in group B, it was 25.3 +/- 0.8. In the recirculation period, there was a prompt and uniform recovery of rCBF in group B. Whereas in group A, a marked diversity of rCBF ranging from oligemia to hyperemia ensued. This is presumably a reflection of inhomogeneous blood flow, or patchy non-filling of the cerebral cortex. The critical values of rCBF as to the occurrence of severe cortical damage in two-hours MCA occlusion is considered to lie between the lowest value of group B and the highest value of group A, i.e., around 12--15 ml/100 gm/min.


[Neuropsychological studies of two subjects after the transection of the splenium of the corpus callosum. (Part 2. The auditory recognition by the dichotic listening test) (author's transl)].

We made the neuropsychological auditory studies of two right-handed subjects who had undergone the transection of the splenium of the corpus callosum for the pineal operation (the teratoma by the histopathological examination). The transection grades were 2.0 cm and 2.5 cm. The truncus and splenium of the second subject were flat by the compression of the tumor. We examined these subjects by the some audiolocigal methods. 1. Pure tone audiometry. 2. Fixed frequency Békésy audiometry. 3. SISI test (short increment sensitivity index test). 4. Speech audiometry. 5. Distorted speech test (filtered speech test). 6. Binaural fusion test. 7. Dichotic listening test. The tasks used for the dichotic listening test were following. Different digits (one pair, three pairs), different words (from two to four syllables) and different vowels and consonants were presented simultaneously to the two ears by means of a dual-channel tape recorder with stereophonic earphone. The result shows that the first subject (whose section of the spelenium was 2.0 cm) shows a slight but not significant superiority on the right ear to the one pair digits and words (p less than 0.1), and the second subject (whose section of the splenium was 2.5 cm and whose splenium and truncus of the corpus callusum were flatten by the compression of the tumor) shows a significant superiority on the right ear to the one pair digits, words, three pairs digits and vowels (p less than 0.05). But there was no definitive abnormalities at the pure tone audiometry, the fixed frequency Békésy audiometry, SISI test, distorted speech test and binaural fusion test of two cases. The result shows that the commissure fibres of the auditory perception of the speech of two hemispheres connect through from splenium to the truncus of the corpus callosum.


[The anti-tumor effect of ACNU and X-irradiation on mouse glioma (author's transl)].

Anti-tumor activities of ACNU and X-irradiation on methylcholanthrene induced glioma in C57BL mice were studied in vitro and in vivo. In vitro experiments using cultured glioma cells (MGB cells), the synchronization of cell cycle was done by excess addition of thymidine, and the anti-tumor cell effect were investigated by mean of determinations of DNA synthesis, mitotic index and the number of the living cells following the treatments. As the results, it appeared obvious that ACNU was most effective on MGB cells in S phase and X-irradiation in M phase. As to the combined therapy of ACNU and X-irradiation, the anti-tumor effect was most remarkable when the cells were treated by X-irradiation in the G2, M phase, which were hervested by addition of ACNU 44 hours before irradiation. However simultaneous treatment of ACNU and X-irradiation on the cells in G1 phase was not so remarkable. In vivo experiments the anti-tumor effect of ACNU and X-irradiation on subcutaneously or intracranially transplanted glioma in mice was investigated. Either ACNU 10 mg/kg or local X-irradiation 1240 rads showed inhibitory effect on the tumor growth and prolonged the survival time of the tumor bearing mice. The combination therapy was more effective than ACNU or X-irradiation alone, particularly combination therapy of ACNU and repeated small doses irradiation of X-ray was remarkably effective. Evidence obtained indicates that the combination therapy of ACNU and X-irradiation have synnergistic anti-tumor effect on experimental mouse glioma.


[Morphological changes of platelets in disturbed cerebral microcirculation--a clinical study using a scanning electron microscope (author's transl)].

Many factors are known that contribute to the pathogenesis of the cerebral microcirculatory disturbances, but, there are few reports investigating the roles of the intravascular components directly. The present study was undertaken to evaluate morphological changes of platelets in patients with cerebral damage, in relation to neurological signs, especially consciousness levels. Morphological changes of platelets were observed in 72 patients with intracranial organic lesions. These lesions included subarachnoid hemorrhages, hypertensive cerebral hemorrhages, cerebral infarctions, brain tumors, chronic subdural hematomas, and acute epidural hematomas. Two blood samples were taken, one from the internal jugular vein (the blood after cerebral perfusion), the other from the cubital vein (systemic blood). After fixative procedures with 1% glutaraldehyde, the differences in the three-dimensional structures of platelets were compared, using a scanning electron microscope. In general, remarkably activated forms of platelets were found in the blood after cerebral perfusion in cases with severely impaired consciousness in the acute stage. But, in cases without severe neurological deficits, such changes of platelet forms were rarely seen. A close relationship was suggested between the degree of neurological damage (especially consciousness levels) and that of platelet activation in the acute stage. In the chronic stage, these changes of platelets in the cerebral blood disappeared. Changes of platelet forms were not found in the systemic blood from the cubital vein, even in the acute stage. It is clinically suggested that morphological changes of platelets play an important role in the pathogenesis of the disturbed cerebral microcirculation. Obstruction of cerebral microvasculature may be caused, mechanically by the activated platelets themselves, and/or chemically by vasoconstrictive substances released from these platelets. Therefore, in the treatment of these intracranial organic lesions, it is concluded that the possible roles of activated platelets should be taken into consideration.