Serum total amylase activity and its isoenzyme fractions in newborn pigs with relation to growth and iron dextran-treatment. Serum amylase activity was analyzed chromogenically (blue starch method) and its isoenzyme was separated by cellulose acetate membrane electrophoresis in newborn pigs comparing with those in adult pigs. Serum amylase activity in newborn pigs was about one half of adults' and increased with age. Serum amylase isoenzymes were separated into 4 fractions from the cathode. The isoenzymes were also classified in 5 types on the basis of the combination of these 4 fractions. Incidences of the fractions and the types were not significantly different between adults and newborns. After the iron dextran treatment, serum amylase activity as well as levels of erythrocytes, hemoglobin and packed cell volume increased. The rates of increase in hemoglobin and packed cell volume were more significant in the double treatment group than in the single treatment group, while serum amylase activity increased similarly in these 2 groups. The increase in serum amylase activity seemed to indicate that the development of amylase-producing organs was reinforced by the iron compound treatment. It is thought that serum amylase activity may be an indicator of healthy growth in newborn pigs.


Plasma and cerebrospinal fluid monoamine metabolism in patients with chronic fatigue syndrome: preliminary findings. The syndrome of chronic fatigue, feverishness, diffuse pains, and other constitutional complaints, often precipitated by an acute infectious illness and aggravated by physical and emotional stressors, has a lengthy history in the medical literature. The Centers for Disease Control (CDC) recently formulated a case definition, renaming the illness "chronic fatigue syndrome." Nevertheless, there remain few biological data that can validate the existence of this syndrome as distinct from a wide variety of other, largely psychiatric disorders, and little understanding of its pathogenesis. In the present study, basal plasma and cerebrospinal fluid levels of the monoamine metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) were determined in 19 patients meeting CDC research case criteria for chronic fatigue syndrome and in 17 normal individuals. Patients with chronic fatigue syndrome showed a significant reduction in basal plasma levels of MHPG and a significant increase in basal plasma levels of 5-HIAA. Although the functional significance of these findings has not been definitively elucidated, they are compatible with the clinical presentation of a syndrome associated with chronic lethargy and fatigue, and with evidence of persistent immune stimulation, and lend support to the idea that chronic fatigue syndrome represents a clinical entity with potential biological specificity.


Growth and microvascular development of the uterus during early pregnancy in ewes. Growth and microvascular development of the uterus were evaluated for ewes on Days 12, 18, 24, and 30 after mating (3-4 ewes/day; Day 0 = day of mating) in two experiments. In experiment 1, fresh weight and dry weight of gravid uterine horns were increased on Days 24 and 30 after mating, whereas those of nongravid uterine horns were elevated only on Day 30. The increased fresh and dry weights of gravid uterine horns on Day 24 were associated with uterine hyperplasia (increased DNA content). Increased fresh and dry weights of gravid uterine horns on Day 30, however, were associated with hypertrophy (increased RNA:DNA and protein:DNA ratios) of uterine tissues. In experiment 2, vascularity of endometrial tissues was elevated on Days 24 and 30 after mating. In addition, dramatic changes in uterine architecture (increased lumenal diameter and decreased endometrial thickness) and in uterine microvascular development (increased abundance of large microvessels and development of a subepithelial capillary plexus) were observed by Day 24 after mating. Characterization of the patterns of uterine growth and microvascular development will enable us to further define the role of previously reported uterine and conceptus-derived growth and angiogenic factors during early pregnancy.


Postnatal development of sympathetic and sensory innervation of the rhesus monkey ovary. We have used immunofluorescence to study the postnatal development of the sympathetic and sensory innervation to the rhesus monkey (Macaca mulatta) ovary. Sympathetic nerves were identified as adrenergic by their content of tyrosine hydroxylase (TH)-like immunoreactivity and as peptidergic by the presence of neuropeptide Y (NPY). Fibers containing substance P (SP) or calcitonin gene-related peptide (CGRP)-like immunoreactivity were considered as sensory, whereas vasoactive intestinal peptide (VIP)-positive fibers were only defined as peptidergic because VIP may be present in both sympathetic and sensory nerves. Ovaries from neonatal (2-mo-old), juvenile (9-18-mo-old), peripubertal (3-3.5-yr-old), adult (9-14-yr-old), and senescent (20-27-yr-old) monkeys were studied. At all ages, with the exception of senescence, TH-, NPY-, and VIP-containing fibers were associated with follicles in different developmental stages. In peripubertal and adult animals, some primordial follicles were found to be selectively innervated by VIPergic fibers that almost completely encircled each follicle. Both sympathetic and VIP fibers were also detected in the interstitial tissue and associated with the ovarian vasculature at all ages. The number of sympathetic and VIP fibers increased significantly (p < 0.01) between 2 mo and 9-18 mo of age, and again increased (p < 0.01) around the age of puberty (approximately 3 yr of age). After this time, the number of NPY and TH fibers remained constant. Conversely, the number of VIP fibers decreased (p < 0.05) by 9-14 yr of age, but remained constant thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)


Androgens are necessary for the establishment of secretory protein expression in the guinea pig seminal vesicle epithelium. The guinea pig seminal vesicle epithelium (GPSVE) synthesizes and secretes milligram quantities of four related secretory proteins in an androgen-dependent manner. To investigate the role of androgens in the establishment of secretory protein synthesis during the development of the GPSVE, animals were castrated at Day 5, approximately 10 days before secretory protein accumulation begins in intact animals. Castration did not eliminate secretory protein mRNA from the SVE, but it did indefinitely postpone the developmentally programmed increase in secretory protein mRNA. Injection of neonatally castrated guinea pigs with either estradiol or dexamethasone did not alter levels of secretory protein mRNAs. However, treatment of castrated neonates with either testosterone propionate or dihydrotestosterone (DHT) led to specific increases in secretory protein mRNAs within 4 days. Although neonatally castrated animals accumulated and translated significant amounts of secretory protein mRNA, the newly synthesized secretory proteins failed to accumulate until exogenous androgens were provided. This observation suggests that androgens regulate both the accumulation of secretory protein mRNA and the accumulation of secretory proteins in the GPSVE.


Electroporation and electrophoretic DNA transfer into cells. The effect of DNA interaction with electropores. It has been shown recently that electrically induced DNA transfer into cells is a fast vectorial process with the same direction as DNA electrophoresis in an external electric field (Klenchin, V. A., S. I. Sukharev, S. M. Serov, L. V. Chernomordik, and Y. A. Chizmadzhev. 1991. Biophys. J. 60:804-811). Here we describe the effect of DNA interaction with membrane electropores and provide additional evidences for the key role of DNA electrophoresis in cell electrotransfection. The assay of electrically induced uptake of fluorescent dextrans (FDs) by cells shows that the presence of DNA in the medium during electroporation leads to a sharp increase in membrane permeability to FDs of M(r) < 20,000. The permeability increases with DNA concentration and the effect is seen even if FD is added to the cell suspension a few minutes after pulse application. The longer the DNA fragment, the greater the increase in permeability. The use of a two-pulse technique allows us to separate two effects provided by a pulsed electric field: membrane electroporation and DNA electrophoresis. The first pulse (6 kV/cm, 10 microseconds) creates pores efficiently, whereas transfection efficiency (TE) is low. The second pulse of much lower amplitude, but substantially longer (0.2 kV/cm, 10 ms), does not cause poration and transfection by itself but enhances TE by about one order of magnitude. In two-pulse experiments, TE rises monotonously with the increase of the second pulse duration. By varying the delay duration between the two pulses, we estimate the lifetime of electropores (which are DNA-permeable in conditions of low electric field) as tens of seconds. The data suggest that the mechanism of cell electrotransfection is underlain by electrophoretic movement of DNA through membrane pores, the size of which is determined by interaction with DNA in an electric field.


The beta subunit controls the gating and dihydropyridine sensitivity of the skeletal muscle Ca2+ channel. The skeletal muscle (SKM) L-type Ca2+ channel is composed of a central subunit designated alpha 1, which contains the pore and the dihydropyridine (DHP) binding domains and three associated subunits, alpha 2/delta, beta, and gamma, which influence the activity of the SKM alpha 1. Coexpression of SKM alpha 1 and SKM beta in stably transfected mouse L cells results in a dramatic increase in DHP binding accompanied by fast gated Ba2+ currents. We report here that this "SKM alpha 1 beta-related phenotype" can be converted upon intracellular trypsin treatment into a slowly inactivating, DHP sensitive "SKM alpha 1 phenotype." These observations indicate that current amplitude, fast inactivation, and DHP sensitivity are modulated by an interaction of SKM alpha 1 and SKM beta on the internal side of the membrane.


Mitochondrial ATP synthase regulation in heart: defects in hypertension are restored after treatment with captopril. Control of mitochondrial ATP synthase capacity was investigated in cultured cardiomyocytes from normotensive (Wistar-Kyoto) and spontaneously hypertensive rats. Cells from spontaneously hypertensive rats have a higher basal ATP synthase capacity than those from normotensives, but lack the normal up-regulation in response to an increased energy demand. After treatment of spontaneously hypertensive rats with captopril (60 mg/kg per day for 12 weeks), cellular hypertrophy characteristic of the hypertensives was abolished and the cardiomyocytes showed a normal ATP synthase capacity. Normal up-regulation of this enzyme was also restored. All cells showed a normal down-regulation of the synthase in response to cyanide. Experiments with the calcium antagonists, verapamil and ruthenium red, suggest that abnormal ATP synthase regulation observed in the untreated spontaneously hypertensive rats results from an alteration of Ca2+ handling in cardiac cells under chronic high workload, which is reversed by captopril treatment.


Cyclic GMP inhibits the inotropic response to alpha 1-adrenoceptors in the papillary muscle of the ferret. The physiological role of cyclic GMP in the heart remains controversial. In the present study we investigated the interaction between a number of agents known to increase the level of cyclic GMP in the myocardium and alpha 1-adrenergic stimulation in isolated preparations of cardiac papillary muscle in the ferret. Inotropic responses to the cumulative addition of phenylephrine were measured in papillary muscles of the ferret in the absence and presence of 1 microM sodium nitroprusside, 1 microM atrial natriuretic peptide, 0.1 microM substance P (which stimulates the release of nitric oxide from endocardial endothelium) or 1 microM 8-bromo-cyclic GMP. In parallel experiments using similar preparations, alpha 1-induced hydrolysis of phosphatidylinositol was assessed by measuring changes in the levels of inositol 1,4,5-trisphosphate in response to 10 microM phenylephrine in the absence and presence of the same agents that increase the level of cyclic GMP. Phenylephrine (0.001-10 microM) induced a concentration-dependent positive inotropic effect that was significantly inhibited by each of the agents that increase cyclic GMP. Phenylephrine (10 microM) induced an approximately three-fold rise in the level of inositol trisphosphate in the myocardium, which was likewise significantly inhibited by each of the agents that increase cyclic GMP. These data show that agents that increase the level of cyclic GMP in the myocardium inhibit both the positive inotropic and phosphatidylinositol response to alpha 1-stimulation in isolated preparations of papillary muscle in the ferret.(ABSTRACT TRUNCATED AT 250 WORDS)


Intercellular adhesion molecules and vascular cell adhesion molecule-1 and the kidney. Adhesion molecules such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 are expressed in the kidney and are regulated by proinflammatory cytokines. These adhesion molecules play an important role in the binding and activation process of leukocytes and are of importance in inflammatory kidney diseases. This review article describes current knowledge regarding the structure, expression, and functional role of adhesion molecules and their significance in immune-mediated renal diseases.


Analysis of leukemic cell activity with a simple acridine orange staining method. Leukemic cells from 28 patients with acute lymphoblastic leukemia (ALL) were supravitally stained with acridine orange (AO). Based on the staining characteristics of their cells, the patients were divided into an orange cell-dominant group (15 patients) and a green cell-dominant group (13 patients). The prognosis was better in the former than in the latter group. Orange cells which had high RNA contents were observed, while the proportion of dividing cells was high. Supravital staining with AO is a very simple and useful method for assessing the metabolic activity of leukemic cells in ALL; this method may thus be useful in assessing the prognosis of these patients.


Cellular localization of IGF-I and IGF-II mRNAs in immature hypophysectomized rat testis and epididymis after in vivo hormonal treatment. IGF-I and II genes expression has been localized by in situ hybridization in testis and epididymis of immature hypophysectomized rats treated in vivo with either pFSH, hLH, bGH, hPRL or with saline. IGF-I mRNA expression was found in both Sertoli and Leydig cells after treatment with either FSH or LH. IGF-I mRNA was highly expressed in germ cells after FSH stimulation and to a lesser extent after GH or LH treatments. However, its expression was very low in hypophysectomized control or PRL treated rats. IGF-I mRNA was also expressed in stromal cells of epididymis after LH treatment and to a lesser extent after GH stimulation. In contrast, IGF-II mRNA expression was detected in all testicular cell types whatever the hormonal treatment (FSH, LH, GH, PRL). For each hormonal treatment testicular sections were examined after immunohistochemical staining with specific antisera against IGF-I and IGF-II. Both in situ hybridization and immunohistochemical data were examined in order to determine the testicular sites of synthesis of IGF-I and IGF-II.


Erucic acid metabolism in rat liver. A combined biochemical and radioautographical study. Metabolism of erucic acid was studied in rat liver in comparison with oleic acid in relation with diet lipids. Rats were fed for 3 or 60 days a balanced diet containing 30% of the calories of either rapeseed oil rich in erucic acid or sunflower seed oil rich in linoleic acid. They were intravenously injected with tritiated erucic or oleic acid. After 1 or 15 min, the radioactivity recovered in liver lipids was 9 to 26% whatever the diet or the acid injected. One minute after injection of erucic acid a high part of radioactivity was recovered in the free fatty acid fraction and as untransformed erucic acid. After 15 min the major part of radioactivity was recovered in the triacylglycerol fraction which contained a high proportion of labelled oleic acid formed by shortening of erucic acid. The autoradiography did not show any marked difference between the labelling of peroxisomes and mitochondria when tritiated erucic or oleic acid was injected. These data do not bring about arguments for a peroxisomal nor for a mitochondrial location of erucic acid shortening in liver.


Long-term effects of dietary monounsaturated and polyunsaturated fatty acids on plasma lipids in dogs. To compare the effect of monounsaturated vs. polyunsaturated fatty acids on plasma lipids, three months old dogs were studied for a period of six months. The dogs were fed a basal diet supplemented with either 14% olive oil or sunflower oil. Blood samples were taken fortnightly during this period. We have found changes in the various unsaturated fatty acids in response to the diet. Oleic and 20:3 n-9 acids were higher in the olive oil group while linoleic acid was increased in the dogs fed the sunflower oil diet. Arachidonic acid and PUFA n-3 > 18C index were nearly similar with both diets. The cholesterol levels were similar to those found in adult humans and no significant differences were brought about diets at any time. Thus a diet rich in monounsaturated fatty acids is as efficient as a polyunsaturated rich in relation to total cholesterol levels but more beneficial because of the antiatherogenic effect of HDL-cholesterol which is increased with this type of dietary fat.


Reproductive function in female rats submitted to chronic hypobaric hypoxia. Female rats were submitted to 5,500 m simulated altitude (50.7 kPa) for 23 weeks in a hypobaric chamber. In vitro biosynthesis of estradiol from labelled pregnenolone was studied in the ovaries of these rats and of their controls at sea level barometric pressure. The weight of the ovaries expressed as mg/rat was 63% higher (p < 0.001) and estradiol biosynthetic capacity expressed as % conversion/rat was 140% higher (p < 0.01) in hypoxic than in control rats. Estrous cycle and fertility were studied in rats submitted to 4,400 m simulated altitude (58.6 kPa) and in their controls. The percentage of estrous was significantly higher in hypoxic than in control animals. The fertility was lower in hypoxic rats. Optical microscopy showed signs of polycystic ovaries in both hypoxic groups. These results may suggest that the normal reproductive function includes oxygen dependent factors.


Brain acetylcholinesterase activity and optomotor behavior in bluegills, Lepomis macrochirus exposed to different concentrations of diazinon. Organophosphorus pesticides inhibit acetylcholinesterase (AChE) activity to varying degrees in different species of fish. Estimation of AChE activity is a useful tool for establishing the degree of pollution caused by these pesticides. Behavioral changes are very good and sensitive indicators of any chemical pollution. Changes in the optomotor behavior are easily quantifiable. Therefore estimation of AChE activity and changes in the optomotor response are taken as criteria to study the effects of different concentrations (15, 30, 45, 60 and 75 micrograms/l) of diazinon, an organophosphorus compound, in bluegill Sunfish, Lepomis macrochirus. The fish were exposed for a period of 24 hours. In this study, AChE activity showed a significant decline above an exposure concentration of 45 micrograms/l exposure concentration. In the case of optomotor behavior, a decline in the scores of the "following" responses of the fish was noticed from an exposure concentration of 30 micrograms/l. It seems that a behavioral bioassay is more sensitive than other types of testing.


Effects of inhalation of ethyl-ether on glycemia and on some variables of intermediate metabolism in rats. The influence of a anesthetic, ethyl-ether, on arterial plasma levels of glucose, insulin and lipids was studied in starved Wistar rats. Ethyl-ether increased significantly (P < 0.05) glucose plasma levels, as a result not only of stress and of the release of catecholamines and glucocorticoids, but also of the decrease in the use of glucose by the tissues. Ethyl-ether did not change significantly the level of triglycerides, cholesterol and phospholipids. Insulin concentration was not increased, even when hyperglycemia was established. Ketonuria, acidosis and hypercapnia were increased. In these rats the administration of insulin produced a diminution in glycemia. The findings suggest that, under anesthesia with ether, the endocrine pancreas is incapable of recognizing glucose as a specific stimulus to promote the release of insulin.


Factors simultaneously affecting the growth of the rainbow trout (Oncorhynchus mykiss). Growth of rainbow trout (Oncorhynchus mykiss) is examined in relation to simultaneous variation of initial weight, initial density, temperature and time (days). Twenty-six lots of medium weight were set up, ranging from 92 to 372 g; initial density ranged from 7.2 to 38.8 kg/m3; and temperatures from 14 degrees C in winter to 20 degrees well into spring. Experimental periods carried out were of 7, 20, 38 and 26 days duration. By multiple correlation and regression analysis, predictive equations for increments in weight, final density were obtained in relation to the afore mentioned variables and ranges. The values of multiple correlation obtained were highly significant. We confirmed that the effect of each factor on growth is modified by the simultaneous action of the other variables.


Endocrine and hemodynamic responses to dopamine infusion in the guinea-pig: effects of ACE inhibition with perindopril. The effects of dopamine on plasma renin-angiotensin-aldosterone system vasopressin levels and blood pressure were studied in anesthetized guinea-pig. The inhibition of the angiotensin converting enzyme with perindopril permitted assessment of the role of the renin-angiotensin system. In perindopril-treated guinea-pigs, the activity of angiotensin-converting enzyme was decreased by 90% with simultaneous increases in plasma renin activity and angiotensin I concentration; aldosterone and vasopressin levels, blood pressure and heart rate were not modified. Dopamine depressed mean arterial pressure by 30% and increased heart rate (8%) in controls. Dopamine infusion did not affect either plasma renin activity or angiotensin I concentration or angiotensin-converting enzyme activity in control animals. But in perindopril pretreated animals it further increased plasma renin activity (88%) and angiotensin I concentration (35%). Finally, in controls, dopamine infusion increased plasma vasopressin concentrations (91%) whereas this increase did not occur in perindopril treated animals.


Characteristics of ryanodine-induced tetani in the perfused rat heart. Tetanic tension is not the highest force that cardiac muscle can generate. The aim of the present study was to elucidate the conditions required to obtain tetanic contractions in rat intact heart and to investigate whether tetanic tension was actually the maximal tension that isolated rat heart is able to generate. Experiments were performed on isolated rat hearts (Langendorff technique) perfused at constant coronary flow (8-9 ml/min). Rapid repetitive stimulation (400 to 3000 pulses/min) failed to elicit a fused tetanus. The first twitch that occurred at the end of the rapid stimulation period was a potentiated beat (PSP) of significantly greater magnitude than that of the regular twitch. This potentiation declined in successive beats. When rapid electrical stimulation (600 to 3000 pulses/min) was applied to hearts treated with 5 x 10(-6) M ryanodine, the result was a fused and steady tetanic tension. Ryanodine suppressed PSP. Tetanic tension could be graded by stepwise increase of [Ca2+]o from 0.25 to 5 mM. Maximal tetanic tension occurred at a [Ca2+]o between 3.85 and 5 mM. At any of the [Ca2+]o, tetanic tension was significantly greater than the tension of the twitch obtained at approximately the natural frequency of rat heart in the intact animal (250 beats/min) but it did not differ significantly from the twitch obtained at 100 beats/min. Moreover, the tension of PSP at 0.25 and 1.35 mM [Ca2+]o was significantly greater than the maximal tetanic tension that could be obtained. Similar results to that obtained with ryanodine, were obtained in additional experiments in which caffeine was used to evoke tetanic contraction.(ABSTRACT TRUNCATED AT 250 WORDS)


Rat neonates renal function after beta-receptors and adrenoceptors blockade during pregnancy. Pregnant Wistar rats were given by subcutaneous route 1 of 3 different adrenoreceptor blockers, 2 of them mainly beta-blockers. P5 and P7 group received propranolol (5 and 7 mg/kg respectively), L10 and L20 groups received labetalol (10 and 20 mg/kg) and B5 group received betaxolol (5 mg/kg). Drugs were given daily from the 7th to the 16th day of gestation. A control group received saline injections. 16 out 24 treated mothers delivered prematurely on the 21st day of gestation. Functional renal parameters were studied in neonates on the first day of life. Renal function of the full term rats prenatally exposed were compared with controls. Average body weight was higher in P5 but lower in L10-L20-B5 groups. Diuresis increased in L20. Creatinine clearance, urinary/plasmatic creatinine ratio and urea clearance decreased in L10-L20 groups and fractional excretion of H2O increased in L20. Thus these adreno- and beta-blockers given to pregnant rats induced a shorter gestation. Moderate functional renal effects were observed in all neonates.


Studies on gamma-aminobutyrate aminotransferase (GABA-T) activities in human and rodent brain homogenates. Differences in the kinetic properties of brain gamma-aminobutyrate aminotransferase (GABA-transaminase; GABA-T) in different species are described in the present investigation. In both rat and human brain enzymes, the effect of temperature on the activity was studied. The maximal activity, for a 30-min incubation period, was attained at an incubation temperature of 45 degrees C for rat and 56 degrees C for human brain tissue. The addition of plasma or plasma proteins was found to induce a two-fold increase of the activity of rat brain GABA-T, whereas a slight inhibitory effect on human brain enzyme and no effect on mouse brain enzyme was observed. The species differences are shown to be the results of differences in the binding of the cofactor pyridoxal phosphate to the apoprotein, which are revealed when the free concentration of pyridoxal phosphate is reduced by binding to serum albumin.


[Blood lactate in the steeplechase horse: triangular and rectangular series of steps during short duration races]. Five steeplechase race horses were observed during incremental and constant-load exercises with the aim of separating effects of work rate and time on blood lactate. Each independent exercise (an incremental and three constant load tests) was a sequence of three two-minute runs, separated by two one-minute rest intervals for jugular blood sampling. The following observations were made: 1. During constant load exercises, in the five horses, blood lactate stabilized below 4 mmol.l-1: lactatemia critical velocity (LVC) = 3.33 +/- 0.16 mmol.l-1. Nevertheless, VCL, critical lactate velocity inducing LVC, was not statistically different from VS4, velocity inducing a 4 mmol.l-1 blood lactate during incremental tests. Remaining reticent on the meaning of "lactate threshold" often attributed to VS4, an incremental exercise thus seemed pertinent for routine long-term surveys of endurance. 2. If delta L is the blood lactate increase within a single short run, delta L increases linearly with running velocity for an incremental test, allowing the calculation of a "null" velocity, the highest velocity for which there is no significant lactate increase. For independent runs, delta L increased exponentially with velocity, with noticeable differences between horses. This individual short-term functional adaptation variability could be considered in assessment and follow-up of race horse fitness.


[Study on the relationship between toddler temperament and development (second report)--the relationship between toddler temperament and developmental delay]. The purpose of this study is to clarify the relationship between toddler temperament and developmental delay, and to examine whether the result could be adapted to the health practice of mother and child. As the conceptual framework, we used A. J. Sameroff's transactional model. Questionnaires concerning toddler temperament, rearing environment and toddler development were sent to mothers whose children were scheduled to receive 1 year and 6 months child health examinations, and collected 306 responses. We assessed the developmental status of 41 children among the 306 by means of the Japanese edition of the Denver Developmental Screening Test. All 306 children were classified into either the developmental delayed group (30) or the normal group (275). The data analyses were conducted both quantitatively and qualitatively with the following results. Compared with normal children, developmentally delayed children showed these characteristics: (1) The temperamental category scores of adaptability and persistence were higher, indicating low adaptability and persistence. The prevalence of difficult child, slow to warm up (STWU) child and intermediate high child was relatively higher, with STWU child the highest. (2) The score for the rearing environment was lower. (3) There were cases where disagreement between a child's temperament and the mother's rearing behavior had an influence on the child's development. As a conclusion, these results indicate that a child's temperament must be considered developmental and child-rearing counseling in child health examinations.


Dietary calcium on vascular reactivity in normotensive and spontaneously hypertensive rats. Vascular reactivity and systolic blood pressure (SBP) were studied in tail artery rings isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive, Wistar-Kyoto rats (WKY). After a control week on a diet with 1% of calcium, the animals were randomly assigned to three groups, which were fed with 1% (control), 0.4% (low) or 2.5% (high) dietary calcium. Both vascular reactivity and SBP were studied in the same animal during 9 weeks after changing diets. In the SHRSP rats on high Ca diet, maximal contractile responses to norepinephrine and serotonin (10(-10) to 10(-4) M) and to KCl (5 to 105 mM) were markedly decreased at the end of the study with respect to the control diet. These vascular changes were accompanied by a decrease of SBP in the same animals. Low calcium diet prevented the age-related increase of SBP in SHRSP rats and produced vascular changes of a lesser magnitude. WKY rats showed no significant modifications of SBP or vascular reactivity. Since plasmatic Ca2+ levels were not altered, the changes detected could not be attributed to a direct depressant effect of high calcium on the vascular smooth muscle cell (i.e. a "stabilizing action" of calcium). It is speculated that high dietary calcium could modulate the synthesis of calcium binding proteins of the plasma membrane, decreasing vascular reactivity and the elevated vascular resistance which is usually present in hypertension.


Seasonal changes in blood parameters in the bat species Rhinolophus ferrumequinum and miniopterus schreibersi. Intersexual and seasonal comparisons of erythrocyte number, hematocrit, and hemoglobin concentration were conducted for two old world temperate bats, Rhinolophus ferrumequinum and Miniopterus schreibersi. Both species had many small erythrocytes and elevated hemoglobin concentrations. Seasonal differences in erythrocyte count, hemoglobin concentration, and mean cell volume were found in each species. The increase in the number of small erythrocytes in the warm season may be related to heightened activity of the bats during this period. High blood-oxygen capacities associated with high hemoglobin concentrations and hematocrit values increase oxygen delivery to tissues in species with small body size and high metabolic rates.


[Variations in the testicular response to HCG during the perinatal period in the rat: influence of estrogens]. The variations of the testicular responsiveness to hCG and the implication of the maternal estrogens in the functioning of the testes were studied in the perinatal male rat. Male rat fetuses treated with hCG at the end of gestation failed to show an increase in serum testosterone (T). The lack of testicular responsiveness to hCG in the fetus is neither due to anesthesia nor to a blocking effect of estrogens directly on the testes. On the other hand, hCG injected either at 4 h or at 48 h after birth increases serum T. The administration of 5 micrograms of estradiol 17 beta (E2) to the newborn male rat at the time of birth blocks the expression of the postpartum testosterone surge. The fall in the plasma estrogens and the increase of the testicular sensitivity to gonadotropic stimulation at the time of birth are factors which are very likely implicated in the determinism of the neonatal testicular hyperactivity.


Dural arteriovenous malformation and sinus thromboses in a patient with prostate cancer: an autopsy case. A 67-year old man with prostate cancer showed Balint's syndrome, memory disturbance, anosognosia and hallucinations after having been comatose. Radiological findings indicated bilateral dural arteriovenous malformation (DAVM) and thrombosis at the bilateral transverse sinuses and superior sagittal sinus. Pathological findings showed abnormally dilated veins, diffuse neuron loss and gliosis in the parieto-occipital lobe. The chlormadinone and prostate cancer are speculated to have caused the dural sinus thrombosis which probably induced the DAVM.


[Uses of duck hepatitis B virus polymerase and reverse transcriptase in the evaluation of anti-hepatitis B virus drugs]. The method of DHBV replication complexes (RCs) purification was modified. In order to screen anti-HBV drugs from Chinese medicinal herbs, the inhibitory effects of the extracts of 14 Chinese recipes and herbs, 30 compounds isolated from Chinese herbs on DHBV DNA polymerase (DNAP) and reverse transcriptase (RT) have been studied. The results showed that extracts of Xiao Chai Hu Tang (small Bupleurum decoction) inhibited DHBV DNAP and RT in less extent. Of the 7 herbs, the components of Xiao Chai Hu Tang, the extracts of S. baicalensis and P. ternata potently inhibited DHBV RT, their concentration of reducing enzyme activity by 50% (IC50) was 1.25 and 1.6 mg/ml respectively. Furthermore, it has been proved that S. baicalensis inhibited DHBV DNA replication in ducklings. It also was found the extract of P. cuspidatum inhibited DHBV RT with IC50 of 1.76 mg/ml. Nine of thirty isolated compounds inhibited both DHBV DNAP and RT in less extent under high concentration, while other did not.


High resistance to cucumber mosaic virus conferred by satellite RNA and coat protein in transgenic commercial tobacco cultivar G-140. A chimeric vector was constructed to express cucumber mosaic virus (CMV) satellite (Sat) RNA and coat protein (CP). Transgenic lines of tobacco cultivar G-140 expressing CP and Sat-RNA were obtained; these lines had high resistance to CMV. Fifty to 70% of the transgenic plants were symptomless 90 days after inoculation with 25-50 micrograms/ml of CMV. Resistance was about twice that conferred by the Sat-RNA or the CP gene alone in transformed plants.


Dynamic aspects of AMPs in the kidney in physiological conditions--their metabolism and turnover. The past few decades have witnessed a number of studies on AMPs in the kidney. Almost all of these studies, however, have dealt with the quantitative and qualitative analysis of AMPs in the kidney using biochemical techniques, whereas the dynamic aspect of AMPs in the kidney has been overlooked and its metabolism and turnover have never been emphasized. On the other hand, the kidneys removed from humans and experimental animals revealed a wide variety in interstitial tissue in the medulla microscopically and in the papilla of the kidney macroscopically. The reasons for these variations in the medulla, its mechanism and the matrical component have not yet been clarified. In an effort to clarify these points, we herein describe our study on the dynamic aspect of AMPs in kidney histologically in relation to their biological turnover which we employed several staining methods. Our results revealed that there was a very active turnover of AMPs present in the kidney confirming that the kidney plays an important role physiologically in AMP metabolism. The degree of the turnover of AMPs in the kidney varies from case to case. In the active phase, AMPs are excreted in the glomerulus and reabsorbed in the proximal portion of the collecting tubules. Most of the absorbed AMPs are finally drained through the lymphatic vessels in situ and a few are excreted into the urine. Contrary cases have been demonstrated, however, only were a few AMPs were noted throughout the nephrons in the kidney. AMP turnover in the kidney is unexpectedly remarkable. The medulla, which has been considered less important, in fact, plays a key role in AMP metabolism.


Functional changes of alveolar macrophages in carragheenan-induced aspiration pneumonia model mice. Alveolar macrophages (AMs) are cells with unique characteristics because of their localization in the aerobic environment and are receiving stimuli by inhalation. To estimate the functional changes of AMs induced by inflammation, a murine model of aspiration pneumonia was made by an intratracheal injection with carragheenan, whose mortality rate was approximately 25%. The cell component which increased predominantly in the inflammatory site was polymorphonuclear leukocytes, and the number of AMs did not show a remarkable increment. Control group showed a high level of intracellular oxidation of 2'7'-dichlorofluorescin (DCFH) by AMs, while that in carragheenan-treated mice decreased significantly (p < 0.05). There were two populations in AMs classified according to the oxidative activity of DCFH; the population showing high oxidative activity of DCFH was asialo GM1 positive, in contrast, that with lower oxidative activity was asialo GM1 negative. Decrease in DCFH-oxidative activity of AMs in control group was observed after a treatment with KCN or deferoxamine. But in the carragheenan-treated group, this decrease was not observed after treatment with KCN. These results show that both oxygen-derived radical produced in mitochondria, which is inhibited by KCN, and cytoplasmic OH radical, which is selectively inhibited by deferoxamine, are concerned with intracellular oxidation of DCFH by AMs, and that a decrease in DCFH-oxidative activity in the carragheenan-treated group was attributed to the depression of mitochondrial respiration. Nevertheless, increased expressions of Ia and F4/80 in AMs of the carragheenan-treated group were observed and phagocytic activity was well preserved at the control level. These results suggest that AMs may play a crucial role, as well as differentiated phagocytes possessing antigen-presenting ability and/or digestive activity against various types of foreign bodies despite showing an obvious decrement in oxidative activity. These results imply that AMs have a strong oxidative activity and deal with various types of antigens in normal states, but in case of acute inflammation they will change into mature type macrophages with high expression of class II molecules which correlates with an antigen-presenting capacity.


Leptospiral antigens in the liver of experimentally infected guinea pig and their relation to the morphogenesis of liver damage. In order to investigate the morphogenes of experimental leptospirosis by morphologic and immunohistologic methods, 24 guinea-pigs were inoculated intraperitoneally with L. interrogans serogroup Icterohaemorrhagiae. They were divided in 6 groups, sacrificed from the 1st to the 6th day of infection. Semiquantitative analyses of histopathological liver lesions were performed in 1 micron sections of tissue embedded in glycol-methacrylate. The distribution of leptospiral antigen (L. Ag) and its glycolipoprotein (GLP) was demonstrated by peroxidase-antiperoxidase on paraffin embedded tissue. Significant lesions appeared at the 4th day of infection, progressing to a peak on the 6th day. Inflammation was associated with injury of the portal triad. Liver cells showed either swelling or acidophilic degeneration and necrosis, together with loss of cell cohesion, leading to disarray of liver cell plates. Mitochondria were found progressively enlarged and irregularly distributed. L. Ag expression was parallel to the morphological changes. Portal distribution was significant at the 4th day and on later stages centrilobular localization became predominant. Spiral forms suggestive of intact leptospires were initially found but, chiefly at the 6th day, L. Ag was seen in granules, probably resulting from phagocytosis. GLP staining was similar to granular L. Ag in morphology, and distribution. Cytokeratin condensation was seen in liver cells with acidophilic necrosis and was marked in areas of disorganization of cell plates. Our findings lead us to hypothesize a direct leptospiral cytotoxic effect on endothelial and on liver-cell membranes. At first, leptospires themselves would induce subcellular changes acting mainly on membrane permeability. Afterwards, their granular forms, including GLP, would act as adjuvant factors. These findings demonstrate that the disarray of liver cell plates at the late phase of the disease is genuine.


Regional distribution of neurofilament and calcium-binding proteins in the cingulate cortex of the macaque monkey. The cingulate cortex is composed of morphologically and functionally distinct areas. It is considered to be a major component of the limbic system and has been shown to subserve a wide range of autonomic and somatic motor functions. The anterior and posterior regions of the cingulate cortex can be differentiated according to their thalamic afferents as well as their patterns of corticocortical connectivity. The primate cingulate cortex is traditionally divided into a series of cytoarchitectonic zones that can be distinguished along a ventral-dorsal axis of differentiation in both the anterior (areas 25, 24a, 24b, and 24c), and posterior (areas 29, 30, 23a, 23b, and 23c) regions. However, little is known about the precise cellular organization of these subareas. In the present study, we attempt to define the neuronal morphological and biochemical composition of the different cingulate cortex subareas, using antibodies to the neurofilament triplet protein and calcium-binding proteins. Results indicate that there is a strong correlation between the structure and functions of the cingulate cortex and the immunostaining patterns. For instance, distribution of neurofilament-rich pyramidal neurons parallels that of specific corticocortical and corticosubcortical systems and is a useful marker to delineate the cingulate motor area. Calcium-binding protein-containing neurons display a high degree of regional and laminar specialization. In particular, parvalbumin-positive interneurons are codistributed with neurofilament-immunoreactive pyramidal cells along the ventrodorsal and rostrocaudal axes of the cingulate cortex. Calbindin- and calretinin-positive immunostaining show more monotonous laminar and regional patterns, although they exhibit a particular labeling in area 29 that may correspond to the termination of select thalamocortical afferents. These chemoarchitectural patterns of regional and laminar neuronal specialization may be envisioned as the reflection of the richness of cortical diversity in the cingulate gyrus, and make it an ideal place to explore the interplay of the distributions of various neuron types in cortical areas of known function.


Genetic novelties in mitochondrial genomes of multicellular animals. Mitochondrial genomes of multicellular animals are mostly small, circular molecules in which 13 protein genes, two ribosomal-RNA genes and 22 transfer-RNA genes are closely packed. Substantial rearrangements of genes have only occurred between phylogenetically distant organisms. However, a wealth of genetic novelties are found among these genomes that include modified genetic codes, unorthodox translation initiation codons, and structurally modified RNA components of the mitochondrion's translation system.


Glutamatergic excitatory responses of anterior cingulate neurons to stimulation of the mediodorsal thalamus and their regulation by GABA: an in vivo iontophoretic study. Anatomical and physiological studies in the rat have shown projections from the medial dorsal thalamus to the anterior cingulate cortex. We used multibarrel iontophoresis to identify the neurotransmitter used in this thalamic projection. Extracellular responses were recorded from 165 cingulate neurons in anesthetized rats after electrical stimulation of the medial dorsal thalamus and vicinity. Forty-four of these cells (27%) showed an excitatory response to thalamic stimulation. In a further 40 cells that showed no baseline excitation, iontophoresis of the GABAA antagonist bicuculline methiodide revealed excitatory responses. The GABAB antagonist CGP-35348 attenuated longer-latency inhibition in 5 of 10 cells. In 23 of 49 (47%) of the above cells, AMPA antagonist iontophoresis (either CNQX or DNQX) selectively decreased the excitatory response to thalamic stimulation. The NMDA antagonist 3[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid had no such effect. These data suggest that the thalamic projection to anterior cingulate cortex is glutamatergic, acting principally via AMPA receptors, and that the response of cingulate neurons to thalamic stimulation is regulated by GABA acting at both GABAA and GABAB receptors.


Neuromodulation of vertebrate motor neuron membrane properties. The short-term function of motor neurons is to integrate synaptic inputs converging onto the somato-dendritic membrane and to transform the net synaptic drive into spike trains. A set of voltage-gated ion channels determines the electro-responsiveness and thereby the motor neuron's input-output function. In addition, several of the decisive ion channels are transmitter controlled, which results in a flexible control of the input-output relationship.


Increased density of glutamate-immunoreactive vertical processes in superficial laminae in cingulate cortex of schizophrenic brain. Recent postmortem investigations have suggested that schizophrenia may involve a defect in associative information processing in the upper layers of limbic cortex. One of these studies reported that vertical processes visualized with antibodies against the neurofilament 200K subunit (NFP-200K) of the axon cytoskeleton were increased in density in layer II and upper portions of layer IIIa of the cingulate region of schizophrenic individuals. Based on this latter finding, it was hypothesized that there may be a superbundance of associative afferents to this region. To explore this possibility further, an immunoperoxidase localization of the amino acid glutamate has been employed to visualize vertical fibers in layers II and IIIa of postmortem anterior cingulate cortex in both normal controls (n = 15) and schizophrenics (n = 17). Vertical fibers were distinguished according to small or large calibers and were differentially counted with a blind computer-assisted technique. The schizophrenic group showed a markedly higher density (77.8%) of small-caliber glutamate-immunoreactive vertical fibers when compared to controls; the density of large-caliber vertical fibers also showed a similar, though smaller (30.2%), increase in the schizophrenic group. There were no differences in the density of either small- or large-caliber processes in prefrontal cortex of the two groups. The effects of age, postmortem interval, fixation, and neuroleptic exposure do not account for the differences between the normal and schizophrenic subjects. Taking together their small caliber, vertical orientation, localization in superficial layers, and marked glutamate immunoreactivity, it seems plausible that the fibers showing an increased density in schizophrenics may be glutamatergic afferents, possibly ones that are associative in nature.(ABSTRACT TRUNCATED AT 250 WORDS)


Temporomandibular joint innervation in rats: a horseradish peroxidase study. In the present study, we have used the horseradish peroxidase (HRP) retrograde transport technique to map the trigeminal primary afferent and motor neurons that innervate the temporomandibular joint (TMJ) and the lateral pterygoid muscle (LPM). One to 3.0 microL of 4% wheatgerm agglutinin conjugated horseradish peroxidase (HRP-WGA) solution was introduced unilaterally into the joint cavity of twelve Sprague-Dawley rats. Injections were made from the above, following trephining of the zygomatic arch with a dental bur. Seventy-two hours after surgery, the animals were sacrificed via perfusion-fixation through the left ventricle. The TMJ, both trigeminal ganglia and brain stem were removed, sectioned serially at 50 microns, and reacted according to the tetramethyl benzidine (TMB) technique of Mesulam. Tissues were then examined at the light microscopic level. The injection site showed that the HRP-WGA filled the upper chamber of the TMJ cavity and extended anteriorly to include the LPM. HRP injected into the joint cavity was transported retrogradely to the ipsilateral trigeminal ganglion, where numerous HRP labeled neurons were found. The greatest number of cells were localized in the dorsolateral posterior portion of the ganglion. In the brain stem, numerous labeled cells representing the motor innervation of the LPM were found in a crescent-shaped array on the ventral side of the trigeminal motor nucleus. No labeled cells were found in the mesencephalic nucleus. The results show substantial trigeminal sensory innervation of the TMJ and LPM with no central projection to the mesencephalic nucleus.


Successful treatment of two viable tubal pregnancies by two-step local injection. Two viable tubal pregnancies were diagnosed by transvaginal ultrasound with a serum beta-hCG level of up to 3,004 mIU/mL in Case 1 and 16,676 mIU/mL in Case 2. Under transvaginal sonographic guidance, a local injection of potassium chloride (0.5 mL = 1.0 mEq) into the embryo was performed for the purpose of embryocide. In Case 1, a follow-up of serum beta-hCG levels showed an initial plateau and subsequent regression to negative, 49 days after the local injection. However, a persistent increase in serum beta-hCG levels was noted in Case 2 for two samples at intervals of two days during follow-up, 27,800 and 36,500 mIU/mL, in spite of the fact that no fetal cardiac activity was visible. Six days later, laparoscopy was done and methotrexate, 50 mg in 6 mL of normal saline, was injected into the ampullar mass of the right fallopian tube in two divided dosages. The serum beta-hCG levels then gradually decreased and returned to negative 60 days after the methotrexate injection. For a viable ectopic pregnancy, this new modality of two-step local injection, first with potassium chloride and then with supplemental methotrexate, separately by two procedures, may offer an additional choice of conservative treatment.


[Molecular genetics of the human brain]. The review discusses the contribution of molecular genetic studies to the understanding of human brain performance and defines three genetic objectives: 1) to reveal structural or functional features of brain genes specific merely to man; 2) to outline the complete spectrum of genes involved in brain activity and their regulation; 3) to search for genes and genetic defects resulting in common mental disorders. The plasticity and great variety of brain functions are shown to be based on the unique diversity of genes actively transcribing in the brain and the molecular mechanisms of various genetic products of the same gene: alternative splicing, "antiparallel" coding, regulation of gene activity by signal DNA sequences. Gene search policies are described for common mental disorders such as schizophrenia, manic-depressive psychosis, Alzheimer's disease. The attempts to map defective genes by "reverse" genetics have proved that there is a genetic heterogeneity of these diseases. The novel directions in the study of the brain molecular genetic apparatus can be examinations of chromosomal behavior in the cells in various brain regions and genome imprinting.


[Nerve growth factor and the state of serotoninergic system in endogenous depression and mental retardation]. Platelet parameters of the serotonin system were studied in patients with endogenous depressions and children with late documented phenylketonuria (PKU) before and after antidepressive therapy. There was a significant decrease in the rate of back platelet uptake of 3H-serotonin and an increase in the sensitivity of serotonin receptors to serotonin in the patients before therapy and normalization of these parameters after therapy. The normalization correlated with clinical improvement in patients with endogenous depression. The course therapy with L-DOPA and the antidepressant azaphen resulted in a substantial mental improvement in children with PKU. There was a significant reduction in the ability of platelets from the patients in question to react by releasing 3H-serotonin in response to nerve growth factor stimulation of cells in vitro.


[Longitudinal approaches to the problem of clinical heterogeneity of Alzheimer-type dementia]. A total of 160 patients with Alzheimer-type dementias (ATD), including 84 with Alzheimer's diseases (AD) and 76 with senile dementia (SD), were examined. The initial signs of the disease were analyzed by making a retrospective assessment of informative history data. The prospective follow-up involved clinical, neuropsychological and electrophysiological (EEC mapping, evoked potentials) studies by applying the standardized assessment of results. There was shown to be a set of clinical and paraclinical parameters for the status of ATD patients, indicating a distinct-quantitative and qualitative difference between patients with AD and those with SD and supporting the heterogeneity of ATD.


[Higher forms of brain activity and psychology]. On the examples of comparison of the evoked potentials with a theory of signal identification (A. M. Ivanitsky) and need-informational theory of emotions (P. V. Simonov) with the "general law of human emotions" (D. Price, J. Barrell) the efficiency is demonstrated of the simultaneous study of the higher brain functions by neurophysiological and psychological methods. Recent experimental data are given on the natural-scientific bases of consciousness. Human personality is considered as an individual unique composition and internal hierarchy of his vital, social and individual needs. Acknowledgement of the supplementary nature of the objective and subjective analysis of the human behavior helps eliminate the contradiction between the determinism and subjectively sensed freedom of choice.


[Clinical and genetic studies of Alzheimer-type dementia]. The families of 128 probands with Alzheimer's disease (AD) and senile dementia (SD) were studied. Genetical and mathematical analyses were employed to estimate the clinico-genealogical findings. The genetic factors were found to be likely to make some contribution to the origin of Alzheimer-type dementia (ATD). The proportion of afflicted relatives considerably exceeded that of the above dementia patients. Two genetic models (monogenic and multifactorial) were tested. The limit estimations of genetic similarity between AD and SD manifestations both in the monogenic and multifactorial models denied the fact that there is a common major gene responsible for liability to Alzheimer-type dementias. The common gene modifiers were assumed to exist in AD and SD. In addition to the differences found between the types of inheritance in patients with these disease, the following features are: an oligogenic type of inheritance in SD and a quasi-dominant one with incomplete manifestations of homo- and heterozygotes in AD. Studies into the clinical polymorphism of Alzheimer-type dementias in hereditary cases enabled the authors to establish the genetically determined signs and the environmentally induced signs. The predisposing features (premorbid characteristic traits and specific features of mnemic and intelligence) were identified, which allowed the development of Alzheimer-type dementias to be predicted in 80% of women from hereditarily aggravated families.


[Neuromorphology and neurochemistry of senile dementias in the light of studies on glial response]. The present study describes a few morphological and neurochemical disturbances in astroglial cells in senile dementia of the Alzheimer type (SDAT). The greatly elevated number of fibrous astrocytes in brain samples with SDAT is observed. The content of glial fibrillar acid protein is elevated in these cells. Glial filaments are detected to surround lipid centers. Moreover, there are deviations in energy metabolism: a profound decrease in the levels of the brain creatine kinase CKBB that is one of the principle ATP-regulation enzyme. It is suggested that there is a relationship between all the disturbances observed in glial cells of SDAT patients. These disturbances are likely to be links of the same process which leads to abnormal brain ageing.


[EEG-mapping in Alzheimer-type dementias]. EEG topographic correlates of the severity and type of Alzheimer-type dementias have been studied in 21 patients with senile dementia (SD) and 18 with Alzheimer's disease (AD) who were subdivided into smaller groups by MMSE grades for the severity of dementia, as well as in 15 mentally normal elderly persons. EEC maps in SD and AD patients differed from those in normal subjects in increased theta-delta EEG spectral power and suppressed alpha-band power that was more pronounced in the left hemisphere in AD than in SD patients. AD and SD patients had also different EEG topographical changes with intensified cognitive dysfunctions. The results suggest that there is a great cholinergic deficiency and cortical rather than subcortical impairments in patients with AD than in those with SD.


[Computerized tomography approaches in the study of dementia]. Computed tomography was used to study the prevalence rates of various types of intracranial pathology, hydrocephalus (HDC) and cortical atrophy (CA) in patients with late dementia (LD) and to comparatively assess the informative value of tomographic methods of cerebral morphometry. Computed tomographic data were obtained from 432 patients with LD. Despite the type of dementia, the authors revealed intracranial abnormalities of various etiology in 24.5%, postischemic foci being prevalent. Tumors, arachnoidal cysts, and chronic subdural hematomas were more infrequently diagnosed (in 2.6% of cases). HDC and CA were detected in 81.5 and 82.2% of patients with LD, respectively.


[Comparative analysis of indicators of the immune status of population of the Eastern regions of the USSR]. Altogether 1,500 healthy residents of seven cities situated in the Asian part of the USSR were examined. In Novosibirsk, Tomsk, Tyumen, Norilsk, Magadan, Yakutsk and Ussuriisk, the people were examined for the blood levels of T and B lymphocytes, the ratio of regulatory subclasses of T lymphocytes, the concentration of IgG, IgM and IgA, and for the content of immune complexes. Analysis was made of the general and regional regularities in changes seen in the immune system depending on climatic and geographic factors. Parameters of the populations similarity in the regions with different environmental conditions were delineated.


[Physiological significance of gastroduodenal blood flow and possibilities of its regulation by drugs]. The authors review the role of the gastroduodenal blood flow as a factor ensuring the secretory activity and protective properties of the gastric mucosa. The possibilities of its pharmacoregulation are also reviewed. It has been shown that the decrease of the gastric blood flow in experimental hemorrhagic shock, extravasal celiac artery stenosis, effects of indomethacin, vasopressin, etc. leads to ischemic injuries to the gastric mucosa accompanied by serious morphological and functional disturbances. The pathogenetic aspects of ischemic injuries to the stomach and duodenum are confirmed by the results of clinical examinations of patients with compression celiac artery stenosis and peptic ulcer. It has been noted that in these patients, the tissue blood flow in the mucosa in considerably decreased in the area of ulcerous defect. The lowering of the content of total phospholipids and changes in their composition were also observed both in relapse and after healing. Out of agents that improve peripheral circulation, propranolol, tavegil combined with cimetidine, trimin appeared most potent. These drugs regulate metabolic processes in gastric tissue, normalizing blood flow, reducing the content of histamine, serotonin, lipid peroxidation products, raising the level of total phospholipids and pepsin.


[Current aspects of the search of effective nootropic drugs]. The authors review different mechanisms of mnemotropic and cerebroprotective effects of nootropic drugs. The data concerning the molecular mechanisms of action of the structural analogs of the memory stimulant ethylnorantifeine (etimizol) have been summarized and analyzed. It is shown that the effects of antifeines on the retention of the conditioned reflexes are independent of their effects on the cAMP system and structural-functional condition of the neuronal membrane. The key role in the action of these compounds on the long-term memory is played by the activity of the genetic apparatus. The existence of nootropic receptors in neuronal chromatin is assumed.


[Computed cluster analysis of citations as a tool in studying structures of research trends]. The method of computer cluster-analysis of citation to determine the structure of a scientific trend is suggested. The map of the current status of research in neurobiology of aging as one of the most promising research areas in gerontology is under consideration. The possibilities and perspectives of this method as a tool of science-of-science research in medicine are analyzed.


[Ways of prolonging the action of neuropeptide]. The paper presents a review of main ways for prolonging the action of neuroregulators (neuropeptides). The method of long-term inverse immunoregulation of immunoregulator levels is regarded as one of the most effective.


Cytoskeleton of podocytes in vertebrate animals and human. Using TEM and immunofluorescence microscope, a study was made on podocytes in vertebrates where an intermediate-sized filament system is replaced by a microtubule system, accompanied by highly developed microfilaments structures. A comparative immunofluorescence study was carried out on cryotome renal sections of plaice (Pleuronectes platessa L.) and rats, using specific antibodies anti-cytokeratins and anti-vimentin. With polyclonal anti-vimentin serum the capillaries of the renal glomeruli showed a bright colour of plaice and only a week one in the rats. Double staining of renal tissue of mongrel rats of different ages (6-7 weeks and 1.8 years old) with antibodies for actin and anti-vimentin polyclonal serum revealed in young rats an intensive fluorescence for actin and a slight fluorescence for the intermediate filaments. Renal glomeruli of old rats demonstrate a strong vimentin-activity and lower actin one. The ultrastructural study of human podocytes showed two different cytoskeleton age-depending types (2, 4, 6, 37 and 65 years old). It is suggested that during individual development and ageing in kidneys of higher animals and human, physiological changes induce morphological cytoskeleton restructuration accompanied by intensive development of intermediate filaments and simultaneous "involution" of microtubules and microfilaments.


Biochemical evidence associating membrane-encapsidated particles with reverse transcription in human gastric cancer. We provide biochemical evidence demonstrating that membrane encapsidated structures present in terminal gastric patients share similar features with retrovirus-like particles. Purified particles reveal few polypeptides, one of them glycosylated. A ribonucleoprotein core-like component is recovered which retains the DNA-polymerizing activity and contains at least one RNA component which can be efficiently translated in vitro.


Immunostaining of nucleolus organizers in mammalian cells by a human autoantibody against the polymerase I transcription factor UBF. A mammalian autoantigen of the nucleolus organizing regions (NORs) was identified by a human autoantibody from the serum of a rheumatoid arthritis patient. The distribution and changes of NORs during the cell cycle of mammals were followed by using this autoantiserum in indirect-immunofluorescence microscopy. In interphase cells the staining pattern indicated that the autoantigen is restricted exclusively within the nucleolus. This fluorescence appeared punctuated rather than uniform, and it was reorganized during inhibition of transcription in cells treated with actinomycin D. During mitosis, the autoantigen was detected by light microscopy at the chromosomal nucleolus organizer regions, indicating that presumably the protein remains bound to the rRNA genes. Biochemical analysis by immunoblotting showed that the NOR autoantigen consists of two polypeptides with molecular masses apparent of 90-92 kDa in all of the mammalian cell lines tested. The identity of some epitopes, recognized by this autoantibody as the ribosomal transcription factor UBF, is discussed.


Evaluation of residual disease in B-cell chronic lymphocytic leukemia patients in clinical and bone-marrow remission using CD5-CD19 markers and PCR study of gene rearrangements. We evaluated minimal residual disease (MRD) in 23 CD5 + B-chronic lymphocytic leukemia (CLL) patients who achieved clinico-hematological remission confirmed by bone-marrow biopsy. MRD was evaluated by dual marker analysis flow-cytometry using CD5 and CD19 markers, and by the study of Ig heavy chain gene rearrangements using the fast polymerase chain reaction (PCR). According to our laboratory conditions patients were considered to be in complete phenotypic remission when total CD19+ cells were < 25% and the ratio of CD5 + CD19 + /CD19 + cells was < 25%. According to these strict criteria only 9 of the 23 patients were in complete phenotypic remission. In order to evaluate the sensitivity of the above method, PCR analysis of the configuration of the Ig heavy chain gene region was performed in 12 of these patients. Five of 7 patients in complete phenotypic remission retained a detectable monoclonal rearrangement of the Ig heavy chain gene. For the remaining 5 patients in partial phenotypic remission, only one failed to show a monoclonal band and this is probably explained by the presence of an unusual gene rearrangement. In conclusion, this study suggests that PCR is more sensitive than dual marker flow-cytometry for evaluation of residual disease and that it is indeed possible to achieve complete remission at the molecular level, in B-CLL. Nevertheless, we suggest a word of caution as this was a retrospective study, and samples were not assessed before treatment. Thus the possibility that apparent molecular remission might correspond to unusual gene rearrangements cannot be completely excluded in these cases.


Right ventricular outflow tract obstruction due to extrinsic compression by non-Hodgkin's lymphoma: importance of echocardiographic diagnosis and follow up. Acquired right ventricular outflow tract obstruction due to extrinsic compression of the pulmonary artery is a rare manifestation of non-Hodgkin's lymphoma (NHL). We report a case of a 17 year old boy who was referred for evaluation of a large anterior mediastinal mass, causing dyspnea and cough and resulting in a harsh systolic murmur. Echocardiography demonstrated compression of the pulmonary artery by the mass, with a severe pressure gradient. Biopsy revealed intermediate grade, diffuse large cell NHL. Systemic chemotherapy rapidly led to a significant decrease in the size of the mass, and virtual disappearance of the pressure gradient. In this report, the use of echocardiography for diagnosis and follow up of extracardiac tumors is reviewed. It is suggested that this technique may also be useful for the routine staging of mediastinal lymphomas because of the potential consequences of clinically undetectable hemodynamic compromise.


PCR-mediated cloning of HpaII tiny fragments from microdissected human chromosomes. Vertebrate DNA contains a small fraction of unmethylated CpG-rich DNA sequences, many of which include the 5' end of a gene. This fraction can be detected by its cleavage to tiny fragments with the methylation-sensitive restriction enzyme HpaII. Thus, the isolation of HpaII tiny fragments (HTFs) from a specific chromosome region may be a useful approach for making an inventory of the genes contained in it. Using microdissection, we have isolated DNA from human chromosome band 8q24.1. The DNA was digested with HpaII, ligated to a ClaI-cut pUC plasmid, and amplified with Taq DNA polymerase and the standard M13/pUC forward and reverse sequencing primers. The amplification products were used to construct an HTF library, which is enriched for CpG-rich single-copy clones.


Detection and identification of multiple mycobacterial pathogens by DNA amplification in a single tube. A comparison of the DNA sequence of the 16S rRNA revealed a region in which there was a minor variation between the species of mycobacteria. This information was used to develop a multiplex amplification system that could identify the genus Mycobacterium and then distinguish between M. avium and M. intracellulare, two commonly encountered mycobacteria other than tuberculosis. The combination of these rRNA gene primers together with primers aimed at the MPB70 gene of M. tuberculosis complex organisms permits the detection and identification of clinically significant mycobacteria in a single tube. An amplification product of 1030 bp is indicative of the genus Mycobacterium and smaller fragments of 850, 372, and 180 bp are the positive signals for M. intracellulare, M. tuberculosis complex, and M. avium, respectively.


In situ localization of PCR-amplified human and viral cDNAs. We describe a technique, called reverse transcriptase (RT) in situ PCR, whereby RNA may be nonisotopically detected in fixed cells when amplified by PCR after cDNA synthesis by RT. RT in situ PCR using primers specific for the measles virus generated an intense signal in most measles-infected HeLa cells, as compared to the weak signal generated in few cells using standard in situ hybridization analysis. The viral RNA that localized to the nucleus spared the nucleoli, was most evident when the RT step used the primer complementary to the negative genomic strand, and was demonstrated in all multinucleated cells and the majority of uninucleate cells. A hybridization signal was evident with standard RNA in situ hybridization using the human megakaryocyte cell line Dami and a probe for glycoprotein IIB (GIIB) mRNA but not a probe for amyloid precursor protein (APP) or gelsolin (GEL) mRNA. After RT in situ PCR, signals were evident for each target localizing to the nucleolus for APP and to perinucleolar and cytoplasmic locations for GEL and GIIB. The latter findings suggest that mRNAs may follow different geographic pathways as they progress from premessage to transcriptionally active message.


Development of a sensitive reverse transcriptase PCR assay, RT-RPCR, utilizing rapid cycle times. We describe a procedure to analyze rare gene transcripts quantitatively using a reverse transcriptase-polymerase chain (RT-PCR) reaction. RNA purified from cells and tissues is reverse-transcribed using random hexamer primers and is amplified using very short cycle times. The products are trace-labeled with [32P[dCTP, which allows for the quantitation of the products by gel electrophoresis and excision of bands. The quantity of the PCR product is directly proportional to the quantity of cDNA added and is reproducible from a single cDNA preparation or from samples derived from separate preparations. Because cDNA synthesis is primed with random oligonucleotides, the same cDNA sample preparation can be examined for many different gene products.


[Secretory meningioma].

[Secretory meningioma]. Pseudopsammomatous inclusions were found in two cases of secretory meningioma. Their description includes ultrastructural and immunohistochemical features.


Effect of bredinin on the primary culture of fetal mouse cells and adult mouse lung cells. The effects of bredinin on the primary culture of fetal mouse cells (fetal cells) and adult mouse lung cells (lung cells) were compared. Bredinin inhibited the growth of both cells, and this inhibition was found to be caused, at least in part, by the inhibition of the S phase and/or the transition from the G1 to S phase of the cell cycle. Bredinin inhibited both DNA and RNA synthesis without affecting protein synthesis. However, the inhibitory effect of bredinin differed between the two cell lines; the fetal cells were more sensitive than the lung cells, and bredinin inhibited DNA synthesis 100 times more potently in the fetal cells. The inhibition of DNA synthesis by bredinin in the fetal cells was gradually lowered by in vitro aging of the fetal cells to a level similar to that in the lung cells. There was no difference in the rate of incorporation of bredinin into the cells between the fetal cells and the lung cells. When fetal tissue was used as an enzyme source, bredinin was converted to bredinin 5'-monophosphate (BMP), but when lung tissue was used, bredinin was not converted. This is in agreement with the finding that bredinin has selective toxicity on fetuses in vivo but is hardly toxic to adult cells, which suggests the involvement of BMP in the selective toxicity of bredinin on the fetus.


Immunosuppressive drugs.

Immunosuppressive drugs. The success rate of clinical transplantation has improved considerably over the last two decades largely due to better immunosuppressive drugs. Allograft rejection remains the major cause of graft loss in renal transplant recipients. This article reviews the mechanisms of action of immunosuppressive drugs and their clinical use.


Macromolecule-macromolecule interaction in drug distribution. II. Effect of alpha-globulin on saturable uptake of fractionated [3H]heparin by rat parenchymal hepatocytes in primary culture. The uptake of fractionated [3H]heparin was investigated in rat parenchymal hepatocytes in primary culture. The initial uptake of fractionated [3H]heparin was found to be saturable with the maximum uptake velocity (Vmax) of 10.1 +/- 1.46 pmol/min/mg protein and the Michaelis constant (Km) of 284 +/- 47.9 nM. The effect of alpha-globulin, the major protein binding to fractionated [3H]heparin, on the saturable uptake profile of fractionated [3H]heparin was also investigated. The uptake clearance was reduced, depending on the concentration of fractionated [3H]heparin, by the addition of 1 mg/ml alpha-globulin. We assumed that fractionated 3H-heparin bound to alpha-globulin was not available for uptake and that the reduction in the uptake clearance was solely attributable to the saturable binding of fractionated [3H]heparin to alpha-globulin. The uptake clearance versus concentration profile was analyzed to obtain the dissociation constant (Kd) of 31.8 nM and the capacity (n) of 0.047 for the binding of fractionated [3H]heparin to alpha-globulin. The saturable binding of fractionated [3H]heparin to alpha-globulin was supported by in vitro binding experiments using gel chromatography, in which bound fractionated [3H]heparin decreased with the concentration of fractionated [3H]heparin in the presence of alpha-globulin. In conclusion, the present study demonstrated the saturable uptake of fractionated [3H]heparin by rat parenchymal hepatocytes and the saturable binding of fractionated [3H]heparin to alpha-globulin. The saturable uptake may suggest the involvement of a specific transport system such as receptor-mediated endocytosis.


Induction of the blood-brain barrier specific HT7 and neurothelin epitopes in endothelial cells of the chick chorioallantoic vessels by a soluble factor derived from astrocytes. Some blood-brain barrier properties of microvascular endothelial cells have been shown to be inducible by astrocytes. We tested the hypothesis that this cellular interaction is mediated by a soluble factor(s). Chick chorioallantoic vessels in ovo were constantly exposed to astrocyte-conditioned medium. We found that endothelial cells exposed to astrocyte-derived factors, but not to glioma- or endothelial cell-derived factors, expressed the HT7 antigen and neurothelin, two specific markers of the blood-brain barrier phenotype. These results indicate that a soluble factor(s) secreted by astrocytes is capable to induce specific blood-brain barrier properties in endothelial cells of non-neural origin.


Patterns of primary degranulation as indicated by the mean myeloperoxidase index (MPXI) during bacteraemia in lymphoma transplants treated with growth factors. The pattern of changes in neutrophil myeloperoxidase (MPO) before, during and after bacteraemia was studied in 34 patients recovering from autologous bone marrow transplantation for relapsed Hodgkin's disease and non Hodgkin's lymphomas. Thirteen patients received haemopoietic growth factors (7 received M-CSF, 3 received G-CSF and 3 GM-CSF). The mean peroxidase index (MPXI) produced as part of a routine FBC performed by a flow cytochemistry blood autoanalyser (Technicon H*1) was used as a parameter to assess the MPO and subsequently the azurophil degranulation. The manufacturer's normal values for MPXI range from -10 to +10. Median MPXI on the day of documented bacteraemia was just below normal in the control and M-CSF groups (-10.8 and -8.9 respectively), but it was much below normal in the G-CSF (-16.5, P < 0.05) and even lower in the GM-CSF group (-39.6, P < 0.02); this correlated well with the decreased bacteraemia incidence in the last two groups. Although contact of neutrophils with bacterial chemoattractants resulted in primary degranulation in all groups, the pattern of changes in MPO content was different, suggesting that neutrophils primed in vivo with various haemopoietins respond to the challenge of microbial agents via different pathways.


On the nature of naming difficulties in aphasia. An extensive naming battery was administered to ten patients representing classical aphasia syndromes. The battery included traditional performance measures and error scoring, phonological cuing, multiple-choice tasks tapping semantic and phonological knowledge, and word repetition tests. Differences in the patients' performance profiles were interpreted as reflecting lexical-phonological, phoneme assembly or multiple deficits. The results suggest that the hypothesized naming deficits have complex relationships to classical aphasia syndromes.


Peculiarities of functioning of protein-synthesizing apparatus of the hibernator (Citellus undulatus). Synthesis of proteins and RNA has been studied by means of labeled precursors of 14C-labeled amino acids and [14C]orotic acid in liver cells of hibernating, arousing, and active ground squirrels (Citellus undulatus). The investigations indicate that cycloheximide (CHI)-inhibited protein synthesis in liver cells of hibernating ground squirrels may occur on preexisting polyribosomes. A low level of protein synthesis in this state results not only from the Arrhenius dependence, but also from the dissociation of polyribosomes into monosomes. During arousal there is an intensive assembly of polyribosomes. This occurs even with the inhibition of RNA synthesis by actinomycin D, testifying to the presence of a pool of iRNA in liver cells, which is necessary to activate translation. The intensity of protein synthesis in arousal is also influenced by the activation of transcription.


Evaluation of the Gen-Probe PACE II assay for the direct detection of Neisseria gonorrhoeae in endocervical specimens. Evaluation of a non-isotopic DNA-rRNA hybridization assay [Probe Assay-Chemiluminescence Enhanced System (PACE II, Gen-Probe, San Diego, CA)] for the direct detection of Neisseria gonorrhoeae from clinical specimens was compared with culture. Culture and probe tests were performed on 795 endocervical specimens. Results demonstrated that total positives by culture were 18 (2.3% of total); both culture and the DNA-rRNA assay agreed in all cases but four. The PACE II yielded four hybridization-positive results with negative companion cultures. The sensitivity, specificity, and positive and negative predictive values for PACE II were 100%, 99.5%, and 82%, and 100%, respectively. The four discrepant results were resolved using a competitive nucleic acid hybridization assay with recalculated sensitivity, specificity, and positive and negative predictive values of 100, 99.7, and 91.6 and 100%, respectively. Overall, the DNA-rRNA assay offered a number of advantages over culture. The assay was more rapid, able to be performed directly on clinical specimens, and provided superior transport stability.


[Detection of serum antibody against hepatitis C virus in patients with hepatitis and liver diseases]. Antibody against hepatitis C virus (anti-HCV) was tested in 658 cases of hepatitis and liver diseases with ELISA, ninety of these cases were positive, with a total infection rate of 13.68% (90/658). The positive rate of anti-HCV was highest in patients with chronic severe hepatitis (33.78%) and CAH accompanied by cirrhosis of liver(31.58%). The infection rate in other types of hepatic diseases in order of frequency was as follows: fulminant hepatitis (18.18%), CAH without cirrhosis (15.13%), subacute severe hepatitis (13.43%), CPH (5.88%), primary hepatocellular carcinoma (3.85%), and acute hepatitis (2.42%). Serological markers of HBV infection were detectable concomitantly in 77 of the 90 cases who were anti-HCV positive, but there was no evidence of mutual inhibition of viral replication. There was neither appreciable difference in the level of hyperbilirubinemia in cases of hepatitis with or without anti-HCV, nor significant diversity in the number of death between cases of severe hepatitis with and without anti-HCV.


Supportive care in oncology.

Supportive care in oncology. Pain management, nutritional support, and psychosocial support are fundamental services that enhance patients' ability to cope with their cancer and its therapy. The common goal of symptom prevention mandates that each of these supportive services be provided to all patients throughout their cancer experience. Comprehensive cancer pain management begins with identifying the origin of all of the patient's pains and treating each one specifically. Pain prevention can be achieved through around-the-clock opioid administration with as-needed supplements for breakthrough pain and dose titration. Common narcotic side effects such as constipation and nausea also must be prevented. Successful opioid analgesia requires that patient and family concerns regarding addiction and tolerance be dispelled at the outset. Cancer pain prevention can be further optimized with the use of appropriate coanalgesics in response to the pathophysiology of the patient's pains. Cognitive and behavioral therapies may also be useful adjuncts to reduce both pain and suffering. Procedure-oriented pain control should be considered when systemic pharmacologic therapy does not provide adequate pain relief or is associated with intolerable side effects. The only absolute contraindications for pain-relieving procedures are untreatable coagulopathy and a decrease in mental status not related to medical pain management. Useful neurodestructive techniques include radiofrequency lesioning, cryoanalgesia, and chemical neurolysis with agents such as phenol, alcohol, and hypertonic saline. The most beneficial pain-relieving procedures and percutaneous cordotomy, spinal narcotics, celiac and hypogastric plexus ablation, spinal neurolysis, and epidural injection of steroids and hypertonic saline. Procedure selection depends on the cause of the pain and the patient's prognosis. Common indications for pain-relieving procedures include unilateral pain below the shoulder, upper abdominal visceral pains, pelvic visceral pain, perineal pain, vertebral body metastasis, discogenic pain, and spinal stenosis. As results of well-conducted scientific trials begin to appear in the literature, the indications for these procedures will be better understood, resulting in their more appropriate use. Principles of nutritional support in patients with cancer include an awareness of the problem of malnutrition and its impact on performance status, quality of life, prognosis, and treatment; identification of those patients at risk; prophylactic versus therapeutic intervention; and analysis and management of the specific impediment(s) to adequate nutrient intake and absorption. The primary goals for nutritional support in cancer patients are prevention of weight loss and maintenance of adequate protein status. Appreciation of practical issues of nutritional support will enable the practicing physician to achieve these goals using primarily oral nutrition options.(ABSTRACT TRUNCATED AT 400 WORDS)


Effect of a prostaglandin I2 derivative (iloprost) on peripheral neuropathy of diabetic rats. PGE1 has been found to improve the symptoms of diabetic neuropathy. We considered that a PGI2 derivative may also have a similar action and therefore studied its effect in diabetic rats. Iloprost was administered intraperitoneally to streptozotocin-induced diabetic rats at a dose of 10 micrograms/kg/day for a month. The changes in nerve conduction velocity (NCV) were measured in the tail. One day after the last dose of iloprost, both sciatic nerves were removed from each rat, homogenized, and extracted with 6% TCA. The sorbitol and myo-inositol concentrations were determined by a combination of HPLC and an enzymatic method. Cyclic AMP (cAMP) levels were determined by RIA, and Na+, K+ ATPase activity was assessed by the enzyme cycling method of Greene and Lattimer. Iloprost was found to improve the NCV in the diabetic rats. The sorbitol content was not affected by iloprost, but the myo-inositol content was higher in the iloprost group than in the untreated group, although the difference was not statistically significant. The Na+, K+ ATPase activity and cAMP content were significantly higher in the iloprost group than in the untreated group. These findings suggest the possibility that the cAMP-dependent protein kinase (A-kinase) system has an important influence on improvement in Na+, K+ ATPase activity.


Human motor evoked responses to paired transcranial magnetic stimuli. We studied the changes in motor pathway excitability induced by transcranial magnetic stimulation of the motor cortex, using paired stimuli (conditioning and test stimulus) and varying interstimulus interval (ISI). The effects induced depended on the stimulus intensity. At a low intensity, there was inhibition of the response to the test stimulus at ISIs of 5-40 msec, followed by facilitation at ISIs of 50-90 msec. At a high intensity, there was facilitation at ISIs of 25-50 msec, followed by inhibition at ISIs of 60-150 msec and, occasionally, by another phase of facilitation at ISIs of more than 200 msec. Only tentative explanations are currently possible for these effects: the inhibition observed at low intensities and short ISIs may be due to activation of cortical inhibitory mechanisms. The facilitation that follows may arise from the coincidence of various factors that transiently increase the excitability in alpha motoneurons. The early facilitation observed at high intensities seems to be a consequence of a rise in cortical excitability induced by the conditioning stimulus, causing an increase in the number or size, or both, of descending volleys from the test stimulus. The profound inhibition that follows probably results from a combination of both segmental and suprasegmental inhibitory mechanisms.


Early and late lower limb motor evoked potentials elicited by transcranial magnetic motor cortex stimulation. Transcranial magnetic motor cortex stimulation can elicit a series of responses recorded with different latencies from relaxed muscles of the lower limbs. In 7 healthy subjects, ranging in age from 16 to 62 years, stimulation was delivered by a 9 cm coil centered over Cz with the subject in the supine position. Surface polyelectromyography was used to record motor evoked potentials (MEPs) from the quadriceps (QD), hamstrings (HS), tibialis anterior (TA) and triceps surae (TS) muscles bilaterally. Three characteristic responses were identified in each muscle group on the basis of amplitude and latency criteria, identified by latencies: the direct oligosynaptic response MEP30 appeared with a latency of 24.3 msec in the QD, 26.3 msec in the HS, 30.5 msec in the TA and 31.3 msec in the TS; MEP70 with latencies of 64 msec in the QD, 59 msec in the HS, 79 msec in the TA and 72 msec in the TS; MEP120 with latencies of 115 msec in the QD, 126 msec in the HS, 117 msec in the TA and 124 msec in the TS. These 3 responses have distinct latencies, amplitudes and durations. MEP70 appears to be the result of activation of long descending tracts which end on spinal interneuronal circuits. As MEP120 has different features, it may have a different mechanism.


Transcranial cortical stimulation. Late excitability changes in the soleus and anterior tibial motoneurone pools. The effect of conditioning magnetic transcranial cortical stimulation (TCCS) on the excitability levels of the soleus and anterior tibial motoneurone pools was studied by Hmax/2 technique 40-400 msec after the stimulus. The target muscles were relaxed throughout the tests. Two periods of facilitation (the first at 80-100 msec and the second at 180-200 msec) were found. They shared approximately the same latencies as the late responses (S100 and S > 150) that we have previously recorded following TCCS. A period of inhibition that started at 150 msec was also recorded. A period of facilitation could also be noted when the conditioning stimulus was applied either over the deltoid muscle or when the click that accompanied the magnetic pulse was used. This suggests that brain-stem areas related to those of the startle reaction play an important role for the appearance of the facilitatory changes. The necessary input probably comes from both peripheral and cortical sources.


Cortical projection to erector spinae muscles in man as assessed by focal transcranial magnetic stimulation. We stimulated the motor cortex in 9 subjects using focal transcranial magnetic stimulation with a figure of 8 coil in order to examine the cortical representation of the erector spinae muscles. Recordings were made from the erector spinae 3.5 cm lateral to the third lumbar vertebra. In 5 subjects clearly reproducible responses could be obtained which had a latency compatible with transmission via fast conducting fibers in a mono- or oligosynaptic pathway. In the remaining 4 subjects responses were poorly defined. Latencies in surface recordings varied between 13 and 24 msec but were longer when needle recordings were used. Mapping of the motor cortex was performed by moving the coil in 2 cm steps on either side of Cz. Different patterns of hemispheric representation were found ranging from a contralateral projection in either hemisphere to a representation of both back muscles in one hemisphere (2 subjects). Responses were followed by a silent period. The latter was interrupted or terminated by a response between 52 and 85 msec post stimulus which was found predominantly in the muscle ipsilateral to the side of stimulation.


Assessment of corticospinal and somatosensory conduction simultaneously during scoliosis surgery. The function of descending motor pathways and that of ascending sensory pathways in the spinal cord were monitored at the same time in 120 patients undergoing surgery for scoliosis. Transcranial electrical stimulation of the motor cortex was performed simultaneously with stimulation of the tibial nerves in the popliteal fossae, and the descending and ascending volleys were recorded from the spinal cord at two levels using epidural electrodes. Stable recordings of both volleys have been obtained in all neurologically normal patients and in many with pre-existing neurological deficits. The experimental conditions which resulted in reliable recordings were explored in select patients and include: a vertex-anode/lateral cathode montage for transcranial stimulation, epidural recording of evoked corticospinal and somatosensory volleys at two spinal levels, a high-pass filter of 500 Hz, and stable anaesthesia. The epidural recording allows full muscle relaxation and the use of volatile anaesthetics; recording at two levels allows a deterioration in function to be identified quickly and distinguished from an artifactual change.


Suppression of cutaneous perception by magnetic pulse stimulation of the human brain. We have demonstrated that magnetic pulse stimulation of the sensorimotor cortex suppresses perception of threshold electrical stimuli to the fingers of the contralateral hand. Maximum suppression of perception occurs when the fingers are stimulated 30-90 msec after the magnetic pulse. Thereafter, errors in perception of the cutaneous stimulus decrease to control levels by 300-400 msec after the magnetic pulse. The period of maximum suppression of perception coincides with the period during which cortically generated somatosensory evoked potentials (SEPs) are enhanced following magnetic pulse stimulation of the brain. The duration of suppression of perception, however, outlasts the duration of SEP enhancement. When the magnetic pulse is delivered after finger stimulation there is also suppression of perception. The suppression of perception is maximal when the magnetic pulse occurs 20-30 msec after finger stimulation. This interval coincides with the arrival of the afferent volley at the primary sensory cortex.


Simultaneous electromyography and 31P nuclear magnetic resonance spectroscopy--with application to muscle fatigue. The electromyogram (EMG) is often used to study human muscle fatigue, but the changes in the electromyographic signals during muscle contraction are not well understood in relation to muscle metabolism. The 31P NMR spectroscopy is a semi-quantitative non-invasive method for studying the metabolic changes in human muscle. The aim of this study was to develop a method by which EMG and NMR spectroscopy measurements could be performed simultaneously. All measurements were performed in a whole body 1.5 Tesla NMR scanner. A calf muscle ergometer, designed for use in a whole body NMR scanner, was used. The subject had the left foot strapped to the ergometer. The anterior tibial EMG was recorded by bipolar surface electrodes. A surface coil was strapped to the anterior tibial muscle next to the EMG electrodes. Simultaneous measurements of surface EMG and surface coil 31P NMR spectroscopy were performed in the scanner during an isometric submaximal voluntary contraction until exhaustion, in 6 normal volunteers. Concentrations of phosphocreatine (PCr), inorganic phosphate (P(i)) and pH were analysed together with root mean square (RMS) and median frequency of the EMG. The fatiguing contractions (endured 5-13 min) produced a rapid decline in PCr and pH accompanied by a rapid rise in P(i). The RMS was approximately constant until the normalized PCr concentration declined below 0.6-0.7 and the pH declined below 6.75-6.85; exceeding these metabolic limits was associated with a rapidly increasing RMS value (2-3 times the previous level by exhaustion). The median frequency declined linearly with time and was found to be highly linearly correlated with the pH value (r = 0.82).(ABSTRACT TRUNCATED AT 250 WORDS)


Mechanical properties of human ankle extensors after muscle potentiation. The contractile properties of a muscle depend on the activation history of its motor units. At the same time as fatigue seems to impair muscle excitation-contraction coupling, post-tetanic potentiation can augment force production. The effects of post-tetanic potentiation on the mechanical muscle properties of the intact human ankle extensor muscles were investigated by a 4 degree dorsiflexion of the ankle joint during a sustained contraction. The contraction was elicited by 10 Hz electrical stimulation of the tibial nerve. The changes in the contraction torque and in the intrinsic muscle stiffness of the ankle extensors before and after prolonged electrically elicited muscle activation were measured. From the onset of continuous synchronized 10 Hz stimulation to the attainment of maximal torque, the ankle joint torque increased by 47%. At matched background contraction, the prolonged electrically elicited contraction increased the intrinsic muscle stiffness by 49%. The first stretch after prolonged stimulation gave rise to a 17% yield in the background contraction and a 73% yield in the torque increment. The findings imply that with fatigue an increase in the intrinsic stiffness of the pre-stretched muscle might operate as a "safety factor" to compensate for a reduced reflex-induced stiffness, keeping the total muscle resistance at a high level in the active muscle.