Growth patterns, cell composition, and mitotic activity of granulocytic aggregates developing in methyl cellulose from human normal marrow cells. Marrow cells from five normal healthy subjects were cultured in methyl cellulose with and without leucocyte conditioned medium. Cultures were examined daily from day 3 to day 14 for the number of granulocytic aggregates and for their cell composition and mitotic activity. Aggregates of different size (small and large clusters, small and large colonies) displayed four distinct and characteristic patterns of growth. Unidentifiable blast cells were very rare throughout culture. The average proportion of recognizable granulocyte precursors (promyelocytes and myelocytes) (PMC + MC) declined during culture from 60% to 34%. There was a negative correlation between the size of the aggregates and their PMC + MC content, but on any day of culture some aggregates consisted mainly or uniquely of PMC + MC, while some others consisted mainly or uniquely of non-proliferating granulocytes. The mitotic index of PMC + MC was much higher than the one previously determined in vivo, and was significantly higher in large colonies than in other aggregates. These results are consistent with the recent demonstration of different CFU-C (sub)populations. It is suggested that differentiation of the aggregates according to their size and kinetics, coupled with cytological examination, can provide a more refined assessment of the assay, which could be useful for further comparison of normal, abnormal, and leukaemic granulocytopoiesis.


Classification of animal lymphomas: the implications of applying Rappaport's classification for human lymphomas to experimental tumors. One hundred and seventy animal lymphomas (species ranging from molluses to monkeys) were reclassified histologically according to the modified Rappaport classification for human lymphomas. The results were correlated with the etiology of the lymphomas, their clinical course, and in selected cases with their immunological type. The study stresses the value of such a procedure for comparative reasons, allowing a more adequate selection of animal models for human lymphomas.


Trochanter bone marrow: a source of normal human colony forming cells. In vitro studies of human hemopoiesis are often limited by the availability of normal bone marrow. We have overcome this difficulty by taking advantage of the bone marrow fragments removed during total hip replacement. We report here a comparative study of the colony forming capacity of trochanter and sternal or iliac crest marrow from five hematologically normal donors. Our data indicate that trochanter marrow is a reliable source of normal in vitro granulocyte/macrophage colony forming cells.


Hydroxyurea suicide study of the kinetic heterogeneity of colony forming cells in human bone marrow. The kinetics of granulomonocyte colony forming cells have been studied in unfractionated normal human bone marrow by hydroxyurea suicide and in cells separated by velocity sedimentation. Sequential studies revealed two subpopulations of colony forming cells, having different sizes and different multiplication potentialities. There are large cells with a high suicide rate which develop small granulocyte and monocyte colonies during the first week of culture in semi-solid agar. Smaller cells develop larger colonies of granulocytes, monocytes and eosinophils between 2 and 3 weeks of culture. Only granulocyte progenitors have a substantial suicide rate in this small cell population. This population is also less responsive to stimulation than is the large cell class, which is a more highly differentiated progeny. The role of these different kinetics of colony forming cells is discussed in the context of the heterogeneity of the in vitro differentiation of neutrophil, monocyte and eosinophil lines.


An improved plasma culture system for the production of megakaryocyte colonies in vitro. A modified culture system has been developed to grow and quantitate megakaryocyte colonies from mouse bone marrow more efficiently than described in other reports. Using this method, it was shown that 30% of CFU-M in normal marrow cells and 70 to 90% of CFU-M in regenerating marrow cells were killed by high specific activity 3H-TdR in vitro. These results indicate that CFU-M are proliferating even in normal adult hemopoietic tissue, but that the proportion of cells that are proliferating is greater in regenerating marrow than in normal intact mice.


Antiserum to mouse hematopoietic pluripotent stem cells (CFU-S): further investigation of its functional properties. Treatment of mouse hematopoietic cells with heterologous antiserum raised against mouse brain markedly reduces the capacity of pluripotent stem cells (CFU-S) to form surface spleen colonies in lethally irradiated mice. To exclude the possibility that such treatment interferes only with the capacity of CFU-S to form surface spleen colonies, we evaluated the capacity of CFU-S which were treated with rabbit anti-mouse brain serum (RAMBS) to restore hematopoiesis and rescue lethally irradiated mice, and to form microscopic spleen colonies. Marrow cells were treated with RAMBS or control rabbit serum. Fifty thousand treated nucleated cells were injected i.v. into lethally irradiated mice, and hematopoietic reconstitution was studied between days 8 and 15; separate groups of mice were observed for survival. We found that treatment with RAMBS impairs the capacity of marrow cells to repopulate the marrow and spleen with CFU-S, to restore blood RBC, to effect an overshoot in spleen weight, and to prolong survival; in addition it reduces the number of microscopic spleen colonies to the same extent that it reduces the number of macroscopic colonies. Hence, RAMBS appears to effect a general inactivation of CFU-S and should prove to be a useful tool in further investigations of mouse hematopoiesis.


Evidence for proliferation of erythroid progenitor cells in the absence of added erythropoietin. The cellular mechanisms underlying the requirement of leukocyte conditioned medium for human erythroid colony formation has been studied. Using photographic methods it was found that erythroid progenitor cells were able to form small colonies in the absence of added erythropoietin (epo). The addition of epo at this time leads to further growth and hemoglobinization of cells within the colony. Leukocyte conditioned medium was found to be required for this early proliferative stage of erythroid colony formation.


Effect of inflammatory serum on 14C-glucosamine incorporation into bone marrow granulocytes in vitro. As a preliminary approach to developing a biochemical assay for detecting humoral regulators of granulocyte maturation in the normal and inflammatory states, studies were carried out on the effects of normal and inflammatory sera on the incorporation of 14C-glucosamine into the glycoproteins of bone marrow granulocytes in vitro. We observed that, relative to normal serum, inflammatory serum had a marked stimulatory effect on 14C-glucosamine incorporation into these glycoproteins. This property of inflammatory serum reached a maximum at about 8 h after the initiation of inflammation in vivo and preceded the maximum increase in the mitotic activity of granulocyte precursors in the marrow by 18 h. It was also found that normal serum contains both dialyzable and heat-sensitive nondialyzable factors that inhibit 14C-glucosamine incorporation into bone marrow granulocytes in vitro. Data are presented which indicate that the stimulatory effect of inflammatory serum is most likely due to a nondialyzable factor which is capable of blocking the effect of the inhibitors present in normal serum.


The dorsal spino-olivocerebellar system in the cat. II. Somatotopical organization. The somatotopical organization of the projection through the dorsal spino-olivocerebellar path (DF-SOCP) to the c3 zone in the cerebellar anterior lobe was studied by recording climbing fiber field potentials in the cerebellar cortex evoked on stimulation of peripheral nerves. The c3 zone was shown to contain a detailed and systematic representation of the ipsilateral body half with the follwing characteristics: 1. Single nerves project to one or two sagittal strips of cortex which extend across several folia. The width of the strips varies between 0.2 and 1 mm and the length may be as long as 15-20 mm along the unfolded cortex. 2. The strips activated from different nerves occur in an order which usually follows the segmental innervation, the hindlimb being represented rostrally and the forelimb caudally in the zone. 3. The double representation of some nerves makes it possible to distinguish one medial and one lateral part of the c3 zone with the projection areas organized approximately as mirror images. Additional observations on other zones activated by the DF-SOCP system (Ekerot and Larson, 1979a) indicate that the c1 zone, has a somatotopical organization which is reminiscent of that of the c3 zone, whereas the x and d1 zones have different topographical organizations.


An electrophysiological study of thalamo-caudate neurones in the cat. Thalamo-caudate projection neurones were identified in cats by antidromic activation from the caudate nucleus, under chloralose anaesthesia or in cerveau isolé preparations. Units in nuclei centralis lateralis, medialis dorsalis, and centrum medianum-parafascicularis responded antidromically to one or more electrodes of a caudate nucleus array at latencies ranging from 0.4 to 16 ms. The responses did not appear to result from stimulus spread to the internal capsule. A separate population of medial thalamic units responded postsynaptically to caudate stimulation, at modal latency exceeding modal antidromic latency by 2 ms. Comparison of apparent conduction velocities for each thalamic nucleus indicated that the postsynaptic responses were activated by collaterals of thalamo-caudate neurones. A proportion of thalamo-caudate neurones responded to somatic stimulation; some of these were inhibited by caudate stimulation, and a few discharged on substantia nigra stimulation. These results demonstrate the possibility of somatic afferent and nigrofugal inputs to the caudate nucleus mediated by neurones of the medial thalamus.


Functional properties of pulvinar-lateral posterior neurons which receive input from the superior colliculus. Focal electrical stimulation of the superior colliculus induced short latency responses and/or a long duration suppression of spontaneous activity in single cells isolated in the pulvinar and lateral posterior (LP) nuclei of the cat. Cells which responded with one or more spikes at short latencies were relatively few in number, and these tended to be encountered in or near the principal tectorecipient zone of LP. In contrast, a suppression response was observed in many more cells which were widely distributed throughout the pulvinar-LP complex. Stimulation of the superficial layers of the colliculus was more effective in driving or suppressing pulvinar-LP cells than that of intermediate and deep layers. There was also an indication of a coarse topography in this projection. On the basis of their sensory response properties the cells responsive to tectal stimulation, at short latency or with a suppression, could not be differentiated from the overall sample of pulvinar-LP neurons.


A method for localized and longlasting microapplication of drugs into nervous tissue of freely moving animals. A method is described for localized microapplication of drugs into nervous tissue of freely moving rats. Fairly constant release of material was observed over a period of more than three weeks. The amount of substance released was small because the rate of release was determined largely by diffusion rather than by mass movement of solution.


The elongation of fatty acids by microsomes and mitochondria from normal and pyridoxine-deficient rat brains. The developmental profile of fatty acid elongation enzymes of rat brain microsomes and mitochondria and the consequences of pyridoxine deficiency have been investigated. The results suggest that a single enzyme system is responsible for elongation of the various fatty acids by mitochondria whereas the microsomal elongation system is diverse.


Activity of ventrolateral thalamic neurons in relation to a simple reaction time task in the cat. Unrestrained cats performed ballistic forelimb flexion movements triggered by an auditory stimulus (CS) on a simple reaction time (RT) paradigm. During the variable foreperiod the subject was required to hold down a lever and to release it on presentation of the CS. The RTs ranged from 200 to 300 ms. The activity of single neurons of the ventrolateral nucleus of the thalamus (VL) was recorded bilaterally. More than 40% of the 166 units recorded in the VL contralateral to the performing limb presented, after the CS, changes of activity with a latency less than 100 ms and were classified into three types: (1) Twenty-five units had a short latency transient increase of activity 10 to 30 ms after the CS, followed by a longer increase or decrease in activity. Short latency increase as well as subsequent increase of the firing rate were not correlated to the RTs. (2) Twenty-nine units showed a 40-60 ms latency increase of activity which lasted long enough to continue during the forelimb movement. These units displayed a correlation between the RTs and the mean firing rate measured in the 40-100 ms period  after the CS. The more the cells were activated, the shorter the RTs. (3) Fifteen units presented a reciprocal pattern of discharge with respect to the type (2) units. The firing rate decreased with latencies ranging from 20 to 90 ms after the CS. Only 14,5% of the 96 units recorded in the VL ipsilateral to the performing limb presented changes of activity starting in the 100 ms period following the CS. Background firing levels as well as phasic activity were rather low compared to those observed contralaterally. Sixteen units showed burst activity while the cat was performing but burst pattern was not time-related to the task. In an unconditioned animal, a very low level of activity and an absence of modulations were observed in both VLs.


Effects of early visual and complex stimulation on learning, brain biochemistry, and electrophysiology. A complex stimulation regimen (visual, auditory, and somesthetic-kinesthetic with forced movements, 30 times for 30 min each within 14 days) increased significantly the amplitudes of visual cortical evoked potentials (EPs) in adult rats if applied during the second postnatal fortnight. The EP increase after stimulation during the first 14 days after birth was not significant. Visual stimulation alone was compared with complex stimulation (visual plus forced movements) during the 2nd postnatal fortnight. More specific local changes in the visual cortex were revealed in brain biochemistry (lower DNA concentration, more RNA and protein per cell) and cortical electrogenesis (enhanced visual EPs) after visual stimulation alone, whereas complex stimulation induced more diffuse changes and rather profoundly influenced higher nervous functions (viz., memory retrieval - improved 24-h). Involvement of both specific and nonspecific mechanisms in the aftereffects of early stimulation is indicated.


Pontine and non-pontine pathways mediating early mossy fiber responses from sensorimotor cortex to cerebellum in the cat. Stimulation of the cat's sensorimotor cortex evokes a short-latency mossy fiber field potential (N2) in the pars intermedia of the cerebellum. The fraction of the response carried by each of the six cerebellar peduncles was determined by comparing the field potentials before and after electrolytic lesions of individual cerebellar peduncles. The response evoked from the contralateral cerebrum is 3.5 times as large as that evoked from ipsilateral cerebrum. The size of the N2 wave from contralateral cerebral cortex is reduced to about half of the original size after electrolytic lesion of either the brachium pontis (BP) or the restiform body (RB) ipsilateral to the recording site, while only a small reduction in the size of N2 is observed after lesions of contralateral BP and RB. This indicates that inputs responsible for the generation of the N2 wave from contralateral cerebral cortex enter the cerebellum primarily through ipsilateral BP and RB. In contrast, the N2 wave from ipsilateral cerebral cortex is reduced by approximately one quarter following lesions of any one of the four RB's and BP's. Fibers in the brachium conjunctivum do not contribute to these responses. Observation on the P2 field potential, representing postsynaptic firing of granule cells, suggest that the cerebro-ponto-cerebellar and cerebro-reticulo-cerebellar mossy fiber pathways converge onto granule cells. Furthermore, these two inputs must arrive within 3 ms of each other in order to activate the granule cells. In addition, it is shown that BP lesions reducing the mossy fiber input lead to an increase in the climbing fiber input.


Evoked potential evidence for differences in binocularity between striate and prestriate regions of human visual cortex. For two components of the visual evoked potential elicited by the onset of a stationary pattern the degree of interocular transfer of the attenuation caused by prior exposure to a similar pattern was measured. The results show almost complete interocular transfer for component CII, thought to originate in prestriate cortex, but only partial transfer of CI, thought to be of striate cortical origin. This suggests that in man, as in monkey, monocularly driven neurones are more common in striate than in prestriate cortex.


A supernormal period in central axons following single cell stimulation. Intracellular recordings were obtained from caudate (Cd) nucleus efferent neurons in the cat. A supernormal period, as characterized by increased excitability and conduction velocity, was found for the Cd efferent fibers following either a conditioning antidromic action potential, or a single orthodromic action potential induced by direct current application through the recording microelectrode. These data indicate that the impulse activity of a single fiber can modulate excitability and conduction velocity independent of surround impulse activity.


Comparison of dynamic properties of canal-evoked vestibulospinal reflexes of the neck and forelimb in the decerebrate cat. The responses of neck and forelimb muscles to sinusoidal polarization of the horizontal canal nerve were compared by recording from these muscles simultaneously. Contrary to results on the vestibulocollic reflex, the central phase lag in the vestibulo-forelimb reflex increases with increasing frequencies up to 3 Hz. This demonstrates a difference in the organization of vestibular-driven pathways to neck and forelimb muscles.


The parieto-rubro-olivary pathway in the cat. Stimulation of the parietal association cortex as well as the frontal motor cortex elicited clearly extracellular unitary activities or field potentials in the ipsilateral inferior olive in the cat. The parietal-induced responses came out generally at a longer and more variable latency than the frontal-induced ones. This suggested the existence of an indirect pathway from the parietal association cortex to the inferior olive. The recording sites for the parietal-induced responses were located not only in the dorsal lamella but also in the ventral lamella of the principal olive and in the medial accessory olive. Such olivary sites were exclusively in the rostral half of the inferior olive, and these areas in the olive were considered to give projection fibres predominantly to the hemispherical parts of the cerebe-lar cortex (neocerebellum). Small neuronal cells were labelled with horseradish peroxidase (HRP) homolaterally in the midbrain tegmentum, after HRP was injected through recording glass microelectrodes into the inferior olive where only the parietal-induced responses were evidently recorded. These small cells were distributed in the rostral one-third of the red nucleus and/or around the adjacent midbrain reticular formation close to the lateral border of the red nucleus. In referring to recent anatomical and physiological data, such small neurones labelled with HRP could be identified as the parvocellular red nucleus neurones. The present results indicate the existence of the parieto-rubro-olivary pathway system in the cat and suggest, in association with our previous studies, that the parvocellular red nucleus neurones participate in control of highly co-ordinated posture and movement predominantly through the neocerebellum.


Suprachiasmatic nucleus neurones: excitation and inhibition mediated by the direct retino-hypothalamic projection in female rats. The suprachiasmatic nucleus (SCN) of female rats was surveyed with microelectrodes under urethane anaesthesia. In rats with bilateral transection of the optic tracts, repetitive three pulses of 100 Hz applied to the contralateral optic nerve excited 8 and inhibited 11 other of the 86 SCN units examined. Transection of the optic tract did not significantly influence frequency of occurrence of the SCN units that were excited or inhibited by stimulation of the optic nerve. Certain SCN units responded to both of contralateral and ipsilateral stimulations of the optic nerve, indicating that bilateral visual inputs converge on the same single SCN neurones. Oscillatory responses with a period of 100--200 msec were occasionally produced by stimulation of the optic nerve. Flash stimuli with relatively weak intensity, even insufficient for producing wavelets in electroretinograms, produced an excitation and inhibition in SCN units. The mean firing rates were significantly altered by either electrical or flash stimuli repeated 500 times at 0.97 Hz in those units which showed no transitory response. Some of the SCN neurones receiving visual inputs were identified to be the tuberoinfundibular neurone and some other SCN neurones were found to receive converging inputs both from the optic nerve and from the axon collaterals of tuberoinfundibular neurones.


The fine structural organization of the locus coeruleus in the rat with reference to noradrenaline contents. Combination of glyoxylic acid perfusion and postfixation in permanganate was used in an electron microscopic study of the locus coeruleus (LC) of the rat to give good preservation of fine structure and a reproducible demonstration of noradrenaline (NA) storage granules. Medium-sized LC cells (18 x 30 microns) contained a moderate number of small granular vesicles (SGV) and a few large granular vesicles (LGV), mainly near the Golgi apparatus. Dendritic branches were identified by their SGV content up to the tip. Dendrites were occasionally in close contact with each other or with the soma of LC cells, forming dendro-dendritic or dendro-somatic contacts. Numerous axon terminals containing many SGV and some LGV were observed in the neuropil, and they tended to contact dendrites and somata of LC cells or dendrites of unknown origin. These neuronal contacts were devoid of synaptic specializations except for an array of dense perpendicular lines between the juxtaposed membranes. Small oval cells (10 x 15 microns) devoid of SGV occurred frequently in the peripheral part of the nucleus, and they were occasionally in direct contact with LC cells.


Visual modulation of otolith-dependent units in cat vestibular nuclei. Vestibular nucleus units responding to translational self-motion are shown to respond also to translational movement of a large visual field. These visual-vestibular interactions in otolith-dependent units are similar to those found in canal-related units and could provide the basis for linearvection.


Functional deficits in the optokinetic system of albino rats. Vestibular nuclear neurons of the horizontal canal system (Vn) of albino rats (Wistar) failed to respond to optokinetic stimulation. Similarly, optokinetic nystagmus (OKN) could not be elicited in these animals. Brown (DA--HAN) rats, however, consistently showed optokinetic responses of Vn and OKN to identical stimuli.


Abnormal orientation selectivity in both eyes of strabismic amblyopes. In normal observers preadaptation to a parallel grating increases the contrast threshold for a line whereas a perpendicular grating has no effect. Such orientation selectivity was not found in the amblyopic eye of two out of five squinters. Only a weak after-effect produced with a grating parallel to the line was obtained in the good eye of four of the amblyopes while all of them show an abnormal threshold reduction following adaptation to a perpendicular grating. This suggests a relationship between abnormal binocular interaction during visual development and the organization of orientational mechanisms but does not explain the loss of visual acuity in amblyopia.


Impairments in limb actions after dorsal funiculi section in cats. A study of the forces exerted by cats against the ground when jumping from a platform equipped with force transducers, was carried out. The study, complemented by film analysis of the jump, attempted to disclose some of the mechanisms underlying the decrease in efficiency and accuracy in releasing a moving piece of liver observed after dorsal funiculi section above C1 level. The results showed that after the lesion, peak force and height of jump were significantly reduced. However, angle of take-off, an index of force distribution in the three axes of rectangular coordinates remained unchanged. Intact cats consistently extend their forelimbs in a smooth and progressive way toward the liver in order to release it. The distance between the tips of the forelimbs remained more or less constant during the flight. Postoperatively, instead of the regular pattern described, the extension of the limbs was interrupted by fast marked flexion movements and the distance between their tips increased significantly during the flight. Peak extension of the forelimbs was also decreased after surgery. The results are interpreted in terms of the different disruption of the various components (proprio and exteroceptive) that make up fasciculus gracilis and cuneatus of the dorsal funiculi.


The role of maturation and visual experience in the development of eye alignment in cats. In the developing kitten, the alignment of the pupils changes from strongly divergent to almost parallel. The visual axes, however, seem to stay almost parallel throughout this period. The infeluence of early visual experience on this development is examined in the present study. The results suggest that the develpment of eye alignment is not controlled by visual experience, but depends on maturational processes, and that normal visual input serves only to halt these processes at the appropriate time.


A visual stimulator for orbiting light spots and equal energy annuli with continuously variable parameters. When a light spot moves at high angular velocity along a circular path on a screen, an annulus is preceived. This principle is used in a simple annulus generator consisting of a plane mirror that rotates about an axis making an angle alpha with the normal in the center point of the mirror. Angle alpha can be varied with a micrometer screw to change the diameter of the annular path (orbit) followed by the light spot that is projected on a screen via the rotating mirror. This results in variable diameter equal energy annuli. The diameter of the light spot can be changed to manipulate the width of the annulus. Finally, at low angular velocities an orbiting light spot is obtained. It is shown in the companion paper (Molenaar and van de Grind, 1979) that this slow orbiting of the light spot allows a precise study of the fine structure of receptive fields.


Deficits in the visual evoked potentials of cats as a result of visual deprivation. Visual evoked potentials in response to contrast reversal of grating patterns were used as a measure of visual function in normal and visually deprived cats. In cats which had been dark reared from birth (BD cats) there was a characteristic change in VEP waveform from normal, for both eyes and for all spatial frequencies of testing stimulus. In cats which had one eye sutured from the age of one week (MD cats), the VEP from the deprived eye was smaller for contrast reversal of coarse patterns. Kittens given only restricted periods of monocular exposure gave VEPs which resembled the pathological responses of the BD cats. However, the amplitudes of response were larger for the more experienced eye at higher spatial frequency. This work reinforces the idea that two factors govern cortical development: competition and experience. Lack of sufficient visual experience leads to severe intracortical pathology.


Mechanisms of the clasp-knife reflex studied in an animal model. The mechanisms of the clasp-knife reflex were studied in the soleus muscle of an animal model, the decerebrate cat with a dorsal hemisection of the lower thoracic cord. The reflex is shown to be autogenetic, and to depend on muscle length in keeping with previous suggestions. However, the magnitude of the inhibition increases with increasing initial force, and the inhibition is mimicked by gentle manipulation of the muscle and tendon surface. Concurrent muscle afferent recordings showed that the electromyogram (emg) reduction was not a result of a decline in Ia afferent input and was not well related to secondary or tendon organ afferent discharge. It is now known that many group III and some group IV muscle afferents are also activated by muscle stretch and contraction, and we here report limited stretch sensitivity in four non-spindle group II afferents. Since these fiber groups each include afferents that produce inhibition of extensor motoneurons, it is proposed that the clasp-knife reflex may result from the activation of these slowly conducting afferent fibers.


Biomimetic synthesis of cannabispiran.

Biomimetic synthesis of cannabispiran. Total synthesis of cannabispiran (1) was accomplished by a biomimetic-type cyclization of the bibenzyl 2, using K3Fe(CN)6 or MoCl4.


Amino acid composition and sequence of crinia-angiotensin, an angiotensin II-like endecapeptide from the skin of the Australian frog Crinia georgiana. Methanol extracts of the skin of the Australian amphibian Crinia georgiana contain large amounts of crinia-angiotensin II, a new angiotensin II-like peptide. This differs sharply from the conventional octapeptide angiotensins II in having attached the tripeptide Ala-Pro-Gly- to the N-terminus, and having an Ile residue substituted for the Val residue at position 6 from the C-terminus. Small amounts of angiotensin-like peptides have been traced, by radioimmunoassay, in skin extracts of some other Crinia species.


Occurrence of Hyp3-bradykinin in methanol extracts of the skin of the South African leptodactylid frog Heleophryne purcelli. Methanol extracts of the skin of the South African amphibians belonging to the genus Heleophryne (H. purcelli purcelli, H. purcelli depressa, H. purcelli orientalis, H. natalensis) contain large amounts (20--500 microgram/g fresh tissue) of Hyp3-bradykinin.


Effect of sodium chloride on the respiratory function of Staphylococcus aureus. Sodium chloride at concentrations below 0.5 M, enhanced the respiratory activity (O2-consumption) of Staphylococcus aureus under endogenous and sugar-supported conditions, but did not overcome the inhibitory action of sodium azide. Several sugars, including the glucose analogue alpha-methylglucoside, and their metabolites enhanced bacterial O2-consumption, but acetylmethylcarbinol was ineffective.


The turnover of F-actin-bound ADP in vivo. A procedure for estimating the rate of turnover of F-actin-bound ADP in vivo is described. A turnover rate of 0.88 h-1 was determined for mouse muscle F-actin. The validity of the method when used to estimate the turnover rate of F-actin per se is discussed in relation to the possible exchange of F-actin-bound ADP.


Evidence of soluble proteins binding adriamycin by affinity chromatography. The presence of various tissues of soluble proteins binding adriamycin is evidenced by affinity chromatography.


The amino acid composition of histidine ammonialyase from Pseudomonas putida NCIB 10807. The amino acid composition of histidine ammonia-lyase from Pseudomonas putida NCIB 10807 suggests that this enzyme may be different from the Pseudomonas testosteroni NCIB 10808 histidine ammonia-lyase, whose amino acid composition is known.


Chloroperoxidase-catalyzed oxidation of N-methyl-4-chloroaniline. Chloroperoxidase catalyzed the H2O2 oxidative conversion of N-methyl-4-chloroaniline to 4-chloronitrosobenzene, 4-chloroaniline and a mixture of complex products.


The role of sialic acid in 5-HT binding to synaptic membranes. The high affinity binding of [14C]5-HT to nerve ending membranes isolated from rat brain is not affected by neuraminidase treatment. The specificity of ligand receptor interaction was demonstrated by displacement studies with tryptamine derivatives, noradrenaline, and acetylcholine.


Bisalbumineamia in a bottlenosed dolphin (Tursiops truncatus). Bisalbuminemia was found in a female bottlenosed dolphin (Turiops truncatus) on routine examination. There is no association with disease.


Denaturation map of the ribosomal DNA of Lytechinus variegatus sperm. Electron microscopy of the partially heat denatured ribosomal DNA (rDNA) from sea urchin (Lytechinus variegatus) sperm has demonstrated that it consists of repeating units of 3.6 +/- 0.2 micron, corresponding to a mol.wt of 7.2 +/- 0.4 x 10(6). Based on differential denaturability, each repeat unit is divided into 2 regions. The larger region of 2.47 +/- 0.11 micron (mol.wt 4.9 +/- 0.22 x 10(6)) corresponds in length to the ribosomal precursor RNA of sea urchins and the smaller, GC-rich, subunit of 1.16 +/- 0.09 micrometer (mol.wt 2.3 +/- 0.18 x 10(6)) is presumed to contain non-transcribed spacer sequences.


Heterogeneity of DNA methylation in murine L5178Y lymphoblasts. Comparison of the extent of methylation in mouse DNA fragments rendered MgCl2 soluble after mild DNase II digestion of nuclei, with different reassociation rate and nucleoli-bound, revealed the existence of 3 regions of the genome particularly 5-methylcytosine-rich: the sequences considered to be related to the transcriptionally active chromatin with the highest content of this base and fast reassociating, as well as nucleolar DNA with somewhat lower proportion of the methylated cytosines.


Colchicine-induced resistance to antibiotic and amino-acid analogue in plant cell cultures. Colchicine-resistant plant cell strains have been isolated from cell suspensions of carrot and sycamore. In the same way as colchicine-resistant animal cell strains, they show an increased resistance towards streptomycin and N-methylalanine. Cultivation under non selective conditions leads to a slow progressive loss of the resistance.


Hydrogen bonding by the sulphydryl group of glutathione. The occurrence of hydrogen bond in the sulphydryl group of glutathione was investigated by means of Raman Spectroscopy. Evidence is obtained that SH group is free and H-bonding does not occur.


GFA expression in aggregation cultures of rat C6 glioma. Few C6 glioma cells synthesize the astroglia-specific GFA protein in monolayer culture. A uniform population of GFA-positive cells was obtained by aggregation C6 cells in suspension culture, as previously reported for C6 glioma maintained on sponge foam matrices. These results strongly suggest that cell-to-cell interactions promote GFA expression.


Comparison of the biological effects of anemia inducing and polycythemia inducing Friend virus complex. The comparison of the biological effects of FVP and FVA showed that leukemogenesis appears to be delayed in FVA infected mice as compared to FVP infected animals after injection of comparable quantities of virus as measured in spleen focus forming units. In addition, no CFU-EI, characteristic for FVP induced leukemia, were found in leukemic spleen or bone marrow of FVA infected mice. Since it was possible to distinguish both viruses by their different host ranges, which are helper virus determined, it is suggested that the observed differences, especially the lack of CFU-EI in FVA infected mice, might be due to differences in the helper virus component of the FV complex.


[An ultrastructural study of the transformation of elementary bodies of Rickettsiella into initial bodies (author's transl)]. An intermediate stage between the elementary and the initial bodies of the Rickettsietta genus is defined as the beginning of an intracellular cycle. It is characterized by several structural changes in the dense elementary body: the cytoplasm becomes less electron-dense; thus, the nucleoid and the ribosomes are visible. The inner layer of the cell-wall becomes progressively clearer and the trilamellar structure of the inner and outer membranes appears distinctly. 'preinitial body' is proposed as name of this stage of development.


Lithium and rubidium: effects on the rhythmic swimming movement of jellyfish (Aurelia aurita). The effects of adding LiCl, RbCl, KCl or NaCl to sea water at concentrations up to 30 mmoles/1 on the frequency of contraction of jellyfish (Aurelia aurita) suggest that studies on phylogenetically low animals with relatively simple nervous systems may be of use to determine mechanisms of action of lithium and rudidium on movements.


Localization of concansvalin-A binding sites in Tetrahymena by scanning electron microscopy. Binding sites of concanavalin-A were detected in Tetrahymena on the body ciliature, while the cell membrane itself and the oral ciliature failed to bind the lectine.


Phosphatase activity in testis and prostate of rats treated with embelin and Vinca rosea extract. Daily administration of Vinca rosea Linn. extract orally and embelin s.c. to male albino rats caused significant rise in levels of acid and alkaline phosphatases of testis and prostate indicating altered metabolic function.


Water regulation in Barmer goat of the Rajasthan desert. The different body fluid compartments in normally watered and 4-day water-deprived goats of Rajasthan desert, India, were measured in autumn. The goats maintained plasma volume and extracellular fluid volume, but lost gut and cell water considerably under the experimental conditions; indicating that the maintenance of the fluidity of the blood has priority over the body's other fluid requirements in this desert-adapted species during water deprivation.


Electrical response of bat retina to spectral stimulation: comparison of four microhiropteran species. Electrical responses of the retinas of 4 species of microchiropteran bats stimulated by spectrally restricted light flashes were found to diverge systematically from the rhodopsin absorption spectrum. The divergence was progressively greater across the 4 species. The results appeared explainable by assuming a second photoreceptor class and photopigment which was present in progressively greater numbers in the retinas of Eptesicus fuscus, Desmodus rotundus, Artibeus jamaicensis and Carollia perspicillata.


Effect of light adaptation on electrical responses of the retinas of four species of bats. The levels of light adaptation at which the retinas of 4 species of microchiropteran bats became unable to generate electroretinograms were progressively ordered. The order correlated well with light preferences based on activity patterns of the 4 species. These results suggest that the ability of the retina to function in ambient light may govern some natural behaviors of these bats.


Resting heartrate variability in man declines with age. The heartrate variability under resting conditions of 14 normal male subjects, age range 22--63 years, declined with increasing age. Mean heartrate did not show age-dependant changes.


Interaction between human evoked electrospinograms elicited by segmental and descending volleys. Interaction between the slow negative-positive waves of human evoked electrospinograms produced by descending and segmental volleys was tested under general anaesthesia. A partial occlusion was demonstrated in these slow waves.


Electrophysiology of mammalian hypothalamic and interpeduncular neurons in vitro. Electrical activities of the hypothalamic and interpeduncular neurons were studied in vitro in brain slices prepared from the guinea-pig brain stem. Neurons preserved resting membrane potentials comparable to those of neurons in vivo, responded to stimulation of the afferent fibres, and retained stable spontaneous firings for more than several hours.


Receptor potential of rat taste cell to potassium benzoate. Rat taste cells responded to relatively low concentrations of K-benzoate with a hyperpolarization and to the high concentrations with a depolarization. During both responses the membrane resistance of a taste cell decreased. Depolarization elicited by application of a combination of 0.25 M NaCl and 0.05 M K-benzoate was smaller than that by the NaCl alone, indicating a depressant action of K-benzoate.


The effects of dopamine on renin release in the isolated perfused rat kidney. In the isolated and perfused kidney of the rat, the stimulant effect of dopamine on renin release is blocked by propranolol and not by haloperidol. This suggests that the release of renin induced by dopamine is due to the activation of beta-receptors.


Severe conditioned taste aversion elicited by venom of Russell's viper. Conditioned taste aversion (CTA) established in rats by associating saccharin drinking with subsequent poisoning by Russell's viper venom. Retention test revealed 76 and 56% reduction of saccharin intake in venom and antivenom-venom groups. No CTA was observed in antivenom and control groups.


The localization of [3H]-desipramine in central nerve terminals studied with electron microscope autoradiography and subcellular fractionation. The cellular and subcellular distribution of [3H]-desipramine (DMI) in rat brain was studied by electron microscope (EM) autoradiography and by subcellular fractionation. A considerable proportion of label was found to be bound to the membranes of presynaptic nerve terminals, as well as to sites inside those terminals.


Dissociation constants of 4-acetoxy-piperidines and -thiacyclohexanes at the muscarinic receptor. The dissociation constants (KA) and the relative intrinsic efficacies (e) of 4-acetoxy-piperidines and -thiacyclohexanes were determined on the guinea-pig isolated left atrium. The differences in the muscarinic potencies are associated with differences in affinities and efficacies, respectively.


Protein synthesis inhibition induced by dimethylnitrosamine and diethylnitrosamine on isolated rat hepatocytes. Time- and dose-dependent protein synthesis inhibition takes place following exposure to high doses of dimethylnitrosamine (DMN) or diethylnitrosamine (DENA) in isolated rat hepatocytes. The ability of DENA to depress protein synthesis is 5-fold higher than that of DMN. Cells inhibited by 60 min exposure to DMN or DENA, and then incubated in a nitrosamine-free medium, regain their initial rate of protein synthesis. This recovery is faster and more complete for DENA-treated cells.


Structural alterations in normal and axotomized facial nucleus neurons after treatment with morphine. Chronic morphine administration induced ultrastructural alterations in neurons of the facial nucleus and increased the incidence of cell death after axotomy. These findings may correlate with the significant depression of neuronal metabolism known to occur after opiate treatment.


Ouabain potentiation of Ca release from fragmented cardiac sarcoplasmic reticulum from isolated cat heart. The present study was performed to determine the effect of ouabain on Ca release from fragmented sarcoplasmic reticulum (FSR) isolated from cat cardiac muscles. The results clearly demonstrate that ouabain potentiates the Ca release from FSR by changing the ionic environment.


Purification and properties of heat-resistant exotoxin produced by Macrophomina phaseolina (Tassi) Goid in culture. A partially purified preparation of a water-soluble, heat-resistant, nonspecific exotoxin produced by a strain of Macrophomina phaseolina, isolated from Phaseolus mungo L. could reduce Cu++ ions and produced a red colour with 2,4-dinitrophenyl hydrazine reagent. It caused inhibition of seed germination, wilting of cult seedlings, stunted growth of young seedlings and loss of permeability of the cell membrane. Seedlings of P. mungo, grown in presence of the toxin showed a slight increase in the contents of protein and total RNA over control, but a significant increase in the specific activities of F-1, 6-BP aldolase and G-6-P isomerase.


Changes in serum proteins and in major liver constituents following carbon tetrachloride and a high-fat choline-free diet in rats. Both carbon tetrachloride and a high-fat, low-protein choline-free diet cause hepatomegaly in rats due to an accumulation of both lipids and proteins with a concomitant increase in deoxyribonucleic acid content. CCl4 causes a decline in hepatic glycogen. Serum albumin level is decreased in CCl4-treated rats and increased in those fed the experimental diet.


Collagenolytic activity of eosinophilic granuloma in vitro. Lytic activity of eosinophilic granuloma and other tumours was studied in vitro on collagen substrate. Collagen degradation was measured through the release of hydroxyproline-rich peptides into the medium. The in vitro lytic action was at a maximum in the case of EG and was correlated with the presence of histiocytic cells.


Ultrastructural localization of vanadium in the blood cells of Ascidiacea. X-ray histospectrographic analysis at the scanning and transmission electron microscope (STEM) are made on the blood cells of Phallusia mamillata Cuvier and Ciona intestinalis, to study the 'direct' intracellular sites of accumulation of vanadium. The results show a clear accumulation of vanadium on the membrane and in the granules of vacuoles of amebocytes, signet ring cell, compartment cell and traces of metal in the 'vanadophores' of vanadocytes.


A histochemical study on the innervation of the cerebral blood vessels in the carp. Adrenergic and cholinergic innervation of the cerebral blood vessels were studied in the carp using fluorescence and cholinesterase histochemistry. Most of the major cerebral and pial arteries were densely innervated with both nerves. Moreover, both nerves, being probably of central origin, were observed frequently on the walls of parenchymal arterioles and capillaries in the sections of the inferior lobe but were only rarely found in the other brain sections.


Patterns of neuroglial proliferation in spinal cord white matter following exposure to ionizing radiation. X-irradiation temporarily decreases the proliferative activity of neuroglia in immature rat spinal cord. Later, the proliferative activity in these irradiated regions surpasses that noted in control rats. Areas adjacent to the irradiated region have a greater than normal percentage of labelled neuroglia and may also be a source of neuroglia which re-populate the irradiated zone.


Regional vascular reactivity in rats with Guérin carcinoma (GC). Increased sensitivity to phenylephrin and a decreased one to isoproterenol has been found in regional vascular beds of GC implanted rats. Circulatory sympathetic reflex adaptation, alfa- and beta-adrenergic stimulation or blockade provoked a uniform response pattern: i.e. increase in vascular resistance of GC.


Nuclear localization of aldosterone in rat brain cells assessed by autoradiography. Autoradiographic studies with 3H aldosterone demonstrate nuclear concentration of hormone in neurons of the hippocampus, septum, allocortical regions and brain stem reticular formation and motor nuclei of cranial nerves and in the meninges. The results suggest that mineralocorticoids have wide ranging effects on different parts of the central nervous system.


Restoration of the poor oxygen transport function of ACD-stored blood by pyridoxal 5'-phosphate. Pyridoxal 5'-phosphate is easily incorporated into ACD-stored erythrocytes without decrease of ATP, and restores the poor oxygen transport function with a similar effect to 2,3'-diphosphoglycerate.


Cerebrospinal fluid immune complexes in multiple sclerosis. Using a C1q binding test, immune complexes have been detected in one half of cerebrospinal fluid samples from patients with multiple sclerosis. These results provide additional evidence for the participation of an immune reaction in the disease process.


Conversion of glycine max seed agglutinins from nonspecific to anti-(A + B). The seeds of glycine max contain agglutinins which are typically nonspecific in their reactivity. Our investigations show that the phytagglutinins in GM can be converted from nonspecific to anti-(A + B) after the lectin is absorbed with horse red cells. The anti-A and anti-B fractions can be further separated by suitably absorbing the lectin with human red cells. The lectin absorbed with horse red cells or with group-0 human red cells shows an A-stressed activity.


Changes in the sialic acid content of chick thymus and bursa of Fabricius during age-involution. The sialic acid content of both thymus and bursa of Fabricius during their growth and involution phases in chick has been reported in this study. It is observed that the sialic acid concentration is very high in 1-week-old chickens. The concentration subsequently decreases to a significant level and rises again prior to the onset of involution. In the post-involution period, a more or less minimal and constant level is maintained. The role of sialic acid in cellular activities of thymo-bursal system has been discussed.


Radioimmunoassay of an invertebrate peptide hormone - the crustacean neurosecretory hyperglycemic hormone. Antibodies against hyperglycemic hormone (CHH) of Carcinus were raised in rabbits by injection of extract from sinus glands which contain high concentrations of CHH. The antiserum neutralizes the biological activity of CHH and binds 125-J-CHH. A RIA for CHH was established and was used to measure the hormone content of sinus glands.


DNA synthesis in the pituitary gland of the rat: effect of sulpiride and clomiphene. Sulpiride administration to rats releases prolactin and increases DNA replication in the anterior pituitary gland. Clomiphene prevents the stimulation of DNA synthesis produced by sulpiride, but does not affect prolactin release from the gland. These findings suggest that the intracellular prolactin content of the anterior pituitary gland plays a role in the regulation of DNA synthesis through a mechanism mediated by oestrogens.


Substance P in medullary carcinoma of the thyroid. High levels of substance P-like immunoreactivity were demonstrated by radioimmunoassay in the plasma and tumour of a patient with a medullary carcinoma of the thyroid.


Effect of phosphate omission on glucose-induced insulin release in vitro. In the isolated perfused rat pancreas, omission of extracellular phosphate (H2PO-4) significantly reduces the insulin secretion in response to 16.7 mM glucose.


Measurement of urinary steroid production rates using stable-isotopes and GC-MS. The urinary production rate of pregnenolone has been determined for a male subject using 7,7-d2-pregnenolone as an isotopic tracer.


Oxygen consumption in the rat following neonatal thyrotoxicosis. Adult rats made thyrotoxic with large doses of thyroxine during the neonatal period had a lower oxygen uptake as compared with neonatal controls and those of neonatal calorically-deprivated ones.


A simple theoretical criterion of chemical carcinogenicity? The simple theoretical criterion for chemical carcinogenicity based on the 'average quasi-valence number' is discussed and shown to be inappropriate as a reliable indicator of carcinogenicity of any organic compound.


A demonstration of the resolution of NMR imaging in biological systems. A proton NMR imaging study of several fruit specimens demonstrates the integrity and resolution of this new imaging method.


Computer-compatible system for continuous volumetric measurement of water consumption? An inexpensive drinkometer system is described that is compatible with most data acquisition systems and can be used for continuously monitoring the drinking pattern of laboratory animals. The change in electrical inductance resulting from the descent of a free-floating ferrite unit through a drinking tube, surrounded by a double coil, is converted to a signal proportional to the volume of fluid consumed.


Training in family therapy: perceptual, conceptual and executive skills. This paper presents a comprehensive and detailed outline of family therapy skills to aid in providing a more precise focus in the training of clinicians in family therapy. The skills are based on an integrated treatment model within a systems framework. Four major functions performed by a family therapist are separated and are further differentiated into general therapeutic competencies. Specific perceptual, conceptual, and executive skills are described in the form of instructional objectives and are listed under each competency. Occasional clarifying notes or examples are cited along with particular skills. Clinicians and trainees should find this outline a useful guide in skill development.


Family treatment approaches to drug abuse problems: a review. This review covers the literature that has emerged specifically on the family treatment of drug abuse problems. Following a brief discussion of patterns and structures prevalent in drug-abusing families, 68 different studies or programs (discussed in 74 papers) are compared as to their techniques and results. These are categorized within the following modalities: marital treatment, group treatment for parents, concurrent parent and identified patient treatment, treatment with individual families (both inpatient and outpatient), sibling-oriented treatment, multiple family therapy, and social network therapy. A table presents the various studies, along with the types of results they provide. Outcomes are contrasted for the 14 studies that quantified their results. The final section presents implications for the following areas: treatment activities (clarification of technique, family recruitment, direction and effectiveness of treatment, confidentiality, and treatment delivery systems), training, prevention, and future research (outcome, technique and responsibility). It is concluded that family treatment for drug abuse is gaining widespread acceptance and shows considerable promise for dealing effectively with problems of this type.


A family-oriented psychiatric inpatient unit. This article presents the structure and policies of a psychiatric inpatient unit that was developed with the goal of fully integrating family-oriented treatment approaches into its therapeutic program. There is an explanation of different methods to involve families in the hospital treatment process and delineation of a variety of treatment techniques specific for families of inpatients. The role of the nursing staff is described as well as some of the contradictions and paradoxes that are inherent in this type of inpatient unit.


Toward a metacommunicational framework of couple interactions. A multi-level, metacommunicational framework to understand couple interactions is presented. Five interactional levels are defined following a mode of abstraction that parallels the theory of logical types; case examples are offered of couples interacting at each of the levels. The clinical implications of the framework, as a metaphor for understanding transactional processes, are discussed with an emphasis on the pragmatics of working with punctuational diffferences, developing therapeutic strategies, measuring progress, and setting goals for therapy with couples.


Structural and strategic approaches to psychosomatic families. Patterns of relatedness characteristic of psychosomatic families are discussed. A step-wise intervention procedure based on structural and strategic approaches is presented. The goals of the procedure are to establish symptomatic relief and modify concurrently the patterns of relatedness. The procedure is applied to a sample of families in which a child presents with psychogenic abdominal pain. This paper is intended as a detailed and practical guide to working with such families; a degree of generalization is possible, as well.


A family myth: sex therapy gone awry.

A family myth: sex therapy gone awry. The treatment of sexual disorders has achieved considerable popularity and respectability within the mental health profession and the lay community. As a consequence, it has become increasingly difficult to elude requests for this type of treatment and even more difficult to balance sexual concerns with the numerous other modes of relating that exist within a dyadic relationship. This paper will report two versions of a case study in which sexual dysfunction served as a myth that was carefully constructed to veil certain more fundamental problems.


Family therapy as a treatment for children: a critical review of outcome research. The value of family therapy as a treatment for child psychopathology is considered by reviewing pertinent outcome research. Fourteen studies that met three criteria are included in the review: (a) a child or adolescent was the identified patient or referral; (b) therapy included at least one parent and the child; and (c) outcome was evaluated in terms of the child's symptoms. There are major shortcomings in most of the available data, with only two well-controlled studies. Some empirical evidence does exist that family therapy is an effective treatment for children; the data from studies of adolescents are especially encouraging. However, insufficient data are available for comparing the relative merits of conjoint family treatment and individual child therapy. If the value of family therapy as a treatment alternative or, ideally, as the "treatment of choice" for a referred individual child is to be established, more and better controlled comparative outcome studies will be necessary. Suggestions for future research are presented emphasizing the need for a developmental perspective by recommending, for example, the use of factorial designs in which the intervenaction of treatment and age can be analyzed.


[Effect of agents that act in the area of cholinergic synapses on the glycolysis process in an ischemic extremity]. Glycolysis intensity in an intact and ischemized muscle of a limb was decreased by prozerin and carbacholine in experiments on 230 noninbred rats with 2 models of acute ischemia. A less pronounced decrease was caused by benzohexonium, cholinesterase and dipyroxim. Meanwhile atropine blocked the glycolysis.


[Effect of neurotropic agents on the healing of experimental mucosal erosions and on the noradrenaline content in the stomach wall]. In immobilized rats with hemorrhagic erosions of gastric mucosa induced by 8-hour electric stimulation, the neurotropic agents were injected intraperitoneally over three days after stimulation was discontinued. Phenamine and melipramine were conductive to healing of the mucous membrane erosions and produced no effect on the recovery of noradrenaline level in the intestinal wall. Clonidin and reserpin inhibited erosion healing and noradrenalline level recovery, whereas eterofen and atropin elicited no effect on the test parameters.


[Effect of apressin on the contractility, blood supply and bioenergetics of the ischemic myocardium]. It has been shown that apressin in doses of 0.5 and 1 mg/kg intravenously prevented a drop of the amplitude of the left ventricular pressure, pressure, maximal speed of its rise and relaxation which developed in control experiments on dogs after ligation of the coronary artery. Apressin increased the volumetrical rate of the collateral coronary blood flow, diminished peripheral vascular resistance in the zone of myocardial ischemia and reduced the ST segment of the heart epicardial electrogram. The drug lowered glucose consumption, lactate content, and "excess' lactate in blood samples collected from the ischemic zone. At succinate and glutamate oxidation, it decreased oxygen consumption by mitochondria from the myocardial ischemic zone in the acceptor-free system, and increased the respiration stimulation coefficient, the respiratory control alccording to Change being improved at glutamate oxidation.


[Effect of potassium glutamate on the manifestation of experimental arrhythmias in rabbits]. In rabbits and rats potassium glutaminate elicits antiarrhythmic effect in experimental arrhythmias induced by intravenous injection of strophanthine and calcium chloride, normalizes the content of electrolytes (potassium, sodium, calcium, magnesium) in the myocardium and blood of animals after they are injected strophanthine.


[Cardiotropic effect of anti-arrhythmia agents]. In experiments on contractile proteins isolated from the myocardium rather than from the musculus gastrocnemius it was shown that in contradistinction to lidocain the drugs quinine, quinidine, novocainamide, papaverin, obsidan and isoptin at a concentration of 3 . 10(-4) M inhibit contraction of actomyosin threads and superprecipitation reaction of actomyosin suspension that occurs under the influence of adenosine triphosphoric acid.


[Action of potassium orotate, hyperbaric oxygenation and their combination on the course of experimental microfocal myocardial infarct]. The efficacy of potassium orotate (200 mg/kg), hyperbaric oxygenation (3 at. abs, totally six 50-minute sessions) and their combinations was studied in experiments on 150 rabbits. According to polarography, analysis of the level of nucleic acids and pathomorphological changes, the best effect can be achieved by combined use of potassium orotate and hyperbaric oxygenation. However, even under these circumstances the cardiac activity is not completely recovered on day 14 after the treatment is commenced.


[Spasmolytic properties of pyrrolizidine alkaloids]. Acute toxicity, spasmolytic and hypotensive properties of the alkaloids senecionine, d-otocenine and floridanin isolated from Senecio Erraticum L. were studied. D-otocenine and floridanin elicited low toxicity, while senecionine and d-otosenine showed spasmolytic and floridanin predominantly hypotensive properties.


[Pharmacological properties of a new benzimidazole derivative]. The pharmacological action of the new benziamidazole derivative 1-(3-diethylamino-2-oxypropyl)-2-propylbenzimidazole (abazol) was studied in experiments on mice, dogs, cats and isolated ears of rabbits. In cats and dogs, abazol produces a hypotensive effect and transient reduction of the EEG wave amplitude. Abazol dilates the vessels of an isolated rabbit ear. It shows less toxicity and less pronounced convulsant effect as compared to dibazol.


[Effect of rheopolyglucin on the aggregation function of erythrocytes stored for different times]. The paper is concerned with changes in the aggregation function of red blood cells at rheopolyglucin dilution of the erythrocyte mass with varying dates of storage. Rheopolyglucin decreases aggregation of red blood cells. It has been also established that aggregation capacity of these cells is reduced on storage of conserved blood.


[Mechanism of the anti-arrhythmia action of potassium and magnesium nicotinates]. It has been shown in rat experimental aconitinic arrhythmia and in dog postinfarction arrhythmia that combined potassium and magnesium nicotinates show a pronounced anti-arrhythmic effect. The studies on the drug distribution in the tissues indicate that the content of potassium, magnesium and total coenzymatic forms of nicotinic acid rises in the myocardium by the 12th hour from the commencement of the drug administration. Intracellular and exocellular content of potassium and sodium has been shown to return to normal.


[Effect of hydrocortisone on 14C-lysine incorporation into the nuclear and mitochondrial proteins of the rat thymus at different times of day]. The data on 14C-lysine incorporation have shown that normally there exists 12-hour periodicity of intensifying the synthesis of nuclear and mitochondrial proteins by the rat thymus, that correlates with similar changes in the DNA synthesis and in the mitotic rate. Administration of hydrocortisone during varying time of the day induces the synthesis of non-histone proteins of chromatin primarily in non-proliferating populations of thymus lymphocytes, the synthesis of histones being induced in proliferating ones.


[Pharmacokinetic characteristics of salicylates in old animals]. Experimental study of absorption, distribution, metabolism and excretion of salicylic acid and salicylate upon ageing showed that the sodium salicylate absorption rate is considerably decreased in old rats and rabbits. As a result, the plasma of old animals shows the low content of salicylates compared to adult ones. The level of salicylic acid in tissues and capacity of serum protein for salicylate binding are decreased. Excretion of salicylates in old rats was delayed compared to that in adult ones, the half-life in old rats was 2--3 times as long as that in adult species. The revealed features of salicylate pharmacokinetics in old animals confirm advisability of their further study in order to determine adequate doses of the drugs to be applied in geriatrics and to prevent their adverse on the ageing organism.


[Acetylation and urinary excretion of norsulfazole in gastrointestinal disease patients of different age groups]. The amount of free and acetylated norsulfazol in the urine of patients with gastrointestinal diseases was analysed 3 hours after peroral administration of the drug (20 mg/kg). The acetylation rate of norsulfazol in patients of 21--30 years of age was significantly lower than that in heathy subjects of the same age. In groups of 31--40, 41--50 and 51--60 years of age the acetylation rate was 47, 42 and 43%, respectively. In patients with chronic cholecystitis excretion with urine of free norsulfazol was 2-fold as increased whereas in chronic gastritis there was a 2.7-fold increase as compared to controls. The acetylation rate of norsulfazole was 1.6, 1.4 and 1.5-fold reduced in duodenal ulcer, cholecystitis and gastritis, respectively.


[Antitumor and immunodepressive action of dexamethasone on a leukemia L-1210 model]. The effect of single administration of dexamethason in doses of 10, 20, 50 and 100 mg/kg on the spleen content of lymphomic colonies, normal colony-forming units and antibody-forming cells was studied in experiments on CBA and DBA/2 mice with transplanted leukemia L-1210. It has bear dependence on the dosage, the immunodepressant action of the drug being more pronounced in CBA mice as compared to DBA/2 mice with leukemia L-1210. The immunodepressant activity of dexamethason is approximately equal to the antineoplasic one. Single administration of the drug has practically no effect on hemopoiesis.


[Effect of cyclophosphane on the function and structure of the kidneys]. In experiments on dogs and rats it has been shown that single administration of cyclophosphane in low doses produces no changes in the renal function or in water-electrolyte metabolism. Material changes in the canalicular apparatus of the kidneys, water-salt equilibrium and organ ultrastructure have been recorded in prolonged administration of the drug.


[Effect of the prolonged exposure to etylene glycol and fatty acid ester on the functional state of the body of experimental animals]. The effect of prolonged (for 1 1/2 month) action of ethylene glycol and fatty acids ester on the bodily function was studied in experiments on rats by means of a complex of techniques. The threshold dose determined in a subacute experiment amounted to 1.8625 g/kg. The cumulative effect of the preparation is evaluated as little and medium cumulative.


[Human pharmacokinetic characteristics of sulfamonomethoxine depending on the drug form]. Comparative study of sulfamonomethoxin pharmacokinetics in the man given the drug per os or parenterally in the form of methylglucaminate showed that the latter favours higher blood concentrations of the drug 12 hours following injection. Sulfamonomethoxinmeglumin is absorbed more rapidly and has a greater bioavailability. The drug is mainly excreted with urine, more than a half being excreted in an acetylated form. It is recommended that the initial and maintenance doses be not less than 1000 and 500 mg for both dosage forms respectively. The interval between sulfanilamide administrations should not exceed 24 hours.


[Immune and autoimmune reactions in the mechanism of action of drug substances, their detoxication and the development of habituation to them]. It has been shown that rausedyl administration is followed by enhanced synthesis of autoantibodies to serotonine and adrenaline. Meanwhile bucarban enhances the synthesis of autoantibodies to endogenous insulin and ACTH to hydrocortisone and testosterone. Activation of the autoimmune system of regulating the balance of endogenous compounds was shown by an increased number of specific antibody-producing cells in the organs and tissues and by the growth of the titer of circulating antibodies in the blood.


The Na:K pump in red cells is electrogenic. The membrane potential, E, of the red cell measured with a fluorescent dye, 3,3'-dipropylthiadicarbocyanine iodide, hyperpolarizes when the Na:K pump is activated by adding external K and depolarizes upon the subsequent addition of ouabain. The electrogenic pump is optimally observed in cells where internal Na+ has been raised, SO2-(4) has replaced Cl-, and SO2-(4) permeability has been inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS)). The change in E associated with the electrogenic component is about 6 mV in human red cells, somewhat smaller in sheep, and larger in duck and Amphiuma red cells. The membrane resistance, Rm, can be estimated from the pump-dependent change in E and from the current flow assumed to be one-third the ouabain-sensitive Na efflux. In human red cells, Rm is about 1 X 10(6) ohm-cm2. Rm calculated from the residual DIDS-insensitive SO2-(4) flux is also about 1 X 10(6) ohm-cm2. The closeness of these two values of Rm is paralleled in the other three types of red cells (even though the absolute values of Rm vary among the four types by a factor of 10), indicating that the net current flow across the membrane can be accounted for by the net transport of Na by the pump.


Euphorigenic drugs: effects on the reward pathways of the brain. This report summarizes a number of experiments designed to examine the changes in the threshold for intracranial self-stimulation (ICSS) in the rat after the administration of morphine and a number of narcotic agonist-antagonists, as well as three nonnarcotic drugs that have extensive nonmedical use (cocaine, d-amphetamine, and phencyclidine). The results of these experiments clearly indicate that morphine lowers the threshold for ICSS and, furthermore, there appears to be little or no tolerance to this effect. The only mixed agonist-antagonist that consistently lowered the ICSS threshold was pentazocine. Cocaine, d-amphetamine, and to a lesser degree, phencyclidine also lowered the ICSS threshold. These results suggest that the abuse liability of these agents may be directly related to their ability to sensitize the neural substrate involved with natural reward.


Cerebral energy state, mitochondrial function, and redox state measurements in transient ischemia. Earlier results are reviewed suggesting that transient pronounced, incomplete cerebral ischemia could be more deleterious for the recovery of brain tissue energy state than a complete interruption of the blood flow. Measurements of respiratory function of brain mitochondria, isolated after 30 min of either complete or incomplete ischemia, demonstrated a similar inhibition of respiratory activity and maximal phosphorylation rates in both situations. This inhibition was totally normalized during recirculation after complete ischemia while a further deterioration was found after incomplete ischemia. The in vivo alterations of the cortical tissue distribution of redox states during transient, incomplete ischemia (15--60 min) were measured using a flying spot fluorometer, which gives a real-time and on-line display of the tissue distribution of NADH and oxidized flavoprotein. A reoxidation in both systems was demonstrated during the recirculation period and the distribution of redox states showed no further heterogeneity in the postischemic period as compared to the preischemic distribution. It is concluded that reoxygenation of the brain tissue is possible even after long periods of incomplete ischemia. The normal distribution of redox states during recirculation suggests that mechanisms other than an impaired or inhomogeneous oxygen delivery during the postischemic period are responsible for the failure in recovery of mitochondrial function and tissue energy state.


Recent advances in the in vivo and in vitro metabolism of retinoic acid. Retinoic acid, a natural metabolite of retinol, has previously been shown to be capable of supporting growth and maintaining proper differentiation in epithelial tissues. Recently, investigation into the in vivo and in vitro metabolism of retinoic acid in hamsters, using both tracheal organ culture and subcellular preparations derived from intestinal mucosa, liver, and testis, has revealed the production of several metabolites more polar than the parent compound. Two of the early products of this metabolic pathway have been identified as 4-hydroxy- and 4-keto-retinoic acid. The formation of these metabolites is maximal in vitamin A-deficient hamsters that have been pretreated with retinoic acid and in vitamin A-normal animals. This fact, together with the decreased biological activity of the two compounds relative to retinoic acid in a tracheal organ culture assay, suggested that oxidative attack at carbon-four of the cyclohexenyl ring may be the first step in the elimination of retinoic acid from tissues. In addition, observations both in vivo and in vitro indicate that all-trans- and 13-cis-retinoic acid at low concentrations may be sharing a common metabolic pathway that includes an isomer of 4-keto-retinoic acid.


Chemoprevention of cancer with retinoids. The importance of retinoids for chemoprevention of cancer has received further emphasis with the finding that retinoids can suppress in vitro expression of the malignant phenotype, whether it be caused by chemical carcinogens, radiation, or viral transforming factors. Retinoids have been found to be potent inhibitors of the tumor-promoting effects of phorbol esters. Further advances in the chemistry of synthetic retinoids have led to the development of new agents that show less toxicity and better targeting to specific organ sites than natural retinoids. Synthetic retinoids have been particularly useful for prevention of bladder and breast cancer in experimental animals.


Hypercarotenemia in hypothalamic amenorrhea. Six patients are described with hypothalamic amenorrhea and associated hypercarotenemia. The commencement of the hypothalamic amenorrhea followed weight reduction or stress in each case. The subjects were otherwise healthy and had none of the associated stigmata of anorexia nervosa. None of the subjects had ingested excessive quantities of vegetables or fruits rich in carotene. Although all six patients had elevated serum carotene levels, only three had clinically apparent yellow pigmentation of the skin. The exact mechanism responsible for hypercarotenemia in patients with hypothalamic amenorrhea is not apparent. Mobilization of lipid stores and catabolic changes occurring with weight-loss states appear to be related in some undefined way to the elevated carotene levels.


New therapeutic approach to the hirsute patient. Spironolactone, an aldosterone antagonist currently used in the treatment of hypertension, has numerous antiandrogenic side effects. Decreased production rates of testosterone in intact (N = 10) and hirsute (N = 6) women, respectively, were noted after short (7 days) or long-term (6 months) administration of the drug, 25 mg twice daily. A 50% diminution in the urinary 17-ketosteroid excretion was also observed after 6 months of therapy. Assessment of the treatment was done by the patients: a reduction in hair growth rate was initially observed after 3 to 4 months, followed by the appearance of a more downy type of new growth and a decrease in diameter of the hair shaft. It is concluded that this beneficial effect is obtained by a decrease in the testosterone production rate and probably through competitive inhibition of spironolactone and/or canrenone with the androgen receptor in human hair follicles.


Subnormal postconceptional levels of prolactin do not interfere with the early events of human pregnancy. To elucidate the role of bromocriptine treatment and serum prolactin levels in peri-implantational events, 30 healthy women asking for "morning after" type contraception were given bromocriptine. Treatment was started 30.6 +/- 18.4 (mean +/- SD) hours after unprotected intercourse and continued until the next menstruation. Blood samples were taken before and 1 and 2 weeks after initiation of treatment, and the samples were assayed for concentrations of prolactin, progesterone, human chorionic gonadotropin (hCG), and pregnancy-specific beta1-glycoprotein (PSBG) by radioimmunoassay. Prolactin concentrations fell significantly (P less than 0.001) from the pretreatment level of 11.4 +/- 7.9 ng/ml (mean +/- SD) to 2.8 +/- 2.3 ng/ml at 1 week and to 1.9 +/- 0.6 ng/ml after 2 weeks of treatment. Five women had demonstrable hCG in serum 8 to 15 days after unprotected intercourse, and one of them also had PSBG 14 days postcoitum. Pregnancy advanced normally until legal termination in three women, whereas menstruation-like bleeding ensued in two. Our results suggest that neither bromocriptine treatment nor a subnormal maternal serum prolactin level interferes with the early development of human pregnancy.


Mode of action of DL-norgestrel and ethinylestradiol combination in postcoital contraception. Possible mechanisms of action of a combination of ethinylestradiol (EE) and dl-norgestrel as a postcoital contraceptive agent were studied in 12 healthy female volunteers. An oral dose of 0.1 mg of EE and 1.0 mg of dl-norgestrel was given at the predicted time of ovulation and again 12 hours later. Serum luteinizing hormone, prolactin, progesterone, 17 alpha-hydroxyprogesterone, and estradiol were measured by specific radioimmunoassays in blood samples obtained daily from the 8th day of the menstrual cycle to the 1st day of menses. Hormone profiles suggested that the medication elicited a range of individual variations in pituitary and/or ovarian responses. Histologic examination of the endometrium consistently showed significant alteration in endometrial development with a dissociation in maturation of glandular and stomal components. This postcoital contraceptive acts either by (1) suppressing ovulation or (2) disrupting luteal function by acting directly on the corpus luteum or by interfering with appropriate endometrial responses to ovarian steroids.


Correlations between seminal radioimmunoreactive prolactin, sperm count, and sperm motility in prevasectomy and infertility clinic patients. Semen samples were collected from 50 prevasectomy patients and 43 infertility clinic patients. Various parameters were measured, including semen radioimmunoreactive prolactin (rPRL) levels. Linear correlations were tested between the measured parameters, and a significant correlation was found between semen rPRL concentration and sperm count for both the prevasectomy (r = 0.73, P less than 0.00002) and the clinic patients (r = 0.72, P less than 0.00002). For the clinic patients a correlation was also found between the amount of ejaculate rPRL and sperm motility (r = 0.46, P less than 0.002) and between ejaculate volume and motility (r = 0.36, P less than 0.02).


Laser light-scattering study of the effect of progesterone on sperm motility. It is known that progestins can induce in the secretory cells of the cervix the excretion of a mucus that is highly viscuos, scanty, and impenetrable to spermatozoa. Mucus of this type is similar to that excreted during the luteal phase of the normal human menstrual cycle and the cow estrous cycle. It is a natural sequence to ask the question, do progestins also have a direct effect on sperm motility? With dynamic laser light-scattering we measured the motility of freshly washed human spermatozoa and of spermatozoa in the presence of a progesterone, both in terms of their swimming speed distribution as expressed in the spectrum of scattered light. The swimming speed was significantly reduced when the concentration of progesterone was three orders of magnitude greater than that of the physiologic level. This finding confirms the finding in earlier biochemical studies that progesterone has a distinct spermiostatic effect. We suggest this answer to the above question: progestin-releasing contraceptive devices may act on spermatozoa directly as well as in the secretory cells of the cervix.


Vasovasostomy: evaluation of four surgical techniques. Four techniques of vasovasostomy were evaluated in two groups of twelve dogs each. In group 1, one side was anastomosed by a standard technique over a Silastic stent and the other side was anastomosed using a two-layer microsurgical technique. In group 2, one side was anastomosed by a standard technique without a stent and the other side was anastomosed using a one-layer microsurgical technique. Patency was evaluated by methylene blue injection distal to the anastomosis and was found to be about the same for all three groups in which anastomosis was performed without stents. The stented group had a high rate of obstruction. Histologic evaluation, however, showed superiority of both microsurgical techniques over each of the stnadard procedures.


Temporary sterility induced by intrascrotal deposition of silastic-polyvinylpyrrolidone-prostaglandin F2alpha tubes in the rabbit: effect on fetal survival after regain of fertility. In male rabbits of proven fertility, the intrascrotal deposition of two Silastic-polyvinylpyrrolidone tubes containing 3 mg of prostaglandin F2alpha (PGF2alpha)/tube induced within 2 to 4 weeks temporary sterility which lasted for 10 to 14 weeks. Associated with induced sterility were reduction in testicular weight, increase in abnormal spermatozoa (8% to 78% versus 0 to 3.7%), and reduction in sperm motility along the reproductive tract and in the semen for a period of 6 to 7 weeks. During the period of temporary sterility the weight of the epididymis, the sexual drive, and semen volume remained unaltered. Normal fertility was associated with an increase in testicular weight, reduction in the proportion of abnormal sperm, and improved sperm motility. In addition to an altered spermatogenesis, the integrity of mature spermatozoa seemed to be severely affected after PGF2alpha treatment. The reduced number of viable young sired by males that recovered from temporary sterility (pregnancy wastage 35%) as compared with sham-treated controls (pregnancy wastage 3%) suggests that a small percentage of spermatozoa might still be defective at the time of testing. A longer waiting period might be needed to ensure a completely normal reproductive process.


A comparison of gross and microsurgical techniques for repair of cornual occlusion in infertility: a retrospective study, 1968-1978. A 10-year experience is recounted moving from traditional gross implantation methods to microsurgical anastomosis in the repair of cornual occlusion in infertility. Two gross surgical implantation techniques, one involving reaming out the intramural portion of the uterine tube and the other dissecting it out via a transfundal incision, are compared with microsurgical uterotubal anastomosis. The author reports a 4.7 times improvement in the term pregnancy rate after turning to microsurgery and describes his method for anastomosing the transected ampulla or isthmus to the intramural portion of the tube.


An analysis of macrosurgical and microsurgical techniques in the management of the tuboperitoneal factor in infertility. One hundred and sixty tubal reconstructions were analyzed according to a classification which describes the type of tubal repair and the tubal segment treated. The results in 80 women who were operated upon just prior to the application of microsurgical principles were compared with those in 80 women in whom these techniques were employed. In expressing the results, no patients were excluded for any reason. Anatomical patency was not evaluated, and functional patency was measured by conception (abortion, tubal, or term pregnancy). Of the 80 women who had tuboplasty with conventional surgery, 10 (12.5%) successfully delivered at term, but 14 (17%) had tubal gestations. Almost 28% of the women (22) had successful pregnancies after microsurgery, but in 9 (11%) extrauterine pregnancies resulted. The three women with current intrauterine pregnancies could improve the microsurgical series to 31% successful pregnancies. Our initial experience with microsurgical techniques seems to show an increased number of term pregnancies, principally in patients who have undergone anastomosis.


Etiologies and subsequent reproductive performance of 100 couples with recurrent abortion. From 1958 through 1977, 100 couples with documented recurrent reproductive failure were evaluated in the reproductive endocrine unit of the Medical College of Georgia. All couples underwent cytogenetic studies, radiologic evaluation of the Müllerian system, and timed endometrial biopsy. Recurrent pregnancy wastage was found to be associated with genetic disorders in 25 couples. Müllerian anomalies in 15, endocrine anomalies in 23, and negative findings in 37. The subsequent reproductive performance of each group is reviewed.


Corpus luteum dysfunction: serum progesterone levels in diagnosis and assessment of therapy for recurrent and threatened abortion. These studies were designed to show that properly timed measurements of serum progesterone (P) can be conveniently used in the diagnosis and treatment of patients with recurrent and threatened abortion. Luteal phase serum P levels between 2 and 10 ng/ml and serum P levels below 15 ng/ml in the first 10 weeks of gestation were considered diagnostic of corpus luteum (CL) dysfunction. Patients were treated with clomiphene, gonadotropins, and/or progesterone suppositories in order to correct serum P levels, thus elevating the serum P into the normal range. When treatment of patients with subnormal P levels resulted in normalization of serum P, successful pregnancies occurred. CL dysfunctions, either before or after conception, were found in eight of the nine patients with histories of recurrent spontaneous abortions. Correction of serum P was associated with successful pregnancy in these eight patients. Twelve patients with threatened abortion were also found to have subnormal serum P levels. Progesterone suppositories corrected the serum P levels in nine of the eleven patients treated, and none of these patients aborted. Serum P measurements provide a means for evaluation of CL function during early gestation. Management of patients with CL dysfunction can also be monitored with serial serum P measurements, provided that progesterone is the therapeutic agent rather than synthetic progestins.


A significant association between spontaneous abortion and tubal ectopic pregnancy. A retrospective study of 83 patients with pathologically documented tubal ectopic pregnancy demonstrated a statistically significant association (P less than 0.005) between prior spontaneous abortion and ectopic pregnancy. In this population with a low incidence of chronic salpingitis, it is suggested that delayed (post-midcycle) ovulation, causing preovulatory over-ripeness of the ovum, may be the common underlying etiologic factor. The clinical significance of this finding is also briefly discussed.


The relation between plasma testosterone levels and the lengths of phases of the menstrual cycle. Plasma testosterone levels were measured in 331 women of reproductive age. The incidence of clinical signs of hyperandrogenism (hirsutism, acne) was recorded. Ovulatory activity was evaluated clinically by basal body temperature and frequent observation of changes in the appearance of the cervical os and cervical mucus. Plasma testosterone levels were abnormally elevated in patients with clinical signs of hyperandrogenism. The highest mean testosterone levels were noted in the group of hyperandrogenic women with amenorrhea. Significant prolongation of the follicular phase and shortening of the luteal phase were demonstrated to be associated with clinical signs of hyperandrogenism and elevated plasma testosterone levels. Statistically significant correlations between plasma testosterone levels and duration of phases of the menstrual cycle were observed. Testosterone levels were directly related to the length of the follicular phase and inversely related to the length of the luteal phase. A significant inverse correlation between the lengths of the two phases of the menstrual cycle was also demonstrated. These results suggest an association between hyperandrogenism and prolongation of the follicular phase and shortening of the luteal phase of the menstrual cycle, possibly related to the high incidence of infertility and menstrual irregularity reported for hyperandrogenic women.


Effect of prednisone on plasma testosterone levels and on duration of phases of the menstrual cycle in hyperandrogenic women. A group of 106 women of reproductive age with laboratory and clinical evidence of hyperandrogenism was treated with prednisone. The daily dosage varied between 7.5 and 10 mg. Ovulatory activity was assessed prior to and during therapy by basal body temperature and observation of changes in the cervical os and cervical mucus. Plasma testosterone levels were significantly suppressed by prednisone therapy. This was associated with initiation of ovulatory activity in 5 of 14 (35.7%) amenorrheic patients and 10 of 11 (90.9%) anovulatory patients. In 81 ovulatory patients, prednisone therapy resulted in statistically significant shortening of the follicular phase and lengthening of the luteal phase of the menstrual cycle. The mean length of the menstrual cycle was unchanged. Significant correlations between percentage suppression of plasma testosterone and shortening of the follicular phase or lengthening of the luteal phase were observed. Suppression of plasma testosterone by prednisone was maximal after 2 months of treatment, while the effect on the phases of the menstrual cycle was progressive with duration of treatment. The effects of prednisone at daily dosages of 7.5 or 10 mg were not significantly different. These results suggest that prednisone therapy in hyperandrogenic women exerts an effect on both phases of the menstrual cycle, possibly related to suppression of plasma testosterone levels.


Early and late hormonal changes following progesterone injection to patients with secondary amenorrhea. In humans, progesterone (Po) administration has been shown capable of eliciting luteinizing hormone (LH) and prolactin surges in a good estrogenic milieu, but whether such changes induce corpus luteum function still remains controversial. We therefore proposed to explore further the second hypothesis in a placebo-controlled type of study. In patients with secondary amenorrhea and low circulating estradiol (E2) levels with or without ovaries, a 50-mg progesterone injection induced only a short and transient rise in plasma Po levels. On the other hand, a similar injection to patients with mid-to late follicular levels of circulating E2 and intact ovaries induced a surge of plasma LH and prolactin which was followed by a sustained elevation in plasma Po. Furthermore, a rise in basal body temperature accompanied by evidence of secretory endometrium was also observed in these patients. It is concluded that, in a proper endocrine milieu, progesterone administration may induce luteinization in human subjects.


A simple and sensitive nonradioactive method for the detection of urinary human chorionic gonadotropin and diagnosis of early human pregnancy. I. Multiple-unit test. A simple, sensitive, and reproducible method for the detection of urinary human chorionic gonadotropin (hCG) and diagnosis of early human pregnancy is reported. A 5-ml aliquot of filtered early-morning urine sample was concentrated in a microconcentrator (M) to 0.1 ml of retentate which was diluted with 0.4 ml of distilled water and tested in a hemagglutination inhibition test (M-HIT). Also, a 0.1-ml aliquot of filtered unconcentrated urine sample was diluted with 0.4 ml of distilled water and tested in the same hemagglutination inhibition test (HIT). Urine samples from women of reproductive age; from perimenopausal, menopausal, and proteinuric women; and from adult males were tested in the HIT and M-HIT. Some of these urine samples were also tested in the mouse ovulation bioassay (MOB). The M-HIT was significantly more reliable than the HIT for diagnosis of early pregnancy 25 to 55 days after menses. Correct negative results with the M-HIT were obtained in urine samples of most of the nonpregnant cycling, perimenopausal, and menopausal women, and adult males. Urine samples from subjects with severe proteinuria gave false-positive types of reactions in the M-HIT. Positive results were obtained in the MOB with a number of urine samples from pregnant, perimenopausal, and menopausal women. A properly conducted M-HIT should be very valuable in diagnosing pregnancy as early as the 26th day of the cycle in regularly menstruating women.


A simple and sensitive nonradioactive method for the detection of urinary human chorionic gonadotropin and diagnosis of early human pregnancy. II. Single-unit test. A simple, sensitive, and reliable single-unit nonradioactive method for the detection of human chorionic gonadotropin (hCG) in concentrated urine and the diagnosis of early pregnancy is reported. This unit, presently termed the Ayerst pregnancy test kit (APTK), consists of four components: a sampler-filter paper cone, an ultrafilter-concentrator to which a vial holder is attached, a support stand with a mirror, and an immunologic reagent vial. In the APTK, 5 to 6 ml of urine were sampled, filtered, and concentrated, and the hCG in the retentate was detected by Ayerst immunologic reagents [APTK(AY)] and by the Pregnosticon "All In" [APTK(P)]. Some of the unconcentrated urine samples (0.1 ml) were also tested in hemagglutination inhibition tests (HIT) using Ayerst [HIG(AY)] and Pregnosticon "All In" [HIT(P)] reagents. Urine samples from pregnant, nonpregnant (ovulating and nonovulating), perimenopausal, and menopausal women were tested. It was found that the APTK(AY) and APTK(P) were significantly more sensitive and reliable than the HIT(AY) and HIT(P) in detecting low levels of urinary hCG for early diagnosis of pregnancy. The sensitivity and specificity of the APTK(AY) were better than those of the APTK(P). The APTK(AY) give significantly more correct positive and negative results than the other tests performed simultaneously. The APTK(AY) is simpler and safer than the serum radioimmunoassays and radioreceptor assay presently used to detect low levels of hCG for the early diagnosis of pregnancy and other hCG-producing states.


Relationship between plasma prolactin and the endocrine microenvironment of the developing human antral follicle. The aim of the present study was to determine whether any obvious relationships exist between the circulating levels of prolactin at the time of ovariectomy and the endocrine microenvironment and developmental status of antral follicles. The concentrations of prolactin, follicle-stimulating hormone (FSH), and estradiol were measured in peripheral plasma and in antral fluid of follicles collected at varying stages of the menstrual cycle. In addition, the granulosa cells were recovered from each follicle (greater than or equal to 4 mm in diameter) and their numbers were quantitated. When the plasma levels of prolactin ranged from 11 to 100 ng/ml, the antral fluid levels of prolactin were uniformly low (less than 20 ng/ml) and the over-all level of intrafollicular activity remained unchanged. However, when the prolactin concentrations in plasma exceeded 100 ng/ml, the levels of prolactin in antral fluid were significantly elevated. Moreover, the high levels of intrafollicular prolactin were associated with a marked reduction in FSH accumulation and low levels of estradiol in antral fluid. Also, these follicles were severely deficient in granulosa cells. This marked reduction in intrafollicular activity was not associated with any significant changes in the mean levels of estradiol and FSH in peripheral plasma. These findings suggest that hyperprolactinemia is associated with a marked reduction in intraovarian activity and that the extent of this reduction may not be always apparent from the levels of circulating estradiol.


Tissue testosterone and dihydrotestosterone from bilateral testis biopsies in males with varicocele. Nine males with varying degrees of subfertility with left varicocele underwent bilateral testicular biopsy for determination of testicular testosterone (T) and dihydrotestosterone (DHT) content. Testicular tissue T and DHT levels varied greatly, and there was no significant difference when the group T and DHT content of the left testis was compared with that of the right testis. When the respective mean preoperative sperm count was compared with the bilateral tissue T and DHT content, no consistent relationship was found.