Biomedical subjects
Publications and source records attributed to B Cohen.
Ureterosigmoidostomy can be complicated by pyelonephritis, renal calculi, hypokalemic hyperchloremic acidosis, and colonic neoplasia. It has been associated with the development of hyperammonemia and encephalopathy in patients with underlying liver disease. We report a rare case of hyperammonemic encephalopathy in a patient with normal liver function.
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In two children with acute lymphocytic leukaemia in whom severe anaemia developed, serum samples collected over 9-12 months showed high concentrations of B19 parvovirus, the aertiological agent of fifth disease. In one patient, anaemia recurred with the reappearance of virus in serum; in the other, the anaemia persisted. Smears of bone marrow aspirates obtained during periods of viraemia showed giant pronormoblasts and either absent mature erythroid cells or erythroid hypoplasia. Parvovirus replication in the marrow was detected by Southern blot of cellular DNA. An underlying immune deficit was suggested by low titres of specific antibodies against B19 parvovirus. Treatment of one patient with plasma containing specific antibodies against parvovirus resulted in a transient fall in serum virus levels, the appearance of reticulocytes, and symptoms of fifth disease.
Omnipause neurons take part in the generation of saccadic eye movements. They lie around the midline in the caudal pontine reticular formation, in an area usually ascribed to the nucleus raphe pontis (rp). In this study of the monkey (Macaca fascicularis and M. mulatta), we describe four series of experiments aimed at establishing that omnipause neurons lie within a distinctive cytoarchitectonic entity, which we call the nucleus raphe interpositus (rip): (1) cytoarchitectural study, (2) recording-lesion experiments to establish in which cell group omnipause neurons lie, (3) cytochrome oxidase distribution in the omnipause region and neighboring structures, and (4) neuroanatomical tracing experiments to demonstrate afferents to the omnipause region. In the detailed cytoarchitectural study of the midline structures in the caudal pons and rostral medulla, a distinctive group of neurons (rip) adjoining the ventrocaudal border of rp and dorsal to the nucleus raphe magnus (rm) is described. The striking features of rip are the uniformly arranged, narrow row of the cells either side of the midline, and the extensive horizontally oriented dendritic trees of its neurons. The abducens rootlets (NVI) pass through the reticular formation at the same rostrocaudal level as rip and form a reliable landmark for its location. Cytochrome-oxidase-stained sections demonstrated additional differences between rip and adjacent cell groups: in rip the neurons and their extensive dendrites stained strongly, but not the surrounding neuropile, whereas in rp both the neurons and the neuropile stained darkly, so that individual neurons were difficult to see. Unlike rp, rip coincides with the location of omnipause neurons, and lesions marking the sites of individual omnipause units lay within its boundaries. Tritiated leucine was injected into superior colliculus (sc), which is known to have monosynaptic connections with omnipause neurons. Labelled axons and patterns of silver grains taken to indicate the presence of terminal branching were found in and around rip, but no significant labelling was seen in rp or rm. It is concluded that the omnipause neurons lie within the rip in the monkey. These functional and morphological differences between rip and the adjacent raphe nuclei are used to justify its characterization as an independent cell group in the monkey. In order to relate these findings to man, cytochrome oxidase experiments were carried out on the human brainstem, and the pattern of staining at the level of the abducens rootlets was correlated with the cytoarchitecture.(ABSTRACT TRUNCATED AT 400 WORDS)
The human (2'-5') oligo(A) synthetase gene contains two independent cis-acting DNA elements, A and B, which act as transcriptional enhancers. Element A alone is not activated by IFN treatment. Element B alone confers IFN-inducibility to the herpes tk promoter. Two murine (2'-5') oligo(A) synthetase genes were isolated and their promoter sequences show high conservation of element A and B. A synthetic oligonucleotide, containing 16 bp of the human element B, or 14 bp of the homologue murine element B, was linked to a TK-CAT construct. These oligonucleotides were shown to be sufficient to activate the TK promoter in the presence of IFN. When multiple repeats of the interferon-responsive sequence (E-IRS) were cloned in 5' of the TK promoter, the activation ratio was increased. In vitro, specific binding of nuclear protein(s) is observed to the radiolabelled synthetic human E-IRS. This binding is competed by the addition of cold synthetic mouse E-IRS or fragments of genomic DNA containing the E-IRS.
1. The nucleus of the optic tract (NOT) was electrically stimulated in alert rhesus monkeys. In darkness stimulation evoked horizontal nystagmus with ipsilateral slow phases, followed by after-nystagmus in the same direction. The rising time course of the slow phase velocity was similar to the slow rise in optokinetic nystagmus (OKN) and to the charge time of optokinetic after-nystagmus (OKAN). The maximum velocity of the steady state nystagmus was approximately the same as that of OKAN, and the falling time course of the after-nystagmus paralleled OKAN. 2. Increases in frequency and duration of stimulation caused the rising and falling time constants of the nystagmus and after-nystagmus to become shorter. Changes in the falling time constant of the after-nystagmus were similar to changes in the time constant of OKAN produced by increases in the velocity or duration of optokinetic stimulation. 3. Stimulus-induced nystagmus was combined with OKN, OKAN and per- and post-rotatory nystagmus. The slow component of OKN as well as OKAN could be prolonged or blocked by stimulation, leaving the rapid component of OKN unaffected. Activity induced by electrical stimulation could also sum with activity arising in the semicircular canals to reduce or abolish post-rotatory nystagmus. 4. Positive stimulus sites for inducing nystagmus were located in the posterolateral pretectum. This included portions of NOT that lie in and around the brachium of the superior colliculus and adjacent regions of the dorsal terminal nucleus (DTN). 5. The data indicate that NOT stimulation had elicited the component of OKN which is responsible for the slow rise in slow phase velocity and for OKAN. The functional implication is that NOT, and possibly DTN, are major sources of visual information related to retinal slip in the animal's yaw plane for semicircular canal-related neurons in the vestibular nuclei. Analyzed in terms of a model of OKN and OKAN (Cohen et al. 1977; Waespe et al. 1983), the indirect pathway, which excites the velocity storage mechanism in the vestibular system to produce the slow component of OKN and OKAN, lies in NOT in the monkey, as it probably also does in cat, rat and rabbit. Pathways carrying activity for the rapid rise in slow phase velocity during OKN or for ocular pursuit appear to lie outside NOT.
Off-vertical rotation (OVAR) in darkness induced continuous horizontal nystagmus in humans at small tilts of the rotation axis (5 to 30 degrees). The horizontal slow eye velocity had two components: a mean velocity in the direction opposite to head rotation and a sinusoidal modulation around the mean. Mean velocity generally did not exceed 10 deg/s, and was less than or equal to the maximum velocity of optokinetic after-nystagmus (OKAN). Both the mean and modulation components of horizontal nystagmus increased with tilt angle and rotational velocity. Vertical slow eye velocity was also modulated sinusoidally, generally around zero. The amplitude of the vertical modulation increased with tilt angle, but not with rotational velocity. In addition to modulations in eye velocity, there were also modulations in horizontal and vertical eye positions. These would partially compensate for head position changes in the yaw and pitch planes during each cycle of OVAR. Modulations in vertical eye position were regular, increased with increases in tilt angle and were separated from eye velocity by 90 deg. These results are compatible with the interpretation that, during OVAR, mean slow velocity of horizontal nystagmus is produced by the velocity storage mechanism in the vestibular system. In addition, they indicate that the otolith organs induce compensatory eye position changes with regard to gravity for tilts in the pitch, yaw and probably also the roll planes. Such compensatory changes could be utilized to study the function of the otolith organs. A functional interpretation of these results is that nystagmus attempts to stabilize the image on the retina of one point of the surrounding world. Mean horizontal velocity would then be opposite to the estimate of head rotational velocity provided by the output of the velocity storage mechanism, as charged by an otolithic input during OVAR. In spite of the lack of actual translation, an estimate of head translational velocity could, in this condition, be constructed from the otolithic signal. The modulation in horizontal eye position would then be compensatory for the perceived head translation. Modulation of vertical eye velocity would compensate for actual changes in head orientation with respect to gravity.
Off-vertical axis rotation in darkness induces a perception of body motion which lasts as long as rotation continues. Perceived body motion is the combination of two simultaneous displacements. The most easily perceived is a translation without rotation along a conical path, at the frequency of the actual rotation. Meanwhile, the subjects feel as if they were always facing towards the same direction. The summit of the cone is generally below the head, from the waist to below the feet, and subjects have a sense of progression in the direction opposite to actual spinning. Some subjects feel, on the contrary, the summit of the cone above their heads, and the progression in the direction of spinning. Subjects also perceived another body motion, although it was faint for some of them. It consists of a rotation at low velocity in the same direction as progression along the cone. The axis of the cone is perceived as slowly rotating along a larger cone. These motion perceptions increase with tilt angle and rotation velocity. They probably result from the analysis by the Central Nervous System of the acceleration acting on the otoliths. The perceived trajectory would be reconstructed from estimates of gravity, and kinematic variables such as head translational acceleration and velocity, and head rotational velocity. The same variables would account for OVAR-induced nystagmus. Motion sickness would result from the impossibility of reconstructing a consistent body movement from most sets of values of these variables.
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We have examined the expression on a panel of 22 human kidneys of polymorphic B-cell determinants recognized by mouse monoclonal antibodies. Monoclonal antibodies from a mouse immunized with an antigenic preparation from a DR4 positive B-cell line reacted preferentially with kidneys from DR4 positive donors (p less than 0.005), and the pattern of reactivity with kidney tissues was similar to that of antibodies to monomorphic determinants of class II. However, these antibodies did not show clear specificity for DR4 on lymphocytes in standard serological analyses. These results provide evidence for the expression of polymorphic class II determinants on human kidneys. Reasons for the differences in the apparent specificities of the monoclonal antibodies when tested on kidney sections and lymphocytes are discussed.
A community-based study investigating the natural history of recurrent and non-recurrent croup is described. Daily temperature data were collected during 1977-83, in order to analyse seasonal variation and the effect of atmospheric temperature on the number of croup episodes per calendar month. A case-control study of 137 cases--consisting of 75 children with recurrent croup and 45 children with non-recurrent croup--and 236 controls matched by age and sex was also conducted. It aimed to study associations between croup and other selected diseases in the patients and their families. Recurrent croup differed from non-recurrent croup in its natural history in a number of ways. There was a winter and autumn peak in the number of episodes per month. These episodes occurred on days with significantly lower maximum and minimum temperatures. Recurrent croup was significantly associated with a patient history of asthma and wheezy bronchitis and a family history of croup. In contrast, non-recurrent croup showed an autumn peak only, as well as no association with atmospheric temperature or other disease in the patients and their families. This study confirms and extends observations indicating that recurrent croup involves a persistent and inherited airways hyper-reactivity that is triggered by viral and other stimuli, including those related to temperature.
1. Optokinetic nystagmus was elicited in alert monkeys by movement of the visual surround in their horizontal or yaw plane, and optokinetic after-nystagmus was recorded in darkness. The animals were upright or were statically tilted at various angles from the upright. While upright, the OKAN was horizontal, and there were no vertical or roll components. When animals were tilted to either side or forward or back, vertical or roll components appeared both in the primary and secondary OKAN. Such components were also observed during nystagmus and after-nystagmus induced by electrical stimulation of the nucleus of the optic tract. The characteristics of the cross-coupled components indicated that they were mediated through the velocity storage mechanism in the vestibulo-ocular reflex. 2. A principle was inferred that explained the appearance of cross-coupled vertical or roll components in the primary and secondary OKAN: With the animal in a tilted position, a vector of eye velocity during OKN along the body-vertical axis was converted during primary OKAN toward a spatial-vertical axis with the same sense by a right hand rule. Thus, slow phase velocity along a vector toward the top of the animal's head during horizontal OKN rotated so that it tended to be directed spatially upward during primary OKAN. The reverse was true for OKN with a velocity vector directed toward the animal's feet. It rotated during primary OKAN so that it tended to be aligned with the direction of gravity. The vector of velocity during secondary OKAN was opposite to the direction of the vector during primary OKAN and was approximately aligned with spatial vertical. 3. OKN and OKAN were elicited about the animal's pitch and roll axes while they were upright and statically tilted at various angles away from the spatial vertical. There was a graded increase in the strength of vertical and roll OKN and OKAN and in the falling time constant of OKAN as the animals were tilted so that the axis of pitch or roll eye movements was moved toward alignment with the spatial vertical. Thus, velocity storage during pure vertical and roll nystagmus was similar to that during yaw OKN and OKAN in tilted positions: it was maximal along the pitch and roll axes when these axes were aligned with gravity. 4. The data indicate that the gravitational field is of fundamental importance in imposing a spatial reference onto the velocity storage integrator.(ABSTRACT TRUNCATED AT 400 WORDS)
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To assess the role of peripheral epinephrine in social anxiety, the authors infused 11 patients meeting DSM-III criteria for social phobia with intravenous epinephrine over 60 minutes. Although the mean plasma epinephrine level increased from 113 to 928 pg/ml, only one of the 11 patients experienced observable anxiety; this finding suggests that an increase in plasma epinephrine level alone is inadequate to cause social anxiety. Of the variables measured, only the average minute volume correlated with self-rated anxiety. Ventilatory indexes might be better correlates of subjective anxiety than other physiological variables.
Six of eight patients with obsessive-compulsive disorder had an exacerbation of symptoms when given m-chlorophenylpiperazine. Fenfluramine and placebo produced mild improvement. Six patients given intravenous clonidine experienced marked reduction in obsessions. Implications for serotonergic and noradrenergic hypotheses of obsessive-compulsive disorder are discussed.
Rabbit antisera have been prepared against isolated rheumatoid factors (RF's). It was considered that RFs are anti-idiotype antibodies and that the anti-RF antisera had anti-anti-idiotype specificity. Furthermore, it was considered that the RF's carry an "internal image" of the putative "antigen X" and that the rabbit antisera would have specificity for this "antigen-X". Reactions of the rabbit antisera with the early and late antigens of CMV, EBV antigens and nuclear antigens suggest that there may be an "internal image" of these antigens in rheumatoid factor molecules and that they all may be related to the immunogenesis of RF.
B19 parvovirus is the etiologic agent of fifth disease and transient aplastic crisis. In natural infections, B19 antigen and DNA have been detected in sera early in the course of aplastic crisis and only rarely in fifth disease. We have found B19 DNA in circulating cells of infected patients by DNA dot blot with a virus-specific probe: in four of four sickle cell patients with aplastic crisis, in one asymptomatic sibling, and in one normal adult with fifth disease. Only two of the sera showed B19 DNA. High-molecular weight intermediate forms were detected by Southern analysis of DNA extracted from cells, thus indicating active replication of virus in cells rather than passive adsorption to their surface membranes. Separation of cells into high- and low-density fractions resulted in a concentration of the virus DNA in the granulocytic fraction.
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