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Biomedical subjects

R Herman

Publications and source records attributed to R Herman.

At least 55 records · Page 3Linked to original sources

Protection against fatal murine Chagas' disease with a Leishmania braziliensis panamensis stock.

Past attempts to immunize mice against a fatal Trypanosoma cruzi infection utilizing related hemoflagellates have been unsuccessful. In the present study, C57BL/6 mice received a footpad inoculation of 10(7) promastigotes of Leishmania braziliensis panamensis. Six and 9 weeks subsequent to this inoculation mice were infected intraperitoneally with the Tulahuen strain of T. cruzi. All immunized mice survived infection over the 6-month period of observation whereas control mice regularly died. There was an early transient T. cruzi parasitemia in the immunized mice. Culture of blood and organs as well as histopathological examination of various organs 6 months post-challenge failed to yield any evidence of T. cruzi. Heat-killed and freeze-thawed extracts of promastigotes did not confer any protection. These observations raise the possibility that certain leishmanial species might confer natural protection against a T. cruzi infection and that this information could be useful in the development of a vaccine.

Animals↗

Modes of action of aspirin-like drugs.

Current dogma holds that nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibition of the synthesis and release of prostaglandins. However, NSAIDs also inhibit the activation of neutrophils, which provoke inflammation by releasing products other than prostaglandins. We now report that NSAIDs (e.g., indomethacin, piroxicam) inhibit activation of neutrophils by inflammatory stimuli, such as C5-derived peptides and leukotriene B4, even when cyclooxygenase products generated in suspensions of stimulated neutrophils (prostaglandin E and thromboxanes) are present. Sodium salicylate (3 mM) greatly inhibited aggregation of neutrophils but had no effect on aggregation of platelets or production of thromboxane induced by arachidonate. Sodium salicylate and other NSAIDs also inhibit calcium movements (45Ca uptake, changes in fluorescence of chlortetracycline and quin-2). Aspirin, sodium salicylate, indomethacin, and piroxicam also enhanced the poststimulation increase in intracellular cyclic AMP. NSAIDs therefore inhibit early steps in neutrophil activation as reflected by their capacity to inhibit movements of Ca and to enhance intracellular levels of cyclic AMP.

Anti-Inflammatory Agents↗

Effects of long-term in vitro cultivation on Leishmania donovani promastigotes.

Promastigotes of Leishmania donovani that had been subcultured in modified Tobie's medium for 2 to 3 years showed decreased infectivity and lack of virulence for hamsters and mice compared to newly transformed promastigotes. Amastigotes derived from these long-term promastigote cultures decreased in number rapidly in hamsters, but only slightly in mice, over a 48-day period. In cultured mouse and hamster macrophages infected in vitro, amastigotes derived from long-term cultures rapidly decreased to low numbers, which persisted. The same pattern was seen in macrophages treated with catalase, an inhibitor of the oxygen-dependent killing mechanism of the macrophage. Promastigotes from long-term cultures also differed from virulent first-passage promastigotes in size, growth patterns in Tobie's medium, and in the quantities of some of their antigens.

Animals↗

Relationship between delayed hypersensitivity response and acquired cell-mediated immunity in C57BL/6J mice infected with Leishmania donovani.

The relationship between the development of acquired cell-mediated immunity and the concomitant level of specific delayed hypersensitivity (DH) in C57BL/6J mice infected with the intracellular protozoan parasite Leishmania donovani was studied. It was determined that the intradermal injection of Leishmania antigen (heat- or phenol-killed flagellated forms of L. donovani) could elicit a DH response as early as day 10 and as late as day 120 postinfection in mice infected by the intravenous route. Dose-response studies showed that there is an inverse relationship between the size of the infecting dose of parasites and the magnitude of the DH response. Thus, increasing the degree of infection depressed the DH response. This depression, however, could be abrogated by treatment of mice with cyclophosphamide (201 mg/kg) before intradermal injection of antigen.

Animals↗

Development and plasticity of visual and vestibular generated eye movements.

Slow phase horizontal eye movements, elicited by the vestibulo-ocular reflex (VOR) and/or visual pursuit (VP) systems, were examined in normal children (NC, 9-16 years) and normal adults (NA). At slow frequencies of sinusoidal stimulation of the body (with the head immobilized) and/or of a visual target, the NC (9-12 years) exhibited (a) immature VP and VOR Suppression and mature VOR Enhancement in the presence of a visual image; (b) immature VOR Suppression and mature VOR Enhancement in the presence of a non-visual image of the spatial location of a visual target, an extra-retinal signal; (c) inability to augment or depress the VOR gain with a non-visual image; (d) mature VOR Suppression ratios; and (e) adjustment of VOR gain to a high value. The maturational process was featured by (a) parallel development of VP and VOR Suppression; (b) modification of the VOR gain; and (c) an increasing ability to augment or depress the VOR with a non-visual image. The observations in NC (9-12) are ascribed to a maturational lag of an extra-retinal process interacting with mature retinal and vestibular processes and, hence, suggest that both the retinal and vestibular contributions to ocular stability predate the development of an extra-retinal signal. When mature, the central nervous system utilizes both extra-retinal and retinal signals to mediate adaptive regulation of VOR gain and to preserve stable visual pursuit motion and VOR Suppression. Our findings also suggest that during tasks requiring visual-vestibular interaction, VP and VOR mechanisms appear to be indirectly rather than directly coupled.

Adolescent↗

An evaluation of brainstem function as a prognostication of early idiopathic scoliosis.

In an attempt to elucidate whether assessment of the brainstem function helps to predict the outcome of early idiopathic scoliosis, a series of neurophysiological studies in children with idiopathic scoliosis was made cooperatively in Japan and the United States. The eye movement in 86 cases with idiopathic scoliosis in the rapidly growing ages was tested and compared with 66 normal control children. About one-half of the patients with idiopathic scoliosis demonstrated dysfunction in the brainstem test. The natural histories of the curves were available in 48 of the 86 cases in a follow-up study ranging from 6 months to 2 1/2 years. Statistically, there was a positive correlation between the brainstem dysfunction and the curve progression. It was concluded that the functional assessment of the brain center of the postural regulation system can be used in predicting the outcome of idiopathic early curves detected in the school screening program.

Adolescent↗

Rehabilitation following brain damage: some neurophysiological mechanisms. Functional recovery in the visual and vestibular pathways.

The visual and labyrinthine sensing systems are often neglected in the rehabilitation process of patients with central nervous system (CNS) lesions. Nevertheless, their integrity is essential for the construction of motor tasks ranging from accurate reaching to the co-ordinated behaviours of posture and locomotion. This tasks may be influenced considerably by the roles of the visual and vestibular systems in the perceptual analysis of localizing objects in space ("egocentric localization") and of spatial orientation of the body ("ego-orientation") and in controlling oculomotor and postural stability. The anatomy, physiology, clinical relevance and patterns of recovery of function of two specific visual-vestibular related behaviours is addressed, namely ocular stability and egocentric localization. Emphasis is placed upon such issues as (a) motor learning in complete and incomplete lesions as adjudged from observations of peripheral vestibular nerve disorders; (b) the role of the cerebellum in calibrating motor performance with particular reference to the modifiability of the vestibulo-ocular reflex to attain ocular stability; (c) the use of redundant or complementary structures as assumed from evidence of recovery from chronic visual field deficits; and (d) specified behavioural tactics as a mechanism for adaptation.

Central Nervous System Diseases↗

Rehabilitation following brain damage: some neurophysiological mechanisms. A therapeutic approach based on theories of motor control.

Rehabilitation programmes concerned with functional recovery of patients with central nervous system (CNS) lesions may be in need of developing processes more consistent with prevailing concepts of motor control and of behavioural requirements by the CNS for motor learning. Both central and peripheral factors can play important roles in providing for finely orchestrated and relatively accurate learned motor performance. The relative influence of each of these factors on motor recovery is determined, in part, by the actions observed, i.e. control of body ("mid-line") and/or limb ("peripheral") position, by the interaction between two principal features of the control system, fixation (stability) and motion, by the inherent plasticity of structures, and by the ability of cerebral mechanisms to code, store and recall information with minimal error and time delay. A functional theory for governing spatial and temporal components of motor performance is presented; this is based upon three attributes: (a) attainment of control of fixation and motion of midline (eye-head-trunk) and peripheral structures in developmental order; (b) organization of serial fixation-motion steps in the guidance-manipulation functions of limbs, and (c) provision for coding spatial and temporal information related to both fixation and motion.

Central Nervous System Diseases↗

Sensitization of offspring of Leishmania donovani-infected hamsters to immunization and of offspring of immunized hamsters to challenge.

Female hamsters, infected intracardially (i.c.) with 1.0--2.0 x 10(5) amastigotes of Leishmania donovani produced offspring, following mating, which, when immunized subcutaneously with 1.0 x 10(7) amastigotes at 8 weeks of age, were more resistant to i.c. challenge 6 weeks later than were hamsters born to non-infected mothers. Offspring of mothers infected with as many as 6.0 x 10(6) amastigotes demonstrated no greater capacity for immunization than did those of mothers infected with 1.0 x 10(5) amastigotes. Sensitization of offspring of infected mothers apparently is transplacental since the effect could only be seen in offspring of infected mothers and not in those of normal mothers weaned by infected dams. Offspring of female hamsters immunized by footpad inoculation of 1.0 x 10(7) amastigotes exhibited reduced spleen parasite burdens when challenged at 8.5 weeks of age and reduced spleen and liver parasite burdens when challenged at 16 weeks of age, compared to offspring of nonimmunized hamsters; this effect was not noted following challenge of offspring of the two groups within 1 day of weaning. The passage of parasites from mother to young during gestation and/or nursing apparently does not occur since, at 125 days of age, no parasites were observed in spleen or liver impression smears of offspring of hamsters infected i.c. with 6.0 x 10(6) amastigotes while parasites were seen in such smears of hamsters infected, 120 days previously, with 10 amastigotes i.c. Thus, sensitization to immunization in offspring of infected hamsters and to challenge of offspring of immunized hamsters is apparently transplacental, effected either by soluble leishmanial antigen, soluble lymphocyte (or transfer) factor, or by cells.

Animals↗

Visually triggered eye-arm movements in man.

The degree of temporal coupling and the nature of temporal ordering between the gaze (eye-head) and arm motor systems was studied in normal subjects by measuring the reaction time, RT, of each system to randomly generated visual signals presented along the horizontal meridian: (1) at two spatial locations, 15.5 degrees and 29.1 degrees, (2) to the right and left of a central fixation point, and (3) with and without room illumination. Upon detecting the visual signal, the subject was instructed to guide the arm from its rest position upon a supporting table and to extinguish the light source by touching a metal disc enclosing the stimulus "as quickly and accurately as possible." The results indicated (1) saccadic eye motion initiated gaze towards the target, (2) a change in the eccentric position of the target was associated with alteration of the eye and arm RT by a similar value; the interval between eye and the subsequent arm RT was invariant with spatial location no matter the presence or absence of room illumination, and (3) the arm RT increased when visual information of the environment was not available. It is postulated that a visual stimulus triggers a command system releasing a patterned sequence of eye-hand-arm motion; the initiation of motion in these motor systems is based upon the same retinal error calculation; however, no rigid rule can be established for the serial ordering or temporal sequencing of motion between the triggered motor systems. The temporal arrangement between head and arm with eye can be modified, at least in part, by alterations in supraspinal control of postural mechanisms and/or motoneuronal excitability of the responding muscles prior to motion.

Adolescent↗

Sensory feedback for head control in cerebral palsy.

Five school-aged children with cerebral palsy were given an auditory feedback signal when their heads tilted past a predetermined angle. After three to seven individual sessions, all of the children were able to work in the classroom on regular school activities while using the sensory feedback to monitor and after head position. Over a period of nine weeks, all children improved their stabilizing skills of the head and neck when responding to the performance information. Three of the children were successful at self-monitoring for up to one hour while maintaining the head within the required zone at least 80 percent of the time. Inability of the other two children to do so was probably related to poorer motor control and possibly to a lack of independent work skills.

Acoustic Stimulation↗

Characterization of populations of promastigotes of Leishmania donovani.

Promastigotes of Leishmania donovani cultured for either 3 or 10 days in vitro and inoculated intracardially into golden hamsters with an equal number of organisms from either population showed a 7-fold difference in infectivity when compared at both 10 and 16 days post-infection. Reproducible histochemical staining for the promastigote enzymes glucose-6-phosphate dehydrogenase (G6PDH) and peptidase after polyacrylamide gel electrophoresis showed two isoelectric variants of G6PDH (Bands 1 and 2) that displayed a 45% decrease (Band 1) and a 60% increase (Band 2) in total activity when 3- and 10-day-old promastigotes were compared. Peptidase activity, present in a single band, increased 7-fold in 10-day-old promastigotes. A decrease in the lectin-induced agglutination of promastigotes by castor bean agglutinin (RCA60), specific for D-galactose and N-acetyl-D-galactosamine, was seen when 3- and 10-day-old promastigotes are compared. Antisera raised against sonicated 10-day-old promastigotes showed a unique precipitin band between the antiserum and sonicated 10-day-old promastigotes not found between the antiserum and sonicated 3-day-old promastigotes.

Acetylgalactosamine↗