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Biomedical subjects

R Herman

Publications and source records attributed to R Herman.

At least 37 records · Page 2Linked to original sources
PubMed1987

Non-steroidal anti-inflammatory drugs: how do they work?

Current dogma holds that non-steroidal 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 (for example, 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 (3mM) 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 post-stimulation rise in intracellular cyclic AMP. NSAIDs therefore inhibit early steps in neutrophil enhance intracellular levels of cyclic AMP.

Adult↗
PubMed1986

Processing of phage T4 td-encoded RNA is analogous to the eukaryotic group I splicing pathway.

Several features of the split td gene of phage T4 suggest an RNA processing mechanism analogous to that of the self-splicing rRNA of Tetrahymena and other group I eukaryotic introns. Previous work has revealed conserved sequence elements and the ability of td-encoded RNA to self-splice in vitro. We show here that a noncoded guanosine residue is covalently joined to the 5' end of the intron during processing. Further, we demonstrate the existence of linear and circular intron forms in RNA extracted from T4-infected cells and from uninfected Escherichia coli expressing the cloned td gene. Sequence analysis of the intron cyclization junction indicates that the noncoded guanosine and one additional nucleotide are lost from the 5' end of the intron upon cyclization. This analysis places a uridine residue upstream of the cyclization site, in analogy to three other group I cyclization junctions. These striking similarities to the splicing intermediates of eukaryotic group I introns point not only to an analogous processing pathway and conserved features of cyclization site recognition but also to a common ancestry between this prokaryotic intervening sequence and the group I eukaryotic introns.

Animals↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1982

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↗
PubMed1982

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↗
PubMed1982

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↗
PubMed1982

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↗