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Biomedical subjects

B J Schmidt

Publications and source records attributed to B J Schmidt.

At least 37 records · Page 2Linked to original sources

Afterhyperpolarization modulation in lumbar motoneurons during locomotor-like rhythmic activity in the neonatal rat spinal cord in vitro.

Motoneuron afterhyperpolarization (AHP) amplitude and somatic input conductance were monitored during pharmacologically induced, locomotor-like ventral root activity using an isolated neonatal rat spinal cord preparation (transected at the C1 level). Nonspontaneously firing motoneurons were selected for study. Single spikes were evoked at regular intervals by brief depolarizing current pulse injections, while somatic input conductance was monitored by hyperpolarizing current pulses. The induction of rhythmic ventral root activity was associated with tonic depolarization of motoneurons as well as superimposed rhythmically alternating membrane depolarization and hyperpolarization (locomotor drive potentials, LDPs). In 9 of 13 trials (six of eight cells) the peak amplitude of AHPs following current-evoked action potentials was reduced during both the hyperpolarized and the depolarized phases of the LDP, compared with the pre-locomotor condition. The peak AHP amplitude increased during the depolarized phase of the LDP in 4 of 13 trials (three of eight cells); however, in 3 of these 4 trials measurement of the AHP later in the course of its trajectory, using a half decay time (HDt) reference point, demonstrated AHP amplitude reduction during rhythmic activity compared with the pre-locomotor condition. In seven of eight motoneurons the induction of rhythmic activity was associated with a decrease in input conductance. The pattern of AHP amplitude and conductance modulation during the two phases of the LDP was consistent for individual trials; however, there was considerable intertrial variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

[Experiences in Kiel with the cochlear implant].

Since 1988 22 deaf patients were provided with a 22-channel cochlear implant at the Kiel University Hospital. No surgical or postoperative complications were seen in any of the patients. Side effects like facial stimulation and pain sensation during electrode activation do not reduce the utility. Tinnitus may initially be severe but usually subsides to preop levels after a few days. A tinnitus masking effect is pronounced during stimulation but hardly lasts long after switch off. Besides an individually arranged hearing training the accurate speech processor fitting to the needs of the patient remains the cornerstone of successful rehabilitation. Objective intraoperative measurements such as the electrically evoked brain stem potentials and the middle ear reflexes yield estimates of the threshold values relevant for initial processor programming. Further information needed for the following extensive fine adjustment is obtained by subjective evaluation of loudness growth during electrical stimulation with variable parameters, by loudness scaling of narrow band noises with different middle frequencies and intensities presented under free field conditions and by speech audiometric procedures. The latter include a monosyllabic rhyme test and a logatom test developed at this institution. More speech testing is applied to document the degree of auditive rehabilitation. The results of speech tracking and the Freiburg tests as well as a new sentence test in silence and noise are discussed. In the multisyllable Freiburg test all but two of the adults understand the complete presented material, in the open set monosyllable test an average of 55% correct is achieved. Speech discrimination-oriented ranking showed 95% of all postlingually deaf patients in the highest performance category.

Adolescent↗

In vitro evaluation of the effects of metronidazole on rabbit corneal epithelial cells.

Because of its usefulness in treating facial rosacea, metronidazole may also be an effective treatment for ocular rosacea. The toxicity of metronidazole on the corneal epithelium has not previously been reported. In this study, the effects of metronidazole on rabbit corneal epithelium in vitro were evaluated. Epithelial cell cultures were exposed to various concentrations of metronidazole to determine its effect on cell morphology, viability, and wound healing. Both morphological changes and cell loss were seen after 1 day of incubation in media containing metronidazole at concentrations of > or = 3.0 mg/ml. In media with metronidazole at 1.0 mg/ml, these toxic effects were not seen. The effects of metronidazole on wound healing were determined by comparing the area of wounds in the epithelial cell layer for time periods of up to 44 h. There was no statistically significant delay in wound closure when cells were incubated in media containing metronidazole at a concentration of 2.0 mg/ml as compared with cultures incubated in media without metronidazole. However, a significant delay in wound closure occurred at concentrations of > or = 3.0 mg/ml. The results at these drug concentrations suggest that metronidazole has low corneal epithelial toxicity. Allowing for the dilutional effects of tears in patients with normal tear function, concentrations of 4.0-5.0 mg/ml (0.4-0.5%) would probably be tolerated by the corneal epithelium. Clinical safety and efficacy studies are necessary to determine if topical metronidazole will prove useful for the treatment of ocular rosacea.

Animals↗

TTX-resistant NMDA receptor-mediated voltage oscillations in mammalian lumbar motoneurons.

1. Whole cell current-clamp recordings were obtained from tetrodotoxin (TTX)-isolated motoneurons in the in vitro neonatal rat spinal cord to examine the effects of N-methyl-D-aspartate (NMDA) receptor activation on membrane voltage. 2. NMDA induced rhythmic membrane voltage oscillations, and injection of current ramps revealed the presence of bistable membrane properties, the base and peak of which corresponded to the base and peak values of the voltage oscillations. 3. Nonlinear motoneuron membrane properties induced by NMDA receptor activation may be well suited to reinforce rhythmic patterns of motor output during certain behaviors such as locomotion.

Animals↗

Paroxysmal dyskinesia associated with hypoglycemia.

The association of movement disorders with hypoglycemia has been rarely noted in the past. We recently observed 2 patients with documented hypoglycemia and paroxysmal dyskinesias. One patient had evidence of an insulin-secreting tumor. The other patient had insulin-dependent diabetes, and also experienced recurrent episodes of hypoglycemic hemiparesis. Classical adrenergic symptoms of hypoglycemia were absent in both patients. Our observations support the concept that the development of neuroglycopenic symptoms cannot be predicted from blood glucose measurements alone, but must depend on other factors controlling the availability or metabolism of glucose in the brain.

Blood Glucose↗

Early immunization of neonates with trivalent oral poliovirus vaccine.

Described is the evaluation in Brazil of the immune response of early immunization with trivalent oral poliovirus vaccine (TOPV). A total of 85 normal neonates from São Paulo were assigned one of the following immunization schedules: group A--one dose of TOPV at birth and subsequent doses at 2, 4, and 9 months of age; or group B--one dose of TOPV at 2, 4 and 6 months of age. Blood samples were collected sequentially from the mother at delivery, from the umbilical cord, and from the child at 2, 4, 6, 9 and 12 months of age for assay of poliovirus neutralizing antibodies. Administration of TOPV at birth, in addition to establishing immunity against poliomyelitis at an earlier stage, produced a superior immune response to poliovirus type 3. At the end of the first year, the proportion of susceptible individuals was 3.7% in group A and 25.9% in group B. When immunization against poliomyelitis is started at birth, excellent seroconversion rates are obtained from the third dose onward.

Age Factors↗

Modulation of short latency cutaneous excitation in flexor and extensor motoneurons during fictive locomotion in the cat.

We examined modulation of transmission in short-latency, distal hindlimb cutaneous reflex pathways during fictive locomotion in 19 decerebrate cats. Fictive stepping was produced either by electrical stimulation of the mesencephalic locomotor region (MLR) or by administration of Nialamide and 1-DOPA to acutely spinalized animals. Postsynaptic potentials (PSPs) produced by electrical stimulation of low threshold afferents (less than 2.5 times threshold) in the superficial peroneal (SP), sural, saphenous or medial plantar nerves were recorded intracellularly from various extensor (n = 28) and flexor (n = 24) motoneurons and averaged throughout the step cycle, together with voltage responses to intrasomatic constant current pulses (in order to monitor relative cell input resistance). Each motoneuron studied displayed rhythmic background oscillations in membrane potential and correlated variations in input resistance. The average input resistance of extensor motoneurons was lowest during mid-flexion, when the cells were relatively hyperpolarized and silent. Conversely, average input resistance of flexor motoneurons was highest during mid-flexion, when they were depolarized and active. The amplitude of the minimum-latency excitatory components of PSPs produced by cutaneous nerve stimulation were measured from computer averaged records representing six subdivisions of the fictive step cycle. Oligosynaptic EPSP components were consistently modulated only in the superficial peroneal responses in flexor motoneurons, which exhibited enhanced amplitude during the flexion phase. With the other skin nerves tested (sural, saphenous, and plantar), no consistent patterns of modulation were observed during fictive locomotion. We conclude that transmission through some, but not all, oligosynaptic excitatory cutaneous pathways is enhanced by premotoneuronal mechanisms during the flexion phase of fictive stepping in several cat hindlimb motor nuclei. The present results suggest that the patterns of interaction between the locomotor central pattern generator and excitatory cutaneous reflex pathways depend on the source of afferent input and on the identity of the target motoneuron population.

Action Potentials↗

Cloning and partial DNA sequencing of two new human papillomavirus types associated with condylomas and low-grade cervical neoplasia.

Using low-stringency Southern blot analysis and cloning in lambda bacteriophage, two new human papillomavirus types (HPV-43 and HPV-44) were identified and their DNAs were cloned from vulvar tissues. The isolates were characterized by restriction endonuclease mapping and shown to be new HPV types on the basis of their minimal hybridization with all other known HPV types at high stringency. Both HPVs are most closely related to types 6, 11, and 13. HPV-43 did not exhibit any cross-reactivity with these HPV types at high stringency. HPV-44 showed minimal cross-reactivity to HPV-13, which was in the range of 20 to 25% according to liquid hybridization analysis. The deduced genomic organization of each of the two new HPVs was colinear with HPV-6b. Prevalence studies revealed that HPV-43 and HPV-44 together were found in 6 of 439 normal cervical tissues, in 8 of 195 cervical intraepithelial neoplasms, but in none of 56 cervical cancers tested thus far.

Bacteriophage lambda↗

Phasic modulation of short latency cutaneous excitation in flexor digitorum longus motoneurons during fictive locomotion.

We examined modulation of transmission of short-latency excitation produced by distal hindlimb cutaneous input, as well as fluctuations in motoneuron membrane potential and input resistance, in flexor digitorum longus (FDL) motoneurons during fictive locomotion. Fictive stepping was induced in unaesthetized, decerebrate cats either by repetitive stimulation of the mesencephalic locomotor region (MLR) or by administration of Nialamide and 1-DOPA after low spinal section. In the MLR preparations, brief depolarizing waves occurred in FDL cells during the early flexion phase of fictive stepping, immediately after cessation of activity in extensor muscles. In some FDL cells, plateau-like depolarizations also occurred during the extensor phase. Fictive stepping induced in acutely spinalized cats by administration of 1-DOPA was slower and more variable; peak polarization in FDL motoneurons always occurred during the early flexion phase but there was usually no distinct depolarization during extension. In both types of preparation, the initial EPSP components in synaptic potentials (SP-EPSPs) produced by electrical stimulation of the cutaneous division of the superficial peroneal nerve (SP) were maximally facilitated during early flexion, coincident with the peak of background depolarization. This enhancement was manifested by an increase in the amplitude of initial SP-EPSP components or by decreased central latency of the initial EPSP components, or both. In most FDL motoneurons, input resistance decreased systematically during late flexion, coincident with relative membrane hyperpolarization. Correction of SP-EPSP amplitudes for changes in input resistance suggested that SP-EPSP facilitation persisted throughout the flexion phase. These findings are discussed with reference to modulation of cutaneous reflexes during locomotion and the possibility that excitatory last-order interneurons in particular cutaneous reflex pathways may distribute excitatory drive from the central pattern generator for locomotion to FDL alpha-motoneurons.

Action Potentials↗

Neural mechanisms generating locomotion studied in mammalian brain stem-spinal cord in vitro.

The neural control system for generation of locomotion is an important system for analysis of neural mechanisms underlying complex motor acts. In these studies, a novel experimental model using neonatal rat brain stem and spinal cord in vitro was developed for investigation of the locomotor system in mammals. The in vitro brain stem and spinal cord system was shown to retain functional circuitry for locomotor command generation, motor pattern generation, and sensorimotor integration. This system was exploited to investigate neurochemical mechanisms involved in neurogenesis of locomotion. Evidence was obtained for peptidergic and gamma-amino-butyric acid-mediated mechanisms in brain-stem circuits generating locomotor commands. Cholinergic, dopaminergic, and excitatory amino acid-mediated mechanisms were shown to activate spinal cord circuits for locomotor pattern generation. Endogenous N-methyl-D-aspartic acid receptors in spinal networks were found to play a central role in the generation of locomotion. The chemically induced patterns of motor activity and rhythmic membrane potential oscillations of spinal motoneurons were characteristic of those during locomotion in other mammals in vivo. The in vitro brain stem and spinal cord model provides a versatile and powerful experimental system with potentially broad application for investigation of diverse aspects of the neurobiology of mammalian motor control systems.

Animals↗

Preventive health for school-age children in a developing country: Brazil.

The vast territorial expanse of Brazil and the great discrepancies of socioeconomic conditions, varying with the geoeconomic area considered, make health education for school-age children (7-14 years) difficult. Besides the shortage of classrooms, there is also a high level of school failure and school evasion in elementary school, especially in the North-East, the poorest region of the country. Of the enrolled children in the 1st grade, less than 20% go through to the 8th grade. School evasion reaches its maximum (44-46%) at the 1st and the 2nd grade levels Despite the 'health integration' programs established by the Government and the building of several thousands of classrooms and countless health units in the last 3-4 years, the provision of preventive health measures and preventive health education for schoolchildren is still far from satisfactory.

Adolescent↗

Secretion of human serum albumin from Bacillus subtilis.

We have fused the structural gene (hsa) for human serum albumin (HSA) to the expression elements and signal sequence coding region of each of two genes from Bacillus amyloliquefaciens P, an alpha-amylase gene (amyBamP) and a neutral protease gene (nprBamP). Bacillus subtilis strains harboring either of these gene fusions synthesized a protein with the antigenic characteristics and size (68 kilodaltons) of HSA. Results from pulse-labeling studies indicated that the bacterially produced HSA was secreted from cells which had been converted to protoplasts. Results from similar studies with intact cells suggested that the signal sequence was removed from the hybrid protein, providing further evidence that B. subtilis can translocate this foreign protein across the cell membrane. Signal sequence removal was efficient when the level of HSA synthesis was low. However, in strains which synthesized HSA at a high level, signal sequence removal was less efficient.

Bacillus subtilis↗

A Bacillus subtilis plasmid that can be packaged as single-stranded DNA in Escherichia coli: use for oligodeoxynucleotide-directed mutagenesis.

A Bacillus subtilis/Escherichia coli shuttle vector was modified to contain the origin of DNA replication of the E. coli filamentous phage f1, in both orientations. Upon superinfection with and f1-related phage of an E. coli strain containing either of the modified vectors, the single-stranded (ss) form of the plasmid was packaged in virions and released to the culture medium. Each of these ss DNAs has been purified from the virions and used as a template for oligodeoxynucleotide-directed mutagenesis. The resulting mutations were demonstrated by DNA sequencing. The capacity of these vectors to be isolated as phage ss DNA from E. coli and to replicate as plasmids in B. subtilis makes them convenient substrates for the production of oligodeoxynucleotide-directed mutations for studies in B. subtilis.

Bacillus subtilis↗