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Biomedical subjects

J D Porter

Publications and source records attributed to J D Porter.

At least 19 recordsLinked to original sources

Interconnections between the primate cerebellum and midbrain near-response regions.

The goal of this study was to determine the pattern of the connections between the midbrain and cerebellum that may play a role in the modulation of the near-response in the macaque. Injection of the retrograde tracer wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) into the physiologically identified midbrain near-response region, which includes the supraoculomotor area, labelled cells throughout the deep cerebellar nuclei. However, labelled cells were particularly concentrated in the ventrolateral corner of the contralateral posterior interposed nucleus and in the contralateral and, to a lesser extent, the ipsilateral fastigial nuclei. Subsequently, injections of WGA-HRP were used to define the midbrain terminations of the deep cerebellar nuclei. Fastigial nucleus injections labelled terminals in a band along the border between the oculomotor nucleus and the supraoculomotor area that included the Edinger-Westphal nucleus. Injections of the posterior interposed nucleus labelled terminals in the portion of the supraoculomotor area dorsal to the fastigial projection and did not involve the Edinger-Westphal nucleus. In both cases, the terminal label was primarily found contralaterally. In contrast, retrogradely labelled cells were primarily found ipsilaterally within the supraoculomotor area following cerebellar injections. Retrogradely labelled cells projecting to the deep nuclei were also found bilaterally in the anteromedian nucleus, along with sparse terminal label. Taken as a whole, these results demonstrate the presence of a highly specific pattern of labelling in the supraoculomotor area, which may indicate that the posterior interposed nucleus and the fastigial nucleus play different roles in the control of the near-response. Alternatively, these projections may subserve other functions, such as modulating the pupillary light reflex. The fact that the projection from the deep nuclei is primarily contralateral, while the supraoculomotor projection to the deep nuclei is primarily ipsilateral, suggests that this may not be a simple feedback system, but may instead be involved in balancing the gains in the two eyes. In sum, physiological experiments have indicated the presence of near-response neurons in the midbrain supraoculomotor area and have indicated that the cerebellum may play a role in modulating the components of the near-response, as well as activity in the intrinsic eye muscles. The present experiments suggest a pattern of connections that might subserve this cerebellar modulation.

Animals

Lack of early antitoxin response to tetanus booster.

Tetanus immune globulin (TIG) continues to be recommended in persons with tetanus-prone wounds who have incomplete or unknown tetanus immunization status. The aim of this study was to determine whether, following a booster dose of tetanus toxoid in adults who had not been immunized in the previous 10 years, there was an antitoxin response to tetanus toxoid booster within 4 days. Thirty-one adults were investigated, baseline levels for tetanus antitoxin assayed using an ELISA technique, and an injection of adsorbed tetanus toxoid (0.5 ml) given. Blood samples for tetanus antitoxin levels were taken at daily intervals for the 4 days following immunization. Tetanus boosters following the primary course but before the present study did not significantly increase the levels of pre-study tetanus antitoxin and following the study booster there was no difference between the preboost levels and the levels on days 1 to 4. This finding indicates that the present recommendations for the use of TIG in tetanus-prone wounds are appropriate.

Adult

The laminar distribution of macaque tectobulbar and tectospinal neurons.

The superior colliculus exerts its most direct influence over orienting movements, and saccades in particular, via its descending projections to the brain stem and spinal cord. However, while there is detailed physiological data concerning the generation of saccade-related activity in the primate superior colliculus, there is relatively little data on the detailed connectivity of this structure in primates. Consequently, retrograde transport techniques were utilized to determine the locations of the cells of origin of these descending pathways in macaque monkeys. Tectal cells that projected to the ipsilateral pontine reticular formation were mainly found in the deep gray layer and occasionally in the intermediate gray layer. Tectal cells that projected to the contralateral pontine reticular formation were predominantly located in the intermediate gray layer. The contralaterally projecting population could be subdivided into two groups. The cells in upper sublamina of the intermediate gray layer project primarily to the saccade-related regions of the paramedian reticular formation. Cells in the lower sublamina project primarily to more lateral regions of the pontine reticular formation and to the spinal cord. We conclude that the primate colliculus is provided with at least three descending output channels, which are likely to differ in their connections and functions. Specifically, it seems likely that the lower portion of the intermediate gray layer may be specialized to subserve combined head and eye orienting movements, while the upper sublamina subserves saccades.

Animals

Prenatal morphogenesis of primate extraocular muscle: neuromuscular junction formation and fiber type differentiation.

Extraocular muscle represents a distinctive class among mammalian skeletal musculature in exhibiting the full range of muscle fiber type variability found in vertebrate species. To better understand the basis for the unique structural/functional diversity of extraocular muscle, the ontogeny of lateral rectus muscles was studied in Macaca nemestrina fetuses of 62-156 days gestation using light and electron microscopy. At E62, myotubes and myofibers are evident, but fiber-type differentiation has not yet occurred and neuromuscular junctions are primitive. By E92, presumptive singly and multiply innervated fiber types could be distinguished on the basis of myofibril delineation. Like other skeletal muscles, extraocular myogenesis proceeds through at least two generations of myofibers. All primary and secondary myofibers were generated and were maturing by E121. The phylogenetically "old" global multiply innervated fiber type was the first to attain adult form. This was followed by maturation of global layer singly innervated fiber types, which are developed by E156, except for attainment of definitive size and mitochondrial content. Orbital layer fiber types, particularly the orbital singly innervated fiber, are the last to mature. Neuromuscular junction maturation paralleled the changes observed during fiber-type differentiation. In summary, the sequential development of their constituent muscle fiber types may reflect the functional pressures the extraocular muscles are exposed to by maturing visual and visuomotor systems. In particular, ontogenic and phylogenic changes observed in the orbital singly innervated fiber type may have direct implications for the types, range, and precision of eye movements used by different species and at different gestational ages.

Animals

Tuberculosis in developing countries.

Every year, between six and eight million people worldwide develop tuberculosis and 2-3 million die of the disease. The situation is worsening due to the epidemic of human immunodeficiency virus (HIV) infection and reactivation of tuberculosis in patients with 'dual infection'. The World Health Organisation estimated that three million persons had 'dual infection' in 1990; 78% occurring in Africa. Tuberculosis, which affects adults during their most productive years and is a curable and preventable disease, has thus become a priority in the 1990s after a period of neglect. It also has some of the most cost effective health interventions available. The thrust of tuberculosis research in developing countries should be to support national tuberculosis control programmes, both in the development of their infrastructure and in research, to assist and develop tuberculosis control strategies.

AIDS-Related Opportunistic Infections

L-dopa-induced air-stepping in developing rats.

Rat pups at postnatal day (PN) 0, 5, 10, 15, and 20 were injected with 100 mg/kg L-3,4-dihydroxyphenylalanine (L-DOPA; s.c.) or the control vehicle and suspended in a sling. L-DOPA induced highly stereotyped air-stepping that varied along several dimensions across development. The latency to air-stepping was constant across age, but the duration was significantly shorter in the older pups. At all ages, air-stepping was preceded or accompanied by raising of the head and dorsiflexion of the tail. The rate of stepping increased across age and gait varied with age. At PN 0, L-DOPA induced alternating forelimb movements with little involvement of the hindlimbs. At PN 5 and 10, both forelimb and hindlimb alternation were observed. At PN 10 and 15 swimming-like behavior emerged, and at PN 10, 15, and 20, episodes of galloping were interspersed with limb alternation. Thus, highly coordinated activity can be elicited by L-DOPA at all ages studied when the rat pup needs not support its own body weight and has no contact with a substrate. Drug-induced air-stepping promises to be an important new paradigm for pharmacological and behavioral studies of the development of locomotor controls in mammals.

Animals

Botulinum-induced changes in monkey eyelid muscle. Comparison with changes seen in extraocular muscle.

Botulin type A was injected into the eyelids of adult monkeys, and structural alterations in the orbicularis oculi muscle were evaluated after survival times of 7 to 84 days. The most profound change seen at both the light- and electron-microscopic levels was nonselective atrophy of virtually all muscle fibers. Moreover, the botulin-induced blockade of neuromuscular transmission was nonspecific in producing alterations in the three orbicularis fiber types. Muscle structural changes appeared to be reversible, with no apparent long-term consequences. While sprouting of preterminal axons was noted in botulin-treated muscle, formation of collateral sprouts did not appear to be widespread. These changes contrast with the fiber type-specific, long-term alterations induced in extraocular muscle by botulin treatment. However, this differential response may be attributed to the very clear differences in fiber type composition and motor control mechanisms between eyelid and extraocular muscle groups. The efficacy of botulin treatments for strabismus and focal dystonia may then be directly related to both the anatomic fiber type composition and the functional properties of motor control systems of the injected muscle.

Animals

Ultrastructural changes in the masseter muscle of Macaca fascicularis resulting from intramuscular injections of botulinum toxin type A.

Intramuscular injections of botulinum toxin type A (Oculinum) is used to treat strabismus and focal dystonias affecting orofacial muscles. However, the toxin-induced morphological changes that underlie the therapeutic alterations of tone in the muscles of mastication have not been described. In this study, paired intramuscular injections of botulinum toxin (10 units) were made in three adult monkeys (Macaca fascicularis) allowed to survive 14, 28 and 63 days. Another monkey received multiple injection-pairs over 84 days. Animals were killed by deep pentobarbital anaesthesia before transcardiac perfusion-fixation. Tissue sampled from comparable regions of the injected masseter, the uninjected masseter and an uninjected animal was processed for ultrastructural analysis. Few changes were found 14 days post-injection. However, muscle fibres showed myofibrillar dissolution, aberrations in the Z-line, and enlarged mitochondria in the region of the I-band by 28 days. In the 63-day and 84-day animals, the injected muscle was considerably smaller than the uninjected, contralateral muscle. Regions of the injected muscle contained fibres with markedly reduced cross-sectional area. Internalization of myonuclei, loss of myofibrillar organization, and helical complexes were common. Toxin-induced changes, though similar to those that follow denervation by axotomy, were not accompanied by degeneration of neuromuscular junctions. Instead, morphological evidence for axonal sprouting in the region of the neuromuscular junction, possibly contributing to functional recovery, was seen as early as 14 days in toxin-treated muscles.

Actin Cytoskeleton

Outbreak of adenoviral infections in a long-term paediatric facility, New Jersey, 1986/87.

During an 8-week period in the winter of 1986-87, there were 11 deaths from an adenovirus infection (case fatality rate = 39%, 11/28) in a long-term care paediatric facility in southern New Jersey. Among the 61 resident children, all with severe congenital and/or acquired disabilities, 28 developed a febrile respiratory illness compatible with adenovirus infection [attack rate (AR) = 46%]. Patients with tracheostomies were three times as likely to become ill [relative risk (RR) = 3.2, 95% confidence intervals (CI) = 1.8-5.6]. Twenty-three members of the staff had a similar febrile illness (AR = 22%, 23/106); nurses were more likely to be ill than other staff (RR = 3.0, 95% CI = 1.1-11.4). Adenovirus 7 was isolated from four of the case patients and adenovirus 1 from one. The findings suggest prolonged transmission between patients and nursing staff with lack of cohorting of ill patients probably contributing to the prolongation of the outbreak. This investigation indicates that adenoviral outbreaks, although rare, can have a high mortality in severely disabled children, and that future outbreak investigations should examine the use of vaccines or antiviral agents to reduce mortality and for outbreak control.

Adenovirus Infections, Human

The anatomical substrate for cat extraocular muscle proprioception.

The localization of cell bodies and of the central terminal projections of extraocular muscle afferent neurons was examined in adult cats using transport of horseradish peroxidase. The results confirm that primary afferent cell somata subserving extraocular muscle proprioception are located within the medial portion of the ipsilateral trigeminal ganglion. Occasional labeling of cell bodies in the mesencephalic nucleus of the trigeminal nerve occurred only in association with evidence of spread of tracer beyond the eye muscles. These results, taken together with work of others, make it unlikely that the trigeminal mesencephalic nucleus participates significantly in eye muscle proprioception. The central projections of extraocular muscle afferent neurons were found consistently in a restricted area in the ventral portion of the pars interpolaris of the spinal trigeminal nucleus. This corresponds exactly with their site of termination in the monkey [Porter (1986) J. comp. Neurol. 247, 133-143]. Terminal labeling was restricted to this area in cases in which there was no evidence of spread of the tracer beyond the extraocular muscles. In contrast to previous findings in the monkey, the cat did not exhibit a second muscle afferent representation in the cuneate nucleus. Though it is known that extraocular muscle afferent signals interact with both retinal and vestibular signals, and thus probably are involved in both visual processing and oculomotor control, the details of their roles in these processes are not yet clear.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways

An open-field activity analysis of labyrinthectomized rats.

A detailed behavioral analysis was performed on rats that received bilateral labyrinthectomies. They were placed in a walled activity monitor (39 x 39 cm) that allowed the animal to move freely within the enclosure. Their behavioral activities were automatically recorded. These activities were placed into twelve different categories. The results show a lower rate of habituation for the labyrinthectomized animal as well as an overall increase in activity over all dimensions as compared to the control. This increase in behavior may be exploratory and a necessary feature in the formation of spatial maps.

Animals

Cerebellotectal pathways in the macaque: implications for collicular generation of saccades.

The cerebellum is thought to modulate saccadic activity in the primate in order to maintain targeting accuracy, and the cerebellotectal pathway has been posited to play a role in this modulation. However, anatomical descriptions of this pathway in primates are sketchy and conflicting. To determine whether the organization of the cerebellotectal projection in primates is similar to that found in other species, neuroanatomical tracer transport techniques were utilized in two species of macaque monkey to label cerebellotectal somata and fiber terminations. Two pathways were found. One, the fastigiotectal pathway, is derived from cells in the caudal fastigial nucleus and projects bilaterally to the rostral end of the intermediate gray layer. The other pathway is derived from cells in the posterior interposed nucleus and the adjacent posterior wing of the dentate nucleus, and it terminates contralaterally throughout the ventral half of the intermediate gray and the deep gray layers. Both of these pathways terminate within the layers of the superior colliculus containing premotor, saccade-related neurons, but the differences in the distribution of their terminals and cells of origin suggest that these two pathways have different functions. Furthermore, the pattern of connections of these two pathways indicates that they do not function as a traditional feedback circuit. We suggest that the cerebellotectal pathways may instead modulate collicular activity in a more complex manner. For example, it may provide signals necessary for corrective saccades or for maintaining spatial registry between the different sensory representations supplied to the superior colliculus and its presaccadic output, which is organized into a motor map.

Animals

Measles outbreaks in the Mozambican refugee camps in Malawi: the continued need for an effective vaccine.

Between November 1988 and January 1989, measles outbreaks occurred in 11 Mozambican refugee camps in Malawi with five camps principally affected. A total of 1214 cases were reported. Despite the reduction of the age of measles vaccination to six months in 1987, attack rates were highest in children aged 6-9 months (10-26%); rates were also high in the 0-5 month age group (3-21%). The case-fatality rate was high among children less than five years old (15-21%). Children were being inappropriately vaccinated, either being vaccinated at less than six months of age (2-29%) or failing to receive a second dose if vaccinated at six months (0-25%). With vaccine coverage between 66-87%, vaccine efficacy in children less than five years old was estimated to be more than 90% in the camps principally affected. Reduction of the age of vaccination leads to logistical problems in vaccine delivery in refugee situations. These outbreaks again indicate the need to improve vaccine coverage with the existing Schwarz vaccine, and also highlight the urgent need for an effective single dose measles vaccine for children less than nine months of age.

Age Factors