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Biomedical subjects

J K Moore

Publications and source records attributed to J K Moore.

At least 55 records · Page 3Linked to original sources
PubMed1996

Auditory evoked potentials in multiple sclerosis: correlation with magnetic resonance imaging.

The present study addresses issues regarding the location of neural sources (i.e. generators) of human auditory evoked potentials (AEPs), and the pattern of neural conduction in the auditory pathway. AEPs were recorded from fifteen patients with multiple sclerosis (MS) and compared to normals. The recordings included auditory brainstem responses (ABRs), mid-latency responses (MLRs), and long-latency responses (LLRs). AEP latency abnormalities were related to the locus of demyelinating lesions, as determined by magnetic resonance imaging (MRI) scans. The data demonstrated several anatomical patterns relating abnormal ABR wave intervals and abnormal MRI signals. From these patterns specific loci for ABR neural sources in the brainstem might be postulated. In addition, the earlier the ABR waves, the more unilateral the abnormalities appeared, suggesting bilateral sources for later waves. The MLRs were highly correlated with ABR wave V and were associated with greater abnormality in MRI signals in midbrain and forebrain regions. In general, patients with abnormal LLRs also had widespread AEP and MRI abnormalities, supporting a multiple source approach for the N1 wave of the LLRs. The observation that LLRs were only abnormal in the presence of bilateral ABR abnormalities suggests a cross wiring which would serve as a compensatory mechanism for unilateral disturbances. The AEP data showed dissociation between early and late wave abnormalities, thus supporting parallel channels for neural conduction in the central auditory system. Such a model calls for some degree of independence of AEP generators along the auditory pathway.

Adult↗
PubMed1996

A simple technique for introducing anterograde and retrograde tracers into the vestibular and cochlear sensory organs.

The standard method for labeling the afferent and efferent innervation of the cochlear and vestibular sensory organs is by microinjection of tracer substances into the labyrinth. Injection of small amounts of tracer often result in incomplete and inconsistent labeling, but large injections can cause spurious labeling of brainstem structures due to diffusion from perilymph to cerebrospinal fluid. Effective labeling with minimal artifact can, however, be achieved by a relatively simple method involving placement of a tracer-saturated pledglet of gelatin sponge in the round window after rupture of its membrane. The gelatin sponge simultaneously acts as a continuous-release vehicle for the tracer and prevents reflux of perilymph and tracer into the middle ear cavity. Use of this technique produces labeling with a degree of intensity and anatomic detail that rivals that seen with more complicated methods of tracer placement.

Animals↗
PubMed1995

Expression of acidic FGF mRNA in rat auditory brainstem during postnatal maturation.

In situ hybridization was used to investigate the mRNA distribution of acidic and basic fibroblast growth factor (aFGF and bFGF) in the auditory brainstem of neonatal and adult rats. bFGF mRNA was not detected at any age. In adult rats, aFGF mRNA was strongly expressed in the principal neurons of the anteroventral and posteroventral cochlear nuclei, but not in the octopus cells. In the dorsal cochlear nucleus, aFGF mRNA was seen only in scattered smaller vertical cells. aFGF was strongly expressed in the nucleus of the trapezoid body and in all periolivary cell groups, but not in the medial and lateral olivary nuclei. No expression was observed in the lemniscal nuclei or in the central nucleus of the inferior colliculus, but large neurons in the external zone of the colliculus were labeled. Developmentally, low levels of aFGF expression appeared in the cochlear nuclei and olivary nuclei between P0 and P6. This expression increased rapidly during the onset of hearing, between P10 and P14, and reached adult level by P14-P17. Labeling in collicular neurons appeared slightly later. The results suggest that the appearance of strong aFGF mRNA expression is related to the onset of function.

Aging↗
PubMed1995

Time course of axonal myelination in the human brainstem auditory pathway.

Structures in the human brainstem auditory pathway, from the proximal end of the cochlear nerve to the inferior colliculus, undergo myelination between the 26th and 29th fetal weeks. By the 26th week of gestation, axons in the cochlear nerve and brainstem pathways have acquired linear arrays of oligodendrocytes, and faint myelin sheaths can be distinguished. By the 29th week, definitive myelination is present in all auditory pathways, including the proximal end of the cochlear nerve, trapezoid body, lateral lemniscus, dorsal commissure of the lemniscus, commissure of the inferior colliculus and brachium of the inferior colliculus. Subsequent to the 29th gestational week, density of myelination increases in all pathways until at least 1 year postnatal age. The time of onset of myelination coincides with the onset of acousticomotor reflexes and brainstem auditory evoked responses, processes which depend on rapid, synchronized conduction of auditory impulses in the cochlear nerve and brainstem. The cotemporality in appearance of myelin, reflex responses, and evoked responses supports the idea that the 26th to 28th gestational weeks are a critical period in the onset of human central auditory function. The subsequent increase in myelin density is likely to be a factor in the steady decrease in ABR wave III-V latencies observed during the perinatal period.

Axons↗
PubMed1994

Making the new deal for junior doctors happen.

How can the new deal for juniors be implemented in today's overstretched health service? How do you get clinicians and management to work together? On the Wirral falling house officer morale and recruitment stimulated a new approach, action learning, which proved to be highly successful. Action learning is not a new approach in management terms, but it is rarely used in the health service. Guided by an experienced facilitator, a group of people learn management skills by exploring and resolving practical problems relevant to them. A group of general practitioners and consultants used action learning to teach themselves more about management and at the same time to make changes which addressed many of the junior doctors' difficulties and solved the hospital recruiting problem.

Group Processes↗
PubMed1994

A multiple interval physical map of the pericentromeric region of human chromosome 10.

Five intervals in the pericentromeric region of human chromosome 10 have been defined using a panel of somatic cell hybrids carrying portions of the chromosome. The map positions of twelve markers, consisting of four genes and eight anonymous DNA segments, have been localized by assignment to one of the five intervals. Several other markers could be placed in specific intervals by genetic linkage to assigned loci. When previously published data are incorporated, the summary map of the pericentromeric region encompasses thirty-two loci in bands 10p11.2-q11.2.

Base Sequence↗
PubMed1994

Two different types of double-strand breaks in Saccharomyces cerevisiae are repaired by similar RAD52-independent, nonhomologous recombination events.

In haploid rad52 Saccharomyces cerevisiae strains unable to undergo homologous recombination, a chromosomal double-strand break (DSB) can be repaired by imprecise rejoining of the broken chromosome ends. We have used two different strategies to generate broken chromosomes: (i) a site-specific DSB generated at the MAT locus by HO endonuclease cutting or (ii) a random DSB generated by mechanical rupture during mitotic segregation of a conditionally dicentric chromosome. Broken chromosomes were repaired by deletions that were highly variable in size, all of which removed more sequences than was required either to prevent subsequent HO cleavage or to eliminate a functional centromere, respectively. The junction of the deletions frequently occurred where complementary strands from the flanking DNA could anneal to form 1 to 5 bp, although 12% (4 of 34) of the events appear to have occurred by blunt-end ligation. These types of deletions are very similar to the junctions observed in the repair of DSBs by mammalian cells (D. B. Roth and J. H. Wilson, Mol. Cell. Biol. 6:4295-4304, 1986). When a high level of HO endonuclease, expressed in all phases of the cell cycle, was used to create DSBs, we also recovered a large class of very small (2- or 3-bp) insertions in the HO cleavage site. These insertions appear to represent still another mechanism of DSB repair, apparently by annealing and filling in the overhanging 3' ends of the cleavage site. These types of events have also been well documented for vertebrate cells.

Base Sequence↗
PubMed1994

Effect of profound hearing loss on a central auditory nucleus.

The present study was designed to investigate the type and extent of degeneration occurring in the human central auditory system subsequent to profound hearing loss. The authors have examined the size of one population of neurons in the ventral cochlear nucleus in seven subjects with profound hearing loss (audiometric responses poorer than 90-100 dB HL). Six normal subjects, ages 35-78, were used as controls. Cell size in the hearing-impaired subjects ranged from normal to reduced by more than 50 percent. Two factors appear to contribute to the variability in cell size reduction. The correlation coefficient (Spearman rs) of cell size with duration of profound deafness was -0.48, indicating a moderate tendency for neurons to become smaller with longer periods of deafness. The correlation coefficient of cell size with number of surviving cochlear ganglion cells was 0.73, indicating a stronger tendency for neurons to be larger with greater eighth nerve innervation of the cochlear nucleus. Two cases of Scheibe degeneration showed the most severe degenerative change in the central auditory system.

Adult↗
PubMed1993

Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A.

Multiple endocrine neoplasia type 2A (MEN 2A) is a dominantly inherited cancer syndrome that affects tissues derived from neural ectoderm. It is characterized by medullary thyroid carcinoma (MTC) and phaeochromocytoma. The MEN2A gene has recently been localized by a combination of genetic and physical mapping techniques to a 480-kilobase region in chromosome 10q11.2 (refs 2,3). The DNA segment encompasses the RET proto-oncogene, a receptor tyrosine kinase gene expressed in MTC and phaeochromocytoma and at lower levels in normal human thyroid. This suggested RET as a candidate for the MEN2A gene. We have identified missense mutations of the RET proto-oncogene in 20 of 23 apparently distinct MEN 2A families, but not in 23 normal controls. Further, 19 of these 20 mutations affect the same conserved cysteine residue at the boundary of the RET extracellular and transmembrane domains.

Amino Acid Sequence↗
PubMed1993

Duplicated KOX zinc finger gene clusters flank the centromere of human chromosome 10: evidence for a pericentric inversion during primate evolution.

Two related zinc finger (ZNF) gene clusters from the pericentromeric region of human chromosome 10, defined by cDNAs of the KOX series, have been cloned in yeast artificial chromosomes (YACs). The two clusters evolved by duplication of an ancestral gene cluster before the divergence of the human and great ape lineages. Included in cluster A are the ZNF gene sequences ZNF11A, ZNF33A, and ZNF37A, while cluster B comprises the related sequences ZNF11B, ZNF33B and ZNF37B. Genes from both clusters are expressed: cDNAs KOX2, KOX31 and KOX21 derive from ZNF11B, ZNF33A and ZNF37A, respectively. Further YACs have been isolated which link ZNF11A and ZNF33A to another gene, ZNF25, defined by cDNA clone KOX19. Therefore ZNF25 also forms part of cluster A, but has no counterpart in cluster B. Surprisingly, the KOX ZNF gene clusters are located on opposite sides of the centromere: cluster A maps to 10p11.2, while cluster B is in 10q11.2. This suggests the occurrence during primate evolution of a previously undescribed pericentric inversion subsequent to the cluster duplication. The evolution of this subset of KOX ZNF genes has therefore involved three types of genetic event: local gene duplication, gene cluster duplication, and chromosome rearrangement.

Amino Acid Sequence↗
PubMed1993

Genetic linkage studies map the multiple endocrine neoplasia type 2 loci to a small interval on chromosome 10q11.2.

We have carried out genetic linkage analyses using fifteen polymorphic loci in the pericentromeric region of chromosome 10 in families with the inherited cancer syndromes multiple endocrine neoplasia (MEN) type 2A or 2B. A highly polymorphic microsatellite from the locus D10S141 in q11.2 was found to be recombinant with respect to the disease locus in two individuals and defines a new proximal flanking marker for both MEN2A and 2B. An additional recombination provides evidence that the locus D10S94, also in q11.2, is the closet distal flanking marker for MEN2A. This localises the MEN2A gene to a small region of 10q11.2 flanked by the loci D10S141 and D10S94, which are separated by a sex-averaged genetic distance of 0.55 cM. The MEN2B gene maps to a larger region, flanked by D10S141 and RBP3.

Chromosome Mapping↗
PubMed1992

Immunohistochemical organization of the ventral lateral geniculate nucleus in the ground squirrel.

The ventral lateral geniculate nucleus (vLGN) of the thirteen-lined ground squirrel (Citellus tridecemlineatus) is a highly differentiated nucleus that is divisible into five major subdivisions on the basis of retinal projections and cytoarchitecture. To pursue the likelihood that these subdivisions (the dorsal cap, intergeniculate leaflet, external magnocellular lamina, internal magnocellular lamina, and parvicellular segment) correlate with the functional diversity of this complex, the present study examined the neurochemical composition of the vLGN with regard to substances that have previously proved useful in distinguishing functionally distinct subregions within nuclei (i.e., neuropeptide Y (NPY), substance P (SP), leucine and methionine enkephalins, gamma-aminobutyric acid (GABA), cytochrome oxidase (CO), acetylcholinesterase (AChE), and NADPH-diaphorase). The results showed a clear differential neurochemical distribution within the nucleus. Neuropeptide Y immunoreactive perikarya were found predominantly in the intergeniculate leaflet and external magnocellular lamina, with only a few present in the internal magnocellular lamina and dorsal cap, and none observed in the parvicellular segment. NPY+ fibers, however, were present in all divisions except the parvicellular segment. The highest concentration of SP immunoreactive cells was observed in the internal magnocellular lamina, and substantial numbers also were scattered in the external magnocellular lamina and parvicellular segment. SP+ fibers were seen predominantly in the intergeniculate leaflet and the magnocellular laminae. The heaviest concentration of enkephalinergic fibers occurred in the internal magnocellular lamina and dorsal cap, but fibers were also observed in the external magnocellular lamina and intergeniculate leaflet. GABA reactivity was widespread throughout the vLGN, with the dorsal cap and external magnocellular lamina most heavily labeled, followed by the intergeniculate leaflet and the internal magnocellular lamina. Cytochrome oxidase, AChE, and NADPH-diaphorase histochemistry revealed rich reactivity within the dorsal cap, and external and internal magnocellular laminae and paler reactivity in the intergeniculate leaflet and parvicellular segment. The external magnocellular lamina was more reactive for CO and NADPH-diaphorase than AChE, while the internal magnocellular lamina showed the opposite pattern of reactivity. In addition, NADPH-diaphorase reactive cells were present in caudal intergeniculate leaflet and lateral external magnocellular lamina. These local differences in the neurochemical character of the vLGN support its parcellation into multiple subdivisions. Taken in conjunction with the differences in cytoarchitecture and retinal projections, these results suggest substantial functional diversity within the ventral lateral geniculate complex.

Acetylcholinesterase↗
PubMed1992

Autologous anti-metatype immune response in rabbits.

Rabbits hyperimmunized with fluorescyl-conjugated KLH exhibited bound ligand associated with a high affinity circulating IgG anti-fluorescein population. After cessation of immunogen administration the liganded complexes were eventually spontaneously cleared from the circulation. Individual rabbits synthesized autologous anti-metatype antibodies specific for ligand-antibody complexes. Autologous anti-metatype antibodies reacted optimally with autologous liganded anti-fluorescein antibodies. However, cross reactivity was noted with allogenic rabbit liganded antibodies from three affinity-purified pools. An autologous anti-metatype response, reminiscent of autoanti-idiotype responses, has important implications concerning in vivo clearance of antigen-antibody complexes and may serve as a model to study immune complex diseases.

Animals↗