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Biomedical subjects

L M Parsons

Publications and source records attributed to L M Parsons.

At least 19 recordsLinked to original sources
PubMed1997

Sensory and cognitive functions.

New neuroimaging studies provide striking evidence that the cerebellum is intensely and selectively active during sensory and cognitive tasks, even in the absence of explicit or implicit motor behavior. Focal activity is observed in the lateral cerebellar hemispheres during the processing of auditory, visual, cutaneous, spatial, and tactile information, and in anterior-medial cerebellar regions during somatomotor behavior. Moreover, a double dissociation exists between (a) cerebellar activity and sensory processing and (b) motor behavior and activity in known motor areas in the cerebral cortex. These findings contradict the classical motor coordination theory of cerebellar function but are predicted by, or are at least consistent with, new alternative theories.

Animals↗
PubMed1997

Alterations in levels of DnaK and GroEL result in diminished survival and adherence of stressed Haemophilus ducreyi.

Haemophilus ducreyi is a hemin-requiring bacterium causing the genital ulcer disease chancroid. Previously we demonstrated that the heat shock protein GroEL was immunogenic and possibly highly expressed in a mammalian host. The present study was initiated to (i) determine the relative amounts of GroEL expressed by H. ducreyi during in vitro exposure to stresses and (ii) evaluate whether a high level of GroEL is directly or indirectly required for survival and adherence of stressed H. ducreyi. Using scanning densitometry of sodium dodecyl sulfate-polyacrylamide gel electrophoresis protein profiles, we found that H. ducreyi expressed high basal levels of GroEL, averaging fivefold greater than in Escherichia coli. These high GroEL levels increased up to twofold upon exposure of the organism to heat shock or high levels of hydrogen peroxide and during adherence to two human genital cell lines. Furthermore, when the gene for DnaK was present on a multicopy plasmid in H. ducreyi, a 1.8-fold increase in DnaK and a 2.3-fold reduction in GroEL were seen. These results suggest that DnaK serves as a negative modulator of H. ducreyi GroEL. Subsequently we found that H. ducreyi with lower GroEL had diminished ability to survive when challenged by heat and oxidative stresses. In addition, the long, parallel chains characteristic of virulent strains of H. ducreyi were absent when GroEL was lowered, so that fewer bacterial cells adhered to the human cells. These results suggest that the unusually high basal levels of GroEL are involved, either directly or indirectly, in the survival, chaining, and adherence of H. ducreyi in the presence of the combined stresses of the host environment.

Bacterial Adhesion↗
PubMed1996

Cerebellum implicated in sensory acquisition and discrimination rather than motor control.

Recent evidence that the cerebellum is involved in perception and cognition challenges the prevailing view that its primary function is fine motor control. A new alternative hypothesis is that the lateral cerebellum is not activated by the control of movement per se, but is strongly engaged during the acquisition and discrimination of sensory information. Magnetic resonance imaging of the lateral cerebellar output (dentate) nucleus during passive and active sensory tasks confirmed this hypothesis. These findings suggest that the lateral cerebellum may be active during motor, perceptual, and cognitive performances specifically because of the requirement to process sensory data.

Adult↗
PubMed1996

Mesoderm-specific expression of the divergent homeobox gene Hlx during murine embryogenesis.

We have determined the expression pattern of the divergent homeobox gene Hlx during post-implantation mouse development, utilizing in situ hybridization. Expression was mesoderm-specific and occurred in a complex tissue distribution. Transcripts were first detected at 9.5 days post coitum (p.c.) in splanchnic mesoderm of the midgut and hindgut region, then during organogenesis, prominently in mesenchyme of the developing liver, gall bladder, and intestines, as well as their mesenteric tissues. In the foregut, lung mesenchyme became positive from 10.5 days p.c. Hlx transcripts were also detected in a subset of skeletal myogenic cells: those within branchial arches from 9.5 days p.c. and within limb buds from 12 days p.c. Hlx was not expressed in myogenic cells which are derived from the myotome and populate the trunk. However, from 10 days p.c., expression was seen in a region of the sclerotome immediately adjacent to the myotome and corresponding to precursors of the ribs and vertebral neural arches. In the anterior-posterior aspect of the developing sclerotome, Hlx expression was out of register with original segmental boundaries (intersomitic fissures), a pattern consistent with a classical hypothesis that the developing vertebral column undergoes resegmentation. Hlx expression was also observed in vibrissae, pericardium, snout mesenchyme, and meningeal epithelium. Overall, expression of Hlx in only a subset of individual lineage progenitors and at know sites of inductive tissue interactions, suggests that the gene regulates local patterning or growth through cell:cell signalling at those embryonic sites.

Animals↗
PubMed1995

Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5.

The murine homeo box gene Nkx2-5 is expressed in precardiac mesoderm and in the myocardium of embryonic and fetal hearts. Targeted interruption of Nkx2-5 resulted in abnormal heart morphogenesis, growth retardation and embryonic lethality at approximately 9-10 days postcoitum (p.c.). Heart tube formation occurred normally in mutant embryos, but looping morphogenesis, a critical determinant of heart form, was not initiated at the linear heart tube stage (8.25-8.5 days p.c.). Commitment to the cardiac muscle lineage, expression of most myofilament genes and myofibrillogenesis were not compromised. However, the myosin light-chain 2V gene (MLC2V) was not expressed in mutant hearts nor in mutant ES cell-derived cardiocytes. MLC2V expression normally occurs only in ventricular cells and is the earliest known molecular marker of ventricular differentiation. The regional expression in mutant hearts of two other ventricular markers, myosin heavy-chain beta and cyclin D2, indicated that not all ventricle-specific gene expression is dependent on Nkx2-5. The data demonstrate that Nkx2-5 is essential for normal heart morphogenesis, myogenesis, and function. Furthermore, this gene is a component of a genetic pathway required for myogenic specialization of the ventricles.

Animals↗
PubMed1995

Use of implicit motor imagery for visual shape discrimination as revealed by PET.

Positron emission tomography (PET) can be used to map brain regions that are active when a visual object (for example, a hand) is discriminated from its mirror form. Chronometric studies suggest that viewers 'solve' this visual shape task by mentally modelling it as a reaching task, implicitly moving their left hand into the orientation of any left-hand stimulus (and conversely for a right-hand stimulus). Here we describe an experiment in which visual and somatic processing are dissociated by presenting right hands to the left visual field and vice versa. Frontal (motor), parietal (somatosensory) and cerebellar (sensorimotor) regions similar to those activated by actual and imagined movement are strongly activated, whereas primary somatosensory and motor cortices are not. We conclude that mental imagery is realized at intermediate-to-high order, modality-specific cortical systems, but does not require primary cortex and is not constrained to the perceptual systems of the presented stimuli.

Adult↗
PubMed1995

Laboratory diagnosis of chancroid using species-specific primers from Haemophilus ducreyi groEL and the polymerase chain reaction.

To enhance laboratory identification of Haemophilus ducreyi, the causative agent of the genital ulcer disease chancroid, a polymerase chain reaction (PCR) assay was developed using target DNA sequences from the essential H. ducreyi gene, groEL. Positive reactions were obtained in this PCR assay with 139 isolates of H. ducreyi from patients in worldwide locations from the 1940s to the 1990s. In contrast, 24 other bacterial species were negative. When genital ulcer specimens from 162 African patients with clinically diagnosed chancroid were evaluated, 66 were culture positive. The sensitivity of PCR as compared with culture was 89% (59 of 66), and specificity was 79% (76 of 96). However, representative samples of the 20 culture-negative, PCR-positive specimens were confirmed as positive by a second PCR assay using different H. ducreyi-specific primers. Thus, combined results of culture and PCR detected H. ducreyi in 86 specimens, with resolved sensitivities of 92% (79 of 86) for PCR, and 77% (66 of 86) for culture. These results suggest that PCR assays for H. ducreyi have great potential for augmenting or replacing problematic cultural techniques.

Bacterial Proteins↗
PubMed1994

Temporal and kinematic properties of motor behavior reflected in mentally simulated action.

Related perceptual, motor, and cognitive performances were examined to reveal the accuracy of the properties of action spontaneously represented when mentally simulating moving one's hand. The kinematic configuration of the body represented and transformed in mental simulations was not fixed or canonical but corresponded to one's current configuration. Mental simulation time mimicked movement time for natural efficient movement from a posture midway between each of the hand's joint limits into many other postures. Equal time was required for simulated and real movements into more common, comfortable postures; shorter but proportional time was required for simulated movement than real movement into less common postures that involved longer trajectories, coordinated activity at more joints, motion near extremes of joint limits, and uncomfortable kinesthetic sensations. The findings suggest that sensorimotor structures support mental simulations of actions.

Functional Laterality↗
PubMed1993

Effect of amitriptyline on neurotransmitter levels in adult mice following infection with the avirulent strain of Semliki Forest virus.

Infection of adult mice with the avirulent strain of Semliki Forest virus (SFV) led to neurochemical abnormalities, notably depressed levels of catecholamines (CATs) such as noradrenaline (NA), adrenaline (A) and 3-methoxy-4-hydroxyphenylglycol (MHPG) (a metabolite of NA) particularly in the hypothalamus and the inferior colliculus but not in the temporal cortex. In addition, depressed levels of NA and A were also found in the cerebrospinal fluid (CSF) and the serum. Administration of a tricyclic antidepressant drug, amitriptyline, kept the levels of NA, A and MHPG similar to those of the saline-treated control mice in the hypothalamus, inferior colliculus and CSF.

Amitriptyline↗
PubMed1993

Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants.

We have isolated two murine homeobox genes, Nkx-2.5 and Nkx-2.6, that are new members of a sp sub-family of homeobox genes related to Drosophila NK2, NK3 and NK4/msh-2. In this paper, we focus on the Nkx-2.5 gene and its expression pattern during post-implantation development. Nkx-2.5 transcripts are first detected at early headfold stages in myocardiogenic progenitor cells. Expression preceeds the onset of myogenic differentiation, and continues in cardiomyocytes of embryonic, foetal and adult hearts. Transcripts are also detected in future pharyngeal endoderm, the tissue believed to produce the heart inducer. Expression in endoderm is only found laterally, where it is in direct apposition to promyocardium, suggesting an interaction between the two tissues. After foregut closure, Nkx-2.5 expression in endoderm is limited to the pharyngeal floor, dorsal to the developing heart tube. The thyroid primordium, a derivative of the pharyngeal floor, continues to express Nkx-2.5 after transcript levels diminish in the rest of the pharynx. Nkx-2.5 transcripts are also detected in lingual muscle, spleen and stomach. The expression data implicate Nkx-2.5 in commitment to and/or differentiation of the myocardial lineage. The data further demonstrate that cardiogenic progenitors can be distinguished at a molecular level by late gastrulation. Nkx-2.5 expression will therefore be a valuable marker in the analysis of mesoderm development and an early entry point for dissection of the molecular basis of myogenesis in the heart.

Amino Acid Sequence↗
PubMed1992

Identification of functional regions of the positively acting regulatory gene amdR from Aspergillus nidulans.

The amdR (intA) regulatory gene of Aspergillus nidulans encodes a 765-amino-acid polypeptide which determines the omega-amino acid induction of at least five structural genes. The AmdR polypeptide contains a potential Zn(II)2Cys6 DNA-binding motif which has been shown to be present in the N-terminal region of a large number of fungal activator proteins. In vitro mutagenesis of the fourth cysteine of this motif abolishes AmdR function as shown by loss of complementation of an amdR- mutation and by the AmdR- phenotype of a mutant gene replacement strain. Studies using constructs in which the proposed AmdR DNA-binding motif is replaced with that from another activator, FacB, shows that induction is independent of DNA-binding specificity and that sequences in the C-terminal region of AmdR are activation domains. Sequencing of several amdR mutant alleles which affect activation and/or induction, together with studies of deletion constructs indicate that changes in the conformation of the protein determines its activity and that this is modulated by inducers.

Aspergillus nidulans↗
PubMed1992

IgG subclass responses in brain and serum in Semliki Forest virus demyelinating encephalitis.

The response of IgG subclasses within the central nervous system (CNS) of the mouse to Semliki Forest virus (SFV), an alphavirus associated with meningoencephalitis and primary immune mediated demyelination, has been measured using immunocytochemistry. The subclass response in serum has been assessed using virus specific enzyme linked immunosorbent assays. In the CNS IgG1 was poorly represented throughout the sampling period of 28 days with a maximum of 3% of the total number of positive cells on day 21 after infection. Of the few IgG positive cells present on day 6, 2a and 3 positive cells were dominant. From day 9 onwards the numbers of 2b positive cells rose and by day 28 IgG2a, 2b and 3 subclasses showed roughly equal percentages of total cells counted. By contrast, in serum, anti-SFV IgG 2a and 2b were the first to appear and were dominant on day 12 and 21. Levels of anti-SFV IgG1 did not rise until after day 12 but rose steeply thereafter. IgG3 was weakly positive at days 9 and 12, rising slightly on day 21. Clearly there are differences in the patterns of subclass response between the CNS and the periphery. This may be important in the context of neurotropic viral infection.

Animals↗
PubMed1992

Molecular analysis of the Haemophilus ducreyi groE heat shock operon.

Chancroid is a sexually transmitted genital ulcer disease caused by Haemophilus ducreyi. Previously, we developed diagnostic DNA probes for H. ducreyi (L. M. Parsons, M. Shayegani, A. L. Waring, and L. H. Bopp, J. Clin. Microbiol. 27:1441-1445, 1989). In the present study, DNA sequencing of one of the diagnostic probes revealed two adjacent open reading frames (ORFs). These H. ducreyi ORFs and the encoded proteins show significant homology with the groE genes and GroES and GroEL heat shock proteins from several bacterial pathogens and with conserved eukaryotic 60-kDa heat shock proteins. The first H. ducreyi ORF (groES) is preceded by sequences similar to those of the Escherichia coli consensus heat shock promoters and is 288 nucleotides long and is capable of encoding a protein of 10.3 kDa. The second ORF (groEL) is 1,641 nucleotides long and is capable of encoding a protein of 57.8 kDa. Northern (RNA blot) analysis demonstrated the presence of a high level of groE mRNA in exponential-phase H. ducreyi grown in hemin broth at the organism's optimal growth temperature (33 degrees C), with increased levels seen following heat shock. Heat shock also increased the thermostability of the organisms, since stressed cells were more resistant to the lethal effects of rapid chilling. Electrophoretic analysis and immunoblots demonstrated that the predominant protein produced by exponential-phase H. ducreyi was a heat-inducible, immunoreactive protein of approximately 60 kDa (GroEL). Also, H. ducreyi groE mRNA and GroEL were expressed and inducible by heat in E. coli. This is the first report describing the cloning, sequencing, and expression of H. ducreyi protein-encoding genes.

Amino Acid Sequence↗
PubMed1991

Molecular relatedness of Staphylococcus epidermidis isolates obtained during a platelet transfusion-associated episode of sepsis.

Staphylococcus epidermidis was isolated from the blood of a 25-year-old pregnant woman following the administration of eight units of platelets. She had developed chills and a fever of 41.4 degrees C soon after the transfusions were completed. S. epidermidis was also obtained from all eight platelet units, as well as from the packed-erythrocyte unit associated with the first unit of platelets. The isolation of the same organism from these epidemiologically related sources provided us with the opportunity to phenotypically and genetically characterize the isolates. Several typing methods, including four molecular techniques, were used to increase our chances of finding any differences between the isolates under investigation. Phenotypic analyses demonstrated that S. epidermidis isolates from the patient, platelet units, and erythrocyte unit reacted in exactly the same manner in 15 biochemical tests, exhibited slime production, and had the same antibiotic susceptibility pattern. Genetic analyses, which included plasmid profiles, plasmid cross-hybridization, field inversion gel electrophoresis, and ribotyping, substantiated the relationships between the S. epidermidis isolates from the patient, platelet units, and erythrocyte unit. Eight S. epidermidis control strains unrelated to the case were found to differ significantly from the platelet-related strain.

Adult↗
PubMed1989

DNA probes for the identification of Haemophilus ducreyi.

Haemophilus ducreyi ATCC 33922, a virulent, well-characterized strain, was used to construct a genomic library in a bacteriophage expression vector. Three DNA fragments were selected for use as probes on the basis of their ability to encode H. ducreyi-specific proteins, as demonstrated by reactivity with rabbit polyclonal antiserum. With DNA-DNA hybridization, the three probes, labeled with 32P, reacted strongly with 16 strains of H. ducreyi obtained from a variety of sources. Thirty-seven other bacterial isolates, representing 33 different species and including organisms likely to be encountered in the urogenital tract, were also tested with the three probes. Twenty-eight of these isolates, including the genital pathogen Neisseria gonorrhoeae, showed no hybridization with the probes. In addition, herpes simplex virus-infected tissue culture cells and Treponema pallidum-infected rabbit testicular fluid were also completely nonreactive. Nine isolates, six belonging to other Haemophilus species and three belonging to Pasteurella species, reacted weakly with the probes when approximately 3.0 x 10(7) to 6.0 x 10(7) CFU was tested. When 10(5) to 10(6) CFU of these organisms was tested, the weak reactions could no longer be seen. Yet this number of H. ducreyi still reacted strongly. In fact, the three probes consistently detected 10(4) CFU of H. ducreyi in pure and mixed cultures and even produced a weak signal when only 10(3) CFU was present. It is clear from our results that use of these probes will greatly facilitate the laboratory diagnosis of this genital pathogen.

Animals↗
PubMed1989

Mirror reversal by blind subjects in cutaneous perception and motor production of letters and numbers.

A letter drawn on the forehead is often perceived as its mirror reversal. Similarly, people produce mirror reversals when asked to write a letter on the underside of a table at which they are sitting. We varied the orientation and position of the stimulated or inscribed surface, and found several examples of these two mirror-reversal phenomena in blind subjects (who had no, or very little, visual experience), as well as in sighted subjects. Furthermore, the mirror-reversal rate of the two groups of subjects as a function of orientation and position of the surface was highly correlated. Thus, the mirror-reversal phenomena should be attributed to a nonvisual, spatial cognitive scheme that is perhaps shared by sighted and blind subjects.

Adult↗
PubMed1989

Identification of immunoglobulin-containing cells in the central nervous system of the mouse following infection with the demyelinating strain of Semliki Forest virus.

Cells within the central nervous system were identified as containing immunoglobulin G, A and M using immunocytochemistry in mice previously infected with Semliki Forest virus, a togavirus causing primary immune-mediated demyelination. Cells positive for these immunoglobulins were counted in cerebellar white matter, parenchyma, meninges and choroid plexus/ventricles. No positively staining cells were seen on day 6 after infection although other inflammatory cells were present at this time and virus-specific immunoglobulin was found in serum. Cells positive for IgG appeared in all areas by day 9 and remained dominant in numbers throughout. IgM-secreting cells appeared in small numbers in the parenchyma first on day 9 and subsequently in other areas, their numbers rising to a maximum on day 12 in all areas and falling thereafter. The number of IgA-secreting cells was small. They appeared by PID 12 and continued to rise on successive sampling days. Initially IgG-positive cells were seen in the perivascular cuffs but by day 12 a few had moved away from the cuffs into the adjacent parenchyma. IgG-positive cells were seen both in and away from cuffs within areas of demyelination. IgM and IgA-positive cells tended to follow the distribution of IgG-positive cells, but in fewer numbers.

Animals↗