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Biomedical subjects

J Higgins

Publications and source records attributed to J Higgins.

At least 55 records · Page 3Linked to original sources

Compartmentalization of Th1/Th2 cytokine responses to experimental Yersinia pseudotuberculosis infection in cats.

Specific pathogen-free cats were inoculated subcutaneously into the drainage areas of the left auricular and popliteal lymph nodes with living Yersinia pseudotuberculosis. Inflammation was evident at the inoculation sites and the regional lymph nodes were palpably enlarged at 48 h post-infection. Lymph node enlargement was due to marked paracortical lymphoid hyperplasia and variable neutrophil infiltrates. Yersinia was cultured from the regional lymph nodes and/or spleens of three of the six cats, indicating systemic spread of bacteria. Specific T-helper 1 and 2 (Th1, Th2) cell-associated cytokine mRNA levels were compared in regional lymph nodes, peripheral blood mononuclear cells (PBMC) and spleen at 48 h post-inoculation. Relative to unstimulated control tissues, there was a significant increase in TNF-alpha, IFN-gamma, IL-12, and IL-10 mRNAs in spleen with down-regulation of IL-4. Significant up-regulation of TNF-alpha and down-regulation of IL-4 were also observed in PBMC. Paradoxically, 48 h stimulated lymph nodes showed only minimal differences in cytokine mRNA expression when compared to lymph nodes from mock-inoculated control animals or unchallenged contralateral lymph nodes from the same animal. This study demonstrated that cats, like mice, respond to an intracellular pathogen such as Y pseudotuberculosis with a predominantly Th1-type immune response. The cytokine responses in regional lymph nodes and spleen were asynchronous, while cytokine stimulation in cells of the spleen was mirrored by PBMC.

Animals↗

Measurement of feline cytokine gene expression by quantitative-competitive RT-PCR.

We have developed a method to quantitate feline cytokine gene expression using competitive RT-PCR. Feline cytokine specific primers were developed that encompass an intron, thus allowing differentiation of cDNA vs. genomic DNA amplification products. The PCR products of the primers were verified by sequencing and Southern blot analysis. For quantitation, a non-homologous RNA competitor was created for each cytokine of interest. The competitor was designed to yield an RT-PCR product 10-20% larger than the native sequence, thereby allowing differentiation of the two products by electrophoresis on an agarose gel. Both competitor and native sequences used the same primer sequences for RT (oligo dT) and PCR (cytokine specific). The amplification efficiency of the competitor and native sequence was shown to be identical which allowed comparison at any point during the amplification, including the plateau phase. The quantity of starting cytokine mRNA was determined by interpolation from a standard curve. As little as 1 microgram of total cellular RNA was required per cytokine determination. The assay can routinely quantify as few as 1000 copies of template and spans a range of up to 4 log.

Animals↗

Listeria monocytogenes and Serratia marcescens infections as models for Th1/Th2 immunity in laboratory cats.

Five species of bacteria known to be naturally-occurring pathogens of cats were screened for their ability to grow in feline macrophages in vitro, and to induce antibodies and delayed type hypersensitivity (DTH) responses in vivo. Two of these organisms, L. monocytogenes and S. marcescens, were selected for further study based on clear-cut differences in their in vitro and in vivo behavior. Listeria was macrophage tropic, induced DTH, and evoked poor antibody responses post-recovery, whereas Serratia remained extracellular, did not induce a DTH reaction, and produced high titer of antibodies. Young specific pathogen free cats were then inoculated subcutaneously into the drainage areas of the right and left popliteal and auricular lymph nodes with either L. monocytogenes or S. marcescens. Each of the four lymph nodes were then removed in sequence over a two week period, weighed, cultured for viable bacteria, and RNA extracted for Th1/Th2 cytokine mRNA quantitation. Antibody responses and delayed type hypersensitivity responses were also measured. Identical to pilot studies, cats infected with Serratia developed very high levels of antibody compared to Listeria infected cats but no DTH, while Listeria infected cats produced negligible or low titers of antibodies and strong DTH. Immunity to Listeria occurred around 168 h post infection as evidenced by the disappearance of living bacteria from the nodes, while immunity to Serratia took over 264 h. Pronounced lymph node hyperplasia occurred in both infections, but persisted longer for Serratia. Enlargement of Serratia infected nodes was associated with marked follicular, primary and secondary germinal center and medullary hyperplasia. Germinal center formation in Listeria stimulated nodes was much less intense and dense accumulations of macrophages dissected between follicles downward from the subcapsular sinuses. Although functional and histologic studies showed a clear-cut cell-mediated vs. humoral response in the respective Listeria and Serratia infections, preferential cytokine mRNA upregulation was observed for only two of the five major Th1/Th2 cytokines measured. Interferon-gamma, a Th1 cytokine, was much more elevated in the Listeria stimulated nodes, but TNF-alpha (also a Th1 cytokine) was more elevated in Serratia infected nodes. Interleukin-12, an important Th1 cytokine, was elevated to equal levels in both infections as were the Th2 cytokines IL-4 and IL-10.

Animals↗

Health policy. HAZs warning.

The government's health action zones are part of a long tradition of area-based social programmes in Britain. Most have had only marginal success. The HAZ programme will rely on partnerships between organisations which are difficult to achieve. The success of HAZs will partly depend on local autonomy which could prove politically risky for a government committed to equality.

Community Health Planning↗

Effects of child-rearing by schizophrenic mothers: a 25-year follow-up.

We conducted a 25-year follow-up study of 50 children of schizophrenic mothers, consisting of 25 children reared by their mothers and 25 children reared apart. The children's adult psychiatric status was evaluated in a 3-h structured interview employing a battery of syndrome check-lists and scales. A slightly higher incidence of psychopathology (including schizophrenia-spectrum disorders) was found among the reared-apart subjects. This may possibly be attributed to their greater genetic predisposition, as suggested by their mothers' more severe illnesses. Lifetime diagnoses do not provide evidence that psychopathology in offspring at genetic risk is increased by rearing by a schizophrenic mother.

Adolescent↗

Photoinduced Chemical Dynamics of High-Spin Alkali Trimers

Nanometer-sized helium droplets, each containing about 10(4) helium atoms, were used as an inert substrate on which to form previously unobserved, spin-3/2 (quartet state) alkali trimers. Dispersed fluorescence measurements reveal that, upon electronic excitation, the quartet trimers undergo intersystem crossing to the doublet manifold, followed by dissociation of the doublet trimer into an atom and a covalently bound singlet dimer. As shown by this work, aggregates of spin-polarized alkali metals represent ideal species for the optical study of fundamental chemical dynamics processes including nonadiabatic spin conversion, change of bonding nature, and unimolecular dissociation.

Journal Article↗

Preserved cognitive processes in cerebellar degeneration.

Aspects of cognitive processing in patients with cerebellar degeneration (CD) were studied in order to examine the validity of recent findings that CD patients demonstrate deficits in visuospatial cognition and verbal-associative learning. Two groups of patients with CD were compared to stratified matched control groups on tests examining selective visual attention, visual spatial attention, mental rotation of geometric designs, and memory for the temporal order of words they were previously exposed to. CD patients performed similarly to their matched controls across all tasks. These results indicate that the reported cognitive deficits of CD patients are quite selective and need further specification in order to more fully describe their relationship to cerebellar dysfunction.

Atrophy↗

Maternal and neonatal hyponatraemia: a comparison of Hartmanns solution with 5% dextrose for the delivery of oxytocin in labour.

We performed a randomised controlled trial to compare the effect on neonatal and maternal serum sodium of using oxytocin in Hartmanns solution compared to the standard 5% Dextrose regimen for induction or augmentation in labour. We found significantly decreased maternal and neonatal serum sodium concentrations in the 5% Dextrose group compared to the Hartmanns group.

Adult↗

Evaluating the 'Labeled Magnitude Scale' for measuring sensations of taste and smell.

The Labeled Magnitude Scale (LMS) is a semantic scale of perceptual intensity characterized by a quasi-logarithmic spacing of its verbal labels. The LMS had previously been shown to yield psychophysical functions equivalent to magnitude estimation (ME) when gustatory, thermal and nociceptive stimuli were presented and rated together, and the upper bound of the LMS was defined as the 'strongest imaginable oral sensation'. The present study compared the LMS to ME within the more limited contexts of taste and smell. In Experiment 1, subjects used both methods to rate either taste intensity produced by sucrose and NaC1 or odor intensity produced by acetic acid and phenyl ethyl alcohol, with the upper bound of the LMS defined as either the 'strongest imaginable taste' or the 'strongest imaginable odor'. The LMS produced psychophysical functions equivalent to those produced by ME. In, Experiment 2 a new group of subjects used both methods to rate the intensity of three different taste qualities, with the upper bound of the LMS defined as the 'strongest imaginable [sweetness, saltiness, or bitterness]'. In all three cases the LMS produced steeper functions than did ME. Experiment 3 tested the hypothesis that the LMS yields data comparable to ME only when the perceptual domain under study includes painful sensations. This hypothesis was supported when the LMS again produced steeper functions that ME after subjects had been explicitly instructed to omit painful sensations (e.g. the 'burn' of hot peppers) from the concept of 'strongest imaginable taste'. We conclude that the LMS can be used to scale sensations of taste and smell when they are broadly defined, but that it should be modified for use in scaling specific taste (and probably odor) qualities. The implications of these results for theoretical issues related to ME, category-ratio scales and the size of the perceptual range in different sensory modalities are discussed.

Acetic Acid↗