Using a community care board to improve aftercare services.
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Biomedical subjects
Publications and source records attributed to J J Miller.
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The evaluation of high-frequency thresholds above 8 kHz has not always been accepted as a reliable, reproducible measure in routine audiological clinics. Using standard equipment we have shown that thresholds at 10 kHz and 12 kHz can be so measured, and that 16 kHz thresholds may be determined with the same degree of reliability with only the minor addition of a signal generator and a set of high performance earphones.
The immunohistochemical localization of calcium-binding protein (CaBP) in the cerebellum, hippocampal formation and olfactory bulb of the rat was examined using rabbit anti-human or sheep anti-chick antisera purified by affinity chromatography. CaBP-like immunoreactivity was observed within the somata and dendrites of: (1) cerebellar Purkinje cells; (2) dentate granule cells, CA1 pyramidal cells and scattered interneurons in the stratum radiatum of the hippocampus; (3) periglomerular cells in the olfactory bulb. Staining was conspicuously absent in certain major cell types in each of these structures including cerebellar granule cells, hippocampal pyramidal cells in the CA3 region and both mitral and granule cells in the olfactory bulb. Immunoreactive fibers in the cerebellum presumably corresponding to climbing fiber inputs from the inferior olive and efferent projections to the deep cerebellar nuclei, were also observed. In the hippocampus intense staining was present in the mossy fiber projection to the CA3 region and in the terminal regions of the perforant path projection from entorhinal cortex.
The distribution in the rat brain of a protein with properties similar to vitamin D-dependent calcium binding protein (CaBP) was measured using a radioimmunoassay developed for mammalian brain CaBP. The cerebellum contained very high levels of CaBP in agreement with reports of CaBP distribution in the chick brain. The protein was distributed in large and unequal concentrations in different regions of the brain. Microdissection of the hippocampus revealed that, within a particular region, CaBP can have a marked differential distribution, suggesting that it is found in specific cell types. The significance of this protein is discussed in relation to the important functions of calcium in the CNS with particular emphasis being placed upon the possible role of CaBP as an intraneuronal calcium ion buffering system.
The relative frequencies of IgM antiIgG autoantibody (rheumatoid factor) producing cells induced by the polyclonal B cell activator Epstein-Barr virus were measured in peripheral blood lymphocyte cultures of normal children and patients with juvenile rheumatoid arthritis. The frequencies of rheumatoid factor precursor B cells in normal children were lower than adults, but higher than neonates. The frequency increased with the age of the donor. In seronegative children with the systemic-onset or pauciarticular-onset types of juvenile rheumatoid arthritis, the number of IgM antiIgG inducible B cells was not significantly different (P greater than 0.05) from age-matched controls. Patients with seropositive juvenile rheumatoid arthritis or seropositive adult rheumatoid arthritis had significantly higher IgM antiIgG precursor cell frequencies than age-matched normal subjects (P less than 0.01 and P less than 0.02, respectively). In contrast, the patients with seronegative polyarticular-onset juvenile rheumatoid arthritis had an average precursor frequency significantly lower than normal age-matched controls (P less than 0.05), analogous to results previously noted in adult seronegative rheumatoid arthritis. Thus, both children and adults with seronegative polyarticular rheumatoid arthritis had a deficiency in B cells that produce IgM antiIgG and that are induced by Epstein-Barr virus. This distinguished them from seropositive juvenile rheumatoid arthritis and rheumatoid arthritis patients, normal subjects, and patients with the pauciarticular-onset and systemic-onset types of seronegative juvenile rheumatoid arthritis.
The effect of a transient increase in extracellular calcium concentration on the Schaffer collateral-commissural evoked excitatory postsynaptic potential and population spike responses of CAI pyramidal neurons was investigated using the rat in vitro hippocampal slice preparation. Brief exposure of slices (5-10 min) to twice the normal concentration of calcium (4 mM) induced a marked potentiation of both the excitatory postsynaptic potential and population spike that could persist for at least 3 h. No long-term changes were observed in either the presynaptic fiber volley of antidromically evoked CAI population spike, indicating that the potentiation could not be attributed to an increase in the number of fibers activated or a generalized increase in cellular excitability. The response of CAI pyramidal neurons to the iontophoretic application of L-glutamate in the apical dendritic zone was also unaffected after exposure to high calcium perfusate, suggesting a lack of alteration in membrane excitability or receptor sensitivity restricted to the region of synaptic input. In addition, total intracellular calcium content of individual slices, measured by atomic absorption spectrophotometry, was significantly increased for at least 1 h following return to the control medium. These data indicate that brief exposure of in vitro hippocampal slices to a high extracellular calcium concentration results in a long-term increase in synaptic efficacy which is similar in many respects to long-term potentiation induced by tetanic stimulation of hippocampal excitatory afferents. The results further suggest that the mechanisms underlying calcium-induced long-term potentiation may reside in presynaptic components and involve an enhanced transmitter release.
One hundred twenty-one young adults 18 years of age or older who had been seen at this hospital with juvenile arthritis since 1955 were surveyed by a series of questionnaires to determine current social function and financial status. Chart reviews and patient questionnaires were used to determine modes of onset and the social circumstances of the family at the onset of the arthritis. The patients as a whole were functioning well: 45 were working full time, 25 were in school full time, 23 were in school and working, and 14 were married women at home. Females had a higher prevalence of persisting disability. Patients who had had a polyarticular onset had lower monthly salaries. No other disease or social variables at onset were statistically associated with any of the outcome variables measured. Fifty of the patients were compared to matched siblings and were found to have achieved comparable educations and salaries, and proportionate numbers of marriages and children.
The electrophysiological characteristics of frequency potentiation and habituation were investigated in two afferent systems of the in vitro hippocampal slice preparation. Low frequency stimulation (1 Hz) of the Schaffer collateral - commissural (Sch-comm) fibers results in a short-term potentiation of the amplitude and rate of rise of the EPSP and population spike responses recorded in the CA1 region. In contrast, 1-Hz stimulation of the perforant path (PP) evokes a short-term, habituation-like depression of the dentate granule cell EPSP and population spike. An inverse relationship was observed between stimulus intensity and the magnitude of frequency potentiation or habituation. Changes in afferent fiber volleys or general excitability of postsynaptic membranes did not contribute significantly to the development of either of these forms of short-term plasticity. Perfusion with a medium containing a high calcium - low magnesium concentration (4 mM Ca+2 and 1 mM Mg+2) produced a differential effect on CA1 and dentate evoked potentials. Following a 20-min exposure to this medium, the amplitude of CA1 potentials was increased while dentate responses were decreased. Frequency potentiation of CA1 responses and habituation of dentate responses were depressed or eliminated by the high calcium medium. The opposing influence of extracellular calcium on CA1 and dentate evoked potentials indicates a fundamental difference in the process of transmitter release in these systems, a characteristic that may contribute to the production of frequency potentiation and habituation.
Alterations in 45Ca uptake and retention as well as total intracellular calcium content were measured in hippocampal 'in vitro' slice preparations following the induction of long-term potentiation (LTP) in CA1 pyramidal neurones. The results indicate that tetanic stimulation of the Schaffer-commissural input produces a significant increase in the uptake and retention of calcium which parallels LTP of the CA1 population spike response.
Glucose capture in the hippocampus and dentate gyrus was studied after administration of [3H]2-deoxy-D-glucose in ketamine-anesthetized rats, using film and fine-grain emulsion autoradiography. On films, the densest label distribution occurred over the distal one-third of CA1 apical dendrites in both the dorsal and ventral hippocampus. The molecular layer of the dentate gyrus was also heavily labeled. On fine-grain emulsions, grain counts in the neuropil of these regions were significantly higher than over CA1 pyramidal cells or dentate granule cell bodies. It is suggested that the greatest label accumulation in the hippocampus occurs in perisynaptic sites in stratum lacunosum-moleculare of CA1.
The effects of conditioning stimuli applied to the commissural pathway on the perforant path (PP) evoked EPSP and population spike response were examined in urethane anaesthetized rats. Whereas conditioning stimuli applied to the PP resulted in a short-term potentiation of both the EPSP and population spike evoked by a test pulse to the same pathway (homosynaptic potentiation), only the population spike was potential when the PP test pulse was preceded by a conditioning volley to the commissural afferent. This form of heterosynaptic potentiation, which occurs in the absence of any significant change in the synaptic currents generated by the perforant path, suggests that alterations in postsynaptic excitability may underly the process of short-term potentiation rather than an augmented transmitter release.
The corpus callosum, a cerebral commissure of 200,000,000 fibres, is thickened in chronic schizophrenia and several neuropsychological and neurophysiological techniques have suggested poor links between the two cerebral hemispheres. The interhemispheric conduction time across the corpus callosum, measured in 12 schizophrenics, using the ipsilateral/contralateral latency differences of the early somatosensory evoked response, was found to be effectively zero. It is suggested that schizophrenia is a split-brain condition akin to agenesis of the corpus callosum, unrecognized through the use of compensatory ipsilateral sensory pathways.
The responses of dentate granule cells to medial septum (MS) and perforant path (PP) stimulation were examined in urethane anaesthetized rats. MS and PP stimulation evoked an orthodromic activation of granule cells which was correlated with the negative transient of the characteristic field potential elicited from each site. The effects of electrophoretic application of acetylcholine (ACh) and glutamate (Glu) were examined on granule cells identified in this manner. The excitatory action of ACh but not that of Glu was antagonized by atropine. Glutamate diethylester (GDEE) blocked the excitation produced by Glu but not ACh. The synaptically evoked excitation elicited by MS was blocked by atropine but unaltered by GDEE whereas the PP excitatory response was blocked by GDEE and unaltered by atropine. The results of this study indicate that two discrete excitatory systems are present in the dentate gyrus of the rat: a cholinergic system originating in the medial septum and a glutamate mediated system originating in the entorhinal cortex.
Determinations of C3, C4, and C5 concentrations by radial immunodiffusion, and assays for the activation products of C3, C3c and C3d by counterimmunoelectrophoresis, were performed on 80 infants. Seven nonbacteremic preterm infants with necrotizing enterocolitis (NEC) or probable NEC (PNEC) were found at the time of diagnosis to have a significantly lower mean concentration of C3 (P less than 0.05, 1-tailed) without C3 activation when compared to other noninfected preterm infants. Ten full-term and 63 preterm infants were studied prospectively during the first days of life, and were then followed for the postnatal development of localized or systemic infection. Assays for the detection of C3 activation products were negative in all these infants. Four preterm infants who developed PNEC after 5 or more days without clinical illness had low original concentrations of complement components. The pathogenesis of NEC may not involve primarily complement activation, and susceptibility to this condition may be related to pre-existing deficiencies in complement component concentrations relative to gestational age, or to defective activation of C3 in the presence of certain bacterial species and strains.
In an apomictic strain of Saccharomyces cerevisiae that normally produces two-spored asci, production of three and four-spored asci was restored by adjusting zinc and carbon source levels in presporulation and sporulation media. Sporogenic capability was compared after growth in defined and undefined presporulation environments. Cultivation in defined presporulation medium containing 6% glucose followed by sporulation in 3.5% acetate yielded 16 +/- 3% three- and four-spored asci. Inclusion of 25 mug of zinc sulfate per ml in presporulation medium or 25 mug of zinc acetate per ml in sporulation medium gave a further increase in yield of three- and four-spored asci; it reached 48 +/- 1% when zinc was added to both media. Cells grown in undefined presporulation medium were incapable of three- and four-spored ascus development in acetate sporulation medium unless zinc was included in the latter medium. Cultivation in defined presporulation medium amended with yeast extract, peptone, or casein hydrolysate greatly reduced three- and four-spored ascus yields. Inclusion of a meiotic inhibitor (glucose) in sporulation medium inhibited three- and four-spored ascus production but not two-spored ascus production. Nuclear staining demonstrated two classes of asci: binucleate (one and two spored) and tetranucleate (three and four spored). Hence, some control over apomictic versus normal ascus development has been gained by nutritional manipulation.
Use of the fluorochrome 4',6-diamidino-2-phenylindole.2 HCl (DAPI) in ultraviolet microscopy revealed fluorescent objects in Brownian motion within the vacuoles of seven species of yeast. The abundance of these bodies increased when cells of Saccharomyces cerevisiae were transferred from growth medium to a glucose-phosphate solution, indicating that they contain polyphosphate. In addition, the effect on vacuolar fluorescence of supplementing a defined growth medium with amino acids provided evidence that they also contained S-adenosylmethionine. These deductions were supported by in vitro studies of the interaction and fluorescence of polyphosphate, S-adenosylmethionine, and DAPI. Vacuolar fluorescence of cells in suspension in flucose-phosphate solution was less after addition of exogenous arginine, lysine, or glutamine but not after addition of alanine, aspartic acid, or methionine. Mithramycin was superior to DAPI as a fluorochrome for ultraviolet demonstration of yeast nuclei since it stained the nuclei much more intensely and did not fluoresce with other material in the cells.
Five imidazole compounds were added to cultures of human lymphocytes which had been stimulated to undergo blast transformation by exposure to phytohaemagglutinin, pokeweed mitogen or allogeneic cells. Two compounds, clotrimazole and dacarbazine (DTIC) produced a dose related suppression of these responses. Nimorazole was largely inactive whereas metronidazole and tinidazole actually enhanced the response--at least in those cultures stimulated by the plant mitogens. It is suggested that experiments of this kind are helpful in identifying those imidazole compounds that could be used as immunosuppressants in vivo.