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Biomedical subjects

J J Miller

Publications and source records attributed to J J Miller.

At least 127 records · Page 7Linked to original sources

Extracellular fields influence transmembrane potentials and synchronization of hippocampal neuronal activity.

The influence of extracellular fields on the transmembrane potential (TMP) of CA1 pyramidal neurons was investigated following both ortho- and antidromic stimulation in the in vitro hippocampal slice preparation. A short latency negative deflection on the intracellular potential coincided with the falling phase of the extracellular population spike. Subtraction of extracellular field potentials from ground referenced intracellular records revealed a sharp depolarizing wave of the TMP superimposed upon the underlying synaptic potential. This graded depolarization was capable of discharging CA1 cells and displayed a parallel shift in latency and amplitude with the extracellular population spike. A similar depolarizing wave was associated with the antidromically evoked population spike which persisted following blockade of synaptic activity. Finally, multiple population spike activity similar to that observed during epileptiform discharge was associated with repetitive depolarizing waves of the TMP. These data suggest that extracellular field potentials can ephaptically discharge CA1 neurons and may play a role in recruitment and synchronization of neuronal activity in the hippocampus.

Animals↗

Human (semisynthetic) insulin and porcine insulin in the treatment of non-insulin-dependent diabetes. A double-blind, comparative clinical trial.

Twenty-one patients with non-insulin-dependent diabetes, who had not previously received insulin therapy, participated in a double-blind comparative trial of six months' duration to evaluate the efficacy of human (semisynthetic) insulin. Patients were allocated at random to treatment either with human (semisynthetic) insulin (10 patients) or with an equivalent porcine insulin regimen (11 patients). Sex ratio, age, body mass index, duration of diabetes, C-peptide concentrations, baseline metabolic control and initial insulin requirements were similar in both groups. After six months, no significant differences between the treatment effects of human (semisynthetic) insulin and porcine insulin, as assessed by measurements of fasting and postprandial plasma glucose levels, the concentration of glycosylated haemoglobin, serum lipid levels, insulin dose, and body weight, were found. No adverse reactions, injection-site anomalies, or drug-related biochemical abnormalities were noted in either group. It was concluded that human (semisynthetic) insulin is as effective as porcine insulin in initiating the treatment of patients with non-insulin-dependent diabetes who require insulin therapy.

Blood Chemical Analysis↗

Anti-F(ab')2 antibodies that interfere with interpretation of the anti-C3 assay for immune complexes in children with rheumatic diseases.

Results of the solid phase F(ab')2 anti-C3 radioimmunoassay for immune complexes were abnormal in sera from some patients with juvenile arthritis and in many patients with other forms of chronic inflammation. However, C3 failed to block positive reactions of sera from patients even though it did block the reaction when aggregated IgG was added to normal sera. Moreover, positive sera reacted with nonspecific F(ab')2 fragments from several species. High correlation coefficients were obtained between abnormal results in the anti-C3 assay with juvenile arthritis sera and reactions with goat, mouse, and rabbit F(ab')2, but less so with human F(ab')2. Sera from patients with systemic lupus erythematosus or cystic fibrosis had similar reactions but different species specificities. After sucrose density fractionation, the reactivity with nonspecific anti-F(ab')2 was only in the IgG-containing fractions, but anti-C3 activity was in both IgG-containing fractions and the fractions between IgG and IgM. We concluded that anti-F(ab')2 antibodies are common in children with inflammation and may interfere with interpretation of assays using F(ab')2 anti-C3 for detection of complexes.

Animals↗

Ephaptic interactions contribute to paired pulse and frequency potentiation of hippocampal field potentials.

The contribution of ephaptic interactions to potentiation of the hippocampal CA1 extracellular population spike during paired pulse or frequency stimulation of stratum radiatum (SR) inputs was investigated using the in vitro hippocampal slice preparation. Records of the transmembrane potential revealed a depolarizing wave with an amplitude and latency that varied directly with that of the extracellular population spike. Paired pulse or repetitive stimulation of SR resulted in a potentiation of the population spike amplitude and a corresponding increase in the amplitude of the TMP depolarizing wave. Action potentials generated during the stimulus train consistently arose from the peak of the depolarizing wave. It is proposed that ephaptic interactions contribute to potentiation of the extracellular population spike through recruitment of subthreshold neurons within the population during repetitive afferent stimulation.

Animals↗

Medial septal projections to the dentate gyrus of the rat: electrophysiological analysis of distribution and plasticity.

Previous electrophysiological experiments in rabbits have suggested that medial septal stimulation activates dentate granule cells and evokes an associated negative field response at the granule cell layer, without an associated "dendritic" response. Anatomical studies have suggested that septal input to the granule cells may be to stratum moleculare, or close to the cell layer, or may not exist at all. The present experiments confirmed in rats anaesthetised with urethane that medial septal stimulation elicits single action potentials from cells in the granule layer. The associated negative field potential was maximal in the granule cell layer and there was no sign of a separate dendritic potential. The fibres responsible for this potential travel to the dorsal hippocampus in the fornix superior rather than the fimbria, taking the same course as the fibres which contribute to the dense cholinesterase staining just above the granule cell layer. Stimulation at 100 Hz for 1 s of either medial septal, or perforant path, input to the dentate granule cell layer produced long term potentiation of the subsequent evoked field responses to the stimulated pathway. The responses to the non-stimulated pathway were unchanged. Paired pulse stimulation produced both homosynaptic and heterosynaptic potentiation. These data suggest that medial septal input synapses close to granule cell bodies and produces a negative field potential which is a combination of dendritic and population spike potentials. Medial septal input also appeared to produce direct activation of hilar neurones, some of which may be basket cells or other interneurones. The data also show that long term potentiation is specific to this input, perhaps dependent on presynaptic mechanisms. Paired pulse potentiation, at least in the heterosynaptic case appears to depend on postsynaptic mechanisms.

Animals↗

Blockade of tetanic- and calcium-induced long-term potentiation in the hippocampal slice preparation by neuroleptics.

The effect of neuroleptics which block calmodulin was studied on two forms of long-term potentiation of field responses evoked by stratum radiatum stimulation of the CA1 region in the in vitro preparation of hippocampal slices. Tetanic stimulation or brief exposure to 4 mM Ca2+ produced a long-lasting augmentation of the extracellular excitatory postsynaptic potentials EPSP) and of the responses of the population spikes. Both forms of potentiation were inhibited by perfusion of 10 microM trifluoperazine (TFP) or pimozide, an effect which is unlikely to involve interactions with dopamine or norepinephrine receptors, but rather a potent blockade of calmodulin-mediated events. The results suggest that induction of the "permanency" of both tetanic- and calcium-induced long term potentiation requires activation of calmodulin and involves some calmodulin-mediated mechanism(s).

Animals↗

Comparison of the sterility of long-term central venous catheterization using single lumen, triple lumen, and pulmonary artery catheters.

The incidence of thrombocytopenia and catheter-induced infection and colonization after the use of triple lumen (TLC), pulmonary artery (PA), and single lumen central venous (CVP) catheters was studied in 29 critically ill patients. Catheter-induced sepsis was documented in 7% of patients with TLC and 10% of patients with CVP and PA catheters. Thirty-three percent of TLC, 20% of PA and 10% of CVP catheters became contaminated during the study. Staphylococcus epidermidis most commonly caused catheter sepsis and contamination. Only patients with PA catheters showed significant decrease in their platelet count. We conclude that use of TLC catheters in critically ill patients does not appear to increase the risk of infectious disease and thrombocytopenia.

Aged↗

Rapid purification of radioiodinated peptides with Sep-Pak reversed phase cartridges and HPLC.

A simple, rapid method is described for the purification of radioiodinated peptides for use in radioimmuno- and in radioreceptor assays. Iodinated reaction mixtures are applied directly onto Sep-Pak disposable, reversed phase cartridges equilibrated with phosphate buffer. Unreacted 125-iodide and other non-peptide reaction components are eluted with buffer. The peptide fraction is then eluted with 70% buffer: 30% acetonitrile. The peptide fraction is further purified by reversed phase high pressure liquid chromatography to separate the native peptide and the mono- and diiodo-derivatives. In this study the method is used to prepare 125-iodide-labeled monoiodo-leucine enkephalin and monoiodo-angiotensin II, which are free of the parent peptides and diiodo-derivatives and are of maximum obtainable specific radioactivity. The usefulness of these labeled peptides in radioimmuno- and radioreceptor assays is demonstrated by their binding to specific antibodies and receptors, respectively.

Chromatography, High Pressure Liquid↗

Lymphocyte subpopulation alterations induced by intravenous megadose pulse methylprednisolone.

Lymphocyte subpopulations from 9 children with different rheumatic diseases were studied before and 5, 24 and 48 h after high dose intravenous methylprednisolone. Leu-1 (+) cells, Leu-2a (+) cells, Leu-3a (+) cells and surface immunoglobulin (+) cells were counted. A panlymphopenia occurred 5 h after infusion, but numbers of all cell types were normal by 48 h. B cells were less affected than T cells. Leu-3a (+) cells were relatively more decreased than the other populations at 5 h and took longer to return to prepulse levels. This suggests a selective difference in distribution of lymphocyte subpopulations after pulse methylprednisolone infusion.

Arthritis, Juvenile↗

The effect of juvenile inflammatory synovial fluid on in vitro cartilage.

Inflammatory and noninflammatory juvenile synovial fluid (SF) samples were examined in vitro for their effect on cartilage. SF from 3 of 6 patients with pauciarticular juvenile arthritis (JA), 7 of 7 patients with polyarticular JA and 2 of 2 patients with ankylosing spondylitis had significantly increased proteoglycan (PG) releasing activity in 4 day cultures of living but not of freeze-killed cartilage. Noninflammatory SF did not cause increased PG release. Cartilage collagen content was not significantly altered by either inflammatory or noninflammatory SF. Our in vitro results showed PG releasing activity was present in inflammatory but not in normal juvenile SF.

Animals↗

Biochemical and immunohistochemical correlates of kindling-induced epilepsy: role of calcium binding protein.

The levels and distribution of calcium binding protein (CaBP) were examined in the central nervous system of rats exhibiting kindling-induced epilepsy. Following commissural kindling, the concentration of CaBP in the hippocampal formation was significantly reduced but no change was observed in levels of total soluble protein or calmodulin, another calcium-related protein. Histochemical examination of kindled animals revealed a localized depletion of CaBP-like immunoreactivity restricted to the dentate granule cell-mossy fiber system of the hippocampal formation. These data demonstrate a correlation between the loss of CaBP from dentate granule cells and kindling-induced epilepsy, the underlying mechanism of which may involve an impairment of granule cells to regulate their intracellular calcium environment when challenged with high frequency electrical stimulation.

Animals↗

Consumption coagulopathy associated with systemic juvenile rheumatoid arthritis.

A coagulopathy resembling disseminated intravascular coagulation may occur in systemic juvenile rheumatoid arthritis. We have seen this in seven patients with three different circumstances of disease activity or drug treatment. In one patient, a coagulopathy was not associated with drug therapy, and required corticosteroid therapy for control. A second group of patients was receiving orally nonsteroidal anti-inflammatory drugs during an acute flare-up of disease associated with low serum albumin concentrations. Coagulopathy in these patients may be a result of reduced vascular endothelial cell cyclooxygenase activity secondary to increased levels of unbound nonsteroidal anti-inflammatory drug. In these children, corticosteroid therapy was required for control. A third form of coagulopathy was seen in patients receiving a second injection of aurothiomalate. This form appears to be idiosyncratic, self-limiting, and relatively benign.

Administration, Oral↗

Events associated with restoration by zinc of meiosis in apomictic Saccharomyces cerevisiae.

The effects of nutritional alterations (carbon source and zinc) on nuclear division and protein synthesis during apomictic and meiotic development in Saccharomyces cerevisiae 19e1 were investigated. Unlike cells cultivated under meiosis-promoting conditions, cells cultured under apomixis-promoting conditions exhibited extensive protein synthesis during the first 3 h of incubation in sporulation medium, and nuclear divisions were evident during this time. Cycloheximide treatment of the latter cells induced meiosis, and maximum yields of meiotic asci resulted when this treatment was given for the first 3 h in sporulation medium. The results indicate that the decision concerning which developmental route cells will follow is made shortly after transfer to sporulation medium. Electrophoretic analysis of labeled proteins synthesized during sporulation revealed bands unique to both developmental routes.

Cell Division↗

Translocation of zinc from vacuole to nucleus during yeast meiosis.

A novel staining procedure employing the UV fluorochrome DAPI (4',6-diamidino-2-phenylindole X 2HCl) and dithizone (diphenylthiocarbazone) was developed for microcytochemical determination of sites of zinc localization in Saccharomyces cerevisiae Hansen. In vegetative cells vacuolar polyphosphate bodies stained with dithizone, whereas in sporulating cells nucleoli and centriolar plaques were dithizone-positive. Hence, dithizone not only permitted localization of zinc but also indicated zinc translocation from vacuolar to nuclear compartments during differentiation from the vegetative to sporulated state.

Cell Nucleus↗

Role of norepinephrine in seizurelike activity of hippocampal pyramidal cells maintained in vitro: alteration by 6-hydroxydopamine lesions of norepinephrine-containing systems.

Perfusion of 50 microM norepinephrine (NE) produced a marked, reversible decrease (range 20-28%) of the extracellular population spike and excitatory postsynaptic potential (EPSP) responses of the CA1 region evoked by stratum radiatum stimulation in the rat hippocampal slice preparation. The effects of NE were dramatically altered in slices obtained from animals which were previously treated with intracerebral or intraventricular injections of 6-hydroxydopamine (6-OHDA) to destroy forebrain catecholamine systems. In the latter preparations NE produced a reduction in the inhibition of the EPSP (50%), enhancement of the population spike amplitude, and multiple spike discharges characteristic of ongoing epileptiform activity. The reversal of NE-induced inhibition and the generation of seizurelike activity in 6-OHDA-treated animals suggests that NE may, in part, act upon interneurons to produce a disinhibition of CA1 pyramidal cells.

Animals↗

Low-frequency stimulation of the perforant path produces long-term potentiation in the dentate gyrus of unanesthetized rats.

Brief periods of high-frequency stimulation of hippocampal afferents produce long-term potentiation (LTP) of synaptic transmission, but the minimum frequency capable of inducing this alteration in synaptic efficacy has not been specified. The present study used the repeated measurement of input-output curves in the perforant path - dentate gyrus system of freely moving rats to monitor synaptic efficacy and found that stimulation at 0.2 Hz, but not 0.04 Hz produced LTP. These results suggest that the minimum stimulation frequency capable of producing LTP is lower than previously described. Possible reasons for the discrepancy between the present and previous findings are discussed, along with the implications of low-frequency potentiation.

Action Potentials↗