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Biomedical subjects

J Smith

Publications and source records attributed to J Smith.

At least 1,009 records · Page 56Linked to original sources

Systematic errors in estimating prevalence and severity of periodontal disease.

Partial-mouth scores are often used in epidemiologic studies to estimate the prevalence and severity of periodontal disease. Such estimates systematically underestimate the prevalence of disease, but the bias can be in either direction for disease severity. Three large data sets containing full-mouth examinations (mesiobuccal, midbuccal, distobuccal, and midlingual (MBDL) sites per tooth) for either attachment loss or probing pocket depths were used to investigate the magnitudes of systemic error that occur by employing four specific partial-mouth scores (M, MB, MBD, and MBDL sites per tooth), which are based on the random half-mouth technique. For prevalence of disease the sensitivity of a partial score was a function of the disease level in the population. All four partial scores were sensitive enough to adequately portray true prevalence using the 2-mm demarcation value, the MBD and MBDL scores might still be considered adequate for the 4-mm value, but none of these partial scores were adequate for the 7-mm value. For disease severity the MBDL score produced unbiased estimates, the others were biased. The relative biases for the MB and MBD scores were all under 10% (in absolute value), but the M score produced severe relative biases, 24% for probing pocket depths and -12% for attachment loss.

Cross-Sectional Studies↗

Hypoglycaemic coma associated with anorexia nervosa.

Profound hypoglycaemia is a rare event which has been described in seven cases of anorexia nervosa. A further case is reported here and the literature regarding this complication is reviewed. The major risk factors identified are body weight below 30 kg, a period of fasting and intercurrent infection. Excessive exercise may also play a role. The precise pathogenesis has not been elucidated but several mechanisms, including depletion of liver glycogen, defective gluconeogenesis or failure of glucagon secretion have been proposed. Although hypoglycaemic coma frequently results in death, prompt treatment may result in full recovery as occurred in the case described here.

Adult↗

The Abbott IMx automated benchtop immunochemistry analyzer system.

We describe a new clinical laboratory instrument, the IMx, used to automate immunoassay testing in the clinical laboratory. The IMx incorporates a novel technology called Microparticle capture Enzyme ImmunoAssay (MEIA) for assays of high-molecular-mass analytes, and fluorescence polarization immunoassay (FPIA) for hapten assays. A front-surface fluorometer is used to quantify the enzymatic generation of fluorescent product at a rate proportional to the concentration of the analyte in an MEIA, and a fluorescence polarization optical system is used to quantify results in an FPIA. The microprocessor-based instrument uses a robotic arm with two degrees of freedom and a rotating carousel to process the samples for assay. One assay can be done on each of 24 patients' specimens in 30 to 40 min with "walk-away" automation. Calibration curves are stable for at least two weeks. Instrument control involves software-labeled "command keys," a numeric keypad, and an interactive display. Results are output to a thermal printer or computer interface.

Autoanalysis↗

High-affinity uptake of noradrenaline in quail dorsal root ganglion cells that express tyrosine hydroxylase immunoreactivity in vitro.

During embryonic life, avian sensory ganglia contain cells with the potential to express, under appropriate experimental conditions, a number of properties characteristic of autonomic sympathetic neurons. Thus, cells capable of synthesizing noradrenaline (NA) from tyrosine differentiate when dorsal root ganglia (DRG) from 10-15 d embryonic quail are grown in culture (Xue et al., 1985a, b). In the present study, we show that cultures of DRG from 10 d embryos can take up 3H-NA by a high-affinity (Km = 1.0 microM), temperature-dependent process that can be inhibited by desmethylimipramine. By means of combined immunocytochemistry and autoradiography, it was demonstrated that the majority (70-80%) of the tyrosine hydroxylase (TH)-immunoreactive cells that developed in the cultures possessed a transport system for NA. Catecholamine (CA) uptake also occurred in a small, but relatively constant, number of TH-negative cells, but was absent from substance P-containing neurons. In contrast to TH, which appears only after 3-4 d in vitro, cells capable of taking up NA with high affinity were found in DRG cultures after only a few hours, and a small number (less than 0.5% of the total cell population) was detected in freshly removed, uncultured ganglia. Such cells did not react with antibodies directed against substance P or neurofilament proteins. We conclude that autonomic precursors are identifiable in a subset of non-neuronal DRG cells, prior to full expression of a noradrenergic phenotype, by their possession of a high-affinity uptake system for CA.

Animals↗

Effects of 5,7-dihydroxytryptamine lesions of the nucleus accumbens in rats responding on a concurrent schedule of food, water and intravenous morphine self-administration.

The role of serotonergic innervations of the nucleus accumbens in the processes maintaining intravenous self-administration was assessed in rats responding on a concurrent schedule of food, water and morphine presentations. Five rats were trained on a concurrent fixed-ratio schedule of food and water presentation. They were then implanted with intravenous jugular catheters and bilateral injection guide cannulae into the central medial nucleus accumbens, made physically dependent on morphine and allowed to choose between intravenous morphine, food and water deliveries. A three-lever choice procedure provided almost continuous access to the three reinforcers. Dose-effect curves were determined by the substitution of the daily dose of morphine (3.3 mg/injection) with other doses (0.83-13.2 mg/injection) or eliminating drug injections (extinction) for 24 hour periods. The behavioral effects of 24 hour food extinction probes were also determined. The rats subsequently received bilateral microinjections of either the vehicle or 5,7-dihydroxytryptamine (5,7-DHT) into the nucleus accumbens. Following the lesion, response independent infusions of morphine were delivered for 24 hours at the previous rate of self-injection. The animals were placed back on the concurrent schedule and morphine dose-effect curves were redetermined. The 5,7-DHT lesion resulted in a significant dose-related decrease in morphine self-administration, and little or no effect on responding maintained by food or water presentations. Serotonergic innervations of the nucleus accumbens appear to participate in the neuronal activity mediating intravenous morphine self-administration.

5,7-Dihydroxytryptamine↗

Heparin-induced thrombocytopenia: laboratory studies.

This report describes studies into the pathophysiology of heparin-induced thrombocytopenia. The IgG fraction from each of nine patients with heparin-induced thrombocytopenia caused heparin-dependent platelet release of radiolabeled serotonin. Both the Fc and the Fab portions of the IgG molecule were required for the platelet reactivity. The platelet release reaction could be inhibited by the Fc portion of normal human or goat IgG, and patient F(ab')2, but not F(ab')2 from healthy controls. These results suggested that the Fab portion of IgG binds to heparin forming an immune complex and the immune complexes initiate the platelet release reaction by binding to the platelet Fc receptors. To directly challenge this hypothesis, we preincubated the serotonin-labeled platelets with the monoclonal antibody against the platelet Fc receptor (IV.3). This monoclonal antibody completely inhibited the release reaction caused by heparin and patient sera, as well as heat aggregated IgG, but did not block collagen or thrombin-induced platelet release. Heparin-dependent platelet release also could be inhibited in vitro by the addition of monocytes and neutrophils, but not by red cells, presumably because the Fc receptors on the phagocytic cells have a higher binding affinity for IgG complexes than do platelets. Platelets from patients with congenital deficiencies of specific glycoproteins Ib and IX (Bernard-Soulier syndrome) and IIb and IIIa (Glanzmann's thrombasthenia) displayed normal heparin-dependent release indicating that the release reaction did not require the participation of these glycoproteins. These studies indicate that heparin-induced thrombocytopenia is an IgG-heparin immune complex disorder involving both the Fab and Fc portion of the IgG molecule.

Antibodies, Monoclonal↗

RAWP revisited.

Explore the source record for details and available documents.

Health Resources↗

Polyclonal activation of the murine immune system by an antibody to IgD. VIII. Stimulation of IgD secretion.

The low levels of serum IgD found in mice and the lack of a typical DNA switch sequence between C delta and C mu raise the possibility that the generation of murine IgD-secreting cells results from a chance "mistake" rather than a controlled process. The recent observation that injection of mice with purified IgD upregulates IgD receptor expression on helper T cells and enhances the ability of these T cells to induce B cells to differentiate into antibody secreting cells led us to look for evidence of controlled differentiation of B cells into IgD-secreting cells. To do this, we injected mice with a goat antibody to IgD (GaM delta), because this antibody stimulates large increases in IgM, IgG1, IgG2a, and IgE secretion. Mice injected with GaM delta demonstrated a large increase in splenic content of mRNA specific for the secreted form of delta-chain, as well as a greater than 100-fold increase in the percentage of splenic IgD-containing plasmablasts. The secretory IgD response was totally T-dependent. Production of the secretory form of IgD was not seen until 7 days after GaM delta injection, and peaked sharply on day 8, whereas by day 6 IgM secretion had already peaked and IgG1 and IgG2 secretion had attained substantial levels. This observation suggests that: 1) either cells that synthesize large quantities of the secretory form of delta-chain, unlike cells that synthesize large quantities of the secretory forms of gamma-, epsilon-, or alpha-chains, do this without deleting C mu, or, despite the absence of a typical DNA switch sequence between C mu and C delta, controls must exist to effect the C mu deletion and VDJ-C delta joining; and 2) if secreted IgD has a role in the regulation of a humoral immune response it most likely is involved in later processes, such as memory cell generation or response termination, rather than in relatively early processes, such as helper T cell activation.

Animals↗

Cytotoxic response of the relatively difluoromethylornithine-resistant human lung tumor cell line NCI H157 to the polyamine analogue N1,N8-bis(ethyl)spermidine.

Difluoromethylornithine (DFMO), an enzyme activated irreversible inhibitor of ornithine decarboxylase (ODC), depletes intracellular putrescine, and spermidine (Spd), but not spermine, and generally leads to an inhibition of cell proliferation, without cell death, in both normal and neoplastic cells. This is the case with a culture line of human large cell undifferentiated lung cancer, NCI H157, which will survive indefinitely in DFMO containing medium and ultimately actually grows through the DFMO block. We now provide evidence that a Spd analogue, N1,N8-bis(ethyl)spermidine (BES) also suppresses ODC activity in H157 cells but leads not only to complete depletion of putrescine and Spd but also reduces intracellular spermine to 20-30% of control levels. This depletion of polyamines is accompanied by a rapid decrease in cell proliferation and ultimately cell death. The cell death resulting from BES treatment is in direct contrast to results obtained with DFMO and occurs at concentrations of less than 10 microM, whereas 5 mM DFMO is required to maintain growth inhibition in NCI H157. The observed suppression of ODC activity by BES is consistent with mechanisms by which Spd itself regulates ODC activity. Our data suggest that although both agents, DFMO and BES, interfere with polyamine metabolism, the differential sensitivities to these agents indicate susceptibility to polyamine depletion may be agent and cell type specific. Such differences may be related to the different requirement of individual cell types for polyamines and different regulatory events in polyamine biosynthesis. These differences may be exploitable in the treatment of neoplastic disease with polyamine analogues or inhibitors of polyamine biosynthesis.

Carcinoma, Non-Small-Cell Lung↗

Major intrinsic polypeptide (MIP26K) of the lens membrane: covalent change in an internal sequence during human senile cataractogenesis.

Polyclonal antisera to three synthetic peptides of bovine MIP26K have been used in combination with Western blot analysis to probe for changes of the MIP26K molecule during human senile cataractogenesis. Anti-MIP26K229-237 binds well to the 26K component from cataractous lens membranes, but binds poorly to the same component from normal lens. In contrast, antisera to two other sequences of MIP26K (anti-MIP26K252-259 and anti-MIP26K256-263) bind approximately equally well to the 26K component from either cataractous or normal lens. Together, these results demonstrate that during cataract development there is a selective covalent change in a region of the MIP26K molecule that may have profound effects upon the ability of this molecule to facilitate intercellular communication between lens fiber cells.

Amino Acid Sequence↗