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P Sze

Publications and source records attributed to P Sze.

11 recordsLinked to original sources
PubMed1998

The evolutional stage changes in sarcoidosis on gallium-67 scintigraphy.

UNLABELLED: Gallium-67 scintigraphy has been proven as the imaging modality of choice in monitoring the presence of active disease in sarcoidosis. The purpose of this study is to analyze the patterns of evolutional stage changes of sarcoidosis while on steroid therapy by Ga-67 scintigraphy. METHODS: Eighty-six consecutive patients with biopsy-proved sarcoidosis are evaluated by Ga-67 scintigraphy. Thirty-six of 86 patients have had a baseline and one to eight follow-up Ga-67 scintigraphs (total 136 studies). The initial follow-up scintigraphs are obtained on average about 4-12 months after the baseline study. RESULTS: Seventeen of 36 patients (47.2%) are in stage IV at the time of the baseline study. Following their first course of corticosteroid therapy, 13 patients remained in the same stage and activity distribution pattern while 13 patients have shown reversion to other stages, eight patients showed complete remission while two patients became active from inactive stage. CONCLUSION: Evolutional stage changes are seen in 23 patients (63.9%), including eight patients (22.2%) who showed complete scintigraphic remission. The evolutionary stage changes remain quite variable and unpredictable. This, however, should not detract from the usefulness of Ga-67 scintigraphy in the diagnosis and prognostic evaluation of sarcoidosis, particularly when extrapulmonary involvement (Stage IV disease) is present.

Adrenal Cortex Hormones↗
PubMed1997

A novel tetrodotoxin-sensitive, voltage-gated sodium channel expressed in rat and human dorsal root ganglia.

Dorsal root ganglion neurons express a wide repertoire of sodium channels with different properties. Here, we report the cloning from rat, dorsal root ganglia (DRG), cellular expression, and functional analysis of a novel tetrodotoxin-sensitive peripheral sodium channel (PN), PN1. PN1 mRNA is expressed in many different tissues. Within the rat DRG, both the mRNA and PN1-like immunoreactivity are present in small and large neurons. The abundance of sodium channel mRNAs in rat DRG is rBI > PN1 >/= PN3 >>> rBIII by quantitative reverse transcription-polymerase chain reaction analysis. Data from reverse transcription-polymerase chain reaction and sequence analyses of human DRG and other human tissues suggest that rat PN1 is an ortholog of the human neuroendocrine channel. In Xenopus oocytes, PN1 exhibits kinetics that are similar to rBIIa sodium currents and is inhibited by tetrodotoxin with an IC50 of 4.3 +/- 0.92 nM. Unlike rBIIa, the inactivation kinetics of PN1 are not accelerated by the coexpression of the beta-subunits.

Amino Acid Sequence↗
PubMed1996

Structure and function of a novel voltage-gated, tetrodotoxin-resistant sodium channel specific to sensory neurons.

Small neurons of the dorsal root ganglia (DRG) are known to play an important role in nociceptive mechanisms. These neurons express two types of sodium current, which differ in their inactivation kinetics and sensitivity to tetrodotoxin. Here, we report the cloning of the alpha-subunit of a novel, voltage-gated sodium channel (PN3) from rat DRG. Functional expression in Xenopus oocytes showed that PN3 is a voltage-gated sodium channel with a depolarized activation potential, slow inactivation kinetics, and resistance to high concentrations of tetrodotoxin. In situ hybridization to rat DRG indicated that PN3 is expressed primarily in small sensory neurons of the peripheral nervous system.

Amino Acid Sequence↗
PubMed1996

The beta 1 sodium channel subunit modifies the interactions of neurotoxins and local anesthetics with the rat brain IIA alpha sodium channel in isolated membranes but not in intact cells.

Mammalian brain sodium channels consist of an alpha subunit and two smaller beta subunits. The role of the beta 1 subunit in modulating ligand interactions at these channels was examined using a cell line stably expressing human beta1 and rat brain IIA alpha subunits. Coexpression of the beta 1 subunit had no effect on the potencies of sodium channel blockers in inhibiting whole cell [3H]batrachotoxinin A benzoate ([3H]BTX) binding or veratridine-stimulated [14C]guanidinium influx. Coexpression of the beta 1 subunit also had no effect on the potencies of alpha scorpion toxin, brevetoxin, or RU 39568 in stimulating [14C]guanidinium influx. By contrast, coexpression of the beta 1 subunit had dramatic effects on ligand interactions in isolated membranes. In isolated membranes of cells expressing only the alpha subunit, the neurotoxins had no stimulatory effect on [3H]BTX binding and the potencies of local anesthetic-like channel inhibitors were 10-100-fold lower than those at native sodium channels. Whereas in membranes of cells coexpressing the beta 1 subunit, the neurotoxins increased [3H]BTX binding 30-fold and the potencies of the sodium channel inhibitors closely matched those found at native sodium channels. These findings indicate that the beta 1 subunit is not required for the binding of sodium channel activators or inhibitors but rather, that the beta 1 subunit may stabilize the alpha subunit in a functional conformation thereby allowing detection of these interactions in disrupted membranes.

Anesthetics, Local↗
PubMed1994

Visual experience during cataract surgery.

Fifty-six sequential patients undergoing cataract surgery using local anaesthesia were invited to complete a questionnaire recording their visual experiences during the surgery. A majority had peribulbar anaesthesia; none had pre- or per-operative sedation. Fifty-four of the patients could see with their eye during the surgery. Two of these patients could perceive only a bright light; the remainder recorded colours (80%), followed by movements (68%), flashes (66%), abstract colour images (55%) and perception of objects (20%). In two-thirds the brightness of the light changed during the course of the operation (most commonly getting brighter) and in one-third the colours perceived changed during the operation. Pictures were drawn by 22 of the patients of their experience during the surgery.

Adult↗
PubMed1992

Expression of synthetic genes encoding fused proteins under tight control of modified regulatory regions of the colicin operon.

A versatile expression vector system for construction of gene and protein fusions, specific radiolabeling of gene products and high-level protein production is described. Expression cassettes were constructed containing structural genes encoding native and analog forms of connective tissue-activating peptide-III (CTAP-III), beta-thromboglobulin, neutrophil-activating protein and modified regulatory sequences derived from the colicin E1 operon. Gene expression was enhanced by changes in the colicin promoter that increased the transcription initiation rate both in vivo and in vitro, and by deletion of a sequence affecting catabolite repression. High-level expression, producing recombinant protein up to 30% of the total cellular protein, was induced rapidly after stimulation of the SOS response by using either mitomycin C or nalidixic acid, by temperature shift using temperature-sensitive mutations in the LexA or RecA proteins, or by UV light. The presence of radiolabeled amino acids during induction resulted in greater than 95% preferential labeling of recombinant proteins. CTAP-III remained stable for more than 6 h following decay of the inducing signal. The use of CTAP-III in protein fusions improved stability of several therapeutically useful proteins including the thrombin-specific inhibitor, hirudin and a cell receptor-binding domain of laminin, when they were produced in Escherichia coli.

Amino Acid Sequence↗
PubMed1992

The herpes simplex virus type 1 ICP6 gene is regulated by a 'leaky' early promoter.

Expression from the promoter for the large subunit (ICP6) of the ribonucleotide reductase encoded by herpes simplex virus type 1 (HSV-1) has been examined. Using the lacZ reporter gene fused in-frame with ICP6 regulatory sequences to assay expression quantitatively, we showed that the ICP6 promoter responded very weakly to the alpha-transinducing factor (TIF) in the absence of all other viral gene products, but much more strongly to immediate early proteins. Similar patterns of regulation were observed when the reporter gene construct was located at two different positions within the the viral genome or in a stably transfected Vero cell line. Infection of the stably transfected cells with various HSV-1 mutants identified ICP0 as the major transactivator of the ICP6 promoter.

Animals↗
PubMed1991

Structure-function and refolding studies of the thrombin-specific inhibitor hirudin.

We have developed a novel expression and purification system that yields recombinant desulfo-hirudin (HV-1) with high specific activity (10,000 antithrombin units/mg) and an inhibition constant (Ki) for human alpha-thrombin of 0.2 pM. Reduced and denatured hirudin rapidly refolds to the native, fully active conformation at high concentration (greater than 50 mg/ml) by incubation at pH 10. Analytical gel filtration studies at neutral pH suggest that hirudin is a multimer. Initial binding of hirudin to thrombin appears to be followed by dissociation of the hirudin multimer to give a tight-binding 1:1 hirudin:thrombin complex. Thrombin inhibition studies showed that hirudin synthetic peptide fragments 42-65 and 51-65 [but not (Ala22)-6-28, containing two of the three disulfide bonds formed in native hirudin] were similarly effective in inhibiting thrombin cleavage of fibrinogen (IC50 = 4.9 and 6.0 microM, respectively, at a thrombin concentration of 1 microM). We conclude that hirudin has unusual structural and refolding properties and that its mechanism of inhibition involves noncovalent interaction with multiple sites on thrombin. The interaction of hirudin (specifically the region of Lys-47) with the basic specificity pocket of thrombin may contribute to the binding but is not essential for its inhibitory activity.

Amino Acid Sequence↗