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Biomedical subjects

J Percy

Publications and source records attributed to J Percy.

15 recordsLinked to original sources

Cyclic AMP-dependent anion secretion in human small and large intestine.

Cyclic AMP-dependent Cl- secretion is the major secretion pathway in human intestine. The aim of the present study was to examine mechanisms involved in cAMP-dependent anion secretion in human small and large intestine. Surgical resection specimens from both jejunum and distal colon were studied under short circuited conditions. Addition of the phosphodiesterase inhibitor IBMX induced an increase in the short-circuit current (Isc) equivalent to the net increase in Cl- secretion. The Isc was inhibited by diphenylamine decarboxylate (DPC; Cl- channel blocker), bumetanide (basolateral Na+/K+/2Cl- cotransporter), BaCl2 (basolateral K+ channel) and Cl- free buffer in both segments and indomethacin (cyclo-oxygenase inhibitor) in colon alone. Diphenylamine decarboxylate appears to directly inhibit secretion in jejunum, although its inhibitory effect is possibly mediated by inhibition of cyclo-oxygenase in the colon. A small component of IBMX-stimulated Isc was inhibited by acetazolamide. Cyclic AMP-dependent secretion is largely apical Cl- secretion, although a small component appears to be HCO3. Secretion is dependent on basolateral K+ channels and Na+/K+/2Cl- cotransporters and, in the colon, is inhibited by indomethacin, implying a role for cyclo-oxygenase metabolites. The chloride channel blocker DPC inhibits secretion in both areas. This class of compounds may have potential for treatment of secretory diarrhoea.

Adolescent

Fixing human factor IX (fIX): correction of a cryptic RNA splice enables the production of biologically active fIX in the mammary gland of transgenic mice.

Transgenic mice and sheep secrete only low levels of human factor IX in their milk because of an aberrant splicing of the transgene RNA in the mammary gland. Removal of the cryptic 3' splice site prevents this splicing and leads to the production of relatively high levels of factor IX. The purified protein is fully active showing that the mammary gland is capable of the efficient post-translational modification of this protein and that transgenic animals are a suitable means of its production.

Animals

Expression of human alpha 1 antitrypsin in transgenic sheep.

We have recently described the production of large amounts (< or = 65 grams per litre) of enzymatically active human alpha 1 antitrypsin in the milk of transgenic sheep (Wright et al., 1991). Here, we describe in more detail the expression of the human protein in the milk of these animals throughout the lactation period. Human alpha 1 antitrypsin is also found at much lower levels in the plasma of transgenic ewes before, during and after lactation. It is also detected in male plasma at very low levels. We have previously shown human alpha 1 antitrypsin purified from transgenic sheep milk to be indistinguishable from commercially available human plasma derived alpha 1 antitrypsin in terms of gross sugar content and in vitro activity. Here we extend this comparison to more detailed analyses of glycosylation state, amino-terminal sequence, pI value, and molecular weight determination by mass spectrometry.

Amino Acid Sequence

The vacuolar H(+)-translocating ATPase of renal tubules contains a 115-kDa glycosylated subunit.

Kidney microsomes were fractionated with Triton X-114, to give a fraction enriched in the renal tubule H(+)-translocating ATPase, as judged by the sensitivity of its ATPase activity to bafilomycin A1, and its content of two polypeptides recognized by antibodies directed against subunits of plant tonoplast ATPases. This fraction contained a polypeptide of apparent molecular mass of 115 kDa, that was recognized by an antibody to the largest (120 kDa) subunit of chromaffin-granule membrane H(+)-ATPase, and, like this subunit, was reduced in molecular weight on treatment with glycopeptidase F. We conclude that, like other mammalian vacuolar H(+)-ATPases, the kidney H(+)-ATPase contains a large, glycosylated subunit.

Adrenal Gland Neoplasms

Herpes labialis treatment with acyclovir 5% modified aqueous cream: a double-blind randomized trial.

The efficacy of 5% acyclovir in a modified aqueous cream vehicle (ACV-MAC) in the treatment of recurrent herpes labialis was tested in a randomized, double-blind clinical trial with the modified aqueous cream vehicle as a control medication. The ACV-MAC formulation has previously been shown to offer superior cutaneous absorption relative to other topical acyclovir formulations. Treatment was initiated by patients within 1 hour of prodrome in an attempt to maximize clinical impact of this virustatic drug. While the patient group receiving active drug showed a trend toward accelerated healing, no significant differences for lesion or healing characteristics could be measured between the two treatment groups. It is suggested that optimal efficacy of ACV-MAC may be predicated on prophylactic treatment, that is, "trigger"-initiated rather than prodrome-initiated treatment.

Acyclovir

Tiger mauling: fatal spinal injury.

A 33 year old zoo keeper was attacked by a Sumatran tiger in captivity. Apart from severe lacerations and penetrating wounds to the head and neck, the patient sustained comminuted fractures of C1 and C2 vertebrae with resultant high laceration of the spinal cord. Major vascular injury as well as trauma to pharynx also occurred. The patient survived these injuries for 15 h.

Accidents, Occupational

Treatment of herpes labialis with acyclovir. Review of three clinical trials.

Three trials with acyclovir in the treatment of recurrent herpes labialis in the same patient population are reviewed. In the first trial, oral acyclovir capsules, five times per day for five days, were shown to be of significant benefit for some parameters of cutaneous resolution in three successive episodes. Topical formulations were evaluated in two separate trials; 5 percent acyclovir in a modified aqueous cream base exhibited favorable trends, but 5 percent acyclovir in a polyethylene base was ineffective. A high dose of oral acyclovir may offer the most effective method of control of recurrent herpes labialis.

Acyclovir

Rectal prolapse: relationship with joint mobility.

Joint mobility was assessed in 25 patients who had undergone surgery for complete rectal prolapse and in 25 age- and sex-matched control subjects. A significant increase in extensibility of the fifth finger was found in the patients with rectal prolapse. It was further found that there was a progressive decrease in joint mobility with age in both groups. The pathophysiology of rectal prolapse is complex. Factors considered to be important include rectal intussusception associated with the commonly observed lack of rectal fixation within the sacral hollow, with a deep Pouch of Douglas and weak pelvic floor musculature. The joint hypermobility demonstrated in these patients suggests an underlying connective tissue abnormality which perhaps contributes to the lack of rectal fixation within the pelvis and to the rectal wall intussusception.

Adolescent

Neutropenia occurring during the course of chrysotherapy: a review of 25 cases.

The records of 25 patients who developed neutropenia (granulocyte count less than or equal to 2500 mm3) while receiving intramuscular gold sodium aurothiomalate (GSTM) were reviewed. According to commonly used clinical criteria, 3 patients developed Felty's syndrome, 8 gold myelotoxicity, and 14 mild, chronic benign granulocytopenia. Myelotoxicity occurred exclusively during the initial course of therapy (less than or equal to 1 g GSTM). Twelve of the patients with chronic granulocytopenia continue to receive gold without other signs of serious toxicity. We conclude that Felty's syndrome can develop during gold administration, and that many patients may continue safely to receive gold despite neutropenia.

Agranulocytosis

Replication and serial passage of a singly enveloped baculovirus of Orgyia leucostigma in homologous cell lines.

A singly enveloped nuclear polyhedrosis virus (SNPV) of the white-marked tussock moth, Orgyia leucostigma, was successfully grown in four continuous cell lines developed from minced neonate larvae of this insect. Level of infection in two cell lines, IPRI-OL-12 and IPRI-OL-13, was 65-90%, but in the other two, IPRI-OL-4 and IPRI-OL-9, it was about 3%. Polyhedral inclusion bodies (PIBs) appeared in the nuclei of cells within 24 h postinoculation. Cytopathological changes and morphogenesis of the virus, as revealed by light and electron microscopy, were in general typical of an SNPV. However, some of the PIBs contained very few virions, and some were fractured. Rate zonal centrifugation of alkali-released occluded virions further confirmed the singly enveloped characteristics of the virus. The SNPV was serially passaged 60 times each in OL-12 and OL-13 cells. Percentage infected cells and PIB production stayed generally high throughout serial passaging in OL-13 cells, but declined sharply after the 41st passage in OL-12 cells. PIBs from the 4th passage of the virus in OL-12 cells were tested and found to be pathogenic to O. leucostigma larvae.

Animals