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Biomedical subjects

T Self

Publications and source records attributed to T Self.

25 records · Page 2Linked to original sources

Immunogold localisation of ubiquitin-protein conjugates in primary (azurophilic) granules of polymorphonuclear neutrophils.

Ubiquitin-protein conjugates are found in the primary (azurophilic) lysosome-related granules but not in the secondary (specific) granules in mature polymorphonuclear neutrophils prepared from bone marrow. This is the first reported demonstration of ubiquitin-protein conjugates in lysosome-related membrane-bound vesicles in granulocytes and complements our previous findings of ubiquitinated proteins in lysosomes of fibroblasts. The significance of the selective presence of conjugates in only one of the two main types of neutrophil granules remains to be elucidated but may relate to the presence of the complement of acid hydrolases, including proteases, in the azurophilic granules compared to the specific granules. Ubiquitin-protein conjugates may enter the primary granules during neutrophil maturation by an autophagic process or by a heterophagic process during the fusion of phagosomes with primary granules. Alternatively protein ubiquitination may be involved in granule biogenesis.

Animals↗

The latent membrane protein-1 in Epstein-Barr virus-transformed lymphoblastoid cells is found with ubiquitin-protein conjugates and heat-shock protein 70 in lysosomes oriented around the microtubule organizing centre.

Immunofluorescence studies on Epstein-Barr virus (EBV)-transformed lymphoblastoid cells have previously shown that the latent membrane transforming protein (LMP-1) is found in patch-like inclusions which also immunostain for vimentin. We now show that EBV transformation causes a major reorganization of intermediate filaments, microtubules, mitochondria, and lysosomal elements, which generally become oriented around the microtubule organizing centre. Immunogold electron microscopy shows that LMP-1 is primarily concentrated in secondary lysosomes together with ubiquitin-protein conjugates and heat-shock protein 70. Intermediate filament inclusion formation with the above characteristics may be a general response triggered by other membrane glycoproteins; as seen, for example, in major human neurodegenerative diseases such as diffuse Lewy body disease.

Antigens, Viral↗

Asthma in the emergency department: impact of a protocol on optimizing therapy.

The objective of this study was to evaluate the impact of a simple educational intervention on the prescribing habits of internal medicine residents in the treatment of acute asthma in a busy emergency department (ED). Prescribing habits for 16 residents were documented for 4 months. The first 2 months served as a control period during which eight residents managed asthma patients without the benefit of any specific educational intervention beyond standard department protocols. A total of 129 patients treated by the residents during this initial phase were assessed. During the second 2-month period, a 10-minute verbal presentation and explicit written treatment protocol were provided to another eight residents, and their treatment of 83 patients was covertly evaluated. Increased prescribing of desired therapy was significantly improved in every area except that of prescribing an inhaled steroid metered dose inhaler for use as a discharge medication. The 10-minute verbal presentation given in conjunction with a three-page handout was found to be highly effective for eliciting improvement in treatment practices during short clinical rotations. The duration of this effect beyond each rotation is unknown. This educational intervention should be presented by the ED medical director, clinical pharmacist, or other appropriate clinician in virtually any ED as quality of patient care can be dramatically improved.

Acute Disease↗

Acute effects of short-term subcutaneous terbutaline on theophylline disposition.

Theophylline and subcutaneous terbutaline are frequently used concurrently in the management of acute asthma. Recent evidence demonstrating a reduction in theophylline serum concentrations during concomitant oral terbutaline therapy prompted our evaluation of subcutaneous terbutaline's effect on theophylline pharmacokinetics. Using a randomized, placebo controlled, crossover design, the disposition of a single oral theophylline dose (7 mg/kg) was studied in eight healthy, adult males before and after repeated subcutaneous administration of terbutaline (0.25 mg). Two-way analysis of variance revealed no significant difference in elimination rate constant (ke), area under the concentration-time curve (AUC), or apparent oral clearance (CL/F) of theophylline following terbutaline administration. These results indicate that subcutaneous administration of terbutaline does not alter the pharmacokinetics of single, oral doses of theophylline in adults.

Adult↗

The lateral reservoir technique of ileal endorectal pull-through for ulcerative colitis and familial polyposis in children.

Total abdominal colectomy and endorectal ileal pull-through have been widely used in children as a definitive continence-preserving procedure for ulcerative colitis (UC) and familial polyposis (FP). Controversy exists in regards to the results achieved with the various techniques utilized to accomplish this procedure, including straight ileal pull-through, pull-through with balloon dilatation of the lower ileal segment, and the construction of a variety of ileal reservoirs: S-shaped, J-shaped, or lateral. We have utilized the two-stage lateral reservoir approach advocated by Fonkalsrud et al, on a total of 12 patients, aged 1 to 17 years, including ten patients with UC and two with FP. Twelve patients have undergone stage 1 and seven of these stage 2. Numerous complications of stage 1 occurred early in the series, including breakdown of the ileoanal anastomosis, 3 patients; cuff abscess, 2 patients; postoperative intestinal obstruction, 2 patients; and intraabdominal abscess, 1 patient. All have fully recovered. The last six stage 1 procedures have been without complications. Five of the seven stage 2 patients are now well, continent, and having four to six controlled bowel movements a day 1 to 2 years postoperatively. Two patients are using small amounts of Immodium and Metamucil. One patient has developed marked dilatation of the pouch at 8 months postoperatively with episodic "pouchitis" requiring operative revision and diversion. One stage 2 patient suffered numerous complications including spontaneous perforation of the reservoir 2 months postoperatively, eventually leading to re-creation of a permanent ileostomy and removal of the pouch. Five patients await further treatment. The lateral reservoir technique is capable of producing a satisfied and continent patient; however, the potential technical problems and early complications are significant. The occurrence of delayed "pouchitis" is worrisome. Although the initial results with the lateral reservoir technique appear encouraging, further longterm evaluation is necessary.

Adolescent↗

Jaundice and rash associated with the use of phenobarbital and hydrochlorothiazide.

Rash, lymphadenopaty, splenomegaly, periorbital edema, and hepatitis occurred in an 18-year-old woman who was taking phenobarbital and hydrochlorothiazide. Tests for fluorescent antinuclear antibody and hepatitis-associated antigen and antibody were negative. Liver biopsy was not characteristic of viral hepatitis. Clinical recovery occurred within two weeks. Treatment consisted of withdrawal of the above drugs plus the administration of methylprednisolone and diphenhydramine.

Adolescent↗