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Biomedical subjects

S C Mitchell

Publications and source records attributed to S C Mitchell.

At least 37 records · Page 2Linked to original sources
PubMed2000

Ethylamine in human urine.

The urinary excretion of ethylamine has been measured in 200 unrelated healthy volunteers (100 male, 100 female) who maintained their normal diet. The average daily output was 7.82+/-7.03 mg (mean+/-S.D.) (8.01+/-7.40 male; 7.64+/-6.67 female) with a range of values spreading from 0.22 to 35.27 mg. Dietary studies investigating 41 food substances did not highlight any major sources of this amine, except that drinking tea increased subsequent urinary ethylamine levels.

Adult↗
PubMed2000

Nonconvulsive status epilepticus causing acute confusion.

PRESENTATION: an elderly patient presented with acute confusion and was found to have nonconvulsive status epilepticus. She responded to treatment with anti-epileptic drugs. OUTCOME: this case illustrates an important, under-recognized and reversible cause of acute prolonged confusion.

Acute Disease↗
PubMed2000

Gamma interferon influences intestinal epithelial hyperplasia caused by Lawsonia intracellularis infection in mice.

Lawsonia intracellularis is a recently identified bacterial pathogen which causes disease in a broad range of animals. Invasion of intestinal epithelial cells and the resultant hyperplasia of infected cells are central processes in disease pathogenesis. In this study, we aimed to establish whether immunocompetent mice were susceptible to infection and whether gamma interferon (IFN-gamma) contributed to the pathogenesis of infection. Wild-type 129-Sv-Ev mice (129 mice) and IFN-gamma receptor knockout mice based on the 129 background (IFN-gammaR(-)) were challenged orally with approximately 5.5 x 10(7) L. intracellularis cells. Both 129 and IFN-gammaR(-) mice became infected, although the extent of infection (as determined by the proportion of infected crypts) was substantially lower in 129 mice than in IFN-gammaR(-) mice. Despite these differences, infected crypts showed characteristics typical of proliferative enteropathies of other animals, i.e., intracellular colonization of epithelial cells by L. intracellularis with resultant epithelial hyperplasia. Infection in 129 mice was cleared between days 21 and 28 postchallenge, whereas infection in IFN-gammaR(-) mice was evident in 100% of animals from day 21 onward. Additionally, in IFN-gammaR(-) mice the infection was so extensive that fatalities resulted. IFN-gamma therefore plays a significant role in limiting intracellular infection and increased cellular proliferation associated with L. intracellularis. L. intracellularis infection is generally associated with modest cellular infiltration; therefore, further comparative examinations will be necessary to determine pathogenicity factors and define the role of IFN-gamma in controlling this infection.

Animals↗
PubMed2000

The fate of diphenyl sulphide, diphenyl sulphoxide and diphenyl sulphone in the rat.

Radiolabelled [UL-14C]-diphenyl sulphide, [UL-14C]-diphenyl sulphoxide and [UL-14C]-diphenyl sulphone were administered by gavage (1.0 mmol/kg body weight) to adult male Wistar rats following an overnight fast. For all compounds, faeces were the major route of excretion of radioactivity (50%). Urinary elimination (40%) was similar during the first (19%) and second (16%) days and a small amount of radioactivity (6%) was found within the carcass after four days. From urinary and faecal data, metabolism occurred via ring hydroxylation with subsequent conjugate formation. Oxidation of the sulphur to form the sulphoxide and sulphone also took place; a small amount of sulphoxide reduction was apparent but no sulphone reduction was found. No evidence for exclusion of the sulphur was obtained, and it appeared unlikely that extensive cleavage of the ring structures occurred.

Animals↗
PubMed1999

STEAP: a prostate-specific cell-surface antigen highly expressed in human prostate tumors.

In search of novel genes expressed in metastatic prostate cancer, we subtracted cDNA isolated from benign prostatic hypertrophic tissue from cDNA isolated from a prostate cancer xenograft model that mimics advanced disease. One novel gene that is highly expressed in advanced prostate cancer encodes a 339-amino acid protein with six potential membrane-spanning regions flanked by hydrophilic amino- and carboxyl-terminal domains. This structure suggests a potential function as a channel or transporter protein. This gene, named STEAP for six-transmembrane epithelial antigen of the prostate, is expressed predominantly in human prostate tissue and is up-regulated in multiple cancer cell lines, including prostate, bladder, colon, ovarian, and Ewing sarcoma. Immunohistochemical analysis of clinical specimens demonstrates significant STEAP expression at the cell-cell junctions of the secretory epithelium of prostate and prostate cancer cells. Little to no staining was detected at the plasma membranes of normal, nonprostate human tissues, except for bladder tissue, which expressed low levels of STEAP at the cell membrane. Protein analysis located STEAP at the cell surface of prostate-cancer cell lines. Our results support STEAP as a cell-surface tumor-antigen target for prostate cancer therapy and diagnostic imaging.

Amino Acid Sequence↗
PubMed1999

Dietary precursors of trimethylamine in man: a pilot study.

An increased urinary excretion of trimethylamine and its N-oxide were observed in man following the oral intake (15 mmol) of choline (63% dose as trimethylamine and its N-oxide), D,L-carnitine (31% dose) and trimethylamine N-oxide (78% dose). Similar ingestion of betaine, creatinine or lecithin failed to elicit any significant increases. Of 46 different foods investigated, only fish and other sea-products gave rise to significant increases in urinary trimethylamine and N-oxide. Ingestion of fruits, vegetables, cereal and dairy produce, and meats had no measurable effects. Reasons for the apparent lack of trimethylamine provision by foods previously thought to be precursors are given and the role of gut microflora highlighted.

Adult↗
PubMed1998

Dimethylamine formation in the rat from various related amine precursors.

Dimethylamine is the immediate precursor of dimethylnitrosamine, a known potent carcinogen in a wide variety of animal species. Although small amounts of dimethylamine are ingested directly, the major dietary source is believed to be via choline and related materials. Owing to quantitative recoveries following oral administration, urinary dimethylamine levels provide good overall measures of body exposure. The oral administration of equimolar amounts (1 mmol/kg body weight) of potential amine precursors to male Wistar rats produced only small increases in urinary dimethylamine after choline (+ 11%; 0.60 +/- 0.36% dose), dimethylaminopropanol (+ 32%; 1.49 +/- 0.30% dose), dimethylaminoethyl chloride (+ 110% 5.38 +/- 1.72% dose) and trimethylamine (+ 51%; 1.6 +/- 0.80% dose) input, whereas significantly larger increases were found following trimethylamine N-oxide ingestion (+ 355%; 12.93 +/- 1.13% dose; t-test, P < 0.001). These data suggest that trimethylamine N-oxide is a major dietary source of dimethylamine, by direct conversion and not by sequential reduction (to trimethylamine) and demethylation, and that in this respect it is of greater importance, on a molar basis, than choline.

Administration, Oral↗
PubMed1998

Disposition of diphenyl sulphoxide in rat.

1. Radiolabelled diphenyl sulphoxide (U-14C- or 35S-) was administered by gavage (1.0 mmol/kg body weight) to the adult male Wistar rat following an overnight fast. 2. For both labelled forms faeces was the major route of excretion of radioactivity (50%) with substantial amounts still being voided during the third and fourth days (13%). Urinary elimination (42%) was similar during the first (20%) and second (17%) days and a small amount of radioactivity (7%) was found within the carcass after 4 days. 3. Plasma data showed a peak concentration at 40 min (tmax), a distribution half-life of 2 h (t1/2 alpha) and an elimination half-life of 22.5 h (t1/2 beta). Biliary studies revealed that 16% of the dose traversed the bile duct during the first day with nearly half of this being excreted in the first 8 h. 4. From urinary data, metabolism occurred via ring hydroxylation with subsequent conjugate formation. Oxidation of the sulphur to form the sulphone also took place. No evidence for sulphoxide reduction, cleavage of the ring structures or exclusion of the sulphur was obtained.

Animals↗
PubMed1998

Fate of thianthrene in rat.

1. Radiolabelled thianthrene was administered by gavage (200 mg/kg body weight) to the adult female Wistar rat following an overnight fast. 2. Faeces was the major route of excretion of radioactivity (62%) with substantial amounts still being voided during the third day (17%). Urinary elimination (26%) peaked during the second and third days and a small amount of radioactivity (7%) remained within the carcass after 4 days. Distribution studies showed that the majority of the compound remained within the gastrointestinal tract. 3. Metabolism was limited to ring hydroxylation with subsequent conjugate formation. Oxidation of the sulphur to form the monosulphoxide and disulphoxide derivatives also occurred. No evidence for cleavage of the ring structures was observed.

Administration, Oral↗
PubMed1997

Trimethylaminuria associated with seizures and behavioural disturbance: a case report.

A 16-year-old left-handed male is presented with a history of seizures associated with a fish-like odour and behavioural disturbances thought to be related to trimethylaminuria. His seizures were complex-partial (cursive) seizures and started at the age of 18 months. They occurred in the context of discrete episodes several times per year. The episodes would start with a fish-like odour, followed by seizures occurring in clusters and behavioural disturbance consisting of agitation, mixed affective symptoms, auditory hallucinations and delusions. A urinary assay of trimethylamine (TMA) was elevated, confirming the diagnosis of trimethylaminuria in this patient. He was treated with a choline-restricted diet with resolution of his symptoms. The occurrence of seizures and psychiatric disturbance in this patient was thought secondary to his trimethylaminuria due to the temporal relationship of his seizures and psychiatric disturbance with the odour and his response to treatment. The possible relationship of trimethylaminuria to seizures and to psychiatric disturbance are discussed and a review of the literature presented.

Adolescent↗
PubMed1997

Metabolic disposition of [14C]-trimethylamine N-oxide in rat: variation with dose and route of administration.

1. Urine was the major route of excretion of radioactivity (95% dose in 0-24 h) following the oral, intravenous or intraperitoneal administration of [14C]-trimethylamine N-oxide dihydrate (1 mmol/kg body wt) to the adult male Wistar rat. A further 3-4% was voided in the urine during 24-72 h. Only fractional amounts were detected in the faeces, or were retained within tissues 3 days after administration. 2. Biliary secretion of radioactivity was insignificant (0.18% in 0-4 h) but larger amounts were secreted directly into the lumen of the gastrointestinal tract, especially the small intestine (2.6% in 0-1 h). 3. The only radioactive compounds identified in the urine were trimethylamine N-oxide and dimethylamine. Larger amounts of dimethylamine were excreted following oral administration (10%) as opposed to intravenous (2.5%) or intraperitoneal (1.5%) input. This production of dimethylamine occurred over a 100-fold oral trimethylamine N-oxide dose range (0.3-30 mmol/kg body wt). Incubation of trimethylamine N-oxide with gut contents (especially colon and rectum) led to the formation of dimethylamine.

Administration, Oral↗
PubMed1997

Studies on the discontinuous N-oxidation of trimethylamine among Jordanian, Ecuadorian and New Guinean populations.

Whilst the majority of individuals within a British white population are able to convert greater than 90% of their dietary-derived trimethylamine to its N-oxide, outliers exist who show varying degrees of impairment. Such individuals excrete unoxidized trimethylamine in their urine and, if sufficiently compromised, may experience malodour problems (Fish-Odour Syndrome). Little information concerning this polymorphic N-oxidation process is available in other ethnic groups and the present study explores Jordanian, Ecuadorian and New Guinean populations. Subjects with a relative deficiency in N-oxidation were found in all three groups, with 1.7% (2/116) Jordanian, 3.8% (3/8) Ecuadorian and 11.0% (11/100) New Guinean excreting 80% or less of their total trimethylamine as the N-oxide. Two subjects from the Ecuadorian population (4% and 33% total trimethylamine as the N-oxide) exhibited frank trimethylaminuria. These observations suggest that a compromised ability to N-oxidize trimethylamine is detectable in several ethnic groups and that this polymorphic phenomenon may have a widespread existence.

Adolescent↗