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Biomedical subjects

M Thomson

Publications and source records attributed to M Thomson.

At least 37 records · Page 2Linked to original sources

The use of ginger (Zingiber officinale Rosc.) as a potential anti-inflammatory and antithrombotic agent.

The effect of an aqueous extract of ginger (Zingiber officinale) on serum cholesterol and triglyceride levels as well as platelet thromboxane-B(2) and prostaglandin-E(2) production was examined. A raw aqueous extract of ginger was administered daily for a period of 4 weeks, either orally or intraperitoneally (IP) to rats. Fasting blood serum was investigated for thromboxane-B(2), prostaglandin-E(2), cholesterol and triglycerides. A low dose of ginger (50 mg/kg) administered either orally or IP did not produce any significant reduction in the serum thromboxane-B(2) levels when compared to saline-treated animals. However, ginger administered orally caused significant changes in the serum PGE(2) at this dose. High doses of ginger (500 mg/kg) were significantly effective in lowering serum PGE(2) when given either orally or IP. However, TXB(2) levels were significantly lower in rats given 500 mg/kg ginger orally but not IP. A significant reduction in serum cholesterol was observed when a higher dose of ginger (500 mg/kg) was administered. At a low dose of ginger (50 mg/kg), a significant reduction in the serum cholesterol was observed only when ginger was administered IP. No significant changes in serum triglyceride levels were observed upon administration of either the low or high dose of ginger. These results suggest that ginger could be used as an cholesterol-lowering, antithrombotic and anti-inflammatory agent.

Administration, Oral↗

Tissue tropism of enteropathogenic Escherichia coli strains belonging to the O55 serogroup.

Four enteropathogenic Escherichia coli (EPEC) strains belonging to the O55 serogroup (G21 and G30 [both O55:H6], G35 [O55:H-], and G58 [O55:H7]) were tested for their tissue tropism by using human intestinal in vitro organ culture. Strains showed restricted adhesion with attaching-and-effacing activity to follicle-associated epithelium of Peyer's patches, with no apparent adhesion to duodenum or colon. G35 and G58 express intimin gamma and show a similar tropism to intimin gamma-expressing enterohemorrhagic E. coli (EHEC) O157:H7. However, strains G21 and G30 were unusual because they expressed intimin alpha and had a restricted tissue tropism of intimin gamma phenotype. The amino acid sequence of the carboxy-terminal 280 amino acids of intimin from G21 was determined. Comparison with the prototype intimin alpha from strain E2348/69 (O127:H6) showed a single amino acid difference (corresponding to Val907 and Ala907 in the whole intimins). This mutation was reproduced by site-directed mutagenesis in an intimin alpha plasmid template, pCVD438, with the hypothesis that it may induce a change in tropism. However, when the mutated plasmid was placed in both EPEC and EHEC backgrounds, duodenal adhesion in a manner similar to strain E2348/69 was evident upon in vitro organ culture. Thus, additional factor(s) unrelated to intimin exist in the O55:H6 genome that influence human intestinal tissue tropism.

Amino Acid Sequence↗

Potential viral pathogenic mechanism for new variant inflammatory bowel disease.

AIMS: A new form of inflammatory bowel disease (ileocolonic lymphonodular hyperplasia) has been described in a cohort of children with developmental disorder. This study investigates the presence of persistent measles virus in the intestinal tissue of these patients (new variant inflammatory bowel disease) and a series of controls by molecular analysis. METHODS: Formalin fixed, paraffin wax embedded and fresh frozen biopsies from the terminal ileum were examined from affected children and histological normal controls. The measles virus Fusion (F) and Haemagglutinin (H) genes were detected by TaqMan reverse transcription polymerase chain reaction (RT-PCR) and the Nucleocapsid (N) gene by RT in situ PCR. Localisation of the mRNA signal was performed using a specific follicular dendritic cell antibody. RESULTS: Seventy five of 91 patients with a histologically confirmed diagnosis of ileal lymphonodular hyperplasia and enterocolitis were positive for measles virus in their intestinal tissue compared with five of 70 control patients. Measles virus was identified within the follicular dendritic cells and some lymphocytes in foci of reactive follicular hyperplasia. The copy number of measles virus ranged from one to 300,00 copies/ng total RNA. CONCLUSIONS: The data confirm an association between the presence of measles virus and gut pathology in children with developmental disorder.

Adolescent↗

Tryptophan hydroxylase polymorphism and suicidality in unipolar and bipolar affective disorders: a multicenter association study.

BACKGROUND: Being the rate-limiting enzyme in the biosynthesis of serotonin, the tryptophan hydroxylase gene (TPH) has been considered a possible candidate gene in bipolar and unipolar affective disorders (BPAD and UPAD). Several studies have investigated the possible role of TPH polymorphisms in affective disorders and suicidal behavior. METHODS: The TPH A218C polymorphism has been investigated in 927 patients (527 BPAD and 400 UPAD) and their matched healthy control subjects collected within the European Collaborative Project on Affective Disorders. RESULTS: No difference of genotype distribution or allele distribution was found in BPAD or UPAD. No statistically significant difference was observed for allele frequency and genotypes counts. In a genotype per genotype analysis in UPAD patients with a personal history of suicide attempt, the frequency of the C-C genotype (homozygosity for the short allele) was lower in UPAD patients (24%) than in control subjects (43%) (chi(2) = 4.67, p =.03). There was no difference in allele or genotype frequency between patients presenting violent suicidal behavior (n = 48) and their matched control subjects. CONCLUSIONS: We failed to detect an association between the A218C polymorphism of the TPH gene and BPAD and UPAD in a large European sample. Homozygosity for the short allele is significantly less frequent in a subgroup of UPAD patients with a history of suicide attempt than in control subjects.

Alleles↗

Small GTP-binding proteins in the nuclei of human placenta.

Mitochondria and crude nuclei containing fractions from human placenta have been shown to contain proteins which bind [alpha(32)P]-GTP. Prior to this study the number of GTP-binding proteins in placental nuclei and their nucleotide specificity was not known. Also unknown was the identity of any of the GTP-binding proteins in mitochondria of human placenta. Nuclei and mitochondria were purified from human placental extracts by sedimentation. Proteins were separated by electrophoresis and transferred to nitrocellulose membranes. Overlay blot with [alpha(32)P]-GTP identified two nuclei proteins with approximate molecular weights of 24 and 27 kDa. Binding of [alpha(32)P]-GTP to the 27 and 24 kDa proteins was significantly displaced by guanine nucleotides but not by adenine, thymine or cytosine nucleotides or deoxy (d) GTP. Western blot with a specific antibody to Ran identified a band at 27 kDa in nuclei and in mitochondrial fractions. These data indicate that both nuclei and mitochondria contain 24 and 27 kDa GTP-binding proteins. The GTP-binding proteins in nuclei display binding specificity for guanine nucleotides and the hydroxylated carbon 2 on the ribose ring of GTP appears essential for binding. It will be important in future studies to determine the functions of these small GTP-binding proteins in the development and physiology of the placenta.

Cell Nucleus↗

Emergence of a distinct pattern of viral mutations in chimpanzees infected with a homogeneous inoculum of hepatitis C virus.

BACKGROUND & AIMS: Prospective, long-term study of viral evolution and immunologic responses in chimpanzees infected with a homogeneous hepatitis C virus (HCV) population is crucial in understanding the pathogenesis of HCV-host interactions. METHODS: A molecular clone was constructed of HCV genotype 1b and RNA transcribed from this clone inoculated intrahepatically into chimpanzee X0142. Serum was taken from X0142 at week 2 and inoculated intravenously into a second chimpanzee (X0234). Detailed virologic, serologic, and immunologic analyses of these 2 chimpanzees were performed. RESULTS: Both chimpanzees developed persistent viremia, with titers of 10(3) to 10(5) genomes/mL, for 80 weeks (X0142) and 55 weeks (X0234) of follow-up. A late antibody response against the nonstructural proteins and a weak, transient T-helper proliferative response were detected in both animals. In X0142, 25 mutations emerged in the virus population by week 78 and 15 in X0234 by week 35. A relatively large proportion of mutations affecting protein sequences appeared in the NS5A gene (33% in X0142 and X0234 combined), and 5 mutations were common to both chimpanzees. CONCLUSIONS: In this long-term study of the molecular evolution of HCV genotype 1b from a cloned source, the appearance of a distinct pattern of mutations is suggestive of an adaptive response of HCV in vivo. In addition, a limited virus-specific immunity may contribute to HCV persistence.

Alanine Transaminase↗

Protein phosphorylation in mitochondria from human placenta.

The aim of this study was to investigate whether mitochondria from human placenta contain phosphorylated proteins and kinases. Interestingly, the placenta contains two types of mitochondria with different sizes. These are 'heavy' mitochondria which sediment at a much lower g force than 'light' mitochondria. Mitochondria were incubated with [gamma32]P-ATP and labelled proteins analysed by electrophoresis and autoradiography. A major protein band of 20 kDa was detected with minor bands at 22, 38 and 85 kDa. The 20 kDa band was attenuated by 83 per cent by the co-incubation of mitochondria with Herbimycin, a tyrosine kinase inhibitor. A 20 kDa protein was also identified using an anti-tyrosine phosphate antibody and detection of this protein was significantly higher in heavy mitochondria as opposed to light mitochondria. Protein kinase A enzyme activity was also detected in mitochondria at a level not significantly different than that found in whole non-fractionated cells. These data indicate that mitochondria from human placenta contains kinase activity and phosphoproteins. These molecules may have functions in signalling systems in this organelle. Phosphoprotein signalling systems may be differentially modulated in heavy mitochondria as compared with light mitochondria.

Adenosine Triphosphate↗

Lethal prenatal onset infantile cortical hyperostosis (Caffey disease).

We describe a sporadic case of lethal prenatal onset infantile cortical hyperostosis (Caffey disease), which resulted in early postnatal death at 30 weeks gestation. The mother presented with antepartum haemorrhage and preterm labour. She was found to have polyhydramnios. The infant showed extensive symmetrical diaphyseal subperiosteal cortical thickening throughout the skeleton with short extremities. Hepatomegaly and lung hypoplasia were present. Currently, in the absence of a specific marker, diagnostic ultrasound offers the only prospect of prenatal diagnosis. This diagnosis should be considered in infants with short angulated long bones, where the diaphyses are irregular and echodense, and where there is no sign of fractures.

Fatal Outcome↗

Comparison of two neurostimulation techniques for axillary brachial plexus blockade.

This prospective, randomized, double-blind study compared two techniques of axillary brachial plexus block using a peripheral nerve stimulator. Both groups received initial musculocutaneous nerve block followed by either a single injection on median nerve stimulation (group 1) or a double injection divided between median and radial nerves (group 2). All 60 patients received a total of 30 ml of lidocaine 15 mg/ml with epinephrine 5 microg/ml. Complete sensory blockade of all six peripheral nerves occurred in 53% and 97% of patients in groups 1 and 2, respectively (P<0.001), with a more rapid onset of blockade occurring in group 2 patients (P<0.001). Complete motor blockade was evident in 30% and 83% of patients in groups 1 and 2, respectively (P<0.001).

Adult↗

Intestinal and systemic infection, HIV, and mortality in Zambian children with persistent diarrhea and malnutrition.

BACKGROUND: Persistent diarrhea-malnutrition syndrome is a complex of infection and immune failure that involves protein, calorie and micronutrient depletion, and metabolic disturbances. We report an analysis of the impact of HIV infection on infectious disease, clinical presentation, and mortality in Zambian children with persistent diarrhea and malnutrition. METHODS: Two hundred children (94 boys and 106 girls, 6-24 months old) were examined on admission to the malnutrition ward of University Teaching Hospital in Lusaka, Zambia. There was then 1 month of follow-up. RESULTS: Antibodies to HIV were found in 108 of the children (54%). The common intestinal infections (Cryptosporidium parvum [26%] and nontyphoid Salmonella spp [18%]), septicemia (17%), and pulmonary tuberculosis confirmed by gastric lavage (13.5%) were not significantly more common in HIV-seropositive than in HIV-seronegative children. HIV-seropositive children were more likely to have marasmus whereas HIV-seronegative children were more likely to have kwashiorkor. Weight-for-age z scores at nadir (postedema) were lower in HIV-seropositive children (median, -4.4; interquartile range [IQR], -5.0 to -3.8) than in HIV-seronegative children (median, -3.7; IQR, -4.2 to -3.1; P < 0.0001). Height-for-age and weight-for-height z scores and mid-upper arm circumference showed a similar difference. Of the 200 children, 39 (19.5%) died within 28 days; cryptosporidiosis and marasmus were the only independent predictors of death. CONCLUSIONS: Although intestinal and systemic infections did not differ for HIV-seropositive and HIV-seronegative children, HIV influenced nutritional states of all children. Cryptosporidiosis and marasmus were associated with higher mortality.

AIDS-Related Opportunistic Infections↗

Colonoscopy and enteroscopy.

This article focuses on technique and clinical application of ileocolonoscopy and enteroscopy in children. The impact of endoscopic investigations and therapies on specific disease processes and comparison with alternative methods are discussed. Pediatric colonoscopy and enteroscopy differ significantly from their adult counterparts in nearly every aspect. The goals of this article are to highlight those differences and to provide a workable guide for those involved or training in the discipline of pediatric endoscopy.

Child↗

Garlic and onions: their effect on eicosanoid metabolism and its clinical relevance.

Garlic (Allium sativum) and onion (Allium cepa) are among the oldest of all cultivated plants. Additionally, both plants have been used as medicinal agents for thousands of years. Both garlic and onion have been shown to have applications as antimicrobial, antithrombotic, antitumor, hypolipidaemic, antiarthritic and hypoglycemic agents. In recent years, extensive research has focussed on the beneficial and medicinal properties of garlic and onions. In particular, the use of these agents in the treatment and prevention of cardiovascular disease and cancer is an area of considerable investigation and interest.

Animals↗

Thromboxane-B(2) levels in serum of rabbits receiving a single intravenous dose of aqueous extract of garlic and onion.

We have shown previously that fresh garlic extract is effective in reducing thromboxane formation by platelets both in vivo and in vitro animal models of thrombosis. In the present study, the effect of different concentrations of a single dose of aqueous extracts of garlic and onion were evaluated on serum thromboxane-B(2)synthesis in rabbits. Different concentrations of garlic and onion were administered as single doses in the ear vein of rabbits. Rabbits were bled before and at different intervals after the infusion of garlic or onion extracts. Venous blood was collected and allowed to clot at 37 degrees C for 1 h. Thromboxane-B(2)level was measured in the serum by radioimmunoassay. It was observed that garlic inhibits the thrombin-induced platelet synthesis of TXB(2)in a dose-and time-dependent manner. Maximum inhibition of TXB(2)occurred between 0.5 h and 6 h at 25 and 100 mg kg(-1)garlic. At 24 h post-garlic infusion TXB(2)inhibition was reduced to 15% of the control and TXB(2)levels were comparable to that of the control values at 72 h pots-garlic infusion. Infusion of 100 mg kg(-1)onion extract did not elicit any inhibitory effect on TXB(2)synthesis in the serum of rabbit during the treatment period. The rapid recovery of platelet cyclooxygenase activity after infusion of a single dose of garlic suggests that garlic should be taken more frequently in order to achieve beneficial effects in the prevention of thrombosis.

Animals↗

Enterocolitis in children with developmental disorders.

OBJECTIVE: Intestinal pathology, i.e., ileocolonic lymphoid nodular hyperplasia (LNH) and mucosal inflammation, has been described in children with developmental disorders. This study describes some of the endoscopic and pathological characteristics in a group of children with developmental disorders (affected children) that are associated with behavioral regression and bowel symptoms, and compares them with pediatric controls. METHODS: Ileocolonoscopy and biopsy were performed on 60 affected children (median age 6 yr, range 3-16; 53 male). Developmental diagnoses were autism (50 patients), Asperger's syndrome (five), disintegrative disorder (two), attention deficit hyperactivity disorder (ADHD) (one), schizophrenia (one), and dyslexia (one). Severity of ileal LNH was graded (0-3) in both affected children and 37 developmentally normal controls (median age 11 yr, range 2-13 yr) who were investigated for possible inflammatory bowel disease (IBD). Tissue sections were reviewed by three pathologists and scored on a standard proforma. Data were compared with ileocolonic biopsies from 22 histologically normal children (controls) and 20 children with ulcerative colitis (UC), scored in an identical manner. Gut pathogens were sought routinely. RESULTS: Ileal LNH was present in 54 of 58 (93%) affected children and in five of 35 (14.3%) controls (p < 0.001). Colonic LNH was present in 18 of 60 (30%) affected children and in two of 37 (5.4%) controls (p < 0.01). Histologically, reactive follicular hyperplasia was present in 46 of 52 (88.5%) ileal biopsies from affected children and in four of 14 (29%) with UC, but not in non-IBD controls (p < 0.01). Active ileitis was present in four of 51 (8%) affected children but not in controls. Chronic colitis was identified in 53 of 60 (88%) affected children compared with one of 22 (4.5%) controls and in 20 of 20 (100%) with UC. Scores of frequency and severity of inflammation were significantly greater in both affected children and those with UC, compared with controls (p < 0.001). CONCLUSIONS: A new variant of inflammatory bowel disease is present in this group of children with developmental disorders.

Adolescent↗