Search PubMed⌕ Search

Biomedical subjects

A Anthony

Publications and source records attributed to A Anthony.

At least 19 recordsLinked to original sources
PubMed2002

Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autism.

We have reported lymphocytic colitis in children with regressive autism, with epithelial damage prominent. We now compare duodenal biopsies in 25 children with regressive autism to 11 with coeliac disease, five with cerebral palsy and mental retardation and 18 histologically normal controls. Immunohistochemistry was performed for lymphocyte and epithelial lineage and functional markers. We determined the density of intraepithelial and lamina propria lymphocyte populations, and studied mucosal immunoglobulin and complement C1q localisation. Standard histopathology showed increased enterocyte and Paneth cell numbers in the autistic children. Immunohistochemistry demonstrated increased lymphocyte infiltration in both epithelium and lamina propria with upregulated crypt cell proliferation, compared to normal and cerebral palsy controls. Intraepithelial lymphocytes and lamina propria plasma cells were lower than in coeliac disease, but lamina propria T cell populations were higher and crypt proliferation similar. Most strikingly, IgG deposition was seen on the basolateral epithelial surface in 23/25 autistic children, co-localising with complement C1q. This was not seen in the other conditions. These findings demonstrate a novel form of enteropathy in autistic children, in which increases in mucosal lymphocyte density and crypt cell proliferation occur with epithelial IgG deposition. The features are suggestive of an autoimmune lesion.

Autistic Disorder↗
PubMed2002

Review article: the concept of entero-colonic encephalopathy, autism and opioid receptor ligands.

There is growing awareness that primary gastrointestinal pathology may play an important role in the inception and clinical expression of some childhood developmental disorders, including autism. In addition to frequent gastrointestinal symptoms, children with autism often manifest complex biochemical and immunological abnormalities. The gut-brain axis is central to certain encephalopathies of extra-cranial origin, hepatic encephalopathy being the best characterized. Commonalities in the clinical characteristics of hepatic encephalopathy and a form of autism associated with developmental regression in an apparently previously normal child, accompanied by immune-mediated gastrointestinal pathology, have led to the proposal that there may be analogous mechanisms of toxic encephalopathy in patients with liver failure and some children with autism. Aberrations in opioid biochemistry are common to these two conditions, and there is evidence that opioid peptides may mediate certain aspects of the respective syndromes. The generation of plausible and testable hypotheses in this area may help to identify new treatment options in encephalopathies of extra-cranial origin. Therapeutic targets for this autistic phenotype may include: modification of diet and entero-colonic microbial milieu in order to reduce toxin substrates, improve nutritional status and modify mucosal immunity; anti-inflammatory/immunomodulatory therapy; and specific treatment of dysmotility, focusing, for example, on the pharmacology of local opioid activity in the gut.

Autistic Disorder↗
PubMed2001

Stage-specific modulation of IFN-regulatory factor 4 function by Krüppel-type zinc finger proteins.

Optimal humoral responses depend on the activation of Ag-specific B cells, followed by their progression toward a fully differentiated phenotype. Acquisition of stage-appropriate patterns of gene expression is crucial to this differentiation program. However, the molecular mechanisms used by B cells to modulate gene expression as they complete their maturation program are poorly understood. IFN-regulatory factor 4 (IRF-4) plays a critical role in mature B cell function. Using the transcriptional regulation of the human B cell activation marker CD23 as a model system, we have previously demonstrated that IRF-4 is induced in response to B cell-activating stimuli and that it acts as a transactivator of CD23 gene expression. We have furthermore found that IRF-4 function can be blocked by B cell lymphomas 6 (BCL-6) protein, a Krüppel-type zinc finger repressor normally expressed in germinal center B cells. However, CD23 expression is known to be down-regulated in plasma cells despite high level expression of IRF-4 and the lack of BCL-6, suggesting that in plasma cells the IRF-4-mediated induction of CD23 is prevented by its interaction with a distinct repressor. In this set of studies, we demonstrate that IRF-4 interacts with B lymphocyte-induced maturation protein/positive regulatory domain I-binding factor 1 (Blimp1/PRD1-BF1), a Krüppel-type zinc finger protein whose expression correlates with terminal B cell differentiation. Functional studies indicate that Blimp1, like BCL-6, can block IRF-4-transactivating ability. These findings thus support a model whereby IRF-4 function is modulated in a stage-specific manner by its interaction with developmentally restricted sets of Krüppel-type zinc finger proteins.

Binding Sites↗
PubMed2001

Does a colostomy alter quality of life in patients with spinal cord injury? A controlled study.

STUDY DESIGN: Prospective controlled comparative analysis. OBJECTIVE: To determine whether a colostomy changes quality of life in patients with a spinal cord injury. METHOD: A previously validated questionnaire designed to assess quality of life in spinal injured patients (Burwood Questionnaire) was sent to 26 spinal cord injured patients with colostomies and 26 spinal cord injured patients without colostomy. The two groups were matched for level of injury, completeness of injury, length of time since injury, age (+/- 5 years) and gender. RESULTS: There was 100% completion of the questionnaire. There was no significant difference (P > 0.05) in the two groups of patients in regard to their general well being, emotional, social, or work functioning. CONCLUSIONS: Patients with colostomy following spinal injury are no worse off in regard to quality of life, than those without. The inference is that perhaps a colostomy should be considered earlier in patients with major bowel dysfunction following spinal cord injury. SPONSORSHIP: Financial support for Dr AC Lynch was provided by Royal Australian College of Surgeons with a Foundation Scholarship and Grant in aid by the Burwood International Spinal Trust. Mr N Randell was supported by the Canterbury Medical Research Foundation with a summer studentship.

Adult↗
PubMed2001

Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in children with autism.

OBJECTIVES: We have reported colitis with ileal lymphoid nodular hyperplasia (LNH) in children with regressive autism. The aims of this study were to characterize this lesion and determine whether LNH is specific for autism. METHODS: Ileo-colonoscopy was performed in 21 consecutively evaluated children with autistic spectrum disorders and bowel symptoms. Blinded comparison was made with 8 children with histologically normal ileum and colon, 10 developmentally normal children with ileal LNH, 15 with Crohn's disease, and 14 with ulcerative colitis. Immunohistochemistry was performed for cell lineage and functional markers, and histochemistry was performed for glycosaminoglycans and basement membrane thickness. RESULTS: Histology demonstrated lymphocytic colitis in the autistic children, less severe than classical inflammatory bowel disease. However, basement membrane thickness and mucosal gamma delta cell density were significantly increased above those of all other groups including patients with inflammatory bowel disease. CD8(+) density and intraepithelial lymphocyte numbers were higher than those in the Crohn's disease, LNH, and normal control groups; and CD3 and plasma cell density and crypt proliferation were higher than those in normal and LNH control groups. Epithelial, but not lamina propria, glycosaminoglycans were disrupted. However, the epithelium was HLA-DR(-), suggesting a predominantly T(H)2 response. INTERPRETATION: Immunohistochemistry confirms a distinct lymphocytic colitis in autistic spectrum disorders in which the epithelium appears particularly affected. This is consistent with increasing evidence for gut epithelial dysfunction in autism.

Adolescent↗
PubMed2000

Age, strain, and semi-chronic hydergine treatment effects on motor activity and neuronal nucleic acid-protein metabolism in male mice.

This study was designed to examine the effects of Hydergine (DHET), co-dergocrine mesylate, treatment on motor activity and neuronal nucleoprotein metabolism in several motor areas of the aging rodent brain, specifically the caudate-putamen (CP), the substantia nigra (SN), and the cerebral cortex layer V (CX). Three age groups of two different strains of mice were used which represented two different aging rates: DBA/2 male mice (short lived) and C57BL/6 male mice (long lived). A representative sample of each age group was injected (IP) daily with a single dose of either DHET (1 mg/kg) or vehicle (0.9% saline) solution for one month. Total spontaneous motor activity was measured using a File apparatus to assess the functional ability of the selected brain areas. Histochemical parameters measured included the relative RNA and protein contents from a homogeneous population of neurons within each nuclei. The RNA and protein contents were assessed with a scanning microdensitometer using azure B and Coomassie staining protocols, respectively. The results of this study provide evidence that DHET does have significant effects on neuronal functioning in the motor compartments studied at the behavioral as well as the histochemical level for DBA/2 male mice. The C57BL/6 strain showed parallel, but less significant, changes in the histochemical parameters and no statistical differences in motor activity. In addition, DHET treatment produced no sign of neurotoxicity within any of the brain nuclei in either strain.

Aging↗
PubMed2000

Bowel dysfunction following spinal cord injury: a description of bowel function in a spinal cord-injured population and comparison with age and gender matched controls.

STUDY DESIGN: A controlled, descriptive and comparative, questionnaire based study. OBJECTIVES: To describe the bowel function of spinal cord injured (SCI) patients and compare this with a general community control group. SETTING: Christchurch, New Zealand. METHODOLOGY: A postal questionnaire was sent out to past SCI patients of the Burwood Spinal Injuries Unit, Christchurch, New Zealand, and age/gender matched with controls randomly selected from the electoral roll. Permission was obtained from SCI participants to retrieve data relating to their injury from hospital case notes. The questionnaire detailed general bowel function, influence of bowel problems on everyday life, incidence of incontinence and methods of defecation. A Faecal Incontinence Score was generated according to an established incontinence grading scheme. RESULTS: Questionnaires were sent out to 1200 SCI patients and 1200 control subjects. Of these, 467 completed questionnaires were returned from SCI patients and age/gender matched from the 668 returned control questionnaires. Mean Faecal Incontinence Score was higher for SCI patients than controls (P<0.0001), and for complete compared with incomplete injury (P=0.0023). Age or time from injury did not affect Faecal Incontinence Score. Incontinence affected quality of life for 62% of SCI patients, compared with 8% of controls. Faecal urgency and time spent at the toilet were also significantly higher for the SCI group (39% of SCI patients use laxatives, compared with 4% of controls (P<0.0001)). Haemorrhoidectomy was more common (P<0.001) in the SCI population (9% vs 1.5%), particularly among those requiring manual evacuations. CONCLUSION: SCI has a significant effect on bowel function in terms of faecal incontinence, urgency, and toileting methods. This results in a marked impact on quality of life. While bowel function may deteriorate with time, most patients with poor function can be identified early implying a role for early intervention in those with potential bowel problems, such as colostomy or ACE procedure.

Activities of Daily Living↗
PubMed2000

Anorectal physiology following spinal cord injury.

PURPOSE: Spinal cord injured (SCI) patients have delayed colonic motility and anorectal dysfunction resulting in functional obstruction and constipation. This may be caused by changes in descending modulation from the central or sympathetic nervous systems. Anorectal dyssynergy may demonstrate similarities to that seen in the bladder following SCI. METHODOLOGY: Anorectal manometry was performed on 37 SCI volunteers. Patterns of rectal and sphincter function were identified. These patterns were then compared with questionnaire answers on bowel function and cystometrograms to identify a relationship between detrusor dyssynergy and anal sphincter tone. RESULTS: Rectal compliance and basal resting sphincter pressures were lower than normal values. Ramp rectal inflation demonstrated patterns of sphincter activity similar to that recorded in the patients' cystometrograms. There is no definite relationship of bowel function to the findings on manometry in SCI patients. CONCLUSIONS: SCI patients have abnormal anorectal function. Anorectal manometry results were able to be classified into four patterns on the basis of rectal pressure and sphincter tone in response to rectal distention. The patterns of anorectal manometry seen were similar to those in cystometrograms, however there is no definite relationship to bowel dysfunction. Spinal Cord (2000) 38, 573 - 580.

Adolescent↗
PubMed2000

Similarities between ileal Crohn's disease and indomethacin experimental jejunal ulcers in the rat.

BACKGROUND: Both Crohn's disease ileal ulcers and indomethacin-induced jejunal ulcers in the rat have a predilection for the mesenteric margin of the bowel wall. Unlike the anti-mesenteric margin, the mesenteric margin is supplied by small end-arteries that might render it more sensitive to ischaemic injury. AIM: To examine, in both situations, the histological relationship between the precise localization of small bowel ulcers and the mesenteric margin. METHODS: Ileal Crohn's disease ulcers identified in surgical resection specimens (n=5) and indomethacin-induced lesions in the rat jejunum (n=6) were examined macroscopically and histologically. RESULTS: In both the human ileum and the rat jejunum, ulcers occurred consistently along the mesenteric margin, with the most extensive mucosal injury occurring at two adjacent sites on either side of the midline of this margin. At these two sites, feeding arteries entered the muscularis propria. CONCLUSIONS: For anatomical reasons apparently related to the vasculature of the human and rodent small bowel, specific sites along the mesenteric margin are susceptible to Crohn's disease ulceration and NSAID damage, respectively.

Animals↗
PubMed2000

Endothelial changes precede mucosal ulceration induced by indomethacin: an experimental study in the rat.

BACKGROUND: Indomethacin has been shown to damage the villous microvasculature concomitant with alterations in villous blood flow in the rat. AIM: To test the hypothesis that alterations in blood flow result from ultrastructural damage to microvasculature endothelium. METHODS: In anaesthetized rats, jejunal villi were exteriorized in a chamber and blood flow in surface capillaries visualized by fluorescence microscopy. Villi were exposed both luminally and systemically to indomethacin (100 microg/mL) for 10 min or until blood slowing or stasis had occurred in superficial capillaries (n=3 per group). Control animals received both a luminal and intravenous vehicle for 45 min (n=3). The small intestines were vascular perfusion-fixed with 1.5% glutaraldehyde and studied by transmission electron microscopy. RESULTS: All controls appeared to be ultrastructurally normal. A 10 min exposure to indomethacin had no effect upon the epithelium but resulted in mild endothelial vacuolization and the development of small finger-like projections into the lumen of villus surface microvasculature. At the point of blood slowing, villus tip epithelium was again normal but the endothelial vacuolization and finger-like projections became more obvious. The endothelial projections and vacuolization became severe at the point of blood stasis; this also coincided with epithelial degeneration. CONCLUSION: This study shows that villus surface microvasculature is the earliest site of morphological damage after indomethacin exposure.

Animals↗
PubMed2000

Beta(beta)3-adrenergic receptors in human pancreatic islet and duodenal somatostatin neuroendocrine cells.

BACKGROUND: We previously localized beta3-adrenergic receptors immunohistochemically in human gastrointestinal smooth muscle and incidently found a population of human pancreatic islet cells and duodenal epithelial neuroendocrine cells that also expressed beta3-adrenergic receptors. AIM: To identify the nature of the islet and duodenal cells that stained positive for beta3-adrenergic receptors. METHODS: Paraffin sections of human pancreas and duodenum and Chinese hamster ovary cells transfected with the human beta3-adrenergic receptor were immuno-stained for beta3-adrenergic receptors using an affinity-purified rabbit polyclonal antibody (anti-P12) raised against a 15 amino acid sequence (P12) of the human receptor. Immunohistochemical staining for the receptor was carried out in the presence and absence of P12 peptide and both somatostatin 14 and 18 peptides. beta3-adrenergic receptor-stained sections were also double-immunostained with anti-insulin, -glucagon, -somatostatin and -pancreatic polypeptide antibodies. RESULTS: A subpopulation of human pancreatic islet cells and duodenal epithelial cells expressed positive cytoplasmic beta3-adrenergic receptor immunostaining. Using distribution and double-staining techniques, these cells were found to be somatostatin-positive D cells but not A or B cells. The positive staining of D cells with anti-P12 antibody was inhibited by prior incubation of the antibody with P12 peptide but not somatostatin-14 or -28 peptides. Pancreatic vascular smooth muscle and duodenal vascular and non-vascular smooth muscle also stained with anti-P12 antibody. Transfected Chinese hamster ovary cells showed positive membrane staining. CONCLUSION: We have identified a population of neuroendocrine cells in the human pancreas and duodenum that express beta3-adrenergic receptors. These cells appear to be somatostatin D cells.

Animals↗
PubMed2000

Monitoring of renal function in patients with spinal cord injury.

OBJECTIVE: To assess the sensitivity of serum creatinine level in detecting clinically important and early deterioration of renal function in patients with spinal cord injury (SCI), and to evaluate the optimal method of determining creatinine clearance in these patients. PATIENTS AND METHODS: The serum creatinine level of 36 patients (25 paraplegics and 11 quadriplegics) was evaluated and compared with the corresponding measured creatinine clearance rate. Correlations were also assessed between the creatinine clearance measured by 24-h endogenous clearance, single-shot 99mTc-labelled diethylenetriamine pentaacetic acid (99mTc-DTPA) clearance technique, and the Cockcroft-Gault formula, to test their validity. RESULTS: Of the 36 patients 11 (31%) had a measured creatinine clearance of < 100 mL/min (mean 84.8) and a corresponding normal serum creatinine level. Creatinine clearance calculated by the Cockcroft-Gault formula did not correlate well with that measured by the 24-h endogenous clearance (r = 0.426) and 99mTc-DTPA clearance (r = 0. 366), overestimating creatinine clearance in all but three patients. The mean (SD) difference between the creatinine clearance measured by the 24-h and DTPA clearance technique was 17.7 (16.5)% and the correlation between these techniques was good (r = 0.71). CONCLUSION: Serum creatinine level is not sensitive in detecting early deterioration of renal function in patients with SCI. The Cockcroft-Gault formula generally significantly overestimates the true creatinine clearance and is not recommended. The 24-h endogenous creatinine clearance measured on appropriately collected urine samples is an acceptable accurate and practical method of determining glomerular filtration rate in patients with SCI.

Adult↗
PubMed2000

Crystal chemistry of some synthetic 2-oxa-steroids: conformation, packing motifs and isostructurality.

The crystal structures of six synthetic 2-oxa-steroids (A-ring lactone steroids) have been determined by single-crystal X-ray diffraction. The conformation and hydrogen bonding in these oxa-steroids is compared with packing motifs in the natural steroids and the anabolic agent, Anavar. O-H...O hydrogen bonding with lactone carbonyl O is the preferred arrangement in molecules with a C-OH group. The donor H atoms of A, B and D rings participate in C-H...O interactions with lactone carbonyl O and D-ring hydroxyl/ketone O acceptor atoms. The conformation of the lactone ring in these analogues is different from the natural androgens because replacement of the C2-methylene group by an O atom changes the geometry of the A ring. Two structurally related lactone steroids provide the first example of O-H...O/C-H...O interaction mimicry and furthermore the two components form a binary solid solution. The O-H...O and C-H...O hydrogen bonds in 2-oxa-steroid crystal structures are analysed and the observed preferences discussed in terms of geometric and chemical factors.

Crystallography, X-Ray↗
PubMed2000

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↗
PubMed1999

Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4.

Interleukin (IL)-4 is an immunoregulatory cytokine that exerts distinct biological activities on different cell types. Our studies indicate that interferon regulatory factor (IRF)-4 is both a target and a modulator of the IL-4 signaling cascade. IRF-4 expression is strongly upregulated upon costimulation of B cells with CD40 and IL-4. Furthermore, we find that IRF-4 can interact with signal transducer and activator of transcription (Stat)6 and drive the expression of IL-4-inducible genes. The transactivating ability of IRF-4 is blocked by the repressor factor BCL-6. Since expression of IRF-4 is mostly confined to lymphoid cells, these data provide a potential mechanism by which IL-4-inducible genes can be regulated in a lineage-specific manner.

B-Lymphocytes↗
PubMed1999

The colonic mesenteric margin is most susceptible to injury in an experimental model of colonic ulceration.

BACKGROUND: Crohn's disease ileal ulcers and indomethacin-induced jejunal ulceration in the rat tend to occur in the mucosa nearest to the mesentery (mesenteric margin), an area of the bowel wall that has a critical blood supply. Mercuric chloride induces caecal and colonic ulceration in the Brown Norway rat. AIM: To examine whether the mesenteric margin is more sensitive to injury by a substance known to be vasculotoxic in the caecum and colon. METHODS: Brown Norway rats received a single subcutaneous dose of either mercuric chloride 1 mg/kg or saline. The gastrointestinal tract was examined macro- and microscopically for lesions 48 h later. The vascular anatomy of the normal rat colon and caecum was also examined using the carbon ink perfusion technique. RESULTS: Mercuric chloride induced caecal and colonic ulceration preferentially along the mesenteric margin of the bowel wall. Histologically, the lesions showed mucosal necrosis and neutrophil infiltration. There was also extensive vascular degeneration/necrosis with microaneurysm formation and extensive submucosal haemorrhage. Cellular infiltration of the vasculature was not a feature. The caecal and colonic mesenteric margins in control rats were supplied by small end arteries. CONCLUSIONS: The colonic and caecal mesenteric margins are susceptible to injury by mercuric chloride, a chemical known to induce haemorrhagic vasculopathy in the rat gastrointestinal tract. The large bowel mesenteric margin may be susceptible to injury by mercuric chloride because of the critical blood supply to that side of the bowel wall.

Animals↗