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Biomedical subjects

C P Braegger

Publications and source records attributed to C P Braegger.

At least 37 records · Page 2Linked to original sources
PubMed1997

Interstitial deletion, del(4)(q12q21.1), owing to de novo unbalanced translocation in a 2 year old girl: further evidence that the piebald trait maps to proximal 4q12.

A very short, microcephalic, and mentally retarded 2 year old girl showed minor anomalies including prominent occiput, delayed closure of the anterior fontanelle, high frontal hairline, prominent ears, upward slanting palpebral fissures, a small nose with bulbous tip, delayed tooth eruption and bone maturation, and short and tapering fingers and toes. She did not have a white forelock. Cytogenetic investigation disclosed a de novo unbalanced translocation between chromosomes 4 and 18 with deletion of 4q12-->q21.1. Molecular investigation showed lack of a paternal allele for the microsatellite markers D4S392 and D4S398. This case shows indirect evidence that the piebald gene maps to proximal 4q12.

Abnormalities, Multiple↗
PubMed1996

Cerebral tuberculosis presenting as complex febrile convulsions.

Complex febrile convulsions were the initial clinical manifestation of miliary tuberculosis in a 4-year-old immigrant girl. The cerebral lesions were visible only after contrast-enhanced cranial computed tomography (CT) while native CT scan as well as cell count and glucose concentration in the cerebrospinal fluid were normal. Mycobacterium tuberculosis was cultured from gastric aspirate and liver biopsy tissue. Treatment with isoniazid and rifampin for 12 months, pyrazinamide for 9 months, and ethambutol for the initial 6 weeks resulted in resolution of the cerebral lesions but a retinal scar after granuloma formation in the right eye caused reduced visus. This case demonstrates the importance of thorough search for tuberculosis even in the absence of overt clinical pulmonary signs especially in high-risk individuals such as immigrants.

Antitubercular Agents↗
PubMed1996

The immunologic basis for celiac disease and related disorders.

Celiac disease is the classical food-sensitive enteropathy and is caused by an antigen-specific immunologic hypersensitivity response to gluten within the small intestinal mucosa. Antibody and T-cell hypersensitivity may play a role in vivo, but it is more likely that the primary problem is an inappropriate T-cell response to gluten. The deleterious effects of gluten in celiac patients can be completely explained by the immune-mediated alterations in upper small-intestinal mucosal shape; these alterations include the replacement of long villi and short crypts with short or absent villi and hyperplastic crypts. It is an extremely unusual disease in that it is highly linked to human leukocyte antigen (HLA)-DQ2, and CD4+ T-cell clones that recognize gluten in the context of DQ2 have been isolated from celiac mucosa lamina propria. HLA-DQ2 is commonly used in Whites, but the incidence of celiac disease varies greatly between different countries and with time, without any obvious explanation. Celiac disease is also unusual in that it has features of autoimmune disease. Patients with active disease have immunoglobulin (Ig)A antibodies in endomysium, an uncharacterized extracellular matrix protein, and the presence of these antibodies is very specific for this condition. However, because celiac disease is more common in IgA-deficient patients, the IgA antiendomysial antibodies are unlikely to be pathogenic.

CD4 Antigens↗
PubMed1994

Immunopathogenesis of chronic inflammatory bowel disease.

The aetiology and pathogenesis of chronic inflammatory bowel disease are unknown. However, there is circumstantial evidence that immune mechanisms may play a significant role in mediating the gut lesion and various systemic manifestations. The role of the cellular immune system, soluble mediators, including proinflammatory and immunoregulatory cytokines, humoral immunity and mucosal complement activation will be discussed.

Antibody Formation↗
PubMed1994

Cyclosporin as initial treatment for Crohn's disease.

Childhood Crohn's disease may cause significant morbidity. T cell activation is considered to be central to Crohn's disease pathology, and as cyclosporin is a powerful inhibitor of T cell activation, and has been used in adult Crohn's disease with encouraging results, it may offer the prospect of remission if given early in the course of disease. Children with newly diagnosed Crohn's disease or those relapsing off treatment were therefore given cyclosporin or conventional treatment (enteral nutrition or corticosteroids) by random allocation. Evaluation was performed initially and at two months. Twenty four children were studied (10 on cyclosporin and 14 on conventional treatment; one child on cyclosporin withdrew). Significant clinical improvement occurred in the group on conventional treatment, but not in the cyclosporin group. Colonoscopic improvement was noted in 5/9 on cyclosporin and 8/14 on conventional treatment, but neither group produced a significant fall in median colonoscopic index. Histological improvement was seen in 7/8 on cyclosporin and 8/13 on conventional treatment, but cyclosporin was not significantly better. Cyclosporin produced improved clinical and histological appearance without matched improvement in blood disease indices. It was not better than conventional treatment, and simple oral administration is probably not suitable for newly diagnosed patients with Crohn's disease.

Adolescent↗
PubMed1994

Immune mechanisms in chronic inflammatory bowel disease.

Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases of unknown etiology. However, there is circumstantial evidence that immune mechanisms play an important role in the pathogenesis of the intestinal lesion, and cytokines produced by lymphoid cells may be critical for the extraintestinal sequelae of the disease. In both Crohn's disease and ulcerative colitis, activation of macrophages seems to be a key feature. Increased production of the macrophage derived cytokines TNF-alpha, IL-1 and IL-6 have been reported in both diseases. Additionally in Crohn's disease, large numbers of activated T lymphocytes can be detected in the lamina propria and the T lymphocyte derived cytokines IL-2 and IFN-gamma are secreted by a higher number of lamina propria T lymphocytes in active Crohn's disease. However, this is not the case in ulcerative colitis. The increased number of activated T lymphocytes secreting IFN-gamma may be responsible for granuloma formation in Crohn's disease, as well as for MHC class II antigen expression on colonic epithelial cells. Lamina propria T lymphocytes seem to have lost their physiological unresponsiveness to several microbial antigens. All these observations suggest that Crohn's disease may be caused by hyperreaction of the local cellular immune system to numerous microbial and nutritional antigens normally present in the intestine. The factor inducing this immune dysregulation remains unknown. Cell-mediated immunity seems to be less important in ulcerative colitis, as activated T lymphocytes are only sparse within the inflamed mucosa, and the T lymphocyte derived cytokines IL-2 and IFN-gamma cannot be detected in the gut lesion or in the serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Formation↗
PubMed1993

T-cell activation can induce either mucosal destruction or adaptation in cultured human fetal small intestine.

BACKGROUND: T-cell hypersensitivity is implicated in the tissue damage in a variety of gastrointestinal diseases. The aim of this study was to characterize the spectrum of pathological changes induced by T-cell activation in explants of fetal human small intestine, to modulate the pathology by immunological intervention, and to define the cellular pathways in intestinal damage. METHODS: Explants of fetal human small intestine were cultured with pokeweed mitogen in the presence or absence of dexamethasone or FK506. Pathological changes were then assessed by morphology or on frozen sections. RESULTS: Activation of lamina propria T cells produced variable mucosal damage that could be classified into two main types. Some explants showed villous atrophy and crypt hyperplasia whereas in others there was almost total mucosal destruction. This latter appearance predominated in explants from older specimens. Explants that were destroyed contained high numbers of T cells and activated macrophages. FK506 could completely inhibit mucosal damage, especially in younger specimens, whereas dexamethasone, even at high doses, prevented mucosal destruction, but individual explants continued to show villus atrophy and crypt hyperplasia. CONCLUSIONS: These results indicate that there is a quantitative relationship between mucosal cell-mediated immunity and the pathological outcome and that large numbers of activated macrophages in the mucosa can result in tissue destruction.

Adaptation, Physiological↗
PubMed1993

T cell activation and cytokine release in streptococcal toxic shock-like syndrome.

A 5-year-old girl with streptococcal toxic shock-like syndrome during varicella infection had high levels of tumor necrosis factor alpha and interleukin-6 but no interleukin-1 or interleukin-2 in the serum. Intravenous administration of gamma-globulin coincided with clinical improvement and with reduction of the levels of tumor necrosis factor alpha and interleukin-6. The data suggest that streptococcal pyrogenic exotoxins trigger synthesis of tumor necrosis factor alpha and interleukin-6 in vivo; intravenously administered gamma-globulin may down-regulate the cytokine response.

Arthritis, Infectious↗
PubMed1993

Urinary growth hormone in growth-impaired children with chronic inflammatory bowel disease.

Growth impairment of undefined aetiology occurs in approximately 30% of children with chronic inflammatory bowel disease. We measured urinary growth hormone concentrations in 36 children with chronic inflammatory bowel disease and 51 normal controls. The median urinary concentration of growth hormone in the stunted children with chronic inflammatory bowel disease was 15.8 ng/g creatinine (range 4.3-32.6), compared with 11.7 ng/g creatinine (range 4.1-35.9) in those with normal growth. The difference was statistically not significant (p = 0.15). Moreover, there was no significant difference between the patients and the control group. One stunted patient had a urinary growth hormone (UGH) concentration below the normal range, whereas four patients with normal height were also below the normal range. Four of these five patients (80%) were on corticosteroid treatment at the time of urinary collection, whereas only 26% of the patients with normal UGH were also on corticosteroid treatment. We conclude that growth retardation in children with chronic inflammatory bowel disease is probably not related to growth hormone deficiency but must involve other mechanisms.

Adolescent↗
PubMed1993

Location of tumour necrosis factor alpha by immunohistochemistry in chronic inflammatory bowel disease.

This study determined the location and tissue density of cells immunoreactive for tumour necrosis factor alpha (TNF alpha) in intestinal specimens from 24 patients with chronic inflammatory bowel disease (15 with Crohn's disease, nine with ulcerative colitis) and 11 controls. There was significantly increased density of TNF alpha immunoreactive cells in the lamina propria of both ulcerative colitis and Crohn's disease specimens, although the distribution of these cells differed in the two conditions. In ulcerative colitis most of the TNF alpha immunoreactivity was seen in the subepithelial macrophages, with comparatively less in the deep lamina propria, while in Crohn's disease immunoreactive cells were distributed evenly throughout the lamina propria. Increased submucosal immunoreactivity was found only in Crohn's disease, in which TNF alpha positive macrophages tended to cluster around arterioles and venules, often infiltrating and disrupting vascular endothelium. It is suggested that this degree of TNF alpha production probably contributes significantly to the pathogenesis of both Crohn's disease and ulcerative colitis, by impairing the integrity of epithelial and endothelial membranes, increasing inflammatory cell recruitment, and by prothrombotic effects on the vascular endothelium.

Adolescent↗
PubMed1993

Cytokines in stools of children with inflammatory bowel disease or infective diarrhoea.

AIMS: To determine the concentrations of interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF alpha) in stools from children. METHODS: Stool samples from 14 healthy children, 32 children with inflammatory bowel disease, and 23 children with acute diarrhoea were emulsified in an equal volume of phosphate buffered saline and then centrifuged to produce a clear supernatant fluid. IL-6 and TNF alpha were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: TNF alpha was detected in the stools of all 14 healthy children (12-130 pg/g stool), but IL-6 was detected only in three. Similar results were seen in children with inactive inflammatory bowel disease. Stool TNF alpha concentrations were raised in samples from children with active inflammatory bowel disease, but in most (11/18) of these samples IL-6 was undetectable. Stool samples contained a heat-labile factor which rapidly destroyed IL-6 immunoreactivity. Most children with diarrhoea had TNF alpha concentrations similar to those of healthy controls and most were also negative for IL-6. Three children with Shigella flexneri infection had extraordinarily high concentrations of both TNF alpha and IL-6 in their stools. CONCLUSIONS: There is constant low grade production of TNF alpha in the intestine of healthy people. Raised values are indicative of mucosal inflammation, but are not specific. Stool IL-6 is of little use in assessing mucosal inflammation because immunoreactivity is rapidly lost in stool samples.

Adolescent↗
PubMed1993

Interleukin-2- and interferon-gamma-secreting T cells in normal and diseased human intestinal mucosa.

A sensitive reverse haemolytic plaque assay to detect lymphokine-secreting T cells, and Northern blot analysis to detect expression of lymphokine messenger RNA (mRNA) were used to study interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) production in the mucosa of children with Crohn's disease or ulcerative colitis (UC), and in histologically normal mucosa from patients without inflammatory bowel disease. In the mucosa of most patients with UC and control patients, IL-2- and IFN-gamma-secreting cells were absent or were present at only low levels. In contrast, in mucosa from patients with Crohn's disease, lymphokine-secreting cells were readily detectable (3-18%). IFN-gamma mRNA was detected by Northern blot analysis in 5/6 Crohn's tissues, but only in 1/5 UC samples and none of nine samples of control mucosa. These studies reveal an ongoing cell-mediated immune response in the mucosa in Crohn's disease.

Adolescent↗