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Biomedical subjects

H Scott

Publications and source records attributed to H Scott.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cytokine profiles differ in newly recruited and resident subsets of mucosal macrophages from inflammatory bowel disease.

BACKGROUND & AIMS: Most macrophages in the normal intestinal mucosa have a mature phenotype. In inflammatory bowel disease (IBD), a monocyte-like subset (CD14+ L1+) accumulates. The aim of this study was to characterize its potential with regard to cytokines. METHODS: Lamina propria mononuclear cells were adherence-separated, with or without depletion of CD14+ cells, and production of cytokines was investigated by bioassay, enzyme-linked immunosorbent assay, or immunocytochemistry. RESULTS: Tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), and IL-1 receptor antagonist were found mainly in cells positive for myelomonocytic L1. In undepleted IBD cultures, TNF-alpha, IL-1alpha and beta, and IL-10 were markedly up-regulated by pokeweed mitogen stimulation; IL-1alpha and beta and IL-10 were also up-regulated by stimulation of interferon gamma and lipopolysaccharide in combination. The latter stimulation had no effect on normal control or CD14-depleted IBD cultures. Indomethacin caused a marked increase of TNF-alpha, particularly in undepleted IBD cultures, whereas IL-10 and IL-4 decreased TNF-alpha and IL-1beta in both CD14+ and CD14 macrophages. CONCLUSIONS: In IBD mucosa, macrophages with a monocyte-like phenotype are primed for production of TNF-alpha and IL-1alpha/beta and may therefore be of significant pathogenic importance [corrected]. However, this CD14+ subset, as well as the mucosal resident macrophages, have preserved responsiveness to several down-regulatory factors such as the macrophage deactivators IL-10 and IL-4.

Adult↗
PubMed1997

Encephaloneuropathy with lysosomal zebra bodies and GM2 ganglioside storage.

An 11-year-old girl died of a neuronal storage disorder that clinically was characterized by failure to thrive and muscular hypotonia from birth, with the subsequent evolution of motor neuron disease, epilepsy, and dementia. A wide range of metabolic disorders, including all forms of GM2 gangliosidosis, could be excluded. Electron microscopy demonstrated neuronal zebra body inclusions, and immunohistochemistry demonstrated that GM2 ganglioside was a major constituent of the storage material. We suggest that the patient died of a lysosomal storage disease that is clinically and biochemically different from Tay-Sachs disease, Sandhoff disease, and other GM2 gangliosidoses described previously. This case also further demonstrates that significant accumulation of GM2 ganglioside, which is crucial for dendritic formation, may occur in neuronal storage diseases lacking known defects in ganglioside catabolism.

Child↗
PubMed1997

Gliadin specific, HLA DQ2-restricted T cells are commonly found in small intestinal biopsies from coeliac disease patients, but not from controls.

The authors have analysed gliadin specific, CD4+ T cells isolated from small intestinal biopsies of 23 adult coeliac disease patients (20 on a gluten-free diet and three untreated) and nine control patients. The biopsies were stimulated ex vivo with a peptic/tryptic digest of gliadin for 24 h, and activated T cells were positively selected with paramagnetic beads coated with an antibody against the interleukin-2 receptor. The T cells were expanded and tested for gliadin reactivity and HLA restriction. Gliadin specific, polyclonal T cell lines were recovered from biopsies of all 23 patients. Inhibition studies of T cell lines from 21 patients with anti-HLA monoclonal antibodies indicated predominant presentation of the gliadin antigen by HLA-DQ2 in T cell lines from 11 patients (lines from seven patients with complete MoAb inhibition, the remaining with incomplete inhibition) and incomplete inhibition by HLA-DR3 in lines from three patients. Nine gliadin specific T cell clones from six patients were established; all of these were HLA-DQ2 restricted. Gliadin specific T cells were not found in biopsies from the non-coeliac controls. Our findings demonstrate that gliadin reactive T cells are commonly found in the intestinal mucosa of CD patients and they support the notion that the majority of T cell recognize gliadin peptide(s) when presented by the disease associated DQ2 molecules.

Adolescent↗
PubMed1997

Developmental dysplasia of the hip in South Australia in 1991: prevalence and risk factors.

OBJECTIVE: To determine the prevalence of developmental dysplasia of the hip (DDH) in South Australia (SA) in 1991, the proportion of cases detected in the neonatal period and the perinatal risk factors for DDH. METHODOLOGY: Cases of DDH born in SA in 1991 were identified from multiple sources and their clinical data linked to perinatal data provided by midwives; five controls per case were obtained randomly from SA livebirths without congenital abnormalities and adjusted odds ratios (OR) for potential risk factors obtained by logistic regression analysis. South Australia perinatal data were also used to estimate numbers of births with perinatal risk factors for targeted screening. RESULTS: Two hundred and six cases of isolated DDH were identified, giving a prevalence of 10.5 per 1000 births. Of these, 173 (84%) had been detected in the neonatal period. The perinatal risk factors for DDH were identified as breech presentation (OR 9.65), female babies (OR 4.04), first births (OR 1.91) and maternal age of 25 years or more (OR 1.53). Screening breech and firstborn female babies (23% of births) would yield approximately 51% of cases of DDH. CONCLUSIONS: Isolated DDH had a prevalence of 10.5 per 1000 births and 84% of cases had been detected in the neonatal period in SA. Repeated screening during infancy of "at risk' groups of babies is recommended.

Breech Presentation↗
PubMed1997

Gliadin specific, HLA DQ2-restricted T cells are commonly found in small intestinal biopsies from coeliac disease patients, but not from controls.

The authors have analysed gliadin specific, CD4+ T cells isolated from small intestinal biopsies of 23 adult coeliac disease patients (20 on a gluten-free diet and three untreated) and nine control patients. The biopsies were stimulated ex vivo with a peptic/tryptic digest of gliadin for 24 h, and activated T cells were positively selected with paramagnetic beads coated with an antibody against the interleukin-2 receptor. The T cells were expanded and tested for gliadin reactivity and HLA restriction. Gliadin specific, polyclonal T cell lines were recovered from biopsies of all 23 patients. Inhibition studies of T cell lines from 21 patients with anti-HLA monoclonal antibodies indicated predominant presentation of the gliadin antigen by HLA-DQ2 in T cell lines from 11 patients (lines from seven patients with complete MoAb inhibition, the remaining with incomplete inhibition) and incomplete inhibition by HLA-DR3 in lines from three patients. Nine gliadin specific T cell clones from six patients were established; all of these were HLA-DQ2 restricted. Gliadin specific T cells were not found in biopsies from the non-coeliac controls. Our findings demonstrate that gliadin reactive T cells are commonly found in the intestinal mucosa of CD patients and they support the notion that the majority of T cells recognize gliadin peptide(s) when presented by the disease associated DQ2 molecules.

Adult↗
PubMed1996

Expression of the L1 antigen (calprotectin) by tissue macrophages reflects recent recruitment from peripheral blood rather than upregulation of local synthesis: implications for rejection diagnosis in formalin-fixed kidney specimens.

The L1 antigen (calprotectin) is present in circulating monocytes but is restricted to certain subsets of tissue macrophages. Its expression is significantly increased in inflammatory bowel disease, apparently because of newly recruited monocytes. In vitro experiments were performed to substantiate lack of L1 upregulation in tissue macrophages, thereby justifying the use of this marker to detect newly recruited cells. Its reliability was further evaluated by studying mononuclear cell infiltrates characteristic of acute kidney rejection. After pro-inflammatory stimulation, monocytes matured in vitro (n = 12) as well as adherent mononuclear cells from normal small intestinal mucosa (n = 5) were examined for L1 expression by immunocytochemistry and by ELISA (cell lysates). In addition, peritubular mononuclear L1+ cells were examined by immunohistochemistry in routine biopsy specimens from transplanted kidneys with (n = 11) or without (n = 14) histopathologically diagnosed acute rejection. L1 was not upregulated in monocytes matured in vitro, nor in mucosal macrophages after stimulation with interferon-gamma, LPS, phorbol ester, or supernatant from activated leucocytes. In transplanted kidneys with signs of acute rejection, the fraction of L1+ macrophages was significantly increased (P < 0.001). Because L1 is persistently downregulated in mature tissue macrophages and is formalin-resistant, it identifies young infiltrating macrophages in routinely processed biopsy material. L1 should therefore be a valuable adjunct in the diagnosis of kidney rejection.

Biopsy↗
PubMed1996

Comparison of the effects of bradykinin and related compounds on isolated mouse and human uterus.

The purpose of this study was to investigate and compare the response of the isolated human myometrium (non-pregnant donors) and mouse uterus to bradykinin (BK), Lys-BK and des-Arg9-BK (+/-2.79 microM indomethacin). The uterine strips were set up for superfusion using Kerbs' solution. On the human myometrium the responses to BK and Lys-BK were biphasic and consisted of an increase in myometrial tension which was followed by a period of inhibition of myogenic activity. Des-Arg9-BK evoked a monophasic contractile response. On the mouse uterus the responses to BK, Lys-BK and des-Arg9-BK were monophasic and contractile only. On both of the tissues the contractile responses to BK and Lys-BK were bell shaped and indomethacin abolished the bell-shaped part of the dose response curves. The response to des-Arg9-BK and the inhibitory response to BK and Lys-BK, on the human tissue, was also significantly reduced in the presence of indomethacin. The results of this study suggest that the human and mouse uterus do posses kinin receptors of the B2 type but on human myometrium these are biphasic responses.

Animals↗
PubMed1996

Is routine drainage of pelvic anastomosis necessary?

The routine use of drains for pelvic anastomosis is controversial. This study was undertaken to determine whether drainage alters leak rate, aids in diagnosing a leak, and/or prevents the need for laparotomy when a leak occurs. Records of 156 consecutive patients who underwent elective resection and pelvic anastomosis for cancer from 1986 to 1994 were retrospectively reviewed. The patients were stratified into two parent groups, I and II. One hundred and eleven Group I patients who routinely had Jackson-Pratt 10-mm drains inserted were subdivided into subgroup I-A (n = 24) with proximal intraoperative diversion and subgroup I-B (n = 87), without diversion. Forty-five Group II patients routinely did not have drains inserted. They were also subdivided, into II-A (n = 3) and II-B (n = 42), i.e., with and without simultaneous diversion, respectively. The overall leak rate was 5.1 per cent (8/156). Subgroups I-A and II-A had leak rates of 8.33 per cent (2/24) and 0 per cent (0/3), respectively. The leak rates were 4.6 per cent (4/87) in subgroup I-B and 4.8 per cent (2/42) in subgroup II-B, with no significant difference (P > 0.05). Also, no significant difference was noted when the overall leak rate for diverted cases was compared with nondiverted ones. Of the four leaks in I-B, three occurred after the drains were removed; two of these required laparotomy, drainage, and diversion. The fourth occurred with the drain in place, but failed to demonstrate feces or pus in the drainage fluid or prevent the need for laparotomy. The presence of a drain did not affect the leak rate (P > 0.10). Drain contents did not aid in diagnosing anastomotic dehiscence. Routine prophylactic use of Jackson-Pratt drains seems unjustified because leaks either occurred after the drains were removed or failed to prevent the need for laparotomy.

Adult↗
PubMed1996

Guided bone regeneration to facilitate implant and prosthodontic therapy: three case reports.

In some patients, lack of bone at a desired fixture site has resulted, by necessity, in the placement of endosseous implants in less than favorable locations. The principles of guided bone regeneration can be used to restore lost alveolar bone and permit the placement of implants at more ideal locations, or to provide a more favorable ridge form to support a removable prosthesis. The advantages of a two-stage technique involving bone grafting followed by a healing period prior to implant placement are discussed. Different methods of membrane tenting to provide space for bone growth are illustrated by three case reports. Evidence of bone augmentation is provided by computed tomography.

Adult↗
PubMed1995

Gliadin-specific T cell responses in peripheral blood of healthy individuals involve T cells restricted by the coeliac disease associated DQ2 heterodimer.

Coeliac disease (CD) is probably caused by an abnormal immune response towards wheat gliadin in the small intestine. We found that gliadin-specific T cells from the small intestinal mucosa of HLA-DQ2 positive CD patients were almost exclusively restricted by the disease-associated DQ2 molecule. In the peripheral blood of CD patients, a large proportion of gliadin-specific T cells were found to be restricted by DQ molecules, including DQ2, but many were instead restricted by DR or DP molecules of the patient. We have now investigated gliadin-specific T cell responses in peripheral blood from healthy individuals. Four of 20 persons tested had strong in vitro responses and were used as donors for gliadin-specific T cell clones. We found gliadin-specific T cells restricted by the CD-associated DQ2 molecule in peripheral blood for two of these four individuals. It is the presence of such T cells also in the small intestinal mucosa which seems typical of CD.

Antibodies, Monoclonal↗
PubMed1995

SIDS cases have increased levels of interleukin-6 in cerebrospinal fluid.

Cerebrospinal fluid (CSF) from 20 infants who died of sudden infant death syndrome (SIDS), 7 cases of infectious death and 5 cases of violent death were examined with respect to concentrations of interleukin-6 (IL-6). The measurements were performed by ELISA. IL-6 levels in SIDS were significantly lower than in infectious death (p < 0.02), but significantly higher than in violent death (p < 0.02). Since IL-6 plays an important role in immune responses and may induce fever, the findings may suggest that immune activation plays a role in SIDS. The presence of cytokines in the central nervous system (CNS) may cause respiratory depression, especially in vulnerable infants.

Enzyme-Linked Immunosorbent Assay↗
PubMed1995

Respiratory burst of intestinal macrophages in inflammatory bowel disease is mainly caused by CD14+L1+ monocyte derived cells.

Macrophages play a crucial role in intestinal mucosal defence, forming dense subepithelial aggregates, particularly in the colon. One of their important bactericidal mechanisms is production of oxygen radicals but this may damage the intestinal epithelium, perhaps as an early step in inflammatory bowel disease (IBD). The potential for release of oxygen radicals from mucosal macrophages in IBD was measured and whether a difference exists between newly arrived (CD14+L1+) monocyte-like cells and resident macrophages (CD14(-)L1-), without or with additional priming in vitro, was investigated. Lamina propria mononuclear cells from six patients with IBD and five with a normal intestine were isolated with an ethylenediaminetetra acetic acid/collagenase/dispase technique and cultured for three days. The cells were tested with or without interferon gamma (200 U/ml) priming in the presence or absence of lipopolysaccharide (1 microgram/ml) for the last 48 hours in cultures. Samples from inflamed IBD mucosa depleted of CD14+ cells by immunomagnetic beads were compared with their undepleted counterparts and with samples from virtually normal mucosa from the same patients. The production of oxygen radicals was measured as the amount of reduced cytochrome C 2.5 hours after triggering with phorbol 12-myristate 13-acetate. The oxygen radical production in macrophages from moderately or severely inflamed mucosa was reduced by median 69% (range 22%-79%, p < 0.027) after depletion of CD14+ cells, reaching a level similar to that found for virtually normal samples from the same IBD patients. Furthermore, this production did not increase significantly in mucosal macrophages from normal reference mucosa and from virtually normal or inflamed IBD mucosa after priming with interferon gamma with or without addition of lipopolysaccharide. Upregulation of a respiratory burst in subepithelial resident macrophages os not a likely pathogenetic step in IBD. The increased oxygen radical production shown by macrophages from IBD lesions can, however, be ascribed to recently extravasated CD14+L1+ monocyte-like cells. Inhibition of extravasation of these reactive cells may form part of a therapeutic approach in the future.

Antigens, Surface↗
PubMed1995

Gluten specific, HLA-DQ restricted T cells from coeliac mucosa produce cytokines with Th1 or Th0 profile dominated by interferon gamma.

Coeliac disease is precipitated in susceptible subjects by ingestion of wheat gluten or gluten related prolamins from some other cereals. The disease is strongly associated with certain HLA-DQ heterodimers, for example, DQ2 (DQ alpha 1*0501, beta 1*0201) in most patients and apparently DQ8 (DQ alpha 1*0301, beta 1*0302) in a small subset. Gluten specific T cell clones (TCC) from coeliac intestinal lesions were recently established and found to be mainly restricted by HLA-DQ2 or HLA-DQ8. Antigen induced production of cytokines was studied in 15 TCC from three patients, 10 being DQ2 and five DQ8 restricted. Cell culture supernatants were prepared by stimulation with gluten peptides in the presence of DQ2+ or DQ8+ Epstein-Barr virus transformed B cells as antigen presenting cells (APC). Supernatants were analysed for cytokines by bioassays, ELISA, and CELISA. Cellular cytokine mRNA was analysed semi-quantitatively by slot blotting and polymerase chain reaction (PCR). All TCC were found to secrete interferon (IFN) gamma, often at high concentrations (> 2000 U/ml); some secreted in addition interleukin (IL) 4, IL 5, IL 6, IL 10, tumour necrosis factor (TNF), and transforming growth factor (TGF) beta. The last TCC thus displayed a Th0-like cytokine pattern. However, other TCC produced IFN gamma and TNF but no IL 4, or IL 5, compatible with a Th1-like pattern. In conclusion, most DQ8 restricted TCC seemed to fit with a Th0 profile whereas the DQ2 restricted TCC secreted cytokines more compatible with a Th1 pattern. The TCC supernatants induced upregulation of HLA-DR and secretory component (poly-Ig receptor) in the colonic adenocarcinoma cell line HT-29.E10, most probably reflecting mainly the high IFN gamma concentrations. This cytokine, particularly in combination with TNF alpha, might be involved in several pathological features of the coeliac lesion. The characterised cytokine profiles thus support the notion that mucosal T cells activated in situ by gluten in a DQ restricted fashion play a central part in the pathogenesis of coeliac disease.

Base Sequence↗
PubMed1995

The etiology and antimicrobial susceptibility patterns of microorganisms in acute community-acquired lung abscess.

OBJECTIVE: To determine the spectrum and antibiotic susceptibility patterns of microorganisms causing acute community-acquired lung abscess. DESIGN: A prospective survey. SETTING: Medical emergency department and wards of a tertiary teaching hospital. PATIENTS: Thirty-four adult patients with both clinical and radiologic features compatible with a diagnosis of acute community-acquired lung abscess who had received less than 48 h of antibiotic therapy. INTERVENTIONS: Microbiologic specimens obtained by percutaneous lung aspiration and with a protected specimen brush via fiberoptic bronchoscopy were submitted for aerobic and anaerobic culture. MAIN OUTCOME MEASURES: Identification of all microorganisms, including anaerobes, and determination of antibiotic susceptibility. RESULTS: A mean of 2.3 bacterial species per patient was isolated, anaerobes alone being isolated in 44% of cases, aerobes alone in 19%, and mixed aerobic and anaerobic isolates in 22%. Aerobic Gram-negative pathogens were uncommon. In seven patients, Mycobacterium tuberculosis was identified; in two it was associated with other bacteria. In four patients, no organisms were isolated. All the nonmycobacterial isolates were susceptible to amoxicillin-clavulanate and in addition the anaerobes were all susceptible to chloramphenicol and almost all to a combination of penicillin and metronidazole. Among the anaerobes, the level of resistance to penicillin, metronidazole, and clindamycin individually was 21%, 12%, and 5%, respectively. CONCLUSIONS: Community-acquired acute lung abscess is usually caused by multiple anaerobic and less frequently aerobic Gram-positive microorganisms, which should respond to empirical therapy with amoxicillin-clavulanate, chloramphenicol, or a combination of penicillin and metronidazole. Tuberculosis, which may be indistinguishable from an acute lung abscess, occurred in 21% of patients in our study. Most bacterial pathogens are sensitive to conventional antimicrobial therapy and further investigation with percutaneous lung aspiration or bronchoscopy is indicated only when there is lack of early response to therapy or there is the presence of atypical clinical features.

Acute Disease↗