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Biomedical subjects

D W Thomas

Publications and source records attributed to D W Thomas.

At least 91 records · Page 5Linked to original sources

Mucosal cell-mediated immunological changes associated with experimental graft-versus-host disease.

This study examined the histological changes and local cellular immune response induced within the lingual mucosa in an allogeneic F1 hybrid rat model of graft-versus-host disease (GvHD) with a view to studying oral lymphocyte-epithelial cell reactions. Highest levels of disease, as reflected by both a GvHD index and the extent of the oral mucosal changes, were obtained using primed donor (Lewis rats) splenocytes and irradiated hosts (Lew/Da rats). The lingual mucosae of test animals were characterised by irregular epithelial keratosis, an absence of basal cell liquefaction and a diffuse inflammatory cell infiltrate, histological features consistent with an oral lichenoid tissue reaction. Immunohistochemical studies showed that mucosal involvement was characterised by infiltration of the lamina propria by NK cells (CD8+, CD5-), "activated" cells (CD25+) and T cells (CD5+) with selective migration of the latter, including a CD5+, CD8- subset (helper/inducer T cell), into the epithelium. Epithelial expression of Ia was invariably associated with these inflammatory cell infiltrates and correlated with the GvHD index. These findings suggest the presence of local mucosal T cell activation in the absence of detectable epithelial cell damage, which may be equivalent to the early initiating events in the pathogenesis of oral lichen planus. However, whilst experimental graft-versus-host disease appears to be a useful model for studying lymphocyte-epithelial interactions, the induced oral mucosal changes are more consistent with a lichenoid reaction rather than lichen planus.

Animals↗

A comparison of the ability of intra-oral and extra-oral fibroblasts to stimulate extracellular matrix reorganization in a model of wound contraction.

Intra-oral wounds, like wounds in children, demonstrate privileged healing when compared with adult wounds at extra-oral sites. This study investigated whether this preferential healing is related to an increased ability of oral mucosal fibroblasts to reorganize extracellular matrix (ECM) when compared with their dermal counterparts. ECM reorganization was investigated by means of a fibroblast-populated collagen lattice (FPCL) system. The effect of donor age was also investigated in this system. Differences in ECM reorganization and FPCL contraction were evident: FPCL contraction was more rapid by oral mucosal fibroblasts than dermal fibroblasts (p < 0.01). FPCL contraction was also greater in child (donor < 10 years) than adult (donor > 18 years) oral mucosal fibroblasts (p < 0.01). These differences were not related to phenotypic differences in cell viability (p > 0.5), DNA synthesis (p > 0.05), and cell number (p > 0.5) within the FPCLs, or cellular attachment to collagen (p > 0.07). FPCL contraction was not stimulated by the addition of conditioned medium from oral mucosal or dermal fibroblasts (p > 0.05). These data show that the significantly increased ability of oral mucosal fibroblasts to reorganize ECM in vitro, when compared with dermal fibroblasts, represents a distinct phenotypic contractile difference, rather than differences in their production of soluble mediators or cell attachment to ECM.

Adolescent↗

Performance characteristics of the Pantak DXT-300 kilovoltage X-ray treatment machine.

The beam and performance characteristics of a new orthovoltage X-ray unit, the Pantak DXT-300 have been evaluated. Data were collated for four qualities: 3.27 mmAl, 7.15 mmAl, 1.65 mmCu and 3.51 mmCu half value layer (HVL) (SE = 0.04 mm). Parameters which were investigated included beam quality, central axis depth dose, relative output, backscatter factors, field uniformity, peripheral dose and head leakage. The calibration procedure and the performance of the dosimetry system have also been described.

Humans↗

Enhanced production of B lymphocytes after castration.

Castration has long been recognized to stimulate thymic growth and augment cellular immunity. We sought to determine whether castration affects B lymphopoiesis by analyzing the phenotype of bone marrow and spleen cells from animals postcastration. In this report, we show that the bone marrow cells from castrated male mice show a sustained, twofold to threefold increase in numbers of B220+/IgM- cells and of newly formed B220+/IgM+ B cells. Most of the expanded B220+/IgM- cell population consisted of small, HSAhi, CD43- cells characteristic of pre-B cells. The castrated animals also showed increased numbers of splenic B cells, primarily consisting of small IgM+, IgDlo, B220lo, HSAhi cells. Taken together, these results show that castration causes dramatic, long-lived enhancement of B lymphopoiesis in bone marrow and increased numbers of mature B cells in the periphery.

Animals↗

Quantitative measurement of 4-hydroxyalkenals in oxidized low-density lipoprotein by gas chromatography-mass spectrometry.

Previously, we reported on the determination of 4-hydroxyalkenals as pentafluorobenzyl oxime derivatives by gas chromatography-mass spectrometry. In this study, an improved method is presented which allows quantitative detection of 4-hydroxyalkenals in tissues by using two stable isotope-labeled internal standards, 9D3-4-hydroxynonenal and 9D3-4-hydroxyhexenal. This assay was used to quantitate 4-hydroxyalkenals in copper-oxidized human low-density lipoprotein, and we found more 4-hydroxynonenal than 4-hydroxyhexenal. This is consistent with the fact that there are more omega-6 than omega-3 fatty acids in human low-density lipoprotein samples, which are the sources of 4-hydroxynonenal and 4-hydroxyhexenal, respectively.

Aldehydes↗

The Kasai procedure in the treatment of biliary atresia.

From 1978 to 1992, 62 patients were diagnosed as having extrahepatic biliary atresia (EHBA) at Childrens Hospital Los Angeles. The patients presented with either persistent jaundice, alcoholic stools, and/or hepatomegaly. Hepatobiliary IDA scans were performed in 47 of the patients; 46 had results typical of EHBA. Fifty-nine of the 62 patients underwent a Kasai portoenterostomy; three patients were more than 4 months of age at initial presentation and were referred directly for liver transplantation. The preoperative total bilirubin level for all patients averaged 8.6 mg/dL (range, 4.1 to 18.1). All patients underwent a standardized Kasai procedure using a 40-cm Roux-en-Y intestinal segment performed in the end-to-side fashion. Postoperative management included oral antibiotics and fat-soluble vitamins for at least 9 months. Long-term complications included cholangitis in 20 cases and portal hypertension in 25, which led to variceal hemorrhage in 12 cases. Growth rates were at or above the 50th percentile for age in 59% of the Kasai patients. Forty-one of the 59 Kasai patients survived (69.5%); six deaths occurred within 2 years after the Kasai procedure. Twelve patients were lost to follow-up within 2 years after surgery, and for calculation of mortality were presumed dead. Seventeen patients had follow-up for 5 or more years, 13 had follow-up for 2 to 5 years, and 29 had follow-up for less than 2 years. The average total bilirubin level for the patients with less than 2 years of follow-up was 7.9 mg/dL (0.3 to 20.8), and that for the patients with more than 2 years of follow-up was 1.6 mg/dL (0.3 to 18.1). Orthotopic liver transplantation was performed in 11 Kasai patients, in whom chronic liver failure eventually developed. Rejection occurred in one of these patients, which required retransplantation. Based on these results, the Kasai portoenterostomy procedure continues to offer palliation, if not long-term success, in a large percentage of patients with EHBA.

Anastomosis, Roux-en-Y↗

The management of soft tissue facial wounds.

The physiological and physical principles involved in the management of facial lacerations are reviewed. Because there have been no previously published descriptions of the actual problems encountered in clinical practice in A & E Departments, a prospective clinical survey of 100 consecutive patients with facial lacerations repaired by oral & maxillofacial house surgeons was undertaken and a series of lacerations was studied in detail. These included periorbital, nasal, labial and neck injuries. High magnification revealed irregularity of wound margins in almost all cases, frequent localised ischaemia, necrosis, localised dehiscence and infection or inadequate closure. Because all of these problems are likely to increase scarring and deformity, this study suggests the need for a re-appraisal of the management of facial lacerations, particularly in relation to local skin edge excision, prevention of infection, and the use of magnification during closure.

Accidental Falls↗

Lhermitte-Duclos disease associated with Cowden's disease.

The twelfth patient in the known literature with Lhermitte-Duclos disease (dysplastic gangliocytoma) occurring in association with Cowden's disease is described. The investigation, aetiology, and management of the case are discussed.

Adult↗

Inflammatory cell infiltrate associated with primary and transplanted tumours in an inbred model of oral carcinogenesis.

This study characterised the nature of the local cellular immune responses associated with an inbred animal model of oral carcinogenesis. Inbred F344 rats developed moderately- to well-differentiated primary oral squamous cell carcinomas (SCC) after treatment with the carcinogen 4-nitroquinoline N-oxide (4-NQO) in vivo for 5-6 months. The inflammatory cell infiltrate associated with the primary tumours was predominantly of the macrophage lineage (CD45+, Ia+) and contained smaller numbers of CD8+ cells (NK cells, cytotoxic/suppressor T cells), CD5+ cells (T cells) and CD25+ cells (activated cells; T and NK cells). Keratinocyte cell lines were established from three lingual and one palatal SCC. By contrast to normal keratinocytes, tumour-derived cell lines were immortal and independent of 3T3 fibroblast support. All of the tumour-derived cell lines were tumorigenic in athymic (nu/nu) mice and showed contrasting latent periods of tumour development and histological differentiation; normal keratinocyte grafts were non-tumorigenic in athymic mice. Three of four malignant cell lines formed well-differentiated tumours in syngeneic F344 rats; the tumours regressed after 10-14 days. Regressing grafts contained significantly larger numbers of NK cells (CD5-, CD8+) in the inflammatory cell infiltrate compared with that associated with primary tumours (p < 0.04). One malignant cell line and normal keratinocytes were non-tumorigenic in syngeneic hosts. The results demonstrate phenotypic variation in the cell-mediated immune responses associated with the actively growing primary SCC and the regressing tumours in syngeneic hosts and suggest that NK cells, possibly activated by local T cell responses, are important for tumour rejection in this model.

3T3 Cells↗

Wandering: a proposed definition.

1. Two typologies of wandering behavior, "continuous" and "sporadic" can be distinguished when time-in-motion is used as a criteria. 2. Interventions for "continuous wanderers" should emphasize modification of the environment while organized activities and verbal communication techniques should be stressed for the "sporadic wanderer." 3. Empirical research is needed that studies the different needs of wanderers based on the percentage of time spent in motion.

Aged↗

Pediatric gastrointestinal endoscopy.

Development of smaller instruments and emergence of pediatric gastroenterology as a legitimate and growing subspecialty have been primary factors involved in effective utilization of gastrointestinal endoscopy in the care of infants and children. Endoscopic gastrointestinal procedures are now common in most major pediatric centers, and they can be safely performed on small infants, including newborns. This review of pediatric endoscopy presents many of the standard techniques that are applied in most pediatric centers in the United States. Some of the important issues and differences between pediatric and adult patients with gastrointestinal diseases are discussed.

Anesthesia, General↗

Oxidative DNA damage induced by potassium bromate in isolated rat renal proximal tubules and renal nuclei.

Oxidative damage caused by potassium bromate (KBrO3), a rat renal carcinogen, was investigated using in vitro preparations of rat renal proximal tubules (RPT) and renal nuclear fractions. Release of lactate dehydrogenase and decrease of SH-group content in RPT (1 mg protein/ml) by KBrO3 (0.5-5 mM) in a concentration- and time-dependent manner were observed. Peroxidized arachidonic acid and 8-hydroxydeoxyguanosine (8-OH-dG) levels in RPT were increased after administration of 2 and 5 mM KBrO3. 8-OH-dG formation was observed after incubation of renal nuclei with a lipid-peroxiding system, autooxidized methyl linolenate, or KBrO3. These findings provide support for involvement of lipid peroxidation in producing oxidized DNA damage by KBrO3 directly to RPT, the target site for renal carcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗

FH-Sydney 1 and 2: two novel frameshift mutations in exon 10 of the low-density lipoprotein receptor gene detected by heteroduplex formation.

We report two novel frameshift mutations in exon 10 of the low-density lipoprotein receptor gene that lead to familial hypercholesterolemia in separate lineages. The lesions, FH-Sydney 1 and FH-Sydney 2, were detected by a modified heteroduplex analysis of exon-specific polymerase chain reaction (PCR) amplified DNA, and characterized at the molecular level by sequencing. Restriction enzyme digestion of PCR amplified DNA confirmed the presence of the mutant alleles in affected family members and their absence in nonaffected family members in both lineages. FH-Sydney 1 is a 4-bp duplication at position 1373, while FH-Sydney 2 is a 2-bp deletion at position 1478. The predicted result of both mutations is the premature truncation of the receptor at stop codons generated downstream of the mutations. Neither mutation was detected in a survey of 54 unrelated familial hypercholesterolemia patients.

Base Sequence↗

A new disposable bite gauge.

A simple method for assessing mouth opening by measuring interincisal distance with a disposable bite gauge is described. In a clinical study the technique has been proven to be both reproducible and reliable.

Calibration↗