Search PubMed⌕ Search

Biomedical subjects

D W Thomas

Publications and source records attributed to D W Thomas.

At least 73 records · Page 4Linked to original sources

Androgen responsiveness of mouse kidney beta-glucuronidase requires 5'-flanking and intragenic Gus-s sequences.

Genetics studies of natural variants of the androgen response of mouse beta-glucuronidase (GUS) reveal a cis-active element closely linked to the GUS structural gene (Gus-s) that is necessary for this kidney-specific response. Results of our previous studies suggested sequences within or near an androgen-inducible deoxyribonuclease I-hypersensitive site (DH site) located in the ninth intron of Gus-s are associated with the androgen response of GUS. Using transgenic mice, we now demonstrate that at least two regions of sequence within Gus-s are involved in regulating the androgen response of GUS. The first, located within 3.8 kb of Gus-s 5'-flanking sequence, directs the response and its tissue specificity, while the second, located within a 6.4-kb fragment of Gus-s extending from the third through the ninth intron of Gus-s, protects the androgen responsiveness of the transgene from repressive influences of the insertion site.

Androgens↗

Trends in the referral and treatment of new patients at a free emergency dental clinic since 1989.

AIM: To investigate the changes in the pattern of new patient referral and treatment at a dental hospital emergency clinic since the introduction of the new dental contract in 1989. DESIGN: A prospective survey and review of clinical records. SETTING: The examination and emergency clinic at Cardiff Dental Hospital. SUBJECTS: 500 consecutive new patients attending the clinic in May/June in 1989, 1993, 1994 and 1995. MAIN OUTCOME MEASURES: Numbers of referrals; source of referral; geographical distribution of patients; registration with general dental practitioners; type of dental disease; treatment received. RESULTS: New patient attendances increased by 56% since 1989. Referrals from family doctors and dentists decreased while self-referrals increased. Self-referral by patients not registered with family dentists increased by 56%. Extraction of teeth was the commonest form of treatment in all years and increased by 72%. CONCLUSIONS: Numbers of patients attending for dental treatment at this setting increased substantially after 1989. Increasing numbers of these patients were inappropriately self-referred for treatment. Patients increasingly selected extraction of teeth as the primary treatment rather than restorative procedures. These changes appeared to be unrelated both to the severity of dental disease at presentation and to socio-economic status.

Adolescent↗

Length of transplanted small bowel required for adequate weight gain in rats.

Progress has been made toward developing a clinically successful small-bowel transplant procedure, but there has been little research concerning the functional aspects of the transplanted small bowel. Using a rat model, our study examined the length of transplanted small bowel required to provide adequate weight gain. The rats were divided into six groups; groups 1 and 2 were considered controls. Group 1 (n = 6) underwent a gastrostomy. Group 2 (n = 3) underwent a jejunoile-ectomy followed by re-establishment of intestinal continuity and anastomosis of the native proximal small bowel to an abdominal stoma and the distal portion to the ascending colon. Groups 3 (n = 5), 4 (n = 4), 5 (n = 5), and 6 (n = 4) underwent small-bowel transplantation, receiving 100%, 50%, 25%, and 15% transplants, respectively. The donor small-bowel anastomoses were the same as the native small-bowel anastomoses in group 2. All of the rats began to produce stool within 4 days of becoming dependent upon the transplanted small bowel. By the end of postoperative week 4, there was no significant difference between the percentages of preoperative body weight in groups 1-4 (range 125.7%-130.0%). Although the weight gain in group 5 was significantly less than that in groups 1-4 (P < 0.05), it was adequate (111.8%); group 6 animals lost weight (94.7%). It is concluded that a 50% or more small-bowel transplant with or without an ileocecal valve provides ample weight gain; minimally adequate weight gain is achieved by a 25% transplant without an ileocecal valve; and the graft begins to function soon after transplantation.

Animals↗

Facultative hypothermia as a thermoregulatory strategy in the phyllostomid bats, Carollia perspicillata and Sturnira lilium.

The present study questions whether hypothermia is an artifact due to captivity-induced stress or a thermoregulatory strategy for bats of the neotropical family Phyllostomidae. In Guanacaste, Costa Rica, Carollia perspicillata and Sturnira lilium exhibited a bimodal distribution of body temperatures when submitted to an ambient temperature of 21 degrees C. Body temperature was highly correlated with body mass in both species. C. perspicillata of mass > or = 20 g and S. lilium of mass > or = 17 g remained normothermic (body temperature > 37 degrees C), whereas at masses below 18 g and 13 g, respectively, > 80% of individuals were hypothermic (body temperature < or 32 degrees C). In two treatment groups for each species, we restricted food intake to ca. 20% of body mass on either night 1 or night 4 following capture. Hypothermia was significantly related to food-restriction, but not time in captivity. Metabolic rate (ml O2. g-1 h-1) at ambient temperature = 21 degrees C was MR = e(-2.11 + 0.101 Tb) (r2 = 0.7, P < 0.001) for C. perspicillata and MR = e(-2.62 + 0.115 Tb) (r2 = 0.89) for S. lilium. Free-ranging, radio tagged C. perspicillata exhibited daily depression of body temperature to 33-34 degrees C. We conclude that hypothermia is an thermoregulatory strategy that allows phyllostomid bats to adjust metabolic rate to feeding success and the level of fat stores.

Adaptation, Physiological↗

An audit of antibiotic prescribing in third molar surgery.

The use of antibiotics as a prophylactic measure against infection is widespread following the removal of impacted third molars. The advantages of using such prophylaxis appear to be marginal and there is little substantial evidence to support the use of second and third generation antibiotics for routine prophylaxis. An audit of antibiotic prescribing practices in the University Dental Hospital National Health Service Trust (Cardiff) was undertaken and demonstrated the potential for saving large sums of money whilst apparently incurring no clinical disadvantage. The value of such audit process in oral and maxillofacial surgery is in identifying best practice followed by measuring and, where possible, improving standards.

Adult↗

The appropriateness of referral of medically compromised dental patients to hospital.

Hospital departments of oral and maxillofacial surgery make a substantial contribution to both managing and treating medically-compromised dental patients. Contracting arrangements should take account of this. Demographic data suggest that the treatment of medically-compromised elderly dentate patients will become increasingly important in the General Dental Service (GDS). To determine the medical conditions and treatment requirements prompting referral of these patients to hospital, a prospective study was undertaken of 75 consecutive adults referred for hospital treatment specifically because of a medical condition which prevented delivery of routine dental care in the GDS. Patients (mean age: 56 years) were referred mainly from general medical (33%) and dental (62%) practitioners. Cardiovascular disease was the most frequently cited medical condition requiring referral (43%; n = 32 cases). Forty-eight patients (64%) were symptomatic on presentation and on average had attended on 2.3 occasions before definitive treatment was instituted. Fifty-two patients (70%) had no special treatment requirements other than those available in the GDS, 11 patients (15%) simply required antibiotic prophylaxis and 81% were treated by undergraduates or junior staff. These data suggest that many patients referred for dental hospital treatment because of underlying medical condition are not in fact medically-compromised and may be treated in the primary care setting.

Adult↗

Salivary epidermal growth factor plays a role in protection of ileal mucosal integrity.

The role of salivary epidermal growth factor (EGF) in the maintenance of ileal mucosal integrity was studied by evaluating the effects of sialoadenectomy on luminal EGF levels, ileal tissue resistance (Rt), and unidirectional flux of [51Cr]EDTA. Mice in groups 1 (SLX) and 2 (SLX + EGF) were subjected to sialoadenectomy, while mice in groups 3 (Sham) and 4 (Sham + EGF) underwent a sham procedure. All animals received normal diet and water, except that EGF (100 ng/ml) was added to water for SLX + EGF and Sham + EGF mice. At seven days after surgery, luminal EGF levels in gastrointestinal segments and ileal Rt were significantly reduced by sialoadenectomy, which was prevented by EGF supplementation. Unidirectional flux of [51Cr]EDTA was 6- to 22-fold greater in the ileum of sialoadenectomized mice, which was prevented by EGF administration. Results suggest that salivary EGF may be the major source of intestinal EGF, and it may play a role in maintenance of ileal mucosal integrity.

Animals↗

The performance of an infra-red interactance instrument for assessing total body fat.

Infra-red interactance has been evaluated as a technique for measuring total body fat in comparison with a range of alternative methods. The alternative techniques employed were neutron activation analysis, tritiated water dilution, whole-body potassium-40 counting, skinfold anthropometry, bioelectrical impedance analysis and the body mass index. The study group consisted of 43 healthy adults (16 males and 27 females). For 11 women, measurements were obtained before and after 11 weeks on a very low-calorie diet, giving a total of 54 sets of data. Correlation coefficients between infra-red interactance and the other techniques varied between 0.58 (p < 0.0002) and 0.80 (p < 0.0001) for females, and between 0.64 (p < 0.009) and 0.94 (p < 0.0001) for males. The average fat for the study group was underestimated by 15% using infra-red interactance in comparison with the average fat obtained from the other techniques. It was also noted that the infra-red interactance instrument yielded a very narrow range of body fats in females in comparison with the other techniques. It is essential that these differences are reconciled before infra-red interactance takes a significant role in body composition analysis.

Adipose Tissue↗

T-cell receptor V beta usage by lesional lymphocytes in oral lichen planus.

To determine whether the T-cell inflammatory infiltrate in oral lichen planus (OLP) represents a selective activation and expansion of a limited repertoire of T-cell receptor (TCR) specific T-cells, V beta gene expression was investigated in lesional T-lymphocytes in OLP. A reverse transcriptase-polymerase chain reaction (RT-PCR) technique was used to amplify the 24 major V beta gene sub-families of infiltrating mucosal lymphocytes and peripheral blood mononuclear cells (PMNC) in seven patients with reticular OLP and four healthy control patients. Specificity of amplified products was confirmed by Southern blotting with a C beta internal probe. TCR V beta usage by lesional T-cells in OLP was markedly heterogeneous 5-23 V beta sub-families). In 6/8 patients with OLP, V beta usage was restricted with < or = 20/25 sub-families detected; only one of the V beta sub-families (V beta 8) was present in all of the OLP patients demonstrating TCR V beta restriction. In contrast, TCR V beta usage was unrestricted in PMNC from OLP patients and controls (> or = 23/ 25 sub-families detected). In three patients, certain V beta sub-families (V beta 13, V beta 14 & V beta 15) were present in the lesional T-cell population but were under-represented in PMNC. These results suggest a selective V beta gene usage by lesional infiltrating T-cells in oral lichen planus. The non-uniformity of V beta restriction in lesional T-cells does not support the concept of a common superantigen in OLP and reflects the heterogeneity of the disease.

Adult↗

Molecular analysis of T cell receptor beta variability in a patient with orofacial granulomatosis.

BACKGROUND: Orofacial granulomatosis (OFG) is a rare chronic inflammatory disorder of unknown causation and is characterised histologically by non-caseating granulomas and aggregates of small lymphocytes. The molecular nature of these T cells is, however, unclear. AIMS: To determine the T cell receptor (TCR) V beta gene usage of the T cell infiltrate associated with the primary lesions in a patient with OFG. METHODS: A molecular method involving reverse transcriptase (RT)-polymerase chain reaction (PCR), DNA cloning, single strand conformation polymorphism (SSCP), length analysis, and nucleotide sequencing was used. RESULTS: Compared with peripheral blood lymphocytes from the same patient, notably restricted TCRV beta gene usage was observed in the T cell infiltrate. Only three of the 24 major TCRV beta gene families were represented in the repertoire. There was preferential usage of the V beta 6 gene. In addition, more than 20% of the V beta 6 TCR transcripts exhibited an identical unique V-D-J junctional sequence, suggesting a local antigen driven V beta 6 T cell clonal expansion in vivo, a phenomenon not observed in normal oral mucosa. CONCLUSIONS: The TCRV beta repertoire of T cells associated with OFG is restricted. It is also associated with a local T cell clonal expansion. The results, therefore, provide a new perspective on the immunopathology of OFG.

Amino Acid Sequence↗

An investigation of preferential fibroblast wound repopulation using a novel in vitro wound model.

To overcome the difficulties of studying wounding and wound repopulation in monolayer systems, a 3-dimensional model of wound repopulation has been developed which allows the in vitro investigation of fibroblast migration in response to experimental wounding. This model was utilized to determine whether fibroblasts derived from sites which demonstrate preferential healing (child and oral mucosal fibroblasts) possessed an increased ability to repopulate experimental wounds when compared to adult dermal fibroblasts. Fibroblasts were established from specimens derived from healthy donors undergoing minor elective surgery. Standard wounds were created in fibroblast populated collagen lattices (FPCLs) which were then overlaid upon an extracellular wound matrix. Fibroblast repopulation of the wounds was studied over 12 days using light- and scanning electron microscopy and quantified using computerized image analysis. Wound repopulation by fibroblasts derived from child donors (n = 3) was significantly (P < 0.001) more rapid than their adult tissue-matched counterparts (n = 3). Wound repopulation by oral mucosal fibroblasts (n = 3) was significantly greater than that exhibited by age-matched dermal fibroblasts (n = 3; P < 0.05). These differences were not reflected in differences in DNA synthesis (P > 0.5) or cell number (P > 0.5) within similar attached FPCL systems. These findings further support the concept of a gradual transition from the fetal to adult phenotype in wound healing. The potential applications of the model are discussed.

Adult↗

Understanding the wandering patient. A continuity of personality perspective.

The purpose of this article is to study the relationship between personality and wandering behavior among individuals with dementia. Surrogates of 20 wanderers and 20 non-wanderers were administered a demographic and personality questionnaire. The findings, which also included a qualitative follow-up, revealed that wanderers scored significantly higher than non-wanders on the personality factors of extroversion (p < or = .01) and agreeableness (p < or = .05). A strong implication of the study, for nurses and other care providers, is that for many people wandering is an expression of one's personality--ingrained over a lifetime of development--rather than solely an expression of dementia.

Aged↗

Nitrogen and energy requirements of the short-tailed fruit bat (Carollia perspicillata): fruit bats are not nitrogen constrained.

Nitrogen (N) and energy (E) requirements were measured in adult Carollia perspicillata which were fed on four experimental diets. Bats ate 1.3-1.8 times their body mass.day-1 and ingested 1339.5-1941.4 kJ.kg-0.75.day-1. Despite a rapid transit time, dry matter digestibility and metabolizable E coefficient were high (83.3% and 82.4%, respectively), but true N digestibility was low (67.0%). Mass change was not correlated with E intake, indicating that bats adjusted their metabolic rate to maintain constant mass. Bats were able to maintain constant mass with digestible E intake as low as 1168.7 kJ.kg-0.75.day-1 or 58.6 kJ.. Metabolic fecal N and endogenous urinary N losses were 0.87 mg N.g-1 dry matter intake and 172.5 mg N.kg-0.75.day-1, respectively, and bats required 442 mg N.kg-0.75.day-1 (total nitrogen) or 292.8 mg N.kg-0.75.day-1 (truly digestible nitrogen) for N balance. Based on E and N requirements and digestibilities, it was calculated that non-reproductive fruit bats were able to meet their N requirements without resorting to folivory and without over-ingesting energy. It was demonstrated that low metabolic fecal requirements allowed bats to survive on low-N diets.

Animals↗

T cell receptor Vbeta repertoire of tumour-infiltrating lymphocytes in oral squamous-cell carcinoma.

Oral squamous cell carcinoma (OSCC) are frequently infiltrated by tumour infiltrating lymphocytes (TILs) which may demonstrate specific anti-tumour cytotoxicity. We have used a panel of family-specific primers in reverse-transcriptase (RT)-polymerase chain reactions (PCR) to determine the TCR Vbeta repertoire of TILs in the primary and metastatic tumours in patients with OSCC. We observed a diverse and heterogenous usage of TCR Vbeta genes by TILs in the primary tumours, a scenario not unlike normal oral mucosal lymphocytes. In one patient with a longstanding history of OSCC, the repertoire was restricted. Restricted TCR Vbeta gene usage also occurred in TILs of metastatic tumours. Within individual patients, discrepancies of TCR Vbeta gene usage were also observed between TILs in the primary OSCC and those in metastatic lymph nodes. Work is ongoing to determine the clonality and functional significance of these TILs.

Biopsy↗

An investigation of the interaction between alcohol and fibroblasts in wound healing.

This study investigated the effect of clinical concentrations of alcohol on fibroblast function (proliferation and ECM synthesis) in vitro. Basal and TGF-beta-induced collagen synthesis was assayed in confluent cultures in serum-free medium at 48 h with a commercial collagen assay system. At concentrations of alcohol > 5%, fibroblast proliferation was significantly inhibited. Although noninhibitory, subclinical concentrations of alcohol failed to inhibit basal collagen synthesis (P > 0.1), they significantly decreased TGF-beta-induced collagen synthesis (P < 0.03). These data support the notion that the local, as well as the systemic, effects of alcohol are important in mediating delayed healing in alcoholic patients.

Cell Division↗

The central role of the CD40-ligand and CD40 pathway in T-lymphocyte-mediated differentiation of B lymphocytes.

This review summarizes recent findings concerning the role of CD40-ligand and CD40 interactions in B-cell differentiation. CD40-ligand on helper CD4+ T lymphocytes interacts with CD40 on B cells and directs the selection and differentiation of clones of B lymphocytes to generate specific antibody-dependent immune responses. CD40-ligand is necessary for normal B-cell differentiation and plays several distinctive roles in this multistage process. The CD40 signaling pathway that normally regulates B-cell death appears to be usurped by the Epstein-Barr virus to mediate B-cell transformation.

B-Lymphocytes↗