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Biomedical subjects

D M Thomas

Publications and source records attributed to D M Thomas.

At least 19 recordsLinked to original sources
PubMed1995

Sequence 104-117 of myelin proteolipid protein is a cryptic encephalitogenic T cell determinant for SJL/J mice.

Immunization of animals with myelin proteolipid protein (PLP) causes experimental autoimmune encephalomyelitis (EAE), a disease model that shares many features with human multiple sclerosis (MS). The SJL/J (H-2s) mouse is widely used in EAE studies because of its high disease susceptibility. Previous studies have shown that sequences 139-151 HCLGKWLGHPDKF and 178-191 NTWTTCQSIAFPSK represent distinct co-immunodominant encephalitogenic determinants of PLP for SJL/J mice. In the present study, we identify a third distinct PLP encephalitogenic peptide for SJL/J mice. Following immunization with PLP 104-117 KTTICGKGLSATVT, 10/14 SJL/J mice developed clinical and histological EAE with a mean time of onset of 38 days (18-65 days). T cell lines generated from SJL/J mice immunized with p104-117 were predominantly (> 90%) CD3+, CD4+, alpha beta TCR+, CD8dim, gamma delta TCRdim T cells and responded in an Ag-specific, I-A(s)-restricted manner to p104-117. Upon adoptive transfer of 16-40 x 10(6) T line cells, EAE was produced in naive SJL/J recipients 20-34 days after transfer. The delayed onset of both active and passive disease may be related to the non-immunodominant, cryptic nature of p104-117 in SJL/J mice. Lymph node cells from SJL/J mice immunized with either whole PLP or with pooled encephalitogenic PLP peptides responded to challenge with the immunodominant PLP determinants p139-151 and p178-191 but did not respond to p104-117. The existence of three distinct PLP encephalitogenic T cell determinants for SJL/J mice suggests that susceptibility to EAE and perhaps MS may be related to promiscuous T cell recognition of multiple myelin protein determinants.

Amino Acid Sequence↗
PubMed1995

An unusual cause of cochlear implant failure.

We present a cochlear implant failure previously unidentified and unreported. Following successful implantation and activation of a Cochlear Mini 22 system, a distressing barrage of crackling noises was heard by the patient despite repeated programming with threshold and comfort level adjustment. The implant soon became nonfunctional and integrity testing showed deficient electrical responses and abnormal surface measured wave forms. Investigation of the explant, following reimplantation with an identical system, showed a defective trim capacitor, an electric component of the internal circuit in the stimulator. Paired Student's t-test showed a marginally significant increase (p = 0.047) in effective threshold level and a highly significant decrease (p = 0.0002) in maximum comfort level for the second implant compared to the first implant.

Cochlear Implants↗
PubMed1995

Atlanto-axial subluxation (Grisel's syndrome) following otolaryngological diseases and procedures.

Grisel's syndrome is a rare condition of uncertain aetiology characterized by atlanto-axial subluxation following an infection in the head and neck region. The condition most frequently affects children and characteristically presents in the post-operative period with cervical pain and torticollis. We describe three cases and discuss the aetiology and pathogenesis. A high index of suspicion may lead to early diagnosis in its natural history thereby preventing potentially serious complications.

Adenoidectomy↗
PubMed1995

Distinguishing homelessness from poverty: a comparative study.

To separate the characteristics of the homeless from those of the housed poor, 144 adults were randomly sampled from several sites, yielding 3 groups: the currently homeless (n = 59), the previously (but not currently) homeless (n = 31), and the never-homeless poor (n = 54). The homeless were significantly less likely to be receiving public benefits, were more likely to have a DSM-III (Diagnostic and Statistical Manual of Mental Disorders [3rd ed.; American Psychiatric Association, 1980]) diagnosis of substance abuse, showed higher levels of self-rated psychological distress and were more likely to be victims of recent domestic violence and to have been physically abused as children. The homeless did not differ from the comparison groups on DSM-III diagnosis of severe mental illness (schizophrenia or major affective disorder). physical health symptoms, and social support and social networks.

Adult↗
PubMed1995

Modulation of glucose transport by parathyroid hormone and insulin in UMR 106-01, a clonal rat osteogenic sarcoma cell line.

This study characterizes the actions of insulin and parathyroid hormone (PTH) on the glucose transport system in the rat osteogenic sarcoma cell line UMR 106-01, which expresses a number of features of the osteoblast phenotype. Using [1,2-3H]2-deoxyglucose (2-DOG) as a label, UMR 106-01 cells were shown to possess a glucose transport system which was enhanced by insulin. In contrast, PTH influenced glucose transport in a biphasic manner with a stimulatory effect at 1 h and a more potent inhibitory effect at 16 h on basal and insulin-stimulated 2-DOG transport. To explore the mechanism of PTH action, a direct agonist of cAMP-dependent protein kinase (PKA) was tested. 8-Bromo-cAMP had no acute stimulatory effect but inhibited basal and insulin-stimulated 2-DOG transport at 16 h. This result suggested that the prolonged, but not the acute, effect of PTH was mediated by the generation of cAMP. Further studies with the cell line UMR 4-7, a UMR 106-01 clone stably transfected with an inducible mutant inactive regulatory subunit of PKA, confirmed that the inhibitory but not the stimulatory effect of PTH was mediated by the PKA pathway. Northern blot data indicated that the prolonged inhibitory effects of PTH and 8-bromo-cAMP on glucose transport were likely to be mediated in part by reduction in the levels of GLUT1 (HepG2/brain glucose transporter) mRNA.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

A lip burn as a consequence of laser laryngeal surgery.

Ignition and subsequent combustion of a gum guard, during laser surgery for tracheal stenosis, resulted in a superficial burn to the lower lip. We present a case report and discuss measures that can be taken to avoid such a complication.

Adult↗
PubMed1994

Age differences in same-different judgments as a function of multidimensional similarity.

Age deficits in visual search often are attributed to difficulties in comparing display items to target representations. In the presence-absence search paradigm, however, these comparisons are frequently confounded with age differences in the latency and velocity of saccadic eye movements, reductions in the useful field of view (FOV), and retention of information concerning previously searched locations. To circumvent these shortcomings, 20 young and 20 older adults were compared in the speed of their same-different judgments of two perifoveal stimuli. The two stimuli were either identical or varied along one or more of the dimensions of size, shape, and color. In both age groups, RT for correct "different" judgments increased with stimulus similarity, an effect which was more pronounced in the elderly subjects. Results suggest that age differences in free search are due, in part, to an age-related decline in the speed of evaluating object congruence.

Adolescent↗
PubMed1994

Age differences in the useful field of view: an eye movement analysis.

Age differences in the useful field of view (UFOV) were examined by asking younger (mean age = 24 years) and older (mean age = 64 years) observers to search for two oriented line targets. These targets were presented at eccentricities ranging from 4 degrees to 14 degrees, and were embedded in either no distractors, homogeneous distractors, or heterogeneous distractors. Eye movements were recorded, along with reaction time (RT) and accuracy. The eye movement data indicated that older observers had more difficulty locating peripheral targets, particularly when they were embedded in heterogeneous distractors. Furthermore, the greater effects of eccentricity and distractor type found in the RT's of older adults were eliminated when age differences in saccade number were partialled out. These findings suggest that age differences in search are largely attributable to factors other than selective attention.

Adult↗
PubMed1994

Permselectivity in thin membrane nephropathy.

The glomerular permselectivity to polydisperse neutral dextrans was compared in 6 patients with thin membrane nephropathy (TMN) and 10 healthy controls. Despite having normal renal hemodynamics and minimal proteinuria, the patients with TMN had significantly increased fractional clearance of neutral molecules with Stokes radius > 42 A. Conventional theories of glomerular barrier size selectivity cannot fully explain these data since they would predict that our patients would have had nephrotic range proteinuria.

Adult↗
PubMed1994

Hormone-binding properties and glycosylation pattern of a recombinant form of the extracellular domain of the luteinizing hormone/chorionic gonadotropin receptor expressed in mammalian cells.

The present studies were undertaken to characterize the properties of a recombinant truncated rat LH/CG (rLH/CG) receptor representing the extracellular domain (rLHR-t338) expressed in mammalian cells. Using detergent-soluble extracts of stably transfected cells, we show that the binding of ovine (o) LH to the extracellular domain is different from the binding of oLH to the full-length receptor. Thus, whereas the full-length receptor from either rat corpora lutea or stably transfected 293 cells binds oLH with two apparent affinities, rLHR-t338 binds oLH with only one affinity, which is intermediate between the high and low affinities of the full-length receptors. However, rLHR-t338 as well as the full-length receptor binds hCG and hLH with similar high affinities and by a model assuming the presence of only one binding site. These data are consistent with the possibility that the carboxyl-terminal half of the LH/CG receptor may contribute (either directly or indirectly) to a second low affinity hormone-binding site. The truncated receptor retains normal binding specificity, as it does not bind hFSH, demonstrating that the extracellular domain alone contains all of the necessary elements for conferring specificity among the gonadotropin hormones. Our studies also show that rLHR-t338 is glycosylated and migrates as two proteins of 48 and 44 kilodaltons (kDa) on sodium dodecyl sulfate gels (where the 44-kDa species is probably a partially degraded form of the 48-kDa protein). However, the N-linked oligosaccharides of the truncated receptor do not appear to be fully processed, as they remain in a high mannose form. rLHR-t338 is not secreted from cells, but remains trapped intracellularly. It can be detected, though, in detergent-soluble extracts of cells or in homogenates. Upon centrifugation of homogenates, it was found that about 90% of the recoverable truncated receptor can be obtained in the supernatant fraction. Thus, mammalian cells could provide a source of a water-soluble extracellular domain of the LH/CG receptor.

Animals↗
PubMed1992

Treatment of adult Langerhans cell histiocytosis with etoposide.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a reactive disease in which abnormal Langerhans cells accumulate in various body sites and cause damage to affected organs. Adults often do not respond to conventional therapy with local or systemic steroids. OBJECTIVE: Our purpose was to investigate intravenous etoposide as monotherapy in the treatment of adult patients with severe or resistant LCH. METHODS: In an open study, three adult patients with LCH (one with single-system skin disease and two with multisystem disease) were treated with etoposide, 100 mg/m2/day, for 3 days. This was repeated every 3 or 4 weeks for three or four cycles. RESULTS: All patients achieved clinical remission that persisted during a 12- to 14-month follow-up. No serious side effects were noted. CONCLUSION: We recommend the use of etoposide monotherapy in severe or restricted LCH in adults.

Adult↗
PubMed1992

Sucralfate diminishes basal acid output without affecting gastrin, H. pylori or gastritis in duodenal ulcer patients.

Twelve patients with active duodenal ulcer disease and Helicobacter pylori infection were treated with 1 g sucralfate q.d.s. for 1 month. Ulcers healed in 8 of the 12 patients without an alteration in the H. pylori-associated antral gastritis. Sucralfate produced a significant fall in basal acid output in all the patients, from a median of 4.8 (range 2.1-12.1) to 1.6 (0.4-8) mmol/h, P less than 0.01, whereas peak acid output was unchanged from 41 (21-59) before to 38 (24-55) mmol/h after treatment. Basal plasma gastrin concentrations and the meal-stimulated integrated gastrin response were not altered significantly by sucralfate: 8 (2-17) pmol/L and 732 (188-1045) pmol. min/L pre-treatment and 6 (2-17) pmol/L and 600 (140-1302) pmol. min/L post-treatment, respectively. The fall in basal acid output observed may contribute to prolonged duodenal ulcer remission after treatment with sucralfate.

Adult↗
PubMed1992

p53 expression is common in malignant mesothelioma.

The p53 tumour suppressor gene has been shown to be frequently mutated in a wide range of human neoplasms. This is accompanied by increased levels of p53 protein which become immunologically detectable in pathological material. We have investigated the possibility that the differential diagnosis between reactive and neoplastic mesothelium might be resolved using a polyclonal serum raised to human p53 protein, CM-1. None of 20 cases of reactive mesothelial proliferation showed p53 immunoreactivity while 70% (14 of 20) of cases of malignant mesothelioma showed p53 staining. We can thus infer that abnormalities of p53 appear to be a common event in malignant mesothelioma and that p53 immunostaining may be of value in the distinction of malignant mesothelioma from reactive hyperplasia.

Adult↗
PubMed1992

Peripheral nerve sheath differentiation in malignant soft tissue tumours: an ultrastructural and immunohistochemical study.

Thirteen soft tissue sarcomas with ultrastructural evidence of nerve sheath differentiation were investigated by immunohistochemistry. Three arose in a major nerve or nerve trunk and four patients had von Recklinghausen's neurofibromatosis. Ultrastructurally, 10 cases showed variable differentiation towards Schwann cells, two resembled perineurial cells and one tumour had features suggestive of both cell types. Immunostaining for S-100 protein was positive in eight Schwann cell tumours, negative in the other two Schwann cell tumours and negative in those with perineurial-like cells. No cases demonstrated epithelial membrane antigen, so that the existence of perineurial cells in malignant nerve sheath tumours remains immunohistochemically unsubstantiated; it may be that the perineurial-like cells are merely incompletely differentiated Schwann cells, with nerve sheath differentiation manifesting a continuous spectrum. Leu 7 was detected in four Schwann cell tumours, three of which were ultrastructurally well differentiated. Cytokeratin and desmin were demonstrated only in an undifferentiated pleomorphic area of one Schwann cell tumour. Electronmicroscopy can aid diagnosis by revealing nerve sheath differentiation in malignant soft tissue tumours without demonstrable S-100 protein.

Adolescent↗
PubMed1992

Transforming growth factor alpha expression in normal gastric mucosa, intestinal metaplasia, dysplasia and gastric carcinoma--an immunohistochemical study.

Using a monoclonal antibody (GF10) and a standard immunohistochemical technique, immuno-expression of transforming growth factor alpha (TGF-alpha) was found consistently within the differentiated compartment of normal adult human gastric mucosa. In 70% of mucosal samples exhibiting intestinal metaplasia there was more or less uniform TGF-alpha immunoreactivity throughout the intestinalized mucosa. Similarly, 60% of cases of dysplasia and 60% of gastric carcinomas showed strong immunoreactivity in most of the cells. However, whereas 93% of intestinal-type cancers showed strong immunoreactivity only 30% of the diffuse type were stained and then only weakly. Transforming growth factor alpha expression is thus a fairly regular feature of several types of differentiated gastric epithelia (normal, metaplastic, dysplastic and intestinal-type carcinoma), while its relative absence may be a factor in the histogenesis of the diffuse type of gastric carcinoma.

Gastric Mucosa↗