Biomedical subjects

M Thomas

Publications and source records attributed to M Thomas.

At least 163 records · Page 9Linked to original sources

PubMed2001

A key role for Pax7 transcripts in determination of muscle and nerve cells.

Embryonic teratocarcinoma mouse cells (P19) and embryonic NIH3T3 fibroblasts were induced chemically to differentiate along neurogenic or myogenic lineages. The expression profiles of Pax7 alternate transcripts were then assessed by RNA isolation and RT-PCR. Only two transcripts, Pax7b and Pax7d, were expressed in the neurogenic lineage. By contrast, in adult skeletal muscle, four transcripts, Pax7a-d, were expressed in the myogenic lineage. Moreover, P19 cells were shown to undergo neural cell differentiation when stably transfected with a single Pax7 transcript, PAX7b, generated from human skeletal muscle. Our results suggest a key role for Pax7 transcripts in lineage determination.

Animals↗

PubMed2001

Effects of ceramide on aggrecanase activity in rabbit articular cartilage.

Ceramide participates in signal transduction of IL-1 and TNF, two cytokines likely involved in cartilage degradation in osteoarthritis. We previously showed that ceramide stimulates proteoglycan degradation, mRNA expression of matrix metalloproteinase (MMP)-1, -3, and -13, and pro-MMP-3 production in rabbit cartilage. Since aggrecan, the main cartilage proteoglycan, can be cleaved by metalloproteinases both of MMP and aggrecanase type, the aim of this study was to determine if ceramide stimulates aggrecanase action and, if that is the case, in which measure aggrecanase mediates the degradative effect of ceramide. To this end, antibodies were used against the C terminal aggrecan neoepitopes generated by aggrecanases (NITEGE(373)) and MMPs (DIPEN(341)). Ceramide C(2) at 10(-5) to 10(-4) M dose-dependently increased NITEGE signal, without changing that of DIPEN, in cultured explants of rabbit cartilage. The effects of 10(-4) M C(2) on NITEGE signal and proteoglycan degradation were similarly antagonized by the metalloproteinase inhibitor batimastat, with return to the basal level at 10(-6) M. These results show that, similarly to IL-1 and TNF, ceramide-induced aggrecan degradation is mainly due to aggrecanases. That no increase of MMP activity was detected, despite stimulation of MMP expression, was probably due to lack of proenzyme conversion to mature form, since addition of a MMP activator to C(2)-treated cartilage increased both DIPEN signal and proteoglycan degradation. These findings support the hypothesis that cytokine-induced ceramide could play a mediatory role in situations of increased degradation of cartilage matrix.

Aggrecans↗

PubMed2001

Contrasting roles of p57(KIP2) and p21(WAF1/CIP1/SDI1) in transplanted human and bovine adrenocortical cells.

Cell transplantation provides a way to compare the regulation of cell proliferation in the same cell type in cell culture and in a vascularized tissue structure in a host animal. The cyclin-dependent kinase inhibitors p57(KIP2), p21(WAF1/CIP1/SDI1) and p27(KIP1) have been extensively studied in cell culture but their role in growth control in tissues is less well understood. In the present experiments we compared the behavior of cell cycle inhibitors in human and bovine adrenocortical cells in culture and following cell transplantation in scid mice. p57 was expressed in the majority of cells in the intact human adrenal cortex. However, double immunofluorescence showed that cells that are in the cell cycle are p57(-) adrenocortical cells, p57 and p27 levels were not affected by inhibition of growth at high cell density, whereas p21 was higher in dividing than growth-inhibited cells. However, p21 was also high in senescent adrenocortical cells. After transplantation of human adrenocortical cells in scid mice, p57 and p27 were observed in most cells in the transplant tissue. Over time the number of p21(+) cells decreased greatly in human adrenocortical cells, but not in bovine adrenocortical cells. This difference correlated with lower levels of cell division (assessed by Ki-67 or incorporation of bromodeoxyuridine) in the human cells in transplant tissues in comparison to bovine cells. The differences between human and bovine cells were observed both when cells were transplanted beneath the kidney capsule and when cells were injected subcutaneously in collagen gel. We conclude that the behavior of p57, but not p21, is consistent with a role as a physiological mediator of proliferative quiescence in the adrenal cortex. The high level of p21 in dividing adrenocortical cells in culture, and in bovine adrenocortical cells in transplant tissues, may be a response to conflicting positive and negative growth influences. Cells may enter the cell cycle under the influence of a strong positive mitogenic signal, but coexisting negative growth stimuli trigger a p21-dependent block to further progression through the cell cycle. This model suggests that bovine adrenocortical cells respond to positive growth stimuli in transplant tissues but human cells lack this response.

Adolescent↗

PubMed2001

Prevalence of dysfunctional breathing in patients treated for asthma in primary care: cross sectional survey.

OBJECTIVES: To estimate the prevalence of dysfunctional breathing in adults with asthma treated in the community. DESIGN: Postal questionnaire survey using Nijmegen questionnaire. SETTING: One general practice with 7033 patients. PARTICIPANTS: All adult patients aged 17-65 with diagnosed asthma who were receiving treatment. MAIN OUTCOME MEASURE: Score >/=23 on Nijmegen questionnaire. RESULTS: 227/307 patients returned completed questionnaires; 219 (71.3%) questionnaires were suitable for analysis. 63 participants scored >/=23. Those scoring >/=23 were more likely to be female than male (46/132 (35%) v 17/87 (20%), P=0.016) and were younger (mean (SD) age 44.8 (14.7) v 49.0 (13.8, (P=0.05). Patients at different treatment steps of the British Thoracic Society asthma guidelines were affected equally. CONCLUSIONS: About a third of women and a fifth of men had scores suggestive of dysfunctional breathing. Although further studies are needed to confirm the validity of this screening tool and these findings, these prevalences suggest scope for therapeutic intervention and may explain the anecdotal success of the Buteyko method of treating asthma.

Adolescent↗

PubMed2001

Applications of in vivo electron paramagnetic resonance (EPR) spectroscopy: measurements of pO2 and NO in endotoxin shock.

Recent developments of EPR instrumentation that allow the use of large tissue samples or whole animals and the ability to image spatially resolved EPR signals has led to novel applications of EPR spectroscopy in vivo. Utilising a 1 GHz EPR spectrometer with a 3.4-cm birdcage resonator, it was possible to detect and measure nitric oxide and oxygen in the livers of mice with lipopolysaccharide (LPS)-induced septic shock. Nitric oxide was detected as the nitric oxide (NO) complex of Fe-diethyldithiocarbamic acid (Fe-DETC) while pO2 was measured from the EPR linewidth of the oxygen-sensitive coal material 'gloxy'. LPS treatment stimulated the production of nitric oxide in the liver and the general circulation and the oxygenation of liver tissue was decreased. Selective placement of the EPR probes allowed images of nitric oxide and oxygen to be obtained in the liver. The spectral and spatial information obtained with this technique will allow improved understanding of the pathophysiology of such diseases.

Animals↗

PubMed2001

[Rapid regression of prolonged pagophagia after treatment of iron deficiency].

BACKGROUND: Pica is an eating disorder characterized by the irrepressible and elective craving for food and non-food substances. Pagophagia is a particular form characterized by an ingestion of ice, often associated with iron deficiency. We report a case of intense and prolonged pagophagia. We also analyse literature about the nature of the link between pica and iron deficiency. CASE REPORT: A forty-two year old woman was admitted for severe anaemia secondary to iron deficiency possibly related to chronic gynaecological bleeding. A diet investigation revealed a pagophagia of about eighty ice cubes per day developing over five years. Iron supplement corrected the anaemia and the pagophagia disappeared in less than fifteen days without recurrence in the following year. CONCLUSION: The disappearance of pagophagia after the correction of iron deficiency supports the theory that pagophagia could well be a symptom of iron deficiency.

Adult↗

PubMed2001

[Perception of pica and its relationship with iron deficiency by hospital physicians in the Paris area].

OBJECTIVES: To ascertain the attitude of hospital physicians in the Paris area concerning pica and its relation to iron deficiency and to compare findings with data in the literature. METHODS: An anonymous questionnaire was sent to 174 department heads of specialty units caring for iron deficiency patients: internal medicine (n = 56), hepatogastroenterology (n = 39), hematology (n = 13), gynecology and obstetrics (n = 34), pediatrics (n = 32). RESULTS: The overall response rate was 40.2%. Ninety-seven percent of all the physicians found pica in less than 10% of patients with iron deficiency, and 95.6% considered geophagia as the most frequent pica. For 58.5% of the adult medicine practitioners, pica was regarded only as a cause of iron deficiency, but for 64.7% of the pediatricians, pica was both a cause and a symptom of iron deficiency was not sought in a systemic way in 88.6% of the physicians when a cause of iron deficiency was known. CONCLUSION: In the majority of the cases, the attitude of hospital physicians concerning pica is in disagreement with published data, suggesting either epidemiological characteristics specific to the Paris area, or unawareness of the phenomenon.

Adult↗

PubMed2001

Endoluminal beta-radiation therapy for the prevention of coronary restenosis after balloon angioplasty. The Dose-Finding Study Group.

BACKGROUND: Beta radiation is effective in reducing vascular neointimal proliferation in animals after injury caused by balloon angioplasty. However, the lowest dose that can prevent restenosis after coronary angioplasty has yet to be determined. METHODS: After successful balloon angioplasty of a previously untreated coronary stenosis, 181 patients were randomly assigned to receive 9, 12, 15, or 18 Gy of radiation delivered by a centered yttrium-90 source. Adjunctive stenting was required in 28 percent of the patients. The primary end point was the minimal luminal diameter six months after treatment, as a function of the delivered dose of radiation. RESULTS: At the time of follow-up coronary angiography, the mean minimal luminal diameter was 1.67 mm in the 9-Gy group, 1.76 mm in the 12-Gy group, 1.83 mm in the 15-Gy group, and 1.97 mm in the 18-Gy group (P=0.06 for the comparison of 9 Gy with 18 Gy), resulting in restenosis rates of 29 percent, 21 percent, 16 percent, and 15 percent, respectively (P=0.14 for the comparison of 9 Gy with 18 Gy). At that time, 86 percent of the patients had had no serious cardiac events. In 130 patients treated with balloon angioplasty alone, restenosis rates were 28 percent, 17 percent, 16 percent, and 4 percent, respectively (P=0.02 for the comparison of 9 Gy with 18 Gy). Among these patients, there was a dose-dependent enlargement of the lumen in 28 percent, 50 percent, 45 percent, and 74 percent of patients, respectively (P<0.001 for the comparison of 9 Gy with 18 Gy). The rate of repeated revascularization was 18 percent with 9 Gy and 6 percent with 18 Gy (P=0.26). CONCLUSIONS: Intracoronary beta radiation therapy produces a significant dose-dependent decrease in the rate of restenosis after angioplasty. An 18-Gy dose not only prevents the renarrowing of the lumen typically observed after successful balloon angioplasty, but actually induces luminal enlargement.

Aged↗

PubMed2001

Cyclin E is the only cyclin-dependent kinase 2-associated cyclin that predicts metastasis and survival in early stage non-small cell lung cancer.

Progression through G1-S transition and S phase of the cell cycle is mediated by cyclin-dependent kinase 2 (cdk2), which interacts with several cyclins. Two of these, cyclin E and cyclin A2 (also known as cyclin A), are overexpressed in many cancers. Cyclin E2 and cyclin A1 are recently discovered cdk2-interacting cyclins that are found in malignant tumor cell lines and in acute myeloid leukemia, respectively. Expression and prognostic role of these cyclins in solid tumors is unknown. Here, we have analyzed expression and prognostic relevance of the cdk2-associated cyclins in non-small cell lung cancer (NSCLC). Fresh-frozen biopsies (n = 70) from completely resected tumors with stage I to IIIA NSCLC were studied. Gene expression was analyzed by quantitative real-time reverse transcription-PCR. Expression levels of cyclin E (P = 0.04) and cyclin A2 (P = 0.004) were significantly higher in the tumor samples than in normal controls. Cyclin A1, cyclin A2, and cyclin E2 expression levels did not have prognostic relevance for survival. The mean survival time associated with low and high levels of cyclin E was 69.4 and 47.2 months, respectively, which was statistically significant (P = 0.03). Differences in survival were particularly pronounced in stages I and II. Cyclin E was also closely associated with the development of distant metastasis (P = 0.01). Finally, we confirmed by immunohistochemistry analyses that cyclin E mRNA expression was closely associated with cyclin E protein expression. In conclusion, cyclin E is a strong independent prognostic indicator in patients with early-stage NSCLC, whereas cyclin E2, cyclin A1, and cyclin A2 do not have a prognostic role in NSCLC.

Adult↗

PubMed2001

The measurement of beclomethasone dipropionate entrapment in liposomes: a comparison of a microscope and an HPLC method.

The purpose of this study was to examine the methodologies that may be used to estimate the maximum incorporation (<5 mole% drug) of beclomethasone dipropionate (BDP) in dipalmitoylphosphatidylcholine (DPPC) multilamellar liposomes. Two approaches are described. First, differential interference contrast (DIC) microscopy and cross-polarisation microscopy have been used to measure the concentration at which BDP crystals become apparent in BDP-containing liposome preparations, thereby allowing a semi-quantitative but simple estimation of entrapment. An alternative method is described whereby the unentrapped solid drug is separated from the liposomes via suspension in D2O, followed by centrifugation and HPLC analysis. The method resulted in an estimate of 1.5-2 mole% BDP, while the HPLC method yielded a value of 2.52 mole% BDP.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2001

Single-nucleotide polymorphism alleles in the insulin receptor gene are associated with typical migraine.

We have identified a migraine locus on chromosome 19p13.3/2 using linkage and association analysis. We isolated 48 single-nucleotide polymorphisms within the locus, of which we genotyped 24 in a Caucasian population comprising 827 unrelated cases and 765 controls. Five single-nucleotide polymorphisms within the insulin receptor gene showed significant association with migraine. This association was independently replicated in a case-control population collected separately. We used experiments with insulin receptor RNA and protein to investigate functionality for the migraine-associated single-nucleotide polymorphisms. We suggest possible functions for the insulin receptor in migraine pathogenesis.

Alleles↗

PubMed2001

Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease.

There is substantial evidence for bioenergetic defects in Huntington's disease (HD). Creatine administration increases brain phosphocreatine levels and it stabilizes the mitochondrial permeability transition. We examined the effects of creatine administration in a transgenic mouse model of HD produced by 82 polyglutamine repeats in a 171 amino acid N-terminal fragment of huntingtin (N171-82Q). Dietary supplementation of 2% creatine significantly improved survival, slowed the development of motor symptoms, and delayed the onset of weight loss. Creatine lessened brain atrophy and the formation of intranuclear inclusions, attenuated reductions in striatal N-acetylaspartate as assessed by NMR spectroscopy, and delayed the development of hyperglycemia. These results are similar to those observed using dietary creatine supplementation in the R6/2 transgenic mouse model of HD and provide further evidence that creatine may exert therapeutic effects in HD.

Animals↗

PubMed2001

Chronic myeloid leukemia presenting as gout.

A 53-year-old man presented with gouty arthritis. A physical examination and haematological and biochemical tests showed that he had chronic myeloid leukemia. He was treated with allopurinol, hydroxyurea and analgesics. The arthritis subsided completely within 2 weeks. He continues in haematologic remission (on interferon) with no further recurrence of the gout.

Arthritis, Gouty↗

PubMed2001

[Basic principles of medical assessment of the locomotor system].

Rendering a medical expert opinion on the musculoskeletal system is an extraordinary responsibility. Nearly all physicians are confronted with this medical task in their daily clinical practice. Difficulties encountered and misjudgments made in formulating an expert opinion are certainly primarily a result of insufficient knowledge of the sociomedical basis. Proper organization and compliance with a standardized structure are especially important for an expert opinion. Intensified teaching of the principles and importance of the medical expert opinion during medical training will not only result in optimization and acceleration of the sociomedical procedures, it will also awaken pleasure in this many-sided activity.

Disability Evaluation↗

PubMed2001

A novel postsynaptic density protein: the monocarboxylate transporter MCT2 is co-localized with delta-glutamate receptors in postsynaptic densities of parallel fiber-Purkinje cell synapses.

Confocal immunofluorescence microscopy showed strong monocarboxylate transporter 2 (MCT2) labeling of Purkinje cell bodies and punctate labeling in the molecular layer. By immunogold cytochemistry, it could be demonstrated that the MCT2 immunosignal was concentrated at postsynaptic densities of parallel fiber-Purkinje cell synapses. The distribution of MCT2 transporters within the individual postsynaptic densities mimicked that of the delta2 glutamate receptor, as shown by use of two different gold-particle sizes. The MCT2 distribution was also compared with the distributions of other monocarboxylate transporters (MCT1 and MCT4). The MCT1 immunolabeling was localized in the endothelial cells, while MCT4 immunogold particles were associated with glial profiles, including those abutting the synaptic cleft of the parallel fiber-spine synapses. The postsynaptic density (PSD) molecules identified so far can be divided into five classes: receptors, their anchoring molecules, molecules involved in signal transduction, ion channels, and attachment proteins. Here, we provide evidence that this list of molecules must now be extended to comprise an organic molecule transporter: the monocarboxylate transporter MCT2. The present data suggest that MCT2 has specific transport functions related to the synaptic cleft and that this transporter may allow an influx of lactate derived from perisynaptic glial processes. The expression of MCT2 in synaptic membranes may allow energy supply to be tuned to the excitatory drive.

Animals↗

PubMed2001

A new approach for detecting and mapping sewage impacts.

Increased nitrogen loading has been implicated in eutrophication occurrences worldwide. Much of this loading is attributable to the growing human population along the world's coastlines. A significant component of this nitrogen input is from sewage effluent, and delineation of the distribution and biological impact of sewage-derived nitrogen is becoming increasingly important. Here, we show a technique that identifies the source, extent and fate of biologically available sewage nitrogen in coastal marine ecosystems. This method is based on the uptake of sewage nitrogen by marine plants and subsequent analysis of the sewage signature (elevated delta 15N) in plant tissues. Spatial analysis is used to create maps of delta 15N and establish coefficient of variation estimates of the mapped values. We show elevated delta 15N levels in marine plants near sewage outfalls in Moreton Bay, Australia, a semi-enclosed bay receiving multiple sewage inputs. These maps of sewage nitrogen distribution are being used to direct nutrient reduction strategies in the region and will assist in monitoring the effectiveness of environmental protection measures.

Environment↗

PubMed2001

Therapy of localized non-small cell lung cancer (take home messages).

Surgery remains the mainstay in curative therapy of stage I and II NSCLC and selected patients with stage III disease. The high rate of distant metastases occurring in patients after complete surgical resection demonstrates the need for effective adjuvant systemic therapy. However, outside of trials, (neo)adjuvant chemotherapy is currently not considered as an established standard in localized NSCLC. Postoperative radiotherapy increases local tumor control in completely resected N2 disease and after R1/R2 resections and is generally recommended in these situations. In inoperable patients radiotherapy offers the only chance of cure. Combined radiochemotherapy and the highly accelerated CHART radiotherapy have been shown to be superior to standard radiotherapy. Progress in the treatment of localized NSCLC over the last decades has been only modest and with the exception of favourable subgroups, prognosis of NSCLC remains grim. In the light of the high rate of local and distant metastases multidisciplinary approaches appear necessary in the vast majority of patients.

Antineoplastic Agents↗

PubMed2001

Development of treatment strategies in locally advanced non-small cell lung cancer (take home messages).

In the last decade combined modality treatment approaches contributed to the progress of therapy in locally advanced non-small cell lung cancer. With this management strategies younger patients (<70 years) with locally advanced disease and a good performance status (ECOG 0,1) have survival benefits compared to sole locoregional treatment. Further development of these treatment concepts is warranted. To adopt optimal tailored therapy to prognostic consistent patient groups exact staging of disease is mandatory. Moreover, refinements of the staging system would be helpful to identify in defined anatomical stages, patient subgroups who will benefit from systemic treatment options different from chemotherapy (i.e. tyrosine kinase-inhibition of the epidermal growth factor receptor family, anti-angiogenic treatment). The current status of developing treatment strategies in locally advanced non-small cell lung cancer is discussed.

Carcinoma, Non-Small-Cell Lung↗