PubMed Health⌕ Search

Biomedical subjects

R Simpson

Publications and source records attributed to R Simpson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Substituted tetrahydropyrrolo[2,1-b]oxazol-5(6H)-ones and tetrahydropyrrolo[2,1-b]thiazol-5(6H)-ones as hypoglycemic agents.

A series of substituted tetrahydropyrrolo[2,1-b]oxazol-5(6H)-ones and tetrahydropyrrolo[2,1-b]thiazol-5(6H)-ones was synthesized from amino alcohols or amino thiols and keto acids. A pharmacological model based on the results obtained with these compounds led to the synthesis and evaluation of a series of isoxazoles and other monocyclic compounds. These were evaluated for their ability to enhance glucose utilization in cultured L6 myocytes. The in vivo hypoglycemic efficacy and potency of these compounds were evaluated in a model of type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus), the ob/ob mouse. 25a(2S) (SDZ PGU 693) was selected for further pharmacological studies.

Animals↗
PubMed1998

STAT3 forms stable homodimers in the presence of divalent cations prior to activation.

We present evidence that the transcription factor STAT3, derived from uninduced cells, can form stable homodimers, which are independent of the tyrosine phosphorylation status of the protein. The strong interaction, which is resistant to many denaturing agents, is dependent on the presence of divalent cations. The presence of the homodimer was initially observed in immunoprecipitates of STAT3 and was detected upon fractionation of cell lysates. These dimers are different in structure from dimers observed after cytokine stimulation of cells, which results in tyrosine phosphorylation of STAT3 and dimerization involving the SH2 domain of STAT3.

Cations, Divalent↗
PubMed1998

Comparison of indomethacin and nimesulide, a selective cyclooxygenase-2 inhibitor, on key pathophysiologic steps in the pathogenesis of nonsteroidal anti-inflammatory drug enteropathy in the rat.

BACKGROUND: The predicted gastrointestinal tolerability of specific cyclooxygenase-2 inhibitors could be due to either a lack of 'topical' irritation and/or lack of effect on cyclooxygenase-1. METHODS: Key pathophysiologic steps (in vitro and in vivo uncoupling, intestinal prostanoid levels (prostaglandin E, thromboxane B2, and 6-keto-prostaglandin F1alpha), intestinal permeability (51Cr-ethylenediaminetetraacetic acid), inflammation (faecal excretion of a granulocyte marker protein), and ulcer counts) in enteropathy induced by nonsteroidal anti-inflammatory drugs were assessed after administration of indomethacin, 10 mg/kg, and 15 (roughly equipotent), 30, and 60 mg/kg of the preferential cyclooxygenase-2 inhibitor nimesulide. RESULTS: Indomethacin uncoupled oxidative phosphorylation at lower concentrations than nimesulide in vitro. Indomethacin was associated with electron microscopy changes suggestive of uncoupling in 60%-70% of enterocytes examined, whereas nimesulide affected 10%-30% of enterocytes, depending on the dose. Indomethacin increased intestinal permeability and caused inflammation and ulcers with 71%-96% reductions in prostanoid levels. Nimesulide at 15 mg/kg caused no damage, whereas 30 and 60 mg/kg nimesulide were associated with significant decreases in mucosal prostanoids (46%-75%), but only the 60-mg/kg dose caused a transient increase in intestinal permeability. However, at none of the doses did nimesulide cause intestinal inflammation or ulcers. CONCLUSIONS: These results endorse the idea that selective cyclooxygenase-2 inhibitors may be associated with some gastrointestinal tolerance due to their selectivity for cyclooxygenase-2, inhibiting cyclooxygenase-1 at only very high doses, and reduced topical irritation.

Animals↗
PubMed1998

Effect of temperature on the optical properties of ex vivo human dermis and subdermis.

The effect of temperature on the optical properties of human dermis and subdermis as a function of near-infrared wavelength has been studied between 25 degrees C and 40 degrees C. Measurements were performed ex vivo on a total of nine skin samples taken from the abdomen of three individuals. The results show a reproducible effect of temperature on the transport scattering coefficient of dermis and subdermis. The relative change of the transport scattering coefficient showed an increase for dermis ((4.7+/-0.5) x 10(-3) degrees C(-1)) and a decrease for subdermis ((-1.4+/-0.28) x 10(-3) degrees C(-1)). Note that the magnitude of the temperature coefficient of scattering was greater for dermis than subdermis. A reproducible effect of temperature on the absorption coefficient could not be found within experimental errors. System reproducibility in transport scattering coefficient with repeated removal and repositioning of the same tissue sample at the same temperature was excellent at +/-0.35% for all measurements. This reproducibility enabled such small changes in scattering coefficient to be detected.

Biophysical Phenomena↗
PubMed1998

Molecular cloning reveals that the p160 Myb-binding protein is a novel, predominantly nucleolar protein which may play a role in transactivation by Myb.

We have previously detected two related murine nuclear proteins, p160 and p67, that can bind to the leucine zipper motif within the negative regulatory domain of the Myb transcription factor. We now describe the molecular cloning of cDNA corresponding to murine p160. The P160 gene is located on mouse chromosome 11, and related sequences are found on chromosomes 1 and 12. The predicted p160 protein is novel, and in agreement with previous studies, we find that the corresponding 4.5-kb mRNA is ubiquitously expressed. We showed that p67 is an N-terminal fragment of p160 which is generated by proteolytic cleavage in certain cell types. The protein encoded by the cloned p160 cDNA and an engineered protein (p67*) comprising the amino-terminal region of p160 exhibit binding specificities for the Myb and Jun leucine zipper regions identical to those of endogenous p160 and p67, respectively. This implies that the Myb-binding site of p160 lies within the N-terminal 580 residues and that the Jun-binding site is C-terminal to this position. Moreover, we show that p67* but not p160 can inhibit transactivation by Myb. Unexpectedly, immunofluorescence studies show that p160 is localized predominantly in the nucleolus. The implications of these results for possible functions of p160 are discussed.

3T3 Cells↗
PubMed1998

About information systems.

Who should be involved when introducing a new information system? How will the budget be used? In this column, experts offer suggestions.

Budgets↗
PubMed1997

Pulmonary resection for metastatic breast cancer.

BACKGROUND: A patient with a solitary pulmonary metastasis who had breast cancer in the past may benefit from pulmonary resection. METHODS: Between 1984 and 1996, 17 patients underwent metastatectomy for metastatic breast cancer. There were 15 females and two males whose average age was 59 (range: 40-74 years). The median tumour-free interval after the primary breast-cancer operation was 5.1 years (range: 8 months-18.2 years). Sixteen patients had complete resections, which included six lobectomies and 10 lesser resections. RESULTS: The postoperative mortality was nil and the morbidity rate was 6%. Follow-up was complete in all patients. Recurrent disease developed in four patients and two patients died of their disease. The 5-year survival was 62%. CONCLUSION: An aggressive surgical approach is warranted in patients with isolated resectable pulmonary metastases from breast cancer.

Adult↗