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Biomedical subjects

M L Freeman

Publications and source records attributed to M L Freeman.

117 records · Page 7Linked to original sources
PubMedDate not supplied

Simvastatin, a competitive inhibitor of HMG-CoA reductase, lowers cholesterol saturation index of gallbladder bile.

We tested the possibility that simvastatin, a competitive inhibitor of HMG-CoA reductase related to mevinolin, might alter cholesterol saturation of gallbladder bile. Ten patients with Type IIa or IIb hypercholesterolemia underwent bile sampling before, and again after, treatment with 20 or 40 mg per day simvastatin for 7 to 13 weeks. Mean cholesterol saturation index of gallbladder bile fell from 1.01 to 0.77 during simvastatin treatment (p less than 0.01). This finding strongly suggests that treatment with HMG-CoA reductase inhibitors will not predispose to development of cholesterol gallstones. Indeed, it raises the possibility that such inhibitors might have a future role to play in treatment of gallstones.

Adult↗
PubMedDate not supplied

Strategies in the treatment of diffuse pontine gliomas: the therapeutic role of hyperfractionated radiotherapy and chemotherapy.

This article will review the current treatment of pediatric patients with diffuse pontine gliomas (DPG) and discuss three potential avenues of therapeutic research including (i) radiotherapy (RT) in combination with radiation sensitizers, (ii) dose-intensive, induction chemotherapy with hematopoietic support followed in sequence with RT applied as a "consolidation' therapy, and (iii) the interleafed application of phase-specific chemotherapeutic agents and hyperfractionated external beam radiotherapy (HFEBRT) referred to as "chemoradiotherapy'.

Antineoplastic Agents↗
PubMedDate not supplied

The non-bleeding visible vessel versus the sentinel clot: natural history and risk of rebleeding.

Non-bleeding visible vessel and sentinel clot are terms used interchangeably to describe protuberances in the base of ulcers that have recently bled, but a consensus as to their definition or natural history does not exist. In patients with severe ulcer hemorrhage, non-bleeding protuberances were classified as vessels, with or without a small attached clot, or as sentinel clots, according to a schema based on the appearance of the protuberance at endoscopy but not subjected to pathologic correlation. Endoscopic therapy was not performed at the index endoscopic evaluation, and natural evolution was prospectively documented with daily videoendoscopy. Eleven (46%) of 24 patients with non-bleeding protuberances had rebleeding. Independent classification by three authors concurred in 18 (75%) of 24 lesions. Ten (91%) of 11 vessels with or without attached clot rebled versus 0 (0%) of 7 sentinel clots and 1 (17%) of 6 lesions without unanimous classification (p < 0.01, vessels versus other groups). Rebleeding occurred in 5 (71%) of 7 nonpigmented (pale or white), 6 (38%) of 16 red or purple, and 0 (0%) of 1 black protuberances. In general, vessels persisted until rebleeding, whereas sentinel clots disappeared within 1 to 3 days. We conclude that nonbleeding protuberances in ulcer bases can be separated into vessels, which have a high risk of rebleeding, and sentinel clots, which have a low risk of rebleeding.

Blood Coagulation↗
PubMedDate not supplied

Clinical implications of postsurgical adhesions.

Adhesion development can have a major impact on a patient's subsequent health. Adhesions are a significant source of impaired organ functioning, decreased fertility, bowel obstruction, difficult re-operation, and possibly pain. Consequently, their financial sequelae are also extraordinary, with more than one billion dollars spent in the USA in 1994 on the bowel obstruction component alone. Performing adhesiolysis for pain relief appears efficacious in certain subsets of women. Unfortunately even when lysed, adhesions have a great propensity to reform. Adhesions are prevalent in all surgical fields, and nearly any compartment of the body. For treatment of infertility and recurrent pregnancy loss, lysis of intrauterine adhesions results in improved fecundability and decreased pregnancy loss.

Adult↗
PubMedDate not supplied

Synthesis of heat shock proteins following oxidative challenge: role of glutathione.

The relationship between glutathione metabolism, menadione sodium bisulphite oxidation of protein thiols, and the synthesis of hsc70 was investigated using CHO cells. A 30-min/37 degrees C exposure to menadione, a compound which redox cycles to produce superoxide anion radicals and hydrogen peroxide, resulted in rapid accumulation of hsc70 mRNA. PAGE and Western blot analysis indicated increased synthesis such that accumulation of hsc70 occurred. These changes were preceded by rapid oxidation of GSH to GSSG, followed by GSH depletion, and subsequent protein thiol oxidation. As a test of whether a correlation existed between GSH oxidation and depletion, protein thiol oxidation and hsp synthesis, cells were exposed to menadione in the absence and presence of glucose. Synthesis of hsc70 was increased in cells exposed to menadione in the absence of glucose compared with its presence. As a further test, cells were exposed to BSO/DEM in order to deplete GSH and then exposed to menadione. The synthesis of hsc70 following exposure to menadione was greatly increased in GSH-depleted cells compared with GSH-replete cells. Experiments were conducted to determine if electroporation of cells in GSSG containing buffer affected hsp synthesis. Electroporation in glucose-free buffer containing 3 mM GSSG did not affect hsp synthesis. We interpret these results to indicate that the inability to maintain glutathione in a reduced form during menadione redox cycling resulted in protein thiol oxidation. This, in turn, resulted in accumulation of hsc70 mRNA with a subsequent increase in the synthesis of hsc70.

Animals↗
PubMedDate not supplied

PEST sequences in proteins involved in cyclic nucleotide signalling pathways.

There is growing evidence that PEST sequences act as proteolytic recognition signals within polypeptides. PEST sequences are rich in proline (P), glutamic acid (E), serine (S), and threonine (T) and can be identified by the PEST-FIND program. Both the catalytic and regulatory subunits of the cAMP-dependent protein kinase have been shown to have conditional PEST sequences which are exposed upon cAMP binding to the enzyme. cAMP binding leads to rapid dissociation of C- and R-subunits, and both subunits have increased sensitivity to proteolysis. It is not known whether other proteins that participate in the cyclic nucleotide signalling pathway have PEST regions in their amino acid sequences. Therefore, we have screened amino acid sequences of proteins that are directly involved in cyclic nucleotide cascade, including cGMP-dependent protein kinases, anchoring proteins for cAMP-dependent protein kinase, cyclic nucleotide-gated ion channels, and cyclic nucleotide phosphodiesterases, for PEST sequences using the PEST-FIND program. Many PEST sequences with high scores have been identified in these proteins. The occurrence of the PEST sequences is very high in proteins involved in cyclic nucleotide signalling pathways (approximately 80%). This value is much higher than the percentage (10%) of PEST sequences that can be found in the primary structures of the proteins listed in the data bank. This frequent occurrence of PEST sequences in proteins involved in cyclic nucleotide action and metabolism suggests an important role of proteolysis of these key proteins of signal transduction.

Adenylyl Cyclases↗