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M Lewitt

Publications and source records attributed to M Lewitt.

5 recordsLinked to original sources
PubMed2005

Insulin-like growth factor-I receptor activity is essential for Kaposi's sarcoma growth and survival.

Kaposi's sarcoma (KS) is a highly vascular tumour and is the most common neoplasm associated with human immunodeficiency virus (HIV-1) infection. Growth factors, in particular vascular endothelial growth factor (VEGF), have been shown to play an important role in its development. The role of insulin-like growth factors (IGFs) in the pathophysiology of different tumours led us to evaluate the role of IGF system in KS. The IGF-I receptors (IGF-IR) were identified by immunohistochemistry in biopsies taken from patients with different AIDS/HIV-related KS stages and on KSIMM cells (an established KS-derived cell line). Insulin-like growth factor-I is a growth factor for KSIMM cells with a maximum increase of 3H-thymidine incorporation of 130 +/- 27.6% (P < 0.05) similar to that induced by VEGF and with which it is additive (281 +/- 13%) (P < 0.05). Moreover, specific blockade of the receptor (either by alpha IR3 antibody or by picropodophyllin, a recently described selective IGF-IR tyrosine phosphorylation inhibitor) induced KSIMM apoptosis, suggesting that IGF-IR agonists (IGF-I and -II) mediate antiapoptotic signals for these cells. We were able to identify an autocrine loop essential for KSIMM cell survival in which IGF-II is the IGF-IR agonist secreted by the cells. In conclusion, IGF-I pathway inhibition is a promising therapeutical approach for KS tumours.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Effect of protein intake on plasma and erythrocyte free amino acids and serum IGF-I and IGFBP-1 levels in rats.

Amino acid (AA) levels in plasma and erythrocytes (RBC) were determined in rats (n = 29) fed diets with 6, 21, and 35% protein, and their association with insulin-like growth factor I (IGF-I), insulin, or IGF-binding protein (IGFBP)-1 levels was studied. Free AA in plasma and RBC were determined by reversed-phase high-pressure liquid chromotography, and IGF-I, IGFBP-1, and insulin plasma levels were determined by RIA. Rats fed the low-protein (6%) diet were growth-retarded and had lower serum IGF-I levels and higher serum IGFBP-1 levels than the other two groups (P < 0.0001). In rats fed the low-protein diet, most of the nonessential AA (NEAA) in both plasma and RBC increased, whereas the essential AA (EAA), with the exception of threonine, decreased. When the groups were combined, both RBC and plasma EAA-to-NEAA ratios were positively correlated to IGF-I (r = 0.76 and 0.80, respectively; P < 0.0001) and inversely correlated to IGFBP-1 levels (r = -0.67, P < 0.001 and r = -0.78, P < 0.0001, respectively). A significant inverse correlation was found between RBC glutamate and IGF-I (r = -0.85, P < 0.0001, n = 25) and insulin (r = -0.72, P < 0.001, n = 21), and a positive correlation was found for IGFBP-1 (r = 0.78, P < 0.0001, n = 24). In multiple regression analysis, only IGF-I remained as an independent variable. Threonine was the only EAA with a significant inverse correlation to insulin (r = -0.66, P < 0.001). We hypothesize that AA metabolism is associated to changes in IGF-I, insulin, and IGFBP-1 levels in rats on different protein intakes.

Aging↗
PubMed1996

Experimental hydranencephaly in the ovine fetus.

Hydranencephaly is defined as the replacement of a previously normal brain, in whole or in part, by membranous fluid-filled sacs. The etiology is not well understood, and the time course of development is unknown. Fifteen ovine fetuses were chronically cannulated and had both carotid arteries ligated at 100 days of gestation (term is 145-150 days). They were killed at 1 (n = 4), 2 (n = 6) and 4 (n = 5) weeks post-surgery, and the findings compared with those of 25 age-matched controls. By 2 weeks post-surgery the entire cerebral hemispheres and diencephalon had been replaced by fluid closely resembling cerebrospinal fluid. The choroid plexus, pituitary and brain stem remained outwardly normal, but the cerebellum showed signs of damage. Fetuses maintained normal values for blood gases and hematocrit up to 4 weeks post-surgery, and grew normally. Light microscopy of the brain stem showed significant losses of cell populations in the medulla by 4 weeks. Vascular casting and acute blood flow studies in an additional group of fetuses showed that the entire brain was perfused via the vertebral-occipital anastomosis immediately after acute bilateral carotid clamping, but that the blood flow rate was insufficient to maintain adequate oxygen delivery.

Animals↗
PubMed1983

Inhibition of pepsin by analogues of pepsinogen-(1-12)-peptide with substitutions in the 4-7 sequence region.

Derivatives of the 1-12 sequence of pig pepsinogen were prepared by solid-phase peptide synthesis. The three derivatives contain substitutions in the 4-7 region of the 1-12 sequence. Glycine was used to replace the hydrophobic residues -Val-Pro-Leu-Val- in pairs. After cleavage and purification, the synthetic peptides were compared with a synthetic peptide of the native sequence, prepared at the same time, with respect to their ability to inhibit the pepsin-catalysed clotting of milk. Inhibitory potency, determined from plots of percentage inhibition versus concentration of synthetic peptide, is inversely correlated with the substitution of glycine residues for the hydrophobic residues. Therefore the equilibrium inhibition of pepsin by these peptides is dominated by the hydrophobic nature of the 4-7 sequence region.

Amino Acids↗