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Biomedical subjects

H Kleinman

Publications and source records attributed to H Kleinman.

14 recordsLinked to original sources

Superradiant and stimulated superradiant emission in a prebunched beam free-electron maser.

An electron beam, prebunched at the synchronous free-electron laser frequency and passing through a magnetic undulator, emits coherent (superradiant) synchrotron undulator radiation at the bunching frequency. If an external electromagnetic wave is introduced into the interaction region, at the same frequency and at a proper phase, the radiation process will be stimulated (stimulated prebunched beam radiation). We report first experimental measurements of stimulated superradiant emission in a prebunched free-electron maser. Measurements are in good agreement with theory.

Journal Article↗

Thymosin beta4 enhances endothelial cell differentiation and angiogenesis.

When human umbilical vein endothelial cells (HUVEC) differentiate into capillary-like tubes, there is a five-fold upregulation of the mRNA for thymosin beta4 (Tbeta4) (Grant et al. J Cell Sci 1995; 108: 3685-94 [1]) and this endogenous expression plays an important role in endothelial cell attachment to and spreading on matrix components. We now show that exogenous addition of thymosin beta4 (in the ng-microg range) to HUVEC in culture can induce several biological responses. These responses include increased tube formation in vitro. Additionally, exogenous thymosin beta4 enhances vascular sprouting in the coronary artery ring angiogenesis assay. Measurements of these vascular sprouts show a doubling of the vessel area (via increased branching) with as little as 100 ng of synthetic thymosin beta4. These processes appear to involve the binding of thymosin beta4 to an unknown cell surface receptor and internalization of the protein. This cell surface-binding appears not to be mediated through the thymosin beta4-actin binding domain LKTET. An increase in thymosin beta4 cytoplasmic staining in HUVEC exposed 10 microg of the peptide appears to occur without increased mRNA translation. In summary Tbeta4 induces an increase in cell-matrix attachment, proliferation, tube formation, internalization of the peptide and rearrangement of the actin cytoskeleton. The data now defines both an autocrine and paracrine role for thymosin beta4 in vessel formation.

Journal Article↗

A new nomenclature for the laminins.

The authors have adopted a new nomenclature for the laminins. They are numbered with arabic numerals in the order discovered. The previous A, B1 and B2 chains, and their isoforms, are alpha, beta and gamma, respectively, followed by an arabic numeral to identify the isoform. For example, the first laminin identified from the Engelbreth-Holm-Swarm tumor is laminin-1 with the chain composition alpha 1 beta 1 gamma 1. The genes for these chains are LAMA1, LAMB1 and LAMC1, respectively.

Animals↗

Scatter factor stimulates migration of vascular endothelium and capillary-like tube formation.

Scatter factors (SFs) are heat- and trypsin-sensitive cytokines secreted by fibroblastic and vascular smooth muscle cell lines which stimulate motility of normal epithelium, carcinoma cells, and vascular endothelium. Human and mouse SFs have been purified and identified as 90 kD heterodimeric proteins consisting of heavy (58 kD) and light (31 kD) disulfide-bonded subunits. Partial amino acid sequence data from SF-derived tryptic peptides indicate marked sequence homology with hepatocyte growth factors, suggesting a common multigene family. In this chapter we describe the regulation by SF of vascular endothelial cell chemotaxis and chemokinesis; migration from microcarrier beads to flat surfaces; invasion through porous filters coated with reconstituted basement membrane; secretion of plasminogen activator; and in vitro capillary-like tube formation on a basement membrane surface.

Animals↗

[Connective matrix and localization of a biological signal: demonstration of a matrix receptor for interferon-gamma in basement membranes].

Extracellular matrix has a variety of biological effects on cells, including increased cell adhesion, migration, division and differentiation. Cells are also regulated by soluble factors such as cytokines. We have investigated the binding of interferon-gamma to basement membrane. Interferon-gamma binds basement membrane with a high affinity (kD = 1.5 x 10(-9) M). The binding site is located on the glycosaminoglycan part of the heparan sulfate proteoglycan. This result suggests that extracellular matrix interacts with interferon-gamma and could modulate the cellular response to such factors.

Basement Membrane↗

Laminin immunized monkeys develop sera toxic to cultured rat embryos and fail to reproduce.

In a previous study antilaminin antibodies in a monkey with a poor reproductive history were found to be the cause of serum toxicity to cultured rat embryos. In the present study four monkeys were immunized with murine tumor laminin and a fifth with bovine serum albumin. Subsequently, sera from only the laminin immunized monkeys became toxic to cultured rat embryos. This serum toxicity was not mediated by complement but did require the antibody to have a divalent structure. Finally, mating trials were conducted with two of the laminin immunized monkeys that previously had excellent reproductive histories. Based on progesterone levels and observation the monkeys continued to have normal menstrual cycles but failed to initiate a successful pregnancy following immunization in over 2 years of mating trials. These data demonstrated that antibodies against laminin could have prevented conception or could have interrupted pregnancy because of embryotoxicity or failure of implantation.

Animals↗