Biomedical subjects

W Rosenblum

Publications and source records attributed to W Rosenblum.

7 recordsLinked to original sources

PubMed2001

Downregulation of matrix metalloproteinases and reduction in collagen damage in the failing human heart after support with left ventricular assist devices.

BACKGROUND: Left ventricular assist device (LVAD) support of the failing heart induces salutary changes in myocardial structure and function. Matrix metalloproteinases (MMPs) are increased in the failing heart and are induced by stretch in cardiac cells in vitro. We hypothesized that mechanical unloading may affect LV plasticity by regulating MMPs and their substrates. METHODS AND RESULTS: LV samples were collected from patients with dilated cardiomyopathy (DCM, n=14) or ischemic cardiomyopathy (ICM, n=16) at the time of implantation of the LVAD and again during cardiac transplantation. MMP-1, -3, and -9 were measured by ELISA, MMP-2 and -9 gelatinolytic activity by gelatin zymography, and tissue inhibitors of metalloproteinases (TIMPs) by Western blot. Total soluble and insoluble collagens were separated by pepsin solubilization, and the contents were determined by quantification of hydroxyproline. The undenatured soluble collagen was measured by Sircol collagen assay. The results showed that MMP-1 and -9 were decreased, whereas TIMP-1 and -3 were increased, but there was no change in MMP-2 and -3 and TIMP-2 and -4 after LVAD support. The undenatured collagen was increased, with the ratio of undenatured to total soluble collagens increased in ICM and that of insoluble to total soluble collagens increased in DCM after LVAD support. CONCLUSIONS: The reduced MMPs and increased TIMPs and ratios of undenatured to total soluble collagens and insoluble to total soluble collagens after LVAD support suggest that reduced MMP activity diminished damage to the matrix. These changes may contribute to the functional recovery and LV plasticity after LVAD support.

Adult↗

PubMed1998

Micromechanical devices for intravascular drug delivery.

Microfabrication technology, more commonly applied to the manufacture of integrated circuits, can be used to build devices useful for mechanical delivery of drugs and genes. Microprobes fabricated using silicon micromachining have been used to deliver DNA into cells as an alternative to bombardment and microinjection. This idea can be extended to intravascular stents with integrated microprobes capable of piercing compressed plaque and delivering anti-restenosis therapies into coronary arteries. Preliminary experiments using filleted rabbit arteries have demonstrated transection of the internal elastic lamina. New nonplanar microfabrication technologies are necessary for creating practical devices with cylindrical symmetry; a promising possibility is to use microfabricated structures of anodic metal oxides.

Animals↗

PubMed1994

Cardiac transplantation at the University of Pittsburgh: 1994 update.

During the past 14 years, 746 hearts have been transplanted at the University of Pittsburgh. Immunosuppression has evolved from a CsA-based protocol with or without lympholytic prophylaxis to a tacrolimus-based protocol. Tacrolimus offers comparable survival to the conventional immunosuppression but is associated with lesser side effects and lower recurrent rejection. It also serves as an effective rescue agent for intractable rejection in patients receiving CsA-based immunosuppression. However, the shortage of donors, chronic rejection, and the morbidity associated with chronic use of nonspecific immunosuppression remain the major limitations in clinical transplantation. Currently, research at the University of Pittsburgh focuses on the induction of donor-specific transplantation tolerance in order to eliminate the morbidity associated with nonspecific immunosuppression and on left ventricular-assist devices as a bridge and/or an alternative to cardiac transplantation.

Actuarial Analysis↗

PubMed1985

Accommodation demand and deprivation in kitten ocular development.

The effects of accommodation demand and deprivation on the development of ocular optics was investigated in four groups of kittens (total n = 29). Group 1 consisted of five normal kittens; group 2 (nine kittens) had monocular radial keratotomy to induce relative hypermetropia and more accommodation demand as well as to impart interocular refractive differences (anisometropia); group 3 (eight kittens) received daily monocular atropine; and group 4 (seven kittens) had binocular radial keratotomy combined with daily monocular atropine. Regular examination provided documentation of ocular development from the first through the sixth months of life. Subsequently, the focal lengths of the crystalline lenses were determined in vitro. An apparent tendency for kitten eye pairs to grow toward isometropia, even when anisometropia had been induced early in life, was seen in those eyes in which the accommodative mechanism had been left intact (groups 1 and 2), but without accommodation anisometropia resulted (groups 3 and 4). There was relatively more elongation of the globe (3.08 +/- 0.22%) as well as shorter than normal focal lengths of the crystalline lens (-4.91 +/- 1.62% anterior, -2.78 +/- 1.54% posterior) in the eyes of the second group, and the eye pairs regained isometropia. In those eyes of the third and fourth groups that received atropine daily, there was relatively less elongation of the globe (-3.09 +/- 0.59% and -3.22 +/- 0.67%, respectively) and shorter crystalline lens focal lengths (-3.50 +/- 1.18% and -4.62 +/- 1.07% anterior, -2.64 +/- 1.02% and -1.59 +/- 0.62% posterior, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Accommodation, Ocular↗

PubMed1984

Staphylococcal plasmid cointegrates are formed by host- and phage-mediated general rec systems that act on short regions of homology.

Cointegrates involving pairs of compatible staphylococcal plasmids can be isolated either by co-selection during transduction (Novick et al. 1981) or by selection for survival at the restrictive temperature of a thermosensitive, replication defective plasmid in the presence of a stable one. Cointegrates are formed by recombination at two specific sites, RSA and RSB. RSB is present on each of six plasmids analyzed, namely pT181, pE194, pC194, pS194, pUB110, and pSN2, and RSA is present on two of these, pT181 and pE194. In this communication, it is shown that the RS represent short regions of homology (RSA is some 70 bp in length and RSB is about 30) embedded in largely non-homologous contexts and that the crossovers take place within these homologous regions. The pT181 and pE194 RSA sequences contain several mismatches which permit the localization of the crossover events to several different sites within the overall RS segment. The recombination system involved is therefore general (homology-specific) rather than site-specific (sequence-specific). Mismatches included within the crossover region are always corrected to the pT181 configuration. The cointegrates are therefore formed by a relatively efficient general rec system that recognizes short regions of homology and gives rise to Holliday junctions that probably involve very short heteroduplex overlaps. The sequence results are consistent with asymmetric single-strand invasion of a contralateral gap with nucleotide conversion by copying. It is noted that RSB has substantial homology with the par sequence of plasmid pSC101, suggesting that it may be involved in plasmid partitioning.

Base Composition↗

PubMed1983

Dimethyl sulfoxide effects on platelet aggregation and vascular reactivity in pial microcirculation.

DMSO is a hydroxyl radical scavenger that inhibits platelet aggregation in vivo in injured microvessels, and that also inhibits the dilation displayed by pial arterioles following a local injury. The injurious stimulus is a result of local excitation of circulating sodium fluorescein by an appropriate light source. It is likely that this excitation results in the generation of hydroxyl radicals, which are the immediately injurious agent. This postulate is supported not only by the inhibitory effect of DMSO but also by the inhibitory effect of glycerol, another hydroxyl scavenger. Both the hypothesis that DMSO inhibits hydroxyl-mediated dilation, and the hypothesis that free radicals can dilate pial arterioles, are further supported by direct evidence from studies employing local application of xanthine oxidase plus acetaldehyde. This well established radical-generating system dilated pial arterioles. The dilation was inhibited by the local application of superoxide dismutase and also by local application of catalase, as well as by intraperitoneal administration of DMSO. Since DMSO failed to inhibit the dilation produced by increases of inspired CO2, we believe that the inhibitory effect of DMSO on the other dilating stimuli in these studies was due to the hydroxyl scavenging properties of this drug, rather than to other nonspecific effects.

Animals↗

PubMed1976

Density of perivascular nerves on some cerebral and extracerebral blood vessels.

The perivascular adrenergic nerves were counted as they crossed a grid-line superimposed on rat cerebral or femoral arteries and arterioles, and on the portal vein and its tributaries. The nerves were visualized with the formaldehyde-vapor, fluorescence technique. No support was received for the hypothesis that cerebral vessels are better innervated than extracerebral vessels. In fact, the density of nerves was significantly greater on the femoral and portal vessels than on the cerebral.

Adrenergic Fibers↗