Renal disease in nail-patella syndrome: Clinical and morphologic studies

Renal disease in nail-patella syndrome: Clinical and morphological studies. Clinical and morphological features of seven patients with the nail-patella syndrome are described. Progression to renal failure after a prolonged period of asymptomatic proteinuria is reported. Kidney tissue from these seven patients studied by light, immunofluorescent and electron microscopy demonstrated abnormalities characteristic of this disease. Focal glomerular basement membrane thickening was observed by light microscopy. Immunofluorescent microscopy showed focal glomerular basement membrane and arteriolar staining with serum proteins, predominantly IgM and β1C. Electron microscopy revealed markedly abnormal glomerular basement membranes containing bundles of cross-striated fibrils. These fibrils were more readily demonstrated in phosphotungstic acid-stained sections. The data presented suggest that the inborn error of connective tissue metabolism of the nail-patella syndrome is associated with renal disease as the result of deposition of collagen moieties in glomerular basement membranes with subsequent alterations of glomerular structure and function

Immunologic aspects of the nephrotic syndrome

The nephrotic syndrome is a clinical entity characterized by proteinuria, hypoalbuminemia, edema and hyperlipidemia. All the features of this syndrome are ultimately related to increased permeability of the glomerular capillary to protein. A specific disease entity in its mildest form may result in mild proteinuria insufficient to cause hypoalbuminemia and the other physiological manifestations of the nephrotic syndrome; the same disease in another patient or at another time in the same patient may cause marked proteinuria and the nephrotic state. The principal difference between proteinuria alone and that associated with the nephrotic syndrome in any specific disease would therefore appear to be quantitative, although it is likely that other factors play a role

Electropermeabilization of endocytotic vesicles in B16 F1 mouse melanoma cells

It has been reported previously that electric pulses of sufficiently high voltage and short duration can permeabilize the membranes of various organelles inside living cells. In this article, we describe electropermeabilization of endocytotic vesicles in B16 F1 mouse melanoma cells. The cells were exposed to short, high-voltage electric pulses (from 1 to 20 pulses, 60 ns, 50 kV/cm, repetition frequency 1 kHz). We observed that 10 and 20 such pulses induced permeabilization of membranes of endocytotic vesicles, detected by release of lucifer yellow from the vesicles into the cytosol. Simultaneously, we detected uptake of propidium iodide through plasma membrane in the same cells. With higher number of pulses permeabilization of the membranes of endocytotic vesicles by pulses of given parameters is accompanied by permeabilization of plasma membrane. However, with lower number of pulses only permeabilization of the plasma membrane was detected

Nuclear spin driven quantum relaxation in LiY_0.998Ho_0.002F_4

Staircase hysteresis loops of the magnetization of a LiY_0.998Ho_0.002F_4 single crystal are observed at subkelvin temperatures and low field sweep rates. This behavior results from quantum dynamics at avoided level crossings of the energy spectrum of single Ho^{3+} ions in the presence of hyperfine interactions. Enhanced quantum relaxation in constant transverse fields allows the study of the relative magnitude of tunnel splittings. At faster sweep rates, non-equilibrated spin-phonon and spin-spin transitions, mediated by weak dipolar interactions, lead to magnetization oscillations and additional steps.Comment: 5 pages, 5 eps figures, using RevTe

Hsp27 regulates podocyte cytoskeletal changes in an in vitro model of podocyte process retraction

Nephrotic syndrome (NS) is characterized by structural changes in the actin‐rich foot processes of glomerular podocytes. We previously identified high concentrations of the small heat shock protein hsp27 within podocytes as well as increased glomerular accumulation and phosphorylation of hsp27 in puromycin aminonucleoside (PAN) ‐induced experimental NS. Here we analyzed murine podocytes stably transfected with hsp27 sense, antisense, and vector control constructs using a newly developed in vitro PAN model system. Cell morphology and the microfilament structure of untreated sense and antisense transfectants were altered compared with controls. Vector cell survival, polymerized actin content, cell area, and hsp27 content increased after 1.25 μg/ml PAN treatment and decreased after 5.0 μg/ml treatment. In contrast, sense cells were unaffected by 1.25 μg/ml PAN treatment whereas antisense cells showed decreases or no changes in all parameters. Treatment of sense cells with 5.0 μ g/ml PAN resulted in increased cell survival and cell area whereas antisense cells underwent significant decreases in all parameters. Hsp27 provided dramatic protection against PAN‐induced microfilament disruption in sense > vector > antisense cells. We conclude that hsp27 is able to regulate both the morphological and actin cytoskeletal response of podocytes in an in vitro model of podocyte injury.—Smoyer, W. E., Ransom, R. F. Hsp27 regulates podocyte cytoskeletal changes in an in vitro model of podocyte process retraction. FASEB J. 16, 315–326 (2002)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154256/1/fsb2fj010681com.pd

Spin-transfer in an open ferromagnetic layer: from negative damping to effective temperature

Spin-transfer is a typical spintronics effect that allows a ferromagnetic layer to be switched by spin-injection. Most of the experimental results about spin transfer are described on the basis of the Landau-Lifshitz-Gilbert equation of the magnetization, in which additional current-dependent damping factors are added, and can be positive or negative. The origin of the damping can be investigated further by performing stochastic experiments, like one shot relaxation experiments under spin-injection in the activation regime of the magnetization. In this regime, the N\'eel-Brown activation law is observed which leads to the introduction of a current-dependent effective temperature. In order to justify the introduction of these counterintuitive parameters (effective temperature and negative damping), a detailed thermokinetic analysis of the different sub-systems involved is performed. We propose a thermokinetic description of the different forms of energy exchanged between the electric and the ferromagnetic sub-systems at a Normal/Ferromagnetic junction. The corresponding Fokker Planck equations, including relaxations, are derived. The damping coefficients are studied in terms of Onsager-Casimir transport coefficients, with the help of the reciprocity relations. The effective temperature is deduced in the activation regime.Comment: 65 pages, 10 figure

Macroscopic quantum coherence in mesoscopic ferromagnetic systems

In this paper we study the Macroscopic Quantum Oscillation (MQO) effect in ferromagnetic single domain magnets with a magnetic field applied along the hard anistropy axis. The level splitting for the ground state, derived with the conventional instanton method, oscillates with the external field and is quenched at some field values. A formula for quantum tunneling at excited levels is also obtained. The existence of topological phase accounts for this kind of oscillation and the corresponding thermodynamical quantities exhibit similar interference effects which resembles to some extent the electron quantum phase interference induced by gauge potential in the Aharonov-Bohm effect and the $\Theta$-vacuum in Yang-Mills field theory..Comment: 12 pages, 4 figures, to appear in Phys. Rev.

Nucleofection induces non-specific changes in the metabolic activity of transfected cells

Transfection has become an everyday technique widely used for functional studies in living cells. The choice of the particular transfection method is usually determined by its efficiency and toxicity, and possible functional consequences specific to the method used are normally overlooked. We describe here that nucleofection, a method increasingly used because of its convenience and high efficiency, increases the metabolic rate of some cancer cells, which can be misleading when used as a measure of proliferation. Moreover, nucleofection can alter the subcellular expression pattern of the transfected protein. These undesired effects are independent of the transfected nucleic acid, but depend on the particular cell line used. Therefore, the interpretation of functional data using this technology requires further controls and caution

Electroporation-Induced Electrosensitization

BACKGROUND: Electroporation is a method of disrupting the integrity of cell membrane by electric pulses (EPs). Electrical modeling is widely employed to explain and study electroporation, but even most advanced models show limited predictive power. No studies have accounted for the biological consequences of electroporation as a factor that alters the cell's susceptibility to forthcoming EPs. METHODOLOGY/PRINCIPAL FINDINGS: We focused first on the role of EP rate for membrane permeabilization and lethal effects in mammalian cells. The rate was varied from 0.001 to 2,000 Hz while keeping other parameters constant (2 to 3,750 pulses of 60-ns to 9-µs duration, 1.8 to 13.3 kV/cm). The efficiency of all EP treatments was minimal at high rates and started to increase gradually when the rate decreased below a certain value. Although this value ranged widely (0.1-500 Hz), it always corresponded to the overall treatment duration near 10 s. We further found that longer exposures were more efficient irrespective of the EP rate, and that splitting a high-rate EP train in two fractions with 1-5 min delay enhanced the effects severalfold. CONCLUSIONS/SIGNIFICANCE: For varied experimental conditions, EPs triggered a delayed and gradual sensitization to EPs. When a portion of a multi-pulse exposure was delivered to already sensitized cells, the overall effect markedly increased. Because of the sensitization, the lethality in EP-treated cells could be increased from 0 to 90% simply by increasing the exposure duration, or the exposure dose could be reduced twofold without reducing the effect. Many applications of electroporation can benefit from accounting for sensitization, by organizing the exposure either to maximize sensitization (e.g., for sterilization) or, for other applications, to completely or partially avoid it. In particular, harmful side effects of electroporation-based therapies (electrochemotherapy, gene therapies, tumor ablation) include convulsions, pain, heart fibrillation, and thermal damage. Sensitization can potentially be employed to reduce these side effects while preserving or increasing therapeutic efficiency