Melvin Silverman

Characterisation of glomerular haemodynamic responses to SGLT2 inhibition in patients with type 1 diabetes and renal hyperfiltration

Abbreviations ΔPF Filtration pressure across the glomerular capillaries πG Glomerular oncotic pressure FENa Fractional excretion of sodium KFG Ultrafiltration coefficient PGLO Glomerular hydrostatic pressure RA Afferent renal arteriolar resistances RAAS Renin–angiotensin–aldosterone system RE Efferent renal arteriolar resistances SGLT2 Sodium–glucose co-transporter 2 T1D-N Type 1 diabetic patients with renal normofiltration T1D-H Type 1 diabetic patients with renal hyperfiltration

ROS stimulate reorganization of mesangial cell-collagen gels by tyrosine kinase signaling

Reactive oxygen species (ROS) initiate multiple pathological and physiological cellular responses, including tyrosine phosphorylation of proteins. In this study, we investigated the effects of ROS on cell-extracellular matrix interactions utilizing the floating three-dimensional collagen gel assay. Exposure of mesangial cells grown in three-dimensional culture to H2O2, 3-amino-1,2,4-triazole (a catalase inhibitor), or puromycin is associated with gel reorganization accompanied by tyrosine phosphorylation of multiple proteins, including focal adhesion kinase (FAK). Neutrophils cocultured with mesangial cells in three-dimensional culture also induce mesangial cell-collagen gel reorganization and initiate tyrosine phosphorylation of a similar set of proteins. Collectively, these results show that ROS of either endogenous or exogenous origin can modulate mesangial cell-extracellular matrix interactions through initiation of a phosphotyrosine kinase signaling cascade. Consequently, ROS may play a role as signaling molecules that regulate mesangial cell-extracellular matrix interactions in both physiological and pathological conditions.Reactive oxygen species (ROS) initiate multiple pathological and physiological cellular responses, including tyrosine phosphorylation of proteins. In this study, we investigated the effects of ROS on cell-extracellular matrix interactions utilizing the floating three-dimensional collagen gel assay. Exposure of mesangial cells grown in three-dimensional culture to H2O2, 3-amino-1,2,4-triazole (a catalase inhibitor), or puromycin is associated with gel reorganization accompanied by tyrosine phosphorylation of multiple proteins, including focal adhesion kinase (FAK). Neutrophils cocultured with mesangial cells in three-dimensional culture also induce mesangial cell-collagen gel reorganization and initiate tyrosine phosphorylation of a similar set of proteins. Collectively, these results show that ROS of either endogenous or exogenous origin can modulate mesangial cell-extracellular matrix interactions through initiation of a phosphotyrosine kinase signaling cascade. Consequently, ROS may play a role as signaling molecules that regulate mesangial cell-extracellular matrix interactions in both physiological and pathological conditions.

Multiple indicator dilution and the kidney : kinetics, permeation, and transport in Vivo

Publisher Summary In Multiple Indicator Dilution (MID), a pulse of chemical signals is introduced in tracer concentration into the microcirculation via the arterial inflow of an organ and the timed fractional recovery for each chemical signal measured in the venous outflow. Provided appropriate reference tracers are included it is possible to extract from the temporal pattern of fractional recoveries considerable information about transport kinetics at the capillary, interstitial, and cell surface within an organ, and utilize these data to obtain a comprehensive quantitative description of transport and metabolic events under in vivo conditions. Vesicle transport studies and micropuncture analyses are good examples of in vitro methods with the capacity to localize function. Recently, this chapter has begun to develop renal MID in a form that realizes the intrinsic information gains of localized tissue characterization while retaining the analytical power of whole-organ MID.

Quantum mechanical effects in molecule-membrane interactions*

The ideal gas thermal de Broglie wavelengths of the proton, the sodium ion, ethanol, glucose, adenosine triphosphate, oxytocin, adrenocorticotrophic hormone and myoglobin are computed for T = 310 K. The molecules are treated as masses with zero internal degrees of freedom. The wavelengths (λj) are compared to length parameters (Li) corresponding to the rise of intramembrane potentials to the values near the classical turning point for perfect gas particles (3/2kT). The meaning for membrane interaction of the velocity dependence of the de Broglie wavelength is examined with respect to the velocity fluctuations expected of a real fluid. The implications of the uncertainty principle for the observation of substrate motion within cell membranes are considered and applied to the observed turnover of the glucose transport carrier in the dog kidney. The combined results suggest that quantum physical processes are important in molecule-membrane interactions for substances of MW 200–500.

Molecular Biology of the Na+—D-Glucose Cotransporter

The sodium-dependent D-glucose carrier protein is one of an important set of plasma membrane constituents that control the traffic of biologically critical molecules between the interior and exterior of the cell. It is found at the mucosal surface of the small intestine and renal proximal tubule. Progress in elucidating its molecular structure and action is reported.

Physical Theory in Biology: An Interdisciplinary Course.

We describe a new interdisciplinary course which explores the relations between physics and biology in terms of their conceptual structures and mathematical frameworks. The course is designed for senior undergraduate physics students who have little or no background in the life sciences. In this paper we highlight the course content, its system of cross‐disciplinary literature resources, and several innovative aspects of the method used for evaluating students.