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Biomedical subjects

J Schaff

Publications and source records attributed to J Schaff.

9 recordsLinked to original sources

Morphological control of inositol-1,4,5-trisphosphate-dependent signals.

Inositol-1,4,5-trisphosphate (InsP(3))-mediated calcium signals represent an important mechanism for transmitting external stimuli to the cell. However, information about intracellular spatial patterns of InsP(3) itself is not generally available. In particular, it has not been determined how the interplay of InsP(3) generation, diffusion, and degradation within complex cellular geometries can control the patterns of InsP(3) signaling. Here, we explore the spatial and temporal characteristics of [InsP(3)](cyt) during a bradykinin-induced calcium wave in a neuroblastoma cell. This is achieved by using a unique image-based computer modeling system, Virtual Cell, to integrate experimental data on the rates and spatial distributions of the key molecular components of the process. We conclude that the characteristic calcium dynamics requires rapid, high-amplitude production of [InsP(3)](cyt) in the neurite. This requisite InsP(3) spatiotemporal profile is provided, in turn, as an intrinsic consequence of the cell's morphology, demonstrating how geometry can locally and dramatically intensify cytosolic signals that originate at the plasma membrane. In addition, the model predicts, and experiments confirm, that stimulation of just the neurite, but not the soma or growth cone, is sufficient to generate a calcium response throughout the cell.

Animals↗

The virtual cell.

This paper describes a computational framework for cell biological modeling and simulation that is based on the mapping of experimental biochemical and electrophysiological data onto experimental images. The framework is designed to enable the construction of complex general models that encompass the general class of problems coupling reaction and diffusion.

Cell Physiological Phenomena↗

A general computational framework for modeling cellular structure and function.

The "Virtual Cell" provides a general system for testing cell biological mechanisms and creates a framework for encapsulating the burgeoning knowledge base comprising the distribution and dynamics of intracellular biochemical processes. It approaches the problem by associating biochemical and electrophysiological data describing individual reactions with experimental microscopic image data describing their subcellular localizations. Individual processes are collected within a physical and computational infrastructure that accommodates any molecular mechanism expressible as rate equations or membrane fluxes. An illustration of the method is provided by a dynamic simulation of IP3-mediated Ca2+ release from endoplasmic reticulum in a neuronal cell. The results can be directly compared to experimental observations and provide insight into the role of experimentally inaccessible components of the overall mechanism.

Animals↗

Extraprostatic production of prostate specific antigen is under hormonal control.

PURPOSE: Prostate specific antigen (PSA) is the most useful tumor marker in urology. It is produced primarily by the epithelial cells of the ducts and acini of the prostate gland. Extraprostatic production of PSA is provided mainly by the periurethral glands, leading to measurable urine but undetectable serum levels of PSA in women and in men following radical prostatectomy for pathologically localized disease. MATERIALS AND METHODS: We investigated the effect of continuous testosterone substitution (250 mg. every 4 weeks) on urinary PSA excretion in 20 patients who converted from the female to male gender. We compared the results to urine levels in 20 women who did not receive testosterone. RESULTS: Mean urinary PSA plus or minus standard deviation was 1.73 +/- 1.68 ng./ml. in controls and 12.03 +/- 10.47 ng./ml. in converted patients, a statistically significant difference (p < 0.0001). Serum PSA did not differ between groups. CONCLUSIONS: Our data demonstrate that extraprostatic PSA production is under androgen control.

Adult↗

Temporary ectopic implantation for salvage of amputated digits.

Temporary ectopic implantation for salvage of amputated parts is a fascinating idea. The first successful case, to our knowledge, of preserving digits by means of temporary ectopic implantation to the contralateral forearm is presented and this treatment concept is discussed. The indication for temporary ectopic implantation is an amputation injury with associated extensive soft tissue damage in which immediate replantation with either adequate shortening or preservation of length does not seem feasible, although the amputated part itself is uninjured and should therefore be salvaged. The groin, axilla and lower arm are compared as possible recipient sites for ectopic implantation. Early replantation of the ectopic implanted parts will provide superior functional results although replantation may be technically more demanding. The function of a replanted extremity after ectopic implantation will probably always be inferior to a comparable, immediately replanted extremity.

Adult↗

[Morbidity of the donor site of the dorsalis pedis flap].

Detailed information on the dorsalis pedis flap donor-site morbidity is still lacking. In a retrospective analysis, wound-healing, cosmesis, mobility, stability, and thermographic studies of the feet were investigated. The results show a high donor-site morbidity of the dorsalis pedis flap. Indications and alternative methods are discussed.

Adolescent↗

DSA--control of implanted devices for arterial hepatic perfusion.

In contrast to conventional film angiography, the perfusion pattern of hepatic arterial chemotherapy was consistently visualized by DSA in 40 patients with implanted Infusaid pump or Port-A devices. Incomplete perfusion of a liver region by the cytotoxic agent was recognized by DSA as accurately as by nuclide scintigraphy. Furthermore, DSA appeared to be more sensitive in determining aberrantly perfused extrahepatic regions; this was especially true when there was a nonligated right hepatic artery. Specific details of vascular lesions and associated complicating events also could be satisfactorily analyzed by DSA only.

Adult↗

Experimental studies of the anatomical and functional characteristics of kangaroo aortic valve bioprostheses.

In many tests done in vitro and in vivo on porcine aortic valve grafts, high pressure gradients were found under normal as well as under stress conditions. The transvalvular pressure difference is due to the immobility of the right aortic porcine leaflet that is fixed tightly to the muscular septum of the ventricle. Our own studies of 24 kangaroo hearts show different anatomical features: the right leaflet is practically free in this movement. Thus the maximum orifice area of the kangaroo aortic valve is reduced by only 24.2 per cent, whereas the porcine valve shows a reduction of 36.5 per cent. This difference proved to be highly significant (P less than 0.001). Therefore, in cooperation with Hancock Laboratories, kangaroo aortic valve grafts were tested as xenotransplants, using a pulse duplicator. The first results show that larger orifice areas are achieved by kangaroo valves one or two sizes smaller than their porcine counterparts.

Animals↗