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Biomedical subjects

L Gunther

Publications and source records attributed to L Gunther.

10 recordsLinked to original sources

Pancreas oxygenation is limited during preservation with the two-layer method.

BACKGROUND: The two-layer method (TLM) for pancreas preservation reportedly improves islet yield and transplantation outcome relative to previous methods. Increased ATP concentrations support the hypothesis that these improvements are related to better oxygenation from the perfluorocarbon solution. However, there are limited direct measurements of oxygen partial pressure, (pO(2)) in pancreata preserved with the TLM. Theory predicts that only a small fraction of a human pancreas can be oxygenated externally. In this report we examine pancreas oxygenation with the TLM using theory and direct pO(2) measurements. METHODS: pO(2) profiles in cylindrical pancreata were calculated at various temperatures with a diffusion-reaction model. The pO(2) was measured using fiber optic sensors in the core of porcine pancreatic tissue preserved with the TLM in media saturated with 100% oxygen. RESULTS: The model predicts that at 8 degrees C, even in the absence of an external pO(2) gradient, oxygen penetration depth is about 1 mm and insensitive to pancreas diameter, while the oxygenated volume fraction is about 15% for a 2.5-cm-diameter pancreas. Experimental measurements verified that pO(2) is virtually zero in the core of a 1-cm-thick pancreatic piece preserved with the TLM. Penetration of solution around the sensor may be responsible for the observed lag and for the previously reported nonzero pO(2) measurements. Reoxygenation of heat-treated tissue took several hours. CONCLUSIONS: The TLM can oxygenate only a small volume fraction of a human pancreas. Pancreas oxygenation through the native vasculature should be explored to further improve yield of viable islets.

Humans↗

The M cell as a portal of entry to the lung for the bacterial pathogen Mycobacterium tuberculosis.

M. tuberculosis accesses the terminal lung and is phagocytosed by alveolar macrophages. Utilizing a mouse intratracheal challenge model, we demonstrate that M. tuberculosis rapidly enters through M cells as well. From there, bacilli are deposited within associated intraepithelial leukocytes and subsequently conveyed to the draining lymph nodes early after infection. Osteopetrotic (Csfm(op)/Csfm(op)) mice, null mutants for macrophage colony-stimulating factor, possess diminished numbers of circulating monocytes and tissue macrophages. Csfm(op)/Csfm(op) mice were highly susceptible to challenge with M. tuberculosis. In contrast to controls, tubercle bacilli were not conveyed to draining lymph nodes early after infection but were instead retained within the mucosa. These results indicate that M cells represent an alternate portal of entry for M. tuberculosis, which may contribute to the rapid development of protective lung immune responses.

Animals↗

Water channel-carrying vesicles in the rat IMCD contain cellubrevin.

Antidiuretic hormone (arginine vasopressin) induces a cyclic process of docking, fusion, and endocytosis of water channel-containing vesicles in the collecting duct. There is now evidence that docking and endocytosis are mediated by an array of proteins associated with vesicles and target membranes. In recent studies, we have shown that cellubrevin, a member of the vesicle-associated membrane protein family, as well as other docking proteins, are expressed in the rat inner medullary collecting duct. We now show by immunogold electron microscopy that cellubrevin is present on vesicles containing water channels, that it is associated with both coated and uncoated vesicles, and that it is present on the apical membrane. Cellubrevin, therefore, is in a position to mediate one or more steps in arginine vasopressin-induced water channel cycling.

Animals↗

The significance for morbidity and mortality of Doppler-absent pedal pulses.

The 1-month prognosis of 91 limbs with a pulseless foot in 49 patients was determined and related to elements of the physical examination, including Doppler ultrasonography. The risk factors that could predict loss of limb and death in this group of patients were determined. Gangrene and atrophy coupled with absent ultrasound signals predicted a 75% risk of loss of limb; this occurred despite attempted surgical intervention. Absence of Doppler signals in both ankle arteries was the strongest risk factor for predicting death. This is probably because ultrasound signals are absent only when arterial disease is far advanced. We conclude that Doppler ultrasound examination of the pulseless foot yields useful prognostic information relative to the fate of the limb and the patient who possesses such a limb.

Amputation, Surgical↗