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P Aronson

Publications and source records attributed to P Aronson.

12 recordsLinked to original sources

A transmembrane segment determines the steady-state localization of an ion-transporting adenosine triphosphatase.

The H,K-adenosine triphosphatase (ATPase) of gastric parietal cells is targeted to a regulated membrane compartment that fuses with the apical plasma membrane in response to secretagogue stimulation. Previous work has demonstrated that the alpha subunit of the H, K-ATPase encodes localization information responsible for this pump's apical distribution, whereas the beta subunit carries the signal responsible for the cessation of acid secretion through the retrieval of the pump from the surface to the regulated intracellular compartment. By analyzing the sorting behaviors of a number of chimeric pumps composed of complementary portions of the H, K-ATPase alpha subunit and the highly homologous Na,K-ATPase alpha subunit, we have identified a portion of the gastric H,K-ATPase, which is sufficient to redirect the normally basolateral Na,K-ATPase to the apical surface in transfected epithelial cells. This motif resides within the fourth of the H,K-ATPase alpha subunit's ten predicted transmembrane domains. Although interactions with glycosphingolipid-rich membrane domains have been proposed to play an important role in the targeting of several apical membrane proteins, the apically located chimeras are not found in detergent-insoluble complexes, which are typically enriched in glycosphingolipids. Furthermore, a chimera incorporating the Na, K-ATPase alpha subunit fourth transmembrane domain is apically targeted when both of its flanking sequences derive from H,K-ATPase sequence. These results provide the identification of a defined apical localization signal in a polytopic membrane transport protein, and suggest that this signal functions through conformational interactions between the fourth transmembrane spanning segment and its surrounding sequence domains.

Amino Acid Sequence↗

Spiny keratoderma: a common under-reported dermatosis.

Spiny keratoderma is a dermatosis consisting of multiple projections located on the palms and soles, with a distinct histology characteristic of a parakeratotic column above a hypogranular epidermis. We report six cases discovered within a year and review the present literature on spiny keratoderma. The average age of the patients was 57 years. Fifty-seven percent of the patients were male and forty-three percent were female. The duration of lesions ranged from 4 months to 40 years. Symptoms were variable, however, lesions were often unnoticed by the patient. The location of the lesions involved the palms and soles or the palms alone. Past medical history was significant for hypertension and hyperlipidemia treated with HMG-CoA reductase inhibitors. Lesions often occurred in patients involved in manual labor. Spiny keratoderma is a relatively common under-reported dermatosis found most often in older patients with history of manual labor and is possibly related to treatment with HMG-CoA reductase inhibitors.

Adult↗

Sodium-hydrogen exchange isoform expression in blood cells: implications for studies in diabetes mellitus.

There have been many reports of increased Na-H exchange (NHE) activity in the peripheral blood cells (erythrocytes, lymphocytes and platelets) of patients with diabetes mellitus compared to nondiabetic controls. This raised NHE activity has been hypothesized to reflect increased NHE activity in kidney and vascular smooth muscle. Raised NHE activity in these tissues could play a pathophysiological role in mediating hypertension, vascular smooth muscle cell proliferation and progressive renal impairment. It is now known that there are at least five NHE isoforms, but a specific study examining expression of NHE isoforms in peripheral blood cells has not been reported. This study used specific antisera to NHE isoforms 1, 3 and 4 to examine NHE expression by immunoblot analysis. Erythrocyte, lymphocyte and platelet membranes from both rabbit and rat were separated by standard methods. A monoclonal antibody to NHE-1 reacted with a 100-110 kDa band in rabbit and rat platelets and lymphocytes (identical to that observed in basolateral-enriched renal cortical vesicles) and a 100 kDa band in rabbit and rat erythrocytes. In both species, the intensity of the staining was greatest in platelet membranes. A polyclonal antibody to NHE-3, the isoform present on the apical membranes of renal proximal tubule, showed no evidence of staining in any of the peripheral blood cell preparations. Similarly there was no evidence of expression of NHE-4 in the peripheral blood cell preparations. Peripheral blood cells express NHE-1, which likely accounts for amiloride-sensitive Na-H exchange in these cells, playing a role in cell volume and pH regulation. However, there is no evidence that there is expression of NHE-3 or NHE-4 in peripheral blood cells. These data have implications for studies in hypertension and diabetes mellitus which measure peripheral blood cell Na-H exchange and hypothesize regarding a direct pathophysiological role for this increased activity.

Animals↗

Litigation by patients as third party beneficiaries of payor-provider contracts.

"No third party beneficiaries" clauses, if drafted with care, can offer some measure of protection to providers. Although courts may give minimal weight to "boilerplate" clauses in determining contractual intent, a more detailed and substantive clause may be more persuasive. In drafting such clauses, however, care should be taken to clearly state the specific intentions of the parties, including the scope and purposes of the contract, the identity of the intended beneficiaries, and the classes of persons that are to be excluded as beneficiaries (e.g., HMO enrollees).

Contract Services↗

Yohimbine-induced cutaneous drug eruption, progressive renal failure, and lupus-like syndrome.

Yohimbine is an indole alkaloid obtained from the yohimbe tree, a common tree in West Africa. We describe a forty-two-year black man in whom a generalized erythrodermic skin eruption, progressive renal failure, and lupus-like syndrome developed following treatment with the drug, yohimbine. A literature review failed to reveal any reported association of these side effects. We review current information on yohimbine's use in male impotence, reported side effects, and its role as a drug allergen.

Acute Kidney Injury↗