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Biomedical subjects

J J Walsh

Publications and source records attributed to J J Walsh.

At least 19 recordsLinked to original sources

Distinct determinants on collagen support alpha 2 beta 1 integrin-mediated platelet adhesion and platelet activation.

Recent studies have revealed that the sequence of amino acids asp-gly-glu-ala represents an essential determinant of the site within the alpha 1(I)-CB3 fragment of collagen recognized by the alpha 2 beta 1 integrin cell surface collagen receptor (Staatz et al., 1991). Studies employing chemical modifications of collagen amino acid side chains confirm both the essential nature of the acidic side chains of aspartic acid and glutamic acid residues and the nonessentiality of lysine epsilon-amino groups in supporting adhesion mediated by the alpha 2 beta 1 integrin. The approach also indicates the presence of a distinct determinant on collagen separate from the alpha 2 beta 1 recognition site that contains essential lysine side chains and that is necessary for subsequent interactions with the platelet surface that give rise to collagen-induced platelet activation and secretion. The two-step, two-site model for cellular signaling involving both an integrin and a signal-transducing coreceptor suggested by these data may be common to other integrin-mediated processes.

Acetylation

Plasma cell pneumonia induced by Legionella pneumophila.

We report a case of severe Legionella pneumonia in which the histopathologic features of an open lung biopsy specimen were characterized by a monotypic plasma cell infiltrate and absence of granulocytes or other acute inflammatory cells. The clinical course was otherwise typical for a severe case of Legionella pneumonia with complete functional and roentgenographic recovery following a prolonged convalescence. We speculate on possible reasons for this patient's unusual histopathologic features.

Female

The alpha 2 beta 1 integrin cell surface collagen receptor binds to the alpha 1 (I)-CB3 peptide of collagen.

We have previously shown that platelets adhere to collagen substrates via a Mg2(+)-dependent mechanism mediated by the surface glycoprotein Ia-IIa (human leukocyte very late activation protein 2, alpha 2 beta 1 integrin) complex. The adhesion is specific for collagen and is supported by collagen types I, II, III, IV, and VI. Several other members of the integrin family of adhesive protein receptors recognize discrete linear amino acid sequences within their adhesive glycoprotein ligands. Experiments with both intact platelets and with liposomes containing the purified receptor complex indicated that the alpha 2 beta 1 receptor recognized denatured type I collagen in a Mg2(+)-dependent manner. To further localize the binding site, the alpha 1 and alpha 2 chains of type I collagen were purified by gel filtration and ion exchange chromatography and tested as adhesive substrates. Both the alpha 1(I) and alpha 2(I) chains effectively supported Mg2(+)-dependent platelet adhesion. The purified alpha 1(I) collagen chain was then subjected to cleavage with cyanogen bromide, and the resultant peptides were separated by chromatography on carboxymethylcellulose. Only the alpha 1(I)-CB3 fragment supported Mg2(+)-dependent platelet adhesion. The monoclonal antibody P1H5 which recognizes an epitope on the alpha 2 subunit of the integrin receptor and which inhibits the adhesion of both intact platelets and liposomes bearing the purified receptor to collagen also inhibited platelet adhesion to the alpha 1(I)-CB3 fragment. These results indicate that the alpha 2 beta 1 receptor recognizes a sequence of amino acids present in the alpha 1(I)-CB3 fragment of type I collagen. An identical or similar sequence likely mediates binding of the receptor to other collagen polypeptides.

Antibodies, Monoclonal

Freedom Set II--a Y-set CAPD system with a novel design.

The Freedom Set II is designed with a three-way valve to control the direction of dialysate flow thus simplifying the procedure and decreasing training time. Twenty-four patients from two centers were trained on the Freedom Set II and were observed for ninety patient months. Five patients who had been on other bagless systems expressed their preference for the Freedom Set II. The peritonitis rate for the observation period was one episode every 21 patient months. We conclude that the Freedom Set II provides safe, cost-effective dialysis and simplifies the CAPD procedure.

Consumer Behavior

Long-term results of infragenicular bypasses with autogenous vein originating from the distal superficial femoral and popliteal arteries.

Forty-nine bypasses originating from the distal superficial femoral artery or popliteal artery in 46 patients were reviewed to examine late patency, limb salvage, and factors leading to graft failure. Operations were performed because of tissue loss in 86%, rest pain in 12%, and limiting claudication in 2% of limbs. Proximal anastomosis was from the distal superficial femoral artery in 12% and the popliteal artery in 88%. Distal anastomosis was to the below-knee popliteal artery or proximal tibial vessels in 20% and the distal tibial vessels in 80%. Life-table analysis showed a primary patency rate of 83%, 62%, and 41%, at 1, 3, and 5 years, respectively. The rate of limb salvage at 6 years for all grafts was 69%. Cox proportional hazards analysis determined that stenosis of 20% or greater in the proximal superficial femoral artery before bypass was a significant risk factor for graft failure (p = 0.02) despite the presence of normal intra-arterial pressure at the site of the proximal anastomosis at the time of bypass. Long-term survival in these patients was low, with a 6-year survival rate of only 24%. Infragenicular bypasses originating from the distal superficial femoral artery or the popliteal artery can be performed with patency and limb salvage rates comparable to bypasses originating from the common femoral artery. These bypasses are more likely to fail when performed in the presence of a stenosis 20% or greater in the superficial femoral or popliteal artery proximal to the graft origin.

Aged

Vein compression by arterial aneurysms.

This study was done to emphasize the importance of early, accurate diagnosis of arterial aneurysms that show the symptoms of venous obstruction. Fourteen patients were identified as having atherosclerotic aneurysms producing venous compression. Nine patients had popliteal aneurysms, causing popliteal vein thrombosis in three patients and vein compression without thrombosis in six patients. Five patients had iliac artery aneurysms, producing left iliac vein thrombosis in one patient and venous compression without thrombosis in four patients. In 10 patients the cause of the venous compression symptoms was correctly identified and appropriate revascularization was performed with successful results. In four patients, two with iliac artery aneurysms and two with popliteal artery aneurysms, the associated aneurysm was not identified. One patient died of a ruptured aneurysm and three patients had below-knee amputations because of untreatable distal ischemia. Inappropriate treatment of patients with venous obstruction from unrecognized arterial aneurysms is associated with unacceptable morbidity and mortality. Accurate diagnosis with timely aneurysm repair eliminates the risk of aneurysm rupture or thrombosis and simultaneously alleviates venous compression symptoms.

Aged

Blood levels of caffeine and results of fetal examination after oral administration of caffeine to pregnant rats.

Pregnant FDA-strain Osborne-Mendel rats were administered repeated doses of caffeine by oral intubation (gavage) and by administration in the drinking water (ad libitum sipping). When [1-methyl-14C]caffeine was administered at a dosage of 80 mg per kg per day by ad libitum sipping on days 12 to 15 of gestation, the amounts of radioactivity in blood were variable; the highest level on day 12 was 0.2% of the dose per ml of blood. The highest blood level of caffeine observed during a 24-h sampling period averaged 5.7 micrograms ml-1. When [14C]caffeine was administered by gavage at a dosage of 80 mg kg-1 on day 12, the blood level of radioactivity reached a peak of 0.4% of the dose per ml of blood and declined rapidly thereafter. The highest amount of caffeine observed in blood averaged 63.1 micrograms ml-1, 1 h after gavage. The overall blood elimination half-life of radioactivity in pregnant rats treated by gavage was 2.6 h, and the half-life of caffeine in blood was 1.7 h. The levels of radioactivity in the fetus and maternal muscle per unit weight were comparable after each method of administration. A comparison of autopsy results from both groups indicated that resorptions were increased when compared with rats that did not receive caffeine; this effect was more marked in the gavage group than in the ad libitum sipping group. Ectrodactyly was observed only in offspring of the gavage group. The incidences of ectrodactyly or resorptions did not appear to be directly related to nutrition or fluid intake.

Administration, Oral

Choice of operation to promote micturition after spinal cord injury.

61 male patients who had resection of the bladder neck alone, internal membranous urethrotomy alone or a combination of the 2 procedures to establish micturition after cord injury are reviewed. The combined operation has the greatest chance of initial success and should be performed if no attempt is to be made or preserve sexual function. Internal membranous urethrotomy is appropriate for lesions at all levels of the cord. Cystometry and cystourethrography are not helpful in the choice of operation.

Humans