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Biomedical subjects

B M Smith

Publications and source records attributed to B M Smith.

At least 73 records · Page 4Linked to original sources
PubMed1986

Extracellular calcium requirement for promotion of transformation in JB6 cells.

Extracellular calcium is required in the induction of neoplastic transformation of preneoplastic mouse JB6 epidermal cells by 12-O-tetradecanoylphorbol-13-acetate (TPA). Depleting extra-cellular calcium by chelation or by use of commercial calcium-depleted medium inhibited TPA-promoted transformation of promotion-sensitive JB6 cells with a half-maximal inhibition at 1.2 mM calcium. Inhibition was reversible by the addition of calcium. The calcium channel blockers lanthanum and nifedipine inhibited promotion of anchorage-independent transformation by TPA maximally at 10.0 microM and 1.0 nM, respectively, suggesting that calcium entry occurs partially via cell channels. None of the above treatments altered expression of transformation in anchorage-independent tumorigenic JB6 cell lines, indicating that the extracellular calcium requirement was at the level of induction, not expression of transformation. The calcium requirement was not merely a requirement for proliferation; calcium concentrations from 0.2 to 1.8 mM had no effect on JB6 cell monolayer growth. Extracellular calcium was required for 7 days for maximal colony induction. The calcium ionophore A23187 was not a promoter and moderately inhibited TPA-promoted transformation, indicating that increases in free cytosolic calcium concentrations are not sufficient for promotion of transformation and may even activate calcium-dependent antipromoting events. The results suggest that a cellular calcium pool supplied by extracellular calcium, but not distinguishable by ionophoretic increases in free cytosolic calcium, is essential in TPA-promoted neoplastic transformation.

Animals↗
PubMed1986

Thoracic and vascular aspects of thoracic outlet syndrome. 1986 update.

Upper extremity symptoms of arterial or venous origin are a rarer manifestation of the thoracic outlet syndrome than those caused by brachial plexus compression. Since the authors' original report in 1967, a better understanding of the necessity for detailed history and physical examination preoperatively and advances in angiography and computed tomography have made the selection of patients for thoracic outlet decompression and vascular reconstruction more reliable. Refinement in vascular surgical techniques and the advent of effective thrombolytic therapy have made the results of therapy more consistent. First rib resection and scalenectomy are curative for the majority of patients whose symptoms are caused by compression of the brachial plexus. Removal of the embologenic focus with vascular reconstruction and thoracodorsal sympathectomy are generally required in the presence of subclavian artery compression or aneurysm producing peripheral emboli. In patients who have venous compromise, thrombectomy or thrombolytic therapy and relief of subclavian venous compression may minimize future disability.

Angiography↗
PubMed1985

Reversibility of phorbol diester-induced macrophage spreading.

Phorbol 12-myristate 13-acetate and phorbol 12, 13-dibutyrate induced spreading of mouse macrophages with 50% effective concentrations of 3 nM and 35 nM, respectively. Macrophages treated with 100 or 1000 nM phorbol 12, 13- dibutyrate showed a time related decrease in spreading after washout. Spreading induced by 1, 10, or 100 nM phorbol 12-myristate 13-acetate was irreversible; however, washed phorbol 12,13-dibutyrate-treated cells respread after a second exposure to this compound. Washout of 3[H]phorbol diesters corroborated these observations in that 5% of 3H-phorbol 12-myristate 13-acetate and only 0.1% 3[H]phorbol, 12,13-dibutyrate remained associated with washed cells. Since phorbol 12-myristate 13 acetate is much more lipophilic than phorbol 12,13-dibutyrate, the reversibility of phorbol diester-induced macrophage spreading may depend upon the lipophilicity of the derivative utilized.

Animals↗
PubMed1985

Alterations in calcium metabolism in phorbol ester-treated mouse peritoneal macrophages.

Phorbol 12-myristate 13-acetate (PMA)-treated macrophages exhibited a two-fold increase in the rate of 45Ca++ efflux and over a three-fold increase in the size of the exchangeable calcium pool, resulting in almost a seven-fold increase in the slow phase of calcium efflux. The calcium antagonist 8-(N,N-diethylamino) octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) by itself did not affect calcium efflux in macrophages; but abolished the PMA-induced increase in the rate of calcium efflux. The divalent cationphore A23187 increased the rate constant of the fast phase of calcium efflux two-fold when applied alone or when applied with PMA. These effects might be linked to ionophore enhancement and TMB-8 inhibition of PMA-induced macrophage chemotaxis and spreading (previously reported in Cell Calcium 3:503-514 and Cancer Research 43:3385-3391). No change in calcium efflux was observed if cells were exposed to PMA only during the efflux experiment suggesting that a prolonged exposure to PMA is required to elicit changes in calcium flux. Increased 45Ca++ remained in treated cells at each time point perhaps reflecting the PMA-induced increase in exchangeable calcium.

Animals↗
PubMed1985

Venous gangrene of the upper extremity.

Gangrene of the hand associated with acute upper extremity venous insufficiency has been seen in four limbs in three patients treated at Vanderbilt University Medical Center. All three patients had life-threatening illnesses associated with diminished tissue perfusion, hypercoagulability, and venous injury. One patient progressed to above-elbow amputation, but venous thrombectomy in one limb and thrombolytic therapy in two others were successful in preventing major tissue loss. All three patients eventually died from their underlying illness. Thirteen previously reported patients with "venous gangrene" of the upper extremity have been analyzed. An underlying life-threatening illness was present in the majority of these patients (7/13, 54%) and, like the Vanderbilt series, amputations were frequent (7/13, 54%) and mortality (5/13, 38%) was high. This unusual form of ischemia appears to be produced by permutations of global circulatory stasis, subclavian or axillary vein occlusion, and peripheral venous thrombosis. Early, aggressive restoration of adequate cardiac output and thrombectomy and/or thrombolytic therapy may provide the best chance for tissue salvage and survival in this group of patients.

Adolescent↗
PubMed1984

Operative management of renovascular hypertension. Results after a follow-up of fifteen to twenty-three years.

From March 1960 through January 1968, 71 patients underwent operations for renovascular hypertension at our center. There were three operative deaths in 94 procedures. Primary nephrectomy was performed in 26 patients. Attempted revascularization of 62 kidneys was successful in 46 (74%). In 13 (87%) of the 15 cases considered operative failures, the patients underwent either secondary nephrectomy (11) or repeat revascularization (two). Based on the results of the final operation, initial blood pressure response (1 to 6 months postoperatively) in the surviving patients indicated 44% cured (30 patients), 40% improved (27), and 16% unchanged (11). The sequential clinical, functional, and anatomic follow-up evaluations to time of death or to date are available in 66 of the 68 patients (97%) who survived operation and form the basis of this report. Fifteen- to 20-year arteriographic follow-up in 16 patients revealed one late neointimal anastomotic stenosis and an additional three aortic suture line false aneurysms in Dacron aortorenal grafts. During this 15- to 23-year follow-up, 71% of atherosclerotic (AS) patients and 23% of fibromuscular dysplasia (FMD) patients died. Cardiovascular (CV) morbid events occurred in 77% of AS patients and in 19% of FMD patients. The cumulative incidence of death and CV morbid events during follow-up is examined by Kaplan-Meier life tables and Cox's proportional hazards regression analysis in these respective groups to identify preoperative markers predictive of longer event-free survival in relation to blood pressure benefit by operation (for example, focal vs. diffuse AS, presence of cerebrovascular disease, ischemic heart disease, left ventricular hypertrophy seen by electrocardiography, azotemia, smoking, diabetes, and hyperlipidemia).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Suprarenal vena caval occlusion. Principles of operative management.

Retrohepatic occlusion of the inferior vena cava caused by tumor complicates complete resection and not infrequently is associated with life-threatening symptoms that accelerate the lethality of the underlying malignant process. This report summarizes our experience with caval thrombectomy and reconstruction that allowed complete removal of all gross tumor in seven patients with malignant occlusion of the retrohepatic inferior vena cava. Included in this group are five patients with renal cell carcinoma and extension of tumor into the retrohepatic vena cava. Three of these patients had extension of tumor thrombus into the right atrium. A sixth patient had recurrent right adrenal cortical carcinoma with tumor invasion of the vena cava and occlusion to the right atrium. Associated hepatic vein occlusion and secondary Budd-Chiari syndrome also was successfully managed in this patient. The final patient with occlusion of the entire suprarenal vena cava required caval reconstruction after resection of a primary leiomyosarcoma of the retrohepatic portion of the vena cava. Careful planning of the operative procedure, adequate exposure, complete mobilization of the retrohepatic vena cava, and control of the hepatic venous effluent will allow patients with retrohepatic vena caval occlusions to be managed with safety and success.

Adenocarcinoma↗
PubMed1984

Renal artery dissection.

Renal artery dissections are stenotic or occlusive lesions most often observed in hypertensive patients with underlying atherosclerosis or fibromuscular disease. Acute dissections may present spontaneously, as a complication of diagnostic or therapeutic angiography or as an agonal event associated with overwhelming systemic illness. Chronic dissections may produce renovascular hypertension or be entirely asymptomatic. Fourteen renal artery dissections have been encountered in nine patients treated at Vanderbilt University Medical Center during the past decade. Eleven dissections have been found in seven patients with renovascular hypertension. Seven of these dissections were chronic (six functional, one silent) and four acute (two spontaneous, two secondary to angiography). Three agonal dissections were found in two additional patients postmortem: one at autopsy and bilateral dissections found at the time of cadaveric donor nephrectomy. Ten bypass procedures, including five complex branch reconstructions of which three were performed ex vivo, have been performed with 100% immediate patency and maintenance or improvement of renal function. Long-term follow-up of these patients has shown sustained patency of the reconstructed renal arteries, excellent blood pressure control, and normal renal function in all. Nephrectomy has not been required and there have been no associated deaths. Seventy-seven additional renal artery dissections in 72 patients collected from previous reports have been analyzed. Patient survival (55/72, 76.4%) and preservation of the involved kidney in surviving patients (26/55, 47.3%) were low in these earlier series. In addition, renal failure was associated with 59% of the deaths. The lethality of renal artery dissections and the ease and success of revascularization, which preserves renal function and ameliorates associated renovascular hypertension, emphasize the need for an aggressive approach to the recognition and treatment of this entity. Therapy should be directed toward arterial reconstructions and the preservation of functioning renal tissue.

Adult↗
PubMed1983

Calcium modulation of phorbol ester-induced alterations in murine macrophage morphology.

The phorbol ester tumor promoter phorbol-12-myristate-13-acetate (PMA) induced mouse resident peritoneal macrophage spreading in an in vitro system in a time- and dose-dependent manner; this process was modified by agents which alter intracellular calcium metabolism. After a 35-min incubation with PMA, 50% of the macrophages were spread (as classified by at least a 2-fold increase in cell surface area). Also at 35 min, the median effective concentration for PMA induction of spreading was 1.6 ng/ml. The intracellular calcium antagonist 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate inhibited PMA-induced cell spreading with a one-half maximal inhibitory concentration of 8.0 microM. The calcium ionophore A23187 enhanced PMA-induced spreading by 30% at 0.1 to 10 nM. The histological dye ruthenium red, which purportedly increases intracellular calcium by displacing membrane-bound calcium stores, enhanced PMA-induced spreading up to 75% at 1.0 pM. The cationic chelator ethyleneglycolbis(beta-aminoethylether)-N,N-tetraacetic acid (1.8 and 3.6 mM) had no effect on PMA-induced spreading. Thus, PMA-induced spreading was independent of extracellular calcium but was modulated by agents altering intracellular calcium metabolism. Microfilament formation, a proposed mechanism of cell spreading, also depends on intracellular calcium availability. The microfilament inhibitor cytochalasin B inhibited PMA-induced spreading with a one-half maximal inhibitory concentration of 1 microM. Future experiments should investigate the hypothesis that calcium availability to the cytoskeletal elements regulates the morphological effects of PMA on macrophages.

Animals↗
PubMed1983

Histoplasma infection of abdominal aortic aneurysms.

Fungal endarteritis resulting from progressive disseminated histoplasmosis may cause arterial aneurysms, or lead to infection of pre-existing aneurysms. Three patients with Histoplasma capsulatum infections of abdominal aortic aneurysms are reported. All had previous disseminated histoplasmosis and atherosclerotic peripheral vascular disease. All were considered cured of systemic infection when their aneurysms were discovered. Atherosclerotic vascular lesions may become infected during the course of systemic fungal disease and may serve as a haven for viable organisms in patients whose dissemination recurs despite seemingly adequate antifungal therapy. In treating these patients, resection of all infected arterial tissue, revascularization through uninfected tissues, and long-term antimicrobial therapy are recommended.

Adult↗
PubMed1983

Activity of two polyene and two imidazole antimicrobics on Candida albicans in human fibrin clots.

The vegetations of infective fungal endocarditis were simulated by preparing human fibrin clots containing 10(5) CFU of Candida albicans per clot. Clots were incubated in human serum without drugs (controls) or with equimolar concentrations (2.5 to 20 nmol/ml) of four antifungal antimicrobics: AMB and miconazole (both colloidal suspensions) and DAB and KET (both molecularly dispersed). Over a period of 4 days of incubation, clots were resuspended in freshly prepared serum-antimicrobic every 12 hr. Cohorts of control and drug-exposed clots were cultured quantitatively at 24 hr intervals. Neither imidazole at any concentration tested prevented growth of C. albicans to an extent that was significantly different from growth in the control clots. Both polyenes reduced the CFU/clot, with AMB significantly more active than DAB.

Amphotericin B↗
PubMed1983

Antagonist of phorbol ester receptor-mediated chemotaxis in mouse peritoneal macrophages.

Biologically active phorbol ester derivatives displace [3H]phorbol-12, 13-dibutyrate from thioglycollate-elicited mouse peritoneal macrophages in a time-, temperature-, and concentration-dependent manner. Scatchard analysis revealed an apparent Kd of 54.1 nM and 8.0 X 10(5) sites/cell, indicating that these macrophages possess saturable, high-affinity phorbol ester-binding sites. These derivatives also act as chemoattractants for the macrophage at equivalent concentrations. A notable exception to this pattern is phorbol-12,13-diacetate. Phorbol-12,13-diacetate inhibits specific binding of [3H]phorbol-12,13-dibutyrate (concentration required for a 50% inhibition of the maximum specific binding of [3H]phorbol-12,13-dibutyrate, 2.6 microM) and chemotaxis to phorbol-12-myristate, 13-acetate (concentration required for a 50% inhibition of the maximum chemotactic response, 0.39 microM) while exhibiting no activity as a chemoattractant at concentrations up to 10(-5) M. The data indicate that phorbol-12,13-diacetate may be an antagonist for receptor-mediated chemotaxis to phorbol-12-myristate, 13-acetate in the macrophage.

Animals↗
PubMed1982

The strength of microvascular anastomoses--an experimental evaluation in rats.

To determine the longitudinal strength of microvascular anastomoses during early healing, the left femoral arteries of 56 rats were divided and anastomosed with six interrupted sutures of 10-0 nylon. The right femoral arteries served as unoperated controls. The vessels were then harvested immediately, or 3, 7, 14, 21, 28, or 120-150 days after surgery. The cross-sectional surface area was measured and the force required to pull the vessels apart (burst strength) was determined with a tensiometer. Fifty-four of the 56 anastomosed vessels were patent at the time of harvest. All of the operated vessels ruptured at the site of anastomosis when the sutures pulled through the vessel wall. The mean burst strength of the anastomosed vessels was 44% of the contralateral unoperated controls immediately after surgery and did not significantly increase for four to five months. It was concluded that early mobilization of replanted parts is not limited by the strength of microarterial anastomoses.

Animals↗
PubMed1982

The role of calcium in macrophage chemotaxis to the phorbol ester tumor promoter TPA.

The significance of the macrophage in the inflammatory response that occurs concurrently with phorbol ester induced tumor promotion has not yet been determined. Biologically active phorbol ester tumor promoters modify several functional responses of macrophages including chemotaxis, cytotoxicity, secretion and prostaglandin synthesis and release. The present study examines calcium metabolism as a possible underlying biochemical mechanism through which 12-0-tetradecanoyl-phorbol-13-acetate (TPA) exerts its effects on macrophage chemotaxis. The chemotaxis of mouse resident peritoneal macrophages was evaluated in the presence of pharmacological agents known to alter cellular calcium metabolism. The calcium ionophore A23187 in microM concentrations enhanced macrophage chemotaxis to TPA by approximately 41%. This enhancement was dependent on the presence of extracellular calcium. TPA-induced chemotaxis was also enhanced by the histological dye ruthenium red (RR), an agent known to modify mitochondrial calcium fluxes and calcium-dependent neuronal transmission. Ruthenium red (0.1 and 1.0 microM) produced a maximal stimulation of macrophage chemotaxis to TPA of approximately 62%. An intracellular calcium antagonist, 8-(N,N-diethylamino) octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) inhibited macrophage chemotaxis to TPA in a dose related fashion (1.0 to 100 microM). Varying extracellular calcium concentrations (0-3.6 mM) had no effect on macrophage chemotaxis in response to TPA. In drug combination studies neither A23187 nor RR was able to overcome the inhibitory effects of TMB-8 on macrophage chemotaxis to TPA. These results indicate that intracellular calcium metabolism may be playing a significant role in modulating TPA's effect on macrophage chemotaxis, while extracellular calcium may be of little import. A possible mode of TPA's effect on the macrophage via mobilization of calcium from cellular storage sites is discussed.

Animals↗