Biomedical subjects

J Woodson

Publications and source records attributed to J Woodson.

At least 19 recordsLinked to original sources

PubMed2001

Binding of regulator of G protein signaling (RGS) proteins to phospholipid bilayers. Contribution of location and/or orientation to Gtpase-activating protein activity.

Regulator of G protein signaling (RGS) proteins must bind membranes in an orientation that permits the protein-protein interactions necessary for regulatory activity. RGS4 binds to phospholipid surfaces in a slow, multistep process that leads to maximal GTPase-activating protein (GAP) activity. When RGS4 is added to phospholipid vesicles that contain m2 or m1 muscarinic receptor and G(i), G(z), or G(q), GAP activity increases approximately 3-fold over 4 h at 30 degrees C and more slowly at 20 degrees C. This increase in GAP activity is preceded by several other events that suggest that, after binding, optimal interaction with G protein and receptor requires reorientation of RGS4 on the membrane surface, a conformational change, or both. Binding of RGS4 is initially reversible but becomes irreversible within 5 min. Onset of irreversibility parallels initial quenching of tryptophan fluorescence (t(12) approximately 30 s). Further quenching occurs after binding has become irreversible (t(12) approximately 6 min) but is complete well before maximal GAP activity is attained. These processes all appear to be energetically driven by the amphipathic N-terminal domain of RGS4 and are accelerated by palmitoylation of cysteine residues in this region. The RGS4 N-terminal domain confers similar membrane binding behavior on the RGS domains of either RGS10 or RGSZ1.

Animals↗

PubMed2001

Contrast-enhanced moving-table MR angiography: prospective comparison to catheter arteriography for treatment planning in peripheral arterial occlusive disease.

PURPOSE: Prospective comparison of contrast-enhanced moving-table magnetic resonance (MR) angiography to catheter arteriography in endovascular and surgical treatment planning in patients with peripheral arterial occlusive disease. MATERIALS AND METHODS: Thirteen patients scheduled for catheter arteriography for lower extremity arterial occlusive disease underwent contrast-enhanced moving-table MR angiography immediately prior to arteriography. A treatment plan was determined by the vascular surgeon, based on MR angiography, who was blinded to the catheter arteriogram. The treatment plan determined by the MR angiogram was compared to the final treatment plan, which was based on the catheter arteriogram and intraluminal pressure measurements. RESULTS: Treatment plans based on MR angiography and catheter arteriography were identical in 10 of 13 patients (71%). For identifying lesions resulting in intervention, MR angiography had sensitivity of 100% and a positive predictive value of 92%. MR angiography had a treatment specific predictive value of 88% for each lesion identified, and 95% for lesions identified in patients evaluated for claudication. If treatment plans were based on MR angiography only, 46% of patients would have avoided catheter arteriography. CONCLUSION: Contrast-enhanced moving-table MR angiography may be an effective alternative to catheter arteriography in endovascular and surgical treatment planning in selected patients with peripheral arterial occlusive disease, but larger studies are necessary to confirm this.

Adult↗

PubMed1999

Activation of the p38 mitogen-activated protein kinase by type I interferons.

The p38 mitogen-activated protein (Map) kinase plays a critical role in the generation of signals in response to stress stimuli, but its role in interferon (IFN) signaling and its potential regulatory role in the activation of Jak-signal transducer and activator of transcription (Stat) pathway are not known. In the present study, we provide evidence that the p38 Map kinase is rapidly phosphorylated and activated during treatment of cells with Type I interferons (IFNalpha and IFNbeta). Furthermore, the Type I IFN-dependent activation of p38 regulates induction of the catalytic domains of MapKap kinase-2 and MapKap kinase-3, strongly suggesting the existence of an IFNalpha signaling cascade activated downstream of the p38 kinase. The engagement of this pathway in interferon signaling plays a critical role in interferon-dependent transcriptional regulation, as evidenced by the fact that inhibition of p38 activation results in abrogation of interferon-dependent gene transcription via interferon-stimulated response elements. Interestingly, inhibition of the kinase activity of the p38 blocks IFNalpha-induced gene transcription without inhibiting DNA binding or tyrosine phosphorylation of Stat proteins, suggesting that the p38 pathway acts in cooperation with the Stat pathway. Thus, the p38 kinase signaling cascade is activated by the Type I interferon receptor and plays a critical role in interferon signaling and interferon-dependent transcriptional regulation.

Base Sequence↗

PubMed1998

Impact of a critical pathway on postoperative length of stay and outcomes after infrainguinal bypass.

PURPOSE: To determine the effect of a critical pathway on postoperative length of stay and outcomes after infrainguinal bypass. METHODS: A critical pathway for care of patients after infrainguinal bypass was introduced in December 1995 to coordinate postoperative care at our institution. We compared care of 67 consecutively treated patients before institution of the pathway with care of 69 consecutively treated patients with the critical pathway in place. Data collection was done by means of chart review. Univariate analyses were used to identify differences between prepathway and postpathway patients and to identify factors influencing postoperative length of stay. Multivariate analysis was used to identify factors that influenced length of stay and to examine the effect of use of the pathway after adjusting for other factors. RESULTS: Patients on the pathway were similar to prepathway controls with respect to comorbid illnesses, vascular risk factors, indications for surgical treatment, type of conduit, and type of operation. Factors associated with longer postoperative stays included distal anastomoses to tibial rather than popliteal vessels (p = 0.02), preexisting cardiac disease (p = 0.005), postoperative complications (p = 0.0003), lower preoperative hematocrit (p = 0.01), and elevated preoperative creatinine level (p = 0.006). Overall, pathway patients had somewhat shorter postoperative lengths of stay (median value 7 days; range 2 to 29 days) than prepathway patients (median value 6 days; range 2 to 35; p = 0.01), and the two groups had similar frequencies of postoperative complications, readmission, and 6-month mortality. However, patients on the pathway were more likely to be discharged to an intermediate-care facility rather than directly home. After 12 patients with extraordinarily prolonged postoperative stays were excluded, multivariate analysis indicated that pathway patients had significantly shorter postoperative stays (p = 0.001). However, the difference was not significant if patients with extraordinarily long postoperative stays were included in the analysis (p = 0.28). CONCLUSION: Use of a critical pathway was associated with a modest decrease in postoperative length of stay for most patients. This was accomplished without an adverse effect on readmission, complication, or mortality rates. However, the decrease in stay may have been achieved primarily by discharging more patients to intermediate-care facilities. The pathway did not appear to have any effect when the subset of patients with extraordinarily long stays because of complex medical problems was included.

Aged↗

PubMed1997

A GTPase-activating protein for the G protein Galphaz. Identification, purification, and mechanism of action.

A GTPase-activating protein (GAP) specific for Galphaz was identified in brain, spleen, retina, platelet, C6 glioma cells, and several other tissues and cells. Gz GAP from bovine brain is a membrane protein that is refractory to solubilization with most detergents but was solubilized with warm Triton X-100 and purified up to 50,000-fold. Activity is associated with at least two separate proteins of Mr approximately 22,000 and 28,000, both of which have similar specific activities. In an assay that measures the rate of hydrolysis of GTP pre-bound to detergent-soluble Galphaz, the GAP accelerates hydrolysis over 200-fold, from 0.014 to 3 min -1 at 15 degrees C, or to >/=20 min-1 at 30 degrees C. It does not alter rates of nucleotide association or dissociation. When co-reconstituted into phospholipid vesicles with trimeric Gz and m2 muscarinic receptor, Gz GAP accelerates agonist-stimulated steady-state GTP hydrolysis as predicted by its effect on the hydrolytic reaction. In the single turnover assay, the Km of the GAP for Galphaz-GTP is 2 nM. Its activity is inhibited by Galphaz-guanosine 5'-O-thiotriphosphate (Galphaz-GTPgammaS) or by Galphaz-GDP/AlF4 with Ki approximately 1.5 nM for both species; Galphaz-GDP does not inhibit. G protein betagamma subunits inhibit Gz GAP activity, apparently by forming a GTP-Galphazbetagamma complex that is a poor GAP substrate. Gz GAP displays little GAP activity toward Galphai1 or Galphao, but its activity with Galphaz is competitively inhibited by both Galphai1 and Galphao at nanomolar concentrations when they are bound to GTPgammaS but not to GDP. Neither phospholipase C-beta1 (a Gq GAP) nor several adenylyl cyclase isoforms display Gz GAP activity.

Animals↗

PubMed1996

Carboxyl-terminal fragments of phospholipase C-beta1 with intrinsic Gq GTPase-activating protein (GAP) activity.

Fragments of the approximately 50 kDa COOH-terminal region of phospholipase C-beta1 (PLC-beta1(1)), ranging in size from 14 to 38 kDa, were expressed in Escherichia coli, purified, and tested for their regulatory activities. As expected, none of the fragments had phospholipase activity. Several fragments, referred to as PLC tails, displayed GTPase-activating protein (GAP) activity for Gq, the G protein class that stimulates the PLC-betas in response to receptors. Gq GAP activity is characteristic of intact PLC-betas. In reconstituted phospholipid vesicles that contained purified Gq and m1 muscarinic cholinergic receptors, the most active tails increased agonist-stimulated, steady-state GTPase activity over 4-fold. Stimulation of steady-state GTPase by the tails depended on receptors for facilitation of GDP-GTP exchange, suggesting that the tails act by accelerating hydrolysis of bound GTP. In addition to intrinsic GAP activity, one tail with high GAP activity and others with low or minimal activity potentiated the GAP activity of intact PLC-beta1. Other tails inhibited PLC-beta1s GAP effect. Both intrinsic GAP activity and potentiation of the PLC-beta1 GAP effect were often biphasic, with maxima as low as 100 nM tail and declining activities at higher concentrations. Several tails inhibited either the phospholipase activity of PLC-beta1, its stimulation by Gq, or both. The tails thus define the region of PLC-beta1 that has Gq GAP activity and suggest a mechanism of action in which the COOH terminus of PLC-betas can interact with Gq and with other PLC-beta1 molecules.

GTPase-Activating Proteins↗

PubMed1996

Multiple mycotic pseudoaneurysms due to Yersinia enterocolitica: report of a case and review of the literature.

The etiology of mycotic aneurysms is variable but most often includes streptococci, staphylococci, Salmonella, and Pseudomonas infections. Yersinia enterocolitica is an organism that has been infrequently associated with vascular infections. We report a case of two ruptured mycotic pseudoaneurysms occurring in the same patient in the superficial femoral artery and the infrarenal abdominal aorta only 10 days apart. The literature is reviewed, and the clinical findings and pathology are discussed. The unique problem of multiple mycotic aneurysms developing at different times as a result of Yersinia bacteremia suggests the need to monitor these patients longitudinally and evaluate multiple sites on the arterial tree to detect occult pseudoaneurysms and prevent late death from rupture.

Aneurysm, False↗

PubMed1994

The retroperitoneal incision. An evaluation of postoperative flank 'bulge'.

OBJECTIVES: To determine if intercostal nerve injury is related to postoperative flank "bulge" and to determine whether the extent of the retroperitoneal incision is related to the incidence of flank bulge following abdominal aortic aneurysm repair. DESIGN: Bilateral dissection of the 11th intercostal nerve on seven cadavers; neurophysiological evaluation of five patients, three with a flank bulge and two without; and retrospective analysis of the extent of retroperitoneal incision and incidence of postoperative flank bulge in 63 consecutive patients. SETTING: Urban academic medical center. PATIENTS: Sixty-three consecutive patients who underwent retroperitoneal repair of an abdominal aortic aneurysm and neurophysiological evaluation of five volunteer patients. INTERVENTIONS: Retroperitoneal repair of abdominal aortic aneurysms. MAIN OUTCOME MEASURE: Reduction of injury to the 11th intercostal nerve by avoiding extension of the retroperitoneal incision into the intercostal space. RESULTS: Of 14 dissections of 11th intercostal nerves, there were bifurcations of the main trunk within the intercostal space in four, at the tip of the 11th rib in seven, and at least 2 cm distal to the tip of the rib in three. Neurophysiological evaluation revealed iterative discharges, polyphasia, fibrillation potentials, and altered recruitment patterns compatible with intercostal nerve injury in patients with a bulge but not in the opposite abdominal wall musculature or in patients without a bulge. Seven (11.11%) of 63 patients had a bulge. Thirty-one of 63 patients had incisions into the 11th intercostal space in which a bulge developed in six (19.35%). Thirty-two patients had incisions that avoided extension into the intercostal space; a bulge developed in one (0.03%) (P = .53). CONCLUSIONS: Postoperative bulge is related to intercostal nerve injury with subsequent paralysis of abdominal wall musculature. Intercostal nerve injury can be reduced by avoiding extension of the incision into the 11th intercostal space.

Action Potentials↗

PubMed1994

Functional outcomes in limb salvage vascular surgery.

BACKGROUND: The crisis in health care brings a new focus to defining successful outcomes of medical treatments. The surgical literature has been criticized for not assessing functional outcomes in addition to technical success. METHODS: We evaluated the functional outcomes of limb salvage surgery over 3 years in 38 patients 65 years of age and older with limb-threatening ischemia. The RAND-36-Item Health Survey 1.0 was used as a health assessment tool. RESULTS: In spite of an 80% limb salvage rate, only 58% of patients survived 3 years and only 25% survived with the index limb and were able to walk. The RAND scores of patients whose limbs were amputated did not significantly differ from those of patients whose surgery was successful. CONCLUSION: Functional outcome goals need to be better defined for patients who need limb salvage vascular operations to enhance the quality of care given these patients and to be in concert with emerging health policy.

Activities of Daily Living↗

PubMed1994

Management of vascular trauma.

The management of victims with vascular injuries is a challenging affair. Speedy transport, prioritizing injuries, and prompt repair of injured vessels produce good results with minimum morbidity and mortality. An increasing trend of urban violence and invasive medical care indicates the importance for having a coherent strategy for managing these problems.

Blood Vessels↗

PubMed1993

Role of arteriography for blunt or penetrating injuries in proximity to major vascular structures: an evolution in management.

Over a 14-month period at Boston City Hospital, 93 consecutive patients who had received a blunt or penetrating extremity injury in proximity to a major vascular structure were evaluated. All patients were totally asymptomatic and underwent arteriography for proximity as a sole indication. Twenty-seven patients (27%) were found to have abnormal arteriograms. Muscular branches of the profunda femoris artery were the most frequently injured arteries (28%). Arterial spasm (41%) was the most common radiographic finding. All patients were managed nonoperatively and followed closely by serial pulse examinations. Follow-up arteriography or duplex scanning was used in isolated cases. No patients in this study required operative intervention based on arteriographic findings. No patients have subsequently required operative intervention for delayed arterial abnormalities. Based on these findings we believe the use of arteriography for asymptomatic injuries in proximity to major vascular structures is unwarranted.

Adolescent↗

PubMed1993

Can air plethysmography accurately identify upper extremity deep venous thrombosis?

PURPOSE: Air plethysmography (APG) is an established, noninvasive means of evaluating lower extremity venous outflow. METHODS: To determine whether APG could identify deep venous thrombosis (DVT) of the upper extremity, we measured the percentage of venous outflow in the first second (maximum venous outflow [MVO]) of four groups of arms: (1) normal volunteers (no previous central vein catheters), (2) the affected, (3) the unaffected arms of the patients with DVT (proven by venography or duplex scanning), and (4) hospital patients (no previous central vein catheters). RESULTS: The results of an analysis of variance were as follows: the mean MVO (%) of the affected arms of patients with DVT, 29.4 +/- 2.6, was significantly less than their unaffected arms, 55.3 +/- 3.9, hospital controls, 64.3 +/- 2.2, and normal volunteers, 64.2 +/- 0.9 (p < 0.05). In addition, the unaffected arms differed significantly from all groups (p < 0.05). An MVO of 45% was 2 SD below the mean MVO of the normal volunteer group. Two unaffected arms of the patients with DVT were below 45%, whereas only one affected arm of the patients with DVT was above 45% (45.6%). Therefore a comparison of the distribution of the MVO values revealed virtually no overlap of the affected arms of the patients with DVT with the other three groups. CONCLUSIONS: We conclude that APG clearly discriminated arms with documented DVT from controls and is a highly accurate means of identifying upper extremity DVT.

Adult↗

PubMed1993

Temporary thoracotomy wound closure following penetrating thoracic aorta injury.

On rare occasions, thoracic injuries require resuscitative efforts including emergent thoracotomy that result in edematous changes to the lungs and heart. Hemodynamic compromise occurs when these organs are placed in their anatomic position and closure of the thoracotomy is attempted. Adaptation of a temporary abdominal closure to a thoracic injury is described.

Aorta, Thoracic↗

PubMed1992

Arteriography for proximity of injury in penetrating extremity trauma.

Arteriography for proximity of injury was studied prospectively at a trauma center. Findings in 85 patients with penetrating extremity wounds were analyzed to determine the prevalence and types of vascular abnormalities seen with these injuries. Ninety-two limb segments were studied for 77 gunshot and 15 stab wounds. Arteriographic findings were positive in 24% overall but in only 5% for injuries confined to major vessels. A 60% positive rate was seen in a small subgroup of 10 patients with fractures due to gunshot wounds. The most frequently injured vessels were muscular branches of the deep femoral artery (59%); the most common injury was focal, non-occlusive spasm (42%). All patients were treated conservatively, without sequelae at follow-up. In this study, the vascular injuries found at arteriography for proximity of injury in penetrating trauma due to bullets of knives, particularly in the thigh, did not require surgical or radiologic intervention.

Adolescent↗

PubMed1992

The role of air plethysmography in monitoring results of venous surgery.

The development of an objective, noninvasive method to assess the hemodynamic effects of venous surgery has long been awaited. Previous methods used to evaluate the results of surgery for varicose veins and venous stasis ulceration have been limited in their quantitative assessment. Now, by use of air plethysmography (APG), we can accurately quantify the effectiveness of corrective venous surgery. Twenty-five extremities that had evidence of venous insufficiency were examined with use of APG before and after venous surgical procedures. Surgery was directed at specific sites of venous incompetence as defined by physical examination and high-resolution duplex imaging. Twenty-one extremities underwent ligation and stripping of the greater saphenous vein. In these patients, APG showed an improvement in venous reflux as demonstrated by a decrease in the venous filling index from 6.6 +/- 0.7 ml/sec to 1.8 +/- 0.3 ml/sec (p = 0.0001) and venous volume from 177.1 +/- 14.5 ml to 139.2 +/- 8.9 ml (p = 0.0008). In addition, these patients showed a mild improvement in calf muscle pump function as noted by an improvement in ejection fraction from 45.8 +/- 2.0% to 50.8% +/- 2.5% (p = 0.07). The residual volume fraction decreased from 45.0% +/- 3.4% to 42.0% +/- 3.7%, a difference that was not statistically significant (p = 0.4). Four extremities with grade III chronic venous insufficiency underwent popliteal vein valve transplantation with use of an autogenous axillary vein valve.(ABSTRACT TRUNCATED AT 250 WORDS)

Air↗

PubMed1992

A prospective, randomized trial of Unna's boot versus Duoderm CGF hydroactive dressing plus compression in the management of venous leg ulcers.

Leg ulcers caused by chronic venous insufficiency plague an estimated 500,000 Americans, but there have been few improvements in conservative treatment in this century, and Unna's boot continues to be a mainstay of therapy. A recent report suggests that Duoderm CGF dressing provides greater patient comfort and enhanced compliance, but Duoderm alone (without compression) resulted in slower healing compared with Unna's boot. We enrolled 30 patients (30 ulcers) in a clinical trial to compare Duoderm CGF plus compression (Coban wrap) to Unna's boot. No significant difference was observed between the two groups with respect to age, sex, initial ulcer area, ulcer duration, or extent of venous insufficiency by duplex scan. Eight of 16 ulcers (50%) in the Duoderm group healed completely versus 6 of 14 ulcers (43%) in the Unna's boot group (p = 0.18). Healing rates (square centimeters per week) correlated significantly with initial ulcer area and initial ulcer perimeter for both groups but best correlated with initial ulcer perimeter (r = 0.88 with Duoderm, p less than 0.0001; r = 0.80 with Unna's boot, p less than 0.002). After adjusting for differences in initial ulcer perimeter, healing rates were significantly faster for patients on Duoderm than patients on Unna's boot during the first 4 weeks of therapy (0.384 +/- 0.059 cm2/wk/cm perimeter for Duoderm versus 0.135 +/- 0.043 cm2/wk/cm perimeter for Unna's boot; p = 0.002). At 12 weeks patients on Duoderm again appeared to heal faster than those on Unna's boot, although the result did not reach statistical significance (0.049 +/- 0.007 cm2/wk/cm perimeter for Duoderm versus 0.020 +/- 0.017 for Unna's boot, p = 0.11).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1991

Intraaortic balloon pump entrapment.

Catheter entrapment is a rare complication of intraaortic balloon counterpulsation caused by the formation of hard blood clot within the balloon itself. We present two cases of intraaortic balloon pump entrapment seen at the University Hospital, Boston. This phenomenon usually presents as a limb threatening vascular emergency. The entrapped catheter becomes stuck fast within the iliac system during withdrawal of the device, occluding arterial flow at that level. The etiology of this phenomenon, and a proposed management scheme is discussed. Preoperative radiographic determination of the level of entrapment may be necessary. We feel it is necessary to control the abdominal aorta prior to removal of an entrapped intraaortic balloon.

Aged↗

PubMed1991

The management of traumatic aortic tear in the multiply-injured patient.

Patients with traumatic aortic tears and severe life-threatening associated injuries require early and expeditious evaluation and treatment in order to improve survival. Diagnostic and treatment priorities, however, are not clearly established in this subset of patients. The purpose of this retrospective analysis was to help identify successful diagnostic and treatment priorities in this group of patients. Between 1979-1989 the medical records of all patients sustaining blunt chest trauma resulting in a traumatic aortic tear were reviewed. There were 11 patients with multiple injuries and this diagnosis was treated at Boston University Medical Center. Five patients had diagnostic peritoneal lavage or an exploratory laparotomy prior to a thoracotomy. Four patients had only a thoracotomy. Two patients in this series had a thoracotomy prior to treatment of suspected intraabdominal injuries. One of these two patients died. Our overall survival rate was 82%. This series suggests that the management sequence in patients with coexistent injuries should include treatment of severe associated injuries prior to treatment of the aortic injury and that initial treatment of traumatic aortic tears is appropriate if there is no evidence of severe life-threatening trauma.

Adult↗