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J V White

Publications and source records attributed to J V White.

At least 37 records · Page 2Linked to original sources
PubMed1994

Protein classification by stochastic modeling and optimal filtering of amino-acid sequences.

The prediction of a protein's tertiary structural class from its amino-acid sequence is formulated as a signal-processing problem. The amino-acid sequence is treated as a "time series" of symbols containing signals that determine the protein's structural class. A methodology is described for building detailed stochastic signal models for recognized structural classes of single-domain proteins. We solve the problem of determining that model, from a set of candidates, which is the most probable generator of a protein's entire amino-acid sequence. The solution employs a nonlinear, optimal filtering algorithm, which is suited for implementation on parallel computer architectures. Previous approaches have only been able to classify correctly 80% of single-domain proteins within three very broad structural types, while our approach achieves this level across twelve much more detailed classes.

Amino Acid Sequence↗
PubMed1994

Modeling protein cores with Markov random fields.

A mathematical formalism is introduced that has general applicability to many protein structure models used in the various approaches to the "inverse protein folding problem." The inverse nature of the problem arises from the fact that one begins with a set of assumed tertiary structures and searches for those most compatible with a new sequence, rather than attempting to predict the structure directly from the new sequence. The formalism is based on the well-known theory of Markov random fields (MRFs). Our MRF formulation provides explicit representations for the relevant amino acid position environments and the physical topologies of the structural contacts. In particular, MRF models can readily be constructed for the secondary structure packing topologies found in protein domain cores, or other structural motifs, that are anticipated to be common among large sets of both homologous and nonhomologous proteins. MRF models are probabilistic and can exploit the statistical data from the limited number of proteins having known domain structures. The MRF approach leads to a new scoring function for comparing different threadings (placements) of a sequence through different structure models. The scoring function is very important, because comparing alternative structure models with each other is a key step in the inverse folding problem. Unlike previously published scoring functions, the one derived in this paper is based on a comprehensive probabilistic formulation of the threading problem.

Amino Acid Sequence↗
PubMed1994

A strategy of aggressive regional therapy for acute iliofemoral venous thrombosis with contemporary venous thrombectomy or catheter-directed thrombolysis.

PURPOSE: Occlusive iliofemoral venous thrombosis is associated with morbid short- and long-term consequences. Having been disappointed with standard anticoagulant therapy and systemic fibrinolysis, we embarked on an aggressive multidisciplinary regional approach to treat these patients, with the goals of therapy being (1) to eliminate iliofemoral venous thrombus, (2) to provide unobstructed venous drainage from the affected limb, and (3) to prevent recurrent thrombosis. METHODS: Twelve consecutive patients were treated for extensive iliofemoral venous thrombosis. Each had thrombus from their infrapopliteal veins through their iliofemoral system, and four had vena caval involvement. The conditions of 11 patients failed to improve when the patients were given anticoagulants, and prior systemic fibrinolysis failed in five patients. The treatment strategy includes catheter-directed thrombolysis with intrathrombus infusion of the plasminogen activator or operative thrombectomy or venous bypass with a permanent 4 mm arteriovenous fistula (AVF). RESULTS: Nine of 12 patients had a good or excellent clinical outcome (mean follow-up 25 months), which correlated with restored unobstructed venous drainage from the affected limb. Seven patients had catheter-directed lytic therapy attempted. In five patients the catheters were appropriately positioned, and lysis was successful. Five of the eight patients who underwent operations had successful procedures. Two of the three patients with poor operative outcomes had residual thrombus in their iliac veins or vena cava after thrombectomy (without bypass). The third patient, in whom anticoagulation was contraindicated, had an initially successful thrombectomy and AVF; however, vena caval thrombosis developed 2 months after operation. No patient had symptomatic pulmonary emboli, and routine posttreatment ventilation/perfusion lung scanning was not performed. CONCLUSIONS: An aggressive multidisciplinary regional approach to patients with obliterative iliofemoral venous thrombosis, designed to remove thrombus and provide unobstructed venous drainage, offers substantially better clinical outcome compared with systemic fibrinolysis and standard anticoagulation. Catheter-directed thrombolysis is successful if the catheter is appropriately positioned within the thrombus. Contemporary venous thrombectomy, which includes thrombus removal, completion phlebography, AVF, and cross-pubic bypass when necessary, is associated with high success rates. Failures can be anticipated and avoided in most patients.

Acute Disease↗
PubMed1994

Mechanisms of fatty acid-induced inhibition of glucose uptake.

Increased plasma FFA reduce insulin-stimulated glucose uptake. The mechanisms responsible for this inhibition, however, remain uncertain. It was the aim of this study to determine whether the FFA effect was dose dependent and to investigate its mechanism. We have examined in healthy volunteers (13 male/1 female) the effects of three steady state plasma FFA levels (approximately 50, approximately 550, approximately 750 microM) on rates of glucose uptake, glycolysis (both with 3-3H-glucose), glycogen synthesis (determined with two independent methods), carbohydrate (CHO) oxidation (by indirect calorimetry), hepatic glucose output, and nonoxidative glycolysis (glycolysis minus CHO oxidation) during euglycemic-hyperinsulinemic clamping. Increasing FFA concentration (from approximately 50 to approximately 750 microM) decreased glucose uptake in a dose-dependent fashion (from approximately 9 to approximately 4 mg/kg per min). The decrease was caused mainly (approximately 2/3) by a reduction in glycogen synthesis and to a lesser extent (approximately 1/3) by a reduction in CHO oxidation. We have identified two independent defects in glycogen synthesis. The first consisted of an impairment of muscle glycogen synthase activity. It required high FFA concentration (approximately 750 microM), was associated with an increase in glucose-6-phosphate, and developed after 4-6 h of fat infusion. The second defect, which preceded the glycogen synthase defect, was seen at medium (approximately 550 microM) FFA concentration, was associated with a decrease in muscle glucose-6-phosphate concentration, and was probably due to a reduction in glucose transport/phosphorylation. In addition, FFA and/or glycerol increased insulin-suppressed hepatic glucose output by approximately 50%. We concluded that fatty acids caused a dose-dependent inhibition of insulin-stimulated glucose uptake (by decreasing glycogen synthesis and CHO oxidation) and that FFA and/or glycerol increased insulin-suppressed hepatic glucose output and thus caused insulin resistance at the peripheral and the hepatic level.

Adult↗
PubMed1994

Risk factors for poor nutritional status.

Nutrition risk can be assessed in elderly populations by evaluating such factors as food intake, income, functional status, socialization, acute and chronic illness, and use of medications. Nutrition screening must become an integral component of the health care services provided for all older Americans. Nutrition screening and early intervention are primary steps in the development of a system of health care that is affordable and accessible to all.

Aged↗
PubMed1993

Structural analysis based on state-space modeling.

A new method has been developed to compute the probability that each amino acid in a protein sequence is in a particular secondary structural element. Each of these probabilities is computed using the entire sequence and a set of predefined structural class models. This set of structural classes is patterned after Jane Richardson's taxonomy for the domains of globular proteins. For each structural class considered, a mathematical model is constructed to represent constraints on the pattern of secondary structural elements characteristic of that class. These are stochastic models having discrete state spaces (referred to as hidden Markov models by researchers in signal processing and automatic speech recognition). Each model is a mathematical generator of amino acid sequences; the sequence under consideration is modeled as having been generated by one model in the set of candidates. The probability that each model generated the given sequence is computed using a filtering algorithm. The protein is then classified as belonging to the structural class having the most probable model. The secondary structure of the sequence is then analyzed using a "smoothing" algorithm that is optimal for that structural class model. For each residue position in the sequence, the smoother computes the probability that the residue is contained within each of the defined secondary structural elements of the model. This method has two important advantages: (1) the probability of each residue being in each of the modeled secondary structural elements is computed using the totality of the amino acid sequence, and (2) these probabilities are consistent with prior knowledge of realizable domain folds as encoded in each model. As an example of the method's utility, we present its application to flavodoxin, a prototypical alpha/beta protein having a central beta-sheet, and to thioredoxin, which belongs to a similar structural class but shares no significant sequence similarity.

Flavodoxin↗
PubMed1993

Registry of laparoscopic cholecystectomy and new and evolving laparoscopic techniques.

To collect information on the rapid application of laparoscopic surgery, the National Laparoscopic Surgery Registry surveyed more than 4,000 of the 16,000 currently practicing laparoscopic surgeons. Preliminary analysis of the data has revealed that most of the respondents had been trained in general surgery, but a small percentage were certified only in surgical subspecialties. Surgeons acquiring skills in laparoscopic surgery had various levels of experience ranging from less than 1 year to more than 38 years in surgical practice. Nearly 90% of the respondents attended a laparoscopic cholecystectomy course with hands-on training. In those courses, an average of 16 hours was devoted to animal laboratories for acquisition of skills. Additional training in the form of a preceptorship is being undertaken by an increasing number of surgeons. The future of minimally invasive surgery is being supported by rapid advances in technology. New video systems capable of displaying three-dimensional images and miniaturized fiberoptic scopes are now available. Computer enhanced three-dimensional ultrasound images provide the surgeon with the ability to examine the content and consistency of tissues in addition to their appearance. Advances in mechanical retraction may eliminate the need for carbon dioxide insufflation of the abdomen. Tissue repair using tissue glues or laser-mediated processes may reduce the need for endocavitary suturing. These advances in technology and techniques may reduce the morbidity and mortality of these surgical procedures and, ultimately, improve the standard of care for surgical patients.

Animals↗
PubMed1993

Adventitial elastolysis is a primary event in aneurysm formation.

PURPOSE: Adventitial elastin degradation is a hallmark of abdominal aortic aneurysm (AAA) formation in human beings, although the quantitative relationship between elastin loss and AAA formation and growth is unknown. This study was undertaken to quantitate the reduction of adventitial elastin for small AAA, to determine whether the loss of this structural component parallels aneurysm growth, and to examine the ultrastructure of the remaining elastin elements. METHODS: Longitudinal strips of anterior aneurysm wall were taken from 12 patients having elective repair of small (diameter < 5 cm, n = 4), moderate (diameter < 5 to 7 cm, n = 4), or large (diameter > 7 cm, n = 4) AAA and from six normal control subjects at autopsy. Specimens were prepared with elastin and collagen stains for histologic examination or formic acid for scanning electron microscopic evaluation of elastin architecture. Adventitial elastin content of aneurysmal and control aortas was quantitated with video microscopy and compared by aneurysm diameter. RESULTS: The inner portion of adventitia of normal aortic wall was composed of densely compacted alternating lamellae of elastin and collagen, which were grossly disrupted in all aneurysms. The remaining elastin fibers were disorganized and tortuous. There was an 81.6% +/- 2.1% reduction in elastin lamellae and an 85.7% +/- 4.2% reduction in fibers per lamellae compared with the number in control aortas (p < 0.001). Size of the aneurysm made no difference in adventitial elastin content. CONCLUSION: These data strongly suggest that elastolysis is a primary event in AAA formation that occurs before over loss of adventitial structural integrity and the development of small aneurysms.

Aged↗
PubMed1993

Popliteal venous aneurysm: report of two cases and review of the world literature.

Two new cases of popliteal venous aneurysm are reported and added to the 22 other cases of popliteal venous aneurysm available for review. Both patients were first seen with acute pulmonary embolism and were treated with thrombolytic therapy followed by anticoagulation. Each had recurrent venous thromboembolism before discovery of the popliteal venous aneurysm. One popliteal venous aneurysm was diagnosed with phlebography and the second with venous duplex imaging, confirmed with phlebography. Both were surgically corrected with tangential aneurysmectomy and lateral venorrhaphy. Twenty-four cases of popliteal venous aneurysm are now available for review. Seventy-one percent (17 of 24) presented with pulmonary embolism, 88% (21 of 24) were saccular, and 96% (23 of 24) were located in the proximal popliteal vein. All but two were diagnosed by ascending phlebography. Three patients received no treatment: in two of these the outcome was not documented and the third had occasional pain. Two patients received anticoagulation without subsequent operative repair and both died of recurrent pulmonary emboli. Operative correction resulted in a 75% patency rate with 21% complications, most of which were related to postoperative anticoagulation. No patient who was operated on had subsequent pulmonary embolism, and there were no operative deaths. We suggest that all patients who have pulmonary embolism have lower-extremity venous duplex imaging. All popliteal venous aneurysms should be surgically repaired, inasmuch as nonoperative therapy results in recurrent thromboembolism and an unacceptably high mortality rate. Tangential aneurysmectomy with lateral venorrhaphy is the recommended procedure.

Adult↗
PubMed1993

An alternative method of salvaging occluded suprainguinal bypass grafts with operative angioscopy and endovascular intervention.

PURPOSE: A study of technical feasibility was undertaken to determine whether angioscopy and parallel endovascular instrumentation could effectively evaluate and restore inflow into occluded suprainguinal grafts. METHODS: Several endobronchial instruments were selected for adaptation for use in clearing occluded grafts under angioscopic guidance. These instruments were used in the treatment of 12 thrombosed grafts limbs in 10 patients who were admitted 1 to 40 days after occlusion. The occluded suprainguinal graft limbs were exposed just proximal to the femoral anastomosis. Blind retrograde balloon thrombectomy and clot extraction were performed. Graft limbs underwent angioscopy, and the presence of luminal defects were recorded. Endoluminal instruments were then inserted parallel to the angioscope, and luminal defects were corrected. After inflow was reestablished, the distal portion of the graft was thrombectomized, and any necessary distal revisions were performed. RESULTS: Blind retrograde thrombectomy was successful in restoring inflow deemed normal in (67%) eight of 12 graft limbs and present but diminished in two (17%) graft limbs. Balloon thrombectomy was ineffective in restoring graft flow in two (17%) graft limbs. Angioscopy revealed luminal defects in 10 (83%) graft limbs after blind retrograde thrombectomy. Only 2 (17%) graft limbs had no luminal defects after thrombectomy. Findings included pseudointimal flap in eight of 12 (67%), adherent residual thrombus in 4 (33%), and kinked graft limbs in 2 (17%) graft limbs. Endovascular instrumentation was successful in resecting all luminal disease under angioscopic guidance. There were no deaths, no episodes of graft injury or distal embolization, and only one groin hematoma. During a mean follow-up period of 6 months (2 to 13 months), there was one late reocclusion at 7 months. CONCLUSION: We conclude that angioscopically guided thrombectomy and endovascular graft revision is a useful approach to the treatment of the occluded suprainguinal graft. Enhanced luminal visualization permits refined diagnostic assessment and definitive therapy. This may prolong the benefit of suprainguinal reconstructions.

Aged↗
PubMed1992

Why does prophylaxis with external pneumatic compression for deep vein thrombosis fail?

External pneumatic compression (EPC) devices are increasing in popularity for deep vein thrombosis (DVT) prophylaxis. Patients who have these devices applied postoperatively are assumed to have effective prophylaxis, although a number of extensive postoperative DVT complications have been observed. This study evaluates the proper application of EPC devices in patients in intensive care units and regular nursing floor units and assesses whether dedicated in-service instruction can improve proper use. In a prospective study of 138 patients with 2 or more risk factors for postoperative DVT, it was found that patients on routine nursing units had properly functioning EPC devices during 48% (306 of 636) of the visits compared with 78% (312 of 398) of the visits in the intensive care unit (ICU) (p less than 0.0001). Follow-up of patients transferred from an ICU to a regular nursing unit showed that functional application decreased from 82% (129 of 157) to 33% (40 of 122) (p less than 0.005). The compression sleeves were not applied in 84% of the nonfunctional devices and were properly in place but the pump nonfunctional in 16%. Unfortunately, dedicated in-service instruction did not improve the proper use of EPC. Although proper application of EPC is better in the ICU compared with regular nursing units, improper use is frequent and failure of DVT prophylaxis with EPC devices may be due to improper use, rather than failure of the method itself.

Adult↗
PubMed1992

Hemodynamic deterioration in chronic venous disease.

Clinical deterioration of patients with chronic venous disease (CVD) has been well described and a standardized classification has been proposed. The progressive hemodynamic deterioration producing these clinical findings is less well appreciated. This study examines and correlates venous hemodynamics with clinical severity in patients with CVD. Two hundred seventy-four extremities from 149 patients with varying degrees of CVD and 56 extremities from 28 symptom-free volunteers were evaluated clinically and hemodynamically. Each limb was assessed for functional venous volume, degree of valvular insufficiency, efficiency of the calf muscle pump, and noninvasive estimate of ambulatory venous pressure. In addition, exercise venous pressures were recorded in 56 extremities from 36 patients and 9 extremities from 6 volunteers. As CVD progresses from class 0 to class 2, venous volume expands, valvular function deteriorates, the calf muscle pump becomes inefficient, and ambulatory venous hypertension develops. However, once extremities develop brawny edema or hyperpigmentation, further deterioration of limb hemodynamics does not occur. Patients with deep venous obstruction have more severe valvular insufficiency, calf muscle pump dysfunction, and ambulatory venous hypertension than have patients without evidence of obstruction. Residual volume fraction offers a reliable noninvasive estimate of ambulatory venous pressure (r = 0.76), although its correlation was significantly better for patients without venous obstruction (r = 0.86) than for those with obstruction (r = 0.40; p < 0.05). Deterioration in venous hemodynamics parallels clinical severity through class 2. Once brawny edema and hyperpigmentation occur, ulceration develops without additional deterioration of venous hemodynamics.

Adult↗
PubMed1992

An approach to nutrition screening for older Americans.

The Nutrition Screening Initiative suggests an adaptable, tiered approach to screening for poor nutritional status in older Americans. The first level of screening is a checklist to be completed by elderly individuals or their caregivers. This checklist, which will be widely disseminated, describes the warning signs of poor nutritional status. It is anticipated that individuals will approach their physicians on the basis of scores on this checklist. Also included are two screening tests designed to help clinicians more easily detect poor nutritional status, or risk factors for poor nutrition, in their patients. The level I screen is to be completed by a social service or health care professional, or by other trained personnel. The level II screen focuses on additional information to be obtained following referral to a physician or other qualified health care professional.

Aged↗