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Biomedical subjects

J R Lee

Publications and source records attributed to J R Lee.

At least 73 records · Page 4Linked to original sources

Increased immunoreactivity for Rab11, a small GTP-binding protein, in low-grade dysplastic Barrett's epithelia.

Adenocarcinoma of the esophagus develops from metaplastic Barrett's columnar epithelia through the evolution of dysplastic epithelial intermediates. Although the role of dysplasia leading to adenocarcinoma is well established, far less is known regarding the cellular changes involved in this process. Because the development of dysplasia is characterized by the loss of apical secretory specializations, we hypothesized that changes in apical trafficking might be involved in the dysplastic process. We have sought to evaluate the expression of an important candidate regulator of apical trafficking, the small GTP-binding protein, Rab11, in resection and biopsy tissue from patients with Barrett's esophagus. Sections from esophageal resection specimens from 4 patients and endoscopic biopsies from 60 patients were stained with antibodies against Rab11 and Rab25 as well as protein markers of the Golgi apparatus and p53 protein. Rab11 staining in low-grade dysplastic regions was similar to that observed with monoclonal antibodies against Rab25 and gamma-adaptin and colocalized with staining for the Golgi marker, the mannose-6-phosphate receptor. In the esophageal adenocarcinoma resections, prominent Rab11 immunostaining was observed in the supranuclear region of low-grade dysplastic cells. In contrast, regions of high-grade dysplasia demonstrating strong nuclear p53 staining showed only diffuse or absent Rab11 staining. In endoscopic biopsies, 91% of biopsies that were read unanimously as low-grade dysplasia demonstrated supranuclear Rab11 staining. Fourteen percent of biopsies unanimously graded as being without dysplasia demonstrated perinuclear Rab11 staining. No p53 immunostaining was observed in any of the low-grade dysplasia biopsy specimens. An increase in Rab11 immunoreactivity seems to correlate with low-grade dysplasia, whereas p53 immunostaining correlates with high-grade dysplasia. The colocalization of Rab11 staining with increased immunoreactivity for markers of the trans-Golgi system is consistent with a defect in apical trafficking due to an expansion of either the trans-Golgi compartment or the apical recycling vesicle system.

Barrett Esophagus↗

L-arginine administration during reperfusion improves pulmonary function.

BACKGROUND: Nitric oxide is crucial to the maintenance of vascular homeostasis. Because nitric oxide levels decline upon lung reperfusion, infusion of L-arginine, a nitric oxide precursor, during reperfusion might prove effective at ameliorating reperfusion injury. METHODS: Neonatal piglet heart-lung blocks were preserved with Euro-Collins solution for 12 hours, rewarmed at room temperature for 1 hour, and reperfused for 10 minutes with either whole blood (n = 5), whole blood containing L-arginine (10 mmol/L; n = 6), or leukocyte-depleted blood (n = 6) on an isolated, blood-perfused, working heart-lung circuit. After the initial 10 minutes, all blocks received whole blood for 4 hours. Control blocks were continuously perfused on the circuit without intervening ischemia (n = 6). RESULTS: The partial pressure of oxygen in the whole blood group (113.8 +/- 33.1 mm Hg) was significantly less than in controls (417.3 +/- 6.2 mm Hg; p < 0.01). Lung compliance was significantly less in the whole blood group (0.8 +/- 0.2 mL/cm H2O) than in controls (2.9 +/- 0.4 mL/cm H2O; p < 0.01). The L-arginine and leukocyte-depleted blood groups showed no significant difference from controls. CONCLUSIONS: L-Arginine infusion during reperfusion improves pulmonary function, making it a simple alternative to leukocyte depletion.

Animals↗

Indications for and timing of surgical intervention in infective endocarditis.

Infective endocarditis, especially when it involves prosthetic valves, is a serious, often fatal illness. Although antibiotics are essential in management, surgery is required in many patients who develop even incipient heart failure and structural complications. Early identification and referral results in improved mortality and morbidity rates, and there is evidence that surgery should play a larger role in managing infective endocarditis. Patients with intracardiac pacemakers and cardioverting devices represent a growing reservoir of patients with the potential to develop endocarditis.

Endocarditis, Bacterial↗

Interaction of the von Willebrand factor (vWF) with collagen. Localization of the primary collagen-binding site by analysis of recombinant vWF a domain polypeptides.

The von Willebrand factor (vWF) mediates platelet adhesion to the vascular subendothelium by binding to collagen, other matrix constituents, and the platelet receptor glycoproteins Ib/IX and IIb/IIIa. Although substantial progress has been made in defining vWF structure-function relationships, there are conflicting data regarding the location of its collagen-binding site(s). Possible collagen-binding sites have been localized in the A1 and A3 domains of vWF. To study the proposed binding sites, we have expressed cDNA sequences encoding the A1 and A3 domains of vWF in Escherichia coli and purified the resulting proteins from bacterial inclusion bodies. In addition, a chimeric molecule containing residues 465-598 of the vWF A1 domain polypeptide (vWF-A1) fused in frame to residues 1018-1114 of the vWF A3 domain polypeptide (vWF-A3) was also expressed. Each of the three recombinant proteins purified as a monomer and contained a single disulfide bond. As previously reported (Cruz, M. A., Handin, R. I., and Wise, R. J. (1993) J. Biol. Chem. 268, 21238-21245), recombinant vWF-A1 inhibited ristocetin-induced platelet agglutination, but did not compete with vWF multimers for collagen binding. In contrast, vWF-A3 inhibited the binding of multimeric vWF to immobilized collagen, but did not inhibit ristocetin-induced platelet agglutination. Metabolically labeled vWF-A3 bound to immobilized collagen in a saturable and reversible manner with a Kd of 1.8 x 10(-6) M. The vWF-A1/A3 chimera was bifunctional. It inhibited vWF binding to platelet glycoprotein Ib/IX with an IC50 of 0.6 x 10(-6) M and inhibited vWF binding to collagen with an IC50 of 0.5-1.0 x 10(-6) M. These results, taken together, provide firm evidence that the major collagen-binding site in vWF resides in the A3 domain.

Base Sequence↗

Prognosis of amyotrophic lateral sclerosis and the effect of referral selection.

We followed two cohorts of Amyotrophic Lateral Sclerosis (ALS) patients to examine the survival and prognostic factors of ALS and the impact of selective referral on prognosis of ALS. The first cohort consisted of population-based incident ALS cases from Harris County, Texas, first diagnosed between 1985 and 1988. The second was a clinical series from a tertiary care center in Houston, Texas, diagnosed between 1977 and 1989. The overall 3-year survival was 29% in the incidence cohort and 32% in the referral cohort; however, the 5-year survival was much lower for the incidence cohort than the referral cohort (4% vs 21%). The large difference in 5-year survival was not explained by the distributions of prognostic factors in the two cohorts but due to stronger unfavorable effects of prognostic factors in the incidence cohort than the referral cohort. In both cohorts, older age at diagnosis, bulbar onset, and positive family history of ALS were unfavorable prognostic factors while blacks had better survival than whites or hispanics. We confirmed that longer duration from onset to diagnosis was a favorable prognostic factor in both cohorts but the effect was more pronounced in the referral series.

Adult↗

Extracellular and standard University of Wisconsin solutions provide equivalent preservation of myocardial function.

The deleterious effect of hyperkalemic cardioplegic solutions on coronary endothelium has been documented and has also been demonstrated with University of Wisconsin solution. We evaluated a new extracellular University of Wisconsin formulation for efficacy in heart preservation. Six neonatal piglet hearts were arrested with and stored in the standard intracellular University of Wisconsin solution (group 1: K+ 125 mEq/L, Na+ 29 mEq/L). Six piglet hearts were preserved for 24 hours with an extracellular University of Wisconsin solution that differed only in the concentrations of potassium and sodium (group 2: K+ 25 mEq/L, Na+ 129 mEq/L). Hearts underwent modified reperfusion with leukocyte-depleted aspartate-glutamate enriched blood cardioplegic solution followed by conversion to a left-sided working mode on a Langendorff circuit with perfusion from a support pig. Stroke work index was calculated at left ventricular end-diastolic pressures of 3, 6, 9, and 12 mm Hg. Sixty minutes after reperfusion, there was no significant difference in stroke work index between group 1 (16.4 +/- 1.9 x 1000 erg/gm) and group 2 (15.3 +/- 2.7 x 1000 erg/gm). There was also no significant difference in high-energy phosphate stores or myocardial water content between the two groups. Extracellular University of Wisconsin solution provides myocardial preservation equivalent to standard University of Wisconsin solution while preventing exposure of coronary endothelium to high levels of potassium, which justifies its use in clinical heart transplantation.

Adenosine↗

Incidence of acute symptomatic seizures in Rochester, Minnesota, 1935-1984.

We determined the incidence of seizures due to acute CNS insults for residents of Rochester, Minnesota, U.S.A., from 1935 through 1984. The age-adjusted incidence rates for 1955-1984, the period of most complete case ascertainment, was 39.0/100,000 person-years (United States 1970 population as standard). The age-adjusted incidence was considerably higher in men: 52.0 as compared with 29.5 in women. The 3.6% risk of experiencing an acute symptomatic seizure in an 80-year lifespan approaches that of developing epilepsy. The major causes of acute symptomatic seizures were traumatic brain injury, cerebrovascular disease, drug withdrawal, and CNS infections. Each type of acute symptomatic seizure has age, gender, and time period patterns that reflect the occurrence of the underlying cause.

Adolescent↗

Secular trends and birth cohort effects in unprovoked seizures: Rochester, Minnesota 1935-1984.

The incidence of idiopathic/cryptogenic epilepsy and isolated unprovoked seizures has been relatively stable in the population of Rochester, Minnesota, for the 50-year period 1935 through 1984. In each decade, the age-specific rates exhibited a consistent U-shaped pattern of decreasing rates from infancy to age 40-49 and a progressive increase thereafter to a second peak at age 70 years. Males had a 15% higher incidence of cryptogenic unprovoked seizures than females. The most pronounced secular trend was a decrease in the incidence in children aged < 10 years for the first 4 decades of the study; however, this trend was interrupted by a slight rebound in the decade 1975-1984. There has been a progressive decrease in the incidence of cryptogenic unprovoked seizures in individuals aged > or = 50 from 1965 through 1984. This decrease paralleled the decrease in cerebrovascular disease in the community. The decrease in idiopathic unprovoked seizures may be related to a concurrent trend in "silent stroke." Plots and Poisson regression analysis did not show patterns in the incidence of idiopathic unprovoked seizures related to successive birth cohorts. However, significantly lower incidence rates were observed for the 1930-1934 birth cohort, about half that of all others, between the ages of 5 and 54 years.

Adult↗

Who uses screening mammography regularly?

We evaluated factors associated with the regular use of screening mammography among women presenting for screening. Six thousand two hundred forty-four women ages 55 and older who participated in the 1991-1992 Texas Breast Screening Project were classified as regular or irregular users of mammography according to self-reported mammographic history since 1986. Logistic regression was applied to determine odds ratios of specified factors. Fourteen % were regular users of mammographic screening. Being older, black or Hispanic, receiving regular care from a family doctor, believing in a lower prospect of cure of breast cancer, and lacking health insurance coverage were associated with less regular use of screening mammography. Higher educational level, family history of breast cancer, prior breast biopsy, annual income > or = +35,000, receiving regular care from a gynecologist, believing that life would be difficult with breast cancer, and believing in a greater personal risk for breast cancer were associated with a greater likelihood of regular use (P < 0.01). Among multiple factors associated with regular use of screening mammography, sociodemographic variables associated with regular mammography use are similar to those influencing initial use of screening mammography. Women who are difficult to persuade to obtain mammographic screening may be equally difficult to persuade to adhere to regular use.

Age Distribution↗

Lecompte procedure for complete transposition of the great arteries with ventricular septal defect and pulmonary stenosis.

From December 1988 to February 1993, 19 patients were treated by the Lecompte procedure for complete transposition of the great arteries associated with a ventricular septal defect and pulmonary stenosis. The mean age at operation was 3.1 +/- 0.8 years (mean +/- standard error). This technique consisted of resecting the outlet septum, constructing a tunnel that connected the left ventricle to the aorta, closing the proximal pulmonary arterial stump, pulling the distal pulmonary artery down to the right ventriculotomy site directly, and covering anteriorly with the fixed autologous pericardium. Operative mortality was 5.3%. The mean follow-up was 24.2 +/- 3 months, with no late death. One reoperation was performed because of residual right ventricular outflow tract obstruction. All survivors were studied by echocardiography at intervals of 6 months to 1 year. In all survivors (except for 1 child who underwent reoperation), the estimated pressure gradient between the right ventricle and the pulmonary artery, the structure of the left ventricular outflow tract, left ventricular function, and right ventricular contractility were all satisfactory.

Abnormalities, Multiple↗

The Angelchik prosthesis behaves as a fundoplication.

It is not known why the Angelchik prosthesis prevents gastro-oesophageal reflux. A review of 53 barium meal examinations in 39 patients with the prosthesis showed that in 43 examinations the prosthesis was below the diaphragm. In 38 of these a small knuckle of stomach had herniated through the prosthetic ring alongside the oesophagus, forming a small intra-abdominal para-oesophageal hernia. Radiological reflux occurred in only one patient with such a hernia. In the remaining five examinations where the prosthesis was correctly situated in the abdomen, there was no hernia within the prosthetic ring and reflux occurred in three. In ten examinations the prosthesis had migrated into the mediastinum. None of these showed a hernia and reflux occurred in eight. It is suggested that the Angelchik prosthesis results in the formation of a small para-oesophageal hernia within a loosely fitting ring within the abdomen and this is a requirement for the success of the Angelchik prosthesis. Radiographically the intra-abdominal para-oesophageal hernia inside the prosthesis results in buttressing of the intra-abdominal oesophagus in a manner similar to a fundoplication.

Barium Sulfate↗

Modified occipital approach to the endolymphatic sac and cochlear aqueduct of the guinea pig.

Obliteration of the endolymphatic sac reliably results in endolymphatic hydrops in some animal species. While this procedure is frequently utilized in the study of experimental Meniere's disease, additional information regarding inner ear fluid hydrodynamics can be obtained by obstructing the cochlear aqueduct to eliminate the influence of the cerebrospinal fluid on the perilymphatic compartment of the inner ear. This report describes a modified extradural occipital approach for surgical obliteration of the endolymphatic sac and obstruction of the cochlear aqueduct in the guinea pig. The extradural approach allows direct visualization of the cochlear aqueduct without manipulation or retraction of the dura, sigmoid sinus, or cerebellum. For experimental studies, which require obliteration of both the endolymphatic sac and cochlear aqueduct, this approach provides improved reliability with reduced morbidity and mortality.

Animals↗