EEA1, an early endosome-associated protein. EEA1 is a conserved alpha-helical peripheral membrane protein flanked by cysteine "fingers" and contains a calmodulin-binding IQ motif

Early endosomes are cellular compartments receiving endocytosed material and sorting them for vesicular transport to late endosomes and lysosomes or for recycling to the plasma membrane. We have cloned a human cDNA encoding an evolutionarily conserved 180-kDa protein on early endosomes named EEA1 (Early Endosome Antigen1). EEA1 is associated with early endosomes since it co-localizes by immunofluorescence with the transferrin receptor and with Rab5 but not with Rab7. Immunoelectron microscopy shows that it is associated with tubulovesicular early endosomes containing internalized bovine serum albumin-gold. EEA1 is a hydrophilic peripheral membrane protein present in cytosol and membrane fractions. It partitions in the aqueous phase after Triton X-114 solubilization and is extracted from membranes by 0.3 M NaCl. It is a predominantly alpha-helical protein sharing 17-20% sequence identity with the myosins and contains a calmodulin-binding IQ motif. It is flanked by metal-binding, cysteine "finger" motifs. The COOH-terminal fingers, Cys-X2-Cys-X12-Cys-X2-Cys and Cys-X2-Cys-X16-Cys-X2-Cys, are present within a region that is strikingly homologous with Saccharomyces cerevisiae FAB1 protein required for endocytosis and with Caenorhabditis elegans ZK632. These fingers also show limited conservation with S. cerevisiae VAC1, Vps11, and Vps18p proteins implicated in vacuolar transport. We propose that EEA1 is required for vesicular transport of proteins through early endosomes and that its finger motifs are required for this activity.     

External dacryocystorhinostomy. Surgical success, patient satisfaction, and economic cost

BACKGROUND: External dacryocystorhinostomy (DCR) is the standard treatment for nasolacrimal duct obstruction, with success rates consistently above 90%. This study reviews the demographics, success, cost, efficiency, and patient satisfaction in external DCR. This information will be useful as comparison criteria for evaluating new surgical techniques. METHODS: Records of 169 external DCR procedures performed over an 8.7-year period were reviewed. All patients had preoperative symptoms of tearing and/or dacryocystitis with a component of nasolacrimal obstruction. Patient demographics, history, examination findings, surgical and anesthesia information, postoperative success, complications, and follow-up course were recorded. Patient satisfaction and long-term success were evaluated by telephone survey. RESULTS: External DCR often required middle turbinectomy (17%), exposure of ethmoid sinuses (17%), and removal of dacryoliths (14%). Most patients (90%) underwent silicone intubation, with the tubes removed at an average of 3.7 weeks after surgery. A patent system was established in 95% of procedures, whereas 92% remained asymptomatic. Postoperative complications included hemorrhage (3.9%) and scarring (2.6%). Of the surveyed patients, 87% denied continued or recurrent symptoms; 97% rated their incision "good" to "excellent" in appearance; and all patients stated they would recommend the procedure to others. CONCLUSION: External DCR is highly successful, requires limited follow-up, and is a cost-effective procedure. Complications are uncommon, and patient satisfaction is high. New lacrimal surgical techniques must be evaluated against the long-proven success of the external approach.     

Behavioral compliance with dialysis prescription in hemodialysis patients

The relationship between compliance and outcome is poorly understood, partially because there has been no gold standard for measuring compliance in hemodialysis patients. To investigate interrelationships between psychological, medical, and compliance factors, hemodialysis (HD) patients were studied with the Beck Depression Inventory, and a subset, the Cognitive Depression Index, the Perception of Illness Effects scale, and the Multidimensional Scale of Perceived Social Support. Behavioral compliance was measured in three ways: (1) percent time compliance (signifying "shortening behavior"); (2) percent attendance (signifying "skipping behavior) (3) percent total time compliance, assessing patients' time on dialysis normalized for prescribed time, including all shortenings and absences. Standard compliance indicators (predialysis serum potassium and phosphorus concentrations and interdialytic weight gain) were also analyzed. The patients' mean Beck Depression Inventory was in the range of mild depression. The prevalence of depression was 25.5%. Both depression indices correlated with Perception of Illness Effects scale scores. In general, social support was related to both measures of depression and perception of illness effects. Total time compliance was 95.8 +/- 5.0%. Younger patients were more likely to skip treatments compared with older patients. Time compliance comprised a wide spectrum, with most patients relatively compliant, whereas a small proportion received far less than their prescribed dialysis. Skipping and shortening behaviors did not correlate, suggesting that these constitute two separate types of noncompliant behaviors. Time compliance parameters did not correlate with potassium levels or interdialytic weight gain, but did correlate with phosphorus levels. Interrelationships between behavioral compliance measures and other parameters varied between units and patients of different gender. Finally, behavioral compliance patterns were stable over months in patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phase III comparative trial using CHOP vs CIOP in the treatment of advanced intermediate-grade non-Hodgkin's lymphoma

Until now, literature data support the fact that the CHOP regimen represents the standard first line treatment for patients with advanced intermediate-grade non-Hodgkin's lymphoma. Recently, idarubicin has been introduced in clinical trials because of its favourable preclinical profile: it is more active than daunorubicin and doxorubicin against a number of experimental tumour systems and is significantly less cardiotoxic in animal models. From March 1991 to June 1993, 115 previously untreated patients with stage II to IV intermediate-grade non-Hodgkin's lymphoma, according to the Kiel classification, were enrolled in a phase III comparative trial. The objectives of the study were to compare the efficacy and safety of using idarubicin instead of doxorubicin in the polychemotherapeutic regimen CHOP (cyclophosphamide, doxorubicin, vincristine, and dexamethasone). Of the 115 patients registered for the trial, 103 were evaluable: 52 received CH (doxorubicin)OP and 51 received CI(Idarubicin)OP. Known prognostic factors were equally distributed among the two groups. There were no significant differences between the 2 groups in the rates of partial and complete response. The overall response rate was 87%, with complete response in 62%: 63% in the CHOP group, and 59% in the CIOP group. At 30 months (median 20 months), 86% of all CR patients were alive without disease in the CHOP group and 85% in the CIOP group. Patients treated with CHOP experienced severe alopecia more frequently (P = .004). Only three patients in the CIOP group showed cardiac adverse events (1 moderate and 2 mild), while in the CHOP group 4 mild, 2 moderate and 1 severe were recorded. LVEF monitoring was carried out in 31 patients of the CHOP group and in 27 of the CIOP group. A median drop of 8.3% of the LVEF was observed in patients treated with CHOP regimen as compared to 4.8% in patients with CIOP regimen (P = .0001). In this trial, the "idarubicin arm" (CIOP regimen) was found to have an equivalent therapeutic efficacy and, slightly, reduced clinical toxicity in comparison to the standard doxorubicin-containing CHOP regimen in patients with intermediate-grade non-Hodgkin's lymphoma.     

Study on fine quartz pre-dose techniques

When using the pre-dose technique in ceramic dating,it is essential to add a calibration dose and to eliminate the background dose.For doing this measurement the sample requires multiple activation following multiple administration of a test dose to induce simulated “ancient” thermoluminescence(TL).However,the procedures introduce many factors that are difficultly corrected.This paper compares existing two kinds of measurement procedures and proposes a new procedure involving single activation following a single test dose administration.AN experiment using the single activation procedure is carried out with natural fine quartz where the results obtained exhibit only 0.07 relative error.It appears that this new procedure increases the precision of the ancient TL measurement by about 0.04 and 0.11 over those of existing two kinds of procedures.In addition this method can give realistic values in TL dating for relatively “young” samples aged tens to hundreds of yesrs where the standard high temperature TL method is relatively insensitive.     

Spirometry reference values for healthy elderly blacks. The Cardiovascular Health Study Research Group

Pulmonary function was assessed by spirometry in 497 black and 2,980 white ambulatory elderly male and female participants of the Cardiovascular Health Study. The quality assurance program prompted technicians to exceed American Thoracic Society recommendations for spirometry. A "healthy" subgroup of 235 black and 1,227 white participants age 65 years and older was identified by excluding current and former smoker, and those with self-reported asthma or emphysema, congestive heart failure, and poor-quality results of spirometry tests, since those factors were associated with a lower FEV1. Reference equations and normal ranges for elderly blacks for measurements of FEV1, FVC, and the FEV1/FVC ratio were then determined from the healthy group. These elderly blacks had an FVC about 6% lower than elderly whites, even after correcting for standing height, sitting height (trunk length), and age. The popular use of spirometry reference values from studies of middle-aged white subjects by applying a 12% race correction factor for black patients appears to overestimate predicted values.     

In situ source zone sediment mixing coupled to groundwater biostimulation to enhance phenol natural attenuation

Phenol is an industrially key compound that has a wide range of applications and also one of the most commonly found toxic pollutants in wastewaters and groundwater. This paper demonstrates the applicability of in situ remediation at a deactivated industrial site using source zone excavation and sediment mixing associated with nutrients delivery into groundwater. Sediment excavation and mixing displaced the entrapped source zone enhancing mass transfer into groundwater and contaminant bioavailability. A nutrient solution prepared with nitrate, phosphate, sodium hydroxide and hydrogen peroxide was continuously delivered into groundwater to stimulate biodegradation and restrict plume migration. The observed correlation between phenol-dependent Enterobacteriaceae concentrations throughout the remediation time frame supported circumstantial evidence of biodegradation. Phenol concentration in groundwater (up to 1,300 mg/L) was reduced >99% after 5 months following remediation and remained under the established site specific target level (4 mg/L). Nitrate and phosphate concentrations returned to background concentrations levels at the end of the remediation. Overall, the proposed in situ remediation scheme was effective to remediate this particular aquifer contaminated with phenol for over 20 years.     

Drawing (Complete) Binary Tanglegrams

A binary tanglegram is a drawing of a pair of rooted binary trees whose leaf sets are in one-to-one correspondence; matching leaves are connected by inter-tree edges. For applications, for example, in phylogenetics, it is essential that both trees are drawn without edge crossings and that the inter-tree edges have as few crossings as possible. It is known that finding a tanglegram with the minimum number of crossings is NP-hard and that the problem is fixed-parameter tractable with respect to that number. We prove that under the Unique Games Conjecture there is no constant-factor approximation for binary trees. We show that the problem is NP-hard even if both trees are complete binary trees. For this case we give an O(n ³)-time 2-approximation and a new, simple fixed-parameter algorithm. We show that the maximization version of the dual problem for binary trees can be reduced to a version of MaxCut for which the algorithm of Goemans and Williamson yields a 0.878-approximation.     

Role of serum nonsuppressible insulin-like activity (NSILA) in wound healing. I. Influence of thyroparathyroidectomy on serum NSILA and wound healing in the rat

Serum contains a 90,000 molecular weight glycoprotein that exhibits insulin-like activity on adipocytes, skeletal muscle, and fibroblasts in tissue culture; however, this protein is physicochemically and immunochemically distinct from insulin and presently is termed "nonsuppressible insulin-like activity ("nsilA)." This study was designed to assess the response of serum NSILA to thyroparathyroidectomy (TPTHX) and to associate this response with tissue repair processes in the injured rat. It was postulated that NSILA modulates the fibroblastic response in wound healing. TPTHX decreased NSILA to 40 percent of control levels (p less than 0.001); 90 male animals subsequently were wounded by either a 10 percent third-degree burn or skin excision. Following injury, NSILA significantly increased in both control and TPTHX groups, but this acute-phase response was attenuated in TPTHX animals. Light microscopy of granulation tissue demonstrated a diminution in the fibroblastic response in TPTHX animals. Hydroxyproline analysis of granulation tissue revealed a significant decrease (p less than 0.025) in collagen content in TPTHX animals with low NSILA levels. The results suggest that serum NSILA levels are controlled, in part, by thyroid hormone and that NSILA may modulate the fibroblastic response of connective tissue repair processes.