Trace metal distribution in sediments of the Pearl River Estuary and the surrounding coastal area, South China.

Surface sediments and sediment cores collected at the Pearl River Estuary (PRE) and its surrounding coastal area were analysed for total metal concentrations, chemical partitioning, and Pb isotopic compositions. The distribution of Cu, Cr, Pb, and Zn demonstrated a typical diffusion pattern from the land to the direction of the sea. Two hotspots of trace metal contamination were located at the mixed zone between freshwater and marine waters. The enrichment of metals in the sediments could be attributed to the deposition of the dissolved and particulate trace metals in the water column at the estuarine area. The similar Pb isotopic signatures of the sediments at the PRE and its surrounding coastal area offered strong evidence that the PRE was a major source of trace metals to the adjacent coastal area. Slightly lower (206)Pb/(207)Pb ratios in the coastal sediments may indicate other inputs of Pb in addition to the PRE sources, including the inputs from Hong Kong and other parts of the region.

G-protein-coupled receptors: turn-ons and turn-offs.

Advances in the study of G-protein-coupled receptor regulation have provided novel insights into the role of G-protein-coupled receptor kinases and arrestins in this process. Of particular interest are recent studies that have dramatically expanded the known cellular functions of these molecules to include roles in receptor endocytosis and activation of MAP kinase signalling pathways.

Body composition and spontaneous growth hormone secretion in normal short stature children.

This study was designed to compare the relationship of measured and estimated indices of adiposity with the spontaneous GH secretion (SGHS) in 37 normal short stature children. Fifteen of the 37 patients (10 males and 5 females) were pubertal, and 22 (17 males and 5 females) were prepubertal. All patients underwent a review of their medical history, a physical exam, laboratory tests, and a nutritional assessment that included anthropometry and evaluation of body composition by bioelectric impedance. The percentage of body fat and body fat mass index were used as measured indices of adiposity. The weight for height ratio, body mass index, and body mass index z-scores were calculated and used as estimated indices of adiposity. Our results showed that SGHS is greatly influenced by variations in adiposity in normal short stature children, and measured indices of adiposity demonstrated the strongest negative correlation with SGHS. Gender differences were apparent in the degree of adiposity that modified SGHS, and it appears that adiposity altered the amplitude of GH pulses in pubertal patients and the number of pulses in prepubertal children. These results suggest that interpretation of SGHS must take into account body composition and gender in addition to pubertal status.

Correcting errors in estimating neuron area caused by the position of the nucleolus.

The technique of measuring soma cross-sectional area at the plane of the nucleolus leads to systematic errors that depend on how far the nucleolus is displaced from the center of the soma. A set of correction factors was produced based on calculations from a geometric model of the measurement process. Applying the correction factors to measurements of second-order auditory neurons led to substantial changes in the estimated soma area.

Nuclear incorporation of [adenine 14C]NAD is altered by compounds which affect poly(ADP-ribose) formation.

The use of a DNA alkylating agent, which induces poly(ADP-ribose) formation, has been employed to study the incorporation of [adenine 14C]NAD into pea root meristem nuclei, which is a prerequisite for poly(ADP-ribose) synthesis. The incorporation of [adenine 14C]NAD is significantly reduced when the poly(ADP-ribose)polymerase inhibitors, 7-methylxanthine and 3-methoxybenzamide are present and this incorporation is augmented when the DNA alkylating agent methyl methanesulfonate is added. Such information supports the hypothesis that poly(ADP-ribose) may be involved in the cell cycle regulation of pea root meristem nuclei.

Cancer of the male breast.

A retrospective review of 28 male breast cancer patients at Eastern Virginia Medical School and affiliated hospitals was performed to learn about patient characteristics, treatment, and outcome. The mean age of the patients was 64 years, and 60 per cent of patients were obese. The most common presenting symptoms were mass in 79 per cent and nipple discharge in 29 per cent. The median duration of symptoms was 3.3 months. All patients except two underwent mastectomy, and most tumors were early stage (0, I, or II). Many patients, particularly those with advanced disease, were also treated with chemotherapy, radiation therapy, and/or endocrine therapy. At a median follow-up of 29 months, the actuarial 5-year survival was 43 per cent, somewhat worse than the survival of female breast cancer patients in the literature. Male breast cancer patients are treated in a similar fashion to female patients. Aggressive systemic treatment should be considered for patients with poor prognosis disease. The high frequency of estrogen receptor positivity suggests tamoxifen may prove to be particularly useful in these patients.

A simple technique for pulmonary function testing in patients with permanent tracheostomies.

UNLABELLED: In patients with permanent tracheostomies, the clinician can encounter difficulty in creating a satisfactory seal between the patient and pulmonary function testing (PFT) equipment. We have developed a simple apparatus and procedure for effecting a tight seal during testing. MATERIALS AND METHODS: The seal around the tracheostomy is made with a newborn-size resuscitation mask, the hole of which is larger than the tracheal stoma. A sealing lubricant is applied to the soft rim of the mask and around the tracheostomy site, and adapters enable connection of the resuscitation mask and the large-bore PFT-equipment tubing. After affixing the adapters to the mask, we check that the seal is tight; if airleak is evident, more lubricant or a mask of different size or style may be necessary. Once a tight seal is achieved without airway compromise, the mask is attached to the PFT equipment and testing can begin. During testing, the patient should wear nose clips to prevent volume loss through the upper airway. COMMENTS: This equipment is simple, inexpensive, and readily available. Further, it permits pulmonary function testing whether or not a tracheostomy tube is in place, an advantage if variable extrathoracic upper airway obstruction is a consideration. If the patient has a cuffed tracheostomy tube in place, the PFT equipment can be connected directly to the tube. We have found that this apparatus and technique are well tolerated and that test results are reproducible.

Image analysis and quantification of atherosclerosis using MRI.

This paper describes an image processing, pattern recognition, and computer graphics system for the noninvasive identification and evaluation of atherosclerosis using multidimensional Magnetic Resonance Imaging (MRI). Particular emphasis has been placed on the problem of developing a pattern recognition system for noninvasively identifying the different plaque classes involved in atherosclerosis using minimal a priori information. This pattern recognition technique involves an extension of the ISODATA clustering algorithm to include an information theoretic criterion (Consistent Akaike Information Criterion) to provide a measure of the fit of the cluster composition at a particular iteration to the actual data. A rapid 3-D display system is also described for the simultaneous display of multiple data classes resulting from the tissue identification process. This work demonstrates the feasibility of developing a "high information content" display which will aid in the diagnosis and analysis of the atherosclerotic disease process. Such capability will permit detailed and quantitative studies to assess the effectiveness of therapies, such as drug, exercise, and dietary regimens.

Identification and 3-D quantification of atherosclerosis using magnetic resonance imaging.

Cardiovascular disease due to atherosclerosis is a leading cause of death in the United States as well as other developed countries. This paper describes the development of image processing, pattern recognition, and graphical display techniques to non-invasively quantify the atherosclerotic disease process using magnetic resonance imaging (MRI). We have demonstrated the ability to identify the soft tissue classes of (1) normal, smooth muscle wall, (2) fatty plaque, (3) complex, fibrous plaque, and (4) calcified plaque. The objective of this work has been to combine functional information, such as plaque tissue type, with structural information, represented by 3-D display of vessel structure, into a single composite display. The results of this work provide a "high information content" display which will aid in the diagnosis and analysis of the atherosclerotic disease process, and permit detailed and quantitative studies to assess the effectiveness of therapies (e.g. changes in diet, exercise and drug administration).

Developing and maintaining of hemophilia programs in developing countries.

There are elements key to the success of developing and maintaining hemophilia programs in developing countries. Health care providers who are dedicated champions of hemophilia care are essential. Their training through the WFH International Hemophilia Training Centers brings them in contact with modern comprehensive care as well as establishes collegial linkages with treaters in developed centers. Affordable, safe, viral free coagulation products are essential for an effective hemophilia program. Developing essential for an effective hemophilia program. Developing countries may have to use intermediate purity products because of economic considerations, but technologies must be used which reduce the risk of viral contamination. Successful programs also result from linking to hemophilia programs with national health care initiatives. Hemophilia health care must be recognized as a priority within the developing country's health care system.

Comparison of ultrasound versus fluoroscopic guided rotator cuff interval approach for MR arthrography.

Our purpose is to compare ultrasound and fluoroscopic-guided approaches to the glenohumeral joint at the rotator cuff interval for magnetic resonance (MR) arthrography of the shoulder. Forty consecutive patients were prospectively studied. 20 patients underwent ultrasound-guided and 20 patients underwent fluoroscopic guided injection. Successful rate of ultrasound guidance is 95%. No significant difference in pain score and duration of injection between two methods (P>.05). Ultrasound-guided rotator cuff interval injection of the glenohumeral joint for MR arthrography is comparable with fluoroscopic-guided injection. Ultrasound is the preferred method as there is no ionizing radiation.

Mercury profiles in sediments of the Pearl River Estuary and the surrounding coastal area of South China.

The spatial and temporal variations of mercury (Hg) in sediments of the Pearl River Estuary (PRE) and the surrounding coastal area (South China Sea) were studied. In surface sediments, the concentrations of Hg ranged from 1.5 to 201ng/g, with an average of 54.4ng/g, displaying a decreasing trend with the distance from the estuary to the open sea. This pattern indicates that the anthropogenic emissions from the Pearl River Delta (PRD) region are probably the main sources of Hg in this coastal region. Using the (210)Pb dating technique, the historical changes in the concentrations and influxes of Hg in the last 100 years were also investigated. The variations in Hg influxes in sediment cores obviously correlate with the economic development and urbanization that has occurred the PRD region, especially in the last three decades.

Treadmill injuries to the upper extremity in pediatric patients.

Injury is the leading cause of preventable death and disability in childhood and early adulthood. Approximately 25,000 children are injured on exercise equipment each year. Although hand injuries sustained on stationary bicycles in the home have been well documented, little has been reported on home treadmill injuries. Between September 1996 and March 2000, the authors treated 12 children at The Children's Hospital of Philadelphia for injuries to the upper extremity sustained on a treadmill. The age at the time of injury ranged from 14 months to 7 years, with a median age of 2.4 years. Average length of follow-up was 11.4 months. Ten of the 12 children sustained partial- or full-thickness burns to the volar aspect of the hand and digits. Overall, 6 patients required surgical repair. A total of 25% of the volar flexion creases involved required surgery. All patients had good functional results. The authors discuss the mechanism of injury, management, and measures to prevent treadmill injuries to children. To their knowledge, this is the first report of such injuries resulting from the use of a treadmill.

Structure-function analysis of G protein-coupled receptor kinase-5. Role of the carboxyl terminus in kinase regulation.

Many G protein-coupled receptors are phosphorylated and regulated by a distinct family of G protein-coupled receptor kinases (GRKs) that specifically target the activated form of the receptor. Recent studies have revealed that the GRKs are also subject to post-translational regulation. For example, GRK5 activity is strongly inhibited by protein kinase C phosphorylation and by Ca2+-calmodulin binding. Ca2+-calmodulin binding also promotes GRK5 autophosphorylation, which further contributes to kinase inhibition. In this study we identify two important structural domains in GRK5, a phospholipid binding domain (residues 552-562) and an autoinhibitory domain (residues 563-590), that significantly contribute to GRK5 localization and function. We demonstrate that the C-terminal region of GRK5 (residues 563-590) contains residues autophosphorylated in the presence of calmodulin as well as the residues phosphorylated by protein kinase C. Deletion of this domain increases the apparent affinity of GRK5 for receptor substrates 3-4-fold but has no effect on nonreceptor substrates. These findings define residues 563-590 of GRK5 as an autoinhibitory domain with efficacy that is regulated by phosphorylation. Another C-terminal domain in GRK5 that appears to be functionally important is found between residues 552 and 562. Deletion of this region significantly inhibits kinase phosphorylation of membrane-bound receptor substrates but has no effect on soluble substrates. Additional studies reveal that this domain is critical for GRK5 interaction with phospholipids and for the intracellular localization of the kinase. Interestingly, similar regions in GRK4 and GRK6 appear to be palmitoylated (and involved in membrane interaction), suggesting evolutionary conservation of the function of this domain.

Regulation of G protein-coupled receptor kinases by caveolin.

G protein-coupled receptor kinases (GRKs) have been principally characterized by their ability to phosphorylate and desensitize G protein-coupled receptors. However, recent studies suggest that GRKs may have more diverse protein/protein interactions in cells. Based on the identification of a consensus caveolin binding motif within the pleckstrin homology domain of GRK2, we tested the direct binding of purified full-length GRK2 to various glutathione S-transferase-caveolin-1 fusion proteins, and we discovered a specific interaction of GRK2 with the caveolin scaffolding domain. Interestingly, analysis of GRK1 and GRK5, which lack a pleckstrin homology domain, revealed in vitro binding properties similar to those of GRK2. Maltose-binding protein caveolin and glutathione S-transferase-GRK fusion proteins were used to map overlapping regions in the N termini of both GRK2 and GRK5 that appear to mediate conserved GRK/caveolin interactions. In vivo association of GRK2 and caveolin was suggested by co-fractionation of GRK2 with caveolin in A431 and NIH-3T3 cells and was further supported by co-immunoprecipitation of GRK2 and caveolin in COS-1 cells. Functional significance for the GRK/caveolin interaction was demonstrated by the potent inhibition of GRK-mediated phosphorylation of both receptor and peptide substrates by caveolin-1 and -3 scaffolding domain peptides. These data reveal a novel mode for the regulation of GRKs that is likely to play an important role in their cellular function.

Hypertension secondary to renin-secreting juxtaglomerular cell tumor: case report and review of 38 cases.

A 15-year-old girl with severe high renin hypertension caused by a juxtaglomerular cell tumor (JCT) was successfully treated with the calcium channel blocker nifedipine until surgical removal effected a permanent cure. This case was incorporated into a review of the 37 cases previously published. Comparison of the children and adolescents with the adult population showed that the features of JCT were similar in the two groups except for the average duration of symptoms prior to diagnosis (pediatric group 2.6 years vs. 6.0 years for the adult group). Analysis of all 38 cases demonstrated the following: 1. Teenagers constituted the largest single population with JCT (39%) and approximately two-thirds of the entire population were female. 2. Many patients failed to show persistent hypokalemia despite high plasma renin activity and secondary hyperaldosteronism. 3. Renal angiography was initially negative in more than half the cases. 4. Renal vein renin failed to show lateralization to the affected kidney in 52% of the cases. 5. Computerized tomography demonstrated a renal mass in all of the cases in which it was performed, even when other imaging studies were negative. 6. Calcium channel blockers may evolve as the preferred treatment for the high renin hypertension of JCT.

Dimerization and the effectiveness of ICAM-1 in mediating LFA-1-dependent adhesion.

Dimeric intercellular adhesion molecule-1 (ICAM-1) binds more efficiently to lymphocyte function-associated antigen-1 (LFA-1) than monomeric ICAM-1. However, it is unknown whether dimerization enhances binding simply by providing two ligand-binding sites and thereby increasing avidity, or whether it serves to generate a single "fully competent" LFA-1-binding surface. Domain 1 of ICAM-1 contains both the binding site for LFA-1, centered on residue E34, and a homodimerization interface. Whether the LFA-1-binding site extends across the homodimerization interface has not been tested. To address this question, we constructed four different heterodimeric soluble forms of ICAM-1 joined at the C terminus via an alpha-helical coiled coil (ACID-BASE). These heterodimeric ICAM-1 constructs include, (i) E34/E34 (two intact LFA-1-binding sites), (ii) E34/K34 (one disrupted LFA-1-binding site), (iii) E34/DeltaD1-2 (one deleted LFA-1-binding site), and (iv) K34/K34 (two disrupted LFA-1-binding sites). Cells bearing activated LFA-1 bound similarly to surfaces coated with either E34/K34 or E34/DeltaD1-2 and with an approximately 2-fold reduction in efficiency compared with E34/E34, suggesting that D1 dimerization, which is precluded in E34/DeltaD1-D2, is not necessary for optimal LFA-1 binding. Furthermore, BIAcore (BIAcore, Piscataway, NJ) affinity measurements revealed that soluble open LFA-1 I domain bound to immobilized soluble ICAM-1, E34/E34, E34/K34, and E34/DeltaD1-D2 with nearly identical affinities. These studies demonstrate that a single ICAM-1 monomer, not dimeric ICAM-1, represents the complete, "fully competent" LFA-1-binding surface.

Binding and phosphorylation of tubulin by G protein-coupled receptor kinases.

Although the beta-adrenergic receptor kinase (betaARK) mediates agonist-dependent phosphorylation and desensitization of G protein-coupled receptors, recent studies suggest additional cellular functions. During our attempts to identify novel betaARK interacting proteins, we found that the cytoskeletal protein tubulin could specifically bind to a betaARK-coupled affinity column. In vitro analysis demonstrated that betaARK and G protein-coupled receptor kinase-5 (GRK5) were able to stoichiometrically phosphorylate purified tubulin dimers with a preference for beta-tubulin and, under certain conditions, the betaIII-isotype. Examination of the GRK/tubulin binding characteristics revealed that tubulin dimers and assembled microtubules bind GRKs, whereas the catalytic domain of betaARK contains the primary tubulin binding determinants. In vivo interaction of GRK and tubulin was suggested by the following: (i) co-purification of betaARK with tubulin from brain tissue; (ii) co-immunoprecipitation of betaARK and tubulin from COS-1 cells; and (iii) co-localization of betaARK and GRK5 with microtubule structures in COS-1 cells. In addition, GRK-phosphorylated tubulin was found preferentially associated with the microtubule fraction during in vitro assembly assays suggesting potential functional significance. These results suggest a novel link between the cytoskeleton and GRKs that may be important for regulating GRK and/or tubulin function.

Supply and need of factor VIII concentrates.

Demand for factor VIII varies greatly and exceeds supply in many places. Logical analysis of this difficult situation has been undertaken by observing actual usage, calculating potential need, and analysing factors which limit or influence production and distribution. Usage exceeds production potential in some places. It is concluded that factor VIII production/usage in the range of 20 000-60 000 IU per hemophilia A patient per year is both feasible and adequate. Production/use below 10 000 IU is not adequate. Production above 60 000 IU is not practicable using current technology.