Signal pathways regulating hyaluronan secretion into static and cycled synovial joints of rabbits.

Joint lubrication, synovial fluid conservation and many pathophysiological processes depend on hyaluronan (HA). Intra-articular HA injection and exercise, which stimulates articular HA production, ameliorate osteoarthritis. We therefore investigated the pathways regulating movement-stimulated articular HA secretion rate ( ) in vivo. Endogenous HA was removed from the knee joint cavity of anaesthetised rabbits by washout. Joints were then cycled passively or remained static for 5 h, with/without intra-articular agonist/inhibitor, after which newly secreted HA was harvested for analysis. Movement almost doubled . Similar or larger increases were elicited in static joints by the intra-articular Ca(2+) ionophore ionomycin, prostaglandin E(2), cAMP-raising agents, serine/threonine phosphatase inhibitor and activation of protein kinase C (PKC). PKC-stimulated secretion was inhibited by the PKC inhibitor bisindolylmaleimide I and inhibitors of the downstream kinases MEK-ERK (U0126, PD98059). These agents inhibited movement-stimulated secretion of HA (MSHA) only when the parallel p38 kinase path was simultaneously inhibited by SB203580 (ineffective alone). The phospholipase C inhibitor U73122 almost fully blocked MSHA (P = 0.001, n = 10), without affecting static . The ENaC channel blocker amiloride inhibited MSHA, whereas other inhibitors of stretch-activated channels (Gd(3+), ruthenium red, SKF96365) did not. It is proposed that MSHA may be mediated by PLC activation, leading to activation of parallel PKC-MEK-ERK and p38 kinase pathways.

Mechanosensitive hyaluronan secretion: stimulus-response curves and role of transcription-translation-translocation in rabbit joints.

Joint movement was recently shown to stimulate the secretion of the lubricant hyaluronan (HA); also, exercise therapy and intra-articular hyaluronan injections are used to treat moderate osteoarthritis. The present study quantifies the stimulus-response curves for HA secretion in vivo and reports a role of transcription-translation-translocation in the secretory response. After washing out endogenous HA from anaesthetized, cannulated rabbit knees, the joints were cycled passively at various frequencies and durations, with or without intra-articular inhibitors of protein synthesis and Golgi processing. Newly secreted HA was harvested for analysis after 5 h. Joints displayed graded, non-linear stimulus-response curves to both duration and frequency of movement; 1 min duration per 15 min or a frequency of 0.17 Hz raised HA secretion by 42-54%, while rapid (1.5 Hz) or prolonged cycling (9 min per 15 min) raised it by 110-130%. Movement-stimulated secretion and phorbol ester-stimulated secretion were partly inhibited by the translation inhibitor cycloheximide, by the transcription-translation inhibitors actinomycin D and puromycin and by the Golgi translocation inhibitor brefeldin A. There is thus a graded coupling between HA secretion and cyclic joint movement that depends partly on new protein synthesis. This is likely to be important for joint homeostasis, providing protection during repetitive cycling and potentially contributing to exercise therapy for osteoarthritis.

Lunar magnetic field: permanent and induced dipole moments.

Apollo 15 subsatellite magnetic field observations have been used to measure both the permanent and the induced lunar dipole moments. Although only an upper limit of 1.3 x 10(18) gauss-cubic centimeters has been determined for the permanent dipole moment in the orbital plane, there is a significant induced dipole moment which opposes the applied field, indicating the existence of a weak lunar ionosphere.

The moon: sources of the crustal magnetic anomalies.

Previously unmapped Apollo 16 subsatellite magnetometer data collected at low altitudes over the lunar near side are presented. Medium-amplitude magnetic anomalies exist over the Fra Mauro and Cayley Formations (primary and secondary basin ejecta emplaced 3.8 to 4.0 billion years ago) but are nearly absent over the maria and over the craters Copernicus, Kepler, and Reiner and their encircling ejecta mantles. The largest observed anomaly (radial component approximately 21 gammas at an altitude of 20 kilometers) is exactly correlated with a conspicuous light-colored deposit on western Oceanus Procellarum known as Reiner gamma. Assuming that the Reiner gamma deposit is the source body and estimating its maximum average thickness as 10 meters, a minimum mean magnetization level of 5.2 +/- 2.4 x 10(-2) electromagnetic units per gram, or approximately 500 times the stable magnetization component of the most magnetic returned sample, is calculated. An age for its emplacement of

Radio Reflection by Free Radicals in Earth's Atmosphere.

Reflections of megacycle-per-second radio signals by free radicals in Earth's ionosphere are observed having about the intensity predicted for induced magnetic-dipole transitions. It seems that magnetic atoms, ions, and molecules in planetary atmospheres may be detected by this method. These cbservations were made with the topside ionosonder of the Canadian satellite Alouette II.

Magnetic Field Signatures Near Galileo's Closest Approach to Gaspra.

Two large magnetic field rotations were recorded by the spacecraft Galileo 1 minute before and 2 minutes after its closest approach to the asteroid Gaspra. The timing and the geometry of the field changes suggest a connection with Gaspra, and the events can be interpreted as the result of the draping of the solar wind field around a magnetospheric obstacle. Gaspra's surface field is inferred to be within an order of magnitude of Earth's surface field, and its magnetic moment per unit mass is in the range observed for iron meteorites and highly magnetized chondrites. The location of the magnetic signatures suggests that perturbations are carried by waves in the magnetosonic-whistler mode with wavelengths between electron and ion gyro radii.

Jupiter's Magnetic Field. Magnetosphere, and Interaction with the Solar Wind: Pioneer 11.

The Pioneer 11 vector helium magnetometer provided precise, contititious measurements of the magnetic fields in interplanetary space, inside Jupiter's magnetosphere, and in the near vicinity of Jupiter. As with the Pioneer 10 data, evidence was seen of the dynanmic interaction of Jupiter with the solar wind which leads to a variety of phenomena (bow shock, upstream waves, nonlinear magnetosheath impulses) and to changes in the dimension of the dayside magnetosphere by as much as a factor of 2. The magnetosphere clearly appears to be blunt, not disk-shaped, with a well-defined outer boundary. In the outer magnetosphere, the magnetic field is irregular but exhibits a persistent southward component indicative of a closed magnetosphere. The data contain the first clear evidence in the dayside magnetosphere of the current sheet, apparently associated with centrifugal forces, that was a donminatnt feature of the outbound Pionieer 10 data. A modest westward spiraling of the field was again evident inbound but not outbound at higher latitudes and nearer the Sun-Jupiter direction. Measurements near periapsis, which were nearer the planet and provide better latitude and longitude coverage than Pioneer 10, have revealed a 5 percent discrepancy with the Pioneer 10 offset dipole mnodel (D(2)). A revised offset dipole (6-parameter fit) is presented as well as the results of a spherical harmonic analysis (23 parameters) consisting of an interior dipole, quadrupole, and octopole and an external dipole and quadrupole. The dipole moment and the composite field appear moderately larger than inferred from Pioneer 10. Maximum surface fields of 14 and 11 gauss in the northern and southern hemispheres are inferred. Jupiter's planetary field is found to be slightly more irregular than that of Earth.

Saturn's Magnetic Field and Magnetosphere.

The Pioneer Saturn vector helium magnetometer has detected a bow shock and magnetopause at Saturn and has provided an accurate characterization of the planetary field. The equatorial surface field is 0.20 gauss, a factor of 3 to 5 times smaller than anticipated on the basis of attempted scalings from Earth and Jupiter. The tilt angle between the magnetic dipole axis and Saturn's rotation axis is < 1 degrees , a surprisingly small value. Spherical harmonic analysis of the measurements shows that the ratio of quadrupole to dipole moments is < 10 percent, indicating that the field is more uniform than those of the Earth or Jupiter and consistent with Saturn having a relatively small core. The field in the outer magnetosphere shows systematic departures from the dipole field, principally a compression of the field near noon and an equatorial orientation associated with a current sheet near dawn. A hydromagnetic wake resulting from the interaction of Titan with the rotating magnetosphere appears to have been observed.

Mariner V: Plasma and Magnetic Fields Observed near Venus.

Abrupt changes in the amplitude of the magnetic fluctuations, in the field strength, and in the plasma properties, were observed with Mariner V near Venus. They provide clear evidence for the presence of a bow shock around the planet, similar to, but much smaller than, that observed at Earth. The observations appear consistent with an interaction of the solar wind with the ionosphere of Venus. No planetary field could be detected, but a steady radial field and very low plasma density were found 10,000 to 20,000 kilometers behind Venus and 8,000 to 12,000 kilometers from the Sun-Venus line. These observations may be interpreted as relating to an expansion wave tending to fill the cavity produced by Venus in the solar wind. The upper limit to the magnetic dipole moment of Venus is estimated to be within a factor of 2 of 10(-3) items that of Earth.

Magnetic field of jupiter and its interaction with the solar wind.

Jupiter's magnetic field and its interaction with the magnetized solar wind were observed with the Pioneer 10 vector helium magnetometer. The magnetic dipole is directed opposite to that of the earth with a moment of 4.0 gauss R(J)(3) (R(J), Jupiter radius), and an inclination of 15 degrees lying in a system III meridian of 230 degrees . The dipole is offset about 0.1 R(J) north of the equatorial plane and about 0.2 R(J) toward longitude 170 degrees . There is severe stretching of the planetary field parallel to the equator throughout the outer magnetosphere, accompanied by a systematic departure from meridian planes. The field configuration implies substantial plasma effects inside the magnetosphere, such as thermal pressure, centrifugal forces, and differential rotation. As at the earth, the outer boundary is thin, nor diffuse, and there is a detached bow shock.

Magnetic field studies of the solar wind interaction with venus from the galileo flyby.

During the 10 February 1990 flyby of Venus, the Galileo spacecraft skimmed the downstream flank of the planetary bow shock. This provided an opportunity to examine both the global and the local structure of the shock in an interval during which conditions in the solar wind plasma were quite steady. The data show that the cross section of the shock in planes transverse to the flow is smaller in directions aligned with the projection of the interplanetary magnetic field than in directions not so aligned. Ultralow-frequency waves were present in the unshocked solar wind, and their amplitude peaked when the spacecraft was downstream of the foreshock. At large distances down the tail, the Mach number of the flow normal to the shock is low, thus providing the opportunity to study repeated crossings of the collisionless shock in an interesting parameter regime. Some of the shock crossings reveal structure that comes close to the theoretically predicted form of intermediate shocks, whose existence in collisionless plasmas has not been confirmed.

Cyclic movement stimulates hyaluronan secretion into the synovial cavity of rabbit joints.

The novel hypothesis that the secretion of the joint lubricant hyaluronan (HA) is coupled to movement has implications for normal function and osteoarthritis, and was tested in the knee joints of anaesthetized rabbits. After washing out the endogenous synovial fluid HA (miscibility coefficient 0.4), secretion into the joint cavity was measured over 5 h in static joints and in passively cycled joints. The net static secretion rate (11.2 +/- 0.7 microg h(-1), mean +/- s.e.m., n = 90) correlated with the variable endogenous HA mass (mean 367 +/- 8 microg), with a normalized value of 3.4 +/- 0.2 microg h(-1) (100 microg)(-1) . Cyclic joint movement approximately doubled the net HA secretion rate to 22.6 +/- 1.2 microg h(-1) (n = 77) and raised the normalized percentage to 5.9 +/- 0.3 microg h(-1) (100 microg)(-1). Secretion was inhibited by 2-deoxyglucose and iodoacetate, confirming active secretion. The net accumulation rate underestimated true secretion rate due to some trans-synovial loss. HA turnover time (endogenous mass/secretion rate) was 17-30 h (static) to 8-15 h (moved) The results demonstrate for the first time that the active secretion of HA is coupled to joint usage. Movement-secretion coupling may protect joints against the damaging effects of repetitive joint use, replace HA lost during periods of immobility (overnight), and contribute to the clinical benefit of exercise therapy in moderate osteoarthritis.

Risk of infection with hepatitis A, B or C, cytomegalovirus, varicella or measles among child care providers.

BACKGROUND: Employment as a child care provider has been suggested as an indication for hepatitis A virus (HAV) immunization; however, whether this occupational group is at increased risk of HAV infection is not well-defined. METHODS: We obtained sera samples for testing for antibodies to hepatitis A, B and C, cytomegalovirus, varicella and measles from a sample of child care providers in King County, WA, and administered a questionnaire to assess employment characteristics and other potential risk factors for infection. We also compared the anti-HAV seroprevalence among providers with that of subjects in the Third National Health and Nutrition Survey, representative of the US general population. RESULTS: Thirteen percent (48 of 360) of providers were anti-HAV-positive (46% (22 of 47) of foreign born vs. 8% (26 of 313) of US-born (P < 0.001)). In multivariate analysis anti-HAV seropositivity was associated with foreign birth, age, income and Hispanic ethnicity but was not associated with characteristics of employment. Seroprevalence among US-born providers tended to be lower than that among Third National Health and Nutrition Survey subjects of similar age, sex, race and income. Sixty-two percent of providers were seropositive to cytomegalovirus, which was associated with nonwhite race, changing diapers > or = 3 days/week while at work and having a child in the household. Antibody prevalence was 1.4% to hepatitis B core antigen, 0.6% to hepatitis C, 94% to measles and 98% to varicella. CONCLUSIONS: The anti-HAV prevalence among US-born providers was low, and seropositivity was not associated with employment characteristics, indicating that occupational exposure to HAV is uncommon under non-outbreak circumstances.

Risk factors for hepatitis C virus infection among health care personnel in a community hospital.

OBJECTIVE: To determine the prevalence of and risk factors for antibody to the hepatitis C virus in hospital employees. METHODS: Retrospective testing of serum samples obtained from 1677 hospital employees during a prehepatitis B vaccination program in a private teaching community hospital. RESULTS: Twenty-three employees (1.4%) were found to have antibody to hepatitis C virus. The prevalence of antibody to hepatitis C virus was higher in blacks (3.4%) than in whites (1.1%, p = 0.03) and Hispanics (2.6%, p = 0.88). In a logistic regression model, factors significantly associated with antibody to hepatitis C virus seropositivity included antibody to hepatitis B core antigen (p = 0.002), a history of blood transfusion (p = 0.03), and needlestick injuries (p = 0.04). CONCLUSION: Although the prevalence of antibody to hepatitis C virus in health care workers was not high, needlestick injuries were associated with an increased risk for acquiring hepatitis C virus infection.

The cost-effectiveness of adolescent hepatitis A vaccination in states with the highest disease rates.

BACKGROUND: The Advisory Committee on Immunization Practices has recommended routine childhood hepatitis A vaccination in states and communities where the incidence of disease exceeds the national average, but most adolescents are currently unprotected from infection. OBJECTIVE: To estimate clinical and economic consequences of vaccinating adolescents against hepatitis A in the 10 states with the highest disease rates. DESIGN: Decision analysis was used to assess cost-effectiveness from societal and health system perspectives. Parameter estimates were obtained from national surveillance data, a study of hepatitis A cases, and an expert panel. MAIN OUTCOME MEASURES: Reduction in disease incidence; costs of vaccination, treatment, and work loss; years of life saved (YOLS); and costs per YOLS. RESULTS: In states with the highest disease rates, vaccination of adolescents against hepatitis A would reduce the lifetime risk of symptomatic infection from 3.3% to 0.7% and prevent loss of 2117 years of life. Vaccination of a single birth cohort would cost $30.9 million, yet treatment and work loss costs would decline $14.2 million and $23.8 million, respectively. Hepatitis A vaccination would cost the health system $7902 per YOLS or $13,722 per discounted YOLS. Results are most sensitive to variation in the discount rate and assumptions regarding long-term vaccine protective efficacy. CONCLUSIONS: Hepatitis A vaccination of adolescents in states with high disease rates would reduce costs to society. Although health system costs would increase, cost-effectiveness is comparable to other recommended vaccines and superior to many commonly used medical interventions. Arch Pediatr Adolesc Med. 2000;154:763-770

A computerized fetal monitoring system.

A computerized fetal monitoring system has been developed at the Cedars-Sinai Medical Center in Los Angeles, California. It utilizes unmodified fetal monitors feeding fetal heart rate and uterine pressure data into a minicomputer. The overall accuracy on internal monitoring is 91%. The concept of on-line computer analysis of fetal monitoring records has met with clinical acceptance and is utilized for all patients in labor at the Cedars-Sinai Medical Center.

A colourimetric enzyme-linked sandwich assay for the detection of human platelets bound to a fibrinogen-coated surface.

A colourimetric enzyme-linked sandwich assay has been developed to investigate the binding of human platelets to fibrinogen. The presence of platelets bound to fibrinogen-coated plastic can easily be detected and quantitated. Platelets treated with chymotrypsin to expose the fibrinogen receptor, are fixed with paraformaldehyde, and stored frozen. The detection sandwich consists of a mouse monoclonal antibody directed against the human platelet CD9 antigen, and a rabbit anti-mouse immunoglobulin conjugated to the enzyme alkaline phosphatase. The cleavage of the phosphatase substrate p-nitrophenyl phosphate can be monitored colourimetrically. The data presented provide evidence that this method is capable of detecting platelet-fibrinogen binding in a physiologically relevant manner. The binding is inhibited by EDTA or excess fibrinogen. The fibrinogen alpha and gamma chain peptides, RGDS and LGGAKQAGDV, and the snake venom echistatin are also inhibitory with IC50 values of 135 microM, 1.8 mM and 100 nM respectively.

Hepatitis B vaccination programs for health care personnel in U.S. hospitals.

A random sample of 232 U.S. hospitals was surveyed. Of those hospitals, 75 percent had hepatitis B vaccination programs. The presence of a program was associated with hospital size (60 percent of those with 100 beds, 75 percent with 100-499 beds, 90 percent with 500 or more beds; P = 0.0013) and hospital location (urban 86 percent; rural 57 percent; P less than 0.001). The frequency of needlestick exposures per month among hospital personnel and hospital location were directly related to and best predicted the existence of hepatitis B vaccination programs. All hospitals with programs offered vaccine to high-risk personnel (as defined by the hospital). Seventy-seven percent of hospitals paid all costs for vaccinating high-risk personnel; 19 percent paid for any employee to be vaccinated regardless of risk status. Forty-six percent of hospitals with programs were estimated to have vaccinated more than 10 percent of all eligible personnel, and 13 percent to have vaccinated more than 25 percent of eligible personnel. The highest compliance rates were associated with hospitals paying for the vaccine and requiring vaccination of high-risk personnel. Fifty-four percent of hospitals attributed noncompliance to concern regarding vaccine safety and effectiveness. The reasons why there was no vaccination program in 58 hospitals were (a) low incidence of hepatitis B virus infections among personnel, (b) cost of vaccine, and (c) vaccination being offered as part of a needlestick protocol. Full utilization of hepatitis B vaccine could eliminate the occupational hazard that hepatitis B virus presents to health care personnel.