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Biomedical subjects

B Kahn

Publications and source records attributed to B Kahn.

At least 19 recordsLinked to original sources

Models of insulin action on metabolic and growth response genes.

In ongoing studies aimed at elucidating the mechanism of insulin action on the expression of genes that modulate glucose utilization and cell growth, we have focused on the inductive effect of insulin on transcription of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the early growth response gene, Egr-1. Insulin acutely stimulates the expression of both genes in 3T3 adipocytes; however, in primary adipocytes, chronic insulin exposure has opposing effects on the expression of these genes. GAPDH mRNA is decreased in the epididymal fat cells of diabetic animals and is increased over control levels when insulin is replaced, while Egr-1 mRNA levels are increased in diabetic animals. These observations, coupled with the finding that insulin-stimulated Egr-1 gene transcription is impaired in a Chinese hamster ovarian (CHO) cell line that displays normal metabolic responses but impaired ability to regulate DNA synthesis, support the conclusion that insulin regulation of Egr-1, a growth response gene, and GAPDH, a metabolic response gene, are mediated by distinct pathways. We present evidence that supports the role of protein phosphorylation in mediating the effect of insulin on activation of Egr-1 and GAPDH gene transcription.

3T3 Cells

Assessing the needs and quality of life of patients with HIV infection: development of the HIV Overview of Problems-Evaluation System (HOPES).

OBJECTIVE: To develop and evaluate the psychometric properties (reliability, validity etc.) of a comprehensive Quality of Life (QOL) tool, for patients infected with the human immunodeficiency virus (HIV), that was adapted from a previously validated cancer tool. DESIGN: Cross-sectional, patient completed written surveys and interviews. SETTING: The Medical Centers serving HIV infected patients in the Los Angeles community including UCLA, community physicians, Veterans Affairs Medical Centers, and a County hospital: and additional data contributed from Johns Hopkins University Medical Center CMV Retinitis Clinic. PATIENTS: Patients (n = 318) with HIV infection including asymptomatic (37%), ARC (20%), AIDS (25%) and AIDS with Cancer (18%) receiving health services at one of the above sites. MEASUREMENTS: The patients self-administered the newly developed instrument, the HOPES (HIV Overview of Problems-Evaluation System), other QOL related tools including the Medical Outcomes Study instrument adapted for HIV (MOS-HIV) the Profile of Mood States (POMS), the Perceived Adjustment to Chronic Illness Scale (PACIS), and the Physical Activity Scale (PAS). Brief interview to assess the Karnofsky Performance Status Score (KPS). Measured sociodemographic characteristics included age, sex, race, HIV risk factor, education etc. Assessed medical history, current medications, HIV clinical classification. MAIN RESULTS: The sociodemographic and medical characteristics of the sample resemble those of the general population with HIV infection in this geographic area: 96% male, 28% nonwhite, 84% homosexual contact as risk factor, 75% receiving antiretroviral therapy. The adaptation of the cancer QOL instrument to HIV appears to have face and content validity according to patients and health professionals who care for HIV infected patients. Analyses of the psychometric properties found that the HOPES has a similar structure to its parent instrument following factor analyses which results in five summary scales representing the Physical, Psychosocial, Medical Interaction, Sexual and Significant Other/Partners domains in addition to a Global Score. Internal consistency of 35 subscales is high with a mean alpha coefficient of 0.82. Correlations of the HOPES summary scales with other QOL instruments are in the predicted directions. Comparing patients within the HIV clinical diagnostic categories on the HOPES Global, Physical, and Psychosocial Summary Scales indicates that Asymptomatic Patients have better QOL than symptomatic patients. This finding is also found in the other QOL instruments which provides evidence of construct validity. CONCLUSIONS: The HOPES is an excellent tool for identifying the problems and needs of patients with HIV infection and for assessing their quality of life. It is reliable, valid and acceptable to patients. The tool may be especially useful in developing a normative data base.

Acquired Immunodeficiency Syndrome

Effect of alcohol chain length on tubule formation in 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine.

Aqueous dispersions of 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine, on cooling below the chain melting temperature, form hollow cylindrical structures known as 'tubules'. We have studied the formation of tubules in methanol/water, ethanol/water and n-propanol/water. For each alcohol, there is a defined window of alcohol/water ratios in which the lipid precipitates with the tubule morphology. As the chain length of alcohol is increased, the window shifts towards lower alcohol fraction. Light scattering studies show that at very low lipid concentrations the tubules self-assemble directly from the isotropic phase where as for lipid concentrations greater than 4 mg/ml an intermediate L alpha phase is observed. These results indicate that the mechanism of tubule formation may be dependent on lipid concentration.

Alcohols

Biocompatibility of lipid microcylinders: effect on cell growth and antigen presentation in culture.

The authors are developing a lipid-based microcylinder for the controlled release of biological response modifiers and as templates for cellular migration and differentiation. These structures are comprised of a photopolymerizable phosphatidylcholine (1,2-ditricosa-10,12-diynoyl-sn-glycero-3-phosphocholine) and form spontaneously as a result of a thermotropic phase transition in aqueous solution or in a cosolvent solution of 70:30 ethanol:water. The hollow cylinders are helically wrapped lipid bilayers, variable in length (50-250 microns, depending on conditions of formation) and are 0.5-1.0 microns in diameter. The interaction has been examined of three types of lipid microcylinders: (1) monomeric, (2) photopolymerized by exposure to 254 nm light, and (3) surface-modified by incorporation of 6 mol% gangliosides, with different human cell lines and peripheral blood leucocytes to evaluate the biocompatibility of these structures. The proliferative status of U937 (a histiocytic monocyte), K562 (an erythroleukaemic cell), and Jurkat's derivative (a T-lymphoblast) as measured by pulsed tritiated thymidine was unaffected by the presence of up to 100 micrograms/ml of lipid microcylinders after 3 d in culture. Adherent human peripheral blood monocytes were shown to form adhesive contacts with the lipid microcylinders. An 'association' index from this interaction shows that after 3 d in culture, the association was much lower for those microcylinders that had incorporated ganglioside compared with monomeric or polymerized structures. The lipid microcylinders do not activate T-cells isolated from human peripheral blood, nor do they inhibit the activation of T-cells by phorbol esters or other mitogens.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens

Self-assembling phospholipid filaments.

Aqueous dispersions of double-chain phospholipids spontaneously assemble into closed bilayers called vesicles (or liposomes). Although the vesicles are in general topologically spherical, cylindrical and helical liposomes have sometimes been observed. We present here video-enhanced microscopic studies of a diacetylenic phospholipid dispersed in ethanol/water, which reveal the existence of unusual bilayer morphologies. On cooling the dispersion from the isotropic phase, we have observed the formation of long (of the order of hundreds of micrometres), thin (0.2-2 microns) filaments, which fluctuate strongly. When the temperature is decreased further, the filaments rapidly retract into a mass of lipid. At constant temperature, on the other hand, the filaments transform into torus or ring-like vesicles. Such non-spherical structures have been predicted theoretically but not previously observed experimentally.

Phosphatidylcholines

Effect of various methods of restoring flexor sheath integrity on the formation of adhesions after tendon injury.

The effect of three different methods of restoring flexor sheath integrity on the formation of adhesions around traumatized flexor tendons was studied by use of a chicken animal model. The three methods were: I, Primary sheath repair; II, a fascia patch; and III, a synthetic polytetrafluoroethylene surgical membrane patch. These were compared with controls in which the flexor sheath was excised. Adhesion formation was assessed both biomechanically by measuring the parameter work of flexion, (which represents the resistance to tendon gliding caused by adhesions), and also histologically. At 3 and 6 weeks there was no significant difference in the work of flexion between either the sheath repair or fascia patch digits, and the sheath excised controls. However, use of the synthetic polytetrafluorethylene patch did result in tendon gliding, which was significantly better than the controls. In contrast, at 12 weeks all three methods of sheath reconstruction had similar tendon gliding biomechanics, and all were significantly better than the controls. Histologically, at 3 weeks, the biologic barriers sheath repair and fascia patch were associated with a layer of granulation tissue, which adhered to the underlying tendon. This was similar to the appearance of the sheath excised control digits. The synthetic patch was not associated with a significant inflammatory reaction at this time period and was clearly separated from the tendon. However, by 6 and 12 weeks the granulation tissue in all three sheath reconstruction groups had undergone remodeling to a greater degree than had the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Analysis of 228Ra and 226Ra in public water supplies by a gamma-ray spectrometer.

Methods for measuring 228Ra were reviewed to select a brief and simple screening procedure under NIPDW Regulations for public water supplies. A two-step method was considered to concentrate Ra by evaporation or co-precipitation and to count it with a gas ionization detector, a liquid-scintillation detector, or a Ge detector with multichannel analyzer. Gross beta particle counting appears to be feasible for screening to meet the 0.04 Bq L-1 detection limit. One can utilize the same sample volume as currently collected and measure radiation with commonly available equipment in reasonable time. The required sample volumes were estimated on the basis of known counting efficiencies and background count rates. Gamma-ray spectral analysis is the recommended option, however, because 226Ra and 228Ra can be determined directly and simultaneously. Several aspects of the method were examined to assure that the concentration procedure is nearly quantitative and that the detection limit can be reached with a 3.8-L sample in a 6000-s counting period. The method was tested with Ra tracer solutions and EPA intercomparison samples over the range of 0.04 to 1 Bq L-1. It was found appropriate for 228Ra and 226Ra analyses.

Radium

Effect of postural changes, nitroglycerin and verapamil on diastolic ventricular function as determined by radionuclide angiography in normal subjects.

Whereas improvement in diastolic function indexes in response to therapeutic interventions has been attributed to a beneficial effect of the intervention, measurements of diastolic function appear to be influenced by changes in loading conditions, heart rate and sympathetic tone. To determine the effect of body position and short-term pharmacologic intervention on radionuclide angiographically determined left ventricular peak filling rate, high temporal resolution time-activity curves and absolute left ventricular volumes obtained by equilibrium-gated blood pool scans were evaluated in 12 normal subjects in the supine position at rest and in response to several postural and pharmacologic manipulations. This study confirmed the reproducibility of the technique and demonstrated that in normal subjects, peak filling rate varies in response to changes in body position and to short-term administration of sublingual nitroglycerin and intravenous verapamil. Peak filling rate ranged from 3.3 to 5.1 end-diastolic volumes (EDV)/s with a variability of 13.7% during five baseline supine measurements in the 12 subjects. Compared with values in the supine position (mean +/- SEM = 4.38 +/- 0.24 EDV/s), peak filling rate increased +16 +/- 6% to 4.75 +/- 0.27 EDV/s in the upright position (p less than 0.05) but did not change significantly with leg elevation. Peak filling rate at baseline and during postural changes correlated significantly with ejection fraction (r = +0.49), with stroke volume (r = +0.26) and inversely with end-systolic volume (r = -0.41), but did not correlate with heart rate or blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Use of environmental TLD data at a nuclear power station to estimate detection limits for radiation exposure due to station operation.

The environmental radiation monitoring network maintained by the Georgia Department of Natural Resources at the Hatch Nuclear Plant, Baxley, GA, was used to determine the variability in measured background exposures in order to estimate the detection limits for radiation due to station operation. Data were obtained from LiF thermoluminescent dosimeters (TLDs) exposed in sets of four at 46 locations for 16 consecutive quarters from 1982 to 1985. The average exposure for 695 values was 11.8 microC kg-1 y-1 (mR/quarter). At individual locations, the averages of quarterly exposures ranged from 9.3 to 14.3 microC kg-1 y-1 and had standard deviations from 0.8 to 2.2 microC kg-1 y-1 with a typical standard deviation of 1.5 microC kg-1 y-1. The standard deviation due to reading the TLDs and subtracting the transit plus storage exposure, estimated as 0.4 microC kg-1 y-1, contributed only a small fraction of the uncertainty of the mean background; the greater contribution is from temporal fluctuations. There is a spatial pattern of higher background along the Altamaha River but no distinct seasonal pattern. The observation that exposure values at most locations rose and fell in unison suggested a calculational model that adjusts the average exposure level at a location by an increment determined each quarter at control locations. This model reduced the standard deviation for a predicted quarterly background exposure to 0.9 microC kg-1 y-1, with a range of 0.5 to 1.3 microC kg-1 y-1. If the standard deviation of the net value is multiplied by an error probability constant of 3.3 (type I and II errors not greater than 5%), the detection limits range from 2 to 5 microC kg-1 y-1 at the individual locations, with an average of 3 microC kg-1 y-1. This approach or two similar ones described earlier are recommended for improving the detection limit where needed. The standard deviation, and hence the detection limit, can be further reduced by selecting a subset of indicator and control locations with more closely matched background exposure fluctuations. This was demonstrated with five indicator and five control locations, but further study is needed to determine selection guides.

Cesium Radioisotopes

Bioaccumulation factor for 32P measured in bluegill, Lepomis macrochirus, and catfish, Ictalurus punctatus.

The ratio of the bioaccumulation factors for 32P and phosphorus was determined for edible tissue in two species of freshwater fish by measuring the specific activity (32P activity per milligram phosphorus) in muscle relative to feed. The 32P tracer was added to the feed at a uniform level throughout the study. Feeding was at two levels: ad libitum and at a lower but constant intake per body weight. In the main experiment, bluegill were maintained in a large flow-through tank and sacrificed at approximately weekly intervals for 51 d of 32P accumulation and 28 d of depuration to compare the specific activity with values predicted with a calculational model. In experiments performed in smaller aquaria, the specific activity in bluegill and catfish muscle was compared at two feeding levels and two temperatures. In addition, unfed fish were exposed to 32P in water at a known specific activity to determine the extent of phosphorus uptake directly from water. The pattern of specific activity increase and decrease in fish muscle during the accumulation/depuration experiment was consistent with a one-compartment model, so that specific activity ratios at steady state could be predicted from measurements during relatively brief exposures. On this basis, the ratio of the bioaccumulation factors of 32P and phosphorus in fish feeding ad libitum was 0.081 for bluegill and 0.17 for catfish. Hence, at a mean phosphorus bioaccumulation factor of 70,000, the factors for 32P are 6,000 and 12,000, respectively. The ratios were less at lower phosphorus intakes associated with lower feeding rates; moreover, the lesser value for bluegill occurred at a much lower phosphorus intake than by catfish. The bioaccumulation factor ratio was lower by an order of magnitude at a water temperature of 11 degrees C than at 16-27 degrees C, and was lower by two orders of magnitude when phosphorus uptake was from water by unfed fish.

Animals

Radiological sampling and analytical methods for National Primary Drinking Water Regulations.

Radiological sampling and analysis performed under the National Interim Primary Drinking Water Regulations were evaluated for the U.S. Environmental Protection Agency (EPA) Office of Drinking Water to consider whether any changes should be recommended. The authors reviewed the analytical screening scheme; sample collection, storage and analysis procedures; selection of analytical methods; reliability of results; and possible future needs. The main problem in the program has been dependence on a screening scheme of gross alpha-particle activity measurement and 226Ra analysis for predicting elevated 228Ra levels to determine compliance with the maximum contaminant level (MCL) for Ra. In some aquifers, 228Ra levels have been found to be unrelated to 226Ra levels. Several alternatives are discussed to eliminate this problem. A secondary problem is that the measurement for assuring compliance with the MCL for gross alpha-particle activity minus Ra, Rn and U uses chemical U analysis and assumes equilibrium of 238U and 234U. Because some ground waters are known to be at disequilibrium, radiometric U analysis is needed for those gross alpha-particle activities and chemical U values that could result in an erroneous conclusion relative to the MCL. In addition, studies were recommended for determining analytical uncertainties and assuring reliable sampling and sample maintenance; improvements in the system for accepting methods were suggested; and methods were identified for several radionuclides not currently in the analytical program that may be needed to assure absence of elevated radiation doses and could be useful for identifying trace contaminants.

Alpha Particles

Behavior of radionuclides in sanitary landfills.

his study was undertaken to evaluate the possibility of disposing low-level radioactive waste in sanitary landfills with leachate containment to prevent environmental releases. To meet this objective, two simulated landfills, each 200 l. in volume and containing 55 kg of municipal refuse, were operated in the laboratory with simulated rainfall additions for a 9-month period to observe the extent to which radio-cobalt, -cesium, -strontium and tritium were leached into the liquid phase. One of the units was operated with leachate recycle, the other as a single pass control. Liquid samples were analyzed weekly for 3H, 58Co, 85Sr and 134Cs tracers. Weekly analyses were also performed for approximately 30 parameters to define the degree of stabilization of the waste. Major parameters included BOD, COD, pH and concentrations of specific organics, metals and gases. Concentrations of stable cobalt, strontium and cesium were also measured periodically. Soluble radioactivity levels in both systems were reduced by factors of 50 for 58Co, 5 for 85Sr and 7 for 134Cs, taking radioactive decay and dilution into account. Some radionuclide removal from the liquid phase was associated with major chemical changes in the landfills that occurred within 80 days for the control system and within 130 days for the recycle unit. Observed acid, sulfide, and CO2 concentrations suggested mechanisms for removing some of the radionuclides from leachate. Detection of 3H in the off-gas indicated that less than 1% of tritiated waste became airborne. The waste in the leachate recycle unit was more completely stabilized than in the control unit.

Environmental Pollution

The bioaccumulation factor for phosphorus-32 in edible fish tissue.

Information used to derive the bioaccumulation factor for 32P in edible portions of fish was reviewed to evaluate the currently recommended values of 100,000 in fresh water and 29,000 in sea water that are applied in calculating radiation doses to persons from nuclear-power reactor effluents. A generic phosphorus bioaccumulation factor of 70,000 was obtained for larger rivers and estuarine waters on the basis of geometric mean phosphorus concentrations of 2 mg/g wet weight in fish muscle and 0.03 mg/l dissolved in water. A 20-fold lower bioaccumulation factor was inferred for 32P because radioactive decay is much faster than phosphorus turnover. A phosphorus turnover rate in muscle of 0.2% per day was estimated as a long-term average for edible-size fish, although more rapid turnover has been observed for brief periods. Large deviations from the generic bioaccumulation factor will occur for different phosphorus concentrations in water and turnover rates in fish. Site-specific determinations are also needed because 32P is bioaccumulated at lower trophic levels in the food web, not in the fish. Hence, the availability of concentrating organisms determines the bioaccumulation factor. Several other conditions that affect the 32P bioaccumulation factor have not been quantified and are suggested for study.

Animals

Radium and uranium concentrations in Georgia community water systems.

The first cycle of statewide radionuclide concentration measurements of public drinking water supplies was completed in accord with the Federal and Georgia Safe Drinking Water Acts. The recommended pattern of analysis is initial screening for gross alpha-particle activity, followed by measuring 226Ra if the gross alpha-particle activity is above 5 pCi/l. and then measuring 228Ra if the 226Ra concentration is above 3 pCi/l; and uranium analysis if the gross alpha-particle activity exceeds 15 pCi/l. Surface water supplies for more than 100,000 persons are analyzed for 3H and 90Sr and screened for gross beta-particle activity, with additional analytical requirements if the latter is above 50 pCi/l. Specified supplies downstream for nuclear facilities are analyzed for 3H, 90Sr and 131I, and further analyses are required if the gross beta-particle activity is above 15 pCi/l. More thorough screening was applied for 1400 public water supplies in Georgia, of which about 90% use groundwater. Radium concentrations exceeded the maximum contaminant level (MCL) of 5 pCi/l. in 24 groundwater supplies, mostly due to elevated 226Ra. The gross alpha-particle activity minus uranium concentrations exceeded the 15 pCi/l. MCL in 3 additional samples. No MCL was exceeded in surface water. The S.D.s of analytical results estimated from replicate analyses were approximately twice those based on counting statistics, suggesting that screening levels should be lowered to assure detection of 226Ra at MCL values.

Georgia

Search for building materials as sources of elevated radiation dose.

A systematic approach to finding materials that cause elevated gamma radiation exposure rates or 222Rn progeny working levels in buildings was tested in the Atlanta area. With the proposed procedure, exposure rates in planned structures would be derived from a radiation survey of the material performed with a NaI(T1) detector. Working level values under specified conditions would be inferred from an additional measurement of 226Ra concentration in the material. To quantify the procedure, surveyed building materials were analyzed for radionuclide content and categorized according to an exposure rate index related both to the survey meter count rate and the radionuclide concentration. An available calculational model was used to predict from the index the exposure rate in a room totally enclosed by radioactive material. An additional model was developed for application to structures where the radioactive material is only in the floor or walls. 222Radon concentrations in an enclosed space were also predicted according to an available model. Exposure rates were measured in newly constructed buildings to test the approach. Measurements in older buildings found elevated gamma-ray emission from concrete blocks made with phosphate slag from a phosphorus producer in Alabama. Buildings with walls of these blocks were used to test the prediction of 222Rn concentrations in building air due to 226Ra in construction material. The calculational models predicted that the 226Ra concentration of approx. 20 pCi/g in these blocks would result in increases of the average exposure rates by 10 mu R/hr and of 222Rn concentrations by 0.2 pCi/l. under specified conditions. Observed levels were consistent with these predictions, but the major fraction of 222Rn in room air was attributed to inflow from the ground beneath the building.

Construction Materials