Forecasted attribution of the human influence on Hurricane Florence.

Changes in extreme weather, such as tropical cyclones, are one of the most serious ways society experiences the impact of climate change. Advance forecasted conditional attribution statements, using a numerical model, were made about the anthropogenic climate change influence on an individual tropical cyclone, Hurricane Florence. Mean total overland rainfall amounts associated with the forecasted storm's core were increased by 4.9 ± 4.6% with local maximum amounts experiencing increases of 3.8 ± 5.7% due to climate change. A slight increase in the forecasted storm size of 1 to 2% was also attributed. This work reviews our forecasted attribution statement with the benefit of hindsight, demonstrating credibility of advance attribution statements for tropical cyclones.

Transport of methotrexate into PC-3 human prostate cancer cells.

Transport of methotrexate (MTX) into human prostatic PC-3 cells was studied. Uptake of MTX vs concentration was saturable at pH 7.4 in cells grown in normal medium and in cells incubated for 24 h in folate-free medium (Km = 3.24 and 4.84 microM, respectively (P > 0.05, n = 3) and Vmax = 0.64 and 0.92 nmol x min(-1) x 10(-9) cells, respectively (P < 0.05, n = 3)). In contrast, uptake at pH 4.5 showed both a saturable component (Km = 1.03 microM, Vmax = 0.42 nmol x min(-1) x 10(-9) cells) and a nonsaturable, linear component. Uptake was inhibited by the structural analogs 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, and folic acid (K(i) = 6.8, 10.9, and 89.6 microM, respectively). Uptake was inhibited by increasing concentrations of chloride ion, suggesting that MTX transport in PC-3 cells may be via an anion-exchange mechanism. Uptake was significantly decreased by high concentrations of sodium cyanide and sodium arsenate but not by sodium azide. Uptake was inhibited by the sulfhydryl inhibitor p-chloromercuriphenylsulfonate and by the anions probenecid and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. Uptake of MTX was independent of sodium ions in the medium. It is concluded that PC-3 human prostate cancer cells have a carrier-mediated system for the uptake of MTX and other folates.

Cell-contact-stimulated formation of filamentous appendages by Salmonella typhimurium does not depend on the type III secretion system encoded by Salmonella pathogenicity island 1.

The formation of filamentous appendages on Salmonella typhimurium has been implicated in the triggering of bacterial entry into host cells (C. C. Ginocchio, S. B. Olmsted, C. L. Wells, and J. E. Galán, Cell 76:717-724, 1994). We have examined the roles of cell contact and Salmonella pathogenicity island 1 (SPI1) in appendage formation by comparing the surface morphologies of a panel of S. typhimurium strains adherent to tissue culture inserts, to cultured epithelial cell lines, and to murine intestine. Scanning electron microscopy revealed short filamentous appendages 30 to 50 nm in diameter and up to 300 nm in length on many wild-type S. typhimurium bacteria adhering to both cultured epithelial cells and to murine Peyer's patch follicle-associated epithelia. Wild-type S. typhimurium adhering to cell-free culture inserts lacked these filamentous appendages but sometimes exhibited very short appendages which might represent a rudimentary form of the cell contact-stimulated filamentous appendages. Invasion-deficient S. typhimurium strains carrying mutations in components of SPI1 (invA, invG, sspC, and prgH) exhibited filamentous appendages similar to those on wild-type S. typhimurium when adhering to epithelial cells, demonstrating that formation of these appendages is not itself sufficient to trigger bacterial invasion. When adhering to cell-free culture inserts, an S. typhimurium invG mutant differed from its parent strain in that it lacked even the shorter surface appendages, suggesting that SPI1 may be involved in appendage formation in the absence of epithelia. Our data on S. typhimurium strains in the presence of cells provide compelling evidence that SPI1 is not an absolute requirement for the formation of the described filamentous appendages. However, appendage formation is controlled by PhoP/PhoQ since a PhoP-constitutive mutant very rarely possessed such appendages when adhering to any of the cell types examined.

Promotion of Salmonella typhimurium adherence and membrane ruffling in MDCK epithelia by staurosporine.

Infection of Madin-Darby canine kidney epithelial cell monolayers with Salmonella typhimurium SL1344 for 60 min results in widespread bacterial invasion which is associated with remodelling of the apical cell membrane to form "membrane ruffles'. Treatment of Madin-Darby canine kidney cell monolayers with the protein kinase inhibitor staurosporine resulted in a 12-fold increase in the number of adhered bacteria without significantly affecting bacterial invasion. Staurosporine treatment also significantly increased both the number and size of membrane ruffles. As S. typhimurium adhere preferentially to these areas of membrane lacking microvilli, the increased extent of membrane ruffling may explain the increased bacterial adherence. These data provide evidence that the propagation of membrane ruffles during S. typhimurium infection is modulated by changes in the phosphorylation state of host proteins.

Invasion of murine intestinal M cells by Salmonella typhimurium inv mutants severely deficient for invasion of cultured cells.

We have examined the role of the Salmonella typhimurium inv locus in invasion of the murine intestine. Previous studies have demonstrated that M cells within the lymphoid-follicle-associated epithelia are the primary site of intestinal invasion by S. typhimurium. In this study, we show that mutants possessing defects in one of two inv genes, invA or invG, which render them severely deficient for invasion of polarized epithelial MDCK cells, retain their ability to actively invade mouse Peyer's patch M cells. The interaction of these mutants with M cells was associated with apical membrane remodelling resembling that induced by wild-type strains. These data demonstrate that Salmonella invasion in vivo can proceed via mechanisms other than those previously defined in cultured cells.

Evidence for a rapid, direct effect on epithelial monolayer integrity and transepithelial transport in response to Salmonella invasion.

In cultured monolayers of high-resistance Madin-Darby Canine Kidney (MDCK) cells, infection with Salmonella typhimurium SL1344 resulted in a dose- and time-dependent increase in transepithelial conductance (Gt) and short-circuit current (Isc). There was a direct linear relationship between the S. typhimurium-induced increments in Isc and Gt suggesting that this early change in epithelial parameters is, in part, the result of a cellular conductance change most probably at the apical membrane. An additional wild-type S. typhimurium strain, SR11, and an invasion-deficient isogenic mutant SB111 carrying a non-polar mutation in invA were used to confirm that the S. typhimurium-induced change in epithelial electrical parameters is directly linked to the invasion process. The S. typhimurium-induced change in epithelial electrical parameters was markedly attenuated in Na+-free choline medium. Addition of piretanide (10(-4) M, basal side) failed to affect the increased epithelial conductance and Isc after a 40-min incubation with S. typhimurium. NPPB (5x10(-4) M) added to the apical medium reduced the S. typhimurium-stimulated Isc by 28%, but Gt was not significantly reduced. It is unlikely that the S. typhimurium-induced Isc is due to Cl- secretion. Staining of S. typhimurium-infected MDCK I monolayers with TRITC-phalloidin revealed marked alterations of F-actin; diffuse intracellular accumulations of F-actin corresponding to the presence of invading bacteria were observed by 15 min. After 60 min, prominent extrusions of the apical membrane corresponding to previously described "membrane ruffles" were noted. Marked accumulations of perijunctional F-actin in infected cells corresponded to contraction of the perijunctional actin ring at the apical pole. In adjacent cells marked distortion and stretch of the apical surface was evident. The invasion-deficient invA mutant SB111 failed to induce these morphological changes. These data demonstrate that S. typhimurium invasion induces increased transcellular conductance which does not result from stimulation of Cl- secretion but instead appears to be predominantly due to increased Na+ permeability. The increased membrane conductance is coincident with increased transepithelial inulin permeability indicating that the increment in Gt has an additional "paracellular" component. The S. typhimurium-induced alterations in epithelial parameters may be related to "membrane ruffling" and/or to the accompanying changes in cell shape.

Methylprednisolone and cortisol metabolism during the early post-renal transplant period.

Despite the widespread use of methylprednisolone and the well-appreciated effects of this drug on HPA suppression, little data is available which describes individual patient exposure to both methylprednisolone and cortisol following renal allograft placement. The clinical utilization of methylprednisolone during the early post-transplant period is based upon standardized dosing protocols that do not consider factors which may influence the pharmacokinetics of this drug during the post-transplant period. Therefore, this study was designed to examine the pharmacokinetics of methylprednisolone (mean dose: 28 mg) and cortisol pharmacodynamics in 9 renal transplant recipients (4 females; 5 males) who were studied during the early post-transplant period (5 to 12 days after surgery). All patients (mean serum creatinine: 1.4 +/- 0.3 mg/dl) had serial blood samples collected over a 12- to 24-hour period (depending upon the dosing schedule) which were analyzed concurrently for methylprednisolone and cortisol. A three-fold variation in drug clearance ranging from 174 to 638 ml/h/kg with a range in the volume of distribution of 0.83 to 2.24 l/kg and resultant half-lives ranging from 1.20 to 3.02 hours was noted. The cortisol response was quantitated by a 12-hour cortisol area under the curve (C-AUC12) to examine the interpatient cortisol patterns during the early post-transplant period. C-AUC12 ranged from 44.0 to 636 ng.h/ml. Significant correlations were noted between the cortisol plasma concentration at 12 hours and methylprednisolone clearance and area under the concentration versus time curve (AUC). Interpatient variability in the disposition of methylprednisolone and cortisol response noted during the early post-transplant period contradict the clinical assumptions which underlie the fixed dosing protocols currently utilized for methylprednisolone.

Estimation of the fermentability of dietary fibre in vitro: a European interlaboratory study.

Five European laboratories tested a simple in vitro batch system for dietary fibre fermentation studies. The inoculum was composed of fresh human faeces mixed with a carbonate-phosphate buffer complex supplemented with trace elements and urea. Five dietary fibre sources (cellulose, sugarbeet fibre, soyabean fibre, maize bran and pectin) were used by each laboratory on three occasions to determine pH, residual non-starch polysaccharides (NSP) and short-chain fatty acid production during fermentation. Cellulose and maize bran degradabilities were very low (7.2(SE 10.8) and 6.2 (SE 9.1)% respectively after 24 h), whereas pectin and soyabean fibre were highly degraded (97.4 (SE 4.4) and 91.1 (SE 3.4)% respectively after 24 h). Sugarbeet fibre exhibited an intermediate level of degradability (59.5 (SE 14.9)%). Short-chain fatty acid production was closely related to NSP degradation (r 0.99). Although each variable was ranked similarly by all laboratories, some differences occurred with respect to absolute values. However, the adaptation of donors to the experimental substrates was not an influential factor. Interlaboratory differences could be reduced either by adding less substrate during incubations or using less-diluted inocula. In vitro fermentations with inocula made from human faeces and from rat caecal contents gave similar results. There was a close correspondence between the data obtained in the present experiment and those previously published in in vivo studies in the rat using the same fibres. The in vitro batch system tested during the present study provides a rapid means of obtaining quantitative estimates of the fermentation and the estimation of the energy content of new sources of dietary fibre.

Post-transplant diabetes mellitus and methylprednisolone pharmacokinetics in African-American and Caucasian renal transplant recipients.

Post-transplant diabetes among renal transplant recipients is more prevalent in the African-American population. However, it is unknown if methylprednisolone (a commonly prescribed glucocorticoid in transplant patients) pharmacokinetics is altered among African-American renal allograft recipients compared to Caucasian counterparts. Therefore, the objectives of this study were to identify the occurrence of post-transplant diabetes in our clinic population and to characterize the pharmacokinetics of methylprednisolone among our African-American and Caucasian renal transplant recipients. A retrospective chart survey was done on African-American and Caucasian recipients with stable renal function and no history of diabetes pre-transplantation in order to characterize the occurrence of post-transplant diabetes in our clinical population. The survey was conducted from January 1985 to January 1992 in recipients with graft survival of at least 3 months. Post-transplant diabetes was defined as two fasting glucose serum concentrations greater than 140 mg/dl or one random serum glucose concentration greater than 200 mg/dl which was confirmed by a fasting serum glucose value greater than 140 mg/dl and a 2 hour post-prandial greater than 200 mg/dl. A 24-hour pharmacokinetic evaluation was conducted in a sub-group of African-American and Caucasian patients after intravenous administration of methylprednisolone. Over the survey period, 75 renal transplants (30 females; 45 males) were performed and 50 of these transplant recipients (24 females; 26 males) were not diabetic prior to the allograft placement. Of these 50 patients, 22 males and 17 females fulfilled the inclusion criteria established for the retrospective survey.(ABSTRACT TRUNCATED AT 250 WORDS)

Repeated assessment of methylprednisolone pharmacokinetics during chronic immunosuppression in renal transplant recipients.

OBJECTIVE: To compare the pharmacokinetics of methylprednisolone in renal transplant recipients on 2 occasions separated by at least 1 month during chronic immunosuppression. DESIGN: A prospective unblinded trial. PATIENTS: Ten renal transplant recipients (aged 25-62 years) evaluated in a public university-affiliated hospital clinic. INTERVENTIONS: All patients received their chronic oral dose of methylprednisolone as a 10-20-minute intravenous infusion during the 2 study periods. MAIN OUTCOME MEASURES: Serum methylprednisolone concentrations were determined by HPLC and were used to generate the pharmacokinetic parameters of the drug. RESULTS: During study 1, which ranged from 1.2 to 24 months posttransplant, the mean +/- SD methylprednisolone dose was 13.2 +/- 6.4 mg. In study 2 (2.5-38.5 mo posttransplant), the mean dose was 10.6 +/- 3 mg. During both study periods, methylprednisolone concentrations exhibited a monoexponential decline. Considerable variability in methylprednisolone clearance was observed between periods in certain patients. Four of the 10 patients demonstrated a reduction in clearance from study 1 to study 2, which ranged from a 28% to a 53% decrease. Two patients exhibited an increase in clearance of 40% and 49%. The mean +/- SD total body clearance in study 1 was 363 +/- 330 mL/min/kg, whereas the mean volume of distribution was 1.18 +/- 0.53 L/kg. The mean elimination rate constant was 0.29 +/- 0.14 h-1, with a mean serum half-life of 2.87 +/- 1.15 h during the first phase. In study 2, the mean methylprednisolone clearance was 261 +/- 150 mL/min/kg (p > 0.05) and the mean volume of distribution was 0.89 +/- 0.31 L/kg (p > 0.05). The mean serum half-life of methylprednisolone was 2.91 +/- 0.60 h (p > 0.05), with the mean elimination rate constant of 0.25 +/- 0.06 h-1 (p > 0.05). CONCLUSIONS: These data demonstrate that intrapatient variability in methylprednisolone clearance exists among certain renal allograft recipients. As a result of the observed variability, patients who are continued on the same dose of methylprednisolone during the posttransplant period of chronic immunosuppression will be subjected to a changing pattern of exogenous glucocorticoid exposure. The impact of these changing patterns requires further prospective evaluation.

Racial differences in the pharmacokinetics of methylprednisolone in black and white renal transplant recipients.

STUDY OBJECTIVE: To examine the comparative pharmacokinetics of long-term methylprednisolone therapy in black and white renal transplant recipients. DESIGN: Comprehensive pharmacokinetic evaluations of patients who participated in our glucocorticoid-monitoring program. SETTING: University-based renal transplantation clinic. PATIENTS: Six white renal transplant recipients with stable renal function, sex- and (approximate) age-matched with six preselected black patients. INTERVENTIONS: The daily oral methylprednisolone dose for each patient was administered intravenously, and serial plasma samples were obtained over 24 hours. MEASUREMENTS AND MAIN RESULTS: Methylprednisolone was analyzed by high-performance liquid chromatography. The drug's pharmacokinetics in black and white patients, respectively, were as follows: mean clearance 234 +/- 124 and 472 +/- 180 ml/hr/kg (p < 0.05); volume of distribution 0.3-2.0 and 0.8-2.0 L/kg; and elimination rate constant 0.13-0.41 and 0.27-0.42 hour-1 (p < 0.06). No statistical difference was noted in the last two parameters. The mean half-life of 3.4 +/- 1.4 hours in black patients compared with 2.1 +/- 0.3 hours in white patients approached statistical significance (p < 0.08). CONCLUSIONS: These preliminary observations suggest that the disposition of methylprednisolone differs between black and white renal transplant recipients. The current method of prescribing glucocorticoids employs a fixed-dose regimen that does not take these possible interracial differences into consideration. Incorporating the differences may allow for more individualized dosing and more efficacious use of the agent in this patient population.

5-Methyltetrahydrofolate transport in basolateral membrane vesicles from human liver.

Transport of 5-methyltetrahydrofolate was studied in vesicles isolated from the basolateral membrane (BLM) of human liver. Uptake was mostly via transport into an osmotically active intravesicular space, with some membrane binding (approximately 20%). Transport was more rapid with an imposed pH gradient (pHout = 5.0, pHin = 7.5) as compared with either pHout = pHin = 5.0 or pHout = pHin = 7.5. Transport under the influence of a pH gradient showed a transient overshoot; uptake at 60 s was 4.2 times higher than at equilibrium (60 min). Transport in the presence of a pH gradient was saturable; apparent Km = 0.55 mumol/L and Vmax = 1.98 nmol.g protein-1.10 s-1. Transport was not saturable at pHout = pHin = 7.5. Transport was inhibited by the structural analogs 5-formyltetrahydrofolate, folic acid, and methotrexate, and was electroneutral in nature. These results suggest that 5-methyltetrahydrofolate transport in human BLM vesicles is via carrier-mediated cotransport with hydrogen ions.

Comparative methylprednisolone pharmacokinetics in renal transplant patients receiving double- or triple-drug immunosuppression.

OBJECTIVE: To assess the pharmacokinetics of chronic methylprednisolone therapy in renal transplant patients receiving double-drug (methylprednisolone and azathioprine) and triple-drug (methylprednisolone, azathioprine, and cyclosporine) immunosuppression. DESIGN: Parallel, randomized trial. PATIENTS: Fourteen renal transplant recipients (aged 29-65 y) evaluated in a public, university-affiliated hospital clinic. INTERVENTIONS: All patients received their chronic oral dose of methylprednisolone via a 10-20-minute intravenous infusion. MAIN OUTCOME MEASURES: Serum methylprednisolone concentrations were determined by HPLC and were used to generate pharmacokinetic parameters for this drug. RESULTS: The mean daily methylprednisolone dosage was 19 +/- 19 mg in the double-drug group and 9 +/- 2 mg in the triple-drug group. Mean serum creatinine concentrations were 124 +/- 44 and 124 +/- 27 mumol/L, respectively. Mean methylprednisolone clearances were similar in both groups: 405 +/- 205 (double-drug) and 373 +/- 365 mL/h/kg (triple-drug) (p > 0.05). Mean steady-state volume of distribution was 1.5 +/- 0.8 L/kg in the double-drug group and 1.3 +/- 0.8 L/kg in the triple-drug group (p > 0.05). Plasma half-life ranged from 1.7 to 4.3 h (mean 2.7) in the double-drug group versus 1.4 to 3.4 h (mean 2.6) in the triple-drug group (p > 0.05). CONCLUSIONS: These data indicate that cyclosporine had no definitive influence on methylprednisolone disposition. The results reveal a wide variation in methylprednisolone metabolism in renal transplant recipients receiving either a double- or triple-drug immunosuppressive regimen. Typically, methylprednisolone is prescribed according to a standardized dosing protocol that assumes minimal interpatient variation. Therefore, the pharmacokinetic variability noted in this study may have important clinical implications regarding the development of chronic toxicity (e.g., osteoporosis, hypothalamic-pituitary-adrenal suppression) and the attainment of successful immunosuppression.

Transport of methotrexate in basolateral membrane vesicles from rat liver.

Transport of the antifolate cancer drug methotrexate was studied in vesicles isolated from the basolateral membrane of rat liver. Transport of methotrexate by basolateral membrane vesicles (BLMVs) was mostly via uptake into an osmotically active intravesicular space, with some binding (approximately 9%), as shown by initial uptake studies and by varying medium osmolarity with increasing concentrations of sucrose. Methotrexate transport was linear for the first 20 s of incubation. Transport was not affected by imposition of a Na+ gradient across the vesicular membrane. Transport of methotrexate displayed a broad pH optimum: at an intravesicular pH of 7.5, the initial rate of uptake was not significantly different at extravesicular pH values ranging from 5.5 to 7.5, but uptake was less at extravesicular pH of 5.0 or 8.0. Methotrexate transport was saturable: Km = 0.15 +/- 0.05 microM and Vmax = 11.4 +/- 1.1 pmol 10 s-1 mg-1 protein. Methotrexate uptake into BLMVs was not inhibited by 5-methyltetrahydrofolate nor by 5-formyltetrahydrofolate but was weakly inhibited by folic acid in a concentration-dependent manner. Uptake was also inhibited by anion-exchange inhibitor 4,4'-diisothio-cyanostilbene-2,2'-disulfonic acid (DIDS), and by the structurally unrelated anions ATP, ADP, Cl-, SO4(2-), and oxalate2-. Adenosine (no negative charge) had no effect on transport. When vesicles were preloaded with anions (ADP, SO4(2-), oxalate2-) such that an anion gradient existed from the intra- to the extravesicular compartment, and methotrexate uptake was measured, no stimulation of uptake was seen. Methotrexate uptake into rat liver BLMVs was electrogenic as shown by stimulation of the initial rate of uptake by a valinomycin-imposed K+ diffusion potential across the vesicular membrane. These results suggest that methotrexate is transported into the hepatocyte across the basolateral membrane by an electrogenic, multispecific anion carrier system.

Transport of 5-methyltetrahydrofolate in basolateral membrane vesicles of rat liver.

We examined 5-methyltetrahydrofolate transport across the basolateral membrane (BLM) of rat liver using isolated membrane vesicles. Uptake of 5-methyltetrahydrofolate by BLM vesicles (BLMV) was found by osmolarity and initial uptake studies to be mostly the result of transport of the substrate into an active, intravesicular space with some binding (approximately 25%) to membrane surfaces. Uptake was similar in the presence of an inwardly directed Na+ or K+ gradient, indicating that transport is not dependent on Na+. Uptake of 5-methyltetrahydrofolate was linear for the first 30 s and was more rapid when an initial pH gradient was imposed across the vesicular membrane [extravesicular pH (pHo) = 5.0, intravesicular pH (pHi) = 7.5]. Under pH gradient conditions, uptake at 3-5 min was about twofold higher than at equilibrium (60 min). The initial rate of uptake at pHo = pHi = 5.0 was more rapid than at pHo = pHi = 7.5, but in neither case was uptake above equilibrium observed. Uptake under pH gradient conditions and at pH 5.0 (no pH gradient) was saturable (apparent Michaelis constants of 0.58 and 0.36 microM, respectively; maximum uptake rates of 1.25 and 0.79 pmol.10 s-1.mg protein-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Oxidative metabolism of 1-nitropyrene by rabbit liver microsomes and purified microsomal cytochrome P-450 isozymes.

Rabbit liver (male) microsomal metabolism of 10 microM [4,5,9,10-3H]-1-nitropyrene (1NP) was investigated. The total metabolism was not appreciably different with rates of 4.44 +/- 0.45, 3.98 +/- 0.19, 3.90 +/- 0.16, and 3.75 +/- 0.27 nmol/min/mg protein, respectively, for microsomes from phenobarbital, Aroclor-1254, ethanol-treated, and untreated rabbits. However, a more noticeable difference was found in the formation of specific metabolites. Phenobarbital treatment induced changes which favored 1-nitropyrene-3-ol formation, and Aroclor-1254 and ethanol-induced changes which favored 1-nitropyren-6-ol and 1-nitropyren-8-ol formation. 1NP was incubated with untreated microsomes and alpha-naphthoflavone, an inhibitor of rabbit cytochrome P-450 form 6 at low concentrations (less than 1 microM), and an activator of form 3c at high concentrations. The presence of alpha-naphthoflavone changed the profile of metabolites while not affecting the total metabolism. Using purified isozymes of rabbit P-450, we found the constitutive form 3b metabolized 1NP at the highest rate with a catalytic activity of 26.8 nmol/min/nmol P-450. Forms 2 and 6 exhibited rates of 2 and 2.2 nmol/min/nmol P-450. Forms 3a, 3c, and 4 had rates about 50- to 300-fold lower than form 3b. High performance liquid chromatography was used to identify the metabolites when the incubations were carried out in the presence of purified rabbit epoxide hydrolase. With form 6, 54% of the metabolites were accounted for as 1-nitropyren-3-ol, while with form 3b, 73% of the metabolites were 1-nitropyren-6-ol and 1-nitropyren-8-ol. The K-region dihydrodiols were formed by forms 2 and 3b, but not by forms 3c or 6. These results demonstrate that 1NP is a preferential substrate for form 3b, and that a preponderance of the metabolism with untreated rabbit liver microsomes can be attributed to this isozyme.

The National Labor Relations Act and health care institutions: the persistent paradox.

In the wake of 1974 amendments to the NLRA, nonprofit health care institutions have been involved in a steady stream of labor relations cases. This article examines some of the new labor relations problems facing these institutions, and it provides valuable information and analysis to help administrators keep abreast of the legal and practical developments stemming from the cases.