Search

We model how a cyber attack may be amplified through the U.S. financial system, focusing on the wholesale payments network. We estimate that the impairment of any of the five most active U.S. banks will result in significant spillovers to other banks, with 38 percent of the network affected on average. The impact varies and can be larger on particular days and geographies. When banks respond to uncertainty by liquidity hoarding, the potential impact in forgone payment activity is dramatic, reaching more than 2.5 times daily GDP. In a reverse stress test, interruptions originating from banks with less than $10 billion in assets are sufficient to impair a significant amount of the system. Additional risk emerges from third party providers, which connect otherwise unrelated banks, and from financial market utilities.

In standard Walrasian macro-finance models, pecuniary externalities due to fire sales lead to excessive borrowing and insufficient liquidity holdings. We investigate whether imperfect competition (Cournot) improves welfare through internalizing the externality and find that this is far from guaranteed. Cournot competition can overcorrect the inefficiently high borrowing in a standard model of levered real investment. By contrast, Cournot competition can exacerbate the inefficiently low liquidity in a standard model of financial portfolio choice. Implications for welfare and regulation are therefore sector specific, depending both on the nature of the shocks and the competitiveness of the industry. (JEL D43, D62, E44, G11, G21, G28, G30)

We construct a new systemic risk measure that quantifies vulnerability to fire-sale spillovers using detailed regulatory balance sheet data for U.S. commercial banks and repo market data for broker-dealers. Even for moderate shocks in normal times, fire-sale externalities can be substantial. For commercial banks, a 1 percent exogenous shock to assets in 2013-Q1 produces fire sale externalities equal to 21 percent of system capital. For broker-dealers, a 1 percent shock to assets in August 2013 generates spillover losses equivalent to almost 60 percent of system capital. Externalities during the last financial crisis are between two and three times larger. Our systemic risk measure reaches a peak in the fall of 2007 but shows a notable increase starting in 2004, ahead of many other systemic risk indicators. Although the largest banks and broker-dealers produce – and are victims of – most of the externalities, leverage and linkages of financial institutions also play important roles.

Why does the market discipline that financial intermediaries face seem too weak during booms and too strong during crises? This paper shows in a general equilibrium setting that rollover risk as a disciplining device is effective only if all intermediaries face purely idiosyncratic risk. However, if assets are correlated, a two-sided inefficiency arises: Good aggregate states have intermediaries taking excessive risks, while bad aggregate states suffer from costly fire sales. The driving force behind this inefficiency is an amplifying feedback loop between asset values and market discipline. In equilibrium, financial intermediaries inefficiently amplify both positive and negative aggregate shocks.

We build a general equilibrium model with financial frictions that impede monetary policy transmission. Agents with heterogeneous productivity can increase investment by levering up, which increases liquidity risk due to maturity transformation. In equilibrium, more productive agents choose higher leverage than less productive agents, which exposes the more productive agents to greater liquidity risk and makes their investment less responsive to interest rate changes. When monetary policy reduces interest rates, aggregate investment quality deteriorates, which blunts the monetary stimulus and decreases asset liquidation values. This, in turn, reduces loan demand, decreasing the interest rate further and generating a negative spiral. Overall, the allocation of credit is distorted and monetary stimulus can become ineffective even with significant interest rate drops., NA

Numerous beneficial effects on cardiovascular health have been described for magnesium (Mg). Intradialytic hypotension (IDH) is a common complication in hemodialysis patients which contributes to cardiovascular mortality. It has been suggested that higher dialysate Mg (DMg) might reduce the risk of IDH.

We analyze the effects and interactions of monetary policy tools that differ in terms of their timing and their targeting. In a model with heterogeneous agents, more productive agents endogenously expose themselves to higher interim liquidity risk by borrowing and investing more. Two inefficiencies impair the transmission of monetary policy: an investment- and a hoarding inefficiency. Heterogeneous agents respond disparately to ex-ante, conventional and ex-post, unconventional monetary policy. However, we show that the two policies are equivalent due to the endogeneity of hoarding. In contrast, targeted interventions such as discount-window lending can alleviate both inefficiencies at the same time.

We argue that post-crisis banking regulations pass through from regulated institutions to unregulated arbitrageurs. We document that, once post-crisis regulations bind post 2014, hedge funds use a larger number of prime brokers and diversify away from GSIB-affiliated prime brokers, and that the match to such prime brokers is more fragile. Tighter regulatory constraints disincentivize regulated institutions not only to engage in arbitrage activity themselves but also to provide leverage to other arbitrageurs. Indeed, we show that the maximum leverage allowed and the implied return on basis trades is considerably lower under post-crisis regulation, in spite of persistently wider spreads.

We study bank supervision by combining a theoretical model distinguishing supervision from regulation and a novel dataset on work hours of Federal Reserve supervisors. We highlight the trade-offs between the benefits and costs of supervision and use the model to interpret the relation between supervisory efforts and bank characteristics observed in the data. More supervisory resources are spent on larger, more complex, and riskier banks. However, hours increase less than proportionally with bank size, suggesting the presence of technological scale economies in supervision. The data also show reallocation of supervisory hours at times of stress and in the post-2008 enhanced supervisory framework for large banks, providing evidence of constraints on supervisory resources. Finally, we show theoretically limits to assessing supervisory success based on ex-post outcomes, as well as benefits of ex-ante commitment policies.Institutional subscribers to the NBER working paper series, and residents of developing countries may download this paper without additional charge at www.nber.org.

The Federal Reserve is responsible for the prudential supervision of bank holding companies (BHCs) on a consolidated basis. Prudential supervision involves monitoring and oversight to assess whether these firms are engaged in unsafe or unsound practices, as well as ensuring that firms are taking corrective actions to address such practices. Prudential supervision is interlinked with, but distinct from, regulation, which involves the development and promulgation of the rules under which BHCs and other regulated financial intermediaries operate. This paper describes the Federal Reserve’s supervisory approach for large, complex financial companies and how prudential supervisory activities are structured, staffed, and implemented on a day‐to‐day basis at the Federal Reserve Bank of New York as part of the broader supervisory program of the Federal Reserve System. The goal of the paper is to generate insight for those not involved in supervision into what supervisors do and how they do it. Understanding how prudential supervision works is a critical precursor to determining how to measure its impact and effectiveness.

In 46 patients of the chronic hemodialysis program blood pressure regulation was studied according to variations of sodium and fluid balance. A strong relationship was observed between blood pressure and the amount of exchangeable sodium. In the hypertensive patients exchangeable sodium was increased depite fulfilled clinical signs of sufficient dehydration. The blood volume was found to be small and the plasma renin activity increased in those hypertensive patients, in which sufficient fluid depletion was inhibited by extreme fluctuations of the blood pressure during dialysis. A diminution of the sodium concentration keeping the fluid balance constant induced an increase of blood pressure and deteriorated the subjective feeling of the patients. By an increase of the sodium concentration up to 155 mEq/l severe blood pressure fluctuations during during dialysis could be prevented, although further fluid was taken off by ultrafiltration. This effect seemed to be mediated--at least partly--by an increase of the low blood volume and a suppression of plasma renin activity. After the patients became normotensive, dialysis procedure could be continued with normal sodium concentration. By a temporary high sodium regimen of the dialysis procedure some patients with renal failure and 'uncontrollable hypertension' can be preserved from bilateral nephrectomy.

Angiotensin-induced proteinuria was examined at the glomerular-tubular level in rats. Ultra-micro-disc electrophoresis was employed to determine albumin concentration of rat proximal tubular fluid samples under control conditions and during the infusion of 0.15 mug/min X 100 g body weight angiotensin II using micropuncture techniques. Under control conditions proximal tubular albumin concentration was 1.32 +/- 0.79 (SD) mg/100 ml (n = 71). There was no correlation between albumin concentration and (TF/P)-inulin ratio indicating an albumin reabsorption in the proximal tubule parallel to fluid reabsorption under control conditions. During angiotensin infusion using re-collection techniques, there is an average increase of 26 times in tubular albumin concentration, indicating an increase in albumin filtered. There was no change in GFR, SNGFR, transit time, (TF/P)-inulin ratio, an increase in urine flow rate, sodium excretion, protein excretion, mean arterial blood pressure during angiotensin infusion. Since effective glomerular filtration pressure was not increased during angiotensin it is concluded that angiotensin-induced proteinuria is due to an increase in filtered protien mediated by a change in glomerular permeability to proteins.

We estimate the term structure of the price of variance risk (PVR), which helps distinguish between competing asset-pricing theories. First, we measure the PVR as proportional to the Sharpe ratio of short-term holding returns of delta-neutral index straddles; second, we estimate the PVR in a Heston (1993) stochastic-volatility model. In both cases, the estimation is performed separately for different maturities. We find the PVR is negative and decreases in absolute value with maturity; it is more negative and its term structure is steeper when volatility is high. These findings are inconsistent with calibrations of established asset-pricing models that assume constant risk aversion across maturities.

The Federal Reserve is responsible for the prudential supervision of bank holding companies (BHCs) on a consolidated basis. Prudential supervision involves monitoring and oversight to assess whether these firms are engaged in unsafe or unsound practices, as well as ensuring that firms are taking corrective actions to address such practices. Prudential supervision is interlinked with, but distinct from, regulation, which involves the development and promulgation of the rules under which BHCs and other regulated financial intermediaries operate. This paper describes the Federal Reserve’s supervisory approach for large, complex financial companies and how prudential supervisory activities are structured, staffed, and implemented on a day‐to‐day basis at the Federal Reserve Bank of New York as part of the broader supervisory program of the Federal Reserve System. The goal of the paper is to generate insight for those not involved in supervision into what supervisors do and how they do it. Understanding how prudential supervision works is a critical precursor to determining how to measure its impact and effectiveness.

We provide a model that rationalizes variation in confidence in the time series and the cross section. Combining horizon-dependent risk aversion (“anxiety”) and selective memory, we show that overly precise beliefs (“overconfidence”) can arise in the equilibrium of a Bayesian agent’s intrapersonal game. In the time series, overconfidence is more prevalent when actual risk levels are high, while underconfidence occurs when risks are low. As more confident agents take more risk, fluctuations in confidence amplify boom-bust cycles. More anxious agents’ beliefs fluctuate more, leading them to buy in booms and sell in crashes.

We address two fundamental critiques of established asset pricing models: that they (1) require a controversial degree of preference for early resolution of uncertainty; and (2) do not match the term structures of risk premia observed in the data. Inspired by experimental evidence, we construct preferences in which risk aversion decreases with the temporal horizon. The resulting model implies term structures of risk premia consistent with the evidence, including timevariations and reversals in the slope, without imposing a particular preference for early or late resolutions of uncertainty or compromising on the ability to match standard moments in the returns distributions.

This article surveys the macroeconomic implications of nancial frictions. Financial frictions lead to persistence and when combined with illiquidity to nonlinear amplication eects.

We model an ‘anxious’ agent as one who is more risk averse with respect to imminent risks than with respect to distant risks. Based on a utility function that captures individual subjects’ behavior in experiments, we provide a tractable theory relaxing the restriction of constant risk aversion across horizons and show that it generates rich implications. We first apply the model to insurance markets and explain the high premia for short-horizon insurance. Then, we show that costly delegated portfolio management, investment advice, and withdrawal fees emerge as endogenous features and strategies to cope with dynamic inconsistency in intratemporal risk-return tradeoffs.

We construct a new systemic risk measure that quantifies vulnerability to fire-sale spillovers using detailed repo market data for broker-dealers and regulatory balance sheet data for U.S. bank holding companies. For broker-dealers, vulnerabilities in the repo market are driven by flight-to-quality episodes, when liquidity and leverage can change rapidly. We estimate that an exogenous 1 percent decline in the price of all assets financed with repos leads to losses due to fire sale spillovers of 8 percent of total broker-dealer equity on average and over 12 percent during the financial crisis. For bank holding companies, vulnerabilities to fire-sales are equally sizable but build up slowly over time. Our measure signals build-up of systemic risk starting in the early 2000s, ahead of many other measures. Our measure also predicts low quantiles of macroeconomic outcomes above and beyond other existing measures, especially at longer horizons.

This article surveys the macroeconomic implications of financial frictions. Financial frictions lead to persistence and when combined with illiquidity to non-linear amplification effects. Risk is endogenous and liquidity spirals cause financial instability. Increasing margins further restrict leverage and exacerbate downturns. A demand for liquid assets and a role for money emerges. The market outcome is generically not even constrained efficient and the issuance of government debt can lead to a Pareto improvement. While financial institutions can mitigate frictions, they introduce additional fragility and through their erratic money creation harm price stability.

Motivated by individuals’ emotional response to risk at dierent time horizons, we model an ‘anxious’ agent ‐ one who is more risk averse with respect to imminent risks than distant risks. Such preferences describe well-documented features of (i) individual behavior, (ii) equilibrium prices, and (iii) institutions. In particular, we derive implications for financial markets, such as overtrading and price anomalies around announcement dates, as well as a downward-sloping term structure of risk premia, which are found empirically. Since such preferences can lead to dynamic inconsistencies with respect to risk trade-os, we show that costly delegation of investment decisions is a strategy used to cope with ‘anxiety.’

Under physiological conditions, kidneys work continuously, 168 h/week. In contrast, patients with end-stage renal disease are usually dialysed only 12 h/week. Even if considered adequate by current Kt/V-based dose estimates, this unphysiological dose is associated with an unacceptable annual mortality rate of 10–20%. Increasing dialysis dose might ameliorate this mortality rate. Eleven patients were switched from their conventional haemodialysis (cHD, 3 × 4 h/week) to an intensified short daily home haemodialysis regimen (sdhHD, 6 × 3 h/week) and followed up for 12 months. Different parameters were evaluated before treatment conversion and quarterly during follow-up [i.e. dialysis efficacy, mean arterial pressure (MAP), antihypertensive drug score, haemoglobin, transferrin saturation, ferritin, dose of erythropoiesis-stimulating agents (ESA), iron requirement, parameters of nutrition (body weight, albumin, protein), C-reactive protein, calcium–phosphate product, alkaline phosphatase (AP), intact parathyroid hormone (iPTH) and amount of phosphate-binding pharmacotherapy]. HD efficacy as assessed by cumulative blood volume increased after dialysis intensification (P

INTRODUCTION Under physiological conditions kidneys work continuously, 168 h/week. In contrast, patients with end-stage renal disease are usually dialyzed only 12-15 h/ week. This unphysiological dialysis dose, even if considered adequate by current Kt/V-based dose estimates, is just capable to maintain the alterations of multiple metabolic parameters at a level that permits an unacceptable annual mortality rate of 10-20%, mainly due to cardiovascular events, protein energy wasting and infections. PATIENTS AND METHODS Thirteen haemodialysis patients were converted from conventional (3 x 4 h/week) to an intensified nocturnal (3 x 8 h/week) dialysis and were longitudinally followed up for 12 months. Different parameters were evaluated before treatment conversion and quarterly during the follow-up period [i.e. dialysis efficacy (eKt/V), mean arterial pressure (MAP), antihypertensive drug score, extra-cellular volume (ECV), haemoglobin, transferrin saturation, ferritin, dose of erythropoiesis-stimulating agents (ESA), iron requirement, parameters of nutrition (body weight (BW), albumin, protein, normalized protein catabolic rate (nPCR), bioelectrical impedance analysis (BIA)), C-reactive protein, calcium-phosphate product, alkaline phosphatase (AP), intact parathyroid hormone (iPTH) and amount of phosphate-binding pharmacotherapy]. RESULTS The calculated dialysis efficacy rose after switching the treatment mode (eKt/V 1.87 versus 2.7, P < 0.0001). Further, a significantly decreased MAP in the pre- (100 versus 89 mmHg) and postdialytic period (97 versus 83 mmHg), and a decreased ECV (13.8 versus 13.2 L; P = 0.03) even though antihypertensive pharmacotherapy could be substantially reduced (P < 0.0001), was found. Concomitant with a reduction of ESA (66.5 versus 45.2 IU/ kg/week; P = 0.006), the haemoglobin level rose significantly (11.4 versus 12.5 g/dL, P = 0.01). Nutritional status assessed by BW (70.9 +/- 20.2 versus 72.1 +/- 19.8 kg, P = 0.02), nPCR (1.39 versus 2.25 g/kg/day, P = 0.02) and BIA (phase angle: 6.2 versus 6.9 degrees, P < 0.001) improved. The calcium-phosphate product slightly declined, without changes in the dose of any phosphate binders. Surprisingly, iPTH of those patients with intact parathyroid glands (n = 7) increased approximately 3-fold (27.9 versus 59.35 pmol/L, P = 0.009), while the AP was found stable. CONCLUSION This study demonstrates improvements in numerous dialysis-associated metabolic variables after intensification of HD time. Of note, an increase of iPTH was detected in those patients with intact parathyroid glands.

One of the major questions in bacterial chemotaxis is how the switch, which controls the direction of flagellar rotation, functions. It is well established that binding of the signaling molecule CheY to the switch protein FliM shifts the rotation from the default direction, counterclockwise, to clockwise. How this shift is done is still a mystery. Our aim in this study was to determine the correlation between the fraction of FliM molecules in the clockwise state (i.e. occupied by CheY) and the probability of clockwise rotation. For this purpose we gradually expressed, from a plasmid, a clockwise FliM mutant protein in cells that express, from the chromosome, wild-type FliM but no chemotaxis proteins. We verified that plasmid-borne FliM exchanges chromosomal FliM in the switch. Surprisingly, a substantial clockwise probability was not obtained before the large majority of the FliM molecules in the switch were clockwise molecules. Thereafter, the rise in clockwise probability was very steep. These results suggest that an increase in the clockwise probability requires a high level of FliM occupancy by CheY approximately P. They further suggest that the steep increase in clockwise rotation upon increasing CheY levels, reported in several studies, is due, at least in part, to cooperativity of post-binding interactions within the switch. We also carried out the inverse experiment, in which wild-type FliM was gradually expressed in a background of a clockwise fliM mutant. In this case, the level of the clockwise mutant protein, required for establishing a certain clockwise probability, was lower than in the original experiment. If our system (in which the ratio between the rotational states of FliM in the switch is established by slow exchange) and the native system (in which the ratio is established by fast changes in FliM occupancy) are comparable, the results suggest that hysteresis is involved in the switch function. Such a situation might reflect a damping mechanism, which prevents a situation in which fluctuations in the phosphorylation level of CheY throw the switch from one direction of rotation to the other.

It is well established that the response regulator of the chemotaxis system of Escherichia coli, CheY, can undergo acetylation at lysine residues 92 and 109 via a reaction mediated by acetyl-CoA synthetase (Acs). The outcome is activation of CheY, which results in increased clockwise rotation. Nevertheless, it has not been known whether CheY acetylation is involved in chemotaxis. To address this question, we examined the chemotactic behaviour of two mutants, one lacking the acetylating enzyme Acs, and the other having an arginine-for-lysine substitution at residue 92 of CheY - one of the acetylation sites. The Deltaacs mutant exhibited much reduced sensitivity to chemotactic stimuli (both attractants and repellents) in tethering assays and greatly reduced responses in ring-forming, plug and capillary assays. Likewise, the cheY(92KR) mutant had reduced sensitivity to repellents in tethering assays and a reduced response in capillary assays. However, its response to the addition or removal of attractants was normal. These observations suggest that Acs-mediated acetylation of CheY is involved in chemotaxis and that the acetylation site Lys-92 is only involved in the response to repellents. The observation that, in the cheY(92KR) mutant, the addition of a repellent was not chemotactically equivalent to the removal of an attractant also suggests that there are different signalling pathways for attractants and repellents in E. coli.

CheY is the response regulator protein serving as a phosphorylation-dependent switch in the bacterial chemotaxis signal transduction pathway. CheY has a number of proteins with which it interacts during the course of the signal transduction pathway. In the phosphorylated state, it interacts strongly with the phosphatase CheZ, and also the components of the flagellar motor switch complex, specifically with FliM. Previous work has characterized peptides consisting of small regions of CheZ and FliM which interact specifically with CheY. We have quantitatively measured the binding of these peptides to both unphosphorylated and phosphorylated CheY using fluorescence spectroscopy. There is a significant enhancement of the binding of these peptides to the phosphorylated form of CheY, suggesting that these peptides share much of the binding specificity of the intact targets of the phosphorylated form of CheY. We also have used modern nuclear magnetic resonance methods to characterize the sites of interaction of these peptides on CheY. We have found that the binding sites are overlapping and primarily consist of residues in the C-terminal portion of CheY. Both peptides affect the resonances of residues at the active site, indicating that the peptides may either bind directly at the active site or exert conformational influences that reach to the active site. The binding sites for the CheZ and FliM peptides also overlap with the previously characterized CheA binding interface. These results suggest that interaction with these three proteins of the signal transduction pathway are mutually exclusive. In addition, since these three proteins are sensitive to the phosphorylation state of CheY, it may be that the C-terminal region of CheY is most sensitive for the conformational changes occurring upon phosphorylation.

Switching flagellar rotation from one direction to another is an essential part of bacterial chemotaxis. Fumarate has been shown to possess the capacity to restore to flagella of cytoplasm-free, CheY-containing bacterial envelopes the ability to switch directions and to increase the probability of reversal in intact cells. Neither the target of fumarate action nor the mechanism of function is known. To distinguish between the two potential targets of fumarate, the response regulator CheY and the flagellar switch-motor complex, we compared flagellar rotation between isogenic strains that lacked CheY and had either low or high levels of fumarate. The difference in the fumarate levels was due to a deletion of the genes encoding the enzymes that synthesize and metabolize fumarate; succinate dehydrogenase and fumarase, respectively. The strains were in a gutted background (i.e. a background deleted for the cytoplasmic chemotaxis proteins and some of the receptors), and switching was achieved by carrying out the measurements at 2.5 degreesC, where it has been demonstrated that gutted cells switch spontaneously. The flagellar rotation of the strain with the highest level of fumarate was the most clockwise-biased and had the highest reversal frequency, indicating that fumarate is effective even in the absence of CheY. Fumarate reduced the free energy difference of the counterclockwise-to-clockwise transition and had no appreciable effect on the activation energy of this transition. Similar observations were made at room temperature, provided that intracellular CheY was present. In a wild-type background, both mutants made rings on semi-solid agar typical of normal chemotaxis. Taken together, the results suggest that the target of fumarate is the switch-motor complex, that fumarate acts by increasing the probability of the clockwise state, and that a fumarate level as low as that found in succinate dehydrogenase mutants is sufficient for normal chemotaxis.

Earlier studies have suggested that CheZ, the phosphatase of the signaling protein CheY in bacterial chemotaxis, may be in an oligomeric state both when bound to phosphorylated CheY (CheY approximately P) (Blat, Y., and Eisenbach, M. (1994) Biochemistry 33, 902-906) or free (Stock, A., and Stock, J. B. (1987) J. Bacteriol. 169, 3301-3311). The purpose of the current study was to determine the oligomeric state of free CheZ and to investigate whether it changes upon binding to CheY approximately P. By using either one of two different sets of cross-linking agents, free CheZ was found to be a dimer. The formation of the dimer was specific, as it was prevented by SDS which does not interfere with cross-linking mediated by random collisions. The dimeric form of CheZ was confirmed by sedimentation analysis, a cross-linking-free technique. In the presence of CheY approximately P (but not in the presence of non-phosphorylated CheY), a high molecular size cross-linked complex (90-200 kDa) was formed, in which the CheZ:CheY ratio was 2:1. The size of the oligomeric complex was estimated by fluorescence depolarization to be 4-5-fold larger than the dimer, suggesting that its size is in the order of 200 kDa. These results indicate that CheZ oligomerizes upon interaction with CheY approximately P. This phosphorylation-dependent oligomerization may be a mechanism for regulating CheZ activity.

CheZ is the phosphatase of CheY, the response regulator in bacterial chemotaxis. The mechanism by which the activity of CheZ is regulated is not known. We used cheZ mutants of Salmonella typhimurium, which had been isolated by Sockett et al. (Sockett, H., Yamaguchi, S., Kihara, M., Irikura, V. M., and Macnab, R. M. (1992) J. Bacteriol. 174, 793-806), for cloning the mutant cheZ genes, overexpressing and purifying their products. We then measured the phosphatase activity, binding to CheY and to phosphorylated CheY (CheY approximately P), and CheY approximately P dependent oligomerization of the mutant CheZ proteins. While all the mutant proteins were defective in their phosphatase activity, they bound to CheY and CheY approximately P as well as wild-type CheZ. However, unlike wild-type CheZ, all the four mutant proteins failed to oligomerize upon interaction with CheY approximately P. On the basis of these and earlier results it is suggested that (i) oligomerization is required for the phosphatase activity of CheZ, (ii) the region defined by residues 141-145 plays an important role in mediating CheZ oligomerization and CheY approximately P dephosphorylation but is not necessary for the binding to CheY approximately P, (iii) the oligomerization and hence the phosphatase activity are regulated by the level of CheY approximately P, and (iv) this regulation plays a role in the adaptation to chemotactic stimuli.

Recent studies have indicated that human spermatozoa respond to follicular fluid by attraction to chemotactic factor(s) in the fluid, accompanied by enhancement of motility and ultimately hyperactivation. In this study, we quantified the sperm response. We exposed spermatozoa to a gradient of a chemotactically active fraction of follicular fluid (denoted as "the attractant") and separated the spermatozoa that accumulated in the attractant and those that did not. We thus obtained two subpopulations: one enriched with chemotactically responsive spermatozoa, and one deficient in such spermatozoa. The fraction of the responsive spermatozoa out of the total sperm population was 2-12% at any measured time point. With time, the responsive spermatozoa lost their ability to be attracted, while such activity was gradually acquired by the subpopulation originally deficient in responsive spermatozoa. These results indicate that the identity of responsive spermatozoa is continuously changing. If the in vitro results are representative of the physiological conditions in vivo, they imply that the role of sperm chemotaxis combined with enhanced motility may be to select capacitated spermatozoa and bring them to the egg. Such a mechanism may, over an extended period of time, increase the prospect that an egg will meet capacitated spermatozoa as soon as it ovulates.

Theoretically plasma exchange is an almost ideal method of artificial liver support. It supports major functions of the liver: synthesis, detoxification, and regulation. Plasma exchange was first applied for liver failure by Lepore in 1967 [11, 12]. However, before the availability of membrane plasma separation, plasma exchange was too labour intensive to be widely applied. Therefore true benefits and dangers could not be evaluated. With the introduction of continuous membrane plasma separation, this treatment experienced a true boom for numerous indications [13, 14]. When applied in fulminant liver disease early effects have been astonishing. The state of consciousness improves regularly and in many cases patients even wake up. Toxins are effectively removed and synthetic products replaced significantly (Tables 1, 2). However, the initial enthusiasm soon faded. Not only did plasma exchange not fullfil its expectations, but actually it frequently induced severe complications and decreased the survival rate. When only one plasma exchange is performed, complications are rare. However, complications increase when the treatment is repeatedly performed [7, 8]. The lung is one of the more sensitive organs in plasma exchange. Pulmonary edema and infiltrations have been reported and aggregates found in the lungs of multiexchanged patients [5, 8].

Renal micropuncture and microdissection techniques with ultramicro fluid analysis have been applied to evaluate single nephron function in the skate, Raja erinacea. We have divided the skate nephron into three proximal tubular segments (PTS I-III), three distal coilings (DC I-III), and a countercurrent loop system located between the proximal segments and the distal coilings. The collecting duct is the principal site of urinary dilution. Following exposure of the fish to 75% seawater for about 24 hours, the sodium concentration difference between the end collecting duct lumen and plasma is decreased sufficiently to account for the urinary dilution. The principal site for magnesium, phosphate and sulphate secretion appears to be PTS II. This segment is located on the ventral surface of the kidney. PTS II is also the main nephron site for reabsorption of sodium and chloride in excess of water.

Beta 2-Microglobulin (beta 2M) plasma levels and levels of a second low-molecular-weight protein (myoglobin) were studied during a 2- to 4-hour sham dialysis period (no dialysate flow, no weight loss) and during a 4- to 5-hour hemodialysis (HD) with a Cuprophan capillary dialyzer. While no rise of the beta 2M or myoglobin levels occurred during sham dialysis, a rise of 22.1 +/- (SD) 8.5% (beta 2M) or 19.9 +/- 12.1% (myoglobin) was seen during regular HD. The increases of both molecules showed a significant correlation (r = 0.44; p less than 0.03). Both rises could not be completely abolished using correction factors for hemoconcentration. The rises occurred irrespectively of the dialysate buffer. The results suggest that neither the Cuprophan membrane nor the extracorporeal circuit were responsible for the rise of both molecules during HD. It seems more likely that changes of the extracellular volume and extra- to intracellular water shifts are involved and account for the majority of the rise. However, the possibility of minor increase in the extracellular mass of beta 2M or myoglobin cannot be excluded completely.

The concentration of nine endogenous free L-alpha-amino acids (ALA, LEU, ILE, PHE, TYR, LYS, GLU, PRO, GLY) and of taurine were determined simultaneously along the nephron of the rat kidney using free-flow micropuncture techniques without altering plasma amino acid concentration or kidney function. The amount of each amino acid was determined after dansylation (14C-labelled dansyl-chloride) in the micropuncture sample followed by thinlayer chromatography. The main site of reabsorption is the proximal tubule. After 15-20% of the proximal tubule length the bulk of reabsorption has taken place (18.9 plus or minus 3.4% S.E. of the filtered load remaining). Net reabsorption continues to a small but significant extent along the distal nephron (disal tubule and collecting duct). Reabsorption of taurine is less rapid (% remaining of filtered load at the early proximal tubule 37.0 plus or minus 4.6%). The transtubular concentration ratio of all amino acids except taurine follows a homogeneous course. Under the experimental conditions of this study no distction with respect to different systems of reabsorption "neutral", "basic", "acidic", "imino-glycine") could be made.

Renal involvement (RI)--defined as proteinuria greater than 150 mg per 24 h with haematuria or impaired glomerular filtration rate--was studied in 80 patients with infective endocarditis (IE). Proteinuria was measured quantitatively and further differentiated by the SDS-polyacrylamide-gel electrophoresis. RI was found in 40 patients (50%) with proteinuria from 150 to 8000 mg per 24 h. SDS-PAGE revealed a tubular protein pattern in 17 patients, a glomerular pattern in 6 and a glomerulo-tubular pattern in 17. Mortality rate was significantly higher in patients with RI (40%) than in those without (7.5%), and was not related to the type of infected valve, infective organisms, method of treatment (surgical or medical) or embolic events. Following successful treatment of IE, 18 out of 23 patients showed complete normalization of renal function. Renal involvement in patients with IE may be of prognostic significance--indicating an impaired prognosis.

An in vitro approach to study bacterial motility and chemotaxis is described. The approach is based on a preparation of flagellated cell envelopes. The envelopes are prepared from bacteria by a penicillin treatment and subsequent osmotic lysis. When the envelopes are energized, their flagella rotate. The direction of rotation in wild type envelopes is counterclockwise. Inclusion of the CheY protein within the envelopes may restore clockwise rotation. The advantages and disadvantages of this approach are pointed out.

Hagfishes (Myxine glutinosa, Cyclostomata) are the only vertebrates whose body fluids are isoosmotic to seawater due to high sodium and chloride concentrations in the plasma. The unique mode of fluid and electrolyte handling of Myxine has been studied by micropuncture methods at the single nephron level. In the archinephric duct, which assumes the function of the tubular apparatus of higher vertebrates, no fluid or sodium is reabsorbed from the glomerular filtrate. Calcium, glucose and magnesium are reabsorbed whereas potassium and phosphate are excreted. The intravascular volume of M. glutinosa is mainly regulated by the filtration rate which greatly increases with increasing arterial as well as venous pressure.

Using the techniques of Lissamine Green passage and micropuncture on the renal cortex of rats we were able to relate a vascular welling point (branching point of vas efferens) to one nephron. The loops of the nephrons studied on the surface were numbered sequentially in the direction of urinary flow. The distance from each loop to its vascular welling point was measured. As the distance between the loops and their glomerulus increased the distance to their welling point decreased. From these observations it was possible to conclude that the flow of blood was opposite to the urine flow. Under direct observation a counter-current flow was noticed in 72.5% of the peritubular capillaries and tubular loops; in 10.5% the flow was in the same direction, and in 17.0% no predominant direction of flow could be seen (n=131).

Micropuncture experiments were carried out on rat kidneys subjected to temporary ischemia (TI). Unilateral TI was performed by clamping the blood supply to the left kidney for 60 min. Time period between TI and investigating the kidney ranged from 1 h to 13 days. In another series of experiments blood supply to the left kidney was severely diminished for 24 h by a clip.-39% of animals developed anuria of the experimental kidney; in the other animals, urine flow rate was markedly decreased after TI (P