Search

To determine whether speed discrimination improves when the retinal image is stabilized against the effects of eye movements, thresholds were measured under stabilized and normal viewing conditions. In the normal viewing conditions, eye movements were recorded and used to estimate retinal-image speeds. Stimulus reference speed for sinusoidal gratings varied from 0.5 to 8.0 deg/sec. Results showed that speed discrimination thresholds, expressed as Weber ratios, decreased with increasing stimulus speed for both the normal and stabilized viewing conditions. Stabilized viewing thresholds were higher than normal viewing thresholds only at the slowest stimulus reference speed. However, when speed discrimination thresholds were expressed as a function of the estimated retinal speed, there was no difference in thresholds for the stabilized and normal viewing conditions. A retinal-image model, whereby speed discrimination depends on retinal-image motion, explains the results.

Monocyte apoptosis in vitro was studied in patients on long-term hemodialysis, CAPD, and in predialytic uremia to gain insight into the high susceptibility of these patients to infections. Monocytes from dialysis and control subjects were cultured for 24 to 120 hours in vitro to analyze the level and progression of DNA fragmentation as a hallmark of apoptosis. After an incubation time of 48 hours chromatin fragmentation of 48.5 +/- 7.7% was found in monocytes from dialysis patients, which significantly exceeded DNA fragmentation of control monocytes (23.1 +/- 9.1%; N = 12; P < 0.01). Over longer culture periods of up to 5 days, a continuous progression of apoptosis occurred with a similar slope of percent DNA fragmentation in the two studied groups. Monocyte viability was > 95% both in the dialysis and control group. Hemodialysis patients also showed elevated levels of monocyte apoptosis when programmed cell death was evaluated by transmission electron microscopy or DNA electrophoresis of cleaved chromatin. To test the functional relevance of monocyte apoptosis, a significant reduction of Candida growth inhibition by monocytes of dialysis patients was found with a strong linkage between percentage of DNA fragmentation and impaired microbicidal capacity. Monocytes obtained from patients after the hemodialysis session and from CAPD patients showed normal DNA fragmentation levels similar to controls. Differences of monocyte apoptosis between patients on cuprophane and high-flux polysulphone dialysis were not found. Uremic predialytic patients also exerted an increased monocyte DNA fragmentation of 44.2 +/- 1.5% (N = 7; P < 0.05 compared to controls). Enhanced apoptosis of uremic monocytes was accompanied by a reduced formation of TNF-alpha over 48 hours, revealing a significant negative correlation between chromatin fragmentation and monokine synthesis. Supplementation of monocyte cultures from dialysis patients with exogenous TNF-alpha turned increased apoptosis back to baseline levels, suggesting that inflammatory mediators may modulate monocyte senescence. In summary, the elevated degree of monocyte apoptosis in end-stage renal failure may contribute to the impaired cellular host defense seen in these patients.

Renal allograft recipients are at risk to acquire infectious disease complications primarily after an intensified immunosuppressive therapy. In this study, serum levels of IgG, IgA, IgM and IgG subclasses were compared between transplant patients after different anti-rejection regimen and evaluated as possible predictive markers for infectious implications. Thirty-six renal transplant recipients in the early posttransplantation period were allocated into three subgroups: group 1 consisted of 15 subjects with good primary graft function standing under a basal triple drug immunosuppression; patients of group 2 (n = 9) had a very early acute rejection episode which was treated by high steroid doses and patients of group 3 (n = 12) required antithymocyte globulin (ATG) therapy for acute rejection. Immune parameters were studied 5 weeks after transplantation, when basal triple drug immunosuppression was continued in all patients. Twenty-three age-matched patients under chronic hemodialysis were recruited as a control group. Total IgG serum levels were reduced in transplant patients compared to dialysis subjects, whereas IgA and IgM levels were not altered. IgG subclass analysis revealed, that IgG1 levels were similar in stable transplant compared to chronic hemodialysis patients, but were significantly reduced in rejection patients after steroid pulses or ATG therapy. IgG3 levels were significantly reduced in all transplant recipients compared to dialysis patients without differences between the transplant subgroups. IgG2 and IgG4 subclass levels were similar in all studied subjects. IgG subclass abnormalities were paralleled by a reduction of lymphocyte subsets in rejection patients of groups 2 and 3, which may be the basis for an altered Ig class switching. Seven out of 36 studied transplant patients had severe infections in the early posttransplantation period with four cases of viral infections. Patients with infections had significantly lower IgG1 levels and CD4 positive lymphocyte numbers but similar total IgG levels compared to patients without infections. So IgG1 levels may be of value to predict the occurrence of infectious complications in renal allograft recipients in the early posttransplantation period.

Diadenosine polyphosphates have been shown to influence renal perfusion pressure. As mesangial cells may contribute to these effects we investigated the effects of diadenosine triphosphate (Ap3A), diadenosine tetraphosphate (Ap4A), diadenosine pentaphosphate (Ap5A) and diadenosine hexaphosphate (Ap6A) on membrane voltage (Vm) and membrane conductance (gm) in mesangial cells (MC) of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats in primary and long-term culture. We applied the patch-clamp technique in the fast-whole-cell configuration to measure Vm and gm. To compare the effects of diadenosine polyphosphates with hitherto known agonists we also tested adenosine 5&acute;-triphosphate (ATP) and angiotensin II (Ang II). As there was no significant difference in the Vm values in MC of WKY (-42 +/- 1 mV, n = 70) and SHR rats (-45 +/- 2 mV, n = 99) as well as in the agonist-induced changes of Vm, all data were pooled. The Vm of all the cells was -44 +/- 1 mV (n = 169) and gm was 15.9 +/- 1.8 nS (n = 141). Ion-exchange experiments showed the presence of a K+ and a non-selective cation conductance in resting MC whereas a Cl- conductance or a Na+-selective conductance could not be observed. Ap3A, Ap4A, Ap5A, AP6A and ATP each at a concentration of 5 micromol/l, led to a significant depolarization of Vm by 5 +/- 2 mV (n = 14), 7 +/- 1 mV (n = 25), 3 +/- 1 mV (n = 23), 2 +/- 1 mV (n = 16), and 14 +/- 2 mV (n = 23), respectively. For Ap4A, the most potent diadenosine polyphosphate, we determined the half-maximally effective concentration (EC50) as 6 micromol/l (n = 5-25), for ATP as 2 micromol/l (n = 9-37), and for Ang II as 8 nmol/l (n = 6-18). Ap4A 100 micromol/l increased gm significantly by 55 +/- 20% (n = 16), 100 micromol/l ATP by 135 +/- 60% (n = 18). The diadenosine polyphosphates examined were able to depolarize Vm (Ang II > ATP > Ap4A > Ap3A > Ap5A > Ap6A) by activation of a Cl- conductance and a non-selective cation conductance, as do ATP or Ang II.

Since renal allograft rejection is frequently associated with a blunted erythropoiesis, we investigated erythropoietin (EPO) serum concentrations in 17 patients with acute rejection, eight patients with chronic rejection, and 18 transplant recipients with stable graft function. All rejection episodes were proven by biopsy. Erythropoietin serum levels were significantly reduced in patients with chronic rejection (6.2 +/- 3.4 mU/mL; P < 0.01) compared with individuals with acute rejection (35.6 +/- 33.9 mU/mL) or stable graft function (24.0 +/- 19.7 mU/mL). Suppressed EPO levels were associated with marked anemia in chronic rejection patients. In a subgroup of patients with acute rejection and bad responses to an intensified immunosuppressive regimen or with transplant failure, we found significantly suppressed EPO levels (11.6 +/- 6.1 mU/mL) compared with a subgroup of patients with a beneficial acute rejection outcome (57.0 +/- 34.2 mU/mL; P < 0.01). A correlation between histologic parameters of acute rejection and hormone levels showed that signs of moderate glomerulitis were associated with elevated EPO levels, whereas lesions of moderate tubulitis were associated with low values. We conclude that serum EPO may have prognostic value for rejection outcome in renal transplant recipients.

Three experiments tested whether motion information for nonequiluminant (luminant) and equiluminant dots affects direction judgments when both types of stimuli are moving simultaneously in the same display. The motion directions for the two sets of dots were manipulated to produce four direction differences (0 degrees, 30 degrees, 60 degrees, and 90 degrees). The equiluminant dots were moved in a perfectly correlated fashion, but the percentage of correlated motion for the luminant dots was varied. When subjects judged whether the directions of the equiluminant and luminant dots were the same or different, performance for the conditions with 0 degrees, 60 degrees, and 90 degrees difference improved as the percentage of correlated luminant motion increased. The same result occurred for a control display that contained two sets of luminant dots. However, for the 30 degrees difference, performance was at chance level for the control display, but dropped below chance for the equiluminant-luminant display. When subjects indicated just the direction of the luminant dots, judgments were not affected by equiluminant motion. Judgments for the equiluminant dots also were accurate, except for the conditions with 30 degrees difference; these responses were biased by the luminant motion, indicating some form of motion capture. The interactive effects are discussed in terms of a directionally selective mechanism that combines equiluminant and luminant motion signals.

To evaluate the underlying mechanism of the putative renal protective effects of angiotensin converting enzyme (ACE) inhibitors, the modulatory action of captopril on the angiotensin II (Ang II) and platelet-derived growth factor (PDGF)-induced increase of cytosolic free calcium concentration ([Ca2+]i) was investigated in cultured glomerular mesangial cells (MC) from spontaneously hypertensive rats from the Münster strain (SHR) and normotensive Wistar-Kyoto rats (WKY). Resting [Ca2+]i was not affected by captopril in MC from either SHR or WKY. Captopril inhibited the Ang II-induced [Ca2+]i increase in MC from both SHR and WKY in a dose-dependent and time-dependent fashion. The preincubation of MC with 1 mumol/liter captopril for 40 minutes significantly reduced the Ang II-induced [Ca2+]i increase in SHR from 167 +/- 30 nmol/liter (N = 17) to 74 +/- 20 nmol/liter (N = 8, P < 0.05) and in WKY from 102 +/- 42 nmol/liter (N = 14) to 43 +/- 12 nmol/liter (N = 7, P < 0.05). After removal of external calcium there was no significant effect of captopril on the Ang II-induced [Ca2+]i increase. With the Mn2+ quenching technique, it was confirmed that captopril affects Ca2+ influx. Phospholipase C activity as estimated by diacylglycerol formation was not changed by captopril. The preincubation of MC with 1 mumol/liter captopril for 40 minutes significantly reduced the PDGF-induced [Ca2+]i increase in SHR from 166 +/-54 nmol/liter (N = 9) to 31 +/- 19 nmol/liter (N = 6, P < 0.01) and in WKY from 127 +/- 31 nmol/liter (N = 11) to 61 +/- 32 nmol/liter (N = 5, P < 0.05). Similarly captopril reduced the [Ca2+]i increase induced by endothelin and vasopressin. The results indicate that the actions of Ang II and PDGF on MC are modulated by captopril, probably resulting in the impairment of the calcium dependent contractile response of mesangial cells.

The mechanisms of glucocorticoid-induced immunosuppression of human monocytes for the defense of Candida albicans were examined in this in vitro study. Dexamethasone at pharmacological concentrations (10(-7)-10(-5) M) dose-dependently attenuated growth inhibition of C. albicans by resident monocytes. In interferon-gamma (IFN-gamma)-primed monocytes, fungal growth inhibition was maximal and not altered by dexamethasone. Similarly, phagocytosis and killing of Candida by monocytes were not affected by steroids. To study the underlying mechanisms, we found that Candida-induced synthesis of tumor necrosis factor-alpha (TNF-alpha) by monocytes was completely abrogated by dexamethasone. Substitution of TNF-alpha to dexamethasone-treated monocytes fully reversed the alterations of growth inhibition of C. albicans induced by steroids. These findings suggest that glucocorticoids affect the growth control of Candida by monocytes indirectly via suppression of the formation of TNF-alpha, which is required as an autocrine cofactor for full monocyte activation.

Albumin excretion, Analysis of urinary proteins by polyacrylamide gel electrophoresis (PAGE), and clinical evaluation were performed in 90 HIV-infected patients to assess subclinical renal involvement in HIV infection. Thirteen percent of all patients showed an albumin excretion > 20 mg/liter. Seven of four homosexual patients had albuminuria. Albuminuria occurred exclusively with T4 cell counts below 200/mm3. Polyacrylamide gel electrophoresis indicated glomerular lesions and showed no tubular proteinuria in patients with increased albumin excretion. It is concluded that subclinical renal involvement is not uncommon in HIV infection with T4 cell counts > 200/mm3. HIV-associated nephropathy and heroin-associated nephropathy may not be the main causes of renal involvement. In some cases, opportunistic viral infections may be the cause of microalbuminuria.

Compliance is an important property of the arterial system and abnormalities in compliance can greatly affect cardiovascular function. The elastic properties of the common carotid artery were therefore studied in 24 normotensive hemodialysis patients and 24 healthy normotensives using a noninvasive technique. The hemodialysis patients and the control subjects were matched for blood pressure. Arterial distension was measured by Doppler analysis of the vessel wall movements and blood pressure was recorded by finger-phlethysmography (Finapres). The vessel wall distensibility (DC: 2.49 +/- 0.23 10(-3)/mm Hg; mean +/- SEM) was significantly reduced and the end diastolic diameter (d: 7.3 +/- 0.3 mm) was significantly increased in younger hemodialysis patients (36.3 +/- 2.0 years) when compared with age-related controls (DC: 3.44 +/- 0.24 10(-3)/mm Hg; d: 6.3 +/- 0.3 mm; mean +/- SEM). In older hemodialysis patients (60.2 +/- 2.3 years), there was no significant difference in vessel wall distensibility (DC: 1.55 +/- 0.15 10(-3)/mm Hg) and vessel diameter (d: 7.8 +/- 0.3 mm) as compared with age-matched controls (DC: 1.77 +/- 0.14 10(-3)/mm Hg; d: 7.2 +/- 0.3 mm). The results show that vessel wall distensibility of the common carotid artery is decreased in younger hemodialysis patients as compared with age-matched healthy subjects. The volume expanded state in hemodialysis patients cannot account for the decreased arterial distensibility, since volume depletion by hemodialysis was not associated with a significant change of arterial distensibility (DC 2.14 +/- 0.44 10(-3)/mm Hg before, DC 2.26 +/- 0.45 10(-3)/mm Hg after ultrafiltration, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the contribution of immune mechanisms in the initiation and progression of chronic renal allograft rejection we investigated monocyte-derived cytokine synthesis in vitro in 16 patients with histologically proven chronic rejection; 22 transplant patients with stable function served as controls. Basal tumour necrosis factor-alpha (TNF-alpha) production, measured by L 929 bioassay, was low and not significantly different in both groups. By triggering TNF-alpha formation in vitro by lipopolysaccharide (LPS), high concentrations of TNF-alpha (155.1 +/- 243.0 ng/ml) were measured in monocyte cultures from chronic rejection patients which greatly exceeded the TNF-alpha levels of 11.5 +/- 14.5 ng/ml in the control group. Measurement of interleukin 6 (IL-6) levels by enzyme immunoassay gave similar results, with significantly higher IL-6 concentrations in LPS-triggered monocyte cultures from chronic rejection compared with stable function patients. Additional stimulation of LPS-treated monocytes with interferon-gamma (IFN-gamma) as a priming agent enhanced TNF-alpha formation in stable function patients and, in contrast, slightly reduced monokine formation in chronic rejection patients, which suggests that in this group a high activation level of monocytes has already been reached in vivo by T cell factors such as IFN-gamma. Treatment of monocyte cultures in vitro with prednisolone reduced TNF-alpha formation differently in most but not all cultures from chronic rejection and stable function patients; thus this in vitro test system might be helpful in predicting the benefit of an intensified immunosuppressive regimen for chronic rejection patients.(ABSTRACT TRUNCATED AT 250 WORDS)

In this study, we compared the cellular functions of cultured glomerular mesangial cells (MC) from spontaneously hypertensive rats (SHR) and from normotensive Wistar-Kyoto rats (WKY) in response to the growth factors insulin-like growth factor I (IGF-I) and platelet-derived growth factor (PDGF). IGF-I and PDGF at a concentration above 2 ng/ml and a combination of both tested growth factors exerted a highly elevated growth response of SHR MC versus WKY MC. The total RNA synthesis induced by IGF-I and PDGF was increased in SHR MC as compared with WKY MC, while the overall protein synthesis showed no differences between both strains. Analysis of cell-associated fibronectin accumulation and incorporation of proline into collagenous proteins revealed an enhanced basal and PDGF-stimulated matrix formation of SHR MC which was not dependent on the increased production of autocrine matrix-stimulatory mediators by SHR MC. Changes of cytosolic free calcium - [Ca2+]i - could not be correlated with the enhanced responsiveness of SHR MC to the tested growth factors. The described differences of cellular functions between SHR and WKY MC may contribute to pronounced glomerular alterations such as glomerulosclerosis seen in primary and secondary forms of hypertension.

This is a case report of heparin-associated thrombocytopenia syndrome (white clot syndrome). An 81-Year-old patient was treated with sodium-heparin for proximal deep-venous thrombosis and pulmonary embolism. During administration of heparin, the platelet count decreased to a nadir of 27/nl on day 14 after initiation of this therapy. We also observed a recurrence of pulmonary embolism as well as arterial thromboembolism in the right arm and the right leg. After immediate discontinuation of heparin therapy and change of anticoagulation to oral anticoagulants with overlapping administration of a low molecular weight heparin and application of immunoglobulins, we observed total recanalization of the arterial occlusions, normalization of lung-perfusion scan and rapid recovery of the platelet count.

Cortical necrosis is a rare complication of renal transplants, which requires urgent diagnosis and management to avoid unnecessary immunosuppression. Seven renal transplants with suspected cortical necrosis were evaluated by Doppler-US, 99mTc-DTPA-perfusion study and Gd-DTPA-enhanced dynamic MRI. In four transplants, cortical necrosis was confirmed by angiography and histology. In diagnosing cortical necrosis with preserved medullary perfusion (n = 2) dynamic MRI was superior to the other modalities. Totally necrotic renal transplants (n = 2) were reliably diagnosed by all imaging methods.

The present study tested the hypothesis that nondominant-eye influences on lateral geniculate nucleus (LGN) neurons affect the processing of spatial and contrast information from the dominant eye. To do this, we determined the effects of stimulating the nondominant eye at its optimal spatial frequency on the responses of LGN cells to sine-wave gratings of different spatial frequency and contrast presented to the dominant eye. Detailed testing was carried out on 49 cells that had statistically significant responses to stimulation of the nondominant eye alone. Spatial-frequency response functions to nondominant-eye stimulation indicated that the responses were spatially tuned, as reported previously (Guido et al., 1989). Optimal spatial frequencies through the nondominant eye were significantly correlated with the optimal spatial frequencies through the dominant eye (r = 0.54; P less than 0.0001), and the optimal spatial frequencies were fairly similar for the two eyes. Nondominant-eye stimulation changed the maximal amplitude of the fundamental (F1) response to dominant-eye stimulation for only about 45% (22 of 49) of the cells that responded to nondominant-eye stimulation alone. The response vs. contrast function through the dominant eye was altered for 73% of the cells (51% independent of spatial frequency). Three types of effects were observed: a change in the initial slope of the response vs. contrast function (contrast gain), a change in the response amplitude at which saturation occurred, or an overall change in response at all contrasts. The incidence of these changes was similar for X and Y cells in LGN layers A, A1, and C (only four W cells were tested). Nondominant-eye stimulation had little or no effect on the sizes or sensitivities of the receptive-field centers or surrounds for the dominant eye. In addition, nondominant-eye stimulation had little or no effect on optimal spatial frequency, spatial resolution, or the bandwidth of spatial-frequency contrast sensitivity curves for the dominant eye. Possible functions of binocular interactions in the LGN are considered. The present results suggest a role in interocular contrast-gain control. Interocular contrast differences can occur before the acquisition of binocular fusion, when the two eyes are viewing different aspects of a visual stimulus. Psychophysical and physiological studies suggest that an interocular mechanism exists to maintain relatively constant binocular interactions despite differences in interocular contrast. The present results suggest that at least part of this mechanism occurs in the LGN.

In this study, erythropoietin serum levels were serially determined in eight patients with acute renal failure to get a lead on the etiology of anemia in acute renal failure and to address the relationship between erythropoietin synthesis and renal excretory performance. Erythropoietin serum levels rapidly decreased after onset of acute renal failure to values of 12.8 +/- 10.3 mU/ml compared to 16.8 +/- 9.4 mU/ml in healthy controls. After restoration of renal function, erythropoietin levels climbed slowly in six patients (15.2 +/- 5.3 mU/ml), and in relation to prolonged anemia in these patients, a relative deficiency of erythropoietin could be observed. In one patient with thrombotic thrombocytopenic purpura causing acute renal failure, the decline of erythropoietin secretion was not observed, and in a phase of the disease when plasma exchange therapy was interrupted, markedly increased erythropoietin levels, up to 182 mU/ml, were detected despite the renal failure. Focusing on erythropoietin secretion in thrombotic thrombocytopenic purpura, we followed hormone synthesis in two other patients with the same disease, one of whom had mild renal insufficiency and one had normal renal function. High erythropoietin levels of up to 205 mU/ml were found in these patients, similar to the peak levels found in the patient with complete renal failure. Plasmapheresis treatment reduced erythropoietin production in all three patients with thrombotic thrombocytopenic purpura. In summary, our study indicates that in most cases of acute renal failure, erythropoietin synthesis is compromised and may contribute to the development of anemia in renal failure and aggravate the persistence of anemia after restoration of renal function.(ABSTRACT TRUNCATED AT 250 WORDS)

The contractile properties of recombinant human erythropoietin (rHuEPO) on isolated resistance vessels of renal and mesenteric vascular beds were studied in an in vitro model using a small vessel myograph. Under isometric conditions, rHuEPO caused a contraction of this vasculature in a concentration range between 10 U/ml and 200 U/ml. A maximal active wall tension of 1.52 +/- 0.19 mN/mm was obtained under a rHuEPO dose of 200 U/ml. In Ca2+ free solution, the pressor response to high rHuEPO-concentrations was attenuated, and the response to low rHuEPO concentrations was abolished. In the presence of verapamil, phentolamine and saralasin, rHuEPO-induced contractions were not affected significantly. A dose-dependent vasodilatation of mounted vasculature to acetylcholine (ACh) indicated that endothelium remained intact in our preparations. rHuEPO-induced vessel contraction was not abrogated after an enzymatical removal of endothelium by collagenase, confirming that the described contractile responses are endothelial independent. These findings suggest that a direct vasopressor effect of rHuEPO on proximal resistance vessels may contribute to development of hypertension seen in rHuEPO-treated hemodialysis patients.

Metronidazole was investigated in the basic dermatologic agent Elacutan W to improve the topical therapy of rosacea. The suitability of that basic dermatologic agent was verified for metronidazole, prednisolone and dexamethasone by stability tests (UV-spectroscopy, pH) and by in-vitro-liberation-measurements (membrane method). The drugs are stable for a period of 100 days.

Since granulocyte-macrophage colony-stimulating factor (GM-CSF) has previously been shown to activate macrophages, it was of particular interest to study its effect on synthesis and release of tumor necrosis factor-alpha (TNF-alpha). GM-CSF alone was incapable of activating murine peritoneal macrophages to TNF-alpha release. However, in response to lipopolysaccharide (LPS), GM-CSF was found to prime macrophages for enhanced TNF-alpha production. This priming effect was short-lived and was superseded by the contrary, an unresponsiveness to LPS. The suppressed response was due to a delayed production of prostaglandin E2 (PGE2) which did not affect GM-CSF-enhanced TNF-alpha gene transcription but blocked TNF-alpha production. When PGE2 synthesis was inhibited by indomethacin, the priming effect of GM-CSF was entirely reconstituted. Thus, GM-CSF initially primes for TNF-alpha and subsequently for PGE2 release which, taken together, may represent an autoregulatory feed-back system that could restrict macrophage activation.

1. The effects of jaundice on renal and circulatory function were investigated in chronic bile duct ligated (CBDL) rats 6 days after surgery. Sham operated (SO) animals served as controls. 2. Body weight was significantly reduced, whereas blood pressure remained unaltered, 6 days after bile duct ligation when serum bilirubin had risen to 169 +/- 18 (SEM) as compared with 2.8 +/- 0.3 mumol/l in SO rats. When compared with control values before surgery, urinary volume had significantly increased and absolute excretion of sodium, potassium, chloride and phosphate had decreased on day 6 after CBDL. Endogenous creatinine clearance was markedly depressed when compared with SO rats. Whereas fractional excretion of potassium remained unaltered, fractional excretion of sodium and of phosphate was significantly increased. 3. Except for a significant increase in urinary thromboxane B2 (TXB2) excretion in CBDL rats, no significant changes were observed in urinary excretion of prostaglandin (PG) E2, in the synthesis of PGE2, 6-keto-PGF1 alpha and TXB2 by isolated aortic tissue in vitro, nor in renal and cardiac adenosine triphosphatase activities or renal cortical mitochondrial function. 4. The adenosine triphosphate content of kidney cortex and cardiac mitochondrial function were significantly depressed in CBDL rats. 5. The results demonstrate that jaundice in CBDL rats is associated with functional and metabolic disturbances of the kidney and cardiac muscle, which may contribute to the renal and haemodynamic characteristics observed in jaundiced animals and humans.

The effect of granulocyte/macrophage colony stimulating factor (GM-CSF) on macrophage activation by interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS) was studied in a murine model system. When peritoneal macrophages were pretreated with GM-CSF for 24 hrs, a strong reduction of IFN-gamma-induced tumor cytotoxicity and LPS-triggered tumor necrosis factor-alpha (TNF-alpha) release was found. In contrast, GM-CSF treatment of macrophages for only 4 to 8 hrs enhanced TNF-alpha production. These data suggest that GM-CSF may affect macrophage activation in a biphasic manner in that a time period of enhanced responsiveness to IFN-gamma is followed by a longlasting period of refractoriness.