[Comparative study of CT relative enhancement value and subjective visual evaluation for intestinal ischemia in patients with closed loop obstruction].

Objective: To compare and evaluate the diagnostic performance of visual evaluation and CT maximal density relative enhancement value in the diagnosis of intestinal ischemia complication in patients with closed loop obstruction and to explore the feasibility of CT maximal density relative enhancement value in quantifying the degrees of intestinal ischemia. Methods: The clinical and CT imaging data of 82 patients, 46 males and 36 females, aged from 19 to 78(52±18) years, with closed loop obstruction were retrospectively analyzed in the First Affiliated Hospital of Zhengzhou University from July 2017 to July 2019. All patients were classified into three groups: necrosis group (28 cases), ischemia group (22 cases), non-ischemia group(32 cases) using clinicopathologic results as reference standard. CT visual evaluation was performed by two experienced radiologists. The sensitivity, specificity, positive and negative predictive values and accuracy of the two observers were calculated respectively. The inter-observer agreement was analyzed by kappa analysis. Maximal density relative enhancement value was defined as the difference CT value of an ROI at dilated obstructed loops between contrast-enhanced and unenhanced CT images. The differences among groups were compared by one-way analysis of variance. Diagnostic performances were evaluated by receiver operating characteristic (ROC) curve analysis. Results: The sensitivity, specificity, positive and negative predictive values and accuracy of observer1 were 62.0%, 87.5%, 88.6%, 59.6%, 72.0%, and 58.0%, 93.8%, 93.5%, 58.8%, 72.0%for observer2, respectively. The kappa value of inter-observer agreement was 0.747. The unenhanced CT value of necrosis group, ischemia group and non-ischemia group was (53.7±9.7), (45.7±7.2) and (44.7±7.0) HU, enhanced CT value was (60.5±10.1), (65.0±11.6) and (87.0±15.8) HU, relative enhancement value was(6.8±8.4), (19.2±12.4) and(44.7±16.2)HU, respectively. All had a statistical difference among three groups (all P<0.05). The unenhanced CT value of necrosis group was higher than that of ischemia group and un-ischemia group (both P<0.05). The enhanced CT value of non-ischemia group was higher than that of ischemia group and necrosis (both P<0.05). The relative enhancement value all had a significant difference between groups (all P<0.05). Taking maximal density relative enhancement value below 19.5 HU as diagnosis threshold, the sensitivity, specificity and area under curve(AUC) were 96.9%, 74.0% and 0.947, respectively. Taking enhanced CT value below 66.5 HU as diagnosis threshold, the sensitivity, specificity and AUC were 93.8%, 60.0% and 0.903, respectively; the sensitivity was higher than that of objective visual evaluation. Conclusion: Maximal density relative enhancement value can quantize the bowel wall enhancement, and is a more reliable way in the diagnosis of intestinal ischemia than visual evaluation.

[Application of preset adaptive statistical iterative reconstruction-V in dual-enhanced abdominal CT].

Objective: To analyze the effect of preset adaptive statistical iterative reconstruction-V (ASIR-V) on image quality and radiation dose in dual-enhanced abdominal CT and to investigate the optimal ASIR-V in clinic use. Methods: From February 13 to April 30 in 2017, one hundred and eighty patients who received up abdominal CT scan in the First Affiliated Hospital of Zhengzhou University were collected prospectively. All patients underwent arterial phase (AP) and portal venous phase (PVP) enhanced abdominal CT(120 kVp, noise index 10) and were randomly divided into 6 groups according to random number table (A-F, 30 cases in each group). In group A-F, 0-50% preset ASIR-V (an interval of 10%) was applied, respectively. Qualitative parameters (subjective image quality, diagnosis confidence and radiation dose) and quantitative parameters[image noise, CT number and contrast to noise ratio (CNR)]were measured and compared among the groups by using one-way analysis of variance or Kruskal-Wallis H test. Results: The CT dose index volume (CTDIvol) decreased with the increasing of preset ASIR-V. The effective radiation dose (ED) was significant different among groups (F=27.598, P<0.05), and the ED of group B-F dropped by 10.8%, 21.7%, 31.2%, 44.9% and 61.9% respectively when compared with that in group A. Group E showed the optimal image quality (Z=18.675, 27.548, 19.761, all P<0.05) and diagnosis confidence(Z=21.387, 17.693, 22.459, all P<0.05) in plain scan, AP and PVP phases. There was no significant differences in image noise and CT value of liver, pancreas and muscle among groups (F=1.468, 0.337, 0.592, 0.284, all P>0.05). There were significant differences in CNRs in liver and portal vein in PVP phase among the groups (F=3.980, 4.681, both P<0.05). Conclusion: In abdominal CT, 40% preset ASIR-V can provides the best image quality and it can reduce radiation dose for 44.9%.

Antiserum to the recombinant truncated VP22 protein of herpes simplex virus type 1 that also recognizes full-length VP22.

The herpes simplex virus type 1 (HSV-1) tegument protein VP22 encoded by the UL49 gene is essential for HSV-1 infection. However, its precise functions in the virus life cycle are unknown. A relatively important tool for disclosing these functions is an antiserum specifically detecting VP22 in the infected cell. To this end, a recombinant truncated VP22 protein consisting of C-terminal 45 aa fused to EYFP (enhanced yellow fluorescent protein) and His-tag was expressed in Escherichia coli, purified by the Ni2+-NTA affinity chromatography, and used for the preparation of antiserum in rabbits. Western blot and immunofluorescence assay showed that this antiserum specifically detected purified truncated VP22 as well as full-length VP22 in the HSV-1 infected cells. These results indicate that the prepared antiserum could serve as a valuable tool for further studies of VP22 functions.

Effects of maize grain and lucerne particle size on ruminal fermentation, digestibility and performance of cows in midlactation.

This study evaluated the effects of, and interactions between, maize grain particle size (MPS) and lucerne particle size (LPS) on dry matter intake, milk production, milk composition, ruminal fermentation, microbial yield, chewing activity and nutrient digestibility in midlactation cows. Four multiparous Holstein cows with ruminal cannulas were assigned randomly to a 4 x 4 Latin square design, averaged 595 kg (SD = 52) of body weight and 121 days in milk (SD = 21) at the start of the experiment. Experimental periods were 21 days in length (14 days of treatment adaptation and 7 days of data collection). All diets were fed as total mixed ration and were formulated to meet or exceed the requirements of a 600 kg multiparous cow producing 20 kg milk/day with 4.0% fat. The ratio of concentrate to forage was 39:61 (dry matter basis). Treatments were arranged in a 2 x 2 factorial design; two levels of LPS (2.54 and 6.22 mm) were combined with concentrates based on either ground maize grain (711 mum) or cracked maize grain (1755 mum). Maize grain and LPS did not affect milk production and milk fat percentage. Milk protein percentage increased when MPS was decreased (p = 0.04). Milk urea nitrogen was lower for cows fed ground maize grain compared with cracked maize grain (118-134 mg/l, p = 0.05). Estimated microbial N supply increased 41.9 g/day for ground maize grain compared with cracked maize grain. Cows fed long lucerne (LL) hay spent more time ruminating compared with cows fed short lucerne (SL) hay ranging from 293 to 336 min/day (p < 0.001). Total time spent chewing by cows increased from 505 to 574 min/day (p = 0.002) for SL and LL respectively. Based on the results from this study, midlactation cows can be fed diets that contain ground maize grain and SL hay without leading to negative effects on ruminal pH and nutrient digestibility.

Effects of beta-glucan extracted from Saccharomyces cerevisiae on growth performance, and immunological and somatotropic responses of pigs challenged with Escherichia coli lipopolysaccharide.

Three experiments were conducted to investigate the effects of beta-glucan supplementation on pig performance and immune function. In Exp. 1, 100 weaned pigs (8.65 +/- 0.42 kg of BW and 28 +/- 2 d of age) were used in a 35-d experiment to determine the effects of graded levels of beta-glucan. Pigs were randomly allotted to 1 of 5 treatments containing beta-glucan supplemented at 0, 25, 50, 100, or 200 ppm. Each treatment was replicated using 5 pens containing 4 pigs per pen. The ADG of pigs between d 14 to 28 and d 0 to 28 responded to dietary beta-glucan in a quadratic fashion (P < 0.05), whereas beta-glucan had no effect on ADFI and G:F in any period. In Exp. 2, 80 crossbred pigs (8.23 +/- 0.56 kg of BW and 28 +/- 2 d of age) were used in a 35-d experiment. Pigs were allotted to 1 of 2 dietary treatments (0 or 50 ppm of beta-glucan in the diet) using 10 pens with 4 pigs per pen. Pigs treated with beta-glucan had greater ADG in the 14- to 28-d (P = 0.05) and 0-to 28-d (P = 0.035) periods. The ADFI of pigs receiving beta-glucan was increased (P < 0.05) in the periods from 0 to 14, 0 to 28, and 28 to 35 d. The lymphocyte proliferation index in response to phytohemagglutinin (P = 0.051) and concanavalin A (P = 0.052) tended to decrease on d 14 in pigs supplemented with beta-glucan compared with pigs without supplementation. In Exp. 3, 24 barrows (8.89 +/- 0.20 kg of BW and 28 d of age) were used to investigate the immunological and somatotropic responses of pigs challenged with lipopolysaccharide (LPS). Experimental treatments were arranged in a 2 x 2 factorial, with the main effects of LPS challenge (saline vs. LPS) and dietary addition of beta-glucan (0 vs. 50 ppm). Pigs were raised individually in metabolic cages. Pigs were fed 0 or 50 ppm of beta-glucan for 28 d and then challenged with LPS (25 microg/kg of BW) or saline. After LPS injection, blood was obtained at 0, 1.5, 3, 4.5, 6, and 7.5 h to determine cytokine production and the somatotropic response. Dietary beta-glucan increased plasma interleukin-6 at 1.5, 3, and 4.5 h and tumor necrosis factor-alpha at 3 and 4.5 h and increased plasma interleukin-10 from 3 to 7.5 h after LPS challenge. The beta-glucan treatments had no effect on growth hormone. In conclusion, beta-glucan can selectively influence performance and partially offer benefits on somatotropic axis and immune function in weaned piglets challenged with LPS.

Effects of feed particle size and feed form on survival of Salmonella typhimurium in the alimentary tract and cecal S. typhimurium reduction in growing broilers.

An in vitro experiment and an in vivo experiment were conducted to investigate the effects of feed particle size (coarse and fine) and feed form (mash and pellet) on the survival of Salmonella typhimurium (ST) in the alimentary tract, and the reduction of cecal ST in growing broilers in a 2 x 2 factorial design. All diets in the 2 trials were corn and soybean meal-based diets that differed only in physical characteristics. Diets were provided for birds from d 1 to 22 of age. In the in vitro trial, the relative gizzard weight was lower in birds that were fed the pellet diet (P < 0.01), whereas the relative weight of the cecum was higher in these birds (P < 0.01). Broilers receiving the pellet diet had enhanced concentrations of volatile fatty acids in contents from both the gizzards and the ceca. In addition, there was an increase in gizzard pH (P < 0.01) with the pellet diet, but a reduction in cecal pH (P < 0.05). Pellet-fed birds showed a significantly decreased and increased in vitro death rate of ST in the contents from gizzards (P < 0.01) and ceca (P < 0.05), respectively. A higher in vitro ST death rate in the gizzard was observed in birds given the coarse mash diet compared with those given the fine mash diet. In the in vivo experiment, cecal volatile fatty acid concentrations were increased, whereas cecal pH was decreased significantly (P < 0.05) when birds were fed the pellet diet compared with the mash diet. Furthermore, cecal ST concentrations were higher (P < 0.05) in broilers fed the pellet diet than in those fed the mash diet. Results indicated that the pellet diet increases the incidence of ST in gizzards and ceca in growing broilers and provide evidence demonstrating that the gizzard may play a critical role in reducing ST contamination in growing broilers.

Effects of beta-glucan obtained from the Chinese herb Astragalus membranaceus and lipopolysaccharide challenge on performance, immunological, adrenal, and somatotropic responses of weanling pigs.

A total of 108 crossbred piglets (7.75 +/- 0.24 kg of BW) weaned at 28 d was used to study the interactive effects of beta-glucan obtained from the Chinese herb Astragalus membranaceus (AM) and Escherichia coli lipopolysaccharide (LPS) challenge on performance, immunological, adrenal, and somatotropic responses of weaned pigs. The treatments were in a 2 x 3 factorial arrangement; main effects were level of Astragalus membranaceus glucan (AMG; 0, 500, or 1,000 mg/kg; as-fed basis) and presence of immunological challenge (with or without LPS). The experiment included six replicate pens per treatment and three pigs per pen. Lipopolysaccharide challenges were conducted on d 7 and 21 of the trial. Blood samples were obtained from the vena cava from one pig per pen at 3 h after LPS challenge to determine plasma responses. Weight gain and feed:gain ratio were unaffected by glucan. However, there was a quadratic effect on feed intake (P < 0.05): pigs fed 500 mg of glucan/kg had the highest feed intake. Immunological challenge with LPS decreased weight gain (P = 0.02). An interaction (P = 0.01 to 0.09) between AMG and LPS was observed for glucose, IL-1beta, PGE2, and cortisol. Astragalus membranaceus glucan had a quadratic effect on the plasma concentrations of glucose, IL-1beta, PGE2, and cortisol (P < 0.05) after both LPS challenges. Plasma concentrations of glucose, IL-1beta, PGE2, and cortisol (P < 0.05) were all increased in LPS-challenged pigs compared with the control pigs after both LPS challenges. The IGF-I concentrations were less for LPS-challenged pigs than for unchallenged pigs. The lymphocyte proliferation response of peripheral blood induced by 5 microg of concanavalin A/mL (P < 0.01) and IL-2 bioactivity (P < 0.05) increased linearly with increasing addition of glucan. Pigs challenged with LPS had greater T-lymphocyte proliferation (P = 0.06) and IL-2 bioactivity (P = 0.07) than unchallenged pigs after the first immunological challenge but not after the second. In conclusion, although glucan did not improve pig performance under the conditions of the present experiment, when included at 500 mg/kg, it decreased the release of inflammatory cytokine and corticosteroid and improved the lymphocyte proliferation response of weanling piglets via enhanced IL-2 bioactivity.

Effects of emulsification, fat encapsulation, and pelleting on weanling pig performance and nutrient digestibility.

Two experiments were conducted to evaluate the effect of lysolecithin on performance and nutrient digestibility of nursery pigs and to determine the effects of fat encapsulation by spray drying in diets fed in either meal or pelleted form. In Exp. 1, 108 pigs (21 d of age; 5.96 +/- 0.16 kg BW) were allotted to one of four dietary treatments (as-fed basis): 1) control with no added lard, 2) control with 5% added lard, 3) treatment 2 with 0.02% lysolecithin, and 4) treatment 2 with 0.1% lysolecithin in a 35-d experiment. Added lard decreased ADG (P = 0.02) and ADFI (P < 0.06) during d 15 to 35 and overall. Lysolecithin improved ADG linearly (P = 0.04) during d 15 to 35 and overall, but did not affect ADFI or G:F. Addition of lard decreased the digestibility of DM (P = 0.10) and CP (P = 0.05) and increased (P = 0.001) fat digestibility when measured on d 10. Lysolecithin at 0.02%, but not 0.10%, tended to improve the digestibility of fat (P = 0.10). On d 28, digestibilities of DM, fat, CP, P, (P = 0.001), and GE (P = 0.03) were increased with the addition of lard, and lysolecithin supplementation linearly decreased digestibilities of DM (P = 0.003), GE (P = 0.007), CP, and P (P = 0.001). In Exp. 2, 144 pigs (21 d of age, 6.04 +/- 0.16 kg BW) were allotted to one of six treatments in a 3 x 2 factorial randomized complete block design. Factors included 1) level (as-fed basis) and source of fat (control diet with 1% lard; control diet with 5% additional lard; and control diet with 5% additional lard from encapsulated, spray-dried fat) and 2) diet form (pelleted or meal). Addition of lard decreased feed intake during d 0 to 14 (P = 0.04), d 15 to 35 (P = 0.01), and overall (P = 0.008), and improved G:F for d 15 to 35 (P = 0.04) and overall (P = 0.07). Encapsulated, spray-dried lard increased ADG (P = 0.004) and G:F (P = 0.003) during d 15 to 28 compared with the equivalent amount of fat as unprocessed lard. Pelleting increased ADG (P = 0.006) during d 0 to 14, decreased feed intake during d 15 to 35 (P = 0.01), and overall (P = 0.07), and increased G:F during all periods (P < 0.02). Fat digestibility was increased (P = 0.001) with supplementation of lard, and this effect was greater when diets were fed in meal form (interaction, P = 0.004). Pelleting increased the digestibility of DM, OM, and fat (P < 0.002). Results indicate that growth performance may be improved by lysolecithin supplementation to diets with added lard and by encapsulation of lard through spray drying.

Prolongation of xenograft survival using monoclonal antibody CD45RB and cyclophosphamide in rat-to-mouse kidney and heart transplant models.

BACKGROUND: Intrigued by the finding that a monoclonal antibody (mAb) directed against the B exon of restricted CD45 (CD45RB mAb) induced renal allograft tolerance in the mouse model, we hypothesized that CD45RB mAb may prevent xenograft rejection. We explored the role of CD45RB mAb in preventing xenograft rejection in rat-to-mouse kidney and heart transplant models. METHODS: Mice with rat kidney and heart xenografts were treated with a short course of mAb, cyclosporine, cyclophosphamide, or mAb + cyclophosphamide combination therapy. Untreated heart and kidney xenografts served as controls. RESULTS: Untreated controls developed acute vascular and cellular rejection rapidly with a median survival time of only 6 days. Long-term kidney (median survival time = 70 days) and heart xenograft survival (median survival time = 65 days) was achieved using the combination therapy of mAb + cyclophosphamide. One-third of the kidney recipients with combination therapy survived 100 days. Immunohistochemistry and xenospecific-antibody analysis demonstrated that combination therapy remarkably reduced IgG and IgM deposition and also inhibited CD4+, CD8+, and Mac-1+ cell infiltration at early stages. This therapy, however, did not induce tolerance in this model as evoked xenoreactive antibodies and cellular responses may be the cause of late xenograft failure. CONCLUSION: A short course of CD45RB mAb combined with cyclophosphamide effectively inhibits cellular and humoral immunoresponses and remarkably prolongs xenograft survival in rat-to-mouse heart and kidney transplant models.

Adoptively transferable tolerance induced by CD45RB monoclonal antibody.

The phenomenon of rejection remains the most serious problem in transplantation. The ultimate goal in transplant immunology is to develop therapeutic strategies that lead to tolerance. It has been shown that two injections of a monoclonal antibody to CD45RB leads to indefinite acceptance of renal allografts in mice. Moreover, the CD45RB monoclonal antibody reverses acute rejection and still induces tolerance. The purpose of this study was to assess mechanisms that could underlie this therapeutic benefit. It was shown that splenic lymphocytes from tolerant animals augmented proliferation in allogeneic mixed lymphocyte reactions against donor alloantigens, and the serum of tolerant mice contained donor-specific antibodies, mainly of the IgG1 isotype, suggesting the presence of TH2 cytokines. Tolerance could not be broken by interleukin-2 infusion, but tolerance could be adoptively transferred by transfusion of tolerant mouse CD4+ splenic lymphocytes into naive allografted animals. These data suggest that an active immunoregulatory mechanism is partly responsible for the therapeutic effect. CD45RB-directed therapy may find clinical application in organ transplantation in human patients.

Suppression of dialysis patients' lymphocyte IL-2R expression by glucocorticoids and cyclosporine.

Previous studies have shown interindividual heterogeneity in the suppressive effects of glucocorticoids and cyclosporine (CsA) on the proliferation responses of dialysis patients' peripheral blood mononuclear cells (PBMC). In addition, methylprednisolone (MP) was shown to be significantly more suppressive than prednisolone (P), and PBMC from patients on peritoneal dialysis (PD) were found to be more sensitive to both glucocorticoids than those from patients on haemodialysis (HD). In order to begin to explore the cellular mechanism(s) underlying these observations, the differential suppressive effects of these drugs on lymphocyte interleukin 2 receptor (IL-2R) expression by mitogen-stimulated PBMC from 23 PD and 30 HD were determined. The mean+/-SD concentrations (ng/ml) of steroid causing 50% inhibition (IC50) of cell proliferation was significantly lower for PD than HD PBMC with both P (94+/-93 vs 148+/-105, P<0.05) and MP (21+/-25 vs 35+/-31, P<0.05). MP was significantly (P<0.001) more suppressive than P of IL-2R expression in both PD and HD. PD IL-2R expression was significantly (P<0.05) more suppressed by CsA alone and by 400 ng/ml CsA+10(-7) MP than was HD IL-2R expression. CsA+10(-7) M MP was significantly (P<0.001) more suppressive of IL-2R expression than the other drugs, alone or in combination, in both groups of patients. In conclusion, these results support the notion that at least one mechanism underlying the significantly greater efficacy of MP compared to P in suppressing PBMC proliferation is its significantly greater suppression of lymphocyte IL-2R expression, either alone or in combination with CsA. Thus, use of MP following allograft transplantation may result in more effective immunosuppression for many recipients.

Differential glucocorticoid responsiveness of hemodialysis patients' lymphocytes.

Acute allograft rejection remains a problem after renal transplantation, even in the cyclosporine era. Interindividual differences in the pharmacodynamic responses of the immune system to immunosuppressive agents might contribute to the vulnerability of some patients to rejection. Having previously demonstrated decreased sensitivity of hemodialysis patients' lymphocytes to glucocorticoid suppression of mitogen induced proliferation, the authors undertook a separate study to assess the suppressive effect of glucocorticoids on lymphocyte responsiveness to allogeneic cells and mitogenic stimulation. Lymphocytes were isolated from 32 hemodialysis patients in clinically stable condition for studies in both phytohemagglutinin (PHA) stimulated cultures and in one-way mixed lymphocyte (MLR) cultures. From the concentration-response relationships derived from stimulated cultures with 10 (-6), 10(-7), and 10(-8) M concentrations of prednisolone and methylprednisolone, the concentration of steroid required to achieve 50% inhibition (IC50) of lymphocyte proliferation was determined. A broad range of IC50 values was found in both PHA and MLR cultures, but within individual patients, the IC50 values for both steroids correlated significantly between PHA and MLR cultures. The inhibitory effect of methylprednisolone was significantly greater than that of prednisolone in both PHA and MLR cultures. These results demonstrate a heterogeneity of pharmacodynamic responsiveness to prednisolone and methylprednisolone that is consistent with individuals in two in vitro models of cellular immune response. Pretransplant evaluation by these methods may help identify patients at risk of suboptimal immunosuppression and assist in selecting the steroid component of the immunosuppressive regimen.

Differential suppression of dialysis patients' lymphocyte IFN-gamma production by glucocorticoids and cyclosporine.

IFN-gamma is a potent pro-inflammatory cytokine involved in the immunologic rejection of transplanted organs. Having previously demonstrated differential suppressive effects of methylprednisolone (MP), prednisolone (P) and cyclosporine (CsA) on dialysis patients' lymphocyte proliferative responses to phytohaemagglutinin (PHA), we studied the effects of these drugs on dialysis patients' lymphocyte IFN-gamma production during mitogenic and allogeneic (MLR) stimulation. The mean +/- SEM 50% inhibitory concentration (ng/ml) on cell proliferation was significantly lower for MP than P in PHA-stimulated haemodialysis (HD) patients' (35 +/- 7 vs 152 +/- 25, P < 0.001) and peritoneal dialysis (PD) patients' (35 +/- 11 vs 134 +/- 33, P = 0.001) cultures and in HD patients' MLR cultures (15 +/- 3 vs 48 +/- 9, P < 0.001). The mean +/- SEM fractional responses (PHA or MLR + drug/PHA or MLR) in culture supernatant IFN-gamma concentrations were significantly lower with 10(-7) M concentrations of MP than P in HD (0.19 +/- 0.05 vs 0.31 +/- 0.06, P = 0.01) and PD (0.30 +/- 0.11 vs 0.46 +/- 0.11, P < 0.05) PHA cultures and in HD MLR cultures (0.15 +/- 0.04 vs 0.28 +/- 0.07, P = 0.01). CsA (400 ng/ml) alone not only caused less than 50% inhibition of IFN-gamma production in 15/27 HD PHA, 6/14 PD PHA and 4/13 HD MLR cultures, but actually stimulated it in 9 HD and 5 PD PHA cultures. The results suggest that: (1) MP has greater immunosuppressive potential than P for renal transplant recipients; (2) the stimulation of IFN-gamma by CsA in some patients could be harmful in patients with initial allograft dysfunction; and (3) pre-transplant in-vitro assessment of recipients' PBMC responsiveness to glucocorticoids and CsA may help individualize the post-transplant immunosuppressive regimen.

Suppression of lymphocyte interleukin-2 receptor expression by glucocorticoids, cyclosporine, or both.

Although glucocorticoids and cyclosporine are frequently used to treat patients with various types of glomerulopathy, clinical responses to treatment vary considerably. Considerable interindividual heterogeneity in the suppressive effects of glucocorticoids on lymphocyte proliferation in vitro has been previously reported, suggesting that differences in the pharmacodynamic responsiveness of the immune system to these agents might be an important determinant of how well an individual patient responds to treatment. It also has been shown that methylprednisolone is significantly more suppressive than prednisolone. To identify cellular mechanisms by which these drugs act, a study of the suppressive effects of prednisolone, methylprednisolone, and cyclosporine on lymphocyte proliferation and the expression of the cell surface receptor for interleukin-2 (IL-2R) was conducted using phytohemagglutin-stimulated peripheral blood mononuclear cells (PBMCs) from 13 patients with glomerulopathy and 12 control subjects. Heterogeneity among individuals in both parameters of lymphocyte responsiveness to these drugs was again found, and the significantly greater suppressive effect of methylprednisolone was confirmed for both proliferation and IL-2R expression in patients and control subjects. Cyclosporine alone was moderately suppressive. For most individuals, the greatest degree of suppression occurred when cells were exposed to both cyclosporine and glucocorticoid. Further studies are being conducted to determine whether pretreatment assessment of in vitro lymphocyte responsiveness has any predictive value regarding therapeutic efficacy of each drug in individual patients and to identify of those patients likely to require a more intensive or multidrug immunosuppressive regimen.