The impact of donor serum creatinine level on long-term outcome of renal allografts.
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Biomedical subjects
Publications and source records attributed to M J Wu.
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We studied the prevalence and the clinical spectrum of cryoglobulinemia (Cryo) among 101 maintenance hemodialysis (HD) patients and 148 kidney transplant (KT) recipients, with or without chronic hepatitis C virus (HCV) infection. Cryo was present in 32% (16 of 50) of the HCV-positive HD patients, 5.9% (3 of 51) of the HCV-negative HD patients, 37.8% (28 of 74) of the HCV-positive KT recipients, and 27% (20 of 74) of the HCV-negative KT recipients. Cryoprecipitate in 56.3% (9 of 16) of the HCV-positive Cryo HD patients and 53.8% (14 of 26) of the HCV-positive Cryo KT recipients contained HCV-RNA. Interestingly, the cryocrit values among HD and KT patients were much lower than these in other reports on nonrenal failure cases. Also, the cryoglobulinemic syndrome (with purpura, arthralgia, etc.) in HD and KT patients with Cryo were not common (Tables 1 and 2). There was not correlation between Cryo and age,sex, and liver function. Only longer duration of end-stage renal disease was noted in these patients. In addition, we suggested that KT patients are more susceptible to having Cryo. Further studies are necessary to better define whether any other subclinical viral or nonviral chronic infection may induce Cryo in HCV-negative KT recipients.
BACKGROUND: It is evident that cytokines play an important role in the pathogenesis as well as disease progression in IgA nephropathy (IgAN). The level of cytokine production is influenced by different genotypes that reflect gene polymorphism of the pertinent cytokine. Interleukin-1 receptor antagonist (IL-1ra) and tumor necrosis factor-alpha (TNF-alpha) gene polymorphism have been found to affect disease susceptibility and activity in several inflammatory diseases. However, the impact of these polymorphisms in IgAN patients has not previously been thoroughly studied. METHODS: We investigated 111 cases of biopsy-proven IgAN and 100 healthy, normal controls for their IL-1ra and TNF-alpha gene polymorphism. IL-1ra gene polymorphism was characterized as a variable number of tandem repeats of a 86 bp sequence within intron 2. Five alleles were identified and were designated as IL1RN*1, IL1RN*2, IL1RN*3, IL1RN*4, and IL1RN*5, corresponding to 4, 2, 5, 3, 6 repeats, respectively. A polymorphism in the promoter region of the TNF-alpha gene was also studied. This polymorphism involved a guanidine to adenosine transition at position -308 and was designated as TNF1 (-308G) and TNF2 (-308A). RESULTS: There were 54 male and 57 female patients with a mean age of 30.3 +/- 12.5 years and a disease duration of 66. 8 +/- 47.2 months. The mean duration of the follow-up period was 47. 3 +/- 32.6 months. In the patient group, the allele frequencies of IL1RN*1, IL1RN*2, IL1RN*3, IL1RN*4, and IL1RN*5 were 89.6%, 9.9%, 0%, 0.5%, and 0%, respectively, whereas the corresponding carriage rates were 100%, 19.8%, 0%, 0.9%, and 0%, respectively. An excessive carriage of IL2RN*2 was found in the patients when compared with normal controls (allele frequency, 9.9 vs. 2.5%, P < 0.0001). The allele frequencies of TNF1 and TNF2 were 94.1 and 5.9%, respectively, and the carriage rates were 99.1 and 10.8%, respectively, in the patients, which was not significantly different from those of normal controls. When the patients were stratified into mild and severe groups according to their initial presentation, none of the studied alleles correlated with the severity. However, patients with gross hematuria were associated with a higher carriage rate of TNF2 when compared with patients without gross hematuria (allele frequency, 15. 4 vs. 4.6%, P = 0.0552; carriage rate, 30.8% vs. 8.2%, P = 0.0272). Renal survival analysis revealed that the TNF2 carrier had a renal survival comparable with TNF2 (-) patients. However, the carriage of the IL1RN*2 allele was associated with a significantly poorer long-term outcome with a median survival time of 72 months, as compared with those without IL1RN*2 (134 months, P < 0.01). CONCLUSION: IL-1ra and TNF-alpha gene polymorphism may affect disease susceptibility as well as disease activity and long-term outcome in human IgAN. Treatment with an IL-1ra or IL-1 blocking agent may be relevant in those carrying the IL1RN*2 allele.
[reaction: see text] Treatment of 2-((3Z)-undecene-1,5-diynyl)benzonitrile with 5 equiv of sodium methoxide in refluxing methanol for 16 h gave 1-pentyl-6-methoxyphenanthridine in 12% yield, 1-pentyl-6-phenanthridone in 6% yield, and 2-(2-pentyl-6-methoxyphenyl)benzonitrile in 4% yield. Under the same reaction conditions, methanolysis of several other benzonitriles gave similar results. Phenanthridine and biphenyl derivatives were obtained as the major products. A mechanism for this novel cycloaromatization reaction of enediynes is proposed.
Skeletal muscle hypertrophy and regeneration are important adaptive responses to both physical activity and pathological stimuli. Failure to maintain these processes underlies the loss of skeletal muscle mass and strength that occurs with ageing and in myopathies. Here we show that stable expression of a gene encoding insulin-like growth factor 1 (IGF-1) in C2C12 skeletal muscle cells, or treatment of these cells with recombinant IGF-1 or with insulin and dexamethasone, results in hypertrophy of differentiated myotubes and a switch to glycolytic metabolism. Treatment with IGF-1 or insulin and dexamethasone mobilizes intracellular calcium, activates the Ca2+/calmodulin-dependent phosphatase calcineurin, and induces the nuclear translocation of the transcription factor NF-ATc1. Hypertrophy is suppressed by the calcineurin inhibitors cyclosporin A or FK506, but not by inhibitors of the MAP-kinase or phosphatidylinositol-3-OH kinase pathways. Injecting rat latissimus dorsi muscle with a plasmid encoding IGF-1 also activates calcineurin, mobilizes satellite cells and causes a switch to glycolytic metabolism. We propose that growth-factor-induced skeletal-muscle hypertrophy and changes in myofibre phenotype are mediated by calcium mobilization and are critically regulated by the calcineurin/NF-ATc1 signalling pathway.
Chromatographic fractionation of a MeOH extract from the stems of Annona cherimola led to the isolation of a new non-adjacent, bis-THF ring acetogenin (one THF ring being at C-4 and the other at C-16), aromin-A (1) along with the known cytotoxic acetogenin squamocin (2). The structures of these isolates were established by means of mass spectrometry and spectroscopic techniques.
Four new compounds, a mixture of 20,23-cis-2,4-trans-bullatalicinone (1) and 20,23-cis-2,4-cis-bullatalicinone (2), rollimusin (3), and rolliacocin (4), along with eight known acetogenins, were isolated from an ethyl acetate extract of the unripe fruits of Rollinia mucosa. The structures and stereochemistry of 1-4 were determined on the basis of spectral data and chemical evidence.
AIM: To define the long-term outcome of patients with minimal urinary abnormalities (defined by the presence of microscopic hematuria with no or less than 1 gm/day proteinuria), and normal renal function (defined by a serum creatinine < 1.3 mg/dl), we retrospectively studied patients who fulfilled the above criteria and had a kidney biopsy done before the year of 1992 (i.e. at least followed up for 5 years), with a definite pathological diagnosis. METHODS: A total of 41 cases among 719 cases of primary glomerulonephritis (5.7%) were enrolled into the study. There were 19 males and 22 females with a mean age of 35.4+/-14.7 years at biopsy. The duration of renal disease was 116.0+/-60.5 months and the duration of follow-up post biopsy was 100.2+/-38.1 months. The pathological diagnosis was: IgA nephropathy (21 cases), focal glomerulosclerosis (9 cases), mesangial proliferative glomerulonephritis (8 cases), membranous glomerulonephritis (2 cases) and acute glomerulonephritis (1 case). RESULTS: At the end of follow-up, 8 cases (19.5%) had a certain degree of renal insufficiency including 2 (4.9%) in end-stage renal disease. The other cases were either in complete remission (6 cases) or stable condition (27 cases) with persistent microscopic hematuria and normal renal function. The long-term outcome was not correlated with any of the following parameters: age, sex, disease duration, serum creatinine at presentation, daily protein loss at presentation, degree of glomerular change and degree of interstitial inflammatory cell infiltration. However, a poor long-term outcome was correlated with tubular atrophy (p < 0.05) and interstitial fibrosis (p < 0.05). CONCLUSION: We conclude that a minimal urinary abnormality with normal renal function at presentation does not necessarily imply a favorable long-term outcome in certain patients. Tubular atrophy and interstitial fibrosis but not glomerular change correlates with a worse prognosis. This further emphasizes the importance of renal biopsy in such cases.
Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3) is caused by unstable CAG trinucleotide repeat expansion in the coding region of the MJD gene. In this study, we describe a non-radioactive polymerase chain reaction (PCR) method to detect the CAG repeat range of the MJD gene. This technique allows direct visualization of the PCR products on ethidium bromide-stained agarose gels within hours. In this study, genomic DNA samples isolated from peripheral lymphocytes, amniotic fluid cells, and chorionic villi were tested with two sets of commonly used MJD primers. PCR conditions were optimized, which resulted in clear visualization of both the primer sets on 3% agarose gels. Ten out of 25 candidate MJD patients have been identified with this method to date, with no false-positive or false-negative diagnoses. This simple, reliable, and cost-effective method can be used for patient diagnosis, pre-symptomatic diagnosis, and prenatal diagnosis.
The shortage of donor kidneys available for transplantation has resulted in an expansion of the criteria used for donor selection. The use of cadaveric pediatric kidneys has been suggested as a means to overcome this shortage, but is debated because of technical complications and an increased incidence of functional allograft impairment. We examined the records of all adult patients receiving renal allograft transplants from January, 1983 through December 1994, to determine whether kidneys from pediatric donors can be used safely for transplantation. During the study period, 204 adult patients received kidney transplants. The patients were divided into three groups by donor age: group 1, 26 months to 7 years old (n = 12); group 2, 7 to 14 years old (n = 19); and group 3, adult donors (n = 173). Cyclosporine- and/or azathioprine-based immunosuppression regimens were used. The three groups did not differ from one anther with respect to recipient age, recipient sex, primary renal disease, human leukocyte antigen (HLA) mismatching, or the proportion of recipients with previous transplants. The graft survival rates at 1 and 3 years, respectively, were 75% and 75% in group 1,84% and 79% in group 2, and 85% and 72% in group 3 (p > 0.05). The patient survival rates at 1 and 3 years, respectively, were 75% and 75% in group 1,95% and 90% in group 2, and 90% and 83% in group 3 (p > 0.05). The frequency of fixed proteinuria (> or = 0.8 gm/day) in the first 3 years was higher in the two pediatric groups (50%) than in the adult group (28%) (p < 0.05). The frequency of surgical complications was higher with pediatric grafts (group 1 vs group 3: 67% vs 24%, p < 0.005). In particular, group 1 patients had much higher rates of lymphocele (50% vs 8%), renal graft artery stenosis (33% vs 11%), and hydronephrosis (33% vs 9%) than group 3. We conclude that pediatric donor kidneys can be used with reasonable safety, although surgical complications remain a major problem.
The MBP content change in serum was observed by ELISA in rats with experimental closed diffuse cranial injury. The MBP content was 6.1633 +/- 1.5301 ng/ml (X +/- S) in the normal group, 11.3818 +/- 2.6574 ng/ml in the first group died immediately after injury, 10.8319 +/- 2.3135 ng/ml in the second group of 15 min after injury. This increased level of MBP was lasting in the following 3 days and returned to normal at the 4th and 5th day after injury. The difference of the MBP levels between the groups after injury and that in the normal group is significant (P < 0.01).
To test the hypothesis that auxin-binding protein 1 (ABP1) is a receptor controlling auxin-mediated plant cell expansion, ABP1 complementary DNAs were expressed in a controllable fashion in tobacco plants and constitutively in maize cell lines. Induction of Arabidopsis ABP1 expression in tobacco leaf strips resulted in an increased capacity for auxin-mediated cell expansion, whereas induction of ABP1 in intact plants resulted in leaves with a normal morphology, but larger cells. Similarly, constitutive expression of maize ABP1 in maize cell lines conferred on them the capacity to respond to auxin by increasing cell size. These results support a role of ABP1 as an auxin receptor controlling plant growth.
Several human hereditary neuromuscular and neurodegenerative diseases are caused by abnormal expansion of triplet repeat sequences (TRSs) CAG/CTG, CGG/CCG, or GAA/TTC on certain chromosomes. It is generally accepted that multiple slippage synthesis accounts for the instabilities of TRS. Earlier in vitro experiments by Behn-Krappa and Doerfler showed that TRS with high GC content can be expanded. In contrast, here we demonstrated that certain AT-rich TRSs, (TTC)17, (GAA)10/(TTC)10 and (GAA)17/(TTC)17, were also expansion-prone in PCR. With respect to the sequence of TRS, surprisingly, we found that the AT-rich (GAA)17/(TTC)17 extended more efficiently than the GC-rich (CAG)17/(CTG)17. This strongly suggested that the AT content of the repeat may influence TRS expansion. Furthermore, to examine the expansion of single-stranded TRS, we showed that only (TTC)17, but not the complementary (GAA)17, can be expanded. This suggested that a T-T mismatch may stabilize compatible secondary structures, most likely hairpins, for slippage synthesis. However, another poly-pyrimidine TRS, (CCT)17, is not amplification-prone in PCR. Due to the high C-content, this TRS is unlikely to adopt hairpin structures at the high pH used for PCR. Thus, the single-stranded PCR experiment may serve as an indirect assay for the ability of a sequence to adopt a hairpin conformation. When amplification was performed in reactions using Klenow DNA polymerase, only the double-stranded TRSs can be expanded. The reaction rate for (GAA)10/(TTC)10 was slower than for (GAA)17/(TTC)17, suggesting that the length of the repeat may be important for the amplification of TRS. The findings of these in vitro experiments may aid in understanding TRS expansion in vivo.
PURPOSE: To report a patient with corneolimbal squamous dysplasia successfully treated with interferon therapy. METHODS: A 78-year-old man had a gelatinous and vascularized lesion involving the left cornea and adjacent limbus. Impression cytology studied with periodic acid--Schiff-hematoxylin stain disclosed severe squamous dysplasia. Topical instillation and subconjunctival injection of interferon alpha-2b was instituted. RESULTS: The gelatinous tumor mass involving the cornea and adjacent limbus completely resolved 2 months after interferon treatment. He showed no sign of recurrence during the 10-month follow-up. CONCLUSION: Interferon therapy may be a therapeutic alternative for treating corneolimbal squamous dysplasia.
Chromatography of an ethyl acetate extract of seeds of Annona reticulata led to the isolation of a new cytotoxic gamma-lactone acetogenin, cis-/trans-isomurisolenin, along with six known cytotoxic acetogenins, annoreticuin, annoreticuin-9-one, bullatacin, squamocin, cis-/trans-bullatacinone and cis-/trans-murisolinone. Structures of these compounds were established by means of mass and related spectral experiments. Some of the compounds isolated, showed potent cytotoxicities against Hep. 2,2,15, Hep. G2, KB and CCM2, four cancer cell-lines.
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Upper gastrointestinal discomforts are common in uremic patients. Investigators have stressed the structural, histopathological, and physiological changes in the gastrointestinal tract in the past decades. Few data are available about the electrophysiological changes in the stomach of uremic patients. It is not known whether hemodialysis alters gastric myoelectrical activity. More interestingly, what is the long-term effect? To address these questions, we measured gastric myoelectrical activity before and after hemodialysis in patients with end-stage renal disease on maintenance dialysis treatment. Twenty-one uremic patients with dyspeptic complaints were enrolled in this study. Gastric myoelectrical activity was measured noninvasively using abdominal surface electrodes (electrogastrography). The paired variables obtained before and after hemodialysis were compared statistically. We also compared the difference between two subgroups defined as new hemodialysis patients and chronic hemodialysis patients. We found that there was a significantly lower percentage of normal slow-wave frequency obtained after hemodialysis in comparison with before hemodialysis (fasting state: 49.1 +/- 4.8% vs 68.1 +/- 5.4%, P < 0.01; fed state: 53.8 +/- 6.9% vs 73.4 +/- 4.1%, P < 0.01). In comparing the subgroups, there were no differences between each EGG variable. We concluded that the hemodialysis itself compromised gastric myoelectrical activity in its immediate effect. However, there were no permanent effects regarding gastric myoelectrical activity itself.
BACKGROUND: Dyspeptic symptoms are common in uremic patients receiving hemodialysis. Investigators have placed emphasis on the changes in histopathology and physiology of the gastrointestinal tract. But not much data about the gastric myoelectric activity are available. The aim of this study was to assess gastric myoelectric activity in uremic patients undergoing hemodialysis. METHODS: Fifty-eight subjects were enrolled. They were assigned to: group I, uremic patients undergoing hemodialysis with dyspeptic complaints (n = 20); group II, non-uremic patients with matched dyspeptic complaints (n = 20); and group III, healthy volunteers without dyspeptic complaints (n = 18). Gastric myoelectric activity was measured with abdominal surface electrodes in each person. Patients in group I were measured twice, before (group Ia) and after (group Ib) hemodialysis. The data were compared between the groups. RESULTS: In the prehemodialysis period there was a significantly lower percentage of normal slow-wave frequency when compared with group III (fasting, 66.54%+/-5.39% versus 84.58%+/-3.63%; P < 0.005; fed, 72.25%+/-4.16% versus 89.06%+/-2.57%; P < 0.01). In the post-hemodialysis period the difference was even more profound (fasting, 46.52%+/-4.26% versus 84.58%+/-3.63%; P < 0.001; fed, 51.49%+/-6.89% versus 89.06%+/-2.57%; P < 0.005). Yet, when compared with group II, a significant difference existed only in the post-hemodialysis period (fasting, 46.52%+/-4.26% versus 67.30%+/-3.46%; P<0.001; fed, 51.49%+/-6.89% versus 70.41%+/-4.39%; P < 0.01). Another finding is that hemodialysis decreased the gastric myoelectric activity after hemodialysis (fasting, 66.54%+/-5.39% versus 46.52%+/-4.26%; P < 0.001; fed, 72.25%+/-4.16% versus 51.49%+/-6.89%; P < 0.005). CONCLUSIONS: Uremic patients undergoing hemodialysis have impaired gastric myoelectric activity. Interestingly, hemodialysis seems to cause deterioration in gastric myoelectric activity.