The changing HIV-1 genetic characteristics and transmitted drug resistance among recently infected population in Yunnan, China.

Multiple human immunodeficiency virus (HIV)-1 genotypes in China were first discovered in Yunnan Province before disseminating throughout the country. As the HIV-1 epidemic continues to expand in Yunnan, genetic characteristics and transmitted drug resistance (TDR) should be further investigated among the recently infected population. Among 2828 HIV-positive samples newly reported in the first quarter of 2014, 347 were identified as recent infections with BED-captured enzyme immunoassay (CEIA). Of them, 291 were successfully genotyped and identified as circulating recombinant form (CRF)08_BC (47.4%), unique recombinant forms (URFs) (18.2%), CRF01_AE (15.8%), CRF07_BC (14.4%), subtype C (2.7%), CRF55_01B (0.7%), subtype B (0.3%) and CRF64_BC (0.3%). CRF08_BC and CRF01_AE were the predominant genotypes among heterosexual and homosexual infections, respectively. CRF08_BC, URFs, CRF01_AE and CRF07_BC expanded with higher prevalence in central and eastern Yunnan. The recent common ancestor of CRF01_AE, CRF07_BC and CRF08_BC dated back to 1983.1, 1992.1 and 1989.5, respectively. The effective population sizes (EPS) for CRF01_AE and CRF07_BC increased exponentially during 1991-1999 and 1994-1999, respectively. The EPS for CRF08_BC underwent two exponential growth phases in 1994-1998 and 2001-2002. Lastly, TDR-associated mutations were identified in 1.8% of individuals. These findings not only enhance our understanding of HIV-1 evolution in Yunnan but also have implications for vaccine design and patient management strategies.

Are clinical outcomes affected by laminoplasty method and K-line in patients with cervical ossification of posterior longitudinal ligament? A multicenter study.

BACKGROUND: Open-door laminoplasty (ODL) and French-door laminoplasty (FDL) are the main laminoplasty techniques used to treat cervical ossification of the posterior longitudinal ligament (C-OPLL). However, few studies have compared the outcomes of ODL and modified FDL (mFDL) for C-OPLL. We explored the differences in outcomes between ODL and mFDL for C-OPLL and analyzed the technical efficacy of each procedure in patients with K-line (+) or (-) C-OPLL. METHODS: From January 2010 to December 2015, 202 patients with K-line (+) or (-) C-OPLL were retrospectively recruited from 4 institutions. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) score, JOA score recovery rate, operative time, blood loss, and complications. Univariate analysis and binary logistic regression models were adjusted for confounding factors. RESULTS: Two hundred patients (mFDL, n = 69; ODL, n = 131) with a median follow-up of 42 months (range 36-54 months) were included. The postoperative JOA score significantly improved in both groups (P < 0.05). After adjusting for confounding factors, there was a statistically significant difference in blood loss (≥ 300 mL) between the two groups (P = 0.005), but there was no significant difference in the postoperative JOA score (≥ 14) (P = 0.062), JOA score recovery rate (≥ 0.82) (P = 0.187), or operative time (≥ 90 min) (P = 0.925). C5 palsy tended to occur more often in the mFDL group, although the difference was not significant (P > 0.05). The stratified analysis of the K-line status showed more blood loss in K-line (+) patients who underwent mFDL, but there was no significant difference in the postoperative JOA score, JOA score recovery rate, or operative time between the ODL and mFDL groups. Additionally, there was no significant difference in blood loss, postoperative JOA score, JOA score recovery rate, or operative time among all patients with K-line (+) or (-) C-OPLL in both groups. CONCLUSIONS: Both ODL and mFDL are effective for patients with C-OPLL. However, more blood loss tends to occur during mFDL. This study showed no significant difference in the operative time or incidence of complications between the two techniques. The efficacy of ODL and mFDL was not affected by the K-line status (+ or -) in patients with C-OPLL.

Porcine bocaviruses: genetic analysis and prevalence in Chinese swine population.

In members of the Bocavirus genus, that contain three open reading frames (ORFs) of the Parvovirinae subfamily, porcine bocaviruses (PoBoVs) exhibit the most genetic diversity. Based on the ORF2-encoded viral protein (VP1) classification, the six reported porcine bocaviruses were grouped into four species: PoBoV1 (porcine boca-like virus or PBoLV), PoBoV2 (porcine parvovirus 4 or PPV4), PoBoV3 (PBoV1/PBoV2) and PoBoV4 (6V/7V), with PoBoV3 and PoBoV4 each having two genotype viruses. All four PoBoV species were detected in the 166 samples collected in 2010 from swine herds located in ten provinces of China. The detection rates for PoBoV1-4 were 28·9%, 6·6%, 19·3% and 39·7%, respectively. The co-infection combinations involving these six porcine bocaviruses in the collected samples were very complex. Furthermore, mixed infections with viruses from other families (porcine reproductive and respiratory syndrome virus, classic swine fever virus and porcine circovirus type 2) were also detected.

Serum alkaline phosphatase and mortality in hemodialysis patients.

BACKGROUND: Alkaline phosphatase is typically considered as an innocent by-stander, but emerging data suggest that alkaline phosphatase might play a pathogenic role in vascular calcification and thus contribute to increased mortality in hemodialysis patients. STUDY DESIGN: Longitudinal analyses of the existing HEMO Study database. SETTING AND PARTICIPANTS: 1,827 HEMO Study participants. PREDICTOR: Serum alkaline phosphatase level. OUTCOME AND MEASUREMENTS: All-cause and cardiovascular mortality. RESULTS: Based on the median serum alkaline phosphatase of 97 IU/l, participants were divided into low (< 97 IU/l) and high (> or = 97 IU/l) serum alkaline phosphatase groups. The lower serum alkaline phosphatase group was associated with older age, male gender, non-black race and shorter dialysis years as well as higher serum calcium, higher serum calcium-phosphorus product and lower parathyroid hormone levels. Mean serum liver enzyme values were in the normal range in both groups, but the high alkaline phosphatase group had slightly higher values. In a multivariate time-dependent Cox model using baseline and follow-up values of serum alkaline phosphatase levels, adjusted for demographics, HEMO Study groups, comorbidity, bone metabolism parameters and liver enzymes, each doubling of serum alkaline phosphatase was significantly associated with increased hazard of all-cause (hazard ratio 1.44, 95% CI 1.30 - 1.59) and cardiovascular mortality (hazard ratio 1.35, 95% CI 1.16 - 1.57). LIMITATIONS: Nonstandardized measurements of alkaline phosphatase. CONCLUSIONS: Serum alkaline phosphatase is associated with increased mortality in hemodialysis patients, independent of bone metabolism parameters and liver enzymes. Alkaline phosphatase might be a potential therapeutic target in hemodialysis patients.

Improving general practitioners' interviewing skills in managing patients with depression and anxiety: a randomized controlled clinical trial.

BACKGROUND: Studies regarding the effectiveness of CME programmes on physicians' behaviour and communication skills showed inconsistent results. Few randomized controlled trials have been conducted in Asia. METHODS: To evaluate the effectiveness of a 4 2-hour education programme to improve GP interviewing behaviours, 16 general practitioners were randomized to the intervention and control groups, respectively. Physicians assigned to the intervention group received 8 hours of training emphasizing interviewing behaviours in the diagnosis and treatment of depression and generalized anxiety disorders (GDS). Those assigned to the control group did not receive any training until the completion of study. Standardized patients were used to evaluate the performance of physicians. Two consultations before and after enrolling in the education programme were videotaped. Independent evaluations of consultations were made by a trained clinical psychologist and a social worker blinded to the study status of physicians. The rating schedule for the videotapes was based on the tasks listed on the Calgary Cambridge Observation Guide. RESULTS: The change of score between the intervention and control physicians was significantly different in 'active listening and facilitating patients' response' (p = 0.011) with the intervention physicians having improvement of score. For 'non-verbals', 'understanding patient's perspective' and 'negotiating mutual plan of action', positive change of score in the intervention physicians were seen when compared to that of the control, although the difference did not reach statistical significance (p = 0.06, p = 0.05, p = 0.06, respectively). However, for 'opening', 'structuring the consultation', 'explanation and planning' and 'closure', there were no statistical significant differences between control and intervention group. CONCLUSIONS: Our results showed that only certain communication skills, such as active listening and facilitating patient's response, can be taught in the management of depression and generalized anxiety disorder (GAD) in Chinese primary care physicians.

Long-Term Follow-Up Results following Elective Treatment of Unruptured Intracranial Aneurysms with the Pipeline Embolization Device.

BACKGROUND AND PURPOSE: Numerous reports of treatment of wide-neck aneurysms by flow diverters have been published; however, long-term outcomes remain uncertain. This article reports the imaging results of unruptured aneurysms treated electively with the Pipeline Embolization Device for up to 56 months and clinical results for up to 61 months. MATERIALS AND METHODS: One hundred nineteen aneurysms in 98 patients from 3 centers admitted between August 2009 and June 2011 were followed at 6-month, 1-year, and 2+-year postprocedural timeframes. Analyses on the effects of incorporated vessels, previous stent placement, aneurysm size, and morphology on aneurysm occlusion were performed. RESULTS: The 1- and 2+-year imaging follow-ups were performed, on average, 13 and 28 months postprocedure. At 2+-year follow-up, clinical data were 100% complete and imaging data were complete for 103/116 aneurysms (88.8%) with a 93.2% occlusion rate. From 0 to 6 months, TIA, minor stroke, and major stroke rates were 4.2%, 3.4%, and 0.8% respectively. After 6 months, 1 patient had a TIA of uncertain cause, with an overall Pipeline Embolization Device-related mortality rate of 0.8%. An incorporated vessel was significant for a delay in occlusion (P = .009) and nonocclusion at 6 months and 1 year, with a delayed mean time of occlusion from 9.1 months (95% CI, 7.1-11.1 months) to 16.7 months (95% CI, 11.4-22.0 months). Other factors were nonsignificant. CONCLUSIONS: The Pipeline Embolization Device demonstrates continued very high closure rates at 2+ years, with few delayed clinical adverse sequelae. The presence of an incorporated vessel in the wall of the aneurysm causes a delay in occlusion that approaches sidewall closure rates by 2 years.

Anti-angiogenic pathway associations of the 3p21.3 mapped BLU gene in nasopharyngeal carcinoma.

Zinc-finger, MYND-type containing 10 (ZMYND10), or more commonly called BLU, expression is frequently downregulated in nasopharyngeal carcinoma (NPC) and many other tumors due to promoter hypermethylation. Functional evidence shows that the BLU gene inhibits tumor growth in animal assays, but the detailed molecular mechanism responsible for this is still not well understood. In current studies, we find that 93.5% of early-stage primary NPC tumors show downregulated BLU expression. Using a PCR array, overexpression of the BLU gene was correlated to the angiogenesis network in NPC cells. Moreover, expression changes of the MMP family, VEGF and TSP1, were often detected in different stages of NPC, suggesting the possibility that BLU may be directly involved in the microenvironment and anti-angiogenic activity in NPC development. Compared with vector-alone control cells, BLU stable transfectants, derived from poorly-differentiated NPC HONE1 cells, suppress VEGF165, VEGF189 and TSP1 expression at both the RNA and protein levels, and significantly reduce the secreted VEGF protein in these cells, reflecting an unknown regulatory mechanism mediated by the BLU gene in NPC. Cells expressing BLU inhibited cellular invasion, migration and tube formation. These in vitro results were further confirmed by in vivo tumor suppression and a matrigel plug angiogenesis assay in nude mice. Tube-forming ability was clearly inhibited, when the BLU gene is expressed in these cells. Up to 70-90% of injected tumor cells expressing increased exogenous BLU underwent cell death in animal assays. Overexpressed BLU only inhibited VEGF165 expression in differentiated squamous NPC HK1 cells, but also showed an anti-angiogenic effect in the animal assay, revealing a complicated mechanism regulating angiogenesis and the microenvironment in different NPC cell lines. Results of these studies indicate that alteration of BLU gene expression influences anti-angiogenesis pathways and is important for the development of NPC.

SAA1 polymorphisms are associated with variation in antiangiogenic and tumor-suppressive activities in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a cancer that occurs in high frequency in Southern China. A previous functional complementation approach and the subsequent cDNA microarray analysis have identified that serum amyloid A1 (SAA1) is an NPC candidate tumor suppressor gene. SAA1 belongs to a family of acute-phase proteins that are encoded by five polymorphic coding alleles. The SAA1 genotyping results showed that only three SAA1 isoforms (SAA1.1, 1.3 and 1.5) were observed in both Hong Kong NPC patients and healthy individuals. This study aims to determine the functional role of SAA1 polymorphisms in tumor progression and to investigate the relationship between SAA1 polymorphisms and NPC risk. Indeed, we have shown that restoration of SAA1.1 and 1.3 in the SAA1-deficient NPC cell lines could suppress tumor formation and angiogenesis in vitro and in vivo. The secreted SAA1.1 and SAA1.3 proteins can block cell adhesion and induce apoptosis in the vascular endothelial cells. In contrast, the SAA1.5 cannot induce apoptosis or inhibit angiogenesis because of its weaker binding affinity to αVß3 integrin. This can explain why SAA1.5 has no tumor-suppressive effects. Furthermore, the NPC tumors with this particular SAA1.5/1.5 genotype showed higher levels of SAA1 gene expression, and SAA1.1 and 1.3 alleles were preferentially inactivated in tumor tissues that were examined. These findings further strengthen the conclusion for the defective function of SAA1.5 in suppression of tumor formation and angiogenesis. Interestingly, the frequency of the SAA1.5/1.5 genotype in NPC patients was ~2-fold higher than in the healthy individuals (P=0.00128, odds ratio=2.28), which indicates that this SAA1 genotype is significantly associated with a higher NPC risk. Collectively, this homozygous SAA1.5/1.5 genotype appears to be a recessive susceptibility gene, which has lost the antiangiogenic function, whereas SAA1.1 and SAA1.3 are the dominant alleles of the tumor suppressor phenotype.

Determinants of bone gamma-carboxyglutamic acid-containing protein in plasma of healthy aging subjects.

The gamma-carboxy glutamic acid (Gla)-containing protein of mammalian bone (BGP, also called osteocalcin) is a 49 amino acid polypeptide containing two to three residues of gamma-carboxyglutamic acid. BGP is synthesized by osteoblastlike cells, and plasma BGP in laboratory animals is derived principally from recently synthesized BGP. These data, taken together with observations that plasma BGP levels are elevated in patients with disorders of high bone turnover, suggest that plasma BGP is a marker of osteoblast activity. Since low bone formation rates may play an important role in the loss of bone mass with age, we have examined the determinants of plasma BGP levels in aging subjects, using a region-specific radioimmunoassay for human BGP based on the synthetic C-terminal peptide hBGP37-49. In 147 carefully screened healthy subjects, aged 23-91, BGP did not change with age, whereas alkaline phosphatase (AP) showed a significant positive correlation (r = 0.30, P less than 0.001). Creatinine clearance (GFR) declined by 0.9 ml/min/yr and correlated with both BGP (r = -0.21, P less than 0.001) and AP (r = -0.21, P less than 0.001). However, correlation of AP with age persisted after controlling for GFR. BGP was not correlated with serum PTH, urine Ca/GFR, or urine cAMP/GFR. In 48 patients with known parenchymal renal disease studied for comparison, plasma BGP was increased at a serum creatinine of greater than or equal to 1.8 mg/dl. Our results indicate that plasma BGP, a specific marker of bone metabolism, is not predictably related to age per se. This result is in contrast to the age-related rise in total AP. Subtle changes in renal function can affect plasma BGP levels.

Retinyl ester retention in chronic renal failure. Further evidence for a defect in chylomicron remnant metabolism.

The metabolic remnants of triglyceride-rich lipoproteins are atherogenic in man and experimental animals. Particles resembling lipoprotein remnants have been found in plasma from patients with chronic renal failure (CRF). In this study we took advantage of the observation that retinyl esters are transported only by lipoproteins that originate in the intestine, that is, by chylomicrons (CM) and their remnants. To investigate further remnant metabolism in CRF, plasma RE were measured by reverse-phase high performance liquid chromatography in 20 non-diabetic hemodialyzed patients with CRF and 20 hospitalized non-diabetic control subjects 12-15 h after the administration of retinyl ester, 25000 IU orally. Total plasma RE were increased 3-fold in the CRF patients (P less than 0.001). Quantitative analysis of retinoids and lipids in fractions separated by unit-gravity flotation and flocculation in 3% polyvinylpyrrolidone indicated that the plasma RE were not contained among intact CM. Mean plasma retinol in CRF was also elevated consistent with previous observations and the known role of the kidney in retinol-binding protein metabolism. Although postabsorptive RE concentration was correlated positively and significantly with plasma triglyceride concentration in both groups, RE were higher in CRF patients at comparable plasma triglyceride concentrations. These data support the proposal that atherogenic lipoprotein remnants accumulate in the plasma of patients with CRF.

Nucleotide sequence of coronavirus TGEV genomic RNA: evidence for 3 mRNA species between the peplomer and matrix protein genes.

The region of the TGEV genome between the E1-matrix protein gene and the E2-peplomer protein gene has been sequenced from a cDNA clone. The consensus recognition sequence, 5'TTAA CTAAAC was found upstream from 3 large open reading frames. In coronaviruses these homologous recognition sequences are involved in the initiation of transcription suggesting that there are 3 mRNA species in this region of the TGEV genome. Northern blot analysis and nuclease S1 mapping confirmed the presence of 3 mRNA species between mRNA 3 encoding the E2-peplomer protein and mRNA 6 encoding the E1-matrix protein. The 5' regions of these 3 mRNAs encode potential polypeptides of predicted molecular weight; 7859, 27744 and 9287, respectively. The potential translation product of ORF B (27744 Da) is considerably larger than previously reported and could be difficult to distinguish by size from the E1-matrix protein.

Increases in mass transfer-area coefficients and urea Kt/V with increasing dialysate flow rate are greater for high-flux dialyzers.

The hemodialyzer mass transfer-area coefficient (K(o)A) for urea increases with increasing dialysate flow rate (Q(d)). The magnitude of the increase in K(o)A varies depending on the particular dialyzer under consideration; however, dialyzer properties that govern this phenomenon have not been established. We hypothesized that Q(d)-dependent increases in K(o)As are influenced by the water permeability of the dialysis membrane. We evaluated in vitro the effect of blood flow rate (Q(b)) and Q(d) on urea and creatinine K(o)As for two low-flux (Polyflux 6L and 8L) and two high-flux (Polyflux 14S and 17S) dialyzers containing Polyamide S membranes with similar membrane surface areas. Additional experiments were also performed on high-flux dialyzers containing Polyamide S membranes with very large surface areas (Polyflux 21S and 24S). K(o)As, calculated from the mean of blood- and dialysate-side clearances, were determined at zero net ultrafiltration for three different Q(b) and Q(d) combinations: Q(b) of 300 mL/min and Q(d) of 500 mL/min; Q(b) of 450 mL/min and Q(d) of 500 mL/min; and Q(b) of 450 mL/min and Q(d) of 800 mL/min. Urea and creatinine K(o)As were independent of the Q(b) but increased when Q(d) was increased from 500 to 800 mL/min. These increases in both urea and creatinine K(o)As were greater for high-flux than low-flux dialyzers (P < 0.0001). As expected, urea and creatinine K(o)As also increased with increasing membrane surface area. We conclude that dialysis membrane water permeability (or flux) is a dialyzer property that influences the dependence of small-solute K(o)As and clearance on Q(d). Whether this phenomenon is caused by enhanced internal filtration for dialyzers containing high-flux membranes requires further study.

Effect of dialysis membranes and middle molecule removal on chronic hemodialysis patient survival.

The type of dialysis membrane used for routine therapy has been recently shown to correlate with the survival of chronic hemodialysis patients. We examined whether this effect of dialysis membrane could be explained by differences in dialyzer removal of middle molecules using data from the 1991 Case Mix Adequacy Study of the United States Renal Data System. The sample analyzed included patients who had been treated by hemodialysis for 1 year or more, who were dialyzed with the 19 most commonly used dialyzers in 1991, and for whom delivered urea Kt/V could be calculated from predialysis and postdialysis blood urea nitrogen concentrations. Vitamin B12 (1,355 daltons) was used as a marker for middle molecules, and the clearance of vitamin B12 was estimated based on in vitro data. After adjustments for case mix, comorbidities, and urea Kt/V, the relative risk of mortality for a 10% higher calculated total cleared volume of vitamin B12 was 0.953 (P < 0.0001 v 1.000). Similar results were obtained when middle molecule removal was adjusted for body size. We conclude that both small and middle molecule removal indices appear to be independently associated with the risk of mortality in chronic hemodialysis patients. Differences in mortality when using different types of dialysis membrane may be explained by differences in middle molecule removal.

Cardiopulmonary events during hemodialysis: effects of dialysis membranes and dialysate buffers.

Adverse cardiac and pulmonary events are frequently observed during hemodialysis and contribute to significant morbidity and mortality. The temporal relationship between these events during the intradialytic period has not been well defined. To examine the event rate and timing of silent ischemia, cardiac ectopy, and hypoxemia, we conducted a prospective, single-blind, randomized study of 10 subjects undergoing maintenance hemodialysis with four contiguous combinations of dialysis membranes (cuprammonium or polysulfone) and dialysates (acetate or bicarbonate). The frequency of oxygen desaturation events peaked during the first 2 hours, whereas silent myocardial ischemia and supraventricular ectopies occurred more often in the later hours. Ventricular ectopy occurred steadily throughout the intradialytic period. The combination of acetate dialysis and cuprammonium membrane is associated with the most frequent events. We conclude that cardiopulmonary events can occur frequently during hemodialysis, and the frequency is dependent on the type of dialysis membrane and dialysate buffer used.

The hemodialysis membranes: a historical perspective, current state and future prospect.

Transport and biocompatibility characteristics are two important considerations when choosing hemodialysis membranes. Dialyzer performance depends on clearances of small solutes, middle molecules, and oncotically active proteins. Although complement and neutrophil activation have become the gold standards for biocompatibility testing of dialysis membranes, alterations of other cellular and noncellular blood elements as a result of blood-membrane interactions are also important. Because of concerns about middle molecule transport and biocompatibility, the original cellophane membrane has been gradually replaced by modified cellulosic membranes and synthetic membranes for clinical use. Recent studies suggest that the choice of dialysis membrane influences the clinical outcome of patients in several areas, including intradialytic acute anaphylactoid reactions, beta 2-microglobulin associated amyloidosis, recovery from acute renal failure, and mortality of chronic hemodialysis patients. However, the relative contributions of middle molecule transport, biocompatibility, and other factors in determining these differences in outcome are unclear. Future development of hemodialysis membranes should focus on improving biocompatibility and enhancing clearances of small solutes and middle molecules, while minimizing the loss of larger plasma proteins.

Fanconi's syndrome due to ifosfamide.

Although renal wasting of phosphate is relatively common, Fanconi's syndrome following ifosfamide chemotherapy is rare. This case illustrates the possibility of developing Fanconi's syndrome despite the apparent lack of toxicity during previous ifosfamide exposure. As the use of high-dose ifosfamide-containing regimens prior to BMT increases, the occurrence of this adverse effect may become more frequent. Morbidity due to Fanconi's syndrome can be decreased by close monitoring and aggressive management of fluid and electrolytes.

Inhibitors of peripheral-type benzodiazepine receptors present in human urine and plasma ultrafiltrates.

Several endogenous substances that inhibit central-type benzodiazepine (BZD) receptor binding have recently been identified. We have found that ultrafiltrates of human uremic plasma, normal plasma, and urine contain competitive inhibitors of peripheral-type benzodiazepine receptors. Using urine as source, we have partially purified a peripheral-type BZD receptor inhibitor(s) by adsorption to and selective elution from small octadecyl-silane (Sep-pak) columns and thin layer chromatography. The inhibitor has a 125-fold greater affinity for peripheral-type than central-type BZD receptors and has been purified 8000-fold from urine.

Increased urinary lipoperoxide levels in renal transplant patients.

Using high performance liquid chromatographic methods, both plasma and urine lipoperoxide concentrations were measured, as malondialdehyde (MDA), in 30 stable renal transplant patients receiving daily cyclosporine and/or azathioprine therapy. Their MDA concentrations were compared with previously reported reliable reference values using the same liquid chromatographic methods. Although their plasma concentrations were within the reference range, their mean urine MDA values averaged 3.7 to 5.0 times the normal reference values (p less than 0.001). The primary cause of the increased urine MDA concentrations following renal transplantation in these patients is unknown; it could be due to (a) renal lipid peroxidation directly related to the cyclosporine/azathioprine therapy, (b) drug-induced or other nephrotoxicity by an alternative mechanism with secondary lipid peroxidation, (c) increased lipid peroxidation owing to an immunologic response to the kidney graft, or (d) a combination of these possibilities.