PubMed Health⌕ Search

Biomedical subjects

Yan Cui

Publications and source records attributed to Yan Cui.

72 records · Page 4Linked to original sources
PubMed2003

Wash-out of DMSO does not improve the speed of engraftment of cord blood transplantation: follow-up of 46 adult patients with units shipped from a single cord blood bank.

BACKGROUND: Prolonged periods of marrow hypoplasia have been a problem in cord blood transplantation. DMSO is thought to produce osmotic shock to the progenitors when the thawed cells are infused into the patients. To solve this problem, a 2x dilution method originally developed in the New York Blood Center showed earlier myeloid engraftment,1 although follow-up clinical studies have not performed. STUDY DESIGN AND METHODS: To clarify the influence of the removal of DMSO by this method on the speed of engraftment in unrelated cord blood transplantation, 46 adult patients with cord blood units processed by the Tokyo Cord Blood Bank from September 1998 to March 31, 2002 were studied. Twenty-four patients received 2.6 +/- 0.71 x 10(7) nucleated cells per kg without washing (nonwashed group), while 22 patients were received 2.7 +/- 0.52 x 10(7) nucleated cells per kg after 2x dilution washing (washed group). RESULTS: The cumulative incidence of engraftment was not significantly different between the two groups. Median neutrophil recovery (>/=5 x 10(9)/L) in the nonwashed and washed groups was 26 and 25 days, respectively, and the median platelet recovery (>/=20 x 10(9)/L) in patients with myeloid engraftment was 44 and 40 days, respectively (NS). On the other hand, the doses of CFCs and CD34+ cells showed the influence on myeloid and platelet recovery. CONCLUSION: A 2x dilution after thawing cord blood did not result in the improvement of myeloid engraftment speed.

Adolescent↗
PubMed2003

Effects of ketamine/xylazine on expression of tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclo-oxygenase-2 in rat gastric mucosa during endotoxemia.

Some anesthetics attenuate expression of endotoxin-induced production of proinflammatory genes. The anesthetic combination of ketamine/xylazine (K/X) decreases lipopolysaccharide (LPS)-induced liver injury in rats. However, the effects of K/X on gut function and gene expression are unknown. The purpose of this study was to examine the effect of K/X on LPS-induced gastric fluid accumulation, and gastric tumor necrosis factor (TNF)-alpha, inducible nitric oxide synthase (iNOS), and cyclo-oxygenase (COX)-2 expression, as well as serum TNF-alpha protein levels over time. We hypothesized that K/X would attenuate these LPS-induced endpoints. Rats were given either intraperitoneal saline or K (70 mg/kg) and X (6 mg/kg) 1 h before saline or LPS (20 mg/kg i.p.) treatment of 1, 3, or 5 h. Serum and gastric fluid and mucosa were collected and TNF-alpha, iNOS, and COX-2 expression were determined. LPS caused a significant increase in early serum and gastric mucosal TNF-alpha protein expression at 1 h, an effect that was significantly attenuated by K/X pretreatment. LPS caused significant gastric stasis and increased iNOS and COX-2 mRNA expression and iNOS protein expression in the stomach when compared with controls. K/X attenuated LPS-induced gastric fluid accumulation and upregulation of iNOS mRNA and protein, but not COX-2. These data indicate that K/X inhibits some proinflammatory genes and pathophysiologic responses in the serum and stomach during endotoxemia. The effects of K/X appear to inhibit transcriptional events in iNOS expression, which may be dependent on K/X-induced inhibition of early TNF-alpha expression. Furthermore, in rat models of endotoxemia, especially those evaluating the stomach, careful consideration needs to be given if anesthetic combinations with ketamine and/or xylazine are used, as they alter LPS-induced responses.

Animals↗
PubMed2003

Ultrasonography guided percutaneous radiofrequency ablation for hepatic cavernous hemangioma.

AIM: Hepatic cavernous hemangioma (HCH) is the most common benign tumor of the liver and its management is still controversial. Recent success in situ radiofrequency ablation of hepatic malignancies has led us to consider using this technique in patients with HCH. This study was to assess the efficacy, safety, and complications of percutaneous radiofrequency ablation (PRFA) under ultrasonography guidance in patients with HCH. METHODS: Twelve patients (four men and eight women, age ranged 33-56 years, mean age was 41.7 years) with 15 hepatic cavernous hemangiomas (2.5 cm to 9.5 cm) were treated using the RF-2000 generator and 10-needle LeVeen electrode percutaneously guided by B-ultrasound. Lesions larger than 3 cm were treated by multiple overlapping ablations that encompass the entire lesion as well as a rim of normal liver tissue (approximately 0.5 cm). RESULTS: All the patients who received PRFA therapy had no severe pain, bleeding or bile leakage during and after the procedures. Nine to 34 months' follow-up (mean, 21 months) by ultrasound and/or spiral CT scan demonstrated that the ablated lesions in this group were shrunk remarkably, and the shrunken range was 38-79 % (mean, 67 % per 21 months). The contrast enhancement was disappeared within the tumor or at its periphery in all cases on spiral CT scans obtained 3 to 6 months after treatment. CONCLUSION: The results of this study suggest that PRFA therapy is a mini-invasive, simple, safe, and effective method for the treatment of selected patients with HCH.

Adult↗
PubMed2002

Cholecystokinin secretagogue-induced gastroprotection: role of nitric oxide and blood flow.

This study was done to examine the role of CCK in gastric mucosal defense and to assess the gastroprotective roles of nitric oxide and blood flow. In rats, the CCK secretagogues oleate and soybean trypsin inhibitor augmented gastric mucosal blood flow and prevented gastric injury from luminal irritants. Type A CCK receptor blockade negated CCK secretagogue-induced gastroprotection and exacerbated gastric injury from bile and ethanol but did not block adaptive cytoprotection. CCK secretagogue-induced gastroprotection and hyperemia were negated by nonselective nitric oxide synthase (NOS) inhibition (N(G)-nitro-L-arginine methyl ester) but not by selective inducible NOS inhibition (aminoguanidine). Gastric mucosal calcium-dependent NOS activity, but not calcium-independent NOS activity, was increased following CCK and CCK secretagogues. The release of endogenous CCK plays a role in the intrinsic gastric mucosal defense system against injury from luminal irritants. The protective mechanism appears to involve increased production of nitric oxide from primarily the constitutive isoforms of NOS and a resultant increase in blood flow.

Acids↗
PubMed2002

[A randomized control trial of mycophenolate mofeil treatment in severe IgA nephropathy].

OBJECTIVE: To investigate the effectiveness safety and tolerance of mycophenolate mofeil(MMF) in severe IgA nephropathy and evaluate the dosage adjustment and course for clinical treatment. METHODS: 62 patients with IgA nephropathy diagnosed by renal biopsy as Lee's grade IV and V with urinary protein > 2.0 g/d were enrolled randomly in the trial. The initial dosage of MMF was 1.0 g/d (body weight < 50 kg) or 1.5 g/d (body weight > 50 kg). The dosage was reduced to 0.75 approximately 1.0 g/d after 6 months treatment, the maintaining dosage was 0.5 approximately 0.75 g/d after 12 months. The total course of treatment lasted at least 12 months. Another 31 patients matched with age gender and severity of renal damage were given prednisone orally (0.8mg(;)kg(;)d) (control group).Blood and urinary tests hepatic and renal function plasma albumin serum triglyceride and cholesterol 24 h protein excretion urinary NAG enzyme, creatinine clearance(Ccr) were performed before and 3 6 12 18 months after treatments in both groups 5 patients in MMF group received repeated renal biopsy. RESULTS: (1) After 3 months treatment, decrease of urinary protein (1.9 g/24 h +/- 1.6 g/24 h vs 3.2 g/24 h +/- 1.7 g/24 h, P < 0.01) and improvement of plasma albumin (41 g/L +/- 6 g/L vs 37 g/L +/- 6 g/L, P < 0.01) were observed in MMF groups while in control group, no significant changes were found in uinary protein (2.3 g/24 h +/- 1.8 g/24 h vs 2.9 g/24 h +/- 1.5 g/24 h, P < 0.05) and plasma albumin (40 g/L +/- 6 g/L vs 37 g/L +/- 6 g/L, P < 0.05). After treatment for 6, 12 and 18 months, both group showed obvious alleviation of proteinuria and albumin. At the 12th and 18th month, the proteinuria in MMF group was significantly improved than that in control group (0.8 g/24 h +/- 0.8 g/24 h vs 1.4 g/24 h +/- 1.6 g/24 h and 0.6 g/24 h +/- 0.7 g/24 h vs 1.4 g/24 h +/- 1.3 g/24 h, P < 0.05 respectively). The remission rate and total effective rate of MMF group were higher than those of the control group (44.4% vs 19.1% and 88.9% vs 61.9%, P < 0.05 respectively). Patients were administered with MMF for 13.8 +/- 6.3 months (6 approximately 30 m). (2) Serum cholesterol and triglyceride were remarkably reduced after 6,12 and 18 months treatment in MMF group, no significant difference was found in control group(P < 0.05). (3) For the 6 patients with renal insufficiency in MMF group, MMF treatment was significantly effective in 1 patient, effective in 2 patients, not effective in 3 patients with an overall effective rate of 50%. For the 7 patients with renal insufficiency in control group, the treatment was significantly effective in 1 patient, effective in 1 patient, not effective in 5 patients and total effective rate is 28.6%. (4) 5 patients in MMF group received repeated renal biopsy after 7 approximately 12 months treatment (mean 9.8 +/- 2.3 m). The results showed that the interstitial lesions were alleviated. No special drug-induced renal damage was obtained. (5) Side effects: 3 patients in MMF group suffered from slight diarrhea, 1 patient herpes zoster, all of them got remission without drug withdrawal. 1 patient suffered nausea in the first weeks. No significant change was found in hepatic function (P > 0.05). CONCLUSIONS: MMF is more effective in reducing proteinuria and serum lipid than the currently widespread use of prednisone therapy in IgA nephropathy patients with Lee SMK's grade IV approximately V and urinary protein > 2.0 g/d. Treatment with MMF associates with less adverse effect and good tolerance.

Adolescent↗
PubMed2002

Induction of NF-kappaB, IkappaB-alpha, and iNOS in rat gastric mucosa during endotoxemia.

Upregulation of inducible nitric oxide synthase (iNOS) contributes to the development of gastric injury during endotoxemia. The molecular mechanisms related to its induction are unknown. Because the transcription factor nuclear factor-kappa B (NF-kappaB) regulates inflammatory genes in response to endotoxemia, we hypothesized that its activity in gastric mucosa would increase while its inhibitor IkappaB-alpha would decrease commensurate with changes in iNOS expression. Rats were given intraperitoneal saline or lipopolysaccharide (LPS; 20 mg/kg) for 5, 15, or 30 min, or for 1, 3, or 5 h, and killed, and the gastric mucosa was prepared for determination of iNOS and IkappaB-alpha by Western immunoblotting, iNOS mRNA by quantitative real-time RT-PCR, and NF-kappaB by electrophoretic mobility-shift assay. LPS caused a significant increase in iNOS mRNA and protein immunoreactivity at 1, 3, and 5 h compared to controls. NF-kappaB-binding activity increased in the nuclear fraction of gastric mucosa at 1 h and steadily increased over time after LPS administration. The activated NF-kappaB consisted mainly of p50 with a lesser amount of p65 subunits as demonstrated by a supershift assay. IkappaB-alpha decreased in gastric cytosolic fractions over time, consistent with its degradation. These data suggest that during endotoxemia expression of the inflammatory mediator iNOS in the gastric mucosa may be upregulated by degradation of IkappaB-alpha and subsequent translocation of NF-kappaB into the nucleus and increased NF-kappaB activity.

Animals↗
PubMed2002

Recombinatoric exploration of novel folded structures: a heteropolymer-based model of protein evolutionary landscapes.

The role of recombination in evolution is compared with that of point mutations (substitutions) in the context of a simple, polymer physics-based model mapping between sequence (genotype) and conformational (phenotype) spaces. Crossovers and point mutations of lattice chains with a hydrophobic polar code are investigated. Sequences encoding for a single ground-state conformation are considered viable and used as model proteins. Point mutations lead to diffusive walks on the evolutionary landscape, whereas crossovers can "tunnel" through barriers of diminished fitness. The degree to which crossovers allow for more efficient sequence and structural exploration depends on the relative rates of point mutations versus that of crossovers and the dispersion in fitness that characterizes the ruggedness of the evolutionary landscape. The probability that a crossover between a pair of viable sequences results in viable sequences is an order of magnitude higher than random, implying that a sequence's overall propensity to encode uniquely is embodied partially in local signals. Consistent with this observation, certain hydrophobicity patterns are significantly more favored than others among fragments (i.e., subsequences) of sequences that encode uniquely, and examples reminiscent of autonomous folding units in real proteins are found. The number of structures explored by both crossovers and point mutations is always substantially larger than that via point mutations alone, but the corresponding numbers of sequences explored can be comparable when the evolutionary landscape is rugged. Efficient structural exploration requires intermediate nonextreme ratios between point-mutation and crossover rates.

Biophysical Phenomena↗
PubMed2002

Targeting transgene expression to antigen-presenting cells derived from lentivirus-transduced engrafting human hematopoietic stem/progenitor cells.

Hematopoietic stem cells (HSCs) represent an important target for the treatment of various blood disorders. As the source of critical cells within the immune system, genetic modification of HSCs can also be used to modulate immune responses. The effectiveness of HSC-mediated gene therapy largely depends on efficient gene delivery into long-term repopulating progenitors and targeted transgene expression in an appropriate progeny of the transduced pluripotent HSCs. Self-inactivating (SIN) lentiviral vectors have been demonstrated to be capable of transducing mitotically inactive cells, including HSCs, and accommodating a nonviral promoter to control the transgene expression in transduced cells. In this study, we constructed 2 SIN lentiviral vectors, EF.GFP and DR.GFP, to express the green fluorescent protein (GFP) gene controlled solely by the promoter of either a housekeeping gene EF-1alpha or the human HLA-DRalpha gene, which is selectively expressed in antigen-presenting cells (APCs). We demonstrated that both vectors efficiently transduced human pluripotent CD34+ cells capable of engrafting nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. When the EF.GFP vector was used, constitutive high-level GFP expression was obtained in all the human HSC progeny detectable in NOD/SCID mice and in subsequent in vitro differentiation assays, indicating that engrafting human HSCs have been transduced. In contrast, the DR.GFP vector mediated transgene expression specifically in human HLA-DR+ cells and highly in differentiated dendritic cells (DCs), which are critical in regulating immunity. Furthermore, human DCs derived from transduced and engrafted human cells potently stimulated allogeneic T-cell proliferation. This study demonstrated successful targeting of transgene expression to APCs/DCs after stable gene transduction of pluripotent HSCs.

Animals↗
PubMed2002

Proteome-wide analysis of protein function composition reveals the clustering and phylogenetic properties of organisms.

A 17-dimensional vector named the proteome vector is defined to represent an organism. The components of the vector reflect the relative contents of protein-encoding genes of the 17 cluster of orthologous groups of proteins (COGs) classes in the whole genome of the relevant organism. Based on the definition of this proteome vector, the fuzzy clustering of 36 completely sequenced organisms (8 archaea, 24 bacteria, and 4 eukarya) was performed and a proteome tree was constructed. Our results show that (1) the 36 organisms can be 100% correctly classified into three clusters corresponding to the three primary kingdoms, (2) our proteome tree is remarkably similar to that derived from 16S rRNA, and (3) the chromosomes and/or plasmids belonging to the same organism have very similar gene composition. Based on these results, we argue that the 17-dimensional proteome vector could be a good criterion for clustering approaches and to a large extent reveals the phylogenetic properties of organisms; the Three Primary Kingdoms Hypothesis is trustworthy although the existence of lateral gene transfer (LGT) brings controversy to the construction of the "universal tree of life."

Algorithms↗
PubMed2002

Oral interferon-alpha treatment of mice with cryoglobulinemic glomerulonephritis.

Cryoglobulins are associated with the development of a membranoproliferative glomerulonephritis, often referred to as cryoglobulinemic glomerulonephritis, particularly in the setting of hepatitis C virus infection. Parenteral interferon-alpha (IFN-alpha) commonly is used therapeutically in humans with cryoglobulinemic glomerulonephritis. We tested the therapeutic impact of oral IFN-alpha treatment in thymic stromal lymphopoietin (TSLP) transgenic mice, a strain that develops mixed cryoglobulinemia with glomerulonephritis closely resembling the disease that occurs in humans. A total of 41 female mice were treated for 21 days with daily ingestion of either 500 IU of Universal type I IFN or placebo. The studied groups included TSLP transgenic mice treated with IFN-alpha (n = 13), TSLP transgenic mice treated with placebo (n = 13), wild-type mice treated with IFN-alpha (n = 5), and wild-type mice treated with placebo (n = 10). A total of 39 mice completed the study; two TSLP transgenic mice treated with IFN-alpha died during the study period. Placebo-treated TSLP transgenic mice showed significantly increased mean glomerular tuft areas, mean glomerular areas occupied by macrophages, and mean cell numbers per glomerulus compared with wild-type controls. All three parameters were decreased in IFN-alpha-treated TSLP transgenic mice, although the differences compared with placebo-treated mice did not reach significance. The changes in glomerular matrix deposition were the same in IFN-alpha-treated and placebo-treated mice. The oral ingestion of IFN-alpha seemed to reduce glomerular macrophage influx, but this did not result in decreased glomerular matrix deposition. The limited positive effect provides experimental support for clinical studies that indicate the beneficial effects of IFN-alpha therapy observed in humans with glomerulonephritis might be attributable to its antiviral effect rather than modulation of intrarenal pathophysiologic pathways.

Administration, Oral↗
PubMed2002

Gastric nitric oxide synthase expression during endotoxemia: implications in mucosal defense in rats.

BACKGROUND & AIMS: This study was performed to examine expression of gastric nitric oxide synthase (NOS) isoforms during endotoxemia in rats and to assess their role(s) in gastric injury from bile and ethanol. METHODS: Lipopolysaccharide (LPS) enhanced the expression and activity of inducible nitric oxide synthase in gastric mucosa in a dose- and time-dependent manner. RESULTS: Endothelial nitric oxide synthase and neural nitric oxide synthase expression did not significantly change, but constitutive nitric oxide synthase activity decreased over time. LPS alone caused injury to the gastric mucosa and disrupted F-actin filaments in the same cells with enhanced immunostaining for inducible nitric oxide synthase. LPS also exacerbated gastric injury from the mild irritants 5 mmol/L acidified taurocholate and 20% ethanol as did local intra-arterial infusion of the nitric oxide donor S-nitroso-N-acetyl-penicillamine. The selective inducible nitric oxide synthase inhibitor aminoguanidine negated LPS-induced exacerbation of gastric injury from these irritants. The nonselective NOS inhibitor N(G)-nitro-L-arginine methyl ester augmented the deleterious effects of LPS, an effect reversed by L-arginine but not D-arginine. Aminoguanidine, but not N(G)-nitro-L-arginine methyl ester, negated LPS-induced accumulation of gastric luminal nitrates. CONCLUSIONS: These data suggest that increased inducible NOS activity and decreased constitutive nitric oxide synthase activity are primarily responsible for exacerbating gastric injury from luminal irritants during endotoxemia. Moreover, septic patients may be more susceptible to gastric injury from bile during gastrointestinal ileus.

Animals↗
PubMed2002

Cellular injury associated with renal thrombotic microangiopathy in human immunodeficiency virus-infected macaques.

Pigtailed macaques infected with a virulent human immunodeficiency virus-2 (HIV-2) strain develop renal thrombotic microangiopathy (TMA), which morphologically resembles aspects of human HIV-associated TMA. Apoptotic cell death of microvascular endothelial cells might be a pathogenetic clue to this disease. For defining further the pattern of cellular injury in this model, serial kidney sections of 58 macaques infected with HIV-2 and 7 uninfected controls were studied by routine microscopy, terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL), 4',6-diamidino-2-phenylindole staining, and immunohistochemistry for single-stranded DNA, p53, the Wilms' tumor suppressor gene-1 peptide product, caspase-3, and the proliferation marker Ki67. Selected cases were further evaluated by in situ end labeling and transmission electron microscopy. Kidneys of 13 HIV-2-infected animals contained a pattern of cellular injury, which was characterized by (1) nuclear swelling with an ultrastructural morphology different from apoptotic nuclei, (2) sharply demarcated areas of renal cells with chromatin nicks (TUNEL positive) and single-stranded DNA, (3) absence of an inflammatory or proliferative response, (4) upregulation of p53 and loss of at least one cellular differentiation marker (Wilms' tumor suppressor gene-1), (5) a tight correlation with the diagnosis of renal TMA, and (6) a contrast between profound changes in the renal cellular morphology and the apparently unaffected clinical condition of the host. This pattern of injury, which shares some features of both apoptotic and oncotic necrosis, might be involved in the pathogenesis of HIV-associated renal TMA in this model.

Animals↗
PubMed2002

[Clinical characteristics of primary biliary cirrhosis: a report of 45 cases].

OBJECTIVE: To study the clinical features of primary biliary cirrhosis (PBC) in order to facilitate cognition of the disease. METHODS: General status, clinical manifestations and laboratory findings of 45 patients with PBC were reviewed. RESULTS: Among the 45 patients, 42 were females and the mean age at diagnosis was (50.8 +/- 8.1) years. The mean time interval between the first visit to physicians to the time of correct diagnosis was about 2 years. The most frequent symptoms were fatigue (66.7%, 30/45), then jaundice (55.6%, 25/45) and pruritus (40%, 18/45). Nine patients (20%) were asymptomatic. Nine patients (20%) were associated with other auto-immune diseases (Sjogren's syndrome and/or rheumatoid arthritis). Serum alkaline phosphatase (ALP) and glutamyl transpeptidase (gamma-GT) levels were markedly elevated in all the patients [(498.5 +/- 369.8) IU/L and (595.2 +/- 518.4) IU/L, respectively], whereas ALT and AST levels were mildly to moderately elevated [(83.9 +/- 58.8) IU/L and (100.8 +/- 48.8) IU/L, respectively]. 25 patients (55.6%) had a total bilirubin level >/= 34.2 micromol/L. 40 patients (88.9%) had elevated serum IgM and 43 patients (95.6%) were anti-mitochondrial antibody (AMA)/AMA-M2 positive. CONCLUSION: In China, PBC is probably not so rare as it was thought before. It is mostly found in middle-aged women. The most frequent symptom is fatigue and some patients are asymptomatic at early stage. Elevated serum ALP and gamma-GT levels together with positive AMA/AMA-M2 can help to diagnose PBC. Liver biopsy is useful to confirm the diagnosis and differentiate histopathological stages.

Adult↗
PubMed2002

[Exclusive identification of gene loci of autosomal dominant nonsyndromic hearing loss].

OBJECTIVE: The purpose is to map related genes of an autosomal dominant nonsyndromic hearing loss kindred. METHOD: Linkage analysis was carried out using screening markers of the 22 reported loci. RESULT: Linkage analysis showed no linkages between pedigree gene and reported loci. CONCLUSION: The autosomal dominant nonsyndromic hearing loss in the kindred may be resulted from a new gene.

Chromosome Mapping↗
PubMed2000

Expression of the chemokine monocyte chemoattractant protein-1 and its receptor chemokine receptor 2 in human crescentic glomerulonephritis.

Crescents are morphologic manifestations of severe glomerular injury. Several chemokines and their receptors have been demonstrated to be involved in animal models of crescentic glomerulonephritis (cGN) and are potential targets for therapeutic interventions. Therefore, the expression of monocyte chemoattractant protein-1 (MCP-1), its receptor chemokine receptor 2B (CCR2B), and CCR5 in human cGN was studied. MCP-1 and CCR2B mRNA expression was evaluated, by in situ hybridization, in serial sections of 23 renal biopsies from patients with cGN. T cells, macrophages, and CCR5-expressing cells were examined by immunohistochemical analysis. MCP-1 mRNA was expressed by cells in crescents, parietal epithelium, and tubular epithelium, as well as by infiltrating leukocytes in the tubulointerstitium. The expression of CCR2B mRNA was observed in cells in glomeruli and crescents and in infiltrating leukocytes in the tubulointerstitium. CCR2B mRNA expression could not be clearly localized to intrinsic renal cells; evidence that most of the CCR2B-expressing cells were leukocytes is provided. CD3-positive T cells formed the major part of the interstitial cell infiltrates but were rare within the glomerular tufts. CD68-positive macrophages constituted a major population of infiltrating cells in crescents and contributed significantly to the interstitial infiltrates. The number of glomerular macrophages was associated with the number of MCP-1- and CCR2B-positive glomerular cells. Expression of CCR2B was significantly correlated with interstitial CD3-positive T cells. CCR5 expression was restricted to infiltrating leukocytes and was correlated quantitatively and by localization with interstitial CD3-positive T cells and CD68-positive macrophages. These first morphologic data on the distribution of CCR2-positive cells in human cGN suggest differential effects of chemokines and their receptors on the distribution of infiltrating leukocytes in different compartments of the kidney.

Antigens, CD↗
PubMed2000

Chemokine receptor CCR5 and CXCR4 expression in HIV-associated kidney disease.

The chemokine receptors CCR5 and CXCR4 have been identified as essential coreceptors for entry of HIV-1 strains into susceptible cells. Direct infection of renal parenchymal cells has been implicated in the pathogenesis of HIV-associated renal disease, although data are conflicting. The localization of CCR5 and CXCR4 in kidneys with HIV-associated renal disease is unknown. Formalin-fixed, paraffin-embedded renal biopsies from patients with HIV-associated nephropathy (HIVAN) (n = 13), HIV-associated immune complex glomerulonephritis (n = 3), HIV-associated thrombotic microangiopathy (n = 1), and HIV-negative patients with collapsing glomerulopathy (n = 8) were analyzed in this study. Cellular sites of expression of CCR5 and CXCR4 were identified by immunohistochemistry and by in situ hybridization. The presence of HIV-1 was detected by immunohistochemistry and by in situ hybridization. Expression of both chemokine receptors CCR5 and CXCR4 was undetectable in intrinsic glomerular, tubular, and renovascular cells in all analyzed cases. In the presence of tubulointerstitial inflammation, CCR5 and CXCR4 expression was localized to infiltrating mononuclear leukocytes. HIV-1 protein was undetectable by immunohistochemistry in all cases of HIV-associated renal disease. HIV-1 RNA was identified in one case of HIVAN but was restricted to infiltrating leukocytes. HIV-1 RNA was not detected in intrinsic renal cells in all analyzed cases. Identifying the cellular expression of HIV-coreceptors CCR5 and CXCR4 may help to clarify which tissues are permissive for direct HIV infection. These data do not support a role of productive HIV-1 infection of renal parenchymal cells in the pathogenesis of HIV-associated renal disease.

AIDS-Associated Nephropathy↗