PubMed Health⌕ Search

Biomedical subjects

J C Papadimitriou

Publications and source records attributed to J C Papadimitriou.

At least 19 recordsLinked to original sources
PubMed2006

Polyomavirus-associated nephropathy: update in diagnosis.

The histological diagnosis of BK or JC polyomavirus allograft nephritis (PVAN) requires evaluation of a renal biopsy with demonstration of the polyomavirus cytopathic changes and confirmation with an ancillary technique such as immunohistochemistry. Three histological patterns of PVAN (A, B, and C) are identified in renal biopsies. Pattern A corresponds to the early disease, whereas patterns B and C identify intermediate and very advanced histological changes, respectively. The histological pattern found in the first biopsy correlates with graft outcome. Because PVAN affects the kidney in a random, multifocal manner, a negative biopsy does not rule out the disease. Patients with BK PVAN characteristically have high levels of BK viruria and viremia. Although the cutoff values of viral loads have not been fully determined, there is general agreement that BK viruria of >10(7)/mL and BK viremia of >10(4) are typical of patients with a biopsy showing BK PVAN. Prospective evaluation of viruria with urine cytology (decoy cells) and/or quantitative polymerase chain reaction can aid in the identification of patients at risk for developing PVAN. In addition to histological evaluation, viremia has emerged as the most specific test for the diagnosis of BK PVAN. JC PVAN is very infrequent in comparison with BK PVAN, but is also characterized by large viruria (>10(4)). On the other hand, JC viremia appears to be lower, in the order of 10(3)/mL. The inflammatory changes in PVAN need further characterization. Currently, there are no tools to differentiate acute cellular rejection from viral specific T-cell response.

BK Virus↗
PubMed2004

Histological findings in "incidental" intraoperative pancreas allograft biopsies.

Thirty intraoperative needle core biopsies of well-functioning pancreas allografts were performed from 2 days to 7 years posttransplantation (mean 15.4 months). Most samples (83.3%) lacked significant inflammation or fibrosis. The five patients who showed features of ongoing low-grade acute rejection experienced premature graft losses due to chronic rejection. There were no complications related to the intraoperative biopsy itself.

Adult↗
PubMed2004

Improved outcome of polyoma virus allograft nephropathy with early biopsy.

Polyoma virus allograft nephropathy often results in accelerated graft loss despite reduction of immunosuppression and/or treatment with antiviral agents. Irreversible renal fibrosis due to late diagnosis is likely to be one of the important causes of treatment failure. Early biopsy in 14 patients resulted in stable graft function after a mean follow-up of 22 months.

Biopsy↗
PubMed2004

Cost efficiency in the prospective diagnosis and follow-up of polyomavirus allograft nephropathy.

Evaluation of urine cytology (UC) for decoy cells and quantitative determinations of viruria (urine viral load [UPCR])and viremia (viral load in blood [VLB]) have been proposed as surrogate markers of polyomavirus allograft nephropathy (PVAN). In this study, we present the experience with the concurrent evaluation of UC, UPCR, and VLB in 349 patients (940 sets of samples). Results were correlated with each other and with a previous, concurrent, or subsequent biopsy diagnosis of PVAN. Patients were followed up for a mean of 27 months posttransplantation. We conclude that both UC and UPCR are useful for screening of renal transplant recipients. Simultaneous performance of both UC and UPCR does not add useful clinical information. In patients with positive UC, performance of UPCR, however, can allow for the distinction between BK and JC polyoma viruses. Quantitative measurement of viremia is not indicated in patients lacking viruria because no patients with PVAN present with this combination of findings. In patients with viruria, a positive viremia strongly correlates with PVAN. Rationale selection of screening protocols based on the current knowledge of the infection and tailored to the available laboratory capabilities in each transplantation center can optimize the use of resources.

Biopsy↗
PubMed2001

Pancreas transplantation: the histologic morphology of graft loss and clinical correlations.

BACKGROUND: Graft losses due to leaks, bleeding, thrombosis, infections, and early pancreatitis are grouped together under the category of technical failure. Among these complications, massive vascular thrombosis continues to be the most important cause of early graft loss due to technical failure. Pathological evaluation of most allografts lost early in the posttransplantation period shows vascular thrombosis with associated proportional parenchymal necrosis. The morphological findings in allografts that are considered to be lost due to technical failure has not been systematically addressed. In particular, the role of acute rejection in early graft loss has not been well studied. METHODS: Seventy-four consecutive pancreas graft pancreatectomies were studied histologically to evaluate for thrombosis (recent versus organized), type of vessel involved by thrombosis (arteries, veins, or both), acute rejection grade, chronic rejection grade, endotheliitis, transplant arteritis, coagulation necrosis, acute pancreatitis, presence of infectious organisms, transplant (obliterative) arteriopathy, neoplasia, relative proportions of alpha and beta islet cells, and immunoglobulin and complement deposition. The histological findings were correlated with donor and recipient data as well as clinical presentation. RESULTS: In 23 out of 39 grafts lost in the first 4 weeks posttransplantation, the only pathological changes found were vascular thrombosis and bland ischemic parenchymal necrosis. In these cases, no underlying vascular pathology or any other specific histological change was identified. Most of these grafts (78%) were lost in less than 48 hr and all in the first 2 weeks posttransplantation. Massive vascular thrombosis occurring in an otherwise histologically normal pancreas was the most common cause of graft loss in the first 4 weeks posttransplantation (59%). In most of the remaining cases (33%), although the clinical presentation suggested technical failure, there was clear histological evidence that the massive thrombosis resulted from vascular injury due to immune damage (acute and hyperacute rejection). Increased incidence of early graft thrombosis was seen in grafts from older donors and longer cold ischemia times. After the first month posttransplantation, graft pancreatectomies revealed a wider variety of pathological processes that included severe acute rejection, combined acute and chronic rejection, chronic rejection, and infections. Acute and chronic vascular thrombosis in large and small vessels was commonly seen at all times posttransplantation; chronic, organized thrombosis was strongly associated with chronic rejection. CONCLUSIONS: (a) Early acute thrombosis occurring in a histologically normal pancreas defines a true technical failure. This study showed that acute rejection leading to massive thrombosis, which clinically simulates technical failure, results in a significant proportion of early graft losses. (b) Systematic histological evaluation of failed grafts is absolutely necessary for the accurate classification of the cause of graft loss. (c) There is morphological evidence that chronically ongoing thrombosis is an important, common, contributing factor for late graft loss.

Adult↗
PubMed2001

A novel role of complement: mice deficient in the fifth component of complement (C5) exhibit impaired liver regeneration.

Components of innate immunity have recently been implicated in the regulation of developmental processes. Most strikingly, complement factors appear to be involved in limb regeneration in certain urodele species. Prompted by these observations and anticipating a conserved role of complement in mammalian regeneration, we have now investigated the involvement of complement component C5 in liver regeneration, using a murine model of CCl(4)-induced liver toxicity and mice genetically deficient in C5. C5-deficient mice showed severely defective liver regeneration and persistent parenchymal necrosis after exposure to CCl(4.) In addition, these mice showed a marked delay in the re-entry of hepatocytes into the cell cycle (S phase) and diminished mitotic activity, as demonstrated, respectively, by the absence of 5-bromo-2'-deoxyuridine incorporation in hepatocytes, and the rare occurrence of mitoses in the liver parenchyma. Reconstitution of C5-deficient mice with murine C5 or C5a significantly restored hepatocyte regeneration after toxic injury. Furthermore, blockade of the C5a receptor (C5aR) abrogated the ability of hepatocytes to proliferate in response to liver injury, providing a mechanism by which C5 exerts its function, and establishing a critical role for C5aR signaling in the early events leading to hepatocyte proliferation. These results support a novel role for C5 in liver regeneration and strongly implicate the complement system as an important immunoregulatory component of hepatic homeostasis.

Animals↗
PubMed2001

Structural similarities between hematoidin crystals and asteroid bodies: evidence of lipid composition.

Hematoidin crystals (HC) are found in tissues where extravasated erythrocytes undergo degradation. Previous studies have determined that hematoidin is composed, in part, of a bilirubin-like pigment. In a previous study (Papadimitriou and Drachenberg, Ultrastruct. Pathol. 16, 413-421, 1992), we demonstrated that giant cell asteroid bodies (AB) are formed by membrane lipid bilayers. We evaluated three cases in which HC developed within splenic infarcts. The crystals were analyzed by light microscopy (LM), electron microscopy (EM), and X-ray microanalysis. A case of sarcoidosis with multiple epithelioid granulomas containing AB was studied for comparison. By LM the HC demonstrated intense, golden-color, fine threads, both intracellularly and extracellularly, in small and large clusters, and in radiating, star-shape patterns ranging in size from 2 to 200 microm. By EM the HC were composed of a core of empty clefts, consistent with dissolved lipids, suggestive of cholesterol crystals, and were surrounded by myelinoid membrane aggregates. The AB showed by LM significant morphological similarities with the intracellular HC. By EM, the AB were composed of a core of dense phospholipid bilayer tubes surrounded by a halo of myelinoid membranes. No accumulation of specific elements was found in either HC or AB by X-ray microanalysis. HC and AB show a similar star-shape morphology by both LM and EM. We postulate that this shape is due to the physicochemical properties of the accumulated lipids which originate from superfluous cell membranes created during cell fusion in the case of AB and after cellular (predominantly red cell) breakdown in the case of HC. The golden color of the HC likely results from adsorption of hydrophobic bilirubin-like pigments left over from erythrocyte breakdown into the accumulated lipids. Thus, this study shows two different (patho)physiological processes that lead to a markedly similar morphological end-product and provides further support to our proposed mechanism for AB formation.

Bilirubin↗
PubMed2001

Pulmonary toxicity syndrome following CDEP (cyclophosphamide, dexamethasone, etoposide, cisplatin) chemotherapy.

We report on three patients with multiple myeloma who developed drug-induced pneumonitis 1-2(1/2) months following maintenance (post autologous transplantation) chemotherapy with CDEP (cyclophosphamide, dexamethasone, etoposide, cisplatin) and 6-20 months after exposure to carmustine (BCNU) 300 mg/m(2), used in combination with melphalan 140 mg/m(2), as pre-transplant conditioning regimen. All patients had either a proven (two) or suspected (one) fungal pneumonia and were treated with liposomal amphotericin B. Dyspnea, fever and cough were the prominent clinical symptoms, while air-space disease with ground glass appearance was seen radiographically. Histologic features typical for drug-induced lung injury were detected. All patients had a dramatic, clinical and radiographic response to a brief course of corticosteroids. Although CDEP-induced pneumonitis appears to be a rare complication, its early recognition and prompt treatment, as well as its possible association with preceding fungal infection may have important clinical implications.

Aged↗
PubMed2001

Control of the epidermal growth factor receptor and its ligands during renal injury.

AIM: We studied control of the epidermal growth factor (EGF) receptor and its ligands during kidney injury, since they may be importantly involved in repair. METHODS: The folic acid model of renal injury was used in these studies. Messenger RNA (mRNA) was evaluated by solution hybridization. Immunohistochemistry of transforming growth factor alpha (TGF-alpha) was also performed. RESULTS: Twenty-four hours after folic acid induced acute renal injury, creatinine increased from 0.3 +/- 0.03 mg/dl in controls to 2.0 +/- 0.8 mg/dl in folic acid injured kidneys (n = 4, p < 0.03). mRNA for the EGF receptor was increased nearly sevenfold by 24 h, and mRNA for the receptor was increased as early as 1 h following folic acid treatment. EGF receptor ligand caused a profound downregulation of the receptors in proximal tubule basolateral membranes, but receptors returned rapidly to the membrane surface in injured kidneys. The mRNA levels for heparin-binding EGF and TGF-alpha, two EGF receptor ligands, increased within 1 h of injury. TGF-alpha mRNA increased from 1.0 +/- 0.09 (relative densitometry units) in control animals to 2.9 +/- 0.13 in folic acid treated rats at 24 h (n = 4, p < 0.01), and immunohistochemical staining for TGF-alpha increased in injured kidneys at distal nephron sites. CONCLUSIONS: These studies indicate that upregulation of the EGF receptor is related to an increase in mRNA. The rapid return of receptors to the membrane surface following ligand stimulation may be useful in maintaining a mitogenic stimulus. Multiple EGF-like ligands may be important in activating the upregulated EGF receptor during repair from renal injury.

Acute Disease↗
PubMed2001

Computerized image analysis of p53 and proliferating cell nuclear antigen expression in benign, hyperplastic, and malignant endometrium.

CONTEXT: The endometrium is an intrinsically dynamic tissue with great capability for regeneration and proliferation; consequently, there is some overlap between features seen in benign, premalignant, and malignant lesions. This leads to marked intrabiopsy, interbiopsy, and interobserver variability. OBJECTIVE: We studied the specificity and sensitivity of computerized image analysis of molecular markers to evaluate its potential use as a diagnostic tool. DESIGN: Specimens from 100 patients were examined and the following histologic diagnoses were assigned: proliferative endometrium (n = 10), secretory endometrium (n = 10), endometrial hyperplasia (n = 40; 30 with no atypia, 10 with atypia), and carcinoma (n = 40; 20 endometrioid, 10 serous, and 10 clear cell). All cases were evaluated immunohistochemically for p53 and proliferating cell nuclear antigen (PCNA) expression. Computerized image analysis was performed with a CAS 200 digital analyzer. RESULTS: Expression of p53 was found only in carcinomas (65%) and endometrial hyperplasia with atypia (30%). Expression of p53 was higher in the poor prognostic categories (serous carcinoma and clear cell carcinoma) than in endometrioid carcinoma. In endometrioid carcinoma, p53 expression correlated with grade. Proliferating cell nuclear antigen showed a similar pattern of results to p53 in the various carcinoma subtypes and endometrioid carcinoma grades. Endometrial hyperplasia PCNA values were the lowest among all the groups. Both carcinomas and proliferative endometrium showed higher glandular and stromal PCNA values, significantly different from endometrial hyperplasia with atypia. In proliferative endometrium, stromal PCNA was the highest among all of the groups. The p53 and PCNA results correlated with each other for carcinoma. CONCLUSIONS: Computerized image analysis correlates well with the established morphologic groups of endometrial pathology and yields results consistent with previous studies. Owing to its higher degree of sensitivity, computerized image analysis is of potential use in cases of diagnostic dilemmas and can help objectively allocate the case in the correct category (e.g., proliferative endometrium vs. endometrial hyperplasia, endometrial hyperplasia with atypia vs. endometrioid carcinoma). It is particularly useful in the evaluation of stromal changes.

Carcinoma↗
PubMed2001

Spontaneous formation of germinal centers in autoimmune mice.

The mechanisms of autoantibody production are not well understood. Germinal centers (GC) may be important sites of immune disregulation in autoimmune diseases. In this study, we document the presence of spontaneous GC formation in the spleens of several autoimmune mouse strains that spontaneously develop autoimmune Type I diabetes and a lupus-like disease. In contrast, mouse strains that do not develop lupus did not exhibit spontaneous formation of GC. In all of the autoimmune strains studied, GC were present at 1-2 months of age, a time that closely parallels the appearance of autoantibodies. Like the GC that develop after purposeful immunization, GC in autoimmune mice contained B220(+), PNA(+), and GL-7(+) B cells, and FDC-M1(+) follicular dendritic cells. In addition, spontaneously formed GC in autoimmunity and those caused by immunization were abrogated in a similar way by a short-term treatment with anti-CD40 ligand antibody. These data indicate that spontaneously forming GC in autoimmunity are similar to those appearing after purposeful immunization.

Animals↗
PubMed2001

Morphological spectrum of polyoma virus disease in renal allografts: diagnostic accuracy of urine cytology.

The morphological features of polyoma virus disease (PVDz) in 571 concurrent urine and biopsy samples from 413 patients are described. In 54 patients PV was found in both biopsy and urine samples. Histologically, PV presented as: (a) mild, viral cytopathic/cytolytic changes, with absent or minimal inflammation involving isolated tubules; (b) moderate and severe, cytopathic/cytolytic changes associated with patchy or diffuse tubulo-interstitial inflammation and atrophy; (c) advanced, graft sclerosis with rare or absent viral cytopathic changes, indistinguishable from chronic allograft nephropathy. Histological progression from mild to moderate or severe disease was seen in 28 patients. The mean post-transplantation time at diagnosis was similar in patients with mild or moderate-severe renal involvement (1.05 and 1.3 years, respectively). All patients presented with similarly increased values of serum creatinine (mean 1.35 mg/dL). There was strong correlation between the number of PV infected cells in urine and the concurrent biopsies (p = 0.0001). In 13 patients PV was found only in urine; of these, two developed PVDz later. The positive predictive value of a positive urine was 90%, the negative predictive value of a negative urine was 99% and the accuracy of the test was 97%. We conclude that urine cytology is useful to evaluate renal transplant patients with PV reactivation because sloughed tubular cells are found in urine and positive urine samples are a consistent manifestation of PV renal involvement.

Atrophy↗
PubMed2000

CMV allograft pancreatitis: diagnosis, treatment, and histological features.

BACKGROUND: Cytomegalovirus (CMV) infection is a common problem in solid organ transplant recipients. CMV infection of pancreas allografts is not, however, well described. METHODS: We report the clinical presentation, histologic findings, treatment, and outcome in four patients with CMV allograft pancreatitis. These patients presented 18 weeks to 44 months after transplantation with elevated serum amylase and lipase and were suspected to have acute rejection. Percutaneous pancreas allograft biopsy specimens showed evidence of tissue invasive CMV infection. One patient had simultaneous CMV infection and acute rejection. RESULTS: Prolonged treatment with ganciclovir resulted in clinical and histologic resolution of the CMV disease. Rejection was successfully treated. Primary CMV infection in seronegative recipients seemed to be a risk factor. Three patients maintain normal allograft function; one patient lost function due to chronic rejection. The histology of tissue-invasive CMV pancreas allograft infection and its differentiation from acute rejection is described. CONCLUSION: Prompt diagnosis and prolonged therapy with antiviral agents can result in maintenance of allograft function.

Adult↗
PubMed2000

Secondary amenorrhea and infertility caused by an inhibin-B-producing ovarian fibrothecoma.

OBJECTIVE: To report a case of secondary amenorrhea and infertility caused by an inhibin-B-producing ovarian fibrothecoma. DESIGN: Case report. SETTING: Academic medical center. PATIENT: A 37-year-old woman with a 2-year history of secondary amenorrhea and infertility. INTERVENTION(S): Operative removal of a 5-cm ovarian fibrothecoma. MAIN OUTCOME MEASURE(S): Luteinizing hormone, FSH, E2, inhibin-B, TSH, and prolactin measured preoperatively and postoperatively. Immunostaining of tumor cells for inhibin and LH. RESULT(S): Preoperative hormone levels were as follows: FSH, 1.7 mIU/mL; LH, 23.4 mIU/mL; E2, 31 pg/mL; and inhibin B, 1,154 pg/mL. Three weeks postoperatively, the FSH was 1.5 mIU/mL, LH decreased to 7.1 mIU/mL, E2 increased to 276 pg/mL, and inhibin-B decreased to 17 pg/mL. The fibrothecoma did not stain for LH but was strongly positive for inhibin. Regular menstrual cycles resumed 28 days postoperatively. CONCLUSION(S): Inhibin-B produced by an ovarian tumor profoundly suppressed FSH levels and resulted in secondary amenorrhea and infertility. Use of sensitive and specific immunoassays for inhibin-A and -B may aid in the differential diagnosis of hormonally active ovarian tumors.

Adult↗