Biomedical subjects

J C Manivel

Publications and source records attributed to J C Manivel.

At least 37 records · Page 2Linked to original sources

PubMed1996

Posttransplant T-cell lymphoproliferative disorders--an aggressive, late complication of solid-organ transplantation.

T-cell non-Hodgkin's lymphomas are an uncommon occurrence after solid-organ transplantation. We describe a morphologically and immunophenotypically distinct group of T-cell lymphoproliferative disorders that occurred late in the course of six patients with solid-organ transplants. The patients ranged in age from 31 to 56 years (median, 43). Three were male; all were splenectomized. The interval from transplant to the diagnosis of lymphoma ranged from 4 to 26 years (median, 15). Symptoms at presentation were related to sites of involvement. Pulmonary, marrow, and CNS involvement were present in five, four, and one case, respectively. No patient had lymphadenopathy. Five patients had an elevated lactate dehydrogenase level (range, 226 to 4,880 IU/L; median, 1,220 IU/L). Five of six patients had a leukoerythroblastic reaction. All cases had large-cell histology and frequently contained cytoplasmic granules. Those cases tested expressed CD2, CD3, and CD8 and were negative for B-cell antigens. T-cell receptor beta- and gamma-chain genes were clonally rearranged in three of three and one of three cases, respectively. All T-cell posttransplant lymphoproliferative disorders (T-PTLDs) studied were negative for Epstein-Barr virus (EBV), human T-cell leukemia/lymphoma virus type 1 (HTLV-1), human T-cell leukemia/lymphoma virus type 2 (HTLV-2), and human herpes virus type 8 (HHV-8) genomes. Treatment with acyclovir (three patients) or chemotherapy (three patients) resulted in two responses. All patients had an aggressive course, with a median survival duration of 5 weeks. In conclusion, a clinically aggressive T-PTLD may be a late complication of solid-organ transplantation and does not appear to be related to EBV, HTLV-1, HTLV-2, or HHV-8 infection.

Adult↗

PubMed1996

Phenotypical and functional characterization of intrahepatic bile duct cells from common duct ligated mice.

Bile duct cells (BDCs), especially intrahepatic cholangiocytes, are primary targets of immune-related injury in such pathologic processes as liver graft rejection, liver graft-versus-host disease, and primary sclerosing cholangitis. Cholestasis and progressive loss of intrahepatic BDCs indicate chronicity in these diseases. The present investigation characterizes the acquisition of immune markers of intrahepatic BDCs isolated from mice after bile duct ligation. Purified BDCs from cholestatic C57BL/6 (H-2b) mice express not only the major histocompatibility complex (MHC) class I and class II antigens but also the costimulatory molecules B7-1 (CD80) and B7-2 (CD86). The expression of the MHC class II molecules on BDCs before and after interferon (IFN)-gamma exposure is also demonstrated by immunohistochemistry on the cultured cells. Cytotoxicity assays indicate the vulnerability of these cells as targets for immunologic injuries. Effector cells generated from B10.BR splenocytes (H-2k) against C57BL/6 splenocytes (H-2b) show comparable killing of BDCs and EL4 cells, the latter being a lymphoma line that was established from the C57BL/6N (H-2b) mouse. An immortalized mouse BDC line (IBDC) is included in this study to validate some of the findings from BDCs isolated from bile duct-ligated mice. We suggest that cholestatic BDCs express surface antigens different from those of normal epithelial cells that result in increased susceptibility to damage by immune mechanisms.

Animals↗

PubMed1996

Synchronous bilateral Wilms' tumor in a neonate.

OBJECTIVES: Wilms' tumor is the most common solid abdominal tumor of childhood. Wilms' tumor is extremely rare in the neonate, with less than 20 well-documented cases. No bilateral lesions in neonates have been described in the literature. METHODS: We report on a neonate who presented with synchronous bilateral Wilms' tumors. RESULTS: Child underwent bilateral partial nephrectomy, followed by standard chemotherapy, and is now well 2 years after completion of the therapy without any evidence for recurrent disease. CONCLUSIONS: Wilms' tumor should be included in the differential diagnosis of the solid renal mass in the neonate.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

Hematuria in a newborn infant caused by bladder hemangioma.

A newborn boy had gross hematuria caused by hemangiomas of the bladder. The sonographic examination and the voiding cystourethrogram showed an irregular and thick bladder wall with a lesion extending into the vesical lumen. Cystoscopic examination and biopsy of the lesions were diagnostic of hemangioma. Immediately after lesion fulguration, the hematuria disappeared, and 3 weeks later the follow-up ultrasound examination showed resolution of the lesion. At 1 year, the patient's urinalysis and ultrasound scan were normal. To our knowledge, this is the first reported case of hematuria in a newborn caused by a bleeding hemangioma of the bladder.

Hemangioma↗

PubMed1996

Epithelioid leiomyoma of the oral mucosa.

Oral leiomyomas are rare because of the paucity of smooth muscle in the mouth. The solid and vascular types are the most frequent variants. The purpose of this article is to present the pathologic features and differential diagnosis of an example of epithelioid leiomyoma. A 50-year-old woman presented with a small raised nonpainful polypoid lesion of unknown duration on the right buccal mucosa. The tumor was well demarcated and consisted of large epithelioid cells with distinct cytoplasmic borders, round to oval nuclei, and prominent nucleoli. A few mitoses (4 in 20 high power fields) were present. Scattered spindle cells were also seen. The cytoplasm was eosinophilic to amphophilic and showed frequent clearing and retraction. Small capillaries were identified and surrounded by neoplastic cells that gave the lesion an angiomyomatous appearance. Masson trichrome stain highlighted focally smooth muscle cells. Immunohistochemical evaluation revealed staining for vimentin, desmin, and muscle-specific actim.

Diagnosis, Differential↗

PubMed1996

Concurrent Epstein-Barr virus associated non-Hodgkin lymphoma and recurrent Hodgkin disease.

PURPOSE: Patients treated for Hodgkin disease (HD) are at increased risk for developing secondary neoplasms, including non-Hodgkin lymphoma (NHL). We present a patient who developed NHL (brain and lungs) as a second malignancy together with recurrent HD (bone marrow). Because HD and NHL have both been associated with Epstein-Barr virus (EBV), especially in the immunodeficient host, the tumor specimens were studied for the presence of EBV, and the possible role of immunodeficiency in the development of this second malignancy was assessed. METHODS AND RESULTS: Tumor specimens were analyzed by conventional histologic and immunohistochemical methods, EBV detection was determined by RNA in situ hybridization for EBV- encoded RNAs (EBERs). Histopathology showed diffuse large cell lymphoma of B-cell phenotype in specimens from lesions in the brain and lungs. These specimens were EBER+. HD specimens from all recurrences were evaluated and were EBER. CONCLUSIONS: This patient had received extensive chemoradiotherapy for recurrent HD, and presented with Pneumocystis pneumonia, a low absolute T-cell count, no response to mitogens in vitro, a second malignancy (EBV+NHL), and recurrent EBV-HD. We propose that the immunocompromised state of the patient played a significant role in the development of his second malignancy.

Child↗

PubMed1996

Cyclophosphamide associated bladder cancer--a highly aggressive disease: analysis of 12 cases.

PURPOSE: We gained knowledge of the etiology, treatment and prevention of cyclophosphamide associated urothelial cancer. MATERIALS AND METHODS: The medical records of 6 men and 6 women (mean age 55 years) with cyclophosphamide associated bladder cancer were reviewed. RESULTS: All tumors were grade 3 or 4 transitional cell carcinoma. Of the 5 patients initially treated with endoscopic resection alone only 1 is alive without disease. Of the 6 patients who underwent early cystectomy 4 were alive at 24 to 111 months. The remaining patient with extensive cancer underwent partial cystectomy for palliation and died 3 months later. CONCLUSIONS: Cyclophosphamide associated bladder tumor is an aggressive disease. However, long-term survival is possible when radical cystectomy is performed for bladder tumors with any sign of invasion and for recurrent high grade disease, even when noninvasive.

Adult↗

PubMed1995

Chronic renal allograft rejection in the first 6 months posttransplant.

Between May 1, 1986 and May 31, 1992 at the University of Minnesota, we interpreted 129 renal allograft biopsy specimens (done in 48 grafts during the first 6 months posttransplant) as showing changes consistent with chronic rejection. For this retrospective analysis, we reexamined these biopsies together with clinical information to determine: (a) whether a diagnosis other than chronic rejection would have been more appropriate, (b) how early posttransplant any chronic rejection changes occurred, and (c) if the diagnosis correlated with outcome. We found that (1) chronic rejection is uncommon in the first 6 months posttransplant; it was documented in only 27 (2.4%) of 1117 renal allografts and was preceded by acute rejection in all but 3 recipients (for these 3, the first biopsy specimen showed both acute and chronic rejection). (2) Chronic vascular rejection was seen in 1 recipient as early as 1 month posttransplant; the incidence increased over time and was associated with an actual graft survival rate of only 35%. (3) The most frequent cause of arterial intimal fibrosis in the first 6 months posttransplant was arteriosclerotic nephrosclerosis (ASNS) of donor origin. Long-term graft function for recipients with ASNS was 67%. (4) Early-onset ischemia or thrombosis was seen in 14 recipients and predicted poor outcome: only 35.7% of these recipients had long-term graft function. (5) Cyclosporine (CsA) toxicity was implicated in only 3 recipients, who had mild diffuse interstitial fibrosis in association with elevated CsA levels. Other variables (including systemic hypertension, urinary tract infection, obstructive uropathy, neurogenic bladder, cobalt therapy, and recurrent disease) were not significantly associated with chronic renal lesions in the first 6 months posttransplant. A significant number of biopsies were originally interpreted as showing chronic rejection, but the diagnosis was changed upon reevaluation in conjunction with clinical data. We conclude that many factors coexist to produce chronic lesions in biopsies during the first 6 months posttransplant, so clinical correlation is needed before establishing a diagnosis of chronic rejection.

Adolescent↗

PubMed1995

Glomerular disease and lung transplantation.

Three patients with lung or heart/lung transplants developed nephrotic-range proteinuria 2 to 5 years posttransplantation. Kidney biopsy showed focal segmental glomerulosclerosis in two patients and probable focal sclerosis in the third. A retrospective review of postmortem kidney specimens from 18 lung transplant recipients who died did not indicate additional cases of glomerular disease. The three patients with glomerular disease after lung transplantation had very few clinical similarities other than nephrotic-range proteinuria and lung transplantation. Their underlying lung diseases were different, and their posttransplantation courses were very different in terms of pulmonary function, cyclosporine nephrotoxicity, and other complications. We did not find in the literature previous reports of de novo focal segmental glomerulosclerosis or other glomerular lesions after lung transplantation. We suspect that additional cases will be identified in the future.

Child↗

PubMed1995

Effect of seromuscular colocystoplasty lined with urothelium and partial detrusorectomy on a new canine model of reduced bladder capacity.

We developed a canine model of reduced bladder capacity by spraying talc on the outer surface of the detrusor after peeling the peritoneum from the bladder. This method was effective to reduce bladder capacity to almost a third of normal and this reduction persisted for the 6-month followup. On this model we performed detrusorectomy (auto-augmentation) and seromuscular colocystoplasty, and compared the results. Following detrusorectomy in talc bladder dogs bladder capacity failed to increase significantly at 3 months and 6 months. In contrast, seromuscular colocystoplasty caused a significant increase in bladder capacity in talc bladder dogs that was sustained for the 6-month followup. We also performed detrusorectomy in dogs with normal bladders and observed a progressive decrease in bladder capacity, which became significant at 6 months. Histology of the bladders after sacrifice revealed that talc induces a desmoplastic reaction around the detrusor that limits bladder distensibility and reduces its capacity. With detrusorectomy the perivesical fibrotic layer induced by talc and the detrusor were effectively removed but a thin layer of fibrosis developed between the bladder mucosa and the peritoneum that may account for the lack of improvement in bladder capacity. Identical observations were made after detrusorectomy in normal bladders. In contrast, following seromuscular colocystoplasty the bladder mucosa was adjacent to the submucosa of the colonic patch without fibrosis, a finding that may account for the restoration of bladder capacity. These experiments confirm previous experimental and clinical observations about seromuscular colocystoplasty, and suggest that it may result in better long-term results than simple auto-augmentation.

Animals↗

PubMed1995

Clusterin promotes the aggregation and adhesion of renal porcine epithelial cells.

The function of clusterin, a heterodimeric glycoprotein markedly induced in renal and other organ injuries, is unclear. Since renal injury is accompanied by alterations in cell attachment, it is possible that clusterin functions to promote cell-cell and cell-substratum interactions. In this study, a single cell suspension of renal epithelial (LLC-PK1) cells was treated with purified human clusterin, resulting in time- and dose-dependent cell aggregation. Electron microscopy of the cell aggregates demonstrated cell junction and lumen formation. To determine the effect of clusterin on cell adhesion, tissue culture plates were coated with clusterin, fibronectin, PBS, or albumin. Clusterin and fibronectin promoted cell adhesion to the same extent. The adhesion to clusterin was dose dependent and specific, as a monoclonal antibody against clusterin inhibited cell adhesion to clusterin but not fibronectin. Perterbations of the cytoskeleton may underlie the alterations in cell attachment which occur in renal injury. Induction of clusterin mRNA was seen after disruption of both microtubules and microfilaments and after inhibition of cell-substratum interactions. In conclusion, clusterin is a potent renal epithelial cell aggregation and adhesion molecule. We speculate that clusterin functions to promote cell-cell and cell-substratum interactions which are perturbed in the setting of renal injury, thereby preserving the integrity of the renal epithelial barrier.

Animals↗

PubMed1995

Microcystic adnexal carcinoma: management options based on long-term follow-up.

Microcystic adnexal carcinoma (MAC), a recently described neoplasm that frequently affects the head and neck, presents a confusing problem for the clinician due to its unusual behavior. The individual cells have a bland microscopic appearance, and there is a predilection for neural invasion. Four cases of MAC are reported. All four cases demonstrate the difficulty with pathologic diagnosis. Follow-up of as long as 33 years begins to delineate the protracted nature of MAC. In addition, this paper includes the first report of a case of lymph node metastasis. Although resection may result in a significant defect, negative margins may not be achieved. Despite this, the defect can heal, as demonstrated by the cases described. In addition, MAC may recur many years later, irrespective of the status of the margins at the time of surgery. Given these unusual characteristics and the slowly progressive nature of MAC, strong consideration must be given to less radical surgical procedures, with close follow-up for grossly recurrent disease.

Aged↗

PubMed1995

Genesis of renal cysts is associated with clusterin expression in experimental cystic disease.

Phenol II is a cystogenic chemical that rapidly induces renal cysts, which regress after drug withdrawal. Cyst formation in this model parallels changes in the tubular basement membrane. Clusterin is a potent cohesive factor induced in states of tissue remodeling. The purpose of this study was to determine if renal clusterin was increased in the Phenol II model and to define the time course and distribution of its induction. Male Sprague-Dawley rats were given, by daily gavage, Phenol II (1.2 mg/kg per day) or vehicle (control). The kidneys were harvested after 1, 2, or 4 days of Phenol II treatment or 3 or 7 days after drug withdrawal. An increase in immunoreactive clusterin was seen in the kidneys of Phenol II-treated rats but not in controls. The appearance of clusterin followed a time course similar to that for cyst formation, with expression confined to the epithelial lining and intratubular casts of dilated or cystic tubules. After Phenol II withdrawal, renal cysts regressed and clusterin staining disappeared. The development of cysts was associated with an increase in clusterin mRNA that decreased after drug withdrawal. In conclusion, a marked, yet reversible induction of clusterin occurred in chemically induced polycystic kidney disease. The function of clusterin in this setting remains enigmatic.

Animals↗

PubMed1995

Epidermal growth factor receptor and transforming growth factor alpha expression in papillary and nonpapillary renal cell carcinoma: correlation with metastatic behavior and prognosis.

Papillary renal carcinomas are a cytogenetically unique subset of renal carcinomas that have been reported to be clinically less aggressive. We have examined 19 papillary tumors for immunohistochemical expression of the epidermal growth factor receptor (EGF-R) and its ligand, transforming growth factor alpha (TGF-alpha). EGF-R and TGF-alpha expression was also studied in 149 nonpapillary tumors and 7 mixed papillary/solid tumors. EGF-R and TGF-alpha expression were compared to histology, stage, metastatic behavior, and survival. Formalin-fixed, paraffin-embedded nephrectomy specimens collected between 1977 and 1986 were stained with antibodies to EGF-R and TGF-alpha. Patients with papillary tumors were found to present with earlier stage disease and had significantly longer survival. Papillary tumors had a significantly lower rate of EGF-R positivity than solid pattern tumors (21% versus 73%, P < 0.001). Intermediate or strong cell membrane immunoreactivity for EGF-R was associated with high tumor grade and poor disease-specific survival. EGF-R positivity in the primary tumor was associated with the presence of metastatic disease and with metastatic spread to lung versus bone. Tumor parenchymal TGF-alpha staining was present in 50% of the cases and was not associated with stage or grade. Unrelated to tumor parenchymal TGF staining, tumor vessels stained for TGF-alpha in 56% of the cases. Vessel TGF-alpha staining was absent in papillary tumors (P < 0.001). The improved clinical behavior of papillary tumors as compared to nonpapillary renal tumors may be related, in part, to their relatively lower levels of EGF-R expression.

Adult↗

PubMed1994

Association of immunohistochemical staining for p53 with metastatic progression and poor survival in patients with renal cell carcinoma.

BACKGROUND: Mutations of the p53 gene have been found in many types of human tumors. In some tumors, p53 gene mutations are associated with advanced disease and poor prognosis. There is wide variation in the reported incidence of p53 mutation in renal cell carcinoma, and its prognostic significance for this tumor is unknown. PURPOSE: This retrospective immunohistochemical study was designed to examine associations between p53 immunostaining and histologic type, tumor grade, clinical behavior, and survival. METHODS: Paraffin-embedded nephrectomy specimens collected from 1978 through 1986 from 175 patients were immunostained for p53 using the D07 monoclonal antibody. Positive staining for p53 has been linked to the accumulation of mutant p53 protein. Thirteen specimens of concurrent metastatic lesions were available from 11 primary cases. Clinical follow-up information was available on 164 patients. RESULTS: Immunostaining for p53 suggested the presence of p53 mutation in 49 (28%) of 175 renal tumors studied. Staining was associated with high tumor grade and stage but not with cell type or histologic pattern. Eleven (85%) of 13 metastatic lesions stained positively for p53, versus only four (36%) of the 11 paired primary tumors. Immunostaining for p53 was strongly associated with poor survival among patients without distant metastases at presentation. In this group, 10-year disease-specific survival was 78% for patients with nonstaining tumors versus 48% for those with p53-positive tumors (P < or = .003). There was an 87% 10-year disease-specific survival rate for patients with nonstaining Robson stage 1 tumors versus a 62% 10-year survival rate for patients with p53-positive Robson stage 1 tumors (P < .01). Multivariate analysis showed p53 immunoreactivity to be an independent predictor of survival for patients with nonmetastatic renal cell carcinoma, whereas tumor grade was not. CONCLUSIONS: Positive p53 immunostaining in renal cell carcinoma is associated with metastatic disease and poor survival in patients with early-stage disease. IMPLICATIONS: In renal cell carcinoma, mutations of the p53 gene may allow or contribute to the acquisition of metastatic potential.

Adult↗

PubMed1994

Pilomatrix carcinoma. A case report with immunohistochemical findings, flow cytometric comparison with benign pilomatrixoma and review of the literature.

We report a case of pilomatrix carcinoma in a 42 year old woman. The patient presented a rapidly growing 4-cm subcutaneous mass in the right preauricular area. She was free of recurrence 24 months after surgery. Immunoreactivity was studied for cytokeratins, epithelial membrane antigen, S-100 protein, blood group antigens, Leu-M1, beta-2-microglobulin, vimentin, neuron-specific-enolase and cellular binding for peanut agglutinin. Squamous cells were reactive for cytokeratin AE1/3, epithelial membrane antigen, blood group antigens B and H, and peanut agglutinin. Basaloid cells were focally reactive for cytokeratin AE1/3 and epithelial membrane antigen. Flow cytometry revealed a euploid DNA content and a high proliferative rate of the pilomatrix carcinoma and in benign pilomatrixoma studied for comparison. The pathological diagnosis must be based on histomorphological criteria.

Adult↗

PubMed1994

Diagnostic difficulties in the interpretation of needle aspiration material from large renal cysts.

In recent years, fine-needle-aspiration biopsies (FNA) have been widely used in the evaluation of renal masses, with false-positive FNA data being very uncommon. We present a case report of a 76-yr-old man with a 16-cm renal cyst and what was interpreted as an isolated calcified mural nodule. Following drainage of the main cyst fluid, FNA biopsy showed atypical cell clusters thought to be positive for malignancy. Subsequent surgery failed to disclose either a residual mural nodule or evidence of malignancy. Immunoperoxidase studies performed on both the cell block and actual cyst wall suggested that the abnormal cells were histiocytes. The diagnostic pitfalls of this case, along with a review of pertinent literature, are discussed.

Aged↗

PubMed1994

Clinical characteristics of post-transplant lymphoproliferative disorders.

PURPOSE: To study the histopathologic findings, clinical course, and therapeutic outcome of patients who developed a lymphoproliferative disorder after undergoing solid organ transplantation. PATIENTS AND METHODS: A series of 26 patients who developed a lymphoproliferative disorder after solid organ transplant during a 27-year period were studied. RESULTS: The 26 patients ranged in age from 6 to 68 years (median 42 years). The lymphoproliferative disorder was diagnosed from 1 to 211 months (median 80 months) after transplantation. The type of transplant was kidney (n = 21), heart or heart-lung (n = 4), or liver (n = 1). Most patients received azathioprine and prednisone, in addition to antilymphocyte globulin or cyclosporine, for post-transplant immunosuppression. Eight patients had lymphoma that could be classified according to the International Working Formulation (IWF-F, IWF-G, IWF-H). Sixteen patients had polymorphic lymphoma, and 2 patients were classified as having polymorphic lymphoid hyperplasia. Patients were staged by the Ann Arbor staging system. Nine patients had stage I disease, 4 stage II, 6 stage III, and 7 stage IV. Central nervous system, lung, or marrow involvement was present in 27%, 23%, and 14% of patients, respectively. In the 17 patients studied, immunophenotype was monoclonal B-cell (n = 12), malignant T-cell (n = 2), or polyclonal B-cell (n = 3). The initial therapeutic approach was generally a reduction in immunosuppression, but, thereafter, the approach to therapy varied. In patients with localized disease, surgical excision and/or involved field radiotherapy were utilized as applicable. For patients with more extensive disease, other approaches such as high-dose acyclovir, combination chemotherapy, or alpha interferon were utilized. Overall, 15 of 26 patients (58%) responded to systemic therapy or were rendered disease-free either by surgery or radiation, including 8 (31%) with a complete remission (CR). Only 3 of 9 patients responded to chemotherapy, whereas 4 of 13 patients responded to acyclovir (including 3 patients who experienced CR). Remission duration ranged from 8 to 122 months (median 32+ months). Twenty-one of 26 patients (81%) have died. Survival ranged from less than 1 to 122 months (median 14 months). CONCLUSION: The outcome of patients with post-solid organ transplant lymphoproliferative disorders is poor, and the optimal approach to therapy is not clear. Newer therapeutic approaches are thus needed to improve the outcome of these patients.

Adolescent↗