Biomedical subjects

D J Lager

Publications and source records attributed to D J Lager.

35 records · Page 2Linked to original sources

PubMed1994

Transplant-associated thrombotic microangiopathy: the role of IgG administration as initial therapy.

Two transplant patients, one a renal-pancreas and the other a liver allograft recipient, are reported. Both developed clinical and histologic evidence of cyclosporine-associated thrombotic microangiopathy and responded favorably to intravenous IgG therapy. An additional 20 cadaveric renal transplant recipients who developed cyclosporine-associated thrombotic microangiopathy are reviewed. The clinical and laboratory presentation of posttransplant thrombotic microangiopathy varied. Elevated serum creatinine and lactic dehydrogenase (LDH) levels were the most consistent, albeit nonspecific, findings at diagnosis. Fourteen of 22 patients (64%) presented with thrombocytopenia and 19 (86%) had a hemolytic anemia verified on diagnosis. Histologic evidence of thrombotic microangiopathy was present in renal biopsies from each of the renal allograft recipients and a skin biopsy from the liver allograft recipient. Treatment included withdrawal or reduction of the cyclosporine dose, plasmapheresis, or administration of intravenous IgG. There was an overall renal allograft loss of 57%, which included five deaths. Symptomatic cytomegalovirus infection was more common than expected in this patient group (P = 0.038) and may, in combination with cyclosporine therapy, have predisposed these patients to develop clinically significant thrombotic microangiopathy. Transplant-associated microangiopathy appears to be a relatively common disorder associated with a substantial increase in early graft loss (P = 0.005) and mortality (P = 0.001).

Adult↗

PubMed1994

Expression of CD24 (BA-1) predicts monocytic lineage in acute myeloid leukemia.

Fifty-seven cases of acute myeloid leukemia (AML), which had been subtyped by French-American-British morphologic and cytochemical criteria as myeloid (M1, M2) or monocytic (M4, M5), were retrieved from the files of the Division of Hematopathology, University of Iowa. Corresponding immunophenotyping data were reviewed with attention to the expression of CD14 (MY4) and CD24 (BA-1). Of 20 cases expressing CD24, 19 were M4 or M5, whereas all 14 cases expressing CD14 were of monocyte lineage. Therefore, CD14 was a highly specific (100%) but only moderately sensitive (58%) marker for distinguishing classes M1 or M2 from M4 or M5. By contrast and unexpectedly, CD24 was nearly as specific (97%), but more sensitive (79%) in marking M4 or M5 cells. This appears to be true even though CD24 is apparently not expressed on normal monocytes. When positive staining for either or both antibodies (CD24 or CD14) was considered indicative of a monocytic leukemia, the sensitivity of immunophenotyping in distinguishing M4/M5 from M1/M2 AML rose to 92%, while maintaining 97% specificity. The authors discuss a recent observation that may help explain the unexpected expression of CD24 in monocytic AML. They conclude that the usefulness of CD24 in identifying monocytic AML may exceed that of CD14, and that the use of CD24 and CD14 in combination improves the ability of flow cytometry to distinguish myeloid from monocytic acute leukemias.

Antigens, CD↗

PubMed1994

Howell-Jolly body-like inclusions in the neutrophils of patients with acquired immunodeficiency syndrome.

The authors have observed discrete, densely basophilic inclusions in the peripheral blood neutrophils of 10 patients with acquired immunodeficiency syndrome (AIDS) and two additional patients without documented evidence of human immunodeficiency virus seropositivity. These inclusions were seen in 3 of 25 (12%) patients with AIDS in a retrospective review. Gram, periodic acid-Schiff, and Gomori methenamine silver stains failed to demonstrate staining of these bodies; however, the Feulgen reaction was positive. The inclusions may represent "apoptotic" nuclear fragments and thus may be similar to Howell-Jolly bodies of normoblasts in abnormal erythropoiesis. An association of these inclusions with nucleoside analogue antiviral therapy is indicated. These inclusions must be differentiated from intracytoplasmic infectious agents, Döhle bodies, and inclusions of inherited disorders.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Thrombomodulin expression by human keratinocytes. Induction of cofactor activity during epidermal differentiation.

Thrombomodulin is an endothelial cell surface glycoprotein that inhibits the procoagulant activities of thrombin and accelerates activation of the anticoagulant protein C. Because protein C deficiency is associated with cutaneous thrombosis, we investigated the expression of thrombomodulin in human skin. Thrombomodulin was detected by immunohistochemical staining both in dermal endothelial cells and in epidermal keratinocytes. Within the epidermis, thrombomodulin staining was limited to keratinocytes of the spinous layer, suggesting that thrombomodulin is induced when basal keratinocytes begin to terminally differentiate. Thrombomodulin expression also correlated with squamous differentiation in epidermal malignancies; little or no thrombomodulin staining was seen in five basal cell carcinomas, whereas strong thrombomodulin staining was observed in each of five squamous cell carcinomas. Human foreskin keratinocytes cultured in medium containing 0.07 mM calcium chloride synthesized functional thrombomodulin with cofactor activity comparable to thrombomodulin in human umbilical vein endothelial cells. Stimulation of keratinocyte differentiation with 1.4 mM calcium chloride for 48 h produced 3.5-, 3.2-, and 5.6-fold increases in thrombomodulin cofactor activity, antigen, and mRNA, respectively. These observations suggest that thrombin is regulated by keratinocyte thrombomodulin at sites of cutaneous injury, and indicate a potential role for thrombomodulin in epidermal differentiation.

Cell Differentiation↗

PubMed1994

Oncogene amplification screening by labeled primer multiplex polymerase chain reaction.

This paper describes an improved procedure for rapid detection of amplified genes in fresh or formalin-fixed, paraffin-embedded tissues. Utilizing a multiplex differential polymerase chain reaction with radioactively labeled primers and electrophoresis of the products through thin gels, it is possible to screen for oncogene amplification more rapidly and reproducibly than has been previously demonstrated. This procedure takes advantage of thin vertical gels with external cooling, which allows sharp band resolution. Four separate gels can be electrophoresed at the same time in a single gel box. Because each gel slab contains 10 or more lanes, 40 or more samples can be assayed for gene amplification simultaneously. The entire procedure can be carried out from formalin-fixed, paraffin-embedded tissue to finish in 8 h when combined with a sonication technique for DNA extraction.

Astrocytoma↗

PubMed1994

The expression of epidermal growth factor receptor and transforming growth factor alpha in renal cell carcinoma.

Immunohistochemical stains using antibody to epidermal growth factor receptor (EGFR) and transforming growth factor alpha (TGF-alpha) were applied to 67 cases of renal cell carcinoma retrieved from the files of the Division of Surgical Pathology. The 64 patients (33 females, 31 males) ranged in age from 35 to 87 years (mean, 61 years). Two patients had more than one renal carcinoma included in this study. Fifty-seven cases (85%) expressed EGFR, with staining largely confined to the cell membrane. Staining intensity was directly correlated with tumor grade (P = 0.02, T test), size (P = 0.04), and stage (P = 0.01). Those cases with more intense EGFR staining also appear to have shorter patient survival than those showing less intense staining (43 mo versus 63 mo, P = 0.05). Forty-nine cases (73%) expressed TGF-alpha in a distribution similar to that of EGFR. There was no significant correlation between TGF-alpha staining intensity and tumor size, stage, or grade. When the tumor expressed either EGFR or TGF-alpha but not both proteins, average patient survival was 38 months, while the average survival of those patients whose tumors expressed both EGFR and TGF-alpha was 61 months (P = 0.04). Three of eleven cases, all of which expressed EGFR, were felt to show EGFR gene amplification using a modification of the differential polymerase chain reaction on archival, formalin-fixed, paraffin-embedded tissue. EGFR and TGF-alpha likely play a role in the progression of renal cell carcinoma, and their coexpression may have favorable prognostic implications.

Adult↗

PubMed1993

Scanning electron microscopic distinction of pleural mesotheliomas from adenocarcinomas.

Cases of mesothelioma and adenocarcinoma involving pleura were examined by light and scanning electron microscopy utilizing H & E stained slides of paraffin-embedded material. Areas of interest were identified and isolated, and the coverslips were removed. The slide fragments were mounted on scanning electron microscopy stubs and coated with gold for 45 sec. Cases were examined in a blinded manner. Microvilli were readily identified by scanning electron microscopy with preservation of morphologic detail through the processing and staining steps required for light microscopy. The length and diameter of 20 microvilli were measured from each tumor. The mean length:diameter ratio for the mesotheliomas (n = 7) was 19.7:1 (range 13.7-23.5:1), and for the adenocarcinomas (n = 7), 2.5:1 (range 1.3-4.1) (P < 0.0005). Correlative transmission electron microscopy was performed on "scanned" specimens, and length:diameter ratios were generated. This technique has utility in distinguishing mesothelioma from adenocarcinoma. It is especially useful when glutaraldehyde-fixed, plastic-embedded tissue is not available for transmission electron microscopy. Additionally, scanning electron microscopy allows more extensive examination than transmission electron microscopy and is far less limited by section thickness and tangential sectioning artifact.

Adenocarcinoma↗

PubMed1993

Epstein-Barr virus detection in sequential biopsies from patients with a posttransplant lymphoproliferative disorder.

Sequential formalin-fixed, paraffin-embedded tissue biopsies from 10 patients with a posttransplant lymphoproliferative disorder (PTLD) were evaluated retrospectively for the presence of Epstein-Barr virus (EBV) DNA using the polymerase chain reaction (PCR). The patients included seven renal and two liver allograft recipients and one renal and cardiac allograft recipient. Sequential biopsies were available on every patient and pre-transplant biopsies in six patients. The EBV primers used amplify a 245-bp fragment of the EBV IR3 sequence and were run in parallel with human beta-globin gene primers. Nine patients (90%) had EBV detected during their posttransplant course: three at the time of diagnosis of the PTLD, and six from 15 to 121 days prior to diagnosis. Sites of presentation of the PTLD included liver (four), brain (two), native kidney (one), renal allograft (one), lymph node (one), and lung (one). Three patients died 61, 56, and 30 days posttransplantation, fourth at 198 days, and a fifth patient at 2 yr. All had clinical or histologic evidence of residual PTLD. In contrast, EBV DNA was detected in tissue from two of 29 "healthy" renal allograft recipients examined 2 to 16 mo posttransplantation. None of these patients has clinical evidence of a PTLD. We conclude that allograft biopsies provide a substrate for early detection of EBV by PCR, particularly when an atypical lymphoid infiltrate is encountered by light microscopy.

Adult↗

PubMed1993

Detection of Epstein-Barr virus DNA in sequential renal transplant biopsy specimens using the polymerase chain reaction. Report of a patient with a posttransplant lymphoproliferative disorder.

The polymerase chain reaction was used to retrospectively examine frozen and paraffin-embedded tissue from four sequential renal biopsy specimens, a pretransplant skin biopsy specimen, a postauricular lymph node, and an allograft nephrectomy specimen for the presence of Epstein-Barr virus (EBV) DNA in a 29-year-old man who developed diffuse lymphadenopathy 2 months after a cadaveric renal transplant. The EBV primers used amplify a 245-base pair fragment of the EBV IR3 sequence and were run in parallel with a pair of human beta-globin gene primers as positive DNA integrity controls. Epstein-Barr virus DNA was detected in three of the four renal allograft biopsy specimens, the post-auricular lymph node, and the renal allograft nephrectomy specimen. Initial detection occurred 34 days posttransplant and 23 days prior to the diagnosis of posttransplant lymphoproliferative disorder. Examination of a skin biopsy specimen obtained prior to transplantation and of the initial posttransplant renal allograft biopsy specimen 15 days posttransplant did not demonstrate EBV DNA. The findings of serologic studies performed at the time of diagnosis of the posttransplant lymphoproliferative disorder suggested a remote EBV infection. These results further demonstrate the association of EBV with posttransplant lymphoproliferative disorder and suggest a possible role for polymerase chain reaction in the early detection of EBV in transplant patients. Larger retrospective studies are needed to determine the prognostic significance of EBV DNA found in routine renal allograft biopsy specimens.

Adult↗

PubMed1991

Primary renal lymphoma.

Lymphoma arising in the kidney is rare. Although 31 cases have been reported in the literature, it is likely that most of these neoplasms do not arise in the kidney. This report describes two cases of primary renal lymphoma and compares their clinical presentation, diagnostic modalities, treatment, and survival with the previously reported patients who satisfied our criteria for the diagnosis of primary renal lymphoma.

Aged↗

PubMed1991

Renal oncocytoma: diagnostic utility of cytokeratin-containing globular filamentous bodies.

Sixty-six renal cortical epithelial tumors were classified by light and electron microscopy into 18 oncocytomas and 48 renal carcinomas, and their pattern of cytokeratin and vimentin reactivity was evaluated by immunoperoxidase using paraffin-embedded tissue. We found by electron microscopy that most oncocytomas (11 of 15) contain globular filamentous bodies that consist of a complex of intermediate filaments and organelles. These structures were found to correlate on immunohistochemistry with a discrete punctate cytoplasmic pattern of cytokeratin reactivity, provided the antibody preparation contained specificity for cytokeratins 8 and 18. A similar punctate finding was not observed in four oncocytomas nor in the 48 renal carcinomas. Although 11 oncocytomas failed to express vimentin, seven tumors showed focal reactivity restricted to rare individual cells in areas of sclerosis (five tumors) or in cell clusters bordering central scars (two tumors). We conclude that many oncocytomas contain a potentially diagnostically useful punctate pattern of cytokeratin reactivity and that focal vimentin reactively may be observed in otherwise typical oncocytomas, restricted to tumor cells appearing to be undergoing atrophy.

Adenoma↗

PubMed1991

Subdiaphragmatic extralobar pulmonary sequestration.

A 21-day-old girl presented with a left subdiaphragmatic retroperitoneal mass discovered on maternal ultrasound at 23 weeks' gestation. The clinical impression was neuroblastoma, and preoperative workup showed no for metastatic disease. Histologically, the lesion proved to be an extralobar pulmonary sequestration. We present this case to remind pathologists of the occurrence of subdiaphragmatic pulmonary sequestration and its potential clinical confusion with other more familiar lesions that may occur in this location in a neonate.

Bronchopulmonary Sequestration↗

PubMed1991

Lecithin cholesterol acyltransferase deficiency: ultrastructural examination of sequential renal biopsies.

We present the renal biopsy findings in two brothers with nephrotic syndrome and lecithin:cholesterol acyltransferase deficiency. Mesangial expansion and capillary wall thickening were accompanied by numerous extracellular osmiophilic membranes within round lucent spaces, by round lamellar deposits, and by amorphous deposits containing thread-like structures with cross-striations. A second biopsy in one of the brothers, when he had developed renal insufficiency 8 yr later, showed increased mesangial and capillary wall thickening. The deposits, which had been in predominantly subepithelial and intramembranous locations, were now in a more prominent subendothelial location. The subepithelial localization of the deposits seen on initial examination may be related to their cationic charge, perhaps with binding to glomerular polyanion, and to uptake by glomerular epithelial cells. The accumulation of lipid is associated with progressive mesangial and glomerular sclerosis.

Adolescent↗

PubMed1990

Chromophobe cell carcinoma: analysis of five cases.

Five cases of a recently characterized renal neoplasm, chromophobe cell carcinoma, encountered during an ultrastructural and DNA flow cytometric study of renal cortical neoplasms are described. These tumors usually are dark on gross examination and often are associated with focal hemorrhage or necrosis. Microscopically the tumor cell cytoplasm ranges from clear to eosinophilic, potentially eliciting a broad differential diagnosis encompassing renal cell carcinoma and oncocytoma. Ultrastructural studies disclosed the diagnostically required numerous complex cytoplasmic vesicles of unknown composition and origin, and DNA ploidy studies revealed an aneuploid cell population in three of five cases, which correlates with the malignant potential.

Adult↗

PubMed1989

Factitious microcalcifications in breast biopsy material: laboratory-induced error by use of tattoo powder for specimen mammography.

A xeromammogram led to the surgical excision of a calcified breast lesion on a 66-year-old female. Before specimen mammography was performed, the excised tissue was oriented with tattoo pigment. The specimen mammogram then revealed multiple calcifications caused by unsuspected radio-opaque material in the tattoo pigment, and the original calcifications were obscured. This case demonstrates the hazards involved utilizing tattoo powders for orienting xeromammographically discovered specimens.

Aged↗

PubMed1988

Squamous metaplasia of the prostate. An immunohistochemical study.

Immunoperoxidase strains for prostate-specific antigen (PSA), prostatic acid phosphatase (PAcP), epithelial membrane antigen (EMA), and cytokeratins (MAK 6 and CK-KES) were performed on 1 case of squamous cell carcinoma of the prostate and on 13 cases of squamous metaplasia of prostatic epithelium in an effort to demonstrate prostatic origin of the neoplastic and metaplastic cells and to differentiate them from primary or metastatic well-differentiated squamous cell carcinoma. The authors found no specific staining of the metaplastic or neoplastic cells for PSA and only focal single cell PAcP positivity in three cases of squamous metaplasia. All cases showed strong staining of surrounding normal glandular epithelium for both antigens. In all but one case, both the metaplastic and glandular epithelium had positive results for MAK 6 and CK-KES. EMA was expressed strongly in ten cases, was weak or variable in two, and had negative results in two cases of squamous metaplasia. In only four cases did the glandular epithelium have positive results for EMA. The remaining cases showed no staining. PSA and PAcP marking, therefore, may not be useful for separating atypical squamous metaplasia from well-differentiated squamous cell carcinoma or even primary prostatic from metastatic squamous cell carcinoma. These findings suggest that although prostatic glandular epithelial cells retain their ability to express some prostate-associated antigens, this ability is greatly reduced, lost, or not developed in cells that undergo metaplasia into squamous cells or that develop into squamous cell carcinoma.

Aged↗

PubMedDate not supplied

Correlative light and scanning electron microscopy of intestinal giardiasis, cryptosporidiosis, and spirochetosis.

Cases of intestinal giardiasis, spirochetosis, and cryptosporidiosis were examined by scanning electron microscopy (SEM) using hematoxylin and eosin (H&E)-stained tissue sections from which the coverslips were removed and the sections coated with gold. The technique is simple and reliably provides excellent morphologic detail that is preserved in the deparaffinized 4 microsections. We present examples of nine intestinal parasites examined in this manner and compare this technique with standard H&E staining and special stains with regard to relative costs, turnaround time, labor input, and morphologic preservation. Scanning electron microscopy is a useful adjunct in providing confirmatory evidence in the diagnosis of intestinal giardiasis, spirochetosis, and cryptosporidiosis.

Biopsy↗