In situ immunodetection of neuronal caspase-3 activation in Alzheimer disease.

The mechanism by which cells die in Alzheimer disease (AD) is unknown. Several investigators speculate that much of the cell loss may be due to apoptosis, a highly regulated form of programmed cell death. Caspase-3 is a critical effector of neuronal apoptosis and may be inappropriately activated in AD. To address this possibility, we examined cortical and hippocampal brain sections from AD patients, as well as 2 animal models of AD, for in situ evidence of caspase-3 activation. We report here that senile plaques and neurofibrillary tangles in the AD brain are not associated with caspase-3 activation. Furthermore, amyloid beta (A beta) deposition in the APPsw transgenic mouse model of AD does not result in caspase-3 activation despite the ability of A beta to induce caspase-3 activation and neuronal apoptosis in vitro. AD brain sections do, however, exhibit caspase-3 activation in hippocampal neurons undergoing granulovacuolar degeneration. Our data suggests that caspase-3 does not have a significant role in the widespread neuronal cell death that occurs in AD, but may contribute to the specific loss of hippocampal neurons involved in learning and memory.

Enzyme-based antigen localization and quantitation in cell and tissue samples (Midwestern assay).

Quantitation of antigen concentration in cell and tissue samples typically requires antigen extraction, which precludes antigen localization in the same sample. Similarly, antigen immunolocalization in fixed cells or tissue sections provides limited information about antigen concentration. We have developed a rapid and sensitive assay for simultaneous antigen localization and quantitation in cell and tissue samples that does not involve antigen extraction, radioactive materials, or image analysis. Fixed cells and/or tissue sections are used with antigen-specific enzyme-linked probes to generate soluble reaction products that are spectrophotometrically quantifiable and deposited reaction products that are microscopically localizable. The amount of soluble reaction product is dependent on several variables, including antigen concentration, probe specificity and sensitivity, sample size, and enzyme reaction time. These variables can be experimentally controlled so that soluble reaction product is proportional to antigen concentration in the sample. This assay was used in multiple applications including detection of Ki-67 nuclear antigen immunoreactivity in human brain tumors, in which it showed a clear relationship with visually determined Ki-67 cell labeling indexes. This assay, termed the Midwestern assay, should be applicable to a wide variety of antigens in both clinical and research samples.

Successful treatment of cerebral toxoplasmosis in a marrow transplant recipient: contribution of a PCR test in diagnosis and early detection.

We report successful treatment of cerebral toxoplasmosis in an unrelated donor marrow transplant recipient. The clinical diagnosis was confirmed by polymerase chain reaction (PCR) amplification for T. gondii-DNA performed both on cerebrospinal fluid and blood leukocytes. Retrospective testing of stored blood samples demonstrated positive leukocyte PCR signal detected up to 52 days prior to onset of clinical symptoms. This case highlights the value of PCR in the diagnosis and early detection of cerebral toxoplasmosis.

Malignant giant-cell tumor of the parietal bone: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Giant-cell tumors (GCTs) are primary bone tumors that involve long bones in 75 to 90% of patients. They seldom develop in the cranium and are very rare in patients older than 60 years of age. A GCT rarely occurs with Paget's disease; when it does, however, it is most commonly associated with the polyostotic form and tends to involve the craniofacial bones. Pagetic GCTs are less aggressive than GCTs that are not associated with Paget's disease. CLINICAL PRESENTATION: We report the case of an 81-year-old woman with a painless left parietal mass and asymptomatic monostotic parietal Paget's disease. INTERVENTION: Surgical resection was performed, and histological examination of the lesion demonstrated Paget's disease with a malignant GCT. An incidental, low-grade, small-cell lymphocytic lymphoma also was noted. The patient experienced local recurrence of the malignant GCT and eventually died after developing pulmonary metastases of the malignant GCT. CONCLUSION: This case is the first reported example of a patient with a malignant GCT of the cranium associated with monostotic Paget's disease. It provides evidence that not all pagetic GCTs in the cranium are benign, as has been reported.

p53: a good diagnostic marker for intratubular germ cell neoplasia, unclassified.

Intratubular germ cell neoplasia, unclassified (IGCNU) is a precursor of germ cell tumors (GCT) of the testis. In routine histologic sections, neoplastic intratubular germ cells may be very few and easily overlooked. The aim of this study is two-fold: to establish the immunohistochemical pattern of expression of p53 in IGCNU and GCT and to determine whether p53 can be used as a marker for IGCNU. Resection specimens from 14 seminomas, 14 mixed germ cell tumors (MGCT), 3 embryonal carcinomas, 2 mature teratomas, 7 IGCNUs, and 11 normal testes were stained for p53. Normal germ cells and Sertoli cells of the seminiferous tubules in all normal testes were negative for p53. The tumor cells of all IGCNU cases were positive for p53. All invasive components of mixed germ cell tumors, embryonal carcinomas, and seminomas exhibited expression of p53. Mature teratoma components were negative for p53. These findings indicate that p53 is a highly sensitive marker of IGCNU and highly specific in distinguishing lesional tissue from normal seminiferous tubules. The current findings also suggest that p53 may be involved as an early step in the malignant progression of most germ cell neoplasias.

Sagittal sinus occlusion by intraluminal dural cysts. Report of two cases.

Lesions involving the sagittal sinus typically present as masses compressing the sinus externally. The authors describe two cases of lesions entirely within the lumen of the sagittal sinus. In one of the cases, syncope was the presenting symptom and surgical resection of the cyst was performed. An entirely intraluminal cyst, consistent with a dural cyst, was resected, followed by reconstruction of the sinus and resolution of symptoms. Entirely intraluminal lesions of the sagittal sinus have rarely been reported as incidental findings. This represents the first report of symptomatic occlusion of a venous sinus by an intraluminal cyst.

Clear cell neoplasms and pseudoneoplastic lesions of the central nervous system.

Mass lesions of the central nervous system (CNS) that may assume a clear cell appearance are diverse in nature. Primary conditions in this category include oligodendroglioma, hemangioblastoma, germinoma (seminoma), clear cell and chordoid meningioma, pleomorphic xanthoastrocytoma, and lipid-rich glioblastoma. These proliferations usually can be identified by attention to clinical presentation, topographic location, radiographic details, and histological nuances. Occasionally, however, electron microscopy or immunohistological analysis may be necessary. A recommended panel of reagents for the evaluation of clear cell primary CNS lesions include antibodies to glial fibrillary acidic proteins, S-100 protein, epithelial membrane antigen, vimentin, keratins, placental-like alkaline phosphatase, and synaptophysin. This article reviews the salient clinicopathologic attributes of such proliferations, elaborates a practical approach to their diagnosis, and discusses important differential diagnostic considerations. The latter include malformative lesions, infarcts, inflammatory conditions, and secondary lymphomas, carcinomas, and melanomas.

The effect of allopurinol pretreatment on intestinal hypoperfusion encountered after correction of intestinal volvulus.

After reversal of blood flow following a prolonged period of ischemia, blood flow returns for a few seconds and is reduced afterward. This is called "no-reflow phenomenon." Antioxidants such as allopurinol have been shown to prevent the occurrence of this phenomenon in organs other than the intestine. An experimental study was conducted to investigate the effect of allopurinol pretreatment on intestinal blood flow after correction of intestinal volvulus in rabbits. In group 1, baseline intestinal blood flow (IBF) was evaluated using radiolabeled red blood cells. In group 2, 720 degrees intestinal volvulus was created and IBF was evaluated 6 hours later. In group 3, intestinal volvulus was created and devolvulus was performed 6 hours later. Intraperitoneal isotonic saline was injected 60 minutes before correction of the volvulus. IBF was evaluated after correction of the volvulus. Group 4 had the same procedures as group 3, but allopurinol (200 mg/kg) was injected in place of the isotonic saline. IBF stopped 6 hours after volvulus. Compared with the baseline group, IBF was significantly lower in the group with volvulus + devolvulus (P < .01). The IBF of the allopurinol-treated group was significantly higher than that of the isotonic saline group (P < .01) and it did not differ significantly from that of the baseline group. Histopathological examination showed that intestinal volvulus leads to histological injury. The histological injury was more pronounced in the devolvulus group and was less severe in the allopurinol group in comparison to the isotonic saline pretreatment group (P < .01). It is concluded that allopurinol pretreatment prevents the intestinal hypoperfusion (no-reflow phenomenon) and histological injury encountered after correction of intestinal volvulus of 6 hours' duration.

Dysembryoplastic neuroepithelial tumor and oligodendroglioma: the diagnostic value of magnetic resonance spectroscopy. Case report and review of the literature.

Preoperative differentiation between dysembryoplastic neuroepithelial tumor (DNT) and low-grade glioma is often not possible. Dysembryoplastic neuroepithelial tumor is a recently described entity of uncertain origin; however, the diagnosis has important clinical implications. Clinical and radiological findings of DNT and low-grade glioma, especially oligodendroglioma, may be similar. Treatment options and prognosis differ significantly between these two lesions; consequently, accurate diagnosis is imperative. The authors describe two individuals who presented simultaneously at their institution: one patient with an oligodendroglioma and a second patient with DNT. The natural history, neurodiagnostic, and pathological features of each are reviewed with special emphasis on the potential utility of magnetic resonance spectroscopy in differentiating these lesions.

Convergence insufficiency in idiopathic Parkinson's disease responsive to levodopa.

We report a patient with pathologically proven idiopathic Parkinson's disease (IPD) who developed diplopia secondary to convergence insufficiency during his motor "off" periods. Diplopia resolved with onset of motor benefit from levodopa. Neuro-ophthalmologic examination demonstrated convergence insufficiency during motor "off" periods that was alleviated after onset of motor benefit from levodopa. This is the first reported case of convergence insufficiency in IPD responsive to levodopa.

Discrimination between uterine serous papillary carcinomas and ovarian serous papillary tumours by gene expression profiling.

High-grade ovarian serous papillary cancer (OSPC) and uterine serous papillary carcinoma (USPC) represent two histologically similar malignancies characterised by markedly different biological behavior and response to chemotherapy. Understanding the molecular basis of these differences may significantly refine differential diagnosis and management, and may lead to the development of novel, more specific and more effective treatment modalities for OSPC and USPC. We used an oligonucleotide microarray with probe sets complementary to >10 000 human genes to determine whether patterns of gene expression may differentiate OSPC from USPC. Hierarchical cluster analysis of gene expression in OSPC and USPC identified 116 genes that exhibited >two-fold differences (P<0.05) and that readily distinguished OSPC from USPC. Plasminogen activator inhibitor (PAI-2) was the most highly overexpressed gene in OSPC when compared to USPC, while c-erbB2 was the most strikingly overexpressed gene in USPC when compared to OSPC. Overexpression of the c-erbB2 gene and its expression product (i.e., HER-2/neu receptor) was validated by quantitative RT-PCR as well as by flow cytometry on primary USPC and OSPC, respectively. Immunohistochemical staining of serous tumour samples from which primary OSPC and USPC cultures were derived as well as from an independent set of 20 clinical tissue samples (i.e., 10 OSPC and 10 USPC) further confirmed HER-2/neu as a novel molecular diagnostic and therapeutic marker for USPC. Gene expression fingerprints have the potential to predict the anatomical site of tumour origin and readily identify the biologically more aggressive USPC from OSPC. A therapeutic strategy targeting HER-2/neu may be beneficial in patients harbouring chemotherapy-resistant USPC.