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B K Kleinschmidt-DeMasters

Publications and source records attributed to B K Kleinschmidt-DeMasters.

At least 37 records · Page 2Linked to original sources
PubMed2004

Gamna-Gandy bodies in surgical neuropathology specimens: observations and a historical note.

Gamna-Gandy (G-G) bodies are classically defined as spheroidal yellow-brown foci consisting of dense fibrous tissue and collagenous fibers encrusted with iron pigments and calcium salts. These siderotic nodules were first described in the spleen early in the twentieth century and for a short time were considered to be caused by fungal infection due to the presence of unusual "bamboo-like and articulated" fibers in the lesions that vaguely mimicked mycelia forms. This notion was proven to be incorrect in the 1930s and G-G bodies are now considered to result from organization of small hemorrhages. Although originally reported in splenomegaly, G-G bodies are well-recognized findings in atrial myxomas where they form linear arrays of mineral-encrusted fibers, often at the edge of resolving hemorrhages. They rarely have been reported in lymph nodes, thymoma, thyroid adenoma, and renal cell carcinoma. Curiously, published examples of G-G bodies in central nervous system (CNS) neoplasms or vascular malformations have not appeared, despite the known tendency for bleeding, even recurrent episodes of bleeding, in several types of these lesions. Since 1999 I have accrued all the examples of G-G bodies that I have observed in my practice of surgical neuropathology. These cases are presented here and the historical aspects of the entity are reviewed.

Calcinosis↗
PubMed2003

Neoplasms involving the central nervous system in the older old.

Geriatric cancer patients present special challenges for clinicians. Few large series have been published in the last 20 years on the types of neoplasms that involve the central nervous system (CNS) in older individuals. To review types of neoplasms involving the central CNS that are currently being encountered by pathologists and neurosurgeons, we identified from our databases for the years 1992-2002, inclusive, patients 75 years or older who had symptomatic lesions requiring neurosurgical interventions. Retrospective characterization of tumors by immunohistochemistry, in situ hybridization, and fluorescence in situ hybridization was performed whenever possible and relevant to tumor type. Neurosurgical procedures (n=125) on 119 patients were identified; 90 patients were diagnosed as having neoplasms, with clot evacuation or infections being the most frequent non-neoplastic conditions necessitating surgery. Tumor types included glioblastomas (36 patients), meningiomas (16), pituitary adenomas (12), lymphomas or other hematological malignancies (8), anaplastic gliomas (5), metastases (6), head and neck malignancies with direct intracranial extension (3), and other miscellaneous tumor types (4). Compared with older literature series, we encountered a larger number of elderly patients with CNS lymphomas and fewer who came to surgery for CNS metastatic disease. In the "older old", glioblastomas are the most frequent symptomatic tumors necessitating surgical intervention. Glioblastomas in this aged cohort display the signature features of the small cell phenotype (62%), high cell cycle labeling indices (mean MIB-1-labeling index=25.1%), and either amplification of epidermal growth factor receptor or gain of chromosome 7 by fluorescence in situ hybridization (93% of assessable cases).

Age Factors↗
PubMed2003

Gliomatosis cerebri: neurobehavioral and neuropathological observations.

BACKGROUND: Gliomatosis cerebri is a rare neoplasm in which individual neoplastic cells diffusely permeate the brain; a cohesive tumor mass may appear late in the disease course, or not at all. The diagnosis can be made either at autopsy or premortem by combining biopsy and neuroimaging findings to demonstrate involvement of more than two lobes of the brain. Extensive hemispheric white matter and corpus callosum infiltration is characteristic, with lesser spread to subcortical and cortical gray matter. Whereas this pattern of localization can be predicted to cause significant disturbances of higher function, the neurobehavioral profile of gliomatosis cerebri patients has not been well described. METHOD: Three patients with gliomatosis cerebri had detailed neurobehavioral assessment, and one had neuropsychological testing early in the disease. Neuropathological investigation focused on the localization of the neoplasm, the correlation between extent of myelin and axon damage with tumor cell density, and the histogenesis of the tumor. RESULTS: The patient with neuropsychological testing had impaired executive function and verbal memory retrieval that reflected bifrontal and left temporal white matter tumor involvement seen on neuroimaging. In the other cases, apathy and fatigue progressed to severe dementia in association with bihemispheric white matter infiltration. Myelin and axon stains and myelin stains showed relative preservation of white matter architecture with severity of damage paralleling increased tumor cell density. Immunostaining for TP53 was found in a high percentage of tumor nuclei in two of three cases, suggesting overlapping features between gliomatosis cerebri and diffuse astrocytomas. CONCLUSIONS: Subtle cognitive and emotional alterations antedate the florid dementia that develops later in the course of gliomatosis cerebri. Clinical, neuroimaging, and neuropathological data suggest that white matter is damaged directly by the tumor and its associated mild edema, although infiltration of subcortical and cortical gray matter also occurs to a variable extent. Strong TP53 immunostaining in gliomatosis cerebri suggests a commonality with diffuse fibrillary astrocytomas that also often show TP53 staining. Gliomatosis cerebri can be considered a cause of white matter dementia resulting from preferential neoplastic disruption of white matter tracts.

Adult↗
PubMed2003

Giant cell glioblastoma and pleomorphic xanthoastrocytoma show different immunohistochemical profiles for neuronal antigens and p53 but share reactivity for class III beta-tubulin.

CONTEXT: Giant cell glioblastoma multiforme (GCGBM) and pleomorphic xanthoastrocytoma (PXA) are clinically, radiographically, and histologically distinct tumors of the central nervous system. However, they share features of gross circumscription, reticulin deposition, lymphocytic infiltrates, and prominent populations of tumor giant cells. Neuronal antigens have been detected in the neoplastic cells of PXAs, but to our knowledge have not been studied previously in GCGBMs. While TP53 is mutated in most GCGBMs, a feature usually paralleled by strong immunostaining of the protein, the expression pattern of PXAs has not been extensively studied. OBJECTIVES: To compare the immunoprofiles of GCGBM and PXA with regard to neuronal antigens and p53 and to evaluate the potential diagnostic utility of such a panel. DESIGN: Archival paraffin sections of 9 GCGBMs and 9 PXAs were immunostained for class III beta-tubulin, neuronal nuclear antigen, neurofilament protein, synaptophysin, glial fibrillary acidic protein, and p53. RESULTS: Giant cell glioblastomas were strongly immunoreactive for class III beta-tubulin and glial fibrillary acidic protein, but showed only rare staining for the other neuronal polypeptides. In contrast, PXAs usually showed at least focal staining of individual tumor cells for most of the neuronal antigens tested. Tubulin was strongly positive in tumor giant cells and in smaller neoplastic cells of both tumor types. Double-immunolabeling revealed distinct populations of tumor cells that expressed either glial fibrillary acidic protein or tubulin and dual-labeling of individual cells in GCGBM and PXA. Strong p53 staining was observed in many tumor cells in 5 of 8 GCGBMs tested, while staining for this antigen was negative or focally positive in 6 of 8 PXAs examined. CONCLUSIONS: Giant cell glioblastoma multiforme and PXA show distinct patterns of immunoreactivity for neuronal antigens and p53 that may be useful diagnostically in difficult cases or in limited samples. These results provide further evidence of neuronal antigen expression by PXA.

Adolescent↗
PubMed2003

Survivin in glioblastomas. Protein and messenger RNA expression and comparison with telomerase levels.

CONTEXT: Survivin is a novel inhibitor of apoptosis that acts via a pathway independent of bcl-2. Little is known about its distribution in brain tumors or how it correlates with other biomarkers of malignancy, such as telomerase, an enzyme that plays a critical role in cellular immortalization and cancer biology. OBJECTIVES: To assess survivin protein expression in gliomas and to compare expression with that of telomerase. DESIGN: Immunohistochemical staining for survivin protein expression was performed using an antibody developed in our laboratory. Quantitative survivin messenger RNA (mRNA) levels were assessed by reverse transcriptase-polymerase chain reaction. In selected cases, survivin results were compared with quantitative telomerase values analyzed by polymerase chain reaction-based telomerase repeat amplification protocol (TRAP) assay. Twenty-five tumor tissue samples from 16 cases of glioblastoma multiforme (GBM; including multiple tissue samples in 6 patients), 2 grade II gliomas, 4 grade III gliomas, and 3 control temporal lobectomy specimens were studied. RESULTS: Nuclear immunoreactivity for survivin protein and survivin mRNA were detectable in most glioma samples, regardless of grade. Glioblastoma multiforme demonstrated moderate protein expression and survivin mRNA levels compared to epithelial malignancies previously tested in our laboratory. Although the association of survivin mRNA with the levels of telomerase within the GBM cases did not reach statistical significance, most GBMs also expressed survivin. The quantitative score for survivin mRNA was higher in GBMs than in grade II and III gliomas (P =.02), after accounting for multiple specimens per patient. CONCLUSIONS: Quantitative survivin mRNA analysis, but not immunohistochemistry, distinguished GBMs from lower grade gliomas. Mechanisms that promote both cell proliferation (telomerase expression) and cell survival (survivin expression) are often activated in GBMs.

Adult↗
PubMed2002

Fulminant ascending paralysis as a delayed sequela of diethylene glycol (Sterno) ingestion.

The authors report a 57-year-old man who survived 18 days after swallowing an 8-oz. can of Sterno in a suicide attempt. Two days after ingestion, he developed confusion and acute renal failure requiring hemodialysis, followed on day 8 by a delayed but rapidly evolving ascending paralysis. Pathologic examination showed severe demyelination, with lesser axonal damage, of virtually all cranial and peripheral nerves sampled and sparing of central myelin. The diethylene glycol in the Sterno was considered responsible for this intoxication.

Acute Kidney Injury↗
PubMed2002

Central nervous system apoptosis in human herpes simplex virus and cytomegalovirus encephalitis.

Central nervous system (CNS) specimens from 10 immunocompetent patients with herpes simplex encephalitis (HSE) and 3 infants with congenital cytomegalovirus (CMV) encephalitis were analyzed to determine whether apoptosis is a feature of CNS injury in these patients. Apoptotic neurons and glia were detected in significant numbers in acute HSE and CMV encephalitis. Occurring predominantly in areas of productive viral infection, apoptosis appeared to result from direct viral injury to neurons and was not dependent on inflammatory T cell responses. In contrast to patients with acute cases, patients with late sequelae of HSE or CMV had no detectable virus and minimal neuronal or glial apoptosis, regardless of the degree of inflammation. This is the first demonstration of apoptotic neuronal death in humans with HSE. These results suggest that neuronal apoptosis is an important contributing factor to acute CNS injury and may serve as a novel therapeutic target in these patients.

Adolescent↗
PubMed2002

Progressive multifocal leukoencephalopathy and apoptosis of infected oligodendrocytes in the central nervous system of patients with and without AIDS.

CONTEXT: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by JC virus (JCV) that occurs in immunocompromised patients. Demyelination of the CNS is a consequence of virus-induced killing of oligodendrocytes, although the exact mechanism of cell death is unknown. OBJECTIVE: To examine archival autopsy and surgical pathologic specimens from 8 patients with PML, including 6 patients with human immunodeficiency virus (HIV)-associated PML and 2 patients with non-HIV-associated PML, for evidence of apoptosis. DESIGN: Apoptotic cells were identified by TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end in situ labeling) or immunohistochemical detection of activated caspase 3. The JCV-infected cells were identified by in situ hybridization for viral transcripts or immunohistochemical analysis for JCV T antigen. RESULTS: Apoptosis of JCV-infected oligodendrocyte apoptosis was a prominent feature in all cases of both HIV- and non-HIV-associated PML. There were no differences between number or distribution of apoptotic cells identified by TUNEL or immunohistochemical analysis for activated caspase 3. Bizarre astrocytes were occasionally positive for JCV but were not apoptotic. Neurons, astrocytes, macrophages, and oligodendrocytes remote from lesions were neither apoptotic nor JCV infected. CONCLUSIONS: Our study demonstrates that apoptosis occurs in oligodendrocytes associated with demyelinated lesions of patients with both HIV-associated and non-HIV-associated PML. There were no differences in degree, location, or type of infected or apoptotic cells between patients with HIV-associated and non-HIV-associated PML. The extent of apoptosis did not correlate with the presence or intensity of host inflammatory response. Accumulation of viral particles in nuclei of infected cells made it difficult to identify morphologic changes in the nucleus typically associated with apoptosis.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Use of PCR for the diagnosis of herpesvirus infections of the central nervous system.

Polymerase chain reaction (PCR) analysis of cerebrospinal fluid (CSF) has revolutionized the diagnosis of nervous system viral infections, particularly those caused by human herpesviruses (HHV). The PCR technique allows the detection of minute quantities of DNA or RNA in body fluids and tissues. Both fresh-frozen and formalin-fixed tissues may be utilized for PCR assays, with the latter making archival studies possible. CSF PCR has now replaced brain biopsy as the gold standard for the diagnosis of herpes simplex virus (HSV) encephalitis. PCR analysis of both CSF and nervous system tissues has also broadened our understanding of the spectrum of disease caused by HSV-1 and -2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV) and HHV-6. PCR results obtained from tissue specimens must be interpreted cautiously, since this highly sensitive technique may detect portions of viral genomic material that may be present even in the absence of active viral infection. Tissue PCR results in particular must be corroborated with clinical and neuropathologic evidence of central nervous system (CNS) infection. In several neurological diseases, negative PCR results have provided evidence against a role for herpesviruses as the causative agents. This review summarizes the role of CSF PCR in the diagnosis and therapeutic management of herpesvirus infections of the nervous system, particularly those caused by HSV and VZV.

Central Nervous System Viral Diseases↗
PubMed2002

Central nervous system aspergillosis: a 20-year retrospective series.

Over the past 20 years at my institution, 71 patients with invasive necrotizing aspergillosis have been encountered; 42 have shown central nervous system (CNS) involvement by autopsy (40) or surgical biopsy (2). Most non-CNS aspergillosis patients had invasive disease confined to the lung, and only 2 with dissemination to 3 or more organs did not have spread to the CNS. In addition to the expected post-transplantation and hematologic malignancy cases, other risk groups identified included those with chronic asthma and steroid use, acquired immunodeficiency syndrome, thermal burn, hepatic failure, and postoperative infection. Unusual cases manifested with basilar meningitis, myelitis, proptosis caused by sino-orbital disease, or epidural and subdural Aspergillus abscesses. The extent of gross neuropathologic disease ranged from subtle abscesses to massive hemorrhagic necrosis causing herniation and death. In addition to the expected hemorrhagic necrosis, extensive hemorrhage, focal purulent meningitis, and subtle bland infarctions were also seen. Distinctive microscopic findings encountered included 1 case with numerous meningeal granulomas and multinucleated giant cells and 4 cases showing the Splendore-Hoeppli phenomenon. During the same period, single cases of cerebritis caused by morphologically similar fungi (Pseudoallescheria boydii [Scedosporium apiospermum], Scedosporium inflatum, Chaetomium sp) were identified and were indistinguishable from CNS aspergillosis clinically and pathologically.

AIDS-Related Opportunistic Infections↗
PubMed2001

Simian varicella virus infects ganglia before rash in experimentally infected monkeys.

Monkeys experimentally infected with simian varicella virus (SVV) develop rash 10-14 days later. However, the route and the time of ganglionic infection are unknown. Using PCR, we analyzed DNA extracted from tissues of 13 monkeys 5 to 60 days after either intratracheal or intravenous inoculation with SVV. SVV DNA was detected in ganglia from four of five monkeys sacrificed 6 to 7 days after intratracheal inoculation. Further, analysis of ganglia from monkeys sacrificed at 10 days revealed that intravenous inoculation produced a higher proportion of SVV DNA-positive ganglia (63%) than that after intratracheal inoculation (13%), pointing to the role of hematogenous spread in ganglionic infection. Like other organs, monkey ganglia become infected with SVV before the appearance of rash.

Animals↗
PubMed2001

N-Methyl-D-aspartate receptor subunit proteins and their phosphorylation status are altered selectively in Alzheimer's disease.

The N-methyl-D-aspartate (NMDA) receptor is a subtype of the ionotropic glutamate receptor that plays a pivotal role in synaptic mechanisms of learning and memory. We tested the hypothesis that NMDA receptor protein levels are abnormal in Alzheimer's disease (AD). By immunoblotting, we assessed levels of both non-phosphorylated and phosphorylated receptor subunit proteins from four separate regions of 16 post-mortem brains. Three patient groups with thorough pre-mortem neuropsychological testing were evaluated, including AD, early AD (p-AD), and control patients. Protein levels and phosphorylation status of NMDA receptor subunits NR1, NR2A and NR2B were correlated with measurements of cognitive performance. Selective regional reductions in NMDA receptor subunit protein levels were found in AD compared to controls, but protein levels in the p-AD group were similar to controls. Reductions of NR1 (53%, P<0.05) and NR2B (40%, P<0.05) were identified in hippocampus. Reductions of NR2A (39%, P<0.05) and NR2B (31%, P<0.01) were found in entorhinal cortex. No reductions were noted in occipital cortex and caudate. Phosphorylated NR2A (30%, P<0.05) and NR2B (56%, P<0.01) were selectively reduced in entorhinal cortex in AD when compared to controls. Both phosphorylated and non-phosphorylated NMDA receptor protein levels in entorhinal cortex correlated with Mini-Mental Status Examination (MMSE) and Blessed (BIMC) scores. The losses of phosphorylated and non-phosphorylated NMDA receptor subunit proteins correlated with changes in synaptobrevin levels (a presynaptic protein), but not with age or post-mortem interval. Our results demonstrate that NMDA receptor subunits are selectively and differentially reduced in areas of AD brain, and these abnormalities correlate with presynaptic alterations and cognitive deficits in AD.

Aged↗
PubMed2001

Molecular immunologic strategies to identify antigens and b-cell responses unique to multiple sclerosis.

Identification of the causative agent of multiple sclerosis (MS) has long eluded investigators and has become the "Holy Grail" of researchers in the field. The immune response in cerebrospinal fluid of patients with MS, indicated by an increased IgG level and the presence of specific oligoclonal bands after electrophoresis, strongly parallels that found in various infectious diseases of the central nervous system. To understand the nature of B-lymphocyte activation in MS, 4 laboratories studied the antigen-binding regions of antibodies found in MS brain demyelinative plaques and cerebrospinal fluid. Each analysis revealed (1) limited germline expression, results not expected for a random bystander response; (2) features consistent with a specific antigen-targeted process; and (3) the clonal expansion of populations of B lymphocytes in MS. The screening of libraries expressing protein products derived from chronic MS plaque messenger RNA with antibodies purified from plaques, cerebrospinal fluid, or serum of patients with MS has thus far not revealed the antigenic target(s) of the MS antibody response. Because putative MS antigens could be in low abundance, the screening of large libraries of random peptides expressed on phage surfaces might offer an alternative approach to identify peptide sequences recognized by MS antibodies. New sophisticated molecular immunologic techniques described herein should enhance our ability to identify putative antigen(s) targets in MS.

Antibodies, Monoclonal↗
PubMed2001

The immunoglobulin G heavy chain repertoire in multiple sclerosis plaques is distinct from the heavy chain repertoire in peripheral blood lymphocytes.

Analyses have shown that the repertoire of Ig heavy chain sequences (VH) expressed in multiple sclerosis (MS) plaques or cerebrospinal fluid is consistent with B cell clonal expansion and affinity maturation. PCR amplification of VH sequences from MS lesions obtained from an acute MS patient at autopsy revealed oligoclonal and extensively mutated VH sequences from plaque-periplaque regions with discrete intraclonal differences indicative of B cell clonal expansion in the groups of overrepresented major sequences. None of the VH sequences expressed in plaque regions were detected in peripheral blood lymphocytes from this patient. These data indicate the presence of a CNS-targeted antigen-driven response in MS plaques.

Amino Acid Sequence↗
PubMed2001

The expanding spectrum of herpesvirus infections of the nervous system.

Herpesviruses cause various acute, subacute, and chronic disorders of the central (CNS) and peripheral (PNS) nervous systems in adults and children. Both immunocompetent and immunocompromised individuals may be affected. Zoster (shingles), a result of reactivation of varicella zoster virus (VZV), is the most frequent neurologic complication. Other neurological complications include encephalitis produced by type I herpes simplex virus (HSV-1), and less frequently HSV-2, as well as by VZV and cytomegalovirus (CMV). Acute meningitis is seen with VZV and HSV-2, and benign recurrent meningitis with HSV-2. Combinations of meningitis/ encephalitis and myelitis/radiculitis are associated with Epstein Barr Virus (EBV); myelitis with VZV, CMV, EBV, and HSV-2; and ventriculitis/encephalitis with VZV and CMV. Brainstem encephalitis due to HSV and VZV, and polymyeloradiculitis due to CMV are well documented. HHV-6 produces childhood exanthem subitum (roseola) and febrile convulsions. Immunocompetent and immunocompromised hosts manifest different incidences and patterns of herpesvirus infections. For example, stroke due to VZV-mediated large vessel disease (herpes zoster ophthalmicus) occurs predominantly in immunocompetent hosts, while small vessel disease (leukoencephalitis) and ventriculitis develop almost exclusively in immunocompromised patients. EBV-associated primary CNS lymphomas also are restricted to immunosuppressed individuals. Recent large CSF PCR studies have shown that VZV, EBV, and CMV more frequently produce meningitis, encephalitis, or encephalopathy in immunocompetent hosts than was formerly realized. We review herpesvirus infections of the nervous system and illustrate the expanding spectrum of disease by including examples of a 75-year-old male on steroid treatment for chronic lung disease with fatal HSV-2 meningitis and an 81-year-old male with myasthenia gravis, long-term azathioprine use, and an EBV-associated primary CNS lymphoma.

Adolescent↗
PubMed2001

Polymerase chain reaction as a diagnostic adjunct in herpesvirus infections of the nervous system.

Polymerase chain reaction (PCR) is a powerful technique that allows detection of minute quantities of DNA or RNA in cerebrospinal fluid (CSF), vesicle and endoneurial fluids, blood, fresh-frozen, and even formalin-fixed tissues. Various infectious agents can be detected with high specificity and sensitivity, including bacteria, parasites, rickettsia and viruses. PCR analysis of CSF has revolutionized the diagnosis of nervous system viral infections, particularly those caused by human herpesviruses (HHV), and has now replaced brain biopsy as the gold standard for diagnosis of herpes simplex virus (HSV) encephalitis. PCR analysis of both CSF and nervous system tissues has also broadened our understanding of the spectrum of disease caused by HSV-1 and -2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), and HHV-6. Nonetheless, positive tissue PCR results must be interpreted cautiously, especially in cases that lack corroborating clinical and neuropathologic evidence of infection. Moreover, positive PCR results from tissues do not distinguish latent from productive (lytic) viral infections. In several neurological diseases, negative PCR results have provided strong evidence against a role for herpesviruses as the causative agents. This review focuses on the use of PCR tests to diagnose HSV and VZV infections of the nervous system.

Body Fluids↗
PubMed2001

May 2001: 32 year old female with dural mass encircling cervical spinal cord.

The May COM. A 32-year-old woman with a history of previous mastoid surgery presented with bilateral extremity weakness and ambulatory instability. MRI revealed a dural-based mass completely encircling the upper cervical spinal cord. Workup was significant for an abnormally elevated c-ANCA, positive at a dilution of 1:128. A portion of the lesion was removed by a posterior surgical approach to decompress the cervical cord. Histologic examination of the dura showed a dense granulomatous infiltrate with vasculitis and giant cells; coupled with the positive c-ANCA, the process was felt to be most consistent with Wegener's granulomatosis. Wegener's granulomatosis infrequently involves the dura or meninges and has not previously been reported to affect dura of the cervical cord. Symptomatic improvement followed surgical decompression and high-dose corticosteroid therapy, with resultant resolution of an elevated c-ANCA titer.

Adrenal Cortex Hormones↗