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L C Ang

Publications and source records attributed to L C Ang.

At least 19 recordsLinked to original sources
PubMed2001

Identification of the motif in versican G3 domain that plays a dominant-negative effect on astrocytoma cell proliferation through inhibiting versican secretion and binding.

This study was designed to investigate the mechanisms by which mutant versican constructs play a dominant-negative effect on astrocytoma cell proliferation. Although a mini-versican or a versican G3 construct promoted growth of U87 astrocytoma cells, a mini-versican lacking epidermal growth factor (EGF) motifs (versicanDeltaEGF) and a G3 mutant (G3DeltaEGF) exerted a dominant-negative effect on cell proliferation. G3DeltaEGF-transfected cells formed smaller colonies, arrested cell cycle at G(1) phase, inhibited expression of cell cycle proteins cdk4 and cyclin D1, and contained multiple nucleoli. In cell surface binding assays, G3 products expressed in COS-7 cells and bacteria bound to U87 cell surface. G3DeltaEGF products exhibited decreased binding activity, but higher levels of G3DeltaEGF products were able to inhibit the binding of G3 to the cell surface. G3DeltaEGF expression inhibited secretion of endogenous versican in astrocytoma cells and also inhibited the secretion of mini-versican in COS-7 cells co-transfected with the mini-versican and G3DeltaEGF constructs. The effect seems to depend on the expression efficiency of G3DeltaEGF, and it occurred via the carbohydrate recognition domain.

Amino Acid Motifs↗
PubMed2001

Epithelioid hemangioendothelioma of the spine presenting as cervical myelopathy: case report.

OBJECTIVE AND IMPORTANCE: We report the first case in the literature of cervical myelopathy caused by progressive cord compression as a result of epithelioid hemangioendothelioma of the cervical vertebra. CLINICAL PRESENTATION: A 58-year-old man presented with progressive cervical myelopathy. Imaging revealed a vascular, expansile lesion of contiguous cervical vertebrae causing cord compression. The surgical pathology revealed epithelioid hemangioendothelioma, a rare tumor not previously reported to present in such a fashion. INTERVENTION: Preoperative embolization and a two-stage anterior and posterior surgical decompression and fusion procedure were performed. The high vascularity of this lesion makes surgery a formidable surgical challenge. Adjuvant radiotherapy was administered to the residual tumor because of its potential for low-grade malignancy. CONCLUSION: The diagnosis relied on accurate histopathological assessment. The general principles of achieving cord decompression and tumor control are important. The literature on epithelioid hemangioendothelioma involving the spine is reviewed, and the tumor biology and the role of adjuvant therapy are discussed.

Angiography, Digital Subtraction↗
PubMed2001

Differential response of sensory and motor axons in nerve allografts after withdrawal of immunosuppressive therapy.

OBJECT: Rejection of nerve allografts and loss of regenerated host axons after withdrawal of immunosuppressive therapy poses an ongoing challenge in peripheral nerve repair. The present report is of a blinded prospective controlled study in which an established rat model of nerve allotransplantation is used to examine the effect of fiber type on survival and degeneration of nerve allografts after discontinuation of immunosuppression. The authors hypothesized that sensory axons will selectively resist a rejection response, whereas motor axons will degenerate. METHODS: Four-centimeter nerve segments from ACI rats were grafted into peroneal and sural (mixed) or saphenous (sensory) nerve gaps in Lewis rats. In some rats, L4-6 dorsal root ganglia were ablated before grafting, creating pure motor sural and peroneal nerves. All rats received 12 weeks of immunosuppressive therapy to support nerve regeneration into allografts. Immunosuppression with cyclosporin was then withdrawn. At planned death (12-18 weeks postsurgery), graft tissue was subjected to histomorphometric analysis for evaluation of axon survival and loss. Graft rejection led to loss of all axons in approximately 60% of the allograft segments. The mixed nerve group was most prone to complete rejection, with significantly lowered axon counts at Weeks 16 and 18 compared with the Week 12 baseline. Axons from the sensory nerve were least likely to degenerate. The pure motor nerve group axons demonstrated intermediate sensitivity, with a selective loss of larger axons at Week 16 and a significant decrease in axon counts from the Week 12 baseline at Week 18. CONCLUSIONS: Whereas the majority of axons are lost after withdrawal of immunosuppressive therapy from nerve allografts, there is a selective survival of axons from cutaneous sensory nerves and smaller-diameter motor fibers. The biological and molecular mechanisms that make some axons impervious to injury remain to be determined.

Animals↗
PubMed2000

Glial intranuclear inclusion bodies in a patient with Alzheimer's disease.

We report a case of dementia in an elderly woman with the pathological findings of Alzheimer's disease and numerous intranuclear inclusions in astrocytes and occasionally in neurons. These inclusions were seen in the cerebral cortex, limbic areas, basal ganglia, thalamus, brain stem and cerebellum. They expressed ubiquitin and were ultrastructurally composed of haphazardly arranged straight filaments. The presence of similar intranuclear inclusions in previous cases of adult-onset dementia without other neuropathological changes suggests an important link between these kind of inclusions and dementia. To our knowledge, this type of intranuclear inclusions has not been previously described in association with Alzheimer pathology.

Aged↗
PubMed2000

Long nerve allografts in sheep with Cyclosporin A immunosuppression.

Rodent studies of nerve allografts are limited by a relatively short length of graft segment. The authors attempted to establish an outbred sheep model that would allow the study of longer, more clinically relevant nerve gaps. Using outbred ewes, two 8-cm long radial sensory nerves were grafted into gaps (5 cm) in the median nerve. Sheep received an autograft and an allograft. Four sheep were immunosuppressed with Cyclosporin A (CsA) and four were controls. Blood CsA levels greater than 1000 microg/L were obtained. Systemic immunosuppression resulted in severe opportunistic infections, and the sheep were sacrificed between 35 and 47 days following surgery. Histologically, in the autografts and CsA-treated allografts, evidence of nerve regeneration was seen. Non-immunosuppressed allografts were clearly rejected. While clear differences in the histology of experimental and control grafted nerve tissues were seen, the sheep allograft model presents considerable challenges due to immunosuppression-related infectious complications.

Animals↗
PubMed2000

Comparison of thermal damage calculated using magnetic resonance thermometry, with magnetic resonance imaging post-treatment and histology, after interstitial microwave thermal therapy of rabbit brain.

Clinical application of high-temperature thermal therapy as a treatment for solid tumours requires an accurate and close to real-time method for assessing tissue damage. Imaging methods that detect structural changes during heating may underestimate the extent of thermal damage. This is due to the occurrence of delayed damage manifested at tissue locations exposed to temperatures lower than those required to cause immediate structural changes. An alternative approach is to measure temperature and then calculate the expected damage based on the temperature history at each tissue location. Magnetic resonance (MR) imaging methods now allow temperature maps of the target and surrounding tissues to be generated in almost real-time. The aim of this work was to evaluate whether thermal damage zones calculated on the basis of MR thermometry maps measured during heating correspond to actual tissue damage as measured after treatment by histological methods and MR imaging. Four male rabbits were treated with high-temperature thermal therapy delivered in the brain by a single microwave antenna operating at 915 MHz. MR scanning was performed before, during and after treatment in a 1.5 T whole-body scanner. Temperature maps were produced using the proton resonance frequency (PRF) shift method of MR thermometry. In addition, conventional T1-weighted and T2-weighted spin-echo images were acquired after treatment. Thermal damage zones corresponding to cell death, microvascular blood flow stasis and protein coagulation were calculated using an Arrhenius analysis of the MR temperature/time course data. The calculated zones were compared with the lesions seen on histopathological examination of the brains which were removed within 6-8 h of treatment. The results showed that calculated damage zones based on MR thermometry agreed well with areas of damage as assessed using histology after heating was completed. The data suggest that real-time calculations of final expected thermal damage based on an Arrhenius analysis of MR temperature data may provide a useful method of real-time monitoring of thermal therapy when combined with conventional T2-weighted images taken after treatment.

Animals↗
PubMed2000

Primary spinal epidural mantle cell lymphoma: case report.

OBJECTIVE AND IMPORTANCE: Mantle cell lymphoma is a distinct clinicopathological type of non-Hodgkin's lymphoma that often presents at an advanced stage, with systemic spread. Spinal involvement is uncommon and generally occurs as part of advanced disease or generalized relapses. Primary spinal epidural lymphoma is a rare initial manifestation of non-Hodgkin's lymphoma, and mantle cell lymphoma with initial presentation in the spinal epidural space is extremely rare, having been previously reported in only two cases. CLINICAL PRESENTATION: We report a case of a 71-year-old man who presented with increasing weakness and numbness of the legs. Magnetic resonance imaging revealed a spinal epidural mass in the lumbosacral region. INTERVENTION: The patient underwent a partial L4 and L5-S1 laminectomy, with incomplete resection of the mass for spinal decompression and tissue diagnosis. Mantle cell lymphoma was diagnosed in the pathological examination. CONCLUSION: After radiotherapy, the disease recurred with a soft-tissue mass in the anterior maxillary area of the face. The patient underwent restaging and was treated with chemotherapy, with only a partial response. Mantle cell lymphoma with primary spinal epidural presentation is rare. This diagnosis can be established and other causes of spinal cord compression can be ruled out by obtaining tissue for proper histopathological examinations. Because of its aggressive behavior and poor prognosis, mantle cell lymphoma should be treated using a combined-modality approach.

Aged↗
PubMed2000

Overexpression of cyclin A and cyclin B1 proteins in astrocytomas.

BACKGROUND: Cyclins are proteins that are expressed during the progression of a normal cell through the cell cycle. In a number of cancers, overexpression of cyclin A and cyclin B1 proteins has been reported, and in some instances the levels of expression correlated well with the grades of malignancy. The expression of cyclin A and cyclin B1 proteins in astrocytoma may be linked to the histologic grade or proliferative activities. OBJECTIVE: To study the expression of cyclin A and cyclin B1 proteins in astrocytomas and correlate the labeling indices (LIs) of cyclin A and cyclin B1 with histologic grade and Ki-67 LI. DESIGN: The surgical biopsy specimens from 65 adults with astrocytomas were reviewed and divided into grades based on the World Health Organization system. The paraffin sections were immunostained using primary antibodies against Ki-67, cyclin A, and cyclin B1. The LIs of these astrocytomas for the 3 different antibodies were determined by computerized image analysis. RESULTS: The cyclin A LI showed good correlation with astrocytoma grade and Ki-67 LI. Both the nuclear and cytoplasmic cyclin B LIs correlated well with the tumor grade but showed poor correlation with Ki-67 LI. CONCLUSIONS: This study suggests that although both cyclin A and B protein expression are related to the grade of malignancy in astrocytomas, cyclin A levels more generally reflect the proliferative state of these tumors. We also provide indirect evidence that cyclin B1 is associated with the aberrant progression through the G2-M phase checkpoint in astrocytomas.

Astrocytoma↗
PubMed2000

Skeletal muscle infarction in diabetes mellitus.

OBJECTIVE: To analyze the risk factors, clinical features, and methods of diagnosis of diabetic muscle infarction (DMI). METHODS: Three patients with diabetes mellitus (DM) and skeletal muscle infarction were studied, and 49 additional cases reported in the English literature (Medline database search) were reviewed. RESULTS: Review of all 52 patients with DMI revealed a number of typical features: equal sex distribution; mean age 41.5 years (range 19-81 yrs); a number of risk factors [long duration of DM (mean 15.2 yrs), poor control and microvascular diabetic complications (neuropathy, retinopathy, nephropathy) (94%), and insulin dependent type I DM (77%)]; a characteristic clinical presentation with painful diffuse muscle swelling (100%); and sometimes a muscle mass (44%), predilection for quadriceps (62%), hip adductors (13%) and leg muscles (13%), elevated serum creatine phosphokinase (47%), abnormal sonograms (81%), abnormal magnetic resonance image (MRI) findings (100%), typical histopathologic findings of a muscle infarct (100%) (ultrastructural evidence of microangiography in one patient); and a tendency toward spontaneous resolution although recurrences are common (51%). CONCLUSION: Skeletal muscle infarction is a rare complication of long standing, poorly controlled DM associated with multiple end organ microvascular sequelae. Increased clinical awareness is important for early recognition, particularly in a diabetic patient presenting with a painful thigh or leg swelling. MR imaging is the diagnostic study of choice, and in the appropriate clinical setting, may obviate the need for a muscle biopsy.

Adult↗
PubMed2000

Hydroxychloroquine neuromyotoxicity.

Hydroxychloroquine (HCQ) is commonly prescribed for treatment of inflammatory arthritis. The most frequently observed serious side effect is retinal toxicity; however, case reports have described HCQ induced neuromyotoxicity. We describe a case of HCQ neuromyotoxicity and a literature review from 1965 to September 1998 using Medline and Embase. Including our patient, there are 10 reported cases of HCQ neuromyotoxicity. Muscle biopsy consistently reveals curvilinear bodies and muscle fiber atrophy with vacuolar changes. Most cases manifest as insidious onset proximal myopathy that may be associated with peripheral neuropathy and cardiac myotoxicity. Resolution of symptoms is slow after discontinuation of therapy and may be incomplete. Possible predisposing factors include Caucasian race and concomitant renal failure. Patients treated with HCQ who develop a proximal myopathy, cardiomyopathy, or neuropathy, especially in the setting of worsening renal function, should be evaluated for possible HCQ neuromyotoxicity.

Aged↗
PubMed1999

Versican enhances locomotion of astrocytoma cells and reduces cell adhesion through its G1 domain.

Versican is a large extracellular proteoglycan and is expressed in a variety of tissues including the central nervous system. A malignant astrocytoma cell line U87 with high motility expressed a higher level of versican than another malignant astrocytoma cell line U343 with lower motility. We observed that the U87 cells were less adherent to tissue culture plates than the U343 cells. To investigate the role of versican in astrocytoma cell migration, we generated recombinant products of a mini-versican construct expressed in COS-7 cells. We found that the mini-versican products enhanced astrocytoma cell migration. Furthermore, enhanced migration was promoted by the G1 domain but not the G3 domain of versican. We introduced culture medium containing products of the mini-versican, the G1, and the G3 constructs separately into the astrocytoma cell lines U87 and U343. The mini-versican and the G1 construct, but not the G3 construct, were shown to reduce astrocytoma cell adhesion. The present data suggest that versican exerts its effect on astrocytoma cell migration and adhesion through the G1 domain.

Astrocytoma↗
PubMed1999

The hPMS2 exon 5 mutation and malignant glioma. Case report.

Patients with Turcot syndrome (TS) are predisposed to colon tumors and primary brain tumors, typically glioblastomas or medulloblastomas. The authors describe a patient with TS featuring a known germline mutation of exon 5 of the hPMS2 mismatch repair gene who developed two metachronous glioblastomas, both with distinct oligodendroglial features. Molecular genetic analysis revealed allelic loss of chromosome 19q in the patient's second tumor but no allelic loss of chromosome 1p. Prominent microsatellite instability was also found in this tumor, consistent with a germline mismatch repair defect. Because this patient had an unusual underlying condition and his tumor had a unique histological appearance for TS, it was hypothesized that this genetic defect may predispose to malignant gliomas with oligodendroglial features. The authors therefore evaluated whether sporadic glioblastomas and oligodendrogliomas undergo mutations of this region of the hPMS2 gene. However, single-strand conformation polymorphism analysis of hPMS2 exon 5 failed to reveal mutations in 20 sporadic glioblastomas and 16 sporadic oligodendroglial gliomas. Thus, although it is possible that the germline hPMS2 exon 5 mutation may predispose to glioblastomas with an oligodendroglial component, the same genetic defect is not commonly involved in sporadic oligodendrogliomas or glioblastomas.

Adenomatous Polyposis Coli↗
PubMed1998

Axonal injury and the neuropathology of shaken baby syndrome.

We examined an autopsy series of 14 children with shaken baby syndrome (SBS) who lacked skull fracture. Evidence of axonal injury was sought using immunohistochemical stains for neurofilament, 68-kDa neurofilament and beta-amyloid precursor protein (betaAPP). BetaAPP-positive axons were present in the cerebral white matter of all cases of SBS but were also present in 6 of 7 children dying of non-traumatic hypoxic ischemic encephalopathy (HIE). Swollen axons were present in 11 of 14 cases of SBS and in 6 of 7 cases of HIE. BetaAPP-positive axons were present in both groups in the midbrain and medulla. The cervical spinal cord in SBS contained betaAPP-positive axons in 7 of 11 cases; 5 of 7 contained swollen axons within the white matter tracts; in 2 immunoreactivity was localized to spinal nerve roots; in all 7 there was a predilection for staining at the glial head of the nerve root. Among cases of HIE, none showed abnormal axons or betaAPP-positive reactivity in the cervical cord white matter. We conclude that cerebral axonal injury is common in SBS, and may be due in part to hypoxic/ischemic injury. Cervical cord injury is also common, and cannot be attributed to HIE. These findings corroborate suggestions that flexion-extension injury about the cervical spinal column may be important in the pathogenesis of SBS.

Amyloid beta-Protein Precursor↗
PubMed1998

Hemorrhagic necrotic schwannoma presenting as purulent meningitis.

BACKGROUND: Intracranial schwannoma involving the XIIth cranial nerve is rare. We report an unusual clinical presentation and pathological verification of a schwannoma, which had become haemorrhagic and necrotic, simulating acute purulent meningitis. METHODS: A literature review of intracranial tumors presenting as acute purulent meningitis, with emphasis on schwannomas, was undertaken. RESULTS: Few cases of hypoglossal schwannoma have been reported; the association with purulent meningitis has not been previously documented. CONCLUSION: In patients presenting with sterile purulent meningitis, a necrotic tumor should be considered as a possible etiology.

Adult↗
PubMed1998

Phenotypic variability of Gerstmann-Sträussler-Scheinker disease is associated with prion protein heterogeneity.

Gerstmann-Sträussler-Scheinker disease (GSS), a cerebello-pyramidal syndrome associated with dementia and caused by mutations in the prion protein gene (PRNP), is phenotypically heterogeneous. The molecular mechanisms responsible for such heterogeneity are unknown. Since we hypothesize that prion protein (PrP) heterogeneity may be associated with clinico-pathologic heterogeneity, the aim of this study was to analyze PrP in several GSS variants. Among the pathologic phenotypes of GSS, we recognize those without and with marked spongiform degeneration. In the latter (i.e. a subset of GSS P102L patients) we observed 3 major proteinase-K resistant PrP (PrPres) isoforms of ca. 21-30 kDa, similar to those seen in Creutzfeldt-Jakob disease. In contrast, the 21-30 kDa isoforms were not prominent in GSS variants without spongiform changes, including GSS A117V, GSS D202N, GSS Q212P, GSS Q217R, and 2 cases of GSS P102L. This suggests that spongiform changes in GSS are related to the presence of high levels of these distinct 21-30 kDa isoforms. Variable amounts of smaller, distinct PrPres isoforms of ca. 7-15 kDa were seen in all GSS variants. This suggests that GSS is characterized by the presence PrP isoforms that can be partially cleaved to low molecular weight PrPres peptides.

Adult↗
PubMed1998

End-Organ reinnervation does not prevent axonal degeneration in nerve allografts following immunosuppression withdrawal.

Previous work indicated that appropriate end-organ reinnervation fails to influence axonal degeneration in nerve allografts following immunosuppression withdrawal. In the present study, we examined if differences existed in axonal degeneration when axons regenerated across nerve allografts are allowed or completely denied end-organ reinnervation. Two ACI rat nerve allografts (3 cm long) were sutured into gaps created in both peroneal nerves in Lewis rats. In the right leg, the distal end of the graft was connected to the distal host nerve stump to allow end-organ reinnervation. In the left leg, the distal end was turned back and double ligated (unconnected) to prevent end-organ reinnervation. Rats received Cyclosporin A daily for 12 weeks to allow for regeneration and were sacrificed at 16 (n = 5) or 18 (n = 5) weeks following engraftment to assess axonal degeneration following immunosuppression withdrawal. Five Lewis rats receiving autografts served as control and were sacrificed at 12 weeks. Morphometric analysis was performed. In the control group (autografts) the cross-sectional area of and the number of myelinated fibres in the unconnected grafts was double that of the connected grafts, suggesting a sprouting effect. There was a tenfold reduction in the mean number of fibres at weeks 16 and 18 in the allografts compared to controls, without any significant differences in the connected versus unconnected sides. End-organ reinnervation decreases sprouting of axons within the graft but does not protect axons from degeneration following immunosuppression withdrawal.

Journal Article↗
PubMed1998

Isolated intracranial involvement in Rosai-Dorfman disease: a report of two cases and review of the literature.

Rosai-Dorfman disease is an idiopathic histiocytic disorder of lymph nodes and extranodal sites. Central nervous system manifestations of this disease are rare, and to our knowledge only 16 cases of intracranial involvement have been reported previously. Intracranial Rosai-Dorfman disease clinically and radiologically resembles meningioma, and histologic examination is essential for a definitive diagnosis. We report two cases of isolated, intracranial, dural-based Rosai-Dorfman disease, review the literature, and discuss the differential diagnoses of this lesion.

Adult↗