Absence of collagen deficiency in familial cerebral aneurysms

1989 ◽  
Vol 70 (6) ◽  
pp. 837-840 ◽  
Author(s):  
Richard Leblanc ◽  
Andrés M. Lozano ◽  
Michel van der Rest ◽  
Ronald David Guttmann
Keyword(s):  
Cell Lines ◽  
Polyacrylamide Gel Electrophoresis ◽  
Control Cell ◽  
Sodium Dodecyl ◽  
Cerebral Aneurysms ◽  
Type Iii Collagen ◽  
Type I ◽  
Content Type ◽  
Type Iii ◽  
Fine Print

✓ It has been suggested that a deficiency in the expression of type III collagen may play a role in the pathogenesis of cerebral aneurysms. To test this hypothesis in cases of familial cerebral aneurysms, fibroblast cell cultures were established and the expression of collagen types I and III was studied in a patient with three cerebral aneurysms whose mother and sister also had cerebral aneurysms. Cultured skin fibroblasts were labeled with tritiated proline. The collagens and procollagens were precipitated and run on sodium dodecyl sulfate-polyacrylamide gel electrophoresis after reduction to analyze procollagen chains. Control cell lines were analyzed simultaneously. Quantitation of the ratios of type III to type I procollagen synthesis was achieved by integration of the intensities of the pro-α1 (III), pro-α1(I), and pro-α2(I) bands on fluorograms of electrophoretic gels of medium proteins. There was no difference in type I and III procollagen levels observed between the cells from the aneurysm patient and those from the control cell lines. These data do not support the hypothesis that familial cerebral aneurysms are caused by a deficiency of type III collagen.

scholarly journals Characterization of pepsin-solubilized bovine heart-valve collagen

1978 ◽  
Vol 173 (3) ◽  
pp. 885-894 ◽  
Author(s):  
R I Bashey ◽  
H M Bashey ◽  
S A Jimenez
Keyword(s):  
Heart Valve ◽  
Sodium Dodecyl Sulphate ◽  
Gel Electrophoresis ◽  
Heart Valves ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Polyacrylamide Gel ◽  
Type Iii Collagen ◽  
Type I ◽  
Type Iii

Collagens extracted from heart valves by using limited pepsin digestion were fractionated by differential salt precipitation. Collagen types were identified by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, amino acid analysis and cleavage with CNBr. Heart-valve collagen was heterogeneous in nature, consisting of a mixture of type-I and type-III collagens. The identity of type-III collagen was established on the basis of (a) insolubility in 1.7 M-NaC1 at neutral pH, (b) behaviour of this collagen fraction on gel electrophoresis under reducing and non-reducing conditions, (c) amino acid analysis showing a hydroxyproline/proline ratio greater than 1, and (d) profile of CNBr peptides on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis showing a peak characteristic for type-III collagen containing peptides alpha1(III)CB8 and alpha1(III)CB3. In addition to types-I and -III collagen, a collagen polypeptide not previously described in heart valves was identified. This polypeptide represented approx. 30% of the collagen fraction precipitated at 4.0 M-NaCl, it migrated between beta- and alpha1-collagen chains on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and its electrophoretic behaviour was not affected by disulphide-bond reduction. All collagen fractions from the heart valves contained increased amounts of hydroxylysine when compared with type-I and -III collagens from other tissues. The presence of beta- and gamma-chains and higher aggregates in pepsin-solubilized collagen indicated that these collagens were highly cross-linked and suggested that some of these cross-links involved the triple-helical regions of the molecule. It is likely that the higher hydroxylysine content of heart-valve collagen is responsible for the high degree of intermolecular cross-linking and may be the result of an adaptive mechanism for the specialized function of these tissues.

Collagen deficiency and ruptured cerebral aneurysms

1983 ◽  
Vol 59 (1) ◽  
pp. 16-20 ◽  
Author(s):  
Glenn Neil-Dwyer ◽  
John R. Bartlett ◽  
Alan C. Nicholls ◽  
Paolo Narcisi ◽  
F. Michael Pope
Keyword(s):  
Gel Electrophoresis ◽  
Matched Control ◽  
Polyacrylamide Gel Electrophoresis ◽  
Cerebral Aneurysms ◽  
Surgical Patients ◽  
Buffer System ◽  
Type Iii Collagen ◽  
Content Type ◽  
Type Iii ◽  
And Control

✓ Skin and temporal arterial biopsies were obtained from 17 patients undergoing surgery for ruptured cerebral aneurysm, and specimens were taken from six age- and sex-matched control surgical patients. Radioactively labeled and control tissue collagen patterns were studied by interrupted polyacrylamide gel electrophoresis (PAGE), using the trisborate buffer system or by carboxymethyl cellulose (CMC) chromatography. Type III/I collagen ratios were then measured from autoradiographs of the radioactively labeled samples using the Joyce Loebl gel scanner adapted for flat bed gels. In the case of the CMC labeled material, the ratios were measured by the ratios of the summed radioactively labeled α1(III), α2(II), and α2(I) peaks. Eleven of the 17 patients were Type III collagen-deficient while all of the six control patients had normal collagen ratios. The implications of these findings are discussed.

scholarly journals Nature of collagens synthesized by monkey periodontal-ligament fibroblasts in vitro

1978 ◽  
Vol 170 (1) ◽  
pp. 63-71 ◽  
Author(s):  
H F Limeback ◽  
J Sodek ◽  
D M Brunette
Keyword(s):  
Periodontal Ligament ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Deae Cellulose ◽  
Type Iii Collagen ◽  
Type I ◽  
Periodontal Ligament Fibroblasts ◽  
Type Iii ◽  
Type I Procollagen

1. First subcultures of fibroblast-like cells from adult monkey periodontal ligament were incubated in the presence of 14C-labelled amino acids and produced significant amounts of type-I and type-III collagens. 2. The proportion of type-III collagen produced was calculated on the basis of the recovery of procollagens from DEAE-cellulose chromatography to be approx. 20%, and at least 10% when analysed as collagens on CM-cellulose chromatography. 3. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of the procollagens, the collagens and their CNBr peptides was used to confirm the identity of the collagen types. 4. In serum-free media extensive conversion of type-I procollagen, but not of type-III procollagen, into collagen was observed, suggesting that a specific type-I procollagen peptidase was produced. 5. The pattern of collagen synthesis was not significantly different from that obtained with fibroblasts derived from skin corium of the same animals.

Prognostic significance of intracranial dissemination of glioblastoma multiforme in adults

2005 ◽  
Vol 102 (4) ◽  
pp. 622-628 ◽  
Author(s):  
Andrew T. Parsa ◽  
Scott Wachhorst ◽  
Kathleen R. Lamborn ◽  
Michael D. Prados ◽  
Michael W. McDermott ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Tumor Progression ◽  
Prognostic Significance ◽  
Type I ◽  
Type Ii ◽  
Content Type ◽  
Type Iii ◽  
Multifocal Lesions ◽  
Tumor Dissemination ◽  
Fine Print

Object. The clinical outcome and treatment of adult patients with disseminated intracranial glioblastoma multiforme (GBM) is unclear. The objective in the present study was to assess the prognostic significance of disseminated intracranial GBM in adults at presentation and at the time of tumor progression. Methods. Clinical data from 1491 patients older than 17 years and harboring a GBM that had been diagnosed between 1988 and 1998 at the University of California at San Francisco neurooncology clinic were retrospectively reviewed. Dissemination of the GBM (126 patients) was determined based on Gd-enhanced magnetic resonance images. Classification of dissemination was as follows: Type I, single lesion with subependymal or subarachnoid spread; Type II, multifocal lesions without subependymal or subarachnoid spread; and Type III, multifocal lesions with subependymal or subarachnoid spread. Subgroups of patients were compared using Kaplan—Meier curves that depicted survival probability. The median postprogression survival (PPS), defined according to neuroimaging demonstrated dissemination, was 37 weeks for Type I (23 patients), 25 weeks for Type II (50 patients), and 10 weeks for Type III spread (19 patients). Patients with dissemination at first tumor progression (52 patients) overall had a shorter PPS than those in a control group with local progression, after adjusting for age, Karnofsky Performance Scale score, and time from tumor diagnosis to its progression (311 patients). When analyzed according to tumor dissemination type, PPS was significantly shorter in patients with Type II (33 patients, p < 0.01) and Type III spread (11 patients, p < 0.01) but not in those with Type I spread (eight patients, p = 0.18). Conclusions. Apparently, the presence of intracranial tumor dissemination on initial diagnosis does not in itself preclude aggressive treatment if a patient is otherwise well. A single focus of GBM that later demonstrates Type I dissemination on progression does not have a worse prognosis than a lesion that exhibits only local recurrence.

Primary extradural meningiomas: a report on nine cases and review of the CT-era literature

2000 ◽  
Vol 93 (6) ◽  
pp. 940-950 ◽  
Author(s):  
Frederick F. Lang ◽  
O. Kenneth Macdonald ◽  
Gregory N. Fuller ◽  
Franco DeMonte
Keyword(s):  
Skull Base ◽  
Death Rate ◽  
Benign Tumors ◽  
Data Sets ◽  
Type I ◽  
Type Ii ◽  
Content Type ◽  
Type Iii ◽  
Clinical Records ◽  
Fine Print

Object. Primary meningiomas arising outside the intracranial compartment (primary extradural meningiomas [PEMs]) are rare tumors. To develop a better understanding of these tumors and to establish a comprehensive classification scheme for them, the authors analyzed a series of patients treated at the M. D. Anderson Cancer Center (MDACC) and reviewed all cases reported in the English-language literature since the inception of the use of computerized tomography (CT) scanning.Methods. Clinical records, results of radiographic studies, and histological slides were reviewed for all cases of PEM at MDACC. Demographic features, symptoms, tumor location, histological grade, and patient outcome were assessed in all cases. A comprehensive literature search identified 168 PEMs in 142 patients reported during the CT era. These reports were also analyzed for common features. Tumors for both data sets were classified as purely extracalvarial (Type I), purely calvarial (Type II), and calvarial with extracalvarial extension (Type III). Type II and Type III tumors were further categorized as convexity (C) or skull base (B) lesions.The incidence of PEMs at MDACC was 1.6%, which was consistent with the rate reported in the literature. In both data sets, the male/female ratio was nearly 1:1. The most common presenting symptom was a gradually expanding mass. The age of patients at diagnosis of PEM was bimodal, peaking during the second decade and during the fifth to seventh decades. In all MDACC cases and in 90% of those reported in the literature the PEMs were located in the head and neck. The majority of tumors originated in the skull (70%).In the MDACC series and in the literature review, the majority (67% and 89%, respectively) of tumors were histologically benign. Although fewer PEMs were malignant or atypical (33% at MDACC and 11% in the literature), their incidence was higher than that observed for primary intracranial meningiomas. Distant metastasis was not a common feature reported for patients with PEMs (6% in the literature).Outcome data were available in 96 of the cases culled from the CT-era literature. The combination of the MDACC data and the data obtained from the literature demonstrated that patients with benign Type IIB or Type IIIB lesions were more likely to experience recurrence than patients with benign Type IIC or Type IIIC tumors (26% compared with 0%, p < 0.05). The more aggressive atypical and malignant tumors were associated with a statistically significant higher death rate (29%) relative to benign tumors (4.8% death rate, p < 0.004).Conclusions. Defining a tumor as a PEM is dependent on the tumor's relation to the dura mater and the extent and direction of its growth. Classification of PEMs as calvarial or extracalvarial and as convexity or skull base lesions correlates well with clinical outcome.

scholarly journals Role of glycoprotein IIa (beta 1 subunit of very late activation antigens) in platelet functions

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 2021-2026 ◽  
Author(s):  
S Parmentier ◽  
B Catimel ◽  
L McGregor ◽  
LL Leung ◽  
JL McGregor
Keyword(s):  
Platelet Adhesion ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Lag Phase ◽  
Type Iii Collagen ◽  
Type I ◽  
Western Blots ◽  
Activation Antigens ◽  
Platelet Functions

Abstract Very late activation antigens (VLAs) are glycoproteins (GPs) that play a major role in platelet adhesion to extracellular matrix. These GPs, members of the integrin family, are heterodimer complexes with different alpha subunits noncovalently associated with a common beta 1 subunit known as GPIIa. GPIa-IIa (also known as VLA2), GPIc-IIa (VLA5), and GPIc*-IIa (VLA6) are involved, respectively, in platelet adhesion to collagen, fibronectin, and laminin. At this stage, very little is known about the role of GPIIa in platelet adhesive functions. In this study, we have generated a monoclonal antibody (MoAb) (LYP22) directed against GPIIa. Immunoaffinity chromatography using LYP22 combined with two-dimensional nonreduced-reduced sodium dodecyl sulfate- polyacrylamide gel electrophoresis shows that the antibody brings down all VLA subunits. Western blots indicate that the binding site of LYP22 on GPIIa is disulfide bridge-dependent. The number of LYP22 binding sites is not increased on stimulation with thrombin and is in the range of what is observed with another anti-GPIIa MoAb (A-1A5). LYP22 is the first anti-GPIIa MoAb to inhibit aggregation and secretion of washed platelets stimulated with collagen, thrombin, or arachidonic acid. Moreover, the lag-phase usually observed on collagen stimulation is significantly prolonged (by 60 seconds) in the presence of LYP22. This lag-phase, mediated by LYP22, is also observed in the presence of plasma proteins and is coupled with a reduced effect on collagen- induced platelet aggregation. In addition, LYP22 affects the adhesion of resting platelets to type III collagen, but not to fibronectin, laminin, or type I collagen. These results strongly indicate that the site on GPIIa, bearing the LYP22 epitope, is an active participant in signal transduction controlling platelet functions.

Collagen type III deficiency in patients with rupture of intracranial saccular aneurysms

1987 ◽  
Vol 67 (5) ◽  
pp. 690-696 ◽  
Author(s):  
John R. Østergaard ◽  
Hans Oxlund
Keyword(s):  
Brachial Artery ◽  
Collagen Type ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Biomechanical Properties ◽  
Control Group ◽  
Type I ◽  
Collagen Type Iii ◽  
Type Iii ◽  
Saccular Aneurysms

✓ Samples of the middle cerebral artery (MCA) and the brachial artery were obtained post mortem from 14 patients who died following rupture of intracranial saccular aneurysms and from a control group of 14 age- and sex-matched patients who died of causes unrelated to aneurysm rupture. The biomechanical properties of ring-shaped arterial specimens were investigated by loading the specimens at a constant deformation rate until rupture. The relative amounts of collagen type I and type III were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) studies of cyanogen bromide peptides of collagen prepared from the arterial samples. A deficiency of collagen type III was demonstrated in specimens of the MCA in six of 14 patients with a ruptured intracranial saccular aneurysm. This deficiency was not accompanied by alterations in the mechanical arterial strength but resulted in a significant increase in the extensibility at stress values corresponding to blood pressures between 100 and 200 mm Hg. No difference was found between aneurysm patients and the control group in regard to the biomechanical properties of the brachial artery, despite the presence of a significant deficiency of collagen type III. The increase in vascular extensibility of the MCA may represent alterations in the fibrous structure and functional integrity of the cerebral arteries of aneurysm patients with collagen type III deficiency. Together with aggravating hemodynamic stresses, this deficiency may be an important factor in the pathogenesis of saccular aneurysms.

Gamma surgery for vein of Galen malformations

2000 ◽  
Vol 93 (2) ◽  
pp. 229-236 ◽  
Author(s):  
Bryan Rankin Payne ◽  
Dheerendra Prasad ◽  
Melita Steiner ◽  
Hernan Bunge ◽  
Ladislau Steiner
Keyword(s):  
Additional Patient ◽  
Consecutive Series ◽  
Type I ◽  
Vein Of Galen ◽  
Content Type ◽  
Type Iii ◽  
Type Iv ◽  
Flow Through ◽  
Fine Print

Object. The goal of this study was to evaluate the results of gamma surgery in nine patients treated for vein of Galen malformations (VGMs).Methods. A consecutive series of nine VGMs in eight children aged 4 to 14 years and in one adult were treated with gamma surgery. Six of the patients were male, including the adult, and three were female. Among these patients there were three Yaşargil Type I, one Type II, two Type III, and three Type IV malformations. Previous embolization had failed in four cases. Three VGMs were treated with gamma surgery twice. An additional patient with a Type III VGM underwent stereotactic angiography in preparation for gamma surgery but was judged to be suitable for direct embolization.Follow-up angiograms were obtained in eight of the VGMs treated. Four no longer filled; one has probably been obliterated, but this cannot be confirmed because the patient refused to undergo final angiography; one patient has residual fistulas not included in the initial treatment field, which were retreated recently; and two other patients have marked reduction of flow through their VGMs.Conclusions. Gamma surgery is a viable option in the treatment of VGMs in clinically stable patients. Combined endovascular therapy and gamma surgery is of benefit in complex malformations.

Partial characterization of a soluble mitogenic factor from medulloblastoma

1988 ◽  
Vol 68 (2) ◽  
pp. 251-258 ◽  
Author(s):  
James T. Rutka ◽  
Jackson Hall ◽  
Jane R. Giblin ◽  
Dolores V. Dougherty ◽  
Michael S. B. Edwards ◽  
...  
Keyword(s):  
Conditioned Medium ◽  
Type I Collagen ◽  
Tritiated Thymidine ◽  
Deae Cellulose ◽  
Type Iii Collagen ◽  
Type I ◽  
Soluble Factor ◽  
Content Type ◽  
Type Iii

✓ To determine how medulloblastoma cells might influence the proliferation and phenotype of normal stromal cells, normal human leptomeningeal cells were treated in culture with medulloblastoma-conditioned medium; their ability to incorporate tritiated thymidine and synthesize collagen was measured. The treated leptomeningeal cells had a significantly greater uptake of tritiated thymidine and grew faster than control leptomeningeal cells. Immunofluorescence studies demonstrated a greater intensity of staining for procollagen type III in the cell layer of the treated cultures than in control cultures; diethylaminoethyl (DEAE)-cellulose chromatography of the medium showed that the treated cells synthesized predominantly type III collagen, whereas control cells synthesized type I collagen. Analysis of the medulloblastoma-conditioned medium revealed that the soluble factor responsible for these effects is an acid- and heat-stable protein. The increased proliferation and altered collagen synthesis induced in leptomeningeal cell cultures by a soluble factor from a medulloblastoma are examples of how tumor and stromal elements interact, and may be related to the process of desmoplasia often observed in medulloblastomas in vivo.

Camptothecin analogs in malignant gliomas: comparative analysis and characterization

2003 ◽  
Vol 98 (3) ◽  
pp. 570-577 ◽  
Author(s):  
Prakash Sampath ◽  
Eric Amundson ◽  
Monroe E. Wall ◽  
Betty M. Tyler ◽  
Mansukh C. Wani ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Cell Lines ◽  
Topoisomerase I ◽  
Glioma Cell ◽  
Malignant Gliomas ◽  
Sodium Dodecyl ◽  
Local Therapy ◽  
Content Type ◽  
Glioma Cell Lines ◽  
Fine Print

Object. The authors compared and characterized several new classes of camptothecin (CPT) analogs (a total of 22 drugs) directed against human and murine glioma cell lines in vitro, trying to identify CPT analogs that can be used for local therapy in future clinical trials. Camptothecin is a naturally occurring alkaloid that inhibits the DNA-replicating enzyme topoisomerase I. Moreover, CPT and its analogs have shown promising antitumor activity against both systemic and intracranial neoplasms. Because the CPTs have poor bioavailability and are unable to cross the blood—brain barrier, they may best be delivered to the central nervous system by polymers. The authors have previously shown that local delivery of Na-CPT by implantable polymers prolongs survival in a rat intracranial glioma model. In recent years, a number of newly synthesized CPT analogs have been developed that exhibit more potency and stability than Na-CPT. Methods. Cytotoxicities of the drugs were tested using modified clonogenic and monotetrazolium assays in three glioma cell lines. A potassium chloride—sodium dodecyl sulfate coprecipitation assay was used to determine the frequency of drug-stabilized cleavable complexes. Of the CPT analogs analyzed, the 10,11-methylenedioxy (MD) class consistently demonstrated the greatest cytotoxicity. Three of these analogs, 10,11-MD-20(RS)-CPT, 10,11-MD-20(S)-CPT-glycinate ester (Gly).HCl, and 9-amino-10,11-MD-20(S)-CPT-Gly, exhibit significantly greater antiproliferative activities than CPT, Na-CPT, or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) against all three glioma cell lines. In addition, the 10,11-MD20(RS)-CPT analog induces more cleavable complexes than Na-CPT at every concentration. Conclusions. The increased potency and greater stability of CPT analogs hold promise for more effective local antitumor treatments against malignant intracranial brain tumors. The greater cytotoxicity of 10,11-MD CPTs in comparison with other CPT analogs as well as CPT, BCNU, or Na-CPT, may present an ideal candidate drug class for development against both primary and metastatic brain tumors.

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