Papers by Charles Malemud
Osteoarthritis and Cartilage, 2006
PubMed, 1984
Proteoglycans were prepared from rabbit articular cartilages by classical techniques employing 4.... more Proteoglycans were prepared from rabbit articular cartilages by classical techniques employing 4.0 M guanidine. HCl by transport ultracentrifugation techniques on the purified proteoglycans, present. A new method of extracting the cartilage with 0.4 M guanidine. HCl in the presence of highly purified collagenase is presented. The same yield of proteoglycans on extraction of normal cartilage was obtained as with the classical technique, but a larger proportion of intermediate and large aggregates was obtained with the new than with the classical methodologies. The osteoarthritic cartilage was obtained from 6 month old animals, 3 months after a partial medial meniscectomy had been performed. The profile of proteoglycans from osteoarthritic cartilage consisted predominately of monomers, and a small content of aggregates spread over intermediate and large size ranges. It is postulated that by the methods of extraction, the profile of proteoglycan aggregates present in vivo is more faithfully reproduced than obtained by the classical methodologies.
PubMed, Mar 1, 1982
A histopathologic system of classifying minced human hip and knee osteoarthritic cartilage often ... more A histopathologic system of classifying minced human hip and knee osteoarthritic cartilage often used in organ cultures was developed. The tissue types characterizing the cartilage fragments were correlated with characteristics noted in full thickness cartilage specimens from young normal, aged and osteoarthritic cartilage. In the minced tissue specimens 3 distinct tissue types (A, B, and C) were discerned. Tissue types A and B were seen in nonfibrillated discolored as well as fibrillated osteoarthritic cartilage. Type C tissue was derived principally from chondroosteophytic spurs. Each tissue type differed in the number and organization of chondrocytes and orthochromatic and metachromatic staining of the perilacunar region and interterritorial matrix. No A, B or C tissue types were seen in normal cartilage samples derived from patients below the age of 50. Cartilage from patients above this age contained elements of all 3 tissue types.
Biochemical journal. Cellular aspects, Aug 15, 1982
Proteoglycan biosynthesis by human osteochondrophytic spurs (osteophytes) obtained from osteoarth... more Proteoglycan biosynthesis by human osteochondrophytic spurs (osteophytes) obtained from osteoarthritic femoral heads at the time of surgical joint replacement was studied under defined culture conditions in vitro. Osteophytes were primarily present in two anatomic locations, marginal and epi-articular. Minced tissue slices were incubated in the presence of [f"Slsulphate or [14C]glucosamine. Osteophytes incorporated both labelled precursors into proteoglycan, which was subsequently characterized by CsCl-isopycnicdensity-gradient ultracentrifugation and chromatography on Sepharose CL-2B. The material extracted with 0.5 M-guanidinium chloride showed 78.1% of [35S]sulphate in the Al fraction after centrifugation. Only 23.0% of the [35S]sulphate in this Al fraction was eluted in the void volume of Sepharose CL-2B under associative conditions. About 60-80% of the [35S]sulphate in the tissue 4 M-guanidinium chloride extract was associated with monomeric proteoglycan (fraction D 1). The average partition coefficient (Ka.) of the proteoglycan monomer on Sepharose CL-2B was 0.28-0.33. Approx. 12.4% of this monomer formed stable aggregates with high-molecular-weight hyaluronic acid in vitro. Sepharose CL-2B chromatography of fractions with lower buoyant densities (fractions D2-D4) demonstrated elution profiles on Sepharose CL-2B substantially different than that of fraction Dl, indicative of the polydisperse nature of the newly synthesized proteoglycan. Analysis of the composition and chain size of the glycosaminoglycans showed the following: (1) preferential elution of both [35S]sulphate and ['4C]glucosamine in the 0.5M-LiCl fraction on DEAE-cellulose; (2) the predomi- nant sulphated glycosaminoglycan was chondroitin 6-sulphate (60-70%), with 9-11% keratan sulphate in the monomer proteoglycan; (3) Kav values of 0.38 on Sephadex G-200 and 0.48 on Sepharose CL-6B were obtained with papain-digested and NaBH4-treated Dl monomer respectively. A comparison of the synthetic9 with endogenous glycosaminoglycans indicated similar types. These studies indicated that human osteophytes synthesized in vitro sulphated proteoglycans with some charac- teristics similar to those of mature human articular cartilage, notably in the size of their proteoglycan monomer and predominance of chondroitin 6-sulphate. They differed from articular cartilage primarily in the lack of substantial quantities of keratan sulphate and aggregation properties associated with monomer interaction with hyaluronic acid.
The Journal of Rheumatology
ABSTRACT
Biochemical Journal, 1982
Proteoglycan biosynthesis by human osteochondrophytic spurs (osteophytes) obtained from osteoarth... more Proteoglycan biosynthesis by human osteochondrophytic spurs (osteophytes) obtained from osteoarthritic femoral heads at the time of surgical joint replacement was studied under defined culture conditions in vitro. Osteophytes were primarily present in two anatomic locations, marginal and epi-articular. Minced tissue slices were incubated in the presence of [35S]sulphate or [14C]glucosamine. Osteophytes incorporated both labelled precursors into proteoglycan, which was subsequently characterized by CsCl-isopycnic-density-gradient ultracentrifugation and chromatography on Sepharose CL-2B. The material extracted with 0.5m-guanidinium chloride showed 78.1% of [35S]sulphate in the A1 fraction after centrifugation. Only 23.0% of the [35S]sulphate in this A1 fraction was eluted in the void volume of Sepharose CL-2B under associative conditions. About 60–80% of the [35S]sulphate in the tissue 4m-guanidinium chloride extract was associated with monomeric proteoglycan (fraction D1). The avera...
The Journal of rheumatology
A histopathologic system of classifying minced human hip and knee osteoarthritic cartilage often ... more A histopathologic system of classifying minced human hip and knee osteoarthritic cartilage often used in organ cultures was developed. The tissue types characterizing the cartilage fragments were correlated with characteristics noted in full thickness cartilage specimens from young normal, aged and osteoarthritic cartilage. In the minced tissue specimens 3 distinct tissue types (A, B, and C) were discerned. Tissue types A and B were seen in nonfibrillated discolored as well as fibrillated osteoarthritic cartilage. Type C tissue was derived principally from chondroosteophytic spurs. Each tissue type differed in the number and organization of chondrocytes and orthochromatic and metachromatic staining of the perilacunar region and interterritorial matrix. No A, B or C tissue types were seen in normal cartilage samples derived from patients below the age of 50. Cartilage from patients above this age contained elements of all 3 tissue types.
The Journal of rheumatology, 1983
In vitro studies suggest that synovial fluid hyaluronic acid may have a role in reducing joint in... more In vitro studies suggest that synovial fluid hyaluronic acid may have a role in reducing joint inflammation. The effect of intraarticular injection of sodium hyaluronate in a model of experimental immune synovitis was assessed. In addition, tissue prostaglandin content of synovia with and without immune synovitis was compared. Intraarticular hyaluronic acid administered at 2 doses was not effective in reducing the induced inflammation. With immune synovitis there was an increase in the total synovial prostaglandins. When related to total prostaglandins, prostacyclin was decreased, prostaglandin F2 alpha and thromboxane were increased and prostaglandin E2 was the same in synovitis as compared to controls.
Acta biologica Hungarica, 1984
Proteoglycans were prepared from rabbit articular cartilages by classical techniques employing 4.... more Proteoglycans were prepared from rabbit articular cartilages by classical techniques employing 4.0 M guanidine. HCl by transport ultracentrifugation techniques on the purified proteoglycans, present. A new method of extracting the cartilage with 0.4 M guanidine. HCl in the presence of highly purified collagenase is presented. The same yield of proteoglycans on extraction of normal cartilage was obtained as with the classical technique, but a larger proportion of intermediate and large aggregates was obtained with the new than with the classical methodologies. The osteoarthritic cartilage was obtained from 6 month old animals, 3 months after a partial medial meniscectomy had been performed. The profile of proteoglycans from osteoarthritic cartilage consisted predominately of monomers, and a small content of aggregates spread over intermediate and large size ranges. It is postulated that by the methods of extraction, the profile of proteoglycan aggregates present in vivo is more faith...
British journal of clinical practice. Supplement, 1986
Seminars in Arthritis and Rheumatism, 1981
Monolayer and spinner cultured rabbit articular chondrocytes released into the medium latent meta... more Monolayer and spinner cultured rabbit articular chondrocytes released into the medium latent metal<iependent enzyme with activity against bovine proteoglycan. Pretreatment of medium with p-aminophenylmercuric acetate or trypsin followed by soybean trypsin inhibitor significantly increased enzyme activity. The monolayer-cultured chondrocytes released more of this activity than spinner cultures. The neutral proteoglycanase activity increased with medium concentration and incubation time. Like the human cartilage proteoglycanase, its pH optimum on proteoglycan subunit was 7.25. Gel filtration on BioGel P-30 indicated that the proteoglycanase occurred in two molecular weight forms: 20 000--30 000 and 13 000. The latent enzyme was about 30 000--40 000. The metalchelators, o-phenanthroline (5 mM) and EDTA (10 mM) inhibited the activated proteoglycanase almost completely , but trypsin and chymotrypsin inhibitors had little effect. The cultured chondrocytes also released into the media a heat-labile inhibitor against the proteoglycanase. The inhibitory activity was present in the nonactivated media and eluted on Sephadex G-100 chiefly at a position corresponding to molecul~ weights of 10 000--13 000.
HSOA journal of clinical immunology & immunotherapy, Dec 31, 2021
InTech eBooks, Aug 23, 2011
Journal of applied microbiology and biochemistry, 2020
InTech eBooks, Sep 19, 2018
Chronic inflammation drives the progression of rheumatoid arthritis (RA) and osteoarthritis (OA) ... more Chronic inflammation drives the progression of rheumatoid arthritis (RA) and osteoarthritis (OA) to synovial joint failure. The inflammatory state in both musculoskeletal diseases is associated with significantly elevated levels of pro-inflammatory cytokines in joint synovial fluid, which is best exemplified by increases in interleukin-1β (IL-1β), IL-6, IL-17, tumor necrosis factor-α, among others, as well as increased activity of soluble mediators such as nitric oxide and certain growth factors including vascular endothelial growth factor and fibroblast growth factor. The multitude of these factors activate chondrocyte signal transduction pathways resulting in programmed cell death, otherwise known as apoptosis as well as compromising chondrocyte autophagy. Importantly, chondrocyte apoptosis causes a loss of articular cartilage vitality which dampens cartilage repair mechanisms because at present, the possibility that chondrocyte progenitor cells could replace those differentiated chondrocytes lost via apoptosis remains debatable. Certain pharmacologic interventions which have been proven to induce apoptosis in various cancer cell studies in vitro suggest the possibility that drugs could be developed to specifically suppress or completely inhibit chondrocyte apoptosis in RA and OA cartilage. This review supports that contention and indicates that apoptosis can be inhibited by identifying novel cellular targets which promote apoptosis and autophagy.
International Journal of Clinical Rheumatology, 2016
Anti-inflammatory & anti-allergy agents in medicinal chemistry, Apr 1, 2011
PubMed, Mar 12, 2010
Objective: To critically evaluate the role of several notable 'pain pathways' in the fibromyalgia... more Objective: To critically evaluate the role of several notable 'pain pathways' in the fibromyalgia syndrome (FMS). Methods: PubMed provided the data base for peer-reviewed basic and clinical science studies on musculoskele-tal and neuropathic pain mechanisms with a principal emphasis on critically appraising papers from 2002 to the present. Results: FMS pharmacotherapy is more prevalent in clinical practice as our understanding of the cellular, molecular and pathophysiologic mechanisms contributing to widespread musculoskeletal and neuropathic pain has emerged. Thus, several 'pain pathways' including high-voltage activated Ca2+ channels and the K(v)1 family of K+ channels ion channels appear related to the efficacy of pregabalin and amitryptyline, respectively, in FMS. Additionally, serotonergic and serotonergic/norepinephrine receptor-mediated mechanisms may explain the reported pharmacologic efficacy in FMS of mirtazapine, duloxetine and milnacipran. By contrast, the decreased level of micro-opioid receptors in the CNS of FMS patients suggests a mechanism as to why opioid therapy should be avoided. However, increased peripheral benzodiazepine receptors on monocytes from FMS patients suggested an explanation for the reported efficacy of olanzapine in FMS. Conclusion: Pregabalin was the first drug approved by the FDA for the treatment of FMS-related pain. Drugs that have been assessed for their potential use in FMS pharmacotherapy include gabapentin and tricylic antidepressants. These drugs appear to target specific Ca2+ or K+ ion channels notable for their involvement in mediating neuropathic pain. Serotonin and norepinephrine reuptake inhibitors including, mirtazapine, duloxetine and milnacipran appear to be more efficacious in FMS than selective serotonin reuptake inhibitors. Milnacipran became the second FDA-approved drug for FMS.
Uploads
Papers by Charles Malemud