Biomedical subjects

A Alam

Publications and source records attributed to A Alam.

At least 37 records · Page 2Linked to original sources

PubMed2001

Lupeol, a triterpene, inhibits early responses of tumor promotion induced by benzoyl peroxide in murine skin.

The modulating effect of Lupeol [lup-20(29)-en-3 beta -ol], a triterpene found in many fruits and medicinal plants, on benzoyl peroxide-induced tumor promotion responses or tumor promotion in murine skin is described. Benzoyl peroxide is an effective cutaneous tumor promoter acting through the generation of oxidative stress, the induction of ornithine decarboxylase activity and the enhancement of DNA synthesis. Benzoyl peroxide treatment increases cutaneous microsomal lipid peroxidation and hydrogen peroxide generation. The activity of the cutaneous antioxidant enzymes, namely catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase, is decreased and levels of cutaneous glutathione are depleted. Benzoyl peroxide treatment also induces ornithine decarboxylase activity and enhances [3H]thymidine uptake in DNA synthesis. Prophylactic treatment of mice with lupeol (0.75 and 1.5 mg per animal) 1 hour before benzoyl peroxide treatment resulted in a diminution of benzoyl peroxide-mediated damage. The susceptibility of cutaneous microsomal membrane to lipid peroxidation and hydrogen peroxide generation was significantly reduced (P< 0.01 and P< 0.01, respectively). In addition, depleted levels of glutathione and inhibited activity of antioxidant enzymes were recovered to a significant level (P< 0.01, P< 0.05 and P< 0.01, respectively). Similarly, the elevated ornithine decarboxylase activity and enhanced thymidine uptake in DNA synthesis were inhibited significantly (P< 0.05) in a dose-dependent manner. The protective effect of lupeol was dose dependent in all parameters. The results suggest that lupeol is an effective skin chemopreventive agent that may suppress benzoyl peroxide-induced cutaneous toxicity.

Animals↗

PubMed2001

Tephrosia purpurea alleviates phorbol ester-induced tumor promotion response in murine skin.

In recent years, considerable emphasis has been placed on identifying new cancer chemopreventive agents, which could be useful for the human population. Tephrosia purpurea has been shown to possess significant activity against hepatotoxicity, pharmacological and physiological disorders. Earlier we showed that Tephrosia purpurea inhibits benzoyl peroxide-mediated cutaneous oxidative stress and toxicity. In the present study, we therefore assessed the effect of Tephrosia purpurea on 12-O-tetradecanoyl phorbal-13-acetate (TPA; a well-known phorbol ester) induced cutaneous oxidative stress and toxicity in murine skin. The pre-treatment of Swiss albino mice with Tephrosia purpurea prior to application of croton oil (phorbol ester) resulted in a dose-dependent inhibition of cutaneous carcinogenesis. Skin tumor initiation was achieved by a single topical application of 7,12-dimethyl benz(a)anthracene (DMBA) (25 microg per animal per 0.2 ml acetone) to mice. Ten days later tumor promotion was started by twice weekly topical application of croton oil (0.5% per animal per 0.2 ml acetone, v /v). Topical application of Tephrosia purpurea 1 h prior to each application of croton oil (phorbol ester) resulted in a significant protection against cutaneous carcinogenesis in a dose-dependent manner. The animals pre-treated with Tephrosia purpurea showed a decrease in both tumor incidence and tumor yield as compared to the croton oil (phorbol ester)-treated control group. In addition, a significant reduction in TPA-mediated induction in cutaneous ornithine decarboxylase (ODC) activity and [3H]thymidine incorporation was also observed in animals pre-treated with a topical application of Tephrosia purpurea. The effect of topical application of Tephrosia purpurea on TPA-mediated depletion in the level of enzymatic and non-enzymatic molecules in skin was also evaluated and it was observed that topical application of Tephrosia purpurea prior to TPA resulted in the significant recovery of TPA-mediated depletion in the level of these molecules, namely glutathione, glutathione S-transferase, glutathione reductase and catalase. From these data we suggest that Tephrosia purpurea can abrogate the tumor-promoting effect of croton oil (phorbol ester) in murine skin.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2001

Tephrosia purpurea ameliorates N-diethylnitrosamine and potassium bromate-mediated renal oxidative stress and toxicity in Wistar rats.

In an earlier communication, we have shown that Tephrosia purpurea ameliorates benzoyl peroxide-induced oxidative stress in murine skin (Saleem et al. 1999). The present study was designed to investigate a chemopreventive efficacy of T purpurea against N-diethylnitrosamine-initiated and potassium bromate-mediated oxidative stress and toxicity in rat kidney. A single intraperitoneal dose of N-diethylnitrosamine (200 mg/kg body weight) one hr prior to the dose of KBrO3 (125 mg/kg body weight) increases microsomal lipid peroxidation and the activity of xanthine oxidase and decreases the activities of renal antioxidant enzymes viz., catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase, phase II metabolizing enzymes such as glutathione-S-transferase and quinone reductase and causes depletion in the level of renal glutathione content. A sharp increase in blood urea nitrogen and serum creatinine has also been observed. Prophylactic treatment of rats with T. purpurea at doses of 5 mg/kg body weight and 10 mg/kg body weight prevented N-diethylnitrosamine-initiated and KBrO3 promoted renal oxidative stress and toxicity. The susceptibility of renal microsomal membrane for iron ascorbate-induced lipid peroxidation and xanthine oxidase activities were significantly reduced (P<0.01). The depleted levels of glutathione, the inhibited activities of antioxidant enzymes, phase II metabolizing enzymes and the enhanced levels of serum creatinine and blood urea nitrogen were recovered to a significant level (P<0.01). All the antioxidant enzymes were recovered dose-dependently. Our data indicate that T purpurea besides a skin antioxidant can be a potent chemopreventive agent against renal oxidative stress and carcinogenesis induced by N-diethylnitrosamine and KBrO3.

Animals↗

PubMed2001

Liposome encapsulated tumor-associated antigens elicited humoral and cellular immune responses in mice bearing tumor.

Chemically induced tumors in mice provide a system to investigate tumor-associated antigens (TAA). The cell surface glycoprotein antigens on such tumor cells have been identified as suitable targets for immune attack. The induction of immune responses against (TAA) in N-nitrosodiethylamine (DEN) exposed mice has been examined. In order to present antigens to the immune system, the liposome was used as vehicle to deliver the TAA. Liposomal-TAA formulation, elicited both humoral and the cellular immune responses, when administered intramuscularly in DEN-exposed mice. Presence of circulatory antibodies against TAA and the induction of cellular responses in immunized mice were monitored using ELISA and in vitro cell proliferation assay of lymphocytes respectively. Specificity of antibody against TAA in immune sera was analysed using immunoblotting technique. Based on these results, it is proposed that the liposome encapsulated TAA may successfully be used to induce humoral and cellular immune responses against tumor.

Animals↗

PubMed2001

Role of positive charge of lysine residue on ribosome-inactivating property of gelonin.

The report that gelonin cross-linked with monoclonal antibodies with the use of 2-iminothiolane (2-IT) exhibited higher cytotoxicity than the conjugates prepared with the use of N-succinimidyl-3-(2-pyridylthio) propionate (SPDP) alone, has prompted us to investigate the effect of epsilon-NH2 group modification with 2-IT on the ribosome-inactivating property (RIP) of gelonin. The purified gelonin was modified with 2-IT at a different molar ratio and their effects on immunoreactivity and ribosome-inactivating property were compared with those of N-succinimidyl 6-[3-(2-pyridyldithio) propionamido] hexanoate (long chain-SPDP) and SPDP modified gelonin derivatives. Modification of single amino group with 2-IT results in about 25-50% inhibition of immunoreactivity and 60-70% loss of protein synthesis inhibition activity. Modification of 2-3 amino groups further hampers both immunoreactivity and protein synthesis inhibition property of gelonin. Both the long chain-SPDP with SPDP modifications showed more pronounced effects on immunoreactivity and RIP activity as compared to the similar ratio of 2-IT modification(s). It may, therefore, be concluded that the positive charge plays an important role in the immunological as well as the protein synthesis inhibitory effect of gelonin.

Antigens↗

PubMed2000

Cutting edge: soluble HLA-G1 triggers CD95/CD95 ligand-mediated apoptosis in activated CD8+ cells by interacting with CD8.

The nonpolymorphic soluble HLA-G1 (sHLA-G1) isoform has been reported to be secreted by trophoblast cells at the materno-fetal interface, suggesting that it may act as immunomodulator during pregnancy. In this paper, we report that affinity-purified beta2-microglobulin-associated sHLA-G1 triggered apoptosis in activated, but not resting CD8+ peripheral blood cells. We demonstrate by Western blotting that sHLA-G1 enhanced CD95 ligand expression in activated CD8+ cells. Cytotoxicity was inhibited by preincubation of the cells with a CD95 antagonist mAb (ZB4) or a soluble recombinant CD95-Fc, indicating that apoptosis is mediated through the CD95/CD95 ligand pathway. Finally, we show that such sHLA-G1-induced apoptosis depends on the interaction with CD8 molecules, with cell death being blocked by various CD8 mAbs.

Adjuvants, Immunologic↗

PubMed2000

Attenuation of benzoyl peroxide-mediated cutaneous oxidative stress and hyperproliferative response by the prophylactic treatment of mice with spearmint (Mentha spicata).

The modulating effect of spearmint (Mentha spicata) on benzoyl peroxide-induced responses of tumor promotion in murine skin was investigated. Benzoyl peroxide (BPO) is an effective cutaneous tumor promoter acting through the generation of oxidative stress, induction of ornithine decarboxylase activity and by enhancing DNA synthesis. BPO treatment (20 mg/animal) increased cutaneous microsomal lipid peroxidation and hydrogen peroxide generation. The activity of cutaneous antioxidant enzymes, namely catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase, was decreased and the level of cutaneous glutathione was depleted. BPO treatment also induced the ornithine decarboxylase activity and enhanced the [3H]thymidine uptake in DNA synthesis in murine skin. Prophylactic treatment of mice with spearmint extract (10, 15 and 20 mg/kg) 1 hr before BPO treatment resulted in the diminution of BPO-mediated damage. The susceptibility of cutaneous microsomal membrane to lipid peroxidation and hydrogen peroxide generation was significantly reduced (P < 0.05 ). In addition, depleted levels of glutathione, inhibited activity of glutathione dependent and antioxidant enzymes were recovered to a significant level (P < 0.01, P < 0.05 and P < 0.01, respectively). Similarly, the elevated ornithine decarboxylase activity and enhanced thymidine uptake in DNA synthesis was inhibited significantly (P < 0.05 ) in a dose-dependent manner. The protective effect of spearmint was dose dependent in all parameters. The result suggests that spearmint is an effective chemopreventive agent that may suppress BPO-induced cutaneous oxidative stress, toxicity and hyperproliferative effects in the skin of mice.

Animals↗

PubMed2000

Evaluation of the efficacy of Lawsonia alba in the alleviation of carbon tetrachloride-induced oxidative stress.

The hepatoprotective activity of the 50% ethanol extract of the bark of Lawsonia alba syn. L. inermis was investigated against the carbon tetrachloride-induced oxidative stress. Pretreatment of rats with doses of 250 and 500 mg/kg of the plant extract significantly (P < 0.001) lowered serum transaminases (GOT and GPT) and LDH levels, respectively, in a dose dependent manner against the significant (P < 0.001) rise of these damage marker enzymes when challenged with CCl4 (1 ml/kg, orally). Parallel to these changes, the plant extract prevented CCl4-induced oxidative stress by significantly maintaining the levels of reduced glutathione (GSH), its metabolizing enzymes and simultaneously inhibiting the production of free radicals. Pretreatment of rats with the extract also inhibited the peroxidation of microsomal lipids in a dose-dependent manner.

Animals↗

PubMed2000

Myrica nagi attenuates cumene hydroperoxide-induced cutaneous oxidative stress and toxicity in Swiss albino mice.

In recent years, considerable efforts have been made to identify new chemopreventive agents which could be useful for man. Myrica nagi, a subtropical shrub, has been shown to possess significant activity against hepatotoxicity and other pharmacological and physiological disorders. We have shown a chemopreventive effect of Myrica nagi on cumene hydroperoxide-induced cutaneous oxidative stress and toxicity in mice. Cumene hydroperoxide treatment at a dose level of 30 mg/animal/0.2 ml acetone enhances susceptibility of cutaneous microsomal membrane for iron-ascorbate-induced lipid peroxidation and induction of xanthine oxidase activity which are accompanied by decrease in the activities of cutaneous antioxidant enzymes such as catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and depletion in the level of cutaneous glutathione. Parallel to these changes a sharp decrease in the activities of phase II metabolizing enzymes such as glutathione S-transferase and quinone reductase has been observed. Application of Myrica nagi at doses of 2.0 mg and 4.0 mg/kg body weight in acetone prior to that of cumene hydroperoxide (30 mg/animal/0.2 ml acetone) treatment resulted in significant inhibition of cumene hydroperoxide-induced cutaneous oxidative stress and toxicity in a dose-dependent manner. Enhanced susceptibility of cutaneous microsomal membrane for lipid peroxidation induced by iron ascorbate and xanthine oxidase activities were significantly reduced (P<0.05). In addition the depleted level of glutathione, the inhibited activities of antioxidants, and phase II metabolizing enzymes were recovered to a significant level (P<0.05). The protective effect of Myrica nagi was dose-dependent. In summary our data suggest that Myrica nagi is an effective chemopreventive agent in skin and capable of ameliorating cumene hydroperoxide-induced cutaneous oxidative stress and toxicity.

Animals↗

PubMed2000

Etiology of sexually transmitted infections among street-based female sex workers in Dhaka, Bangladesh.

An etiological study of sexually transmitted infections (STIs) was conducted among female sex workers (FSWs) in Dhaka, Bangladesh. Endocervical swab and blood samples from 269 street-based FSWs were examined for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis as well as for antibodies to Treponema pallidum and herpes simplex virus 2 (HSV-2). Sociodemographic data and data regarding behavior were also collected. A total of 226 of the 269 FSWs (84%) were positive for the STI pathogens studied. Among the 269 FSWs, 35.5% were positive for N. gonorrhoeae, 25% were positive for C. trachomatis, 45.5% were positive for T. vaginalis, 32.6% were seropositive for T. pallidum, 62.5% were seropositive for HSV-2, and 51% had infections with two or more pathogens.

Animals↗

PubMed2000

Incoming human cytomegalovirus pp65 (UL83) contained in apoptotic infected fibroblasts is cross-presented to CD8(+) T cells by dendritic cells.

Human cytomegalovirus (HCMV) infection is well controlled mainly by cytotoxic CD8(+) T lymphocytes (CTL) directed against the matrix protein pp65 despite the numerous immune escape mechanisms developed by the virus. Dendritic cells (DCs) are key antigen-presenting cells for the generation of an immune response which have the capacity to acquire antigens via endocytosis of apoptotic cells and thus present peptides to major histocompatibility complex class I-restricted T cells. We examined whether this mechanism could contribute to the activation of anti-pp65 CTL. In this study, we show that infection by HCMV AD169 induced sensitization of MRC5 fibroblasts to tumor necrosis factor alpha-mediated apoptosis very early after virus inoculation and that pp65 contained in apoptotic cells came from the delivery of the matrix protein into the cell. We observed that immature DCs derived from peripheral monocytes were not permissive to HCMV AD169 infection but were able to internalize pp65-positive apoptotic infected MRC5 cells. We then demonstrated that following exposure to these apoptotic bodies, DCs could activate HLA-A2- or HLA-B35-restricted anti-pp65 CTL, suggesting that they acquired and processed properly fibroblast-derived pp65. Together, our data suggest that cross-presentation of incoming pp65 contained in apoptotic cells may provide a quick and efficient way to prime anti-HCMV CD8(+) T cells.

Antigen Presentation↗

PubMed1999

Early activation of caspases during T lymphocyte stimulation results in selective substrate cleavage in nonapoptotic cells.

Apoptosis induced by T cell receptor (TCR) triggering in T lymphocytes involves activation of cysteine proteases of the caspase family through their proteolytic processing. Caspase-3 cleavage was also reported during T cell stimulation in the absence of apoptosis, although the physiological relevance of this response remains unclear. We show here that the caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD) blocks proliferation, major histocompatibility complex class II expression, and blastic transformation during stimulation of peripheral blood lymphocytes. Moreover, T cell activation triggers the selective processing and activation of downstream caspases (caspase-3, -6, and -7), but not caspase-1, -2, or -4, as demonstrated even in intact cells using a cell-permeable fluorescent substrate. Caspase-3 processing occurs in different T cell subsets (CD4(+), CD8(+), CD45RA(+), and CD45RO(+)), and in activated B lymphocytes. The pathway leading to caspase activation involves death receptors and caspase-8, which is also processed after TCR triggering, but not caspase-9, which remains as a proenzyme. Most importantly, caspase activity results in a selective substrate specificity, since poly(ADP-ribose) polymerase (PARP), lamin B, and Wee1 kinase, but not DNA fragmentation factor (DFF45) or replication factor C (RFC140), are processed. Caspase and substrate processing occur in nonapoptotic lymphocytes. Thus, caspase activation is an early and physiological response in viable, stimulated lymphocytes, and appears to be involved in early steps of lymphocyte activation.

Amino Acid Chloromethyl Ketones↗

PubMed1999

Massively dilated esophagus in achalasia: response to pneumatic balloon dilation.

OBJECTIVE: Pneumatic balloon dilation is considered by many to be the treatment of choice for achalasia of the esophagus. Patients with untreated, long standing achalasia may develop massively dilated esophagi, sometimes difficult to dilate with a pneumatic balloon and, rarely, may require esophagectomy. We present our experience with nine such patients out of 110 who underwent pneumatic dilation. METHODS: Of 110 patients treated for achalasia by pneumatic balloon dilation, from January 1989 until December 1996, nine patients had massively dilated esophagi with transverse diameter >7 cm. Results of these patients are presented with pre- and postdilation symptom scores and barium esophagograms. This study was conducted at the Department of Gastroenterology, Shaikh Zayed Postgraduate Medical Institute, Lahore, Pakistan. A Microvasive Rigiflex 35 mm (Boston Scientific, Watertown, MA) pneumatic balloon was used for dilation. RESULTS: Although it is often tedious to perform pneumatic dilation in massively dilated esophagus, it was possible to dilate adequately, in all nine cases without complications, with good symptomatic improvement at 12-month follow-up. CONCLUSIONS: We recommend pneumatic balloon dilation in achalasia with massively dilated esophagus as a first line treatment, the failure of which requires surgical intervention.

Adult↗

PubMed1999

Purification and characterisation of gelonin from seeds of Gelonium multiflorum.

Gelonin, a ribosome-inactivating protein has been isolated from the seeds of Gelonium multifluorum of Euphorbiaceae family by two methods and the results are compared. In method-I conventional aqueous extraction, cation-exchange and gel-filtration chromatography has been used. In method-II S-Sepharose fast flow gel has been used to purify the proteins from the seed extract, followed by ammonium sulfate fractionation, cation-exchange and gel-filtration chromatography. Extensive physico-chemical and immunological characterizations show that molecular weight of gelonin as determined by gel-filtration chromatography and SDS-PAGE is approximately 30 kDa. The non-proteinous material which binds to CMC-gel in association with gelonin in method-I is substantially removed when gelonin is purified by method-II. Cation exchange, G-100 chromatography, RP-HPLC and SDS-PAGE show that method-II yields 50% more purified gelonin when compared to the yield by method-I. The immunoreactivity of gelonin obtained by methods I and II vary from 22-26% and 50-66% respectively and the ribosome-inactivating property vary from 46-56% and 70-87% respectively.

Chromatography, Gel↗

PubMed1998

The role of caspases in T cell development and the control of immune responses.

Apoptosis is responsible for the removal of potentially autoreactive or useless T cells during thymic selection and activated T cells in the periphery. Specific families of receptors, kinases, transcription factors, and cysteine proteases, termed caspases, are involved in the apoptotic cascade leading to proteolysis of specific substrates and to morphological changes associated with programmed cell death. Although common members of the apoptotic cascade are shared between different cell types, it appears that cell-specific factors can influence the response to a given apoptotic stimuli. Characterization and understanding of the basic mechanisms involved in the different pathways protecting or leading to cell death may provide novel ways to control inappropriate apoptosis involved in several diseases.

Animals↗

PubMed1998

Pneumatic balloon dilation in achalasia: a prospective comparison of balloon distention time.

OBJECTIVE: Duration of Inflation in pneumatic balloon dilatation as treatment of achalasia has been variable ranging from 15 s to 6 min. A 60 s duration appears to be most often used. We compared the efficacy of dilation of achalasia with either 6- or 60-s inflation duration using a Rigiflex dilator of 3.0 cm diameter. METHODS: Eighty-one consecutive patients were prospectively studied in a randomized fashion, 41 in the 60-s group (A) and 40 patients in the 6-s group (B). Mean age of group A was 43 +/- 16.2 yr and of group B was 40 +/- 16.4 yr. Symptoms of dysphagia, chest pain, heartburn, regurgitation, and night cough were evaluated at basal (before dilation), 1- and 6-month intervals after dilation in both groups. Barium swallow was done to assess esophageal emptying 1 wk before dilation and 5 min postdilation in both groups. RESULTS: Significant and sustained improvement was seen for all symptoms in both groups. In addition, the degree of improvement in symptom scores between the two groups was similar. Barium esophagram in both groups at basal and immediately postdilation showed significant improvement in barium emptying but there was no significant difference between the two groups, indicative of equal efficacy in both distention times. Two patients needed repeat dilatation in group A and one in group B, with one drop out from group A, who was lost to follow-up, and was excluded from the analysis. No perforation occurred. CONCLUSION: Short duration of pneumatic balloon dilatation (6-s) is as effective as longer duration (60-s) in treatment of achalasia.

Adult↗

PubMed1998

Predicting hospital mortality in cirrhotic patients: comparison of Child-Pugh and Acute Physiology, Age and Chronic Health Evaluation (APACHE III) scoring systems.

OBJECTIVE: The severity of hepatic abnormalities and extent of dysfunction of other organ systems influences prognosis for cirrhosis. The Child-Pugh system has been used to classify cirrhotic patients into good, intermediate, or poor risk categories in evaluation and therapy. Disregard for cardiorespiratory, renal, electrolyte balance, and acid base status limits its predictive accuracy. We evaluated the accuracy of Acute Physiology and Chronic Health Evaluation (APACHE III) to predict short term hospital mortality in patients with liver cirrhosis. METHODS: A total of 282 patients were prospectively enrolled. Child-Pugh and APACHE III scores were recorded on day 1 for each patient. RESULTS: Mean age was 51.7+/-11.3 yr, with 65% men and 35% women; 57% presented with upper GI bleeding, 47% encephalopathy, 9% hepatorenal syndrome, and 7% hepatocellular carcinoma. Sixty-three patients (22%) died. Major causes of death were upper GI bleeding 38%, liver failure 21%, hepatorenal syndrome 19%, hepatocellular carcinoma 4%, and spontaneous bacterial peritonitis 6%. Child-Pugh and APACHE III scores for survivors (8.6+/-2.3 and 58.9+/-35.1) were lower than those for nonsurvivors (10.9+/-2.7 and 87.4+/-30.3) (p < 0.001). Using discriminant analysis, APACHE III correctly identified 75% of cases vs 67% of cases for Child-Pugh (p < 0.05). When information regarding ascites and prothrombin time was added to APACHE III, 81% of cases were correctly classified. CONCLUSION: The APACHE III scoring system is superior to Child-Pugh for prognosticating short term survival of cirrhotic patients. Prognostic accuracy of APACHE III can be enhanced by incorporating information regarding ascites and prothrombin time prolongation.

APACHE↗

PubMed1998

T cell receptor gene in synovial tissues of rheumatoid arthritis.

Rheumatoid arthritis is a chronic and destructive autoimmune joint disease characterized by inflammation of synovial tissue of unknown aetiology. Studies on TCR genes expressed by infiltrating T cells in synovial tissues have attempted to identify mechanism and specificity of the recruitment. T cell infiltrate in rheumatoid arthritis appears to be an association of a polyclonal non specific infiltrate with dominant clones or clonotypes. T cell repertoire in synovial tissue is biased compared to peripheral blood but no TCR V gene can be identified as commonly over-used. Comparison of motifs found in the CDR3 region of dominant clones from different studies has currently failed to identified a commonly motif. The fact that a number of dominant clones or clonotypes is present in different joints and at different times of the disease suggests a selective expansion of T lymphocytes in rheumatoid arthritis synovial membrane. Further investigations are needed to characterize the specificity of these dominant clonotypes.

Animals↗