26 results on '"Light chain"'
Search Results
2. Dual expression of surface immunoglobulin light chains is real: First reported case in mantle cell lymphoma.
- Author
-
Wang, Wei J., Gehris, Brandon T., Ahmed, Ahmed A., Naik, Udit, and Chen, Lei
- Subjects
- *
PHYSICAL diagnosis , *FLOW cytometry , *STAINS & staining (Microscopy) , *CANCER chemotherapy , *GENE expression , *IMMUNOGLOBULIN light chains , *BLOOD testing , *NON-Hodgkin's lymphoma , *NEEDLE biopsy - Abstract
The article reports a rare case of mantle cell lymphoma (MCL) with dual expression of kappa and lambda light chains, which is a phenomenon rarely observed in bursa (B) -cell non-Hodgkin lymphomas. It highlights the importance of careful analysis and avoiding diagnostic pitfalls when interpreting flow cytometry results, particularly in cases of dual expression, to ensure accurate diagnosis and appropriate treatment.
- Published
- 2023
- Full Text
- View/download PDF
3. Violaceous truncal plaques consistent with amyloid light‐chain amyloidosis.
- Author
-
Beer, Jacob, Bittar, Julie, Hedberg, Matthew L., and Seykora, John T.
- Subjects
- *
AMYLOIDOSIS , *LIQUID chromatography-mass spectrometry , *AMYLOID plaque , *ITCHING , *ADIPOSE tissues - Abstract
Hepatic AL amyloidosis patients have hepatomegaly and elevated alkaline phosphatase levels; and gastrointestinal AL amyloidosis presents with dysphagia or loss of appetite. AL amyloidosis, also known as primary systemic amyloidosis, is a rare disease with an estimated incidence of 9.7 to 14.0 cases per million person years.1 Ninety-five percent of AL amyloidosis patients are >40 years old with a median age of 64 to 70 years old; 65% to 70% of patients are male. Keywords: amyloid; light chain; liquid chromatography mass spectrometry EN amyloid light chain liquid chromatography mass spectrometry 889 892 4 09/21/22 20221001 NES 221001 INTRODUCTION The three main types of systemic amyloidosis are: primary amyloid light-chain (AL), secondary, and familial amyloidosis. [Extracted from the article]
- Published
- 2022
- Full Text
- View/download PDF
4. Prevalence of plasma cell and lymphoproliferative disorders among blood relatives of patients with light chain amyloidosis.
- Author
-
Staron, Andrew, Verma, Karina, and Sanchorawala, Vaishali
- Subjects
- *
CARDIAC amyloidosis , *PLASMA cell diseases , *AMYLOIDOSIS , *LYMPHOPROLIFERATIVE disorders , *MULTIPLE myeloma - Abstract
Summary: With limited existing data on hereditary factors in light chain (AL) amyloidosis, we conducted a study of patients with plasma cell dyscrasias or lymphoproliferative disorders in their family history. Among 1621 patients, we identified 44 probands (2·7%) with 52 relatives affected. The most common disorders in family members were multiple myeloma (48%) and AL amyloidosis (18%). Light chain isotype was 100% congruent in families with known clonal immunoglobulin for both members. Despite matching light chain isotype, organ involvement varied between members in families with multiple cases of AL amyloidosis. These findings help generate hypotheses about familial influences in AL amyloidosis. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
5. Light chain consensus reinforcement machine learning: An effective blockchain model for Internet of Things using for its advancement and challenges.
- Author
-
Priyadharshini, K. and Canessane, R. Aroul
- Subjects
- *
REINFORCEMENT learning , *BLOCKCHAINS , *INTERNET of things , *MACHINE learning , *DATA structures , *ELECTRONIC data processing , *SCALABILITY - Abstract
Recently, blockchain intersected the Internet of Things (IoT) has come up with an integrated opportunity for different applications such as industries, medical diagnosis, and the education sector. Several conflicts have risen during the intersection, where the purpose of addressing the enormous resource utilization of blockchain, efficiency, and security issues of massive IoT has not been tackled in the present scenario. Presently, Ruff‐chain, blockchain consortium basis, mobile cloud blockchain (MCBC), probed IoT, and proof of work deployed to overcome the drawback of blockchain intersected IoT demands high resource utilization and power consumption. To address this issue, a light chain consensus reinforcement machine learning (LCC‐RML) method has been developed to optimize the blockchain effectively intersected IoT system and it assists in providing a learning methodology from the aspects of resource utilization, data security decentralization, scalability, and latency. In LCC‐RML, without affecting the decentralization system, security, and latency, scalability has been improved with the underlying blockchain approach. Here, a lighter model is designed especially for the blockchain intersected IoT platform, which contains optimized learning procedures, reduced block size, lightweight consensus data structure, and related effective block interval to streamline the data processing. The experimental analysis has been evaluated in the learning framework to improve the performance of the blockchain intersected IoT system with a computational speed of 84.89% and resource utilization reduction of 85.88%. Further in the power consumption has been reduced up to 57.55% with the computation cost of 29.55% with the scalability ratio of 86.88%. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
6. Progress and challenges in the treatment of cardiac amyloidosis: a review of the literature.
- Author
-
Adam, Robert Daniel, Coriu, Daniel, Jercan, Andreea, Bădeliţă, Sorina, Popescu, Bogdan A., Damy, Thibaud, and Jurcuţ, Ruxandra
- Subjects
CARDIAC amyloidosis ,HEART failure treatment ,TRANSTHYRETIN - Abstract
Cardiac amyloidosis is a restrictive cardiomyopathy determined by the accumulation of amyloid, which is represented by misfolded protein fragments in the cardiac extracellular space. The main classification of systemic amyloidosis is determined by the amyloid precursor proteins causing a very heterogeneous disease spectrum, but the main types of amyloidosis involving the heart are light chain (AL) and transthyretin amyloidosis (ATTR). AL, in which the amyloid precursor is represented by misfolded immunoglobulin light chains, can involve almost any system carrying the worst prognosis among amyloidosis patients. This has however dramatically improved in the last few years with the increased usage of the novel therapies such as proteasome inhibitors and haematopoietic cell transplantation, in the case of timely diagnosis and initiation of treatment. The treatment for AL is directed by the haematologist working closely with the cardiologist when there is a significant cardiac involvement. Transthyretin (TTR) is a protein that is produced by the liver and is involved in the transportation of thyroid hormones, especially thyroxine and retinol binding protein. ATTR results from the accumulation of transthyretin amyloid in the extracellular space of different organs and systems, especially the heart and the nervous system. Specific therapies for ATTR act at various levels of TTR, from synthesis to deposition: TTR tetramer stabilization, oligomer aggregation inhibition, genetic therapy, amyloid fibre degradation, antiserum amyloid P antibodies, and antiserum TTR antibodies. Treatment of systemic amyloidosis has dramatically evolved over the last few years in both AL and ATTR, improving disease prognosis. Moreover, recent studies revealed that timely treatment can lead to an improvement in clinical status and in a regression of amyloid myocardial infiltration showed by imaging, especially by cardiac magnetic resonance, in both AL and ATTR. However, treating cardiac amyloidosis is a complex task due to the frequent association between systemic congestion and low blood pressure, thrombo‐embolic and haemorrhagic risk balance, patient frailty, and generally poor prognosis. The aim of this review is to describe the current state of knowledge regarding cardiac amyloidosis therapy in this constantly evolving field, classified as treatment of the cardiac complications of amyloidosis (heart failure, rhythm and conduction disturbances, and thrombo‐embolic risk) and the disease‐modifying therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
7. Serum Hevylite® assay in the differential diagnosis of patients with high suspicion of AL Amyloidosis.
- Author
-
Yogev, Dean, Pick, Marjorie, Slyusarevsky, Elena, Pogrebijski, Galina, Pickin, Anna, and Gatt, Moshe E.
- Subjects
- *
AMYLOIDOSIS diagnosis , *BIOMARKERS , *AMYLOIDOSIS , *IMMUNOGLOBULINS , *CONFIDENCE intervals , *MULTIVARIATE analysis , *DIFFERENTIAL diagnosis , *DESCRIPTIVE statistics , *BIOLOGICAL assay , *ODDS ratio , *LONGITUDINAL method , *SYMPTOMS - Abstract
Introduction: AL amyloidosis (AL) is a malignant form of plasma cell dyscrasia (PCD). It is insidious, and its end‐organ damage can mimic that of common diseases. At diagnosis, routine tests for monoclonal protein are insufficient for the differential diagnosis. We hypothesized that Hevylite® (HLC) isotype patterns may help discriminate between AL and benign PCD states. Methods: Serum samples of patients with a high clinical suspicion of AL were prospectively tested for IgGκ, IgGλ, IgAκ, IgAλ, IgMκ, and IgMλ concentrations and ratios using Hevylite® assays in a blinded manner. The results were correlated with the final diagnosis. Results: Of the 99 samples analyzed, 46 were newly diagnosed AL, and the majority, 38 (82.6%), presented with suppression of at least one HLC isotype. Of the 53 benign PCD patients, 36 (67.9%) presented with elevation of at least one HLC isotype. By multivariate analysis, Hevylite® was the best independent test predictor of AL amyloidosis. HLC suppression had an odds ratio (OR) of 14.591, and elevation an OR of 10.149, and thus were significant variables in the diagnosis and exclusion of AL. Furthermore, patients with both HLC suppression, together with no elevation, had an OR of 316.69 to be diagnosed with AL rather than a benign PCD. Conclusions: Hevylite® HLC analysis for Ig isotypes patterns offers an effective non‐invasive tool in the evaluation of patients with high suspicion of AL and may assist further explorative decisions for diagnosis. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
8. Daratumumab for relapsed or refractory AL amyloidosis with high plasma cell burden.
- Author
-
Schwotzer, Rahel, Manz, Markus Gabriel, Pederiva, Stefanie, Waibel, Christine, Caspar, Clemens, Lerch, Erika, Flammer, Andreas J., Brouwers, Sofie, Seeger, Harald, Heimgartner, Raphael, Fehr, Thomas, Rossi, Davide, Bianchi, Elena, Stüssi, Georg, Ghilardi, Guido, and Gerber, Bernhard
- Subjects
PLASMA cells ,AMYLOIDOSIS ,BONE marrow cells ,CARDIAC amyloidosis ,DARATUMUMAB - Abstract
Daratumumab, an anti-CD38 antibody, is effective in AL amyloidosis with low tumor burden. Data of daratumumab treatment in patients with AL amyloidosis but high tumor burden (≥10% bone marrow plasma cells) are limited. We report retrospective data of 10 consecutive patients with high tumor burden treated with daratumumab for relapsed/refractory AL amyloidosis. The median age at diagnosis was 62.3 years; all patients had cardiac involvement, and six (60%) patients had renal involvement. Median bone marrow plasma cell infiltration was 15% (range 10%-40%), and the median difference between involved and noninvolved free light-chains (dFLC) was 446 mg/L (range 102-1392 mg/L). Patients had a median of three prior lines of therapy, including bortezomib in all patients and lenalidomide in seven (70%) patients. The median time to first hematological response was 14 days (range 7-28 days), and the median time to best hematological response was 64 days (range 7-301 days). The hematological overall response was 90%, with high-quality response (≥ very good partial remission [VGPR]) in 70% of the patients. Fifty percent of the patients had a cardiac response after a median of 3.8 months (range 0.7-9.1). Infusion-related adverse events ≤ grade 2 occurred in seven (70%) patients and grade 3 adverse events in one patient. After a median follow-up time of 10 months, eight (80%) patients continued to receive daratumumab. We conclude that daratumumab is a very effective and safe treatment option in AL patients with relapsed/refractory disease and high disease burden at diagnosis. Daratumumab leads to rapid disease control and improvement of organ function. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
9. Neurofilament light chain levels in pregnant multiple sclerosis patients: a prospective cohort study.
- Author
-
Cuello, J. P., Martínez Ginés, M. L., Kuhle, J., García Domínguez, J. M., Lozano Ros, A., Romero Delgado, F., Higueras, Y., Meldaña Rivera, A., Goicochea Briceño, H., García‐Tizon Larroca, S., De León-Luis, J., Michalak, Z., Barro, C., Álvarez Lafuente, R., Medina Heras, S., Fernández Velasco, J. I., Tejeda‐Velarde, A., Domínguez‐Mozo, M. I., Muriel, A., and de Andrés, C.
- Subjects
- *
MULTIPLE sclerosis , *CYTOPLASMIC filaments , *LONGITUDINAL method , *PREGNANT women , *COHORT analysis - Abstract
Background and purpose: Neurofilament light chain is a cytoskeletal protein of neurons. Its levels are increasingly recognized as measures of neuroaxonal damage. The aim of this study was to explore serum neurofilament light chain (sNfL) levels in multiple sclerosis (MS) patients and healthy controls during pregnancy and puerperium. Methods: This was a prospective, longitudinal, single‐center study. sNfL concentration was assessed using a highly sensitive single‐molecule array during pregnancy and in puerperium, in a cohort of 39 pregnant patients with relapsing multiple sclerosis (P‐MS). Twenty‐one healthy pregnant women (HPW) served as a control group. Eight P‐MS suffered relapses during pregnancy (P‐MS‐R) in the first or second trimesters. Results: No differences in pregnancy and delivery data were observed between P‐MS and HPW. P‐MS showed higher sNfL values than HPW in the first trimester, independently of the presence (P = 0.002) or not (P = 0.02) of relapses during pregnancy. However, in the third trimester, only P‐MS‐R showed higher sNfL values than HPW (P = 0.001). These differences extended to the puerperium, where P‐MS‐R showed higher sNfL values than those with no relapses during gestation (P = 0.02). Conclusion: These data strongly suggest that sNfL levels reflect MS activity during pregnancy. Additionally, the absence of relapses during pregnancy may have a beneficial effect on neurodegeneration during puerperium. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
10. Unsuppressed serum albumin levels may jeopardize the clinical relevance of the international staging system to patients with light chain myeloma.
- Author
-
Kasamatsu, Tetsuhiro, Ozaki, Shuji, Saitoh, Takayuki, Konishi, Jun, Sunami, Kazutaka, Itagaki, Mitsuhiro, Asaoku, Hideki, Cho, Takaaki, Handa, Hiroshi, Hagiwara, Shotaro, Wakayama, Toshio, Negoro, Akiko, Takezako, Naoki, Harada, Naoko, Kuroda, Yoshiaki, Nakaseko, Chiaki, Miyake, Takaaki, Inoue, Nobumasa, Hata, Hiroyuki, and Shimazaki, Chihiro
- Subjects
CLINICAL trials ,COMPARATIVE studies ,IMMUNOGLOBULINS ,RESEARCH methodology ,MEDICAL cooperation ,MULTIPLE myeloma ,RESEARCH ,RESEARCH funding ,TUMOR classification ,EVALUATION research - Abstract
The international staging system (ISS) is the most commonly used risk-stratification system for patients with multiple myeloma (MM) and is determined by serum albumin and β2-microglobulin levels. In the two determinants, β2-microglobulin levels are frequently observed to be elevated in patients with myeloma, particularly in those with renal impairment. In comparison with patients with intact immunoglobulin myeloma, patients with LC myeloma do not necessarily show decreased levels of serum albumin. The clinical impact of ISS in patients with LCMM, in particular the distinction between ISS I and II, may be complicated due to non-decreased levels of serum albumin in both stages. Accordingly, we have attempted to assess clinical relevance of the ISS in patients with LC myeloma. The clinical data of 1899 patients with MM diagnosed between January 2001 and December 2012 were collected from 38 affiliated hospitals of the Japanese Society of Myeloma. Significant difference was not found between stage I (n = 72) and stage II (n = 92) in LC myeloma patients (n = 307). The mean serum albumin concentration of patients with LC myeloma was within the reference range but higher than that of patients with IgG + IgA myeloma (n = 1501), which complicates the distinction between ISS stage I and II myeloma. Patients with LC myeloma had low frequencies of t(4; 14) and high frequency of elevated lactate dehydrogenase, and despite a relevant amount of missing data in our registry (R-ISS stage I; n = 11, stage II; n = 32, and stage III: n = 18), the information included in the R-ISS scoring system seems to be more accurate than ISS to obtain a reliable risk stratification approach in non-ISS stage III LC myeloma patients. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
11. Serum free immunoglobulin light chain fingerprint identifies a subset of newly diagnosed multiple myeloma patients with worse outcome.
- Author
-
Avivi, Irit, Cohen, Yael C., Joffe, Erel, Benyamini, Noam, Held‐Kuznetsov, Viki, Trestman, Svetlana, Terpos, Evangelos, Dimopoulos, Meletios A., and Kastritis, Efstathios
- Subjects
PROGNOSIS ,TREATMENT effectiveness ,IMMUNOGLOBULIN light chains ,MULTIPLE myeloma ,LONGITUDINAL method - Abstract
Multiple myeloma (MM) is a multi-subclonal malignancy with relatively high heterogeneity. Patients who initially presented with both monoclonal-protein (MP) and free light chain (FLC) secretion but then relapsed with a light chain escape pattern have been shown to reflect disease clonal evolution and to bare a worse prognosis. We hypothesized that a discordant MP/FLC pattern at diagnosis may reflect a similar clonal evolution that had occurred prior to diagnosis of active myeloma, conferring a worse outcome. We analyzed 255 consecutive newly diagnosed MM patients who received first line bortezomib-based therapy between 2007 and 2014, hypothesizing that their MP/FLC fingerprint at diagnosis reflects clonal heterogeneity and, therefore, affects outcome. An involved FLC level ≥ 700 mg/L and MP ≥ 2.5 g/L were used as cutoffs for low vs high FLC and MP levels, respectively. Patients were divided into 4 subgroups according to their involved FLC and MP blood levels at diagnosis: HiLC and HiMP for patients with either a predominant FLC or a predominant MP, respectively, and HiLC-MP and LoLC-MP when both FLC and MP were increased or decreased, respectively. There were 68 (27%) patients with HiLC, which presented more often with International Staging System-3 stage (P < .0001). Multivariate analysis showed that HiLC was associated with a 5.1-fold risk for mortality in a multivariate model (95% confidence interval [CI], 1.34-19.68). Both HiLC and HiLC-MP phenotypes were associated with shorter progression-free survival (hazard ratio of 2.66 [95% CI, 1.33-5.32] and 2.82 [95% CI, 1.37-5.83], respectively), independently of other prognostic factors, including the use of autograft. Thus, we identified an LC predominant secretory fingerprint (HiLC phenotype) at diagnosis as a potential independent risk factor that may affect disease control and survival in newly diagnosed MM patients treated with bortezomib-based induction therapy; this may represent increased subclonal heterogeneity. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
12. Immunoglobulin light chain allelic inclusion in systemic lupus erythematosus.
- Author
-
Fraser, Louise D., Zhao, Yuan, Lutalo, Pamela M. K., D'Cruz, David P., Cason, John, Silva, Joselli S., Dunn‐Walters, Deborah K., Nayar, Saba, Cope, Andrew P., and Spencer, Jo
- Abstract
The principles of allelic exclusion state that each B cell expresses a single light and heavy chain pair. Here, we show that B cells with both kappa and lambda light chains (Igκ and Igλ) are enriched in some patients with the systemic autoimmune disease systemic lupus erythematosus (SLE), but not in the systemic autoimmune disease control granulomatosis with polyangiitis. Detection of dual Igκ and Igλ expression by flow cytometry could not be abolished by acid washing or by DNAse treatment to remove any bound polyclonal antibody or complexes, and was retained after two days in culture. Both surface and intracytoplasmic dual light chain expression was evident by flow cytometry and confocal microscopy. We observed reduced frequency of rearrangements of the kappa-deleting element (KDE) in SLE and an inverse correlation between the frequency of KDE rearrangement and the frequency of dual light chain expressing B cells. We propose that dual expression of Igκ and Igλ by a single B cell may occur in some patients with SLE when this may be a consequence of reduced activity of the KDE. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
13. Management of systemic AL amyloidosis: recommendations of the Myeloma Foundation of Australia Medical and Scientific Advisory Group.
- Author
-
Weber, N., Mollee, P., Augustson, B., Brown, R., Catley, L., Gibson, J., Harrison, S., Ho, P. J., Horvath, N., Jaksic, W., Joshua, D., Quach, H., Roberts, A. W., Spencer, A., Szer, J., Talaulikar, D., To, B., Zannettino, A., and Prince, H. M.
- Subjects
- *
AMYLOIDOSIS treatment , *AMYLOIDOSIS , *BLOOD diseases , *ORTHOSTATIC hypotension , *THALIDOMIDE , *DECISION making in clinical medicine , *BORTEZOMIB , *MELPHALAN , *PROGNOSIS - Abstract
Systemic AL amyloidosis is a plasma cell dyscrasia with a characteristic clinical phenotype caused by multi-organ deposition of an amyloidogenic monoclonal protein. This condition poses a unique management challenge due to the complexity of the clinical presentation and the narrow therapeutic window of available therapies. Improved appreciation of the need for risk stratification, standardised use of sensitive laboratory testing for monitoring disease response, vigilant supportive care and the availability of newer agents with more favourable toxicity profiles have contributed to the improvement in treatment-related mortality and overall survival seen over the past decade. Nonetheless, with respect to the optimal management approach, there is a paucity of high-level clinical evidence due to the rarity of the disease, and enrolment in clinical trials is still the preferred approach where available. This review will summarise the Clinical Practice Guidelines on the Management of Systemic Light Chain ( AL) Amyloidosis recently prepared by the Medical Scientific Advisory Group of the Myeloma Foundation of Australia. It is hoped that these guidelines will assist clinicians in better understanding and optimising the management of this difficult disease. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
14. Guidelines on the diagnosis and investigation of AL amyloidosis.
- Author
-
Gillmore, Julian D., Wechalekar, Ashutosh, Bird, Jenny, Cavenagh, Jamie, Hawkins, Stephen, Kazmi, Majid, Lachmann, Helen J., Hawkins, Philip N., and Pratt, Guy
- Subjects
- *
AMYLOIDOSIS diagnosis , *CLINICAL medicine , *MEDICAL care , *DIAGNOSTIC examinations , *MEDICAL screening - Abstract
The article looks at a guideline for the diagnosis and investigation of amyloid light-chain (AL) amyloidosis provided by the British National Amyloidosis Centre. Topics discussed include histological diagnosis of AL amyloidosis, use of Bone marrow aspirate and trephine biopsy in diagnosis, and role of echocardiography in assessing amyloid involvement.
- Published
- 2015
- Full Text
- View/download PDF
15. Mutational and genetic determinants of λ6 light chain amyloidogenesis.
- Author
-
González‐Andrade, Martín, Becerril‐Luján, Baltazar, Sánchez‐López, Rosana, Ceceña‐Álvarez, Héctor, Pérez‐Carreón, Julio I., Ortiz, Ernesto, Fernández‐Velasco, D. Alejandro, and Pozo‐Yauner, Luis
- Subjects
- *
GENETIC mutation , *GLYCINE , *ALLELES , *AMYLOID , *PROTEIN folding , *GENETIC databases , *GERM cells - Abstract
Approximately 25% of the λ6 light chains have glycine rather than arginine at position 25, which is an allelic variant of the IGLV6-57 ( 6a) locus. The Gly25 variant has been shown to decrease the folding stability of the germline λ6 VL protein 6aJL2 by 1.7 kcal·mol−1. In this work, we compared the thermodynamic and fibrillogenic properties of the amyloidosis (AL) derived recombinant (r) VL protein AR, which contains the allelic variant Gly25, with those of germline rVL 6aJL2-R25G and the λ6 disease-associated VL proteins Wil (AL) and Jto (myeloma). Our experiments show that of the four proteins AR is the least stable; forms amyloid fibrils at physiological temperature, pH and ionic strength; has the shortest lag time; and elongates homologous seeds most efficiently. We conclude that the Gly25 allelic variant, together with the somatic mutations, contributes importantly to the extremely low stability and high amyloidogenicity of the AL-derived protein AR. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
16. Shoulder pad and macroglossia: "two signs of AL amyloidosis".
- Author
-
Suganthan, Navaneethakrishnan, Navaradnam, Piratheepan, and Sujanitha, Vathulan
- Subjects
- *
AMYLOIDOSIS , *SHOULDER , *CARDIAC amyloidosis , *AMYLOID , *DIAGNOSIS , *TISSUES - Abstract
"Shoulder pad" sign resulting from deposition of amyloid in the periarticular soft tissue is rare but it is pathognomonic for immunoglobulin amyloidosis (AL). Although the detection remains a challenge, it gives a strong clue leading to prompt diagnosis. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
17. Relative stabilities of IgG1 and IgG4 Fab domains: Influence of the light-heavy interchain disulfide bond architecture.
- Author
-
Heads, James T., Adams, Ralph, D'Hooghe, Lena E., Page, Matt J. T., Humphreys, David P., Popplewell, Andrew G., Lawson, Alastair D., and Henry, Alistair J.
- Abstract
The stability of therapeutic antibodies is a prime pharmaceutical concern. In this work we examined thermal stability differences between human IgG1 and IgG4 Fab domains containing the same variable regions using the thermofluor assay. It was found that the IgG1 Fab domain is up to 11°C more stable than the IgG4 Fab domain containing the same variable region. We investigated the cause of this difference with the aim of developing a molecule with the enhanced stability of the IgG1 Fab and the biological properties of an IgG4 Fc. We found that replacing the seven residues, which differ between IgG1 C
H 1 and IgG4 CH 1 domains, while retaining the native IgG1 light-heavy interchain disulfide (L-H) bond, did not affect thermal stability. Introducing the IgG1 type L-H interchain disulfide bond (DSB) into the IgG4 Fab resulted in an increase in thermal stability to levels observed in the IgG1 Fab with the same variable region. Conversely, replacement of the IgG1 L-H interchain DSB with the IgG4 type L-H interchain DSB reduced the thermal stability. We utilized the increased stability of the IgG1 Fab and designed a hybrid antibody with an IgG1 CH 1 linked to an IgG4 Fc via an IgG1 hinge. This construct has the expected biophysical properties of both the IgG4 Fc and IgG1 Fab domains and may therefore be a pharmaceutically relevant format. [ABSTRACT FROM AUTHOR]- Published
- 2012
- Full Text
- View/download PDF
18. Effect of temperature, pH, dissolved oxygen, and hydrolysate on the formation of triple light chain antibodies in cell culture.
- Author
-
Gomez, Natalia, Ouyang, Jun, and Nguyen, Mary D. H.
- Subjects
CELL culture ,HYDROGEN-ion concentration ,CYSTEINE proteinases ,IMMUNOGLOBULINS ,ANTIBODY-drug conjugates ,GLUTATHIONE - Abstract
THIOMABs are recombinant antibodies with reactive cysteine residues used for forming THIOMAB-drug conjugates (TDCs). We recently reported a new impurity associated with THIOMABs: one of the engineered cysteines forms a disulfide bond with an extra light chain (LC) to generate a triple light chain antibody (3LC). In our previous investigations, increased LC expression increased 3LC levels, whereas increased glutathione (GSH) production decreased 3LC levels. In this work, on three stably transfected CHO cell lines, we investigated the effects of temperature, pH, dissolved oxygen (DO), and hydrolysate on 3LC formation during THIOMAB fed-batch cell culture production. Although pH between 6.8 and 7.0 had no significant impact on 3LC formation, temperature at 35°C instead of 33 or 31°C generated the lowest 3LC values for two cell lines. The decreased 3LC level correlated with increased GSH production. We implemented a 35°C temperature process for large-scale (2,000 L) production of a THIOMAB. This process reduced 3LC levels by ∼50% compared with a 33°C temperature process. By contrast, DO and hydrolysate had modest effect on 3LC levels for the model cell line studied. Overall, we did not find significant changes in LC expression under the conditions tested, whereas changes in GSH production were more evident. By investigating the impact of bioreactor process and medium conditions on 3LC levels, we identified strategies that reduced 3LC levels. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010 [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
19. Bone marrow findings correlate with clinical outcome in systemic AL amyloidosis patients.
- Author
-
Hasserjian, R. P., Goodman, H. J. B., Lachmann, H. J., Muzikansky, A., and Hawkins, P. N.
- Subjects
- *
BONE marrow , *AMYLOIDOSIS , *LYMPHOMAS , *DISEASES , *PLASMA cells , *PATIENTS - Abstract
Aims: Bone marrow sampling is a key investigation in the work-up of amyloid light chain (AL) amyloidosis, but the relationship between bone marrow findings and the varied phenotype and clinical outcome of AL amyloidosis is unclear. The aim was to determine if bone marrow pathological parameters at diagnosis were related to clinical behaviour in AL amyloidosis patients. Methods and results: Bone marrow findings, clinical features and outcome of 80 patients referred with a diagnosis of systemic AL amyloidosis were evaluated; six patients were subsequently excluded due to re-categorization as other forms of amyloidosis. At latest follow-up (median 66 months), 11 of the 18 patients with no identifiable bone marrow neoplastic cells (61%) versus only seven of the 56 patients with neoplastic plasma cells or non-Hodgkin's lymphoma (13%) were alive ( P = 0.0046). However, neither the quantity of the neoplastic cells nor the serum light chain levels were correlated with amyloid burden or patient survival. Conclusions: Identification of a neoplastic population in the bone marrow of AL amyloidosis patients by histology and immunohistochemistry correlates with poor outcome; however, the neoplastic cell burden is not prognostically significant, suggesting that additional factors are important in determining disease behaviour in AL amyloidosis. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
20. A novel subunit of axonemal dynein conserved among lower and higher eukaryotes
- Author
-
Yamamoto, Ryosuke, Yanagisawa, Haru-aki, Yagi, Toshiki, and Kamiya, Ritsu
- Subjects
- *
MICROTUBULES , *ADENOSINE triphosphatase , *ORGANELLES , *PHOSPHATASES - Abstract
Abstract: To elucidate the subunit composition of axonemal inner-arm dynein, we examined a 38kDa protein (p38) co-purified with a Chlamydomonas inner arm subspecies, dynein d. We found it is a novel protein conserved among a variety of organisms with motile cilia and flagella. Immunoprecipitation using specific antibody verified its association with a heavy chain, actin and a previously identified light chain (p28). Unexpectedly, mutant axonemes lacking dynein d and other dyneins retained reduced amounts of p38. This finding suggests that p38 is involved in the docking of dynein d to specific loci. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
21. Treatment of Renal Failure Associated with Multiple Myeloma and Other Diseases by PACAP-38.
- Author
-
ARIMURA, AKIRA, LI, MIN, and BATUMAN, VECIHI
- Subjects
- *
KIDNEY diseases , *IMMUNOGLOBULINS , *PLASMA cells , *CYTOKINES , *EPITHELIAL cells - Abstract
Myeloma kidney injury is caused by the large amount of light chain (LC) of immunoglobulins produced by cancerous plasma cells through stimulation of proinflamatory cytokines like TNF-α and IL-6. PACAP-38 suppressed LC-stimulated cytokine production by tubular epithelial cells in vitro and in vivo, and prevented injury of these epithelial cells . The suppressive effect is comparable or greater than dexamethasone (dex). Although dex produces adverse side effects when it is given for a long time period, PACAP-38 is a natural and safe neuropeptide and no adverse effect has been reported when administered to produce significant biological effects. Furthermore, PACAP-38 suppressed growth of myeloma cells in culture and also suppressed production of their growth factor, IL-6, production from the bone marrow stromal cells that was stimulated by adhesion of myeloma cells. These findings render PACAP-38 worth evaluation as a safe and potent renoprotectant in myeloma kidney as well as a new antitumor agent for myeloma cells. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
22. Differential Control of Clathrin Subunit Dynamics Measured with EW-FRAP Microscopy.
- Author
-
Loerke, Dinah, Wienisch, Martin, Kochubey, Olexiy, and Klingauf, Jurgen
- Subjects
- *
GREEN fluorescent protein , *PROTEINS , *FLUORESCENT polymers , *CHEMICAL reactions - Abstract
The clathrin triskelion is composed of three light chain (LC) and three heavy chain (HC) subunits. Cellular control of clathrin function is thought to be aimed at the LC subunit, mainly on the basis of structural information. To test this hypothesis in vivo, we used evanescent-wave photobleaching recovery to study clathrin exchange from single pits using LC (LCa and LCb) and HC enhanced green fluorescent protein fusion constructs. The recovery signal was corrected for cytosolic diffusional background, yielding the pure exchange reaction times. For LCa, we measured an unbinding time constant τLEa = 18.9 ± 1.0 seconds at room temperature, faster than previously published; for LCb, we found τLCb = 10.6 ± 1.9 seconds and for HC τHC = 15.9 ± 1.0 seconds. Sucrose treatment, ATP or Ca2+ depletion blocked exchange of LCa completely, but only partially of HC, lowering its time constant to τ = 10.0 ± 0.9 seconds, identical to the one for LCb exchange. The latter was also not blocked by Ca2+ depletion or sucrose. We conclude that HCs bound both to LCa and to LCb contribute side by side to pit formation in vivo, but the affinity of LCa-free HC in pits is reduced, and the Ca2+- and ATP-mediated control of clathrin function is lost. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
23. Specific degradation of H. pylori urease by a catalytic antibody light chain.
- Author
-
Hifumi, Emi, Hatiuchi, Kenji, Okuda, Takuro, Nishizono, Akira, Okamura, Yoshiko, and Uda, Taizo
- Subjects
- *
HELICOBACTER pylori , *IMMUNOGLOBULINS , *PATHOGENIC bacteria , *BACTERIA , *THERAPEUTICS , *HELICOBACTER - Abstract
Catalytic antibodies capable of digesting crucial proteins of pathogenic bacteria have long been sought for potential therapeutic use. Helicobacter pylori urease plays a crucial role for the survival of this bacterium in the highly acidic conditions of human stomach. The HpU-9 monoclonal antibody (mAb) raised against H. pylori urease recognized the α-subunit of the urease, but only slightly recognized the β-subunit. However, when isolated both the light and the heavy chains of this antibody were mostly bound to the β-subunit. The cleavage reaction catalyzed by HpU-9 light chain (HpU-9-L) followed the Michaelis-Menten equation with a Km of 1.6 × 10−5 m and a kcat of 0.11 min−1, suggesting that the cleavage reaction was enzymatic. In a cleavage test using H. pylori urease, HpU-9-L efficiently cleaved the β-subunit but not the α-subunit, indicating that the degradation by HpU-9-L had a specificity. The cleaved peptide bonds in the β-subunit were L121-A122, E124-G125, S229-A230, Y241-D242, and M262-A263. BSA was hardly cleaved by HpU-9-L, again indicating the digestion by HpU-9-L was specific. In summary, we succeeded in the preparation of a catalytic antibody light chain capable of specifically digesting the β-subunit of H. pylori urease. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
24. Genomic Organization of the Serine Protease Light Chain of Mouse Complement Factor I Gene.
- Author
-
Jiang, Ning and Molina, Hector
- Subjects
- *
SERINE proteinases , *GENES , *EXONS (Genetics) , *INTRONS - Abstract
A portion of the mouse complement factor I (mCFI) gene encoding for the mCFI light chain was cloned from a mouse 129/SVJ1 bacterial artificial chromosome library. It contains five exons and four introns. The intron sizes are remarkably different from the human homolog. Several polymorphisms were found in exon 13. One polymorphism was in the coding region, which causes a threonine in the Balb/c mCFI to be replaced by an isoleucine in the 129/SVJ1 mCFI. The other two polymorphisms are located in the 3' untranslated region. The organization of the serine protease domain in mCFI is similar to that of trypsin but very different from that of the other complement serine proteases. [ABSTRACT FROM AUTHOR]
- Published
- 2000
- Full Text
- View/download PDF
25. A novel structural model for regulation of clathrin function.
- Author
-
Pishvaee, Babak, Munn, Alan, and Payne, Gregory S.
- Subjects
- *
PROTEINS , *MUTAGENESIS , *GENES , *YEAST , *PROTEIN binding - Abstract
The distinctive triskelion shape of clathrin allows assembly into polyhedral lattices during the process of clathrin-coated vesicle formation. We have used random and site-directed mutagenesis of the yeast clathrin heavy chain gene (CHC1) to characterize regions which determine Chc trimerization and binding to the clathrin light chain (Clc) subunit. Analysis of the mutants indicates that mutations in the trimerization domain at the triskelion vertex, as well as mutations in the adjacent leg domain, frequently influence Clc binding. Strikingly, one mutation in the trimerization domain enhances the association of Clc with Chc. Additional mutations in the trimerization domain, in combination with mutations in the adjacent leg domain, exhibit severe defects in Clc binding while maintaining near normal trimerization properties. The position of these trimerization domain mutations on one face of a putative α-helix defines a region on the trimer surface that interacts directly with Clc. These results suggest that Clc extends into the Chc trimerization domain from the adjacent leg, thereby bridging the two domains. On the basis of this conclusion, we propose a new model for the organization of the triskelion vertex which provides a structural basis for regulatory effects of Clc on clathrin function. [ABSTRACT FROM AUTHOR]
- Published
- 1997
- Full Text
- View/download PDF
26. Signet ring-like light chain myeloma with systemic spread.
- Author
-
Haidar, Joud H., Bazarbachi, Ali, Nasr, Michel R., El-Sabban, Marwan E., and Daher, Rose
- Subjects
- *
MULTIPLE myeloma , *PLASMA cells , *CELL morphology - Abstract
Abstract: The morphological presentation of malignant plasma cells in multiple myeloma (MM) varies from mature to anaplastic plasma cells with only one reported case of signet ring variant. We describe here another case of signet ring-like lambda light chain MM associated with extra-skeletal spread to lymph nodes, spleen and liver. The clinical and pathological presentations were atypical with no evidence of bone-lytic lesions or monoclonal component on protein electrophoresis, leading to a delay of several years in the diagnosis. Recognition of this morphological entity of MM may help in an early diagnosis of this rare variant. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.