Establishment of monoclonal antibodies against cell surface domains of ASCT2/SLC1A5 and their inhibition of glutamine-dependent tumor cell growth.

Human alanine-serine-cysteine transporter 2 (ASCT2; SLC1A5) is a major transporter of the amino acid glutamine that is known to be overexpressed in certain malignant tumors. In this study, we generated specific monoclonal antibodies (MAbs) against ASCT2 by establishing an ASCT2-expressing Chinese hamster ovary cell line that was used to immunize mice and rats. The MAbs KM4008, KM4012, and KM4018 against ASCT2 were isolated through a cell-based screen; these specifically bound to ASCT2-positive cells, as determined by flow cytometry and immunoprecipitation. In addition, the antibodies suppressed glutamine-dependent growth of WiDr colorectal cancer cells. These results provide evidence supporting the use of MAbs against ASCT2 as an effective therapeutic strategy for cancer treatment.

Establishment of a novel monoclonal antibody against LGR5.

LGR5 is an orphan G-protein-coupled receptor (GPCR) that is expressed on the cell surface membrane. LGR5 is reported to be overexpressed in colon, liver, and ovary tumor compared to normal tissue. However, a specific ligand for LGR5 has not yet been determined, and the function is still not clear. An LGR5-specific monoclonal antibody (mAb) is needed as a tool for detection and analysis of LGR5 biological function and cancer therapy. To date, no mAb against LGR5 that retains high affinity and specificity has been reported. Here, we report successful establishment and characterization of a mAb (KM4056) that specifically recognizes the extracellular N-terminal domain of human LGR5, but not LGR4 or LGR6. This mAb has potent complement-dependent cytotoxicity (CDC) activity in vitro and shows strong anti-tumor activity in vivo against xenograft model by transplanting LGR5 expressing CHO transfectants into SCID mice. Thus, KM4056 can be a useful tool for detection of LGR5 positive cells and analysis of LGR5 biological function.

Multiple extensor tendon ruptures caused by tophaceous gout.

A 54-year-old woman presented with painless subcutaneous masses on her right hand and spontaneous loss of extension of her ring finger. Surgical exploration of the wrist showed hypertrophic white-colored crystal deposits that both surrounded and invaded into the extensor tendons (intratendinous invasion). Histopathologic examination of the specimen demonstrated findings consistent with gouty tophi. We conclude that tophaceous gout needs to be included in the differential diagnosis of chronic extensor tenosynovitis of the hand.

Prediction of wrist prognosis in patients with early rheumatoid arthritis according to radiographic classification.

PURPOSE: We conducted a prospective study of patients with recent-onset rheumatoid arthritis to determine the importance of carpal height ratio (CHR) or ulnar translation ratio (UTR) in predicting radiographic progression of rheumatoid arthritis in the wrist, especially with regard to stable or progressive wrist arthritis. METHODS: We evaluated 106 wrists with early rheumatoid arthritis. Radiologic misalignment was assessed by measuring CHR and UTR. The modified Schulthess classification of rheumatoid wrist involvement was used to classify the subtypes of wrist joint destruction radiographically types I, II, III, and IV, defined as ankylosing, osteoarthritis, disintegrating, and normal, respectively. We evaluated the wrist joints as stable or progressive by measuring the values of CHR and UTR indices. We also examined whether the modified Schulthess classification of rheumatoid wrist involvement subtypes are associated with radiographic progression over 10 years using the baseline CHR and UTR indices. RESULTS: The mean CHR values of types I and III were 0.42 (95% confidence interval [CI], 0.40-0.43) and 0.37 (95% CI, 0.34-0.39), respectively. The mean UTR values of types I and III were 0.348 (95% CI, 0.336-0.360) and 0.351 (95% CI, 0.339-0.367), respectively. These values indicated that degradation was faster in types I and III than in other types. We then found type I and III wrists to have progressive arthritis, and type II and IV wrists stable arthritis. We also found that the baseline CHR index was a significant (p < .05) predictor of radiographic progression. CONCLUSIONS: Our results indicated that type I and III wrists had radiographic progression and ultimately underwent deformation. This analysis also showed that the baseline CHR index was even more useful in predicting radiographic progression after 10 years.

Risk factors for wrist surgery in rheumatoid arthritis.

To assess the risk factors for wrist surgery in a cohort of rheumatoid arthritis (RA) patients recruited and followed prospectively for 6 years. A linked registry study was performed using information from a large observational cohort of RA patients followed at the Institute of Rheumatology, Tokyo Women's Medical University. Baseline routine clinical and laboratory assessments were recorded. The data were analyzed using the multivariate Cox regression model that included variables such as gender, age, disease duration, a visual analog scale (VAS) generated by physicians, a patient-reported VAS for pain (VAS-pain), a VAS for general health, disability level using the Japanese version of the Health Assessment Questionnaire (J-HAQ), erythrocyte sedimentation rate, and serum levels of C-reactive protein and rheumatoid factor as potential risk factors. Of the 5,497 patients registered at baseline, 122 (2.22%) had surgery on one or both wrist joints. Multivariate Cox regression analysis of the variables revealed positive coefficients for J-HAQ and VAS-pain and that advanced age and long RA duration were associated with a reduced risk of wrist surgery. The hazard ratios were: 1.515 for J-HAQ, 1.126 for VAS-pain, 0.985 for age, and 0.964 for RA duration. Advanced age and long RA duration were associated with a decreased risk of wrist surgery, while J-HAQ and VAS-pain were associated with an increased risk. The identification of the risk factors for wrist surgery provides important insights into the course of the disease and its impact on patients, as well as the potential consequences for health care resource utilization planning.

Iliopsoas bursitis-associated femoral neuropathy exacerbated after internal fixation of an intertrochanteric hip fracture in rheumatoid arthritis: a case report.

We present the case of a 63-year-old woman with a six-year history of rheumatoid arthritis (RA) and a left iliopsoas bursitis. Radiography had detected destructive changes in her hip joint associated with her bursitis, and she had reported some paresthesia along the left anterior distal thigh. Her pain and numbness remained tolerable, and her disease activity was well controlled until she accidentally fell on the floor, which resulted in an unstable intertrochanteric fracture of left femur with displacement of the proximal portion. The fracture was successfully treated with open reduction and internal fixation, but after the surgery, her femoral nerve palsy worsened. She subsequently underwent bursa excision after the failure of conservative treatment. Accordingly, after bursa excision, the postoperative course was uneventful, and her neurological symptoms gradually disappeared. We would recommend that bursa excision be considered even in cases of iliopsoas bursitis associated with mild femoral neuropathy when destructive changes in the hip joint are also present.

Risk factors for total knee arthroplasty in rheumatoid arthritis.

We conducted a study to assess the predictive factors for total knee arthroplasty (TKA) in a cohort of rheumatoid arthritis (RA) patients recruited and followed prospectively for 5 years. A linked registry study using information from a large observational cohort of RA patients followed at the Institute of Rheumatology, Tokyo Women's Medical University (IORRA) was done. Baseline routine clinical and laboratory assessments were recorded. The data were analyzed using the multivariate piecewise-linear Cox (PL-Cox) regression model; the model initially included variables such as gender, age, duration of the disease, visual analog scale (VAS) generated by physicians (VAS-physician), patient-reported VAS for pain (VAS-pain), VAS for general health (VAS-GH), disability level using the Japanese version of the Health Assessment Questionnaire (J-HAQ), C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor (RF), and hemoglobin. Of the 3945 patients registered at baseline, 955 (24.2%) had pain or tenderness in their knee joints, and 114 (11.9%) had TKA surgery in one or both knee joints. On PL-Cox regression, the variables with positive coefficients were J-HAQ, VAS-pain, VAS-physician, and RF positive; advanced age was associated with a reduced risk of TKA. The hazard ratios were: 0.920 for age >60 years; 2.64 for J-HAQ <1.5; 1.01 for J-HAQ >1.5; 1.47 for VAS-pain >6 (cm); 1.20 for VAS-physician >4 (cm); and 2.08 for RF positive. The consistently predictive factors for TKA in RA were age, J-HAQ, VAS-pain, VAS-physician, and RF positive. Age greater than 60 years was associated with a decreased risk of TKA, while J-HAQ from 0 to 1.5, VAS-pain >6 (cm), and VAS-physician >4 (cm) were associated with an increased risk for TKA surgery. These results suggest that, when treating RA patients, physicians should pay particular attention to pain complaints, the patient's daily activity level, and the RF factor status.