Comparison of Treatment Outcomes of Different Immobilized Finger Positions After Repair of Flexor Tendon Rupture in Zones I and II: A Nonrandomized Controlled Trial With Historical Control Group.

Introduction The position of finger immobilization after flexor tendon rupture repair is changed to the extended position to prevent flexion contracture of the interphalangeal (IP) joint. However, in Strickland's assessment, We believe that a reduction in TAF (total active flexion) affects the outcome and that extension fixation is not necessarily the primary focus. For example, there are management methods that swap the fixed position between day and night. It is assumed that some effect is sought by placing the fingers in the flexed position. That is, the method of fixation is currently selected at individual facilities through twists and turns; however, the indications and criteria for selecting finger fixation positions are ambiguous, and they are apparently subject to the experience of therapists. This study aimed to characterize follow-up outcomes of flexion and extension fixation after zones I and II flexor tendon rupture repair. Methods This nonrandomized controlled trial with historical controls included 25 patients with flexor tendon ruptures of 30 fingers. The flexion fixation group consisted of 12 patients (n=16 fingers) and the extension fixation group consisted of 13 patients (n=14 fingers). The group with flexion fixation comprised patients who slept with their injured fingers in the flexed position (intervention group). The group with extension was retrospectively selected between April 2017 and March 2019, who slept with their injured finger in the extended position (historical control group). Strickland assessments of the range of motion (ROM) of each joint at the conclusion of hand therapy, the ratio of total active motion of the repaired, to the healthy finger (%TAF), and IP joint extension limitation angles were compared using Mann-Whitney U tests. Ratios of excellent and good ratings based on the Strickland assessment were compared using Fisher exact tests. Result The results of the Strickland assessment showed excellent or good outcomes for 22 (73%) of 30 fingers, which was in line with our previous findings. Strickland ratings of excellent were achieved in seven (44%) of 16 fingers and four (28%) of 14 fingers in the groups with flexion and extension fixation, respectively. The outcomes for two (22%) of 16 fingers and seven (78%) of 14 fingers in the groups with flexion and extension fixation were, respectively, rated as good. The proportion of patients rated as excellent was significantly higher in the group with flexion than extension fixation (p=0.040). The %TAF and the active flexion angle of the distal interphalangeal (DIP) joint were higher in the group with flexion than extension fixation (p=0008 and p=0.025, respectively). Furthermore, the total angle of the IP joint limit of extension did not significantly differ between the groups. Conclusion Flexion fixation after flexor tendon rupture achieved an excellent Strickland rating and was more effective than extension fixation, especially in terms of the active flexion ROM of the DIP joint. Flexion fixation might be an alternative to extension fixation because the range of flexion should be greater and might provide a range of finger extension motion equivalent to that of extension fixation.

Comprehensive gene expression analysis using RNA sequencing between male and female patients with idiopathic carpal tunnel syndrome.

Idiopathic carpal tunnel syndrome is the most common entrapment neuropathy in hand surgery, and it is characterized by Noninflammatory fibrosis of subsynovial connective tissues. The prevalence and incidence differ between male and female individuals, and the mechanism underlying this difference remains largely unclear. In the present study, we collected subsynovial connective tissues from six male and six female patients diagnosed with idiopathic carpal tunnel syndrome during surgery. We performed a comprehensive gene expression analysis using RNA sequencing to compare the gene expression profiles between male and female patients with idiopathic carpal tunnel syndrome. We identified 26 genes with significantly different expressions between male and female patients, in which POSTN, COL1A1, and COL3A1, which are involved in extracellular matrix organization, and IGF1, an important fibrotic factor, were significantly upregulated in male patients. Immunohistochemistry confirmed the expression of proteins encoded by these genes in tissues, and male patients tended to show increased POSTN expression. Our results indicate that fibrosis of subsynovial connective tissues is induced by different mechanisms in male and female patients, and genes involved in extracellular matrix organization, especially POSTN, might be important factors in male patients. This study provides insight into the pathogenesis of idiopathic carpal syndrome and might contribute to the development of new treatment strategies.

Treatment of Capitellum and Trochlea Fractures Using Headless Compression Screws and a Combination of Dorsolateral Locking Plates.

Introduction This study aimed to evaluate the clinical outcomes of 16 patients with capitellum and trochlea fractures that were treated using isolated headless compression screws or a combination of dorsolateral locking plates and anterior-to-posterior screws. We also investigated the presence of lateral epicondyle fragments because this fragment is especially important when making decisions regarding the surgical approach and implants. Materials and methods We conducted a retrospective analysis of 16 patients with capitellum and trochlea fractures. Clinical, radiographic (based on CT scans), and elbow-specific outcomes, including the Mayo Elbow Performance Index (MEPI), were evaluated at a mean of 23.5 months postoperatively. Results The average MEPI scores in patients with Dubberley type A (non-posterior comminution) and type B (posterior comminution) fractures were 88 and 78, respectively (p=0.08). Headless compression screws were used in 10 cases of type A fracture and one case of type B fracture. A combination of dorsolateral locking plates and anterior-to-posterior screws was used in five cases of type B fracture. Hardware loosening was seen in one case of type B fracture with isolated screw fixation. The presence of a lateral epicondyle fragment was significantly associated with the type B group (6/6 patients; 100%). In contrast, patients in the type A group rarely had posterior comminution of the lateral epicondyle fragment (2/10 patients; 20%). Conclusions Capitellum and trochlea fractures with posterior comminution, which typically presented with lateral epicondylar fragments, were safely and effectively treated with a combination of dorsolateral locking plates and anterior-to-posterior screws through lateral approaches. Cases without posterior comminution were treated with headless compression screws with no complications. The Dubberley classification system provides helpful information to determine the fixation strategy.

Multiple large pancreaticoduodenal artery aneurysms due to celiac artery occlusion: Combination of the aorto-hepatic bypass and coil embolization with a dual approach through both the superior mesenteric artery and bypass.

Pancreaticoduodenal artery aneurysm can occur from occlusion or stenosis of the celiac artery due to arteriosclerosis or median arcuate ligament compression. The risk of rupture of the aneurysm is independent of the aneurysmal diameter. A 78-year-old woman presented with multiple large aneurysms of the anterior superior pancreaticoduodenal artery. To preserve arterial flow to the liver, bypass grafting from the supra-celiac aorta to the common hepatic artery was performed at first. Coil embolization was successfully performed 10 days later with a dual approach through both the superior mesenteric artery and bypass. It was considered that the combination of the aorto-hepatic bypass and coil embolization was effective for the pancreaticoduodenal artery aneurysms due to celiac artery occlusion.

Iliac intramedullary stabilization for Type IIIA fragility fractures of the pelvis.

There have been few reports on fixation of Rommens classification Type IIIA fragility fractures of the pelvis (FFPs). Here, we present our less invasive surgical technique, called iliac intramedullary stabilization (ILIS), for the internal fixation of Type IIIA FFPs. The technique involves a closed reduction, termed the femur internal rotation reduction method (FIRM), whereby the fracture fragments are repositioned using lateral rotators by internally rotating the femur while the patient is in the prone position. Two iliac screws are inserted on the ilium bilaterally via the supra-acetabular bone canal during FIRM and connected with two transverse rods and two cross connectors. We refer to this internal fixation procedure as ILIS. We retrospectively recruited patients with Type IIIA fractures, treated using this procedure, at our institute between October 2017 and October 2019. We evaluated operative and post-operative outcomes. We enrolled 10 patients (9 women and 1 man; mean age, 85.2 years) who were followed up for over 6 months. All patients suffered FFPs after falling from a standing position. The mean operative time was 145.1 (range, 94-217) minutes, and the mean blood loss was 258.5 (range, 100-684) ml. All patients were allowed full weight bearing from post-operative day 1. All patients achieved bone union and regained their pre-injury walking ability at 6 months after surgery without evident secondary displacement. In conclusion, our ILIS technique allows less invasive internal fixation of Type IIIA FFPs with adequate stability for full weight bearing from post-operative day 1.

Utility of 70-kV single-energy CT in depicting the extent of breast cancer for preoperative planning.

PURPOSE: To evaluate the detectability of breast cancer and visibility of the tumor extent using 70-kV single-energy contrast-enhanced (CE) breast computed tomography (70-kV CECT) compared with CE breast magnetic resonance imaging (CEMR). METHODS: Between 2013 and 2015, 110 patients with 112 breast cancer lesions who underwent breast surgery after undergoing both 70-kV CECT and CEMR were enrolled. The major axis lengths of the breast lesion were measured and compared with the pathologically determined major axes. Agreement in the measured major axes was evaluated using the intra-class correlation coefficient (ICC). RESULTS: Both 70-kV CECT and CEMR depicted all breast cancer lesions. The mean major axis was 3.0 (95% confidence interval [CI], 2.5-3.4) cm on CECT and 2.9 (2.6-3.3) cm on CEMR. The mean differences between the pathologically and radiologically measured major axes on 70-kV CECT and CEMR were 0.9 (0.7-1.1) and 1.0 (0.8-1.2) cm, respectively. The accuracy of the radiological major axes compared with the pathological major axes was 82.1% and 80.4% on CECT and CEMR, respectively (p = 0.81). The major axes on the two modalities demonstrated moderate agreement (ICC = 0.69, 95% CI 0.58-0.77). Pathologically and radiologically measured major axes on 70-kV CECT and CEMR demonstrated excellent agreement (ICC = 0.91, 95% CI 0.93-0.96). CONCLUSIONS: Low-tube voltage (70-kV) CECT is the preferred modality to identify breast cancer lesions and tumor extent for preoperative planning because it has a similar diagnostic ability to CEMR and can be performed in the supine position.

Comparison of End-to-End Technique, Helicoid Technique, and Modified Helicoid Weave Repair Technique in a Rat Sciatic Nerve Model: A Pilot Study.

Background The gold standard for nerve repair is end-to-end (ETE) repair. Helicoid technique (HT) has also been previously described. In this pilot study, HT was compared to ETE and a modified helicoid weave technique (MHWT). In MHWT, recipient nerve is passed through rather than around the donor nerve, allowing for greater nerve-to-nerve interaction. Methods Eighteen adult male Lewis rats received a 2-cm sciatic nerve transection and were divided into three groups: ETE, HT, and MHWT. Five months later, electromyography (EMG), tetanic force of contraction, and wet weight of the extensor digitorum longus muscle were recorded in both the operated and non-operated sides. Nerve biopsies were taken proximal and distal to the site of the nerve graft for histological examination. Results One rat died following repair surgery and three rats died during the second surgery. The mean threshold of stimulation for ETE, HT, and MHWT were 183.3 µA, 3707.5 µA, and 656.6 µA, respectively. EMG analysis revealed that latency and duration are both affected by surgical repair type and injured or uninjured conditions. Threshold ratio (injured:non-injured) revealed pilot-level significant differences between HT and both MHWT (p = 0.069) and ETE (p = 0.082). Nerve biopsy demonstrated fascicles distally in all three groups. Conclusions While HT and MHWT function as a nerve repair technique, they are not superior to ETE. ETE remains the gold standard for nerve repair. While mean values were in favor of ETE, no statistical significance was attained.

Clinicopathological value of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) expression in synovium of patients with rheumatoid arthritis.

The etiology of rheumatoid arthritis (RA) is thought to involve dysfunction of the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway; PD-1 negatively regulates autoimmunity by interacting with its ligand, PD-L1. We therefore investigated PD-1/PD-L1 expression in synovial tissue of patients with RA. We immunohistochemically stained synovial specimens from 51 patients with RA and assessed the association between PD-1/PD-L1 expression and rheumatoid factor (RF), the total count of infiltrating T cells, C-reactive protein (CRP), and Krenn's synovitis score. PD-1 expression on infiltrating lymphocytes was detected in 34/51 RA cases (66.7%), while PD-1 expression was very mildly correlated only with the number of total infiltrating T cells (R2 = 0.1011, P = 0.0230). On the other hand, PD-L1 expression on synovial lining cells was observed in 37/51 RA cases (72.5%). Furthermore, a higher PD-L1 expression was significantly associated with RF positive state (P = 0.0454), and the correlations between PD-L1 expression and the number of infiltrating T cells (R2 = 0.5571, P < 0.0001), CRP (R2 = 0.4060, P < 0.0001), and Krenn's synovitis score (R2 = 0.7785, P < 0.0001) were confirmed. PD-1 was expressed on infiltrating lymphocytes, while PD-L1 was expressed on synovial lining cells; the expression of PD-L1 on synovial lining cells was significantly correlated with the active state of the disease. These data suggest that PD-1/PD-L1 pathway may have an important role in the pathogenesis of RA.

Primary Hinged External Fixation of Terrible Triad Injuries and Olecranon Fracture-Dislocations of the Elbow.

This study aimed to introduce a new treatment that apples primary hinged external fixation for complex fracture-dislocations of the elbow in 12 cases. We retrospectively assessed the functional outcomes of eight patients with terrible triad injuries and three patients with an olecranon fracture-dislocation of the elbow, who were treated at our hospital using a primary hinged external fixator between June 2012 and December 2014. Ten patients underwent repair or replacement of the radial head, while three underwent repair of the olecranon. In principle, they were treated without reconstruction of the coronoid fracture and collateral ligament injury. The patients were evaluated for a mean follow-up period of 16 months after the initial surgery. Early mobilization was encouraged while the hinged external fixator was in place. At the follow-up, the mean Mayo Elbow Performance Score was 93 points; the results were "excellent" in six cases and "good" in five. No patients had recurrent elbow instability. Only one patient needed an additional procedure after the initial operation. These results suggested that primary hinged external fixation without repair of the ligament and soft tissue is an effective minimally invasive surgery for the management of terrible triad injuries and olecranon fracture-dislocations of the elbow.

Frequency of Scapholunate Ligament Injuries Associated with Distal Radius Shearing Fracture: Correlation of Fracture Patterns and Ligament Tear.

BACKGROUND: This retrospective study assessed the prevalence and outcome of intercarpal ligament injuries in non-osteoporotic patients with AO/ASIF classification type B distal radius shearing fractures treated with or without scapholunate temporary fixation. METHODS: Fifteen patients (mean age, 33 years) were analyzed according to their scapholunate ligament status at the time of injury and graded with a modified Geissler classification system. Each patient's postoperative pain and occupational status were assessed in the context of the Modified Mayo wrist score. Second-look arthroscopy was performed for all cases. RESULTS: Scapholunate ligament injuries were present in 14 of 15 type B fractures. Surgical outcomes yielded an improvement in the Mayo wrist score with pinning in cases involving grade 3 or 4 scapholunate injuries. Two cases without pinning had a worse score, as well as a persistent scapholunate tear that was not healed at second-look arthroscopy after eight postoperative months. However, in grade 1 or 2 scapholunate injuries, the Mayo wrist score did not differ between those treated with and without pinning. CONCLUSIONS: Scapholunate ligament injury is an important risk factor associated with high-energy distal radius shearing fractures. To prevent these problems, temporary scapholunate joint fixation is a recommended treatment for grade 3 or 4 scapholunate injuries.

Psoriasis vulgaris caused by ceramic inserts used in total hip replacement.

BACKGROUND: Ceramics are inorganic nonmetallic materials and are used as bioinert components in joint replacement surgeries. Ceramics are known to be low allergenic. We experienced a ceramic-induced psoriasis. OBJECTIVE: We report a first case of possible ceramic-induced psoriasis caused by a ceramic insert. METHODS: A 55-year-old female received an implanted ceramic-on-ceramic total hip replacement for osteoarthritis of the right hip joint. Following surgery, she developed psoriatic lesions, which continued for 10 years. We suspected that psoriasis was caused by a ceramic insert and removed it surgically. RESULTS: When the ceramic insert was replaced with a polyethylene-on-metal hip joint, the psoriatic lesions completely disappeared. CONCLUSION: The pathogenesis of psoriasis is still an enigma, although deregulation of nuclear factor κB signaling and resulting abnormal cytokine secretion are speculated to be involved. Ceramics may affect these signaling events and cause the onset of psoriasis.

Hyperadiponectinemia enhances bone formation in mice.

BACKGROUND: There is growing evidence that adiponectin, a physiologically active polypeptide secreted by adipocytes, controls not only adipose tissue but also bone metabolism. However, a role for adiponectin in bone development remains controversial. METHODS: We therefore investigated the endocrine effects of adiponectin on bone metabolism using 12-week-old male transgenic (Ad-Tg) mice with significant hyperadiponectinemia overexpressing human full-length adiponectin in the liver. RESULTS: In Ad-Tg mice, the serum level of osteocalcin was significantly increased, but the levels of RANKL, osteoprotegerin, and TRAP5b were not. Bone mass was significantly greater in Ad-Tg mice with increased bone formation. In contrast, bone resorption parameters including the number of osteoclasts and eroded surface area did not differ between Ad-Tg and their littermates. CONCLUSIONS: These findings demonstrate that hyperadiponectinemia enhances bone formation in mice.

A case of vasa previa diagnosed prenatally, and review of the literature.

The perinatal mortality rate of vasa previa is high if it is not prenatally diagnosed. In this report, a case of vasa previa diagnosed prenatally is presented. Antepartum hemorrhage at 24 weeks of gestation prompted a close investigation of the uterine cervix, internal os, and placenta. We detected a low-lying bilobed placenta with umbilical cord insertion in the lower uterine segment. Furthermore, one of the connecting vessels of the bilobed placenta passed directly above the internal os. Vasa previa was suspected and confirmed with color Doppler and MRI. The fetus was delivered uneventfully by planned Cesarean section at 38 weeks of gestation. It should be considered that placenta previa (including low-lying placenta), bilobed placenta, and umbilical cord insertion in the lower uterine segment are associated with high risk of vasa previa. Ultrasound screening for cord insertion and placenta around the internal os enables efficient and certain detection of vasa previa.

Mantle cell lymphoma shows three morphological evolutions of classical, intermediate, and aggressive forms, which occur in parallel with increased labeling index of cyclin D1 and Ki-67.

Although the 2008 World Health Organization classification defines two subtypes of mantle cell lymphoma (MCL), classical and aggressive, we often encounter MCL with both features in the same site. We named this feature "MCL with focal aggressive form (intermediate MCL)". In the present study, we reclassified 237 patients with cyclin D1 (CCND1)-positive MCL on the basis of the concept of intermediate MCL, and analyzed the correlation of this reclassification with immunohistochemical detection of CCND1, Ki-67, p53, p27(Kip1), and p21(WAF/Cip1). The median overall survival was 77, 31, and 18 months for classical, intermediate, and aggressive MCL, respectively, showing a statistically significant difference (P < 0.0001). The expression levels of CCND1, Ki-67, p53, and p21(WAF/Cip1) in aggressive MCL (mean 80.1 +/- 27.8%, 73.7 +/- 28.9%, 31.0 +/- 69.0%, and 10.4 +/- 24.8%, respectively) were higher than those in classical MCL (mean 58.1 +/- 36.7%, 25.2 +/- 25.5%, 6.5 +/- 24.3%, and 2.5 +/- 13.0%, respectively) and intermediate MCL (mean 75.7 +/- 31.4%, 30.8 +/- 33.3%, 21.0 +/- 57.4%, and 4.8 +/- 16.5%, respectively). Significantly different levels of Ki-67 and p21(WAF/Cip1) were only recognized between intermediate and aggressive (P < 0.05 and P < 0.0001, respectively), whereas those of CCND1 and p53 were only between classical and intermediate (P < 0.0001 and P < 0.05, respectively). There were no significant differences in p27(Kip1) among the three groups. The subsequent discriminant analysis with independent prognostic factors clearly demonstrated that the morphological evolution of MCL occurs in parallel with increased labeling index of CCND1 and Ki-67. The diagnosis of intermediate MCL thus proved to be of major significance and should enable the design of more tailored therapies.

Phenotype for activated tissue macrophages in histiocytic necrotizing lymphadenitis.

Macrophage polarization is divided into M1 and M2 type based on membrane receptors, cytokines, and chemokines. M1 expresses CD80, interleukin (IL)-6, IL-12, and chemokine receptor (CCR)7, while M2 expresses CD163, IL10, and chemokine ligand (CCL)22. The aim of the present study was to identify the properties of infiltrating tissue macrophages in histiocytic necrotizing lymphadenitis (HNL). Twenty patients with HNL were studied, and immunohistochemistry for CD68 (KP1), CD163, CCL22, CCR7, and CD123 was done, along with myeloperoxidase (MPO). To evaluate the phenotypes of tissue macrophages in HNL, the number of cells stained positively for CD163, CCL22, CCR7, CD123 and MPO concurrently with CD68 was counted, and the ratio was calculated for each antibody to CD68+ cells. There was a high rate of co-expression for CD163 (median, 78%) or CCL22 (80%) and a low rate for CCR7 (5%) in CD68+ cells. It is therefore conceivable that infiltration by M2 macrophages is dominant in HNL. Furthermore, some CD68+ tissue macrophages in HNL co-express MPO or CD123 (range, 5-80%; median, 23% and 40%, respectively). It is suggested that these characteristic tissue macrophages may be associated with the pathogenesis of HNL and that M2 macrophages may infiltrate to repair the lymphoid tissue injured by cytotoxic T cells in HNL.

Hepatocellular apoptosis associated with cytotoxic T/natural killer-cell infiltration in chronic active EBV infection.

The aim of the present study was to identify the mechanism of hepatocellular apoptosis induced by EBV-infected cytotoxic T/natural killer (NK) cells in chronic active EBV infection (CAEBV). Eight patients with CAEBV were studied, and infected T-cell expansion and NK-cell expansion were detected in four patients each. Biopsy or necropsy was performed on lymph node, liver, or spleen, and each specimen was subjected to immunohistochemical double staining of CD3 plus caspase-3 with the addition of cytotoxic markers of T-cell restricted intracellular antigen-1 (TIA-1), perforin, and granzyme B, as well as EBV in situ hybridization (EBV-ISH). In the liver, some of the infiltrating CD3-positive lymphocytes stained positively for EBV-ISH and cytotoxic markers. Double staining of CD3 plus caspase-3 indicated caspase-3 positive hepatocytes with apoptotic features, accompanied by extensive infiltration of CD3-positive cells, which were directly attached to the apoptotic caspase-3 positive hepatocytes. In contrast, far fewer cells stained positive for caspase-3 in lymph node and spleen than in liver. The present findings suggest that in patients with CAEBV, cytotoxic T/NK cells may directly induce hepatocytes to undergo apoptosis more frequently than they do cells in other organs of the reticulo-endothelial system.

Estimation of the relationship between caspase-3 expression and clinical outcome of Burkitt's and Burkitt-like lymphoma.

Burkitt's lymphoma and atypical Burkitt/Burkitt-like lymphoma (BL/BLL) are considered highly aggressive B-cell lymphomas with a rapid proliferative rate and high rate of apoptosis. The aim of the present study was to confirm whether apoptotic and cell proliferative factors affect BL/BLL clinical outcomes. We retrospectively analyzed the relationship between the clinical and immunophenotypic features of 43 BL/BLL patients by immunohistochemical staining for bcl-2 and double staining for Ki-67 plus caspase-3. In double staining experiments, all patients were divided into high and low groups for the expression of caspase-3, Ki-67, and both Ki-67 and caspase-3, by using the medians of their percentages as limits. The 43 BL/BLL patients were divided into high caspase-3 (n = 19) and low caspase-3 (n = 24) groups. There was a significant difference in the overall survival between the high (77%) and low caspase-3 (33%) groups; the survival rate of patients in the low caspase-3 group who received aggressive short-term chemotherapy (58%) was significantly better than that of patients who received cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) therapy (17%). All patients positive for bcl-2 were in the low caspase-3 group (high caspase-3 group, 0%; low caspase-3 group, 42%). The overall survival tended to be better in the high caspase-3 and bcl-2-negative group (76%) than in the low caspase-3 and bcl-2-negative (50%) group. In addition, the low caspase-3 and bcl-2-positive group tended to show the worst prognosis (16%). We suggest that caspase-3 may function as an indicator of the prognosis of BL/BLL. Furthermore, intensive short-term chemotherapeutic regimens may improve the prognosis of the patients in the low caspase-3 group.

Downregulation of RCAS1 and upregulation of cytotoxic T cells affects synovial proliferation and apoptosis in rheumatoid arthritis.

OBJECTIVE: The main histological change in rheumatoid arthritis (RA) is the villous proliferation of synovial lining cells. This seems to be the result of the proliferation and apoptosis induced by immune balance. We studied the involvement of RCAS1 and the infiltration of cytotoxic T lymphocytes (CTL), and examined the synovium immunohistochemically to determine the involvement of proliferation and apoptosis in synovial lining cells, and their relationship with the activity of RATreg cells in the germinal center. METHODS: We used double-immunological staining of Ki-67 and caspase-3 to investigate proliferation and apoptosis. We analyzed CTL, regulatory T cells (Treg), and receptor-binding cancer antigen expressed on SiSo cells (RCAS1), recently recognized to play a role in immune evasion. Proliferation and apoptosis were more frequently encountered in synovial lining cells in RA than in those in osteoarthritis (OA) that were used as a control. RESULTS: High expression of RCAS1 was detected more frequently in the synovial lining cells of OA, but CTL infiltration into the synovium was rarely found. In RA, on the other hand, CTL were observed, while RCAS1 expression was lacking. We compared the presence of Foxp3-positive cells with the level of C-reactive protein (CRP) that served as an active inflammatory marker. Foxp3-positive cells in the germinal center and in CRP showed possible correlation in terms of the range of inflammatory states. CONCLUSION: In RA, the lack of RCAS1 is thought to induce CTL infiltration through loss of the ability to evade immune attack, thus leading to apoptosis of the synovial lining cells. In addition, Treg cells may play a role in the downregulation of activated T cells.

The relationship of FOXP3 expression and clinicopathological characteristics in adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma is an aggressive malignant disease associated with regulatory T cells as discussed in some recent reports. We analyzed the expression of FOXP3, a key molecule of regulatory T cells, in adult T-cell leukemia/lymphoma and its association with clinicopathological features. Of 169 adult T-cell leukemia/lymphoma cases examined, 60 (36%) showed FOXP3 expression in lymphoma cells. Morphologically, 22 cases were classified as anaplastic large cell variant and 147 as pleomorphic cell variant. Only 1 (5%) of the anaplastic large cell variant cases and 59/147 (40%) of the pleomorphic cell variant cases expressed FOXP3. Epstein-Barr virus-infected cells were significantly more frequently found in FOXP3(+) cases (23/60; 38%) than in FOXP3(-) cases (12/109; 11%) (P<0.0001). Cytogenetic analysis showed that FOXP3(+) cases had simpler chromosomal abnormalities than FOXP3(-) cases. Clinically, FOXP3(+) and FOXP3(-) cases did not differ significantly in age distribution, clinical stage, lactate dehydrogenase and calcium in serum and overall survival. However, 8 of 34 FOXP3(+) cases suffered a severe infectious state, an indication of immunosuppression, while only 2 of 62 FOXP3(-) cases did so (P<0.005). FOXP3 expression in adult T-cell leukemia/lymphoma thus reflects morphological features and is clinically and pathologically associated with an immunosuppressive state.

Estimation of apoptosis and cell proliferation in histiocytic necrotizing lymphadenitis using immunohistochemical double staining.

The aim of the present study was to estimate the relationship between apoptosis and cell proliferation in histiocytic necrotizing lymphadenitis (HNL). Fifteen patients with HNL were retrospectively analyzed. The patients were divided into three groups according to the proportion of the necrotic area as follows: necrosis (+), necrotic area <25%; necrosis (++), necrotic area 25-50%; and necrosis (+++), necrotic area >50%. Immunohistochemical double staining was performed for CD3 plus caspase-3 and for Ki-67 plus caspase-3 and positive cells were counted in two areas: one without and one with obvious apoptotic features. Most caspase-3-positive cells were also stained for CD3 (area exhibiting obvious apoptotic features: average, 92.3%). Furthermore, various proportions of both Ki-67- and caspase-3-positive cells were detected in all the groups (range, 5-70%). In the area with obvious apoptotic changes, the average percentage of both Ki-67- and caspase-3-positive cells (38.6%) was higher than that in the area without obvious apoptotic features (16.3%). A proportion of cells in HNL undergo proliferation and apoptosis simultaneously, such as neoplastic cells, thereby exhibiting rapid cell cycles.