Biomedical subjects
Hideto Nakajima
Publications and source records attributed to Hideto Nakajima.
Flow cytometric immunophenotyping of adult T-cell leukemia/lymphoma using CD3 gating.
Adult T-cell leukemia/lymphoma (ATLL) is a lymphoproliferative neoplasm of helper T lymphocytes caused by human T-cell leukemia virus type-1 (HTLV-1). The disease was first described in Kyushu, in southwestern Japan, and most frequently occurs in endemic areas, such as Japan, the Caribbean basin, West Africa, Brazil, and northern Iran. ATLL is essentially a disease of adults, characterized clinically by generalized lymphadenopathy, hepatosplenomegaly, skin lesions, and hypercalcemia. The prognosis of most patients is quite poor, with a median survival time of only 13 months, even if multiagent combination chemotherapy is given. In the present study, flow cytometric immunophenotyping with CD3 gating was performed on 30 samples from 26 patients who had been given a diagnosis of ATLL. The records of these patients also were reviewed retrospectively. In 14 of the 30 samples, an abnormal CD3(low) T-cell population was distinguishable from the normal T-cell populations by flow cytometric analysis. Herein we report a novel strategy for flow cytometric immunophenotyping of ATLL facilitated by CD3(low) gating.
Expression of TH1/TH2-related chemokine receptors on peripheral T cells and correlation with clinical disease activity in patients with multiple sclerosis.
Th1 cells play an important role in the pathogenesis of multiple sclerosis (MS), a disease likely linked to an autoimmune process. We measured the levels of chemokines in serum or cerebrospinal fluid (CSF) samples by ELISA, and also studied the expression of Th1-related CXCR3/CCR5 chemokine receptors and Th2-related CCR4/CCR3 chemokine receptors on blood cells from MS patients using three-color flow cytometry. The Bonferroni correction was used for the statistical analysis. The levels of CXCL10, CCL3, and CCL5 in the CSF samples for the MS groups were significantly higher than those for the control group. However, the levels of CCL2 in both the CSF and serum samples for the remission group were significantly higher than those for the active group. The percentage of CXCR3-expressing CD4+ T cells in patients with MS was significantly elevated compared with the healthy controls. Moreover, MS patients in an active phase showed a more increased CD4+CXCR3+/CD4+CCR4+ ratio than patients in a remission phase. The increased percentage of CD4+CXCR3+ cells in the blood was associated with relapses in MS. This study suggested that the CD4+CXCR3+/CD4+CCR4+ ratio could be a sensitive maker of immune dysfunction in MS.
Decreased CD14+CCR2+ monocytes in active multiple sclerosis.
The expression of CCR2, a receptor to MCP-1, on blood monocytes was measured in 15 patients with active multiple sclerosis (MS). We determined the ratio of CD4+CXCR3+cells (Th1), CD4+CCR4+cells (Th2), and CD14+CCR2+ cells using 3-color flow cytometry. The CD4+CXCR3+/CD4+CCR4+ ratio, which represents the Th1/Th2 balance, was significantly elevated in the active MS patients compared to the healthy controls. The expression of CCR2 and CD14 on the monocytes in the MS patients was markedly decreased. There was a significant negative correlation between the Th1/Th2 ratio and the CCR2 and CD14 expression on monocytes. In the pathogenesis of MS, the CD14+CCR2+ blood monocytes may play an important role in the shift from active MS to a state in which the disease is in remission.
Distribution of type VI collagen in chondrocyte microenvironment: study of chondrons isolated from human normal and degenerative articular cartilage and cultured chondrocytes.
The chondron is the microanatomical unit composed of a chondrocyte and its pericellular microenvironment (PCME), including the pericellular matrix and capsule. In the present study, we extracted chondrons from human articular cartilages and investigated the relationship between the distribution of the matrix molecules, including type VI collagen, and the degeneration of articular cartilage. We also investigated the effects of interleukin-1beta (IL-1beta) and transforming growth factor beta-1 (TGF-beta1) on the distribution of type VI collagen in cultured chondrocytes. Chondrons were extracted by low-speed homogenization from cartilage pieces obtained from forensic autopsies and from patients with knee osteoarthritis (OA) undergoing total knee arthroplasty. Cartilage sections were classified into three groups (normal, slight degeneration, and moderate degeneration) based on the degree of degeneration according to Mankin's score. Extracted chondrons were immunostained, and the distribution of the matrix molecules, including type VI collagen, was investigated using a confocal laser scanning microscope (CLSM). The chondrocytes isolated by enzymic treatment were subjected to three-dimensional culture in agarose gel and then treated with IL-1beta or TGF-beta1. The distribution of newly synthesized type VI collagen in agarose gel was also investigated using the CLSM. Type VI collagen was localized specifically within the PCME of chondrons. The volume ratio of PCME to chondrocyte (P/C ratio) was significantly higher in the moderate degeneration group than in the other two groups. The accumulation of type VI collagen around a chondrocyte was obviously increased by the addition of TGF-beta1. The P/C ratio significantly increased as the severity of the OA progressed, suggesting that type VI collagen distributed specifically in the PCME was playing a protective role for chondrocytes by maintaining the pericellular microenvironment in OA.
Repair of full-thickness cartilage defects using liposomal transforming growth factor-beta1.
Transforming growth factor-beta1 (TGFbeta1) is a well- known, potent growth factor implicated in both in vitro and in vivo chondrogenesis. Liposomes have been employed as a drug delivery system to promote the efficient use of drugs. The objective of this study was to demonstrate that a single injection of liposomal TGFbeta1 has an accelerating effect on the repair of an articular cartilage defect. Full-thickness articular cartilage defects were prepared on the patellar grooves of the femurs in knee joints of Japanese white rabbits. One week after surgery, various reagents including liposomal TGFbeta1, free TGFbeta1, and phosphate-buffered saline were injected into the operated knee joints. At 3 weeks after surgery the specimens obtained from the lesions were evaluated histologically, and the glycosaminoglycan content was quantified. Histological examination revealed that the defects were filled with thicker fibrous cartilage and showed more intense metachromatic staining in the liposomal TGFbeta1 group than in the other groups. The glycosaminoglycan content of the repair tissue was also significantly higher in the liposomal TGFbeta1 group than in the other groups. This study indicated that the intraarticular injection of liposomal TGFbeta1 could accelerate the early-stage repair of full-thickness articular cartilage defects.
Primary repair of the collateral ligament of the proximal interphalangeal joint using a suture anchor.
Ten out of 12 complete ruptures of the collateral ligament of the proximal interphalangeal joint were repaired primarily using a suture anchor. Active finger exercise was started gently by taping the injured finger to adjacent one one week postoperatively. All patients returned to their original occupation or sports activities within seven weeks of operation. No patients complained of pain on the involved finger at rest or during movement. There was no instability of the proximal interphalangeal joint on manual lateral stress test postoperatively.
Multiple sclerosis after allergen-specific immunotherapy and influenza vaccination.
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[The changes of clinical characteristics in 100 Japanese amyotrophic lateral sclerosis patients between 1980 and 2000].
OBJECTIVE: To define changes of clinical features in amyotrophic lateral sclerosis (ALS) over the past 20 years and prognostic indicators of ALS from a single hospital-based retrospective survey. BACKGROUND: One of the important tasks in ALS research is to determine differences between patients who progress at different rates. Predicting survival time in ALS helps both physicians and patients to make decisions regarding assisted ventilation. PATIENTS/METHODS: A total of 100 patients (61 men, 39 women) hospitalized between 1980 and 2000 were investigated in the study. Subjects were divided into Groups A and B (Group A: n = 50, diagnosed between 1990 and 2000; Group B: n = 50, diagnosed between 1980 and 1990). Group C comprised 34 patients supported by artificial ventilation between 1980 and 2000. Information was obtained for all patients regarding time of individual primary end-point (PEP, time of death or required ventilation support), secondary end-point (SEP, time of death after artificial ventilation) or being alive with or without ventilation support. Combined type of ALS was defined as two or more regions presenting simultaneously at initial onset. Progression rate was calculated as the time (months) required for a 1-point loss on the ALS functional rating scale (ALS-FRS), using 1/delta FS:1/delta FS = duration (months) from onset to diagnosis/(48-ALSFRS at diagnosis) RESULTS: Mean age at onset has increased in the past 20 years from 59.4 years (group B) to 62.5 years (group A). An increased incidence has been observed in the patients over 70 years with ALS (A:n = 8 vs. B:n = 4). The frequency of assisted ventilation support had been significantly increased for 22 of 44 group A patients (50%) including 5 patients supported by non-invasive positive pressure ventilation, compared to 12 of 48 group B patients (25%, P < 0.01). Two patients in group B and 6 patients in group A who were still alive at time of the investigation were excluded. Mean interval between symptom onset and diagnosis was 14.7 months (A:14.0 months; B:15.4 months). No differences were observed between groups A, B and C regarding sex ratio, mean total ALS-FRS score at diagnosis. Mean survival times were as follows obtained from Kaplan-Meier survival curves; group A:30.8 months, group B:31.0 months until the time of PEP, group C:67.2 months until the time of SEP. Symptoms started in the upper limbs (U) in 37 patients, in the lower limbs (L) in 34, in the bulbar region (B) in 19, as combined type in 9 and in respiratory muscles in 1. Mean survival time until PEP was 33.9 months for U, 34.8 months for L, 28.6 months for B and 18.2 months for C (P < 0.001). Combined-type patients with ALS revealed shorter the time until diagnosis (*P < 0.01) and faster the time until PEP than the other ALS types (P < 0.001 Log-rank test). A significant correlation was found between 1/delta FS and the time until PEP (y = 9.64x + 12.6, r2 = 0.545, p < 0.001, y = PEP, x = 1/delta FS). CONCLUSIONS: Combined type ALS displayed significantly shorter time to PEP than other types. ALS outcome was significantly related to the progression rate of symptoms from total score for ALS-FRS at time of diagnosis.
[Preferential distal muscle involvement in case of oculopharyngeal muscular dystrophy with (GCG) 13 expansion].
We reported a 52-year-old woman with oculopharyngeal muscular dystrophy (OPMD) harboring expanded (GCG) 13 mutation of the poly (A) binding protein 2 gene. She presented not only ptosis and dysphagia but distal dominant muscle atrophy in four extremities. CT demonstrated distal muscle atrophy with marked fat replacement in the biceps femoris, semitendinosus, membraneous, soleus, and gastrocnemius muscles. Although OPMD is considered to be a muscle disease, this patient showed even neurogenic features in the electrophysiological and pathological findings. Although previous reports indicate that OPMD is genetically homogeneous disease, some cases with OPMD may show some atypical features associated with neurogenic involvement.
Hypercreatine kinasemia normalized during complete bed-rest in patients with X-linked spinobulbar muscular atrophy.
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[Herpes simplex encephalitis with expanded cerebral cortex lesions on T1-weighted MRI after clinical improvement: a case report].
We described a 58-year-old woman with herpes simplex encephalitis (HSE), who initially had fever and developed impaired consciousness. Cerebrospinal fluid (CSF) examination showed mononuclear pleocytosis and the existence of herpes simplex virus (HSV) DNA. The first T1-weighted MR image showed symmetrical swelling and low signal intensity lesions in the medial temporal lobes and hippocampus. T2-weighted MR image showed high signal intensity lesions in the medial temporal lobes, the amygdala, the hippocampus, the insula and the cingulate gyri bilaterally. After the treatment with intravenous acyclovir and betamethasone, impaired consciousness and recent memory disturbance gradually improved. On the second T1-weighted MR image examination, eighteen days after the onset, high signal intensity lesions were demonstrated in the right medial temporal lobe, the right hippocampus, the left insula and the bilateral cingulate gyri. Although the clinical symptoms had improved significantly over three months, the high signal intense lesions on T1-weighted MR images were also detected in the left medial temporal lobe, the right insula, and the straight gyrus. Brain CT did not demonstrate any abnormalities. The repeated CSF examinations showed negative HSV DNA and a decreased number of WBC. However, oligoclonal IgG bands were continuously positive. Myelin basic protein level and IgG index increased in parallel with the expansion of the cerebral lesions on T1-weighted MR images. In the present case, the abnormality of T1-weighted MRI was thought to indicate hemorrhagic inflammatory lesions that could not be detected by CT. The increased level of myelin basic protein, the elevated IgG index and the continuous positive oligoclonal IgG indicated continuous immunologic response against HSV in these lesions.