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Biomedical subjects

Y Nonomura

Publications and source records attributed to Y Nonomura.

At least 19 recordsLinked to original sources

MR detection of iliac bone marrow involvement by malignant lymphoma with various MR sequences including diffusion-weighted echo-planar imaging.

OBJECTIVE: To assess the diagnostic accuracy of MR imaging for detecting bone marrow infiltration by malignant lymphoma. PATIENTS AND DESIGN: Fifty-three patients with malignant lymphoma underwent MR imaging and bone marrow biopsy. In 80 iliac crests of the 53 patients (13 positive specimens in 9 patients and 67 negative specimens in 44 patients), biopsy results and the signal intensity characteristics were compared. MR sequences included T1-weighted SE, T2-weighted FSE with fat suppression, FSE STIR, and diffusion-weighted EPI with fat suppression at 1.5 T. RESULTS AND CONCLUSIONS: To detect lymphoma infiltration, T1-weighted SE had the highest sensitivity (92%) and diffusion-weighted EPI with fat suppression and FSE STIR had the highest specificity (92.5% and 92%, respectively). A combination of T1-weighted SE and FSE STIR yielded the highest sensitivity and specificity (85% and 97%, respectively). A combination of T1-weighted SE and FSE STIR sequences seems to be the current choice of imaging protocol for detecting bone marrow infiltration by malignant lymphoma.

Biopsy↗

Intramedullary teratoma of the spine: report of two adult cases.

STUDY DESIGN: Two case reports of intramedullary teratoma in the spinal cord of adults, and a review of the literature. OBJECTIVE: To investigate and describe unusual cases of spinal teratoma using MRI to define features that may be used to avoid misdiagnosis. SETTING: A department of orthopedic surgery in Japan. METHODS: One patient, a 37-year-old woman, was referred because of gait disturbance. She was evaluated by myelography, CT scan with myelography, and MRI. T12 through L1 laminoplasty was performed and the tumor was subtotally removed. The other patient, a 56-year-old man, was referred because of muscle weakness and sensory disturbance. MRI revealed multiple spinal tumors. C4 through C6 laminoplasty and T12 through L2 laminoplasty were performed, and the tumors in these regions were subtotally removed. RESULTS: In Case 1, the postoperative course was excellent, and histological examination of the resected specimen revealed a spinal teratoma consisting of ectodermal and mesodermal elements. In Case 2, the symptoms were resolved after surgery, and ectodermal, mesodermal and endodermal elements were revealed. CONCLUSIONS: Although intramedullary teratomas are very rare in adults, they need to be considered in differential diagnosis.

Adult↗

Effects of point defects on the phase diagram of vortex states in high- T(c) superconductors in the B parallel to c axis.

The phase diagram for the vortex states of high- T(c) superconductors with point defects in the B--> parallel to c axis is drawn by large-scale Monte Carlo simulations. The vortex slush (VS) phase is found between the vortex glass (VG) and vortex liquid (VL) phases. The first-order transition between this novel normal phase and the VL phase is characterized by a sharp jump of the density of dislocations. The first-order transition between the Bragg glass (BG) and VG or VS phases is also clarified. These two transitions are compared with the melting transition between the BG and VL phases.

Journal Article↗

Relationship between bone marrow cellularity and apparent diffusion coefficient.

This study was performed to determine if there is a relationship between apparent diffusion coefficient (ADC) and cellularity of bone marrow of the posterior ilium. Four groups of various marrow cellularity underwent diffusion-weighted echo-planar imaging: 1) adults with normal hypocellularity (21 patients); 2) adults with normal normocellularity (13 patients); 3) young children with normal hypercellularity (5 patients); and 4) adults with lymphoma-related hypercellularity (3 patients). In all adults, marrow cellularity was confirmed by uni-or bilateral bone marrow biopsies. In children, the iliac marrow was presumed hypercellular because of their ages. A total of 66 ADC values of bone marrow calculated from diffusion-weighted images with b-values of 30 and 300 seconds/mm(2) was evaluated. Hypercellular marrow (normal and lymphoma-related) showed the highest mean ADC, and hypocellular the lowest ADC. Statistically significant differences were found between three groups of normal marrow: hypocellular, normocellular, and hypercellular. There is a positive correlation between ADC and cellularity of bone marrow. J. Magn. Reson. Imaging 2001;13:757-760.

Adult↗

Suppression of arthritis by forced expression of cyclin-dependent kinase inhibitor p21(Cip1) gene into the joints.

Rheumatoid synovial fibroblasts (RSF) express cyclin-dependent kinase (CDK) inhibitors p16(INK4a) and p21(Cip1) when they are growth-inhibited in vitro. The induction of p16(INK4a) is characteristic of RSF and intra-articular p16(INK4a) gene therapy has been shown to suppress adjuvant arthritis (AA) of rats. The other inducible CDK inhibitor, p21(Cip1), has multiple functions depending on the cell type. They include inhibition of CDK as well as promotion of active CDK complex formation and induction of apoptosis. This study is to discern the biological effects of p21(Cip1) gene transfer into RSF and its therapeutic effects on AA. A recombinant adenovirus containing a human p21(Cip1) gene and control adenoviruses were prepared. RSF infected with these viruses were examined for their cell growth. Apoptotic cell death was evaluated by nuclear staining and DNA fragmentation analysis. In vivo gene therapy of rat AA was carried out by intra-articular injection of the viruses. Severity of the arthritis was clinically scored. The treated joints were examined histologically and proliferating cell nuclear antigens (PCNA) were detected immunohistochemically. The adenoviral p21(Cip1) gene transfer inhibited growth of RSF without inducing apoptosis. p21(Cip1) gene therapy suppressed AA clinically and histologically. The effects were comparable to p16(INK4a) gene therapy. PCNA expression was reduced in the p21(Cip1)-treated joints. The adenoviral gene transfer of p21(Cip1) ameliorated rat AA. The effect was attributable to inhibition of proliferation. Because p21(Cip1) is induced more easily by many chemicals than p16(INK4a), it also appears to be a feasible target in developing anti-rheumatic drugs.

Adenoviridae↗

[A case of sarcoidosis characterized by a nasopharyngeal tumor and neurological lesions].

A 20-year-old man was admitted to a hospital complaining a slight fever lasting for 3 months associated with a dull headache and weight loss. A tumor was found in the nasopharynx of which biopsy specimen revealed granulomas with Langhans' giant cells. He was given antituberculous agents without symptomatic improvement, and transferred to our hospital. Serum levels of soluble IL-2 receptor and lysozyme were increased, and a significant uptake was observed by Ga scintigraphy at the nasopharynx and bilateral hilar lymphnodes. Furthermore, spinal fluid contained increased number of mononuclear cells, and T2-weighted MRI scans showed an enhanced lesion at the pituitary stalk. The specimen of both TBLB and repeated biopsy of the nasopharyngeal tumor showed granulomas without caseous necrosis. Taken together with these findings, a diagnosis of sarcoidosis with CNS involvement was finally made, and he made a favorable progress by treatment with prednisolone. This is an unique case which emphasizes importance of differential diagnosis of nasopharyngeal tumors with neurological manifestations in the clinicalsetting of rheumatology.

Adult↗

[A case of dermatomyositis complicated with pneumomediastinum that was successfully treated with cyclosporin A].

We reported the case of a 39-year-old man with dermatomyositis (DM) complicated with subcutaneous emphysema and pneumomediastinum during steroid therapy. The patient had complained of muscle weakness, dyspnea and skin eruption on his anterior chest wall 6 months prior to admission. He was diagnosed as having DM on the basis of an elevation in myogenic enzymes, myogenic changes in electromyography, a skin biopsy and a muscle biopsy. Chest roentgenogram revealed interstitial pneumonia (IP) in the lower lobes of the lungs. The administration of prednisolone (60 mg/day) was initiated, which resulted in improvement of DM. Fifteen days after the initiation of the steroid therapy, the patient developed subcutaneous emphysema and pneumomediastinum. Additional administration of cyclosporin A (CsA) enabled us to rapidly taper the dose of prednisolone without aggravating the diseases. Several reports have shown that vasculitis might be involved in the pathogenesis of pneumomediastinum in DM patients. Infection and tissue fragility due to steroid therapy worsen the outcome of those patients. CsA therapy may improve the outcome through the anti-vasculitic- and steroid sparing-effects.

Adult↗

Adenoviral transfer of cyclin-dependent kinase inhibitor genes suppresses collagen-induced arthritis in mice.

In rheumatoid synovial tissues, synovial fibroblasts are activated by proinflammatory cytokines and proliferate to develop hyperplastic pannus tissues, which irreversibly damage the affected joints. We recently reported that the cyclin-dependent kinase inhibitors p16(INK4a) and p21(Cip1) are not expressed in vivo in rheumatoid synovial fibroblasts, but are readily inducible in vitro. This observation was followed by the successful treatment of rat adjuvant arthritis by local p16(INK4a) gene transfer, showing that the inhibition of the cell cycle of the synovial cells ameliorates the arthritis. In this study, we show that another animal model of rheumatoid arthritis, murine collagen-induced arthritis, can be effectively treated by local gene transfer of p21(Cip1) as well as that of p16(INK4a). The anti-arthritic effects were observed even when the treatment was conducted after the arthritis had developed. Furthermore, the effects included suppression of the expression of proinflammatory cytokines such as IL-1ss, IL-6, and TNF-alpha. Our results demonstrate that the ectopic expression of cyclin-dependent kinase inhibitors not only prevents synovial overgrowth but also ameliorates the proinflammatory milieu in the affected joints. The induction of p21(Cip1) in rheumatoid synovial tissues by pharmacological agents may also be an effective strategy to treat rheumatoid arthritis.

Adenoviridae↗

[A patient with dysphagia treated successfully and discharged without nutritional support].

One of the main targets of medical care provided in our ward, which specializes in the cooperative practice of hospital- and home-doctors, is to maintain the quality of patients' lives after they are discharged from our hospital through home medical care by home-doctors. Intravenous hyperalimentation and tube-feeding at home are suitable solutions for some patients with dysphagia after cerebral infarction. However, the difficulties faced in their management are the burden on the families, which tends to be an obstacle for at-home-practice. We describe herein a case of severe dysphagia treated successfully through our rehabilitation program and discharged without nutritional supports. An 82-year-old man was admitted to our hospital suffering from pyrexia and dysbasia. The man, who lives with his wife and his son's family, was diagnosed with aspiration pneumonia and multiple cerebral infarctions. The test for swallowing reflex revealed an impaired first phase reflex and intravenous hyperalimentation was performed for his nutritional support. He was still suffering from dysphagia but had the desire to eat orally after his dysbasia and aspiration pneumonia were cured. A rehabilitation program was scheduled with the aims of 1) recovery of ingestion and 2) sufficient expectoration, with an ongoing teaching program for the management of intravenous hyperalimentation. After one month of rehabilitation (ice-massaging, muscle rehabilitation of the tongue and neck and expectoration training in a prone position and after gorging), his ability to swallow was gradually recovered. With the frequent confirmation of absence of aspiration, special forms of diets were served and upgraded from jelly, paste-like-food to soft-cooked steamed rice. The patient is now at home without any nutritional support. Nutritional management without intravenous hyperalimentation or tube-feeding is important or even essential for some families providing home-care for patients. The problem of aging requires us to reduce the burden that families (who may be also getting older) should carry. We try to support patients and families for better home-care through cooperation with society and home-doctors.

Aged↗

Increased sarcolemmal permeability in the cerebral artery during chronic spasm: an assessment using DNA-binding dyes and detection of apoptosis.

Alteration of sarcolemmal permeability was evaluated in the cerebral artery after subarachnoid hemorrhage. Significance of membrane dysfunction in the pathogenesis of chronic spasm and contribution of apoptosis were investigated in a canine model. Permeability of the smooth muscle cell (SMC) membrane was assessed by double staining with a hydrophilic (ethidium bromide [EB]) and a lipophilic (Hoechst 33342) DNA-binding dye. Quantitative observations were made with a ultraviolet-fluorescence microscope and a ultraviolet-laser confocal microscope. Occurrence of apoptosis was studied using electrophoresis and TUNEL method. In the normal arteries, nuclei of SMC were stained with Hoechst 33342 but not with EB. In the spastic arteries, SMC in the inner layer of the tunica media were stained with EB. The incidence of EB-positive cells reached maximum on day 7 (45 +/- 19%) and decreased in 2 to 4 weeks (13 +/- 5.2% and 5.0 +/- 2.1%, respectively), in parallel with amelioration of spasm. Electron and light microscopic observations revealed increased density of SMC cytoplasm with widening of the extracellular space. Necrosis was not evident. Apoptosis was not detected by the two methods. These results demonstrate that an augmentation in sarcolemmal permeability takes place during the course of chronic vasospasm and suggest its close correlation to pathogenesis.

Animals↗

Growing and differentiating characterization of aortic smooth muscle cell line, p53LMAC01 obtained from p53 knock out mice.

Recently we have established an aortic smooth muscle cell line, p53LMAC01 obtained from p53 knockout mice. This cell line showed some differentiated properties which were accelerated by 5-azacytidine treatment [1]. In this study, further characterization of p53LMAC01 cell line was investigated according to cell growth and differentiation, and especially focused into the changes of cell feature, actin filaments' formation, and changes of intracellular calcium concentrations to sympathetic nerve transmitter, norepinephrine. While the cell feature was changed from flattened shape to extended form during 4 days, actin filaments were developing, arranging in parallel to longitudinal direction, and gathering under the surface membrane. In 11 days many cells died and detached from substrate, while actin filaments became poor except for the surface membrane in the remained cells. Appearance of calcium response to noradrenalin needed several days after passage as well as a morphological change of the cells for the extended form and development of actin filaments. The calcium response was maintained on 11 days, which coincided with the result that the cells hold actin filaments under the surface membrane. These results suggest that p53LMAC01 cell line maintains several differentiated characters of adult smooth muscle cell and that their expression needs several days after passage.

Animals↗

Differential effects of wortmannin on the release of substance P and amino acids from the isolated spinal cord of the neonatal rat.

1. Effects of wortmannin, an inhibitor of myosin light chain kinase, on the release of substance P and amino acids, GABA and glutamate, were investigated in the isolated spinal cord preparation of the neonatal rat. 2. Wortmannin at 0.5 - 10 microM depressed the release of substance P evoked by high-K+ (90 mM) medium from the spinal cord (IC50 = 1.1 microM). Wortmannin also depressed the high-K+ (70 mM)-evoked release of substance P from cultured dorsal root ganglion neurons of neonatal rats. In contrast, the high-K+ (90 mM)-evoked release of GABA and glutamate from the spinal cord was not affected by wortmannin (0.1 - 10 microM). 3. Upon stimulation of a dorsal root, a monosynaptic reflex and a subsequent slow ventral root depolarization were evoked in the ipsilateral ventral root of the same segment in the isolated spinal cord preparation. The magnitude of the slow ventral root depolarization was depressed gradually to about 70% of the control during the course of 30 min under wortmannin (1 microM). In contrast, the monosynaptic reflex was unaffected by wortmannin. 4. Immunofluorescent staining revealed that immunoreactivities of substance P and myosin II were colocalized at presynaptic terminals in the dorsal horn of the neonatal rat spinal cord. 5. The present results suggest that myosin phosphorylation by myosin light chain kinase may play a crucial role in the release of substance P, but not in the release of GABA and glutamate in the neonatal rat spinal cord. This may reflect a difference in the exocytic mechanisms of substance P-containing large dense core vesicles and amino acid-containing small clear vesicles.

Amino Acids↗

A novel aortic smooth muscle cell line obtained from p53 knock out mice expresses several differentiation characteristics.

Here we report that we could obtain a highly differentiated smooth muscle cell line by screening the expression of a-smooth muscle actin from p53 knook out mice aorta. This cell revealed extended bipolar shape and expressed h-caldesmon and calponin as well as a-smooth muscle actin as protein markers of differentiated smooth muscle. Further intracellular calcium increase was induced by application of noradrenaline in a dose dependent manner and calcium oscillation was also observed in a higher dose (100 microM). Appropriate application of 5-azacytidine enhanced these tendencies and induced slow contraction by endothelin-1 and phenylephrine.

Animals↗

T/G polymorphism at intron 9 of presenilin 1 gene is associated with, but not responsible for sporadic late-onset Alzheimer's disease in Japanese population.

To investigate whether presenilin 1 (PS1) gene, a major causative gene of familial early-onset Alzheimer's disease (AD), also contributes to the etiology of sporadic AD, we evaluated associations between Japanese AD and polymorphisms located at 14q24.3. While the D14S43 and FOS loci showed no association with either early- or late-onset AD, late-onset AD carrying no APOE-epsilon4 allele was associated with the G allele of the T/G polymorphism located at intron 9 of the PS1 gene (P = 0.016). Considering another study showing a positive association between AD and the T allele, this polymorphism is associated with, but not responsible for sporadic late-onset Alzheimer's disease.

Age of Onset↗

Association between early-onset alcoholism and the dopamine D2 receptor gene.

We examined the allelic association between the dopamine D2 receptor (DRD2) gene and alcoholism in 100 biologically unrelated Japanese alcoholics and 93 unrelated controls. Genomic DNA was prepared from peripheral white blood cells using the phenol-chloroform method. A 310-bp region surrounding the TaqA site at the DRD2 locus was amplified by polymerase chain reaction (PCR), and the PCR product was incubated with TaqI. The A1 allele remained intact while the A2 allele was cut. The frequency of the A1/A1 genotype and the frequency of the A1 allele were higher in early-onset alcoholics than in controls, P < 0.05 and P < 0.01, respectively. Moreover, the frequency of the A1/A1 genotype and the frequency of the A1 allele were higher in early-onset alcoholics with family histories of alcohol dependence than in controls, P < 0.01 and P < 0.01, respectively. The results indicate that the DRD2 gene is associated with susceptibility to early-onset alcoholism, and that each additional A1 allele shifts onset of alcoholism to an earlier age.

Adult↗