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Biomedical subjects

N Suzuki

Publications and source records attributed to N Suzuki.

At least 451 records · Page 25Linked to original sources

High pressure conditions promote the proliferation of rat cultured mesangial cells in vitro.

Glomerular capillary pressure is involved in the development of chronic renal failure and has at least two effects on mesangial cells: transmembrane hydrostatic pressure and stretch. To clarify whether pure hydrostatic pressure itself affects the proliferation of cultured rat mesangial cells, we compared the cell number under atmospheric pressure condition with high pressure condition. At 24 and 48 h with 0.5% serum, cell number was significantly higher under high pressure condition than under atmospheric pressure condition. At 48 h, cell number under high pressure condition was increased in a pressure-dependent manner. Furthermore, flow cytometric assay indicated that pressure-load could promote DNA synthesis rate at S phase and enhance G1/S progression induced by low concentration of serum (0.5%). These results suggest that pure hydrostatic pressure itself can promote the proliferation of cultured rat mesangial cells by advancing cell cycle progression in vitro.

Air Pressure↗

Inhibition of Fas/Fas ligand-mediated apoptotic cell death of lymphocytes in vitro by circulating anti-Fas ligand autoantibodies in patients with systemic lupus erythematosus.

OBJECTIVE: The Fas/Fas ligand (FasL) system has been assigned a pivotal role in the establishment and maintenance of peripheral tolerance, and mice having defects in the Fas/FasL system are known to develop lupus-like symptoms. However, it remains unclear whether the Fas/FasL system is involved in the pathogenesis of systemic lupus erythematosus (SLE) in humans. This study examined whether there are circulating anti-FasL autoantibodies in the peripheral blood of patients with SLE that would interfere with Fas/FasL-mediated apoptosis. METHODS: Anti-FasL autoantibodies were detected by Western blot analysis using the recombinant extracellular domain of human FasL as the antigen. Apoptosis of Fas-expressing Jurkat cells, induced by recombinant soluble FasL (sFasL) in the presence of anti-FasL autoantibodies, was assessed by DNA staining with propidium iodide, followed by flow cytometric analysis. Apoptosis of Jurkat cells by cell-bound FasL was assessed by 2-color analysis, involving TUNEL staining with fluorescein isothiocyanate-dUTP and phycoerythrin-labeled anti-CD3 monoclonal antibodies. RESULTS: Among the 21 patients with SLE, 7 had IgG-isotype anti-FasL autoantibodies in their circulating blood. In addition, these autoantibodies inhibited both sFasL-mediated and cell-bound FasL-mediated apoptosis of Fas-expressing Jurkat cells. Thus, it is plausible that anti-FasL autoantibodies in patients with SLE disturb the establishment and maintenance of peripheral tolerance in vivo by inhibiting the Fas/FasL-mediated elimination of autoreactive lymphocytes. CONCLUSION: These results suggest that anti-FasL autoantibodies that inhibit Fas/FasL-mediated apoptosis are involved, at least in part, in immune abnormalities and may possibly be involved in the pathogenesis of SLE.

Adolescent↗

Possible correction of abnormal rheumatoid arthritis synovial cell function by jun D transfection in vitro.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints, and excessive proliferation of and proinflammatory cytokine and collagenase production by synovial cells are a principal cause of joint destruction. Recent studies have revealed that c-jun and jun B promote growth of fibroblasts, whereas jun D suppresses fibroblast proliferation and even antagonizes Ras-mediated transformation of the fibroblasts. We analyzed effects of gene transfer-mediated jun D overexpression of synovial fibroblast-like cells in patients with RA. METHODS: RA synovial fibroblast-like cells were transiently transfected with jun D expression vector. The transfectants were stimulated with tumor necrosis factor alpha, and their subsequent proliferative responses and proinflammatory cytokine and matrix metalloproteinase (MMP) production at the messenger RNA and protein levels were measured. RESULTS: Transfection with jun D inhibited the proliferation of, and proinflammatory cytokine and MMP production by, RA synovial cells, mainly due to inhibiting their transcription via down-modulation of AP-1 transcription factor. CONCLUSION: Localized jun D transfection into the synovial cells of affected joints may inhibit aberrant synovial cell function in patients with RA by down-regulating gene transcription. This function suggests a possible clinical application of this gene therapy.

Arthritis, Rheumatoid↗

Assay of centromere function using a human artificial chromosome.

In order to define a functional human centromere sequence, an artificial chromosome was constructed as a reproducible DNA molecule. Mammalian telomere repeats and a selectable marker were introduced into yeast artificial chromosomes (YACs) containing alphoid DNA from the centromere region of human chromosome 21 in a recombination-deficient yeast host. When these modified YACs were introduced into cultured human cells, a YAC with the alphoid DNA from the alpha21-I locus, containing CENP-B boxes at a high frequency and a regular repeat array, efficiently formed minichromosomes that were maintained stably in the absence of selection and bound CENP-A, CENP-B, CENP-C and CENP-E. The minichromosomes, 1-5 Mb in size and composed of multimers of the introduced YAC DNA, aligned at metaphase plates and segregated to opposite poles correctly in anaphase. Extensive cytological analyses strongly suggested that the minichromosomes had not acquired host sequences and were formed in all cases by a de novo mechanism. In contrast, minichromosomes were never produced with a modified YAC containing alphoid DNA from the alpha21-II locus, which contains no CENP-B boxes and has a less regular sequence arrangement. We conclude that alpha21-I alphoid DNA can induce de novo assembly of active centromere/kinetochore structures on minichromosomes.

Autoantigens↗

Colchicine-induced cell death and proliferation in the olfactory epithelium and vomeronasal organ of the mouse.

The cytotoxic agent colchicine induced apoptotic cell death and subsequent regeneration in the mouse olfactory epithelium and vomeronasal organ. The TUNEL method revealed the presence of many apoptotic bodies in the middle to basal region of the septal olfactory epithelium and vomeronasal organ near the boundary of the respiratory epithelium at 1 day after a single i.p. injection of colchicine (4 mg/kg b.w.). In some regions of the third and the fourth nasal turbinates, massive apoptosis was observed in the olfactory epithelium. Electron micrographs of the septum showed that immature olfactory cells and globose basal cells were killed by the colchicine and had been phagocytized by the supporting cells and macrophages. In the vomeronasal organ, immature sensory cells and precursors died in response to the colchicine. In response to cell death, active proliferation of precursor cells (globose basal cells) and subsequent regeneration of olfactory cells occurred in the olfactory epithelium and vomeronasal organ. Incorporation of the mitotic tracer BrdU by precursor cells reached its peak at 4 days after colchicine treatment in the vomeronasal organ, and at 6 to 7 days in the olfactory epithelium; however, in some regions in the third and the fourth nasal turbinates, where many olfactory cells and globose basal cells had died by colchicine effect, the regeneration did not occur even in 1 month, forming the epithelium of only supporting cells and horizontal basal cells. In the next month, these regions became normal olfactory epithelium. This suggests that the globose basal cells in the surrounding normal olfactory epithelium might invade these regions to give rise to the olfactory cells.

Animals↗

Cervical curvature in acute whiplash injuries: prospective comparative study with asymptomatic subjects.

The cervical curvature of 488 patients with acute whiplash injury was prospectively studied by comparison with 495 asymptomatic healthy volunteers. Plain radiography of the cervical spine in the neutral position was evaluated qualitatively. No significant difference was noted in frequencies of non-lordotic cervical curvature and local angular kyphosis between acute whiplash injury patients and asymptomatic subjects. No significant association was apparent between clinical symptoms and cervical curvature. These results suggest that non-lordotic cervical curvature and angular kyphosis in acute whiplash injury patients constitute normal variants rather than pathological findings.

Acute Disease↗

Surgical treatment of neuroblastomas in infants under 12 months of age.

BACKGROUND: Surgical treatment of neuroblastomas, both those detected by screening and those detected clinically, in infants less than 12 months of age, is controversial, because some tumors in this age group potentially have the ability to regress spontaneously. METHODS: From January 1985 to March 1997, the authors treated 50 infants (under 1 year of age) with neuroblastoma: 23 boys and 27 girls. Forty-one cases were detected preclinically by screening when the patients were 6 to 11 months of age (median, 7 months), and nine patients were discovered to have clinical manifestations at the age of 1 to 10 months (median, 4 months). RESULTS: The tumor was INSS stage 3 or 4 in 10 patients (24%) with screening-detected tumor and in five (56%) with clinically detected tumor, although the difference was not statistically significant. Four screening-positive patients had multifocal primary tumors, and three of them were synchronous bilateral adrenal neuroblastomas. There was no statistically significant difference between the screening-detected tumors and the clinically detected tumors in biological characteristics such as Shimada's histology, DNA ploidy, and N-myc amplification. Complete resection of the primary lesion was accomplished by either primary surgery or second look (delayed primary) surgery in 46 patients (92%), and the resection was incomplete in the remaining four. In patients with bilateral adrenal tumors, the larger one was primarily resected, and the smaller contralateral tumor was enucleated or resected by partial adrenalectomy. Surgical complications included postoperative adhesive ileus (n=2), Horner's syndrome (n=2), renal atrophy (n=1), renal failure (n=1), phrenic nerve injury (n=1), chylous ascites (n=1), chylothorax (n=1) and intussusception (n=1). One patient died of respiratory failure caused by a complication, but 49 patients (98%) were alive at the time of evaluation. CONCLUSION: When considering surgical treatment of infants with biologically favorable neuroblastoma, the risk involved in treatment should be weighed against the risk inherent in a tumor capable of spontaneous regression, and aggressive surgery is unacceptable.

Adrenal Gland Neoplasms↗

Prenatally diagnosed cystic lymphangioma in infants.

BACKGROUND/PURPOSE: Prenatally diagnosed cystic lymphangioma (CL) is often associated with chromosomal anomalies, hydrops fetalis, and, in the case of cervical CL, occasionally respiratory distress just after birth. Often it is difficult to treat prenatally diagnosed CL because of the large size and associated symptoms. METHODS: Between 1988 and 1997, 11 cases of prenatally diagnosed CL were treated. Five pregnancies were terminated electively and one aborted spontaneously (nondelivered, non-D group), and another five delivered (delivered, D group). Thirteen infants nondiagnosed prenatally were also seen in the same period (prenatally nondiagnosed, without pre-D group). RESULTS: In the non-D group, massive CLs were diagnosed by ultrasound scan between 16 and 20 weeks' gestation. They occurred in the head and neck in all six cases, and four had associated pleural effusions or hydrops. In the D group, CL occurred in the face and neck in four cases. Three were born by cesarean section with neonatologists and surgeons standing by, then transferred to our hospital immediately after birth. Respiratory distress appeared in two cases; tracheostomy was carried out in one case. One patient with a huge CL in the chest and abdominal wall necessitated partial resection after OK-432 sclerotherapy. In the without pre-D group, there was CL in the face or neck in 10 cases, abdominal wall in two cases, and chest wall in one case. Respiratory distress was observed in three cases of cervical CL, and tracheostomy was required in two cases. One patient with hypoxic brain damage sequela died of pneumonia afterward. CONCLUSIONS: Prenatal diagnosis permits planned delivery, prompt postnatal resuscitation, and improve prognosis. Infants with massive CL diagnosed early in pregnancy have other associated anomalies as well as hydrops fetalis, and a poor outcome or difficult management can be expected.

Diagnosis, Differential↗

Accumulation of IL-12-activated antitumor effector cells into lymph nodes of tumor-bearing mice.

Simultaneous administration of high dose of IL-12 into tumor-inoculated mice resulted in a marked reduction of tumor growth in parallel with the augmented generation of cytotoxic T-cells, natural killer (NK) cells and IFN-gamma-producing Th cells. We found that these IL-12-activated antitumor effector cells preferentially accumulated in peripheral lymph nodes concomitantly with lymphadenopathy. However, IL-12 rather induced disappearance of antitumor effector cells including CD4+ T, CD8+ T and NK cells from spleen in spite of inducing splenomegaly. Lymph node cells obtained from IL-12-treated B16F0-bearing mice showed a marked IFN-gamma production in response to not only IL-2, IL-12, anti CD3 mAb but also B16F0 melanoma cells. Moreover, they could lyse B16F0 melanoma cells in a long-term cytotoxicity assay. It was also confirmed that IL-12-activated IFN-gamma producing Th1 cells were accumulated in tumor local site. Thus, IL-12 appeared to have a capability of stimulating selective migration of antitumor cells into lymph nodes and tumor local sites.

Animals↗

Effects of aluminum ions on K(+)-induced contraction in ileal longitudinal smooth muscle.

The mechanism of the inhibition of K(+)-induced contraction caused by aluminum ions (Al3+) was analyzed in ileal longitudinal muscle and taenia coli of guinea-pig. Al3+ (2-5 mM) inhibited dose-dependently the high-K+ (60 mM, hypertonic)-induced contraction in ileal muscle. Al3+ reduced the size of the maximal response to Ca2+ without shifting the concentration-response curves to Ca2+ in taenia coli. Al3+ caused a significant decrease in Ca uptake, measured by the lanthanum method, during the K(+)-induced ileal first phase of the response. Following treatment with 5 mM Al3+ for 0.5-20 min, the ileal K(+)-induced contraction returned to a greater extent, after washing with medium containing the chelator deferoxamine, compared to normal medium. However, with increasing duration, > 30 min of Al3+ treatment, the K(+)-induced contraction did not recover, despite washing with deferoxamine. The aluminum in the cells was even more eliminated by washing with deferoxamine when the duration of Al3+ treatment was < 20 min. The present findings indicate that the inhibitory action by Al3+ on K(+)-induced contraction at the shorter treatment (< 20 min) may result from the interference of calcium permeability at the cell membrane in ileal muscle. However, with increasing duration of Al3+ treatment, Al3+ ions accumulate in intracellular compartments where deferoxamine cannot reach, and it may exert an inhibitory action on internal sites in ileal cells.

Aluminum↗

Role of the carboxy-terminal region of the GluR epsilon2 subunit in synaptic localization of the NMDA receptor channel.

The synaptic localization of the N-methyl-D-aspartate (NMDA) type glutamate receptor (GluR) channel is a prerequisite for synaptic plasticity in the brain. We generated mutant mice carrying the carboxy-terminal truncated GluR epsilon2 subunit of the NMDA receptor channel. The mutant mice died neonatally and failed to form barrelette structures in the brainstem. The mutation greatly decreased the NMDA receptor-mediated component of hippocampal excitatory postsynaptic potentials and punctate immunofluorescent labelings of GluR epsilon2 protein in the neuropil regions, while GluR epsilon2 protein expression was comparable. Immunostaining of cultured cerebral neurons showed the reduced punctate staining of the truncated GluR epsilon2 protein at synapses. These results suggest that the carboxy-terminal region of the GluRepsilon2 subunit is important for efficient clustering and synaptic localization of the NMDA receptor channel.

Afferent Pathways↗

Pregnant women with transient gastric obstruction managed by Naso-Jejunal nutrition.

A pregnant woman with transient gastric obstruction was fed by enteral nutrition alone for 11 wk and 6 d. Her body mass index of 23.2 kg/m2 before pregnancy declined to 21.8 kg/m2 after delivery. Although she did not gain weight during enteral nutrition, fetal growth, estimated by ultrasonography, was normal, and she delivered a 3030-g female infant at 38 wk gestation. The blood laboratory data during pregnancy and the breast milk after pregnancy were also normal. The results suggest that factors other than maternal weight gain alone should be considered in the evaluation of nutritional status for the pregnant woman.

Adult↗

Enhancement of XPG mRNA expression by human interferon-beta in Cockayne syndrome cells.

Using PCR-differential display, we have searched for genes expressed specially in human interferon (HuIFn)-beta-treated Cockayne syndrome (CS) fibroblast cells. Eighteen expressed genes induced by HuIFN-beta were identified, the sequences of seven of which were highly homologous to previously cloned sequences. The cDNAs of six of these seven clones were similar to expression tagged sequences from unknown genes in databases and the remaining one was identical to the cDNA of the xeroderma pigmentosum XPG gene. These results, together with our previous finding of increased resistance to ultraviolet (UV) cell-killing of CS cells pretreated with HuIFN-beta prior to UV irradiation suggest that XPG might be one of the genes possibly involved in the HuIFN-beta-induced UV-resistance.

Cells, Cultured↗

CMV retinitis after cessation of ganciclovir therapy for CMV antigenemia in an unrelated BMT recipient.

An 11-year-old boy with severe aplastic anemia underwent unrelated BMT following TBI, antithymocyte globulin and CY. On day +23, CMV antigenemia was detected which resolved with ganciclovir. Eight days after discontinuing ganciclovir, he complained of impaired visual acuity. Ophthalmologic findings and a positive PCR study using anterior chamber fluid from the right eye confirmed the presumptive diagnosis of CMV retinitis, although CMV antigenemia and PCR studies using PBMC were then negative. He was successfully re-treated with ganciclovir. CMV retinitis should be considered even when CMV antigenemia is not present or PCR using PBMC is negative.

Anemia, Aplastic↗