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Biomedical subjects

H Nitta

Publications and source records attributed to H Nitta.

At least 19 recordsLinked to original sources

Spontaneous emission of bound photons from relativistic free electrons.

If the states of photons are bound, another type of spontaneous emission becomes possible for a relativistic electron due to the symmetry breaking in space. We obtain the radiation probability for a relativistic electron passing through a box-shaped cavity. The radiation spectrum is discrete in which line positions are determined by the boundary condition of the cavity.

Journal Article↗

Standard radiation spectrum of relativistic electrons: beyond the synchrotron approximation.

Radiation emitted by an electron in arbitrary, extreme relativistic motion, has been described for the first time in terms of a standard spectrum of nonsynchrotron type. Ultimately, such a nonsynchrotron spectrum is dependent not only on instantaneous trajectory curvature, but also upon its first two time derivatives and helicity, to provide a basic correction to the synchrotron approximation (SA). A strong deviation from SA has been predicted for above GeV electrons in oriented crystals.

Journal Article↗

Stopping power of charged particles due to ion wave excitations.

Stopping power due to ion wave excitations is derived for a charged particle moving in a two-component plasma. Unlike previous theories based on ion-acoustic-wave approximation (IAWA), the excitation of short-wavelength ion waves is taken into account. The obtained stopping power has a magnitude larger than that of IAWA. Stopping power at subsonic velocities, where stopping power in IAWA disappears, is even larger than that of supersonic velocities.

Journal Article↗

Involvement of cyclooxygenase-2 in serum-induced prostaglandin production by human oral gingival epithelial cells.

The purpose of the present study was to investigate the involvement of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in prostaglandin (PG) production by human oral gingival epithelial (OGE) cells stimulated with proinflammatory cytokines including interleukin(IL)-1alpha, IL-1alpha and tumor necrosis factor alpha (TNFalpha), and serum. Fetal bovine serum (FBS)-stimulated OGE cells produced significant levels of PGE2, whereas IL-1alpha, IL-1beta and TNFalpha could not induce significant PGE2 production. FBS induced PGE2 production in a dose- and time-dependent manner. NS-398, a selective COX-2 inhibitor, inhibited PGE2 production by FBS-stimulated cells as completely as indomethacin, a non-selective COX-1/COX-2 inhibitor. Expression of COX-2 protein in FBS-stimulated cells was increased, compared with that in unstimulated cells, whereas COX-1 protein expression was similar both in unstimulated and in FBS-stimulated cells. COX-2 mRNA was detected in FBS-stimulated cells, but not in unstimulated cells. We suggest that COX-2 is responsible for PG production by human OGE cells stimulated with serum and that OGE cells may be involved in PG production in periodontal lesions. Selective COX-2 inhibitors, which have the advantage of reduced gastric toxicity, may provide a useful approach to treatment of periodontal disease.

Analysis of Variance↗

Prognostic significance of lymph node involvement in middle and distal bile duct cancer.

BACKGROUND: Although lymph node involvement is considered an important prognostic factor, a detailed analysis has not been conducted in middle (Bm) and distal (Bi) bile duct cancer. METHODS: The histopathology of resections taken from 59 patients with Bm and Bi disease (Bm, 33 patients; Bi, 26 patients) was examined. The prevalence of lymph node involvement and its relationship to recurrence and prognosis were investigated. Survival rates were investigated according to the number of metastatic lymph nodes found, the TNM nodal stages, and the nodal stage classifications of The General Rules of the Japanese Society of Biliary Surgery. RESULTS: The frequency of nodal involvement in Bm and Bi was 45.5% and 30.8%, respectively. A significant correlation existed between a patient's prognosis and his TNM nodal stage, Japanese Society of Biliary Surgery nodal stage, and the number of metastatic lymph nodes found (P <.0001, respectively). Among 8 sites of postoperative recurrence, metastasis occurred most frequently in the liver (16/23). Patients with nodal involvement had a significantly higher rate of liver metastasis (10/23) than those without it (6/36) (P =.024). CONCLUSIONS: The number of metastatic lymph nodes found in patients with Bm or Bi cancer, and the nodal stage of their nodes, are significant prognostic indicators. Patients with nodal involvement are at high risk for liver metastasis in Bm and Bi disease.

Adult↗

Magnetic fields (MF) of 50 Hz at 1.2 microT as well as 100 microT cause uncoupling of inhibitory pathways of adenylyl cyclase mediated by melatonin 1a receptor in MF-sensitive MCF-7 cells.

Magnetic fields (MF) of 60 Hz at 1.2 microT were previously shown to inhibit the antiproliferative effect of melatonin on MCF-7 cells (Liburdy,R.P., 1993, J. Pimeal Res. 14, 89-97). In addition, three laboratories (Blackman,C.F. and Benane,S.G., 1998; Luben,R.A. and Morgan,A.P., 1998; Morris,J.E., Chrisler,W.B., Miller,D.L., Sasser,L.B. and Anderson,L.E., 1998; 20th Annual Meeting of the Bioelectromagnetics Society, At. Pete Beach, FL) independently reported results consistent with this finding. In this study, we investigated the molecular basis of the biological effects of MF using MCF-7 cells. Only 1a melatonin receptors were identified by the [125I]melatonin binding assay and RT-PCR analysis. Moreover, preceding exposures to MF of 100 microT for 3, 5 and 7 days blocked the melatonin-induced inhibition of cAMP accumulation in a time-dependent manner, while none of the melatonin receptor functions or GTPase and adenylyl cyclase activities were affected. Estrogen-evoked cell proliferation was not altered by MF either. Exposure to 1.2 microT MF exerted the same effects on the melatonin-signaling pathway as that to 100 microT. Thus, this is the first study to provide evidence that MF may cause uncoupling of signal transduction from melatonin receptors to adenylyl cyclase.

Adenylyl Cyclase Inhibitors↗

Alterations of the INK4a/ARF locus in human intracranial germ cell tumors.

Little is known about the molecular mechanisms responsible for the development of intracranial germ cell tumors (ICGTs). Recently, we demonstrated that the balance of the p53-mdm2 interactions is disrupted in ICGTs. The p14ARF product, a tumor suppresser gene located on the INK4a/ARF locus, acts as one of the major factors affecting p53-mdm2 interactions via its binding to mdm2 and the stimulation of mdm2 degradation. To evaluate whether genetic alterations of the INK4a/ARF locus occur in the genesis of ICGTs, we analyzed the INK4a/ARF genes in 21 ICGTs-10 pure germinomas and 11 nongerminomatous germ cell tumors. Fifteen (71%) of the 21 ICGTs displayed genetic alterations, including 14 homozygous deletions and 1 frameshift mutation. Furthermore, the frequency of the alterations was higher in pure germinomas [9 (90%) of the 10] than in nongerminomatous germ cell tumors [6 (55%) of the 11; P = 0.09]. These data suggested that INK4a/ARF gene abnormalities could play an important role in the genesis of ICGTs, especially in pure germinoma.

Adolescent↗

Molecular analysis for p53 and mdm2 in intracranial germ cell tumors.

Intracranial germ cell tumors (ICGTs) are uncommon neoplasms. The histological appearance of ICGTs is indistinguishable from that of the usual testicular germ cell tumors (TGTs). Recently, several reports have associated molecular abnormalities of p53 and mdm2 in TGTs with their malignancies. However, whether ICGTs are associated with molecular abnormalities is still unknown. We analyzed a series of 16 ICGTs for mutations in the TP53 gene by single-strand conformation polymorphisms, and for amplification of the MDM2 gene using differential PCR. In addition, the same 16 tumors were examined for p53 and mdm2 protein overexpression using antibodies directed against p53 [monoclonal antibodies (mAb) 1801 and DO7] and mdm2 (IF2), respectively. Twelve (75%) and 2 (13%) of the 16 ICGTs reacted with DO7 and PAb1801, respectively, and 1 (6%) carried a TP53 gene mutation. Thirteen (81%) of the 16 ICGTs reacted with IF2, and 3 (19%) carried MDM2 gene amplification. The less frequent TP53 gene mutation compared with MDM2 gene amplification, and the frequently expressed p53 and mdm2 protein, are similar to the case for TGTs. It is tempting to speculate that ICGTs might have the same cellular origins as TGTs with abnormalities in p53 and mdm2, which could play an important role of tumorigenesis.

Adolescent↗

New ocular movement detector system as a communication tool in ventilator-assisted Werdnig-Hoffmann disease.

A non-contact communication system was developed for a ventilator-assisted patient with Werdnig-Hoffmann disease who had lost all voluntary movements except for those of the eye. The system detects the extraocular movements and converts them to either a 'yes' signal (produced by one lateral eyeball movement) or a 'no' signal (produced by two successive lateral eyeball movements) using a video camera placed outside the patient's visual field. The patient is thus able to concentrate on performing a task without any intrusion from the detection system. Once the setting conditions of the device have been selected, there is no need for any resetting, as the patient is unable to move his body. In addition to playing television games, the child can use the device to select television channels, compose music, and learn written Japanese and Chinese characters. This seems to broaden the patient's daily world and promote mental development.

Activities of Daily Living↗

Expression of multidrug resistance-associated protein (MRP) in human gliomas.

Drug resistance is a major clinical problem in the chemotherapy of human gliomas. The multidrug resistance-associated protein (MRP), a membrane transporter related to non-P-glycoprotein multidrug resistance, is overexpressed in some drug-selected cancer cell lines. To investigate whether MRP is involved in the intrinsic drug resistance of human gliomas, surgical specimens of 20 gliomas (11 glioblastomas, 6 anaplastic astrocytomas, and 3 astrocytomas), 3 normal brain specimens, and 4 glioma cell lines (U87MG, U251MG, U373MG, and T98G) were analyzed. The expression of MRP was studied by RT-PCR and immunohistochemistry in the surgical specimens. The MRP expression levels in the cell lines were assessed by the quantitative RT-PCR and Western blot analyses. Sensitivity to adriamycin (ADM), etoposide (VP-16), cisplatin (CDDP), and 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), were determined by MTT assay, and antisense treatment was evaluated in the cell lines. The expression of MRP was detected in 9 of 11 glioblastomas and 3 of 6 anaplastic astrocytomas. The quantitative analyses of the cell lines revealed that the MRP mRNA and protein levels were increased 4.5-fold in the T98G cells as compared to U87MG. T98G cells showed the highest resistance to all drugs. Western blot analysis revealed that treatment with the antisense oligonucleotide reduced the level of MRP expression to 25% of the sense oligonucleotide treatment in T98G cells. The sensitivity to ADM, VP-16 and CDDP was significantly increased in the antisense-treated cells as compared with the sense-treated cells. These results suggest that the MRP expression may be related to the intrinsic multidrug resistance in human gliomas.

ATP-Binding Cassette Transporters↗

Papillon-Lefèvre syndrome: analysis of HLA antigens.

OBJECTIVES: Papillon-Lefèvre syndrome (PLS) is a rare disease associated with prepubertal periodontitis. Our previous studies demonstrated that three unrelated patients with PLS showed the similar antigen-specific immune responses to Actinobacillus actinomycetemcomitans. The initiation of antigen-specific immune responses was involved with human leukocyte antigens (HLA) on antigen-presenting cells. The aim of this study was to examine HLA haplotypes in the three patients with PLS. SUBJECTS AND METHODS: The three PLS patients, their mothers and the father of one patient participated in this study. HLA class I and class II antigens were determined serologically and DNA typing for DRB1 and DQB1 was performed using the restriction fragment length polymorphism-polymerase chain reaction method. RESULTS: The distribution of serologic HLA haplotypes, in two of three patients, was found to be quite similar. The DNA typing revealed that DRB1*0406, DRB1*08032, DQB1*0302, DQB1*06011 genotypes were shared in the two patients. The probability of sharing these four DNA types in unrelated individuals was nearly 1:40,000 in the Japanese population. CONCLUSION: Our results suggest that HLA antigen may be included as a possible host factor in the pathogenesis of PLS and that a genetically controlled immune response may account for an increased susceptibility to periodontal infection.

Aggressive Periodontitis↗

A de novo splice donor site mutation causes in-frame deletion of 14 amino acids in the proteolipid protein in Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease (PMD) is a leukodystrophy associated with mutations in the proteolipid protein (PLP) gene. Jimpy is a mouse model of human PMD, and a splice site mutation in Jimpy causes the deletion of exon 5 from the PLP mRNA, producing a truncated form of PLP. We describe a de novo point mutation at the 5' splice donor site of exon 5 in a 17-year-old male with PMD, which results in the skipping of 42 base pairs of exon 5. The mutation removes only 14 amino acids in-frame of PLP. This is a novel splice donor site mutation in the human PLP gene. Moreover, the results indicate that the 14-amino acid deletion in the PLP is responsible for oligodendrocyte cell death and the development of PMD.

Adolescent↗

Effect of intravenous omega-6 and omega-3 fat emulsions on nitrogen retention and protein kinetics in burned rats.

The effect of omega-3 fat emulsion on nitrogen retention and kinetics in relation to fatty acid profile were investigated in burned rats receiving total parenteral nutrition (TPN). A fat emulsion of a structured symmetrical triacylglycerol containing only eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (2:1) was prepared. Sprague-Dawley rats were fed by fat-free chow for 2 wk. Then rats were fed exclusively with one of three types of TPN for 7 d. Animals in group C received fat-free TPN (n = 11). Group omega 6 received safflower oil fat emulsion, which accounted for 20% of total caloric intake (n = 11). Group omega 3 received fat emulsion containing only EPA and DHA (1% of total calories, n = 11), in addition to safflower oil emulsion (19% of total calories). On day 5, each rat was subjected to 20% full-thickness scald burns. Rats were sacrificed under ether anesthesia 48 h after burning. The rats in group C became deficient in omega-6 essential fatty acids. Cumulative nitrogen balance was decreased significantly in group omega 6. The rates of whole-body protein synthesis were increased significantly in both groups omega 6 and omega 3. In omega 6, however, the rates of whole-body protein breakdown were increased significantly. In conclusion, the rates of whole-body protein breakdown increased and nitrogen retention was aggravated significantly in animals administered the safflower oil emulsion. Significant increases of urinary excretion of total catecholamine were also observed. Prostaglandin E2 and thromboxane B2 concentrations were not significantly different among three groups. Supplementation with the new omega-3 fat emulsion, however, improved protein metabolism in burned rats receiving TPN.

Animals↗

Changes in immune function following surgery for esophageal carcinoma.

Changes in immune function due to surgical injury have been well-documented. Immunosuppression is one of the causes of infectious complications leading to organ dysfunction in critical illness. It is not known what kind of surgery in the daily clinical practice causes immunosuppression. Stress response and immune function following surgery for esophageal carcinoma, assuming a highly-stressed operation, were studied and then compared with the stress response and immune function following gastric surgery, a moderately-stressed procedure. Forty patients who underwent esophagectomy and 39 patients receiving gastric operation were studied. The concentrations of serum interleukin-6 (IL-6) were measured preoperatively, at 1, 2, and 6 h, and at 1, 3, and 10 d after operation. Total protein, serum albumin, rapid turnover protein, serum CRP, and cortisol were measured before operation and at 1, 3, 7, and 21 d after operation. ConA- and PHA-stimulated lymphocyte proliferation, IgA, IgG, and IgM were also measured preoperatively, and on 7 and 21 d following surgery. The patients were fed exclusively by total parenteral nutrition (TPN). A striking rise of IL-6 was observed, with a peak in both groups at 1 to 6 h following operation. The peak values were 419+/-30 pg/mL, which was approximately twice as high in the esophagectomy patients as in the gastrectomy patients (195+/-40 pg/mL). CRP and cortisol also increased after operation, and these increases were also significantly greater in the esophagectomy patients. ConA- and PHA-stimulated lymphocyte proliferation decreased significantly 7 d after esophagectomy (P<0.05), but was unchanged in the patients receiving gastrectomy. Suppression of cellular immunity correlated significantly with serum cortisol, and was preceded by a rise in serum IL-6. The IgA, IgG, and IgM levels, however, remained unchanged from their preoperative values throughout the study in both groups. Nutritional status in terms of serum protein, albumin, and rapid turnover protein, decreased postoperatively, but there was no difference between the two groups. It is, therefore, concluded that cell-mediated immunosuppression, preceded by a hyperinflammatory response, is an observable reaction in patients following esophageal surgery, but not in patients undergoing gastric surgery.

Aged↗

Down-regulation of p27Kip1 expression is correlated with increased cell proliferation but not expression of p21waf1 and p53, and human papillomavirus infection in benign and malignant tumours of sinonasal regions.

AIMS: Although p27Kip1(p27) is a cyclin-dependent kinase inhibitor and a contribution to tumorigenesis has been hypothesized, the possible role in tumours arising in the nasal and paranasal sinus regions is still unknown. METHODS AND RESULTS: Seventy-six sinonasal tumours, including 28 inverted papillomas (IPs) and 48 squamous cell carcinomas (SCCs), were immunohistochemically investigated, along with 46 exophytic papillomas (EPs) of upper respiratory tract and 34 samples of normal paranasal sinus epithelium. The results were also compared with expression of p21WAF1 (p21) and p53, cell proliferation assessed in terms of Ki67 labelling indices (LIs), and human papillomavirus (HPV) infection. The average p27 scores decreased from normal through to malignant lesions, while Ki67 LI scores showed a stepwise increase, the inverse correlation between scores for all categories being significant (r = - 0.639, P < 0. 0001). In the SCCs, p27 expression was significantly higher in keratinizing than nonkeratinizing type tumours (P < 0.05), while there was no association with p21 and p53 expression. Although HPV DNAs for type 16 and 18 were detected in two (7.4%) of 27 EPs, six (35.8%) of 28 IPs, and nine (28.1%) of 32 SCCs, no relation with p27 scores was evident. CONCLUSION: Loss of p27 expression correlates with increased cell proliferation in sinonasal tumours. Moreover, the expression appears to be associated with keratinization in SCCs of the paranasal sinus. These findings indicate that p27 expression may be a useful marker for the dysregulation of cell kinetics in these tumours.

Blotting, Southern↗