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Biomedical subjects

S Fukuda

Publications and source records attributed to S Fukuda.

At least 145 records · Page 8Linked to original sources
PubMed2000

Fractionated stereotactic radiotherapy for vestibular schwannoma (VS): comparison between cystic-type and solid-type VS.

PURPOSE: To compare the effectiveness and complications of fractionated stereotactic radiotherapy (SRT) for cystic-type vestibular schwannoma (VS) with those of solid-type VS. METHODS AND MATERIALS: In 65 patients treated with fractionated SRT between 1991 and 1999, 20 were diagnosed with cystic VS, in which at least one-third of the tumor volume was a cystic component on magnetic resonance imaging (MRI), and 45 were diagnosed with solid VS. Thirty-six Gy to 50 Gy in 20-25 fractions was administered to the isocenter and approximately 80% of the periphery of the tumor. All cystic and solid components were included in the gross tumor volume. The mean follow-up period was 37 months, ranging from 6 to 97 months. RESULTS: The actuarial 3-year rate of no episode of enlargement greater than 2.0 mm was 55% for cystic-type and 75% for solid-type VS; the difference was statistically significant (p = 0.023). The actuarial 3-year tumor-reduction (reduction in tumor size greater than 2.0 mm) rates were 93% and 31%, respectively (p = 0.0006). The overall actuarial tumor control rate (no tumor growth greater than 2. 0 mm after 2 years or no requirement of salvage surgery) was 92% at 5 years in 44 patients with a follow-up period of 2 or more years. There was no difference in the class hearing preservation rate between cystic VS and solid VS. No permanent trigeminal or facial nerve palsy was observed in either group. CONCLUSION: Transient tumor enlargement occurs in cystic VS more frequently than in solid-type VS, but the subsequent tumor-reduction rate in cystic VS is better.

Actuarial Analysis↗
PubMed2000

A portion of the nucleotide sequence corresponding to the N-terminal coding region of livJ is essential for its transcriptional regulation.

We investigated the regulation of the livJ and livKHMGF operons, which are involved in branched-chain amino acid high-affinity transport in Salmonella typhimurium. When livJ was fused to lacZ at the second codon of livJ to make a livJ-lacZ protein fusion, expression from the livJ promoter was not repressed even under repressing growth conditions; however, expression of an analogous construct of livK-lacZ was repressed. When livJ was fused to lacZ at the twelfth codon of livJ, the expression level under unrepressing growth conditions was elevated, resulting in apparent repressibility of the livJ-lacZ protein fusion. Expression from the livJ-lacZ operon fusion, in which livJ was fused to lacZ 159 bp downstream from the A of the start codon of livJ, was relatively normal under unrepressing growth conditions. Deletion analysis and site-directed base-substitution analysis strongly suggested that cis-acting element for regulation of livJ transcription, 5'-GGCAGGATGTATCG-3', starting at +21 and ending at +34 downstream from the A of the start codon of livJ, was present in the N-terminal coding region of livJ.

Bacterial Proteins↗
PubMed2000

Tau neutrinos favored over sterile neutrinos in atmospheric muon neutrino oscillations.

The previously published atmospheric neutrino data did not distinguish whether muon neutrinos were oscillating into tau neutrinos or sterile neutrinos, as both hypotheses fit the data. Using data recorded in 1100 live days of the Super-Kamiokande detector, we use three complementary data samples to study the difference in zenith angle distribution due to neutral currents and matter effects. We find no evidence favoring sterile neutrinos, and reject the hypothesis at the 99% confidence level. On the other hand, we find that oscillation between muon and tau neutrinos suffices to explain all the results in hand.

Journal Article↗
PubMed2000

Early diagnosis of zoster sine herpete and antiviral therapy for the treatment of facial palsy.

The effect of antiviral agents on recovery from facial palsy in patients with zoster sine herpete (ZSH; varicella zoster virus reactivation without zoster) has not been evaluated because ZSH is difficult to diagnose early after onset. In this study, all 13 patients who received acyclovir-prednisone treatment within 7 days of onset, as confirmed by a positive PCR result, showed complete recovery. PCR-based early diagnosis of ZSH and antiviral therapy elicited an excellent outcome for recovery from facial palsy due to ZSH.

Acyclovir↗
PubMed2000

Essential role of signal transducer and activator of transcription (Stat)5a but not Stat5b for Flt3-dependent signaling.

The receptor tyrosine kinase Flt3 plays an important role in proliferation and survival of hematopoietic stem and progenitor cells. Although some post-receptor signaling events of Flt3 have been characterized, the involvement of the Janus kinase/signal transducer and activator of transcription (Jak/Stat) pathway in Flt3 signaling has not been thoroughly evaluated. To this aim, we examined whether Flt3 activates the Jak/Stat pathway in Baf3/Flt3 cells, a line stably expressing human Flt3 receptor. Stat5a, but not Stats 1-4, 5b, or 6, was potently activated by Flt3 ligand (FL) stimulation. Interestingly, FL did not activate any Jaks. Activation of Stat5a required the kinase activity of Flt3. A selective role for Stat5a in the proliferative response of primary hematopoietic progenitor cells to FL was documented, as FL did not act on progenitors from marrows of Stat5a(-/-) mice, but did stimulate/costimulate proliferation of these cells from Stat5a(+/+), Stat5b(-/-), and Stat5b(+/+) mice. Thus, Stat5a is essential for at least certain effects of FL. Moreover, our data confirm that Stat5a and Stat5b are not redundant, but rather are at least partially distinctive in their function.

Animals↗
PubMed2000

Three-dimensional small-volume irradiation for residual or recurrent nasopharyngeal carcinoma.

PURPOSE: To minimize side effects and to achieve a high local control rate, three-dimensional (3D) small-volume irradiation was used for locally residual or recurrent nasopharyngeal carcinoma. METHODS AND MATERIALS: Between July 1992 and March 1998, 18 tumors (12 residual and 6 local recurrent cases) were treated with 3D planned small-volume irradiation. The total dose (i.e., the dose of conventional radiotherapy plus that of the 3D irradiation) was 78.4 Gy (74.8-91.0 Gy) in its mean value for residual disease and 105.0 Gy (94.8-125 Gy) for recurrence. The mean value of the 90% isodose volume was 40.3 cc (8.0-94.0 cc). The mean follow-up period from the start of the boost or re-irradiation was 39 months. RESULTS: The 3-year local control rate of the 12 residual tumors was 70%. Of 9 T4 residual tumors, 7 were controlled at a follow-up period between 17 and 70 months (median of 42 months). Of 6 recurrent tumors treated with re-irradiation, 3 were controlled at a follow-up period between 7 and 28 months. In the case of booster therapy, trismus occurred in 1 patient with a total dose of 91 Gy. Among the patients receiving re-irradiation, a temporary ulceration of the nasopharyngeal mucosa developed in 1 patient with a total dose of 111 Gy. CONCLUSION: 3D small-volume irradiation was effective and safe in treating residual or recurrent nasopharyngeal carcinoma.

Follow-Up Studies↗
PubMed2000

Dominant negative isoform of the Ikaros gene in patients with adult B-cell acute lymphoblastic leukemia.

Gene targeting studies in mice have shown that the transcription factor Ikaros plays an essential role in lymphoid development and as a tumor suppressor in T cells, whereas the related gene Aiolos functions as a tumor suppressor in B cells. We analyzed the expression levels of the Ikaros gene family, Ikaros and Aiolos, in human bone marrow samples from patients with adult acute lymphoblastic leukemia [ALL (n = 46; B-cell ALL = 41; T-cell ALL = 5)]. Overexpression of the dominant negative isoform of Ikaros gene Ik-6 was observed in 14 of 41 B-cell ALL patients by reverse transcription-PCR, and the results were confirmed by sequencing analysis and immunoblotting. None of the other dominant negative isoforms of the Ikaros gene were detected by reverse transcription-PCR analysis. Southern blotting analysis with PstI digestion revealed that those patients with the dominant negative isoform Ik-6 might have small mutations in the Ikaros locus. We did not detect any overexpression of dominant negative isoforms of Aiolos in adult ALL patients. These results suggest that Ikaros plays a key role in human B-cell malignancies through the dominant negative isoform Ik-6.

Adolescent↗
PubMed2000

Identification of fractalkine, a CX3C-type chemokine, as a direct target of p53.

Fractalkine is a CX3C-type chemokine that induces chemotaxis of monocytes and cytotoxic T cells. Using the differential display method for examining gene expression in p53-defective cells transfected by adenovirus containing wild-type p53, we observed that fractalkine was induced by ectopic expression of p53. An electrophoretic mobility shift assay showed that a potential p53-binding site present in the promoter of the fractalkine gene could bind to p53 protein. Moreover, a heterogeneous reporter assay indicated that this promoter sequence possessed p53-dependent transcriptional activity. The strong induction of fractalkine when p53 protein was expressed by a wild-type transgene in p53-defective cells brought to light a novel role for p53; that is, potential elimination of damaged cells by the host immune response system through transcriptional regulation of fractalkine. Our results imply a pivotal role of p53 in immunosurveillance to prevent cells from undergoing malignant transformation.

Adenoviridae↗
PubMed2000

The contribution of the median preoptic nucleus to renal sympathetic nerve activity increased by intracerebroventricular injection of hypertonic saline in the rat.

The median preoptic nucleus (MnPO) of the hypothalamus is involved in the osmotic control of neurohypophysial hormone release and drinking behavior. At the same time, renal sympathetic nerves exert multiple effects on renal functions such as regulating renal blood flow and urinary sodium excretion. We made the hypothesis that the MnPO may also regulate body fluid balance by exerting an influence on renal sympathetic nerve activity (RSNA). In this study we examined the effect of electrical stimulation of the MnPO on RSNA and the contribution of the MnPO to the change of RSNA induced by intracerebroventricular injection of hypertonic saline in the male Wistar rat. Electrical stimulation of the MnPO and the paraventricular nucleus of the hypothalamus (PVN) elicited an increase in RSNA. This increase of RSNA elicited by electrical stimulation of the MnPO was reduced by microinjections (100 nl) of 10% lidocaine or 4 mM cobaltous chloride (a synaptic transmission blocking agent) bilaterally into the PVN. Both RSNA and the mean arterial pressure (MAP) were increased by the injection of 1.5 M NaCl into the third ventricle, although heart rate (HR) was not significantly changed. These responses of RSNA and MAP were diminished by microinjection of 10% lidocaine (100 nl) into the MnPO. Our results suggest that the MnPO is involved in body fluid regulation not only by controlling vasopressin secretion and water intake but also by modulating central sympathetic outflow which regulates body fluid balance through an effect on the kidney.

Anesthetics, Local↗
PubMed2000

Prevention of rat cerebral aneurysm formation by inhibition of nitric oxide synthase.

BACKGROUND: Cerebral saccular aneurysm is a major cause of subarachnoid hemorrhage, one of the cerebrovascular diseases with the highest mortality. The mechanisms underlying the development of aneurysms, however, still remain unclear. We have made a series of reports on an animal model of experimentally induced cerebral aneurysms that resemble human cerebral aneurysms in their location and morphology, suggesting that the arterial wall degeneration associated with aneurysm formation develops near the apex of arterial bifurcation as a result of an increase in wall shear stress. Using the animal model and human specimens, we examined the role of nitric oxide (NO) in the degenerative changes and cerebral aneurysm formation. METHODS AND RESULTS: Inducible NO synthase (iNOS) was immunohistochemically located at the orifice of human and rat aneurysms. Nitrotyrosine distribution was also seen in the human aneurysm. Although no iNOS immunostaining was found in normal arteries, iNOS immunoreactivity was observed in parallel with the development of early aneurysmal changes in rats. In contrast, during the early development of aneurysm, endothelial NOS immunostaining in the endothelium was weakened compared with that in the control arteries. An NOS inhibitor, aminoguanidine, attenuated both early aneurysmal changes and the incidence of induced aneurysms. A defibrinogenic agent, batroxobin, which may diminish shear stress by reduction of blood viscosity, prevented iNOS induction as well as early aneurysmal changes. CONCLUSIONS: The evidence suggests that NO, particularly that derived from iNOS, is a key requirement for the development of cerebral aneurysm. The iNOS induction may be caused by an increase in shear stress near the apex.

Animals↗
PubMed2000

Skull-base invasion of nasopharyngeal carcinoma: magnetic resonance imaging findings and therapeutic implications.

PURPOSE: To evaluate the value of skull-base abnormality on MRI for predicting local recurrence in nasopharyngeal carcinoma. MATERIALS AND METHODS: Between November 1988 and February 1997, 48 patients with NPC were examined with both MRI (1.5 T) and CT prior to radiation therapy. T classification (1987 UICC) based on physical examination and CT findings were T1 in 3 cases, T2 in 22, T3 in 9, and T4 in 14. On MRI, low-intensity tissue with Gd enhancement in the marrow of the skull was considered to be a suspicious finding of skull-base invasion. CT simulation was performed in all patients. The total dose to the primary tumor was 60-75 Gy (mean, 67 Gy). The mean follow-up period was 42 months. RESULTS: All 14 T4 patients had abnormal tissue in the marrow of the skull base on MRI. Thirty-eight percent (13 of 34) of T1-3 patients were suspected to have skull-base invasion based on MRI (0% for T1, 27% [6 of 22] for T2, and 78% [7 of 9] for T3). The 5-year local control rate was significantly different between T1-3 and T4 tumors (97% vs. 69%, p < 0.025) but was not different by the presence of the MRI abnormality in the skull base. CONCLUSION: Skull-base invasion suspected solely by MRI does not relate to local recurrence provided that careful treatment planning is performed with the aid of MRI and CT simulator.

Bone Marrow Examination↗
PubMed2000

The mouse N-acetylgalactosamine-6-sulfate sulfatase (Galns) gene: cDNA isolation, genomic characterization, chromosomal assignment and analysis of the 5'-flanking region.

Deficiency of lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS) leads to mucopolysaccharidosis IV A (MPS IV A), for which there is no definitive treatment so far. Although a number of mutations of the GALNS gene of MPS IV A patients have been described, pathogenesis of the disorder still remains elusive. In order to facilitate in vivo studies using model animals for MPS IV A, we isolated and performed molecular characterization of the mouse homolog of human GALNS. The 2.3-kb cDNA contains a 1560-bp open reading frame encoding 520 amino acid residues. The coding region has 84% similarity to the human GALNS cDNA at amino acid level. The mouse Galns gene was mapped by interspecific backcross analysis to the distal region of chromosome 8 where it co-segregates with Aprt. Northern blot analysis showed a wide expression of a single-copy gene, being higher especially in liver and kidney. The Galns gene was isolated from S129vJ genomic library and its genomic organization was characterized. The mouse Galns gene was about 50-kb long and organized into 14 exons and 13 introns. All intron-exon splice junctions conformed to the GT/AG consensus sequence except exon 8/intron 8 junction. Primer extension shows multiple transcription initiation sites between -44 and -75 although major transcription initiation site was observed at -90 bp from the ATG codon. The 5'-flanking region lacks canonical TATA and CAAT box sequences, but is G+C rich with 10 GC boxes (potential Sp1 binding sites), characteristic of a housekeeping gene promoter.

Amino Acid Sequence↗
PubMed2000

A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage.

The p53 gene is frequently inactivated in human cancers. Here we have isolated a p53-inducible gene, p53R2, by using differential display to examine messenger RNAs in a cancer-derived human cell line carrying a highly regulated wild-type p53 expression system. p53R2 contains a p53-binding sequence in intron 1 and encodes a 351-amino-acid peptide with striking similarity to the ribonucleotide reductase small subunit (R2), which is important in DNA synthesis during cell division. Expression of p53R2, but not R2, was induced by ultraviolet and gamma-irradiation and adriamycin treatment in a wild-type p53-dependent manner. Induction of p53R2 in p53-deficient cells caused G2/M arrest and prevented cells from death in response to adriamycin. Inhibition of endogenous p53R2 expression in cells that have an intact p53-dependent DNA damage checkpoint reduced ribonucleotide reductase activity, DNA repair and cell survival after exposure to various genotoxins. Our results indicate that p53R2 encodes a ribonucleotide reductase that is directly involved in the p53 checkpoint for repair of damaged DNA. The discovery of p53R2 clarifies a relationship between a ribonucleotide reductase activity involved in repair of damaged DNA and tumour suppression by p53.

Amino Acid Sequence↗
PubMed2000

Cloning and nucleotide sequence of a gene encoding a glycogen debranching enzyme in the trehalose operon from Arthrobacter sp. Q36.

A gene located just upstream of the treYZ operon was isolated from Arthrobacter sp. strain Q36. The gene, designated treX, encoded an 823-amino acid protein. The amino acid sequence of the protein had 50% identity with the TreX protein (isoamylase) from Sulfolobus acidocaldarius ATCC 33909 which has a treZXY operon on the genome. We suggest that Arthrobacter treX is an isoamylase gene, and that it is a component of a treXYZ operon.

Amino Acid Sequence↗
PubMed2000

Mechanisms for regulation of fluid shear stress response in circulating leukocytes.

We have shown that leukocytes retract their pseudopods and detach from substrates after exposure to physiological fluid shear stresses ( approximately 1.5 dyn/cm(2)). In inflammation, however, pseudopod projection during spreading and firm adhesion on endothelium is observed even in microvessels with normal blood flow and fluid shear stresses. Thus, we examined mechanisms that may serve to regulate the shear stress response of circulating leukocytes. In the presence of inflammatory mediators (platelet-activating factor [PAF] f-met-leu-phe), a subgroup of cells ceases to respond to shear stress. cGMP analogs and nitric oxide (NO) donors enhance the shear stress response and reverse the inhibitory effect of inflammatory mediators on the shear stress response, whereas depletion of cGMP leads to cessation of the shear stress response even in unstimulated leukocytes. The ability of cGMP to enhance the shear stress response is not associated with CD18 expression, because cGMP has no effect on CD18 expression in response to shear stress. The shear stress response of leukocytes in endothelial nitric oxide synthase (-/-) mice, in which NO level in blood is decreased, is attenuated compared with that in wild-type mice. In rat mesentery venules stimulated by PAF under normal blood flow, a cGMP analog diminishes pseudopod projection of leukocytes, whereas inhibition of NO leads to enhanced pseudopod projection and spreading. The evidence suggests that inflammatory mediators suppress the shear stress response of leukocytes leading to spreading even under normal physiological shear stress, whereas cGMP may serve to maintain shear stress response even in inflammation.

Aminoquinolines↗
PubMed2000

Fatal hypertrophic cardiomyopathy associated with an A8296G mutation in the mitochondrial tRNA(Lys) gene.

We describe an 8-day-old baby girl presenting a fatal infantile form of hypertrophic obstructive cardiomyopathy, associated with an A8296G mutation in the mitochondrial tRNA(Lys) gene. She was born from a healthy unrelated couple, and was the first infant of dizygotic twins. Soon after birth, she was noted to have tachypnea and generalized hypotonia. She had high levels of lactate and pyruvate, and was diagnosed as having hypertrophic cardiomyopathy using echocardiography. She died by cardiac failure. Mitochondrial DNA analysis was performed by sequencing after PCR-subcloning methods, and the percentage of mutation was measured using PCR-RFLP methods. In various tissues obtained at autopsy, analysis showed a heteroplasmic population of A8296G mutation in the mitochondrial tRNA(Lys) gene in all the tissues examined. Maternal inheritance was demonstrated in the family members. Our data demonstrated that an A8296G mutation in the mitochondrial tRNA(Lys) gene showed clinical heterogeneity from a milder form previously reported as mitochondrial diabetes mellitus, to a more severe form as hypertrophic obstructive cardiomyopathy, according to the spatial distribution of this mutation. Hum Mutat 15:382, 2000.

Cardiomyopathy, Hypertrophic↗
PubMed2000

Evaluation of the applicability of the gastric carcinoma risk index for intestinal type cancer in Japanese patients infected with Helicobacter pylori.

The gastric carcinoma risk index is a histological criteria to Helicobacter pylori-infected patients with a high risk of gastric cancer. The aim of this study was to examine the applicability of this index for the intestinal-type gastric cancer in Japanese patients with H. pylori infection. In 55 patients with early intestinal-type gastric cancer and 69 control subjects, we calculated the gastric cancer risk index score by evaluating the grade of mononuclear cell (MNC) and polymorphonuclear cell (PMN) infiltration and the presence of intestinal metaplasia. The gastric cancer index score was significantly higher in patients with gastric cancer (P<0.01). The presence of intestinal metaplasia was significantly more frequent in cancer patients than in controls, while infiltration of MNCs or PMNs in the corpus was not different in the two groups. Within the gastric cancer risk index, the presence of intestinal metaplasia was the only criteria associated with the development of intestinal-type gastric cancer in Japan. The gastric cancer risk index may not be applicable to identify H. pylori-positive patients at high risk of developing intestinal-type gastric cancer in Japan.

Duodenal Neoplasms↗