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Biomedical subjects

Y Fukuda

Publications and source records attributed to Y Fukuda.

At least 325 records · Page 18Linked to original sources
PubMed1998

Amplification on double-minute chromosomes and partial-tandem duplication of the MLL gene in leukemic cells of a patient with acute myelogenous leukemia.

Partial-tandem duplication (PTD) of an internal portion of MLL occurs in some cases of acute myelogenous leukemia (AML) with trisomy 11 or a normal karyotype. This type of MLL rearrangement may be transcribed into an mRNA species that is capable of encoding a partially duplicated protein associated with leukemogenesis. However, although several kinds of oncogenes, especially MYC, are often amplified on double-minute chromosomes (dmins) in hematological malignancies, no amplification of MLL has been reported in AML. Here, we report the first documented case of a patient with AML whose leukemic cells exhibited amplification of MLL on dmins. Furthermore, in this patient, MLL was rearranged in a PTD manner, with in-frame fusion of exons 2 and 6.

Chromosome Aberrations↗
PubMed1998

Pathological changes in glandular stomach of Helicobacter pylori-infected Mongolian gerbil model.

We have established a Helicobacter pylori-infected Mongolian gerbil model, following Hirayama's method, to clarify gastric diseases associated with H. pylori infection. We administered the culture broth of H. pylori ATCC 43504 orally to 8-week-old male Mongolian gerbils. After H. pylori inoculation, the gerbils were fed in a vinyl isolator. Subsequently, over the course of 48 weeks, they were killed for histopathological examination, H. pylori culture, and serum antibody measurement. H. pylori colonization in the glandular stomach was seen in all the infected gerbils, but only a few H. pylori were detected histologically. The serum antibody titer in the H. pylori-inoculated group increased gradually in comparison with controls. Acute inflammation, immature epithelium, and erosion were observed 2 weeks after H. pylori infection. Chronic inflammation was noted from 4 weeks after H. pylori infection. We also found intestinal metaplasia and gastric ulcers from 12 and 24 weeks after inoculation, respectively. Some histological findings were similar to those in humans, but the chronic inflammation in the gerbils was present mainly in the deep mucosa and submucosa. This appears to be a good animal model for H. pylori-associated gastric diseases and it may be useful for investigating the pathogenesis of H. pylori infection.

Animals↗
PubMed1998

Helicobacter pylori infection affects gastric ulcer healing in Japanese monkeys.

Although peptic ulcer frequently recurs in the presence of Helicobacter pylori infection, the effects of H. pylori on ulcer healing have yet to be studied in detail. Using an animal model, we examined the effects of H. pylori infection on the healing of peptic ulcer in Japanese macaques. Forty-four Japanese macaques, aged 5 years, were randomly divided into two groups, an H. pylori-infected group and a control group, with 22 animals in each. A total of 10(9) colony forming units per ml of an H. pylori strain clinically isolated from patients positive for the cagA gene, the vacA gene, and vacuolizing toxin production, was inoculated into the stomachs of the monkeys to induce H. pylori-associated gastritis. The monkeys were examined by endoscopy, and then 0.1 ml of 10% ammonia solution was injected into the angulus to produce an active ulcer. Endoscopic observations was performed every week for 8 weeks. Acid-reducing drugs and other cytoprotective agents were not administered during the 8-week observation period. No difference in the healing of the ulcers was seen between the two groups from the first to the third week. However, a significant delay in healing was noted in the H. pylori-infected group from the fourth week on wards (P < 0.05). At the sixth week, the proportion of ulcers in the S2 stage (presence of a complete scar) was 0% in the H. pylori-infected group and 38% in the control group, again indicating that healing was significantly delayed in the H. pylori-infected group (P = 0.0187). By the eighth week, the proportion of ulcers in S2 stage had increased to 18% in the H. pylori-infected group and 67% in the control group (P = 0.0719). In Japanese macaques with persistent H. pylori infection in the stomach, the speed of repair of the ulcer surface was reduced, leading to delayed ulcer healing, compared with the controls.

Animals↗
PubMed1997

In vitro and in vivo evidence for high frequency of I-Ab-reactive CD4+ T cells in HLA-DQ or HLA-DRA transgenic mice lacking endogenous MHC class I and/or class II expression.

Although T cells are educated to recognize foreign antigenic peptides in the context of self MHC molecules during their development in the thymus, peripheral T cells also recognize allo- and xeno-MHC molecules. The lower frequency of xeno-MHC-reactive T cells than that of allo-MHC-reactive T cells is often explained by the difference in the degree of homology between xeno- or allo-MHC and self MHC molecules, as well as by the species barrier of the molecules involved in immune recognition. To distinguish these two possibilities, we estimated the frequency of I-Ab-reactive CD4+ T cells selected by HLA-DQ or DR alpha E beta b molecules, using HLA-DQ6 and HLA-DRA transgenic C57BL/6 (B6) mice lacking endogenous MHC class I and/or class II molecules (DQ6A0/0 and DR alpha 30A0/0 beta 20/0). CD4+ lymph node T cells from DQ6A0/0 and DR alpha 30A0/0 beta 20/0 showed the strong proliferative response to I-Ab molecules. In addition, DQ6A0/0 and DR alpha 30A0/0 beta 20/0 rejected the skin graft from mice expressing I-Ab molecules irrespective of MHC class I expression, indicating that the CD4+ T cells recognizing I-Ab molecules are directly involved in this rejection. The estimated frequency of I-Ab-reactive CD4(+)CD8- thymocytes in DR alpha 30A0/0 beta 20/0 and DQ6A0/0 was comparable with that observed in the MHC class II-disparate strains. Our findings thus indicate that CD4+ T cells selected to mature on xeno-MHC class II molecules such as HLA-DQ6 or DR alpha E beta b, when these molecules are expressed in mice, recognize I-Ab molecules as allo-MHC class II, despite the less structural homology.

Animals↗
PubMed1997

A late ON response remains in visual response of the mGluR6-deficient mouse.

In a previous study, we showed that the visual ON response recorded from the superior colliculus is absent in the metabotropic glutamate receptor subtype 6 (mGluR6) knockout mice. However, these mutant mice can respond to some visual inputs and are able to learn a light-dark discrimination task. Here, we systematically investigated the possibility that some ON responses could remain in the mutant mice. Recording light evoked field potentials from the superior colliculus of mGluR6-deficient mice at scotopic and mesopic backgrounds, we found a characteristic ON response that differs from the ON response of wild-type mice. The ON responses recorded from the mutant mice appeared with a latency (200-300 ms) longer than that of the wild-type mice (50-100 ms) and amplitudes of this late ON response decreased upon increase of the light intensity in most cases examined. The late ON response may contribute to the apparent normal behavior and some physiological responses to light stimuli in mGluR6-deficient mice.

Animals↗
PubMed1997

Nuclear and cytosolic calcium signaling induced by extracellular ATP in rat kidney inner medullary collecting duct cells.

Using a laser scanning confocal microscopy of fluorescent Ca2+ indicator (Fluo-3-AM) the spatiotemporal Ca2+ dynamics in cultured kidney inner medullary collecting duct cells was investigated. In response to extracellular ATP (100 microM), nuclear (Fln) and cytosolic (Flc) fluorescence intensity increased simultaneously. UTP similarly increased Fln and Flc, but ADP and AMP did not. A ratio between Fln and Flc was about 1.06 +/- 0.03 at rest and increased 1.71 +/- 0.02 at the peak of stimulation (n = 74). In Ca(2+)-free condition, ATP increased Fln and Flc with a smaller peak intensity, but the peak ratio was similar (1.52 +/- 0.03, n = 70). Faster time resolution of 100 ms in line scanning mode did not detect the delay between nuclear and cytosolic Ca2- responses. Our results indicate that nuclear Ca2+ was not diffused from the cytoplasm and that it may be directly released from the nuclear envelope, a possible Ca2+ store.

Adenosine Triphosphate↗
PubMed1997

Clinical results of radiofrequency hyperthermia for malignant liver tumors.

PURPOSE: To evaluate thermometry and the clinical results of radiofrequency (RF) hyperthermia for advanced malignant liver tumors. METHODS AND MATERIALS: One hundred seventy-three patients with malignant liver tumors treated between 1983 and 1995 underwent hyperthermia. The 173 tumors consisted of 114 hepatocellular carcinomas (HCCs) and 59 non-HCCs (47 metastatic liver tumors and 12 cholangiocarcinomas). Eight-megahertz RF capacitive heating equipment was used for the hyperthermia. Two opposing 25-cm electrodes were generally used for heating the liver tumors. Our standard protocol was to administer hyperthermia 40-50 min twice a week for a total of eight sessions. The liver tumor temperature was measured by microthermocouples when possible. Transcatheter arterial embolization, radiotherapy, immunotherapy, and chemotherapy were combined with hyperthermia treatment in accordance with each patient's liver function. RESULTS: One hundred forty (81%) of the 173 patients who underwent more than four sessions of hyperthermia were evaluated in this study. Thermometry was performed in 77 (55%) of these 140 patients. The maximum tumor temperature, average tumor temperature, and minimum tumor temperature in the HCC were (mean +/- standard error) 41.2 +/- 0.2 degrees C, 40.3 +/- 1.3 degrees C, and 40.1 +/- 0.2 degrees C, respectively. The same thermometry results for non-HCC were 42.3 +/- 0.2 degrees C, 41.2 +/- 0.2 degrees C, and 40.9 +/- 0.2 degrees C, respectively. The maximum and minimum temperatures (41.8 +/- 0.2 degrees C and 40.3 +/- 0.4 degrees C) in the patients with a complete or partial response (CR or PR) were higher than those in the patients with no response or progressive disease (NR or PD) (41.3 +/- 0.5 degrees C and 39.8 +/- 0.4 degrees C), but the difference was not significant. Of the 73 cases with HCC who were evaluated by computed tomography (CT), CR was achieved in 7 (10%), PR in 15 (21%), NR in 37 (51%), and PD in 14 (19%). Of the 45 cases involving liver metastases evaluated by CT, CR was achieved in 3 (7%), PR in 17 (38%), NR in 12 (27%), and PD in 13 (29%). The 1-year cumulative survival rate for HCC patients was 30.0%, and the 5-year survival rate was 17.5%. The 1-year survival of non-HCC patients was 32.5%, and the longest survival was 30 months. The sequelae of hyperthermia included focal fat necrosis in 20 patients (12%), gastric ulceration in 4 (2%), and liver necrosis in 1 (1%). The sequelae of thermometry were severe peritoneal pain in seven patients (11%), intraperitoneal hematoma in one (1%), and pneumothorax in one (1%). CONCLUSION: Even though the thermometry results for liver tumors were not satisfactory, the treatment results are promising. Further clinical trials of RF capacitive hyperthermia for the treatment of advanced liver tumors should be encouraged.

Bile Duct Neoplasms↗
PubMed1997

Effect of gonadotropin releasing hormone on thermoregulatory vasomotor activity in ovariectomized female rats.

To investigate the effect of gonadotropin releasing hormone (GnRH) on thermoregulatory skin vasomotion, we injected GnRH into various brain regions in both anesthetized and unanesthetized ovariectomized female rats. Local warming of preoptic area (PO) elicited skin vasodilation in anesthetized rats. Injection of 2 microg GnRH into the septal area lowered the threshold hypothalamic temperature for skin vasodilation at least for 2 h. Similar injections of 2 microg GnRH into the lateral ventricle (LV) and PO were ineffective. Although this vasodilative effect was also obtained after the injection of 20 ng GnRH into the septal area, injections of 2 ng GnRH were without effect. Not only injections of 20 ng Antide, a potent GnRH antagonist, but also injections of the mixed solution of 20 ng GnRH and 20 ng Antide were also without effect. In unanesthetized and unrestrained rats at an ambient temperature of 17 degrees C, injections of 20 ng GnRH into the septal area elicited tail vasodilation lasting for 30 minutes, whereas vehicle injections were ineffective. Injections of 20 ng GnRH into LV and PO were also ineffective. These results indicate that GnRH can elicit thermoregulatory skin vasomotion by acting on GnRH receptors in the septal area. This thermoregulatory vasodilative effect of GnRH might be possibly related to the etiology of climacteric hot flush.

Animals↗
PubMed1997

Prognostic factors in carcinoma of the external auditory canal.

BACKGROUND: Carcinomas of the external auditory canal are rare neoplasms (< 1% of all head and neck malignant neoplasms). OBJECTIVE: To evaluate the prognostic factors in 79 patients treated in a single institution. PATIENTS AND METHODS: The disease was staged as follows: 34 patients with stage T1 to T2 tumors; 43 patients with stage T3 to T4 tumors; 2 patients with stage TX tumors; 68 patients with stage N0 tumors; and 11 patients with stage N1 tumors. The initial treatment was surgery in 59 patients and radiotherapy in 9 patients. Eleven patients were not considered candidates for treatment. RESULTS: To date, 29 patients have experienced local recurrences and 2, neck metastases. The 5-year survival rates were 65% for patients who underwent surgery, 29% for patients who underwent radiotherapy, and 63% for patients who underwent a combination of surgery and radiotherapy. Univariate survival analysis showed statistical difference according to tumor type (P = .003), bone involvement (P = .002), and tumor stage (P < .001). CONCLUSION: Every effort must be undertaken to make an early diagnosis and perform radical surgical resection of squamous cell carcinomas in the external auditory canal. This study validates the staging system used for squamous cell carcinoma of the ear treated with surgery.

Adult↗
PubMed1997

A two-dimensional NMR study of exchange behavior of amide hydrogens in a lysozyme derivative with an extra cross-link between Glu35 and Trp108--quenching of cooperative fluctuations and effects on the protein stability.

Two-dimensional nmr spectra [correlated spectroscopy (COSY), homonuclear Hartmann-Hahn (HOHAHA), nuclear Overhauser effect spectroscopy (NOESY)] have been observed for cross-linked lysozyme, a chemically modified lysozyme derivative with an extra ester cross-link between residues E35 and W108. Eight shifted cross-peaks were found in the fingerprint region of COSY spectra. By searching COSY, HOHAHA and NOESY spectra, they have been assigned to A32, E35, S36, 158, A107, W108, V109, and A110. The NOE connectivities (dNN and d alpha N) found for the cross-linked lysozyme are quite similar to those for the intact lysozyme. Exchange behavior of amide hydrogens has been studied for both intact and cross-linked lysozymes by observing the fingerprint region of COSY spectra. Hydrogen exchange reactions were carried out at pH 7.0 and at several temperatures. There exist 41 amide hydrogens whose exchange reactions are detectable under this experimental condition. Not only exchange rates but also their activation enthalpies were determined for individual amide hydrogens. They are classified into two groups, which are called categories III and IV. Category III hydrogens are distributed in relatively flexible peripheral parts of protein, and category IV hydrogens are deeply buried in the core region of protein. Category III hydrogens are exchanged through localized unfolding around their sites with a low activation enthalpy ranging from 10 to 25 kcal/mol. The formation of an extra cross-link affects neither the exchange rate nor the activation enthalpy of category III hydrogens. However, amide hydrogens of residues 34-39 in the vicinity of the hinge are exceptions. They are easily exchanged in the intact lysozyme but their exchange rates are drastically retarded by cross-linking. In the intact lysozyme, structural fluctuations mediating the exchange of category IV hydrogens are highly cooperative with a large activation enthalpy. These large-scale structural fluctuations are the global unfolding of the overall structure and also concerted motions within a domain. Especially near 38 degrees C, it was found that the dominant fluctuation occurring in the alpha-domain is different from that in the beta-domain. However, these concerted motions are strongly quenched by the formation of the cross-link because of the cooperativity of such a large-scale fluctuation. The stabilization of a localized area of protein by cross-linking results in the great suppression of large-scale and concerted motions. The exchange rates of category IV hydrogens are extremely retarded in the cross-linked lysozyme, so that they are exchanged through the so-called penetration mechanism characterized by a low activation enthalpy. These experimental results are discussed with regard to the contribution of cross-linking to the stabilization of the folded structure of protein.

Cross-Linking Reagents↗
PubMed1997

Capacitative Ca2+ influx in the neural retina of chick embryo.

Depletion of intracellular Ca2+ stores induces a capacitative Ca2+ influx in non-neural cells. It has been unknown whether the capacitative Ca2+ influx occurs in the cells of nervous systems. We found the capacitative Ca2+ influx in the neural retina of early embryonic chick with Fura-2 fluorescence measurements. A Ca(2+)-free medium containing thapsigargin (500 nM), an inhibitor of Ca(2+)-ATPase of intracellular Ca2+ stores, was applied to the neural retina of embryonic day 3 (E3) chick. A rise in intracellular Ca2+ concentration was evoked after the reintroduction of extracellular Ca2+, and this Ca2+ rise was suppressed by Zn2+ (1 mM) and Ni2+ (5 mM). The developmental changes in the Ca2+ rise induced by thapsigargin (250 nM) were studied from E3 to E13. The thapsigargin-induced Ca2+ rise was largest at E3, declined rapidly toward E6, and then decreased gradually until E13, when the Ca2+ rise almost disappeared. This developmental profile correlated with the decline in the mitotic activities of the retinal cells studied by Prada et al. The fluorescence imaging with the vertical slice of the E9 retina showed that the site at which the thapsigargin-induced Ca2+ rise was largest was the most outer layer of the retina, where proliferating cells are located. This spatial distribution and the above developmental profile may suggest that the capacitative Ca2+ influx occurs at the early period of neurogenesis when the cells have mitotic activities.

Animals↗
PubMed1997

Proportions of ON-center versus OFF-center cells in retinal ganglion cells with regenerated axons of adult cats.

Axons of retinal ganglion cells (RGCs) of adult cats were transected and regenerated by the transplantation of peripheral nerves. Two months after transplantation dendritic arbors of RGCs with regenerated axons (r-RGCs) were visualized with intracellular injections of horseradish peroxidase (HRP). The HRP-filled r-RGCs were classified as alpha, beta, gamma, or unclassified cells. The r-RGCs were then sectioned vertically and their dendritic ramification in the inner plexiform layer (IPL) was examined to distinguish them as OFF- or ON-center cells. Seventy-nine cells extended their dendrites into either sublamina a (OFF) or sublamina b (ON) of the IPL. Two gamma cells spread dendrites into both ON and OFF sublaminae. The numbers of ON-center cells were greater than those of OFF-center cells in three classes: 22 of 24 beta cells, 4 of 6 gamma cells, and 16 of 18 unclassified cells. These data confirmed the predominance of ON-center cells among X/beta and W cells in previous physiological recordings from regenerated axons of r-RGCs. However, only 4 cells were ON-center among 33 r-RGCs with alpha cell morphology. The result apparently conflicts with the predominance of ON-center Y cells in physiological sampling. Possible explanations for the apparent discrepancy are discussed.

Animals↗
PubMed1997

Inhibition of warm ischemic injury to rat liver, pancreas, and heart grafts by controlling the nutritional status of both donor and recipient.

In this study, we tested the effect of donor fasting with or without the use of an essential fatty acids deficiency (EFAD) diet in the recipient using rat heart, pancreas, and liver transplant models. We then compared the survivals, tumor necrosis factor alpha (TNF-alpha) response, and white cell accumulation in rats in order to clarify the mechanisms of the beneficial effect of donor fasting and recipient EFAD. It was found that when the grafts were obtained from fasted donors and then transplanted into fed recipients, the survival rate was significantly higher for all three grafts than for those obtained from fed rats and transplanted into fed rats. The best survival was seen for pancreas grafts obtained from fasted donors and then transplanted into EFAD recipients. TNF-alpha secretion was significantly suppressed in both fasted and EFAD rats, and both the total cell count and neutrophil count were suppressed in EFAD rats. These results clearly indicate that in addition to liver grafts, both heart and pancreas grafts obtained from fasted animals are more tolerant to warm ischemic injury. Furthermore, the combination of donor fasting and recipient EFAD acts synergistically to inhibit the post-transplantation inflammatory reaction (through decreased TNF-alpha secretion and white cell accumulation), thus resulting in an improved survival.

Animals↗
PubMed1997

Fucoidin, a potent inhibitor of L-selectin function, reduces contact hypersensitivity reaction in mice.

In order to investigate the role of L-selectin (CD62L) in delayed-type hypersensitivity (DTH) reaction, effect of fucoidin, a potent inhibitor of CD62L function, was examined in a model of mouse contact hypersensitivity reaction. Intravenous injection of fucoidin to sensitized mice just before hapten challenge resulted in a significant and dose-dependent reduction of the ear swelling in contact hypersensitivity. The ear swelling caused by the hapten challenge was also inhibited when fucoidin was administered at the sensitization phase. Histological analyses of the ear sections revealed that the fucoidin-induced suppression of contact hypersensitivity reflected a marked inhibition of the ear edema and the leukocyte infiltration. The activity of fucoidin was specific in that its related saccharides exerted little effect on the reaction. These results suggest that CD62L may play an important role in both afferent and efferent phases of cutaneous DTH reaction. Since DTH response is one of the most significant features of several chronic inflammatory diseases, our data also show that blocking of CD62L function may be beneficial for the treatment of these diseases in humans.

Animals↗
PubMed1997

Changes in blood supply in small hepatocellular carcinoma: correlation of angiographic images and immunohistochemical findings.

BACKGROUND/AIMS: To assess the changes occurring in blood flow with growth in small hepatocellular carcinomas, we analyzed the angiographic features and immunohistochemical findings in 35 hepatocellular carcinomas less than 2 cm in diameter. METHODS: Hepatocellular carcinomas were evaluated by digital subtraction angiography (DSA), ultrasound angiography with intraarterial CO2 microbubbles (USAG), and computed tomography during arterial portography (CTAP). Immunohistochemically, hepatocellular carcinomas were evaluated using QB-end/10 (QB) monoclonal antibody. RESULTS: All 18 moderately-differentiated hepatocellular carcinomas stained positively with QB antibody. No hepatocellular carcinomas without attenuation on CTAP were positive by immunohistochemistry, and two hepatocellular carcinomas with attenuation on CTAP also lacked staining. We observed four hepatocellular carcinomas without hypervascularity on DSA or USAG, which stained positively with QB antibody; these hepatocellular carcinomas had fatty metamorphosis. CONCLUSIONS: 1. Immunohistochemical findings are closely associated with angiographic findings regarding changes in blood supply. 2. All moderately-differentiated hepatocellular carcinomas have characteristics of hypervascularity, both by angiographic images and by immunohistochemistry. 3. The increase in arterial blood supply occurs later than the decrease in portal perfusion, which may indicate that the decrease in portal perfusion may not be the direct result of replacement by angiogenesis. 4. Some hepatocellular carcinomas with fatty metamorphosis, which are often hypovascular by angiographic evaluation, have hypervascular immunohistochemical characteristics.

Aged↗
PubMed1997

Effect of immunosuppression on composition of quasispecies population of hepatitis C virus in patients with chronic hepatitis C coinfected with human immunodeficiency virus.

BACKGROUND/AIMS: To study the effects of the immunosuppression caused by the reduction of CD4 activity on the composition of hepatitis C virus (HCV) populations, we analyzed the number of HCV quasispecies clones and the nucleotide diversity of the hypervariable region 1 (HVR1) of HCV in 37 patients with hemophilia with persistent HCV infection, with or without human immunodeficiency virus (HIV). METHODS: The numbers of HCV quasispecies clones were measured by fluorescence single-strand conformation polymorphism analysis. Direct sequencing was used to analyze the degree of diversity of HVR1. We compared these values according to coinfection with HIV, and CD4 counts of patients. RESULTS: There were no differences in either the number of HCV clones or the diversity between patients with and without HIV coinfection. In HIV coinfected patients the diversity decreased in association with the decrease in CD4 count while the number of HCV clones did not. The diversity of HVR1 was 3.64 +/- 5.03% in patients with a CD4 count < 50/microliters and 14.92 +/- 6.03% in patients with a CD4 count > or = 50/microliters; it was significantly lower in the former (p = 0.0002). CONCLUSIONS: A severe reduction in the CD4 count, which is considered to cause a decline in the activity of helper T-lymphocytes, induced changes in the composition of HCV populations; one or a few quasispecies clones are predominant in the HCV population in the serum of individual patients.

Adult↗