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T Sakamoto

Publications and source records attributed to T Sakamoto.

At least 55 records · Page 3Linked to original sources

Vascular endothelial growth factor-D is an independent prognostic factor in epithelial ovarian carcinoma.

We assessed the presence of vascular endothelial growth factor (VEGF)-C, VEGF-D and their receptor VEGFR-3 by immunohistochemistry in 59 epithelial ovarian carcinomas, 11 borderline tumours and 20 benign cystadenomas. VEGF-C and VEGF-D were generally expressed in tumour cells and also in endothelia adjacent to tumour nests which showed a strong staining for them. VEGFR-3 was expressed in lymphatic and vascular endothelial cells adjacent to tumour nests. Immunoreactivity was significantly more frequent as lesions progressed from a benign tumour to advanced carcinoma. A strong correlation was found between VEGF-C and VEGF-D detected in carcinoma and VEGFR-3 detected in neighbouring endothelial cells. Increased expression of VEGF-C, VEGF-D and VEGFR-3 was significantly associated with lymph node metastasis and peritoneal metastasis outside the pelvis. There was a significant correlation between the high levels of VEGF-C and VEGF-D proteins, and poor survival. The presence of VEGF-D was an independent prognostic indicator by multivariate analysis. We conclude that VEGF-C, VEGF-D and VEGFR-3 play an important role in lymphatic spread and intraperitoneal tumour development in ovarian carcinoma. Since VEGF-D was found to be an independent predictor of poor outcome, its measurement, together with other prognostic markers may improve prospective identification of patients with a poor prognosis.

Adenocarcinoma, Clear Cell↗

Basal ganglia efferents to the brainstem centers controlling postural muscle tone and locomotion: a new concept for understanding motor disorders in basal ganglia dysfunction.

The present study is designed to elucidate how basal ganglia afferents from the substantia nigra pars reticulata (SNr) to the mesopontine tegmental area of the brainstem contribute to gait control and muscle-tone regulation. We used unanesthetized and acutely decerebrated cats (n=27) in which the striatum, thalamus and cerebral cortex were removed but the SNr was preserved. Repetitive stimulation (50 Hz, 10-60 microA, for 5-20 s) applied to a mesencephalic locomotor region (MLR), which corresponded to the cuneiform nucleus, and adjacent areas, evoked locomotor movements. On the other hand, stimulation of a muscle-tone inhibitory region in the pedunculopontine tegmental nucleus (PPN) suppressed postural muscle tone. An injection of either glutamatergic agonists (N-methyl-D-aspartic acid and kainic acid) or GABA antagonists (bicuculline and picrotoxin) into the MLR and PPN also induced locomotion and muscle-tone suppression, respectively. Repetitive electrical stimuli (50-100 Hz, 20-60 microA for 5-20 s) delivered to the SNr alone did not alter muscular activity. However stimulating the lateral part of the SNr attenuated and blocked PPN-induced muscle-tone suppression. Moreover, weaker stimulation of the medial part of the SNr reduced the number of step cycles and disturbed the rhythmic alternation of limb movements of MLR-induced locomotion. The onset of locomotion was delayed as the stimulus intensity was increased. At a higher strength SNr stimulation abolished the locomotion. An injection of bicuculline into either the PPN or the MLR diminished the SNr effects noted above. These results suggest that locomotion and postural muscle tone are subject to modulation by GABAergic nigrotegmental projections which have a partial functional topography: a lateral and medial SNr, for regulation of postural muscle tone and locomotion, respectively. We conclude that disorders of the basal ganglia may include dysfunction of the nigrotegmental (basal ganglia-brainstem) systems, which consequently leads to the production of abnormal muscle tone and gait disturbance.

Animals↗

The prevalence of IgE sensitization to formaldehyde in asthmatic children.

BACKGROUND: Formaldehyde (FA) is well documented as a cause of occupational asthma. Recently, attention has been paid to FA as an allergen and a pollutant that enhances allergic sensitization. We have investigated the prevalence of FA-specific IgE in asthmatic children and the correlation between IgE sensitization to FA and the severity of asthma. METHODS: One hundred and fifty-five children were investigated, 122 of them asthmatic and 33 nonallergic. Specific IgE against FA was measured by CAP RAST. In addition, the patients answered a questionnaire, containing questions on clinical features of their asthma, their living conditions, and symptoms of mucosal irritation. RESULTS: Of all the subjects assessed, FA-specific IgE was detected in only two asthmatics, and their IgE levels of FA were low (0.42 and 0.46 UA/ml). One of the two patients with FA-specific IgE had severe asthma and frequent symptoms of mucosal irritation, but the other had mild asthma and only rare symptoms of mucosal irritation. CONCLUSIONS: The prevalence of IgE sensitization to FA appears very low in Japanese children, whether or not they have asthma. Therefore, it appears likely that FA is not one of the major allergens causing childhood asthma.

Adolescent↗

Simian immunodeficiency virus-based lentivirus vector for retinal gene transfer: a preclinical safety study in adult rats.

Although lentivirus vectors hold promise for ocular gene therapy, they also have potential safety issues, particularly in the case of the current human immunodeficiency virus-based vectors. We recently developed a novel lentivirus vector derived from the nonpathogenic simian immunodeficiency virus from African green monkeys (SIVagm) to minimize these potentials. In this preclinical study, we evaluated whether SIV vector could be efficiently and safely applicable to retinal gene transfer by assessing the transgene expression, retinal function and histology over a 1-year period following subretinal injection in adult rats. The functional assessment via electroretinogram after both titers of SIV-lacZ (2.5 x 10(7) or 2.5 x 10(8) transducing units/ml) injection revealed both the dark and light adaptations to soon be impaired, in a dose-dependent manner, after a buffer injection as well, and all of them recovered to the control range by day 30. In both titers tested, the retinas demonstrated a frequent transgene expression mainly in the retinal pigment epithelium; however, the other retinal cells rarely expressed the transgene. Retinas exposed to a low titer virus showed no significant inflammatory reaction throughout the observation period, and also maintained the transgene expression over a 1-year period. In the retinas exposed to a high titer virus, however, mononuclear cell infiltration persisted in the subretinal area, and the retina that corresponded to the injected area finally underwent degeneration by around day 90. No retinal neoplastic lesions could be found in any animals over the 1-year period. We thus propose that SIV-mediated stable gene transfer might be useful for ocular gene transfer; however, more attention should be paid to avoiding complications when administering high titer lentivirus to the retina.

Animals↗

Simian lentiviral vector-mediated retinal gene transfer of pigment epithelium-derived factor protects retinal degeneration and electrical defect in Royal College of Surgeons rats.

Retinitis pigmentosa (RP) is a heterogenous group of inherited retinal diseases resulting in adult blindness caused by mutations of various genes. Although it is difficult to cure the blindness that results from these diseases, delaying the disease progression may be of great benefit, since the majority of RP diseases are seen in middle age or later. To test a gene therapy strategy for RP using a neurotrophic factor gene, we assessed the effect of simian lentivirus (SIV)-mediated subretinal gene transfer of pigment epithelium-derived factor (PEDF), a potent neurotrophic factor, during the disease progression in Royal College of Surgeons (RCS) rats, a well-accepted animal model of RP. Regional gene transfer via SIV into the peripheral subretinal space at the nasal hemisphere was performed in all animals to monitor site-specific transgene expression as well as the therapeutic effect in each retina. Gene transfer of lacZ and PEDF was observed in the regional pigment epithelium corresponding to the regional gene transfer. Histologically, PEDF gene transfer significantly protected the loss of photoreceptor cells (PCs) corresponding to the regions of the gene transfer, compared to those of control groups during the course of the experiment. The antiapoptotic effect of PEDF on PCs is likely to be a related mechanism, because a significant reduction of terminal dUTP-nicked end labeling-positive PC numbers was found in PEDF-treated eyes compared to those of the control group (P<0.05). PEDF-treated eyes also retained a significant sensitivity to light flash during the experimental course. These findings clearly show that neuroprotective gene therapy using PEDF can protect retinal degeneration and functional defects in individuals with RP.

Animals↗

Pars plana vitrectomy assisted by triamcinolone acetonide for refractory uveitis: a case series study.

AIM: To examine the outcome of a triamcinolone acetonide (TA) assisted pars plana vitrectomy (PPV) for refractory uveitis. METHODS: Six patients suffering from proliferative vitreoretinopathy (PVR) with refractory uveitis underwent a TA assisted PPV. The patients consisted of one with Vogt-Koyanagi-Harada disease, one with acute retinal necrosis, one with Behçet's disease, and three with sarcoidosis. TA was inoculated into the vitreous cavity to visualise the vitreous. In four of six patients, 4 mg of TA were intentionally left in the vitreous cavity to reduce the degree of postoperative inflammation. RESULTS: The vitreous body was clearly seen using TA during surgery, which greatly helped us to perform a posterior hyaloid resection safely and thoroughly. As we previously observed in other disease, TA allowed us to visualise the transparent vitreous and thus was helpful in removing the vitreous cortex from the retina completely in uveitis. One patient (Behçet's disease, in whom TA was intentionally left) showed an elevated intraocular pressure (IOP) transiently after surgery which was controllable by topical eye drops. The remaining TA diminished day by day and had almost completely disappeared within a month from operation. CONCLUSION: TA improved the visibility of the hyaloid and the safety of the surgical procedures and no serious complications were observed after TA assisted PPV in uveitis. Although the long term effects are still unknown, this method appears to be potentially useful as an improved treatment for PVR associated with refractory uveitis.

Adult↗

Comparison of the effects of sevoflurane and propofol on cooling and rewarming during deliberate mild hypothermia for neurosurgery.

BACKGROUND: Because the time available for cooling and rewarming during deliberate mild hypothermia is limited, studies of the rate of the cooling and rewarming are useful. The decrease in core hypothermia caused by heat redistribution depends on the anaesthetic agent used. We therefore investigated possible differences between sevoflurane and propofol on the decrease and recovery of core temperature during deliberate mild hypothermia for neurosurgery. METHODS: After institutional approval and informed consent, 26 patients were assigned randomly to maintenance of anaesthesia with propofol or sevoflurane. Patients in the propofol group (n=13) received propofol induction followed by a continuous infusion of propofol 3-5 mg kg(-1) h(-1). Patients in the sevoflurane group (n=13) received propofol induction followed by sevoflurane 1-2%. Nitrous oxide and fentanyl were also used for anaesthetic maintenance. After induction of anaesthesia, patients were cooled and tympanic membrane temperature was maintained at 34.5 degrees C. After surgery, patients were actively rewarmed. RESULTS: There was no difference in the rate of decrease and recovery of core temperature between the groups. There was also no difference in skin surface temperature gradient (forearm to fingertip), heart rate and mean arterial blood pressure between the groups. CONCLUSIONS: Sevoflurane-based anaesthesia did not affect cooling and rewarming for deliberate mild hypothermia compared with propofol-based anaesthesia.

Adult↗

[The stratification of surgically treated T4 (stage IIIb) primary lung cancers; analysis of cases with intrapulmonary metastases in the same lobe as the primary tumors (pm 1) and invading adjacent organs].

OBJECTIVE: The purpose of this article was to investigate the validity of T4 classification of primary non-small cell lung cancer. METHODS: We retrospectively reviewed the clinical outcome of cases with pm 1 (n = 65) and T4 tumors invading adjacent organs (n = 36). RESULTS: When the pm 1 tumors were excised completely (n = 57), the prognosis of these cases was affected by the pN factor (5-year survival rate: pN 0-1; 70.1%, pN 2-3; 7.7%, p = 0.0002) and comparable to that of T2 diseases (pN 0-1 cases: p = 0.7315). The patients who underwent complete resection for their pm 1 tumors had a significantly better prognosis than cases with disseminations or malignant pleural effusions which had the same T4 classification (p < 0.0001). The prognosis of the patients who underwent complete resection for the tumors invading adjacent organs (classified under T4) was similar to that of T3 diseases (pN 0-1 cases: p = 0.7116). CONCLUSIONS: Patients whose lung cancer is classified as T4 comprise 2 subgroups; those whose tumors can be completely resected, and those in whom complete resection is impractical. There is a significant difference in the management and the prognosis between these 2 groups although they share the same T4 classification.

Adolescent↗

A case of adenocarcinoma of the endometrial type mixed with a clear cell component that metastasized to the vagina.

We present a patient with adenocarcinoma of the endometrial type mixed with a clear cell component (AMC) that metastasized to the vagina and one of the pelvic lymph nodes. She underwent a radical hysterectomy and pelvic and paraaortic lymphadenectomy, and then received postoperative adjuvant chemotherapy. Histologic features of the endometrial tumor included clear cell adenocarcinoma with an approximate 10% extent to endometrioid adenocarcinoma. On the other hand, histologic examination on the vaginal tumor predominatly showed clear cell adenocarcinoma and also revealed endometrioid adenocarcinoma to a very small extent, suggesting metastasis to the vagina from AMC. On immunohistochemical examination, expression of vascular endothelial growth factor (VEGF)-A, VEGF-C and VEGF-D was apparently stronger in the component of clear cell adenocarcinoma than in that of endometrioid adenocarcinoma. She has been a disease-free survivor for 26 months. Interestingly, locations of endometrial and vaginal lesions were consistent with the sites of an intrauterine device and ring pessary insertion, respectively.

Adenocarcinoma, Clear Cell↗

Purification and characterisation of two exo-polygalacturonases from Aspergillus niger able to degrade xylogalacturonan and acetylated homogalacturonan.

Two exo-polygalacturonases (EC 3.2.1.67) were purified from a commercial Aspergillus niger enzyme preparation by ammonium sulfate precipitation, preparative electrofocusing, anion-exchange and size-exclusion chromatographies. The enzymes had molar masses of 82 kDa (exo-PG1) and 56 kDa (exo-PG2). Exo-PG1 was stable over wider pH and temperature ranges than exo-PG2. Addition of 0.01 mM HgCl(2) increased the exo-PG2 activity 3.4 times but did not affect exo-PG1. Analysis of the reaction products of (reduced) pentagalacturonate by high-performance anion-exchange chromatography revealed that both enzymes split the substrate from the non-reducing end in a multi-chain attack mode. Exo-PG1 had a broad specificity towards oligogalacturonates with different degrees of polymerisation, while digalacturonate was the most favorable substrate for exo-PG2. Both enzymes degraded xylogalacturonan from pea hull in an exo manner to produce galacturonic acid and Xyl-GalA disaccharide, as identified by electrospray ionization-ion trap mass spectrometry (ESI-ITMS). Moreover, exo-PGs split acetylated homogalacturonan in an exo manner, producing galacturonic acid and acetylated galacturonic acid, as shown by ESI-ITMS.

Aspergillus niger↗

Differential display of skin mRNAs regulated under varying environmental conditions in a mudskipper.

To understand the molecular mechanisms underlying the terrestrial adaptation, as well as adaptation to different salinities, of the euryhaline and amphibious mudskipper ( Periophthalmus modestus), we have looked for the skin mRNAs that change during varying environmental conditions. Using differential mRNA display polymerase chain reaction, we compared skin mRNAs in mudskipper transferred from isotonic 30% seawater to fresh water or to seawater for 1 day and 7 days, as well as those kept out of water for 1 day. At the end of these periods, poly(A(+))RNA was prepared from the Cl(-)-secreting pectoral skins and also from the outer opercular skins where ion transport is negligible, and analyzed by differential display. We identified four cDNA products expressed differently under various environments as homologues of known genes. A further 34 cDNAs were expressed differentially, but they have no significant homology to identified sequences in GenBank. Northern blots demonstrate that mRNA levels of the actin-binding protein and the platelet-activating factor acetylhydrolase increased in the pectoral skins during seawater acclimation. The mRNA of the 90 kDa heat shock protein was down-regulated in water-deprived and freshwater fish, whose plasma cortisol levels were high. The aldolase mRNA was induced in both skins after desiccation. These four genes may be involved in the environmental adaptations.

Adaptation, Physiological↗

Calcium ion triggers rapid morphological oscillation of chloride cells in the mudskipper, Periophthalmus modestus.

Euryhaline teleosts rapidly regulate their ion flux at the chloride cells on entry to different salinities. The external trigger(s) for the rapid opening and closing of the chloride cell apical surface, the site of salt secretion, were examined in the skin of the mudskipper. With DASPEI (a mitochondrial probe) and Concanavalin-A (an apical surface marker of chloride cells), chloride cells were classified into two groups: those in contact and those not in contact with the external water. The fraction of chloride cells in contact with the water increased dramatically 1.5 h after transfer to seawater, and similarly after transfer to 10 mmol x l(-1) CaCl(2) solution. In comparison, transfer to 1.1 mol x l(-1) mannitol, 0.5 mol x l(-1) NaCl or 50 mmol x l(-1) MgCl(2) resulted in increases of only 40-60% of those in the seawater-transfer group. After return of the fish from 10 mmol x l(-1) CaCl(2) to freshwater, the cells in contact with the water decreased. Environmental Ca(2+) is the trigger for the morphological oscillation of chloride cell apical surface, presumably through modifications in Ca(2+) flux.

Animals↗

Isolation and characterization of a homologue of mammalian prolactin-releasing peptide from the tilapia brain and its effect on prolactin release from the tilapia pituitary.

In the tilapia (Oreochromis mossambicus), as in many teleosts, prolactin (PRL) plays a major role in osmoregulation in freshwater. Recently, PRL-releasing peptides (PrRPs) have been characterized in mammals. Independently, a novel C-terminal RF (arginine-phenylalanine) amide peptide (Carrasius RF amide; C-RFa), which is structurally related to mammalian PrRPs, has been isolated from the brain of the Japanese crucian carp. The putative PrRP was purified from an acid extract of tilapia brain by affinity chromatography with antibody against synthetic C-RFa and HPLC on a reverse-phase ODS-120 column. The tilapia PrRP cDNA was subsequently cloned by polymerase chain reaction. The cDNA consists of 619 bp encoding a preprohormone of 117 amino acids. Sequence comparison of the isolated peptide and the preprohormone revealed that tilapia PrRP contains 20 amino acids and is identical to C-RFa. Incubation of the tilapia pituitary with synthetic C-RFa (100 nM) significantly stimulated the release of two forms of tilapia PRL (PRL188 and PRL177). However, the effect of C-RFa was less pronounced than the marked increase in PRL release in response to hyposmotic medium. The ability of C-RFa to stimulate PRL release appears to be specific, since C-RFa failed to stimulate growth hormone release from the pituitary in organ culture. In contrast, rat and human PrRPs had no effect on PRL release. C-RFa was equipotent with chicken GnRH in stimulating PRL release in the pituitary preincubated with estradiol 17beta. Circulating levels of PRL were significantly increased 1 h after intraperitoneal injection of 0.1 microg/g of C-RFa in female tilapia in freshwater but not in males. These results suggest that C-RFa is physiologically involved in the control of PRL secretion in tilapia.

Amino Acid Sequence↗

High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI.

The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image.

Aged↗