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Tadashi Matsuda

Publications and source records attributed to Tadashi Matsuda.

At least 19 recordsLinked to original sources
PubMed2025

Ozonated olive oil inhibits melanoma proliferation by inducing ferroptosis.

Although ozone is a potent oxidant that can damage lungs and skin after prolonged exposure, ozonated olive oil (OZO) exhibits antimicrobial, anti-inflammatory, and wound-healing effects. Here, we describe a novel application of OZO in melanoma therapy. Treatment with OZO markedly inhibited the proliferation of both human and murine melanoma cells, while sparing normal human keratinocyte. At the molecular level, OZO upregulated ferroptosis-related genes, decreased intracellular glutathione (GSH) and GPX4 protein levels and accelerated lipid peroxidation. Critically, OZO-induced growth inhibition in melanoma cells was prevented by ferroptosis inhibitors (ferrostatin-1 and deferiprone), but not by inhibitors of apoptosis or necroptosis. Taken together, these findings offer new therapeutics strategy for treating melanoma by inducing ferroptosis.

Ferroptosis↗
PubMed2006

A case surviving for over a year of renal tubular dysgenesis with compound heterozygous angiotensinogen gene mutations.

Renal tubular dysgenesis (RTD) is a developmental abnormality of the renal proximal tubules found in patients with Potter syndrome. We report a female newborn with RTD who has survived for more than 18 months. Infusions of fresh frozen plasma (FFP) in the early neonatal period were effective in raising and maintaining her blood pressure. Peritoneal dialysis was required until the appearance of spontaneous urination at 29 days after birth. Histopathological examinations of the kidney revealed dilated renal tubular lumina and foamy columnar epithelial cells in the renal tubules. Endocrinological studies showed a discrepancy between low plasma renin activity (<0.1 ng/ml/hr) and high active renin concentration (135,000 pg/ml), suggesting an aberration in the renin substrate, angiotensinogen. Direct sequencing analysis revealed two novel mutations in the coding region of the angiotensinogen gene (AGT): a nonsense mutation in exon 2 (c.604C > T) and a frameshift deletion at nucleotide 1290 in exon 5 (c.1290delT). The mutations were in the compound heterozygous state, because each parent had each mutation. These findings suggest that angiotensinogen deficiency is one of the causes of RTD. A treatment of the condition with FFP may help to promote long survival.

Angiotensinogen↗
PubMed2006

Receptor specific downregulation of cytokine signaling by autophosphorylation in the FERM domain of Jak2.

The tyrosine kinase, Janus kinase-2 (Jak2), plays a pivotal role in signal transduction through a variety of cytokine receptors, including the receptor for erythropoietin (Epo). Although the physiological relevance of Jak2 has been definitively established, less is known about its regulation. In studies assessing the roles of sites of tyrosine phosphorylation, we identified Y(119) in the FERM (band 4.1, Ezrin, radixin and moesin) domain as a phosphorylation site. In these studies, we demonstrate that the phosphorylation of Y(119) in response to Epo downregulates Jak2 kinase activity. Using a phosphorylation mimic mutation (Y(119)E), downregulation is shown to involve dissociation of Jak2 from the receptor complex. Conversely, a Y(119)F mutant is more stably associated with the receptor complex. Thus, in cytokine responses, ligand binding induces activation of receptor associated Jak2, autophosphorylation of Y(119) in the FERM domain and the subsequent dissociation of the activated Jak2 from the receptor and degradation. This regulation occurs with the receptors for Epo, thrombopoietin and growth hormone but not with the receptor for interferon-gamma.

Amino Acid Substitution↗
PubMed2006

Tyk2 mutation homologous to V617F Jak2 is not found in essential thrombocythaemia, although it induces constitutive signaling and growth factor independence.

A single somatic mutation, V617F, in the pseudokinase domain of the Jak2 is the primary cause of many chronic myeloproliferative diseases. As valine 617 of Jak2 is conserved as valine 678 of Tyk2, we examined the effect of a homologous mutation in Tyk2 (V678F Tyk2) on cell growth. V678F Tyk2 augmented the transcriptional activity of Stat3 and Stat5. The expression of V678F Tyk2 in Ba/F3 cells induced autonomous cell growth and showed hyper-responsiveness to IL-3. Although V678F Tyk2 might cause MPD, no cases of ET patients lacking the V617F Jak2 mutation harbored the Tyk2 mutation.

Adult↗
PubMed2006

[PADAM].

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Aging↗
PubMed2006

In vitro screening of 200 pesticides for agonistic activity via mouse peroxisome proliferator-activated receptor (PPAR)alpha and PPARgamma and quantitative analysis of in vivo induction pathway.

Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors and key regulators of lipid metabolism and cell differentiation. However, there have been few studies reporting on a variety of environmental chemicals, which may interact with these receptors. In the present study, we characterized mouse PPARalpha and PPARgamma agonistic activities of 200 pesticides (29 organochlorines, 11 diphenyl ethers, 56 organophosphorus pesticides, 12 pyrethroids, 22 carbamates, 11 acid amides, 7 triazines, 8 ureas and 44 others) by in vitro reporter gene assays using CV-1 monkey kidney cells. Three of the 200 pesticides, diclofop-methyl, pyrethrins and imazalil, which have different chemical structures, showed PPARalpha-mediated transcriptional activities in a dose-dependent manner. On the other hand, none of the 200 pesticides showed PPARgamma agonistic activity at concentrations <or =10(-5) M. To investigate the in vivo effects of diclofop-methyl, pyrethrins and imazalil, we examined the gene expression of PPARalpha-inducible cytochrome P450 4As (CYP4As) in the liver of female mice intraperitoneally injected with these compounds (< or =300 mg/kg). RT-PCR revealed significantly high induction levels of CYP4A10 and CYP4A14 mRNAs in diclofop-methyl- and pyrethrins-treated mice, whereas imazalil induced almost no gene expressions of CYP4As. In particular, diclofop-methyl induced as high levels of CYP4A mRNAs as WY-14643, a potent PPARalpha agonist. Thus, most of the 200 pesticides tested do not activate PPARalpha or PPARgamma in in vitro assays, but only diclofop-methyl and pyrethrins induce PPARalpha agonistic activity in vivo as well as in vitro.

Animals↗
PubMed2006

Sumoylation of Daxx regulates IFN-induced growth suppression of B lymphocytes and the hormone receptor-mediated transactivation.

Daxx has been shown to play an essential role in type I IFN-mediated suppression of B cell development and apoptosis. Recently, we demonstrated that Tyk2 is directly involved in IFN signaling for the induction and translocation of Daxx, which may result in growth arrest and/or apoptosis of B lymphocyte progenitors. To clarify the molecular mechanisms of how Daxx acts on growth suppression of B lymphocytes, we examined functions of a sumoylation-defective Daxx KA mutant (Daxx K630/631A), which substituted Lys 630 and Lys 631 to Ala. Importantly, Daxx KA localized in the cytoplasm, whereas wild-type Daxx localized in the nucleus. Murine pro-B cell line Ba/F3 expressing Daxx KA revealed a resistance to the IFN-induced growth suppression. It is noteworthy that treatment with an exportin inhibitor, leptomycin B, resulted in nuclear localization of Daxx KA and recovery of the IFN-induced growth suppression in Ba/F3 cells. Moreover, Daxx KA decreased the binding potential to promyelocytic leukemia protein (PML), and overexpression of PML recruited Daxx KA into PML oncogenic domains. Notably, a Daxx-small ubiquitin-related modifier fusion protein exhibited increased nuclear localization and ability to suppress cell growth in Ba/F3 cells. These results demonstrate that the IFN-induced growth suppression of B lymphocytes requires nuclear localization of Daxx through its sumoylation and proper interactions with PML.

Active Transport, Cell Nucleus↗
PubMed2006

[Varicocele testis].

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Embolization, Therapeutic↗
PubMed2006

Modulation of TLR4 signaling by a novel adaptor protein signal-transducing adaptor protein-2 in macrophages.

Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains pleckstrin and Src homology 2-like domains as well as a YXXQ motif in its C-terminal region. Our previous studies have demonstrated that STAP-2 binds to STAT3 and STAT5, and regulates their signaling pathways. In the present study, STAP-2 was found to positively regulate LPS/TLR4-mediated signals in macrophages. Disruption of STAP-2 resulted in impaired LPS/TLR4-induced cytokine production and NF-kappaB activation. Conversely, overexpression of STAP-2 enhanced these LPS/TLR4-induced biological activities. STAP-2, particularly its Src homology 2-like domain, bound to both MyD88 and IkappaB kinase (IKK)-alphabeta, but not TNFR-associated factor 6 or IL-1R-associated kinase 1, and formed a functional complex composed of MyD88-STAP-2-IKK-alphabeta. These interactions augmented MyD88- and/or IKK-alphabeta-dependent signals, leading to enhancement of the NF-kappaB activity. These results demonstrate that STAP-2 may constitute an alternative LPS/TLR4 pathway for NF-kappaB activation instead of the TNFR-associated factor 6-IL-1R-associated kinase 1 pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Cerebral hemodynamics during the induction of antenatal periventricular leukomalacia by hemorrhagic hypotension in chronically instrumented fetal sheep.

OBJECTIVE: Our purpose was to determine the characteristics of cerebral ischemia during the induction of antenatal periventricular leukomalacia by hemorrhagic hypotension in premature fetal sheep. STUDY DESIGN: The hemorrhage group received an acute withdrawal of 40% of the fetoplacental blood volume (n = 7), whereas an isovolemic exchange transfusion was performed in the control group (n = 7). Changes in the total hemoglobin, oxy-hemoglobin, and deoxy-hemoglobin levels in the cerebral tissue were assessed with the use of near-infrared spectroscopy and compared statistically. RESULTS: Of 7 fetuses in the hemorrhage group, 5 exhibited periventricular leukomalacia but none in the control group (P < .05). In the hemorrhage group, both brain total-hemoglobin and deoxy-hemoglobin decreased seriously after insult, and the decreased levels persisted even after recovery of systemic blood pressure, whereas such drastic changes were not observed in the control group, suggesting the occurrence of reperfusion failure in the fetal brain in the hemorrhage group. CONCLUSION: The no-reflow phenomenon and successive reperfusion injuries after cerebral ischemia could be closely involved in the induction of antenatal periventricular leukomalacia in this experimental condition.

Animals↗
PubMed2006

The endoscopic surgical skill qualification system in urological laparoscopy: a novel system in Japan.

PURPOSE: The Japanese Urological Association, and Japanese Society of Endourology and ESWL have established the Endoscopic Surgical Skill Qualification System in urological laparoscopy. The system consists of a urological section as well as gynecology and general surgery sections. We present details of the Endoscopic Surgical Skill Qualification System and year 1 results. MATERIALS AND METHODS: Endoscopic Surgical Skill Qualification System requirements test the ability to complete common laparoscopic surgeries in each field. In urology applicants are required to complete adrenalectomies or nephrectomies appropriately and safely. Applicants should have 2 years of experience with laparoscopic practice, in addition to having completed a 6-year formal urological training program. Also, each surgeon must have performed more than 20 laparoscopic surgeries. According to assessment guidelines applicant skills are assessed by 2 referees who view unedited videotapes showing the entire laparoscopic procedure. To establish these referees 6 expert referees were first selected and 23 were then chosen from 36 referee applicants. Each referee had completed more than 100 laparoscopic surgeries and was chosen after video assessments by the 6 initial expert referees. RESULTS: Of 5,600 certified urologists in Japan 205 applied to this system in its first year, including 6 expert referees and 36 referee applicants. After video assessments by the referees 136 applicants were certified as having appropriate skills, resulting in a 66% pass rate. CONCLUSIONS: The Endoscopic Surgical Skill Qualification System has just started but it has drawn a lot of attention from the public. We hope that this qualification system will help prevent complications of urological laparoscopic surgeries and promote safer surgical procedures.

Clinical Competence↗
PubMed2006

Successful treatment of congenital pulmonary alveolar proteinosis with intravenous immunoglobulin G administration.

The authors report a female patient with congenital pulmonary alveolar proteinosis (PAP). She had two brothers who died from the same disease. BAL did not improve her progressive respiratory failure. After intravenous immunoglobulin G (IVIG) administration for complicated hypogammaglobulinemia, she recovered from respiratory failure. The efficacy of IVIG was confirmed by recovery from deterioration in respiratory status and improvement in chest CT findings on two separate occasions. Subsequently, the patient remains free from respiratory symptoms for more than 3 years on an ongoing regimen of monthly IVIG. She had no surfactant protein (SP) B deficiency. Alveolar macrophages (AM) obtained from her BAL fluid were small and showed decreased phagocytotic activity. Immunostaining revealed weak expression of PU.1 in her AM, a key protein in AM maturation. All nucleotide sequences of granulocyte-macrophage colony stimulating factor (GM-CSF), GM-CSF-receptor and PU.1 were normal. Endotoxin-induced GM-CSF release from peripheral mononuclear cells (PMNC), and proliferation of PMNC in response to GM-CSF were normal. In addition, an antibody against GM-CSF, as seen in adult patients with idiopathic PAP, was not detected in the serum or BAL fluid. Although the patient's PMNC secreted only small amounts of IgG and IgM, an EB virus-derived cell line of her B cells secreted IgM as much as normal control cells. In a flow cytometric study, IgM was expressed on the cell surface. In conclusion, an abnormality in a single gene may have decreased secretion of immunoglobulin from the B cells and the AM phagocytotic activity in the patient.

Agammaglobulinemia↗
PubMed2006

Retroperitoneoscopic pyeloplasty: using reconstructive methods based on intraoperative findings.

AIM: Reconstructive laparoscopic procedures have been recognized as a less invasive treatment than conventional open procedures. However, although the laparoscopic pyeloplasty has also been accepted as useful, few findings have been reported relevant to the retroperitoneal approach. To elucidate its effectiveness and safety, laparoscopic surgery via the retroperitoneal approach was examined in our institution. Furthermore, the importance of laparoscopic observation for ureteropelvic junction and urine passage ureteropelvic junction without indwelling ureteral stent. METHODS: Between July 1998 and December 2004, 13 men and 15 women underwent laparoscopic retroperitoneal surgery for ureteropelvic junction obstruction. The mean patient age was 33.6 years (range: 13-70 years). Methods of repair were determined by intraoperative findings for the relationship between the ureteropelvic junction and surrounding vessels. An indwelling ureteral stent was removed before initiating laparoscopic operation to observe the relationship between ureteropelvic junction and aberrant vessels more precisely. RESULTS: An aberrant renal vessel was found in 13 patients (46%). Dismembered pyeloplasty was carried out in 21 patients, Y-V plasty in five patients and Hellstrom technique in two patients. Ureteral transposition was not required in dismembered pyeloplasty cases. All patients achieved retroperitoneoscopic pyeloplasty without open conversion. The mean operative time was 272 min (range: 155-490 min). The mean estimated blood loss was 44 mL (range: 10-200 mL). No major complications were observed during the intraoperative period, but urinary tract infection occurred in two patients in the postoperative period. In all patients except one, obstruction was improved or resolved. CONCLUSIONS: Laparoscopic retroperitoneal surgery is not only able to repair ureteropelvic junction obstruction, but can also be done safety and less invasively. We believe that laparoscopic observation without indwelling stent will contribute to a more appropriate choice of pyeloplasty.

Adolescent↗
PubMed2006

Surgical treatment for urethral recurrence after ileal neobladder reconstruction in patients with bladder cancer.

OBJECTIVE: To report a retrospective study evaluating the management of superficial urethral recurrence after ileal neobladder construction in patients with bladder cancer. PATIENTS AND METHODS: In 77 consecutive patients with ileal neobladder after radical cystectomy for invasive bladder cancer, urethral recurrence was evaluated and transurethral resection (TUR) used as an initial treatment for superficial urethral recurrence. Urethrectomy with urinary re-diversion was performed when further recurrence developed. RESULTS: Four patients (5%) presented with a superficial urethral recurrence and all four were treated by TUR as initial therapy. One patient has had no evidence of recurrence after initial TUR, although the other three patients were later treated with salvage urethrectomy due to repeated urethral recurrence. As a result, the stage of urethral recurrence advanced from pTa to pT1-pT2 in two of the three patients. For urinary re-diversion, one patient had a conversion from a Studer pouch to an ileal conduit, using the afferent limb, and the other two were converted from a Hautmann pouch to a continent reservoir using the Appe-Mainz procedure. There was no evidence of metastasis or local recurrence in any of the four patients. CONCLUSION: Urethral preservation at initial therapy for superficial recurrence might be reasonable, and sequential urethrectomy after attempted urethral preservation might be strategically feasible. Urinary re-diversion from a neobladder to a catheterizable continent reservoir using the appendix would be a good choice and maintains the quality of life.

Aged↗
PubMed2006

A rat model for arrest of alveolarization induced by antenatal endotoxin administration.

A possible association between intrauterine inflammation and impairments of lung development has been suggested. The purpose of this study is to determine the influence of a potent proinflammatory agent, intra-amniotic lipopolysaccharide (LPS), on lung development. At 21 d gestation, an intra-amniotic injection of 1 microg LPS was administered to two subgroups of WKAH rats. One subgroup received only LPS and the other received LPS plus a fetal intraperitoneal dose of 0.25 microg granulocyte-colony stimulating factor (hrG-CSF) to produce peripheral blood neutrophilia. A third subgroup received hrG-CSF only, and a control group received maternal intraamniotic and fetal intraperitoneal normal saline. All pups were delivered by cesarean section at 22 d (term, 22.5 d) and maintained under identical conditions. Left upper lungs were obtained for morphometric analysis at 1, 3, 7, 14, 21, 45, and 60 d of age. Morphometric analysis indicated that changes in alveolar surface density (Sv), average alveolar radius (r), and numerical density of alveoli (nv) all showed that there were fewer and larger alveoli in rat lungs that had been exposed to LPS, but not to hrG-CSF alone or saline. LPS-exposed alveoli showed fewer secondary septa, suggesting an arrest of alveolarization. No destructive changes were observed in any alveoli. We concluded that these changes could be caused purely by intra-amniotic LPS. These abnormalities closely mimic those of new bronchopulmonary dysplasia. The LPS damage model may be applicable to further studies of the pathophysiology of new BPD.

Animals↗
PubMed2006

[Experience of laparoscopic nerve-sparing radical cystectomy and construction of ileal neobladder at Kansai Medical University].

Laparoscopic nerve-sparing radical cystectomy and construction of ileal neobladder was performed on a 76-year-old man with atrophic bladder after the intravesical instillation therapy for bladder cancer. Ileal neobladder was constructed by the combined extracorporeal technique through the camera port dilated to 45 mm. Operation time was 8 hours, with 3.5 hours for the nerve-sparing cystoprostatectomy, 2.5 hours for the extracorporeal neo-bladder construction and 2 hours for the laparoscopic urethra neo-bladder anastomosis and wound closing. The post-operative course was uneventful with minimum use of analgesia. This operation was minimally invasive therapy and from the functional aspect the potency was preserved. Although this method was technically challenging, various advantages can be promising for the patients compared to the standard open technique. Indication of this operation should be carefully expanded. Various methods, such as the complete intracorporeal technique and minimally invasive laparoscopic neobladder (MILaN) technique, have been reported for urinary diversion. In this report, we compared our method with other techniques.

Aged↗
PubMed2005

Physical and functional interactions between STAT3 and Kaposi's sarcoma-associated herpesvirus-encoded LANA.

The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA) is known to modulate viral and cellular gene expression. We show that LANA directly associates with an interleukin-6 signal transducer, signal transducer and activator of transcription 3 (STAT3) and that LANA enhances the transcriptional activity of STAT3. Coimmunoprecipitation studies documented a physical interaction between LANA and STAT3 in transiently transfected 293T cells as well as the KSHV-infected primary effusion lymphoma (PEL) cell line. Furthermore, small-interfering RNA-mediated reduction of LANA expression decreased the STAT3-dependent transcription in KSHV-positive PEL cells, whereas overexpression of LANA enhanced STAT3 activity in KSHV-negative B lymphoma cells. These data demonstrate that LANA is a transcriptional co-activator of STAT3, and may have implications for the pathogenesis of KSHV-associated diseases.

Antigens, Viral↗